Midwifery and sexual misconduct.
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Adult↗
Biomedical subjects
S Brill
Publications and source records attributed to S Brill.
Hepatogenous diabetes: reduced insulin sensitivity and increased awareness.
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Diabetes Mellitus↗
Evaluation of the VersaMed portable ventilator: clinical trials.
The VersaMed 201 is a lightweight, computer-controlled, electrically driven ventilator, designed for transport, home-ventilation and field use. We have evaluated the device in human beings with healthy and pathological lungs. In the first part of the study, the VersaMed was substituted for a standard operating room ventilator for 15-30 min during elective surgery in 20 subjects. In the second stage of the study, 20 patients with lung pathology who were being ventilated in the critical care department were transferred to the VersaMed for a 30-min period. In all the patients studied, arterial blood gases, haemodynamic parameters and other respiratory variables were maintained at similar values seen with the standard ventilators used. We conclude that the VersaMed 201 is suitable for use in human beings with healthy and pathological lungs as a reliable, portable ventilator.
Adult↗
The role of the liver environment in the regulation of colon cancer metastasis.
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Autocrine Communication↗
Additive deleterious effect of smoking on gastroduodenal pathology and clinical course in Helicobacter pylori-positive dyspeptic patients.
BACKGROUND: Cigarette smoking has long been regarded as an important factor in the pathogenesis of peptic ulcer disease. OBJECTIVE: To investigate whether cigarette smoking has an additive effect on the clinical presentation and course of disease in Helicobacter pylori-positive dyspeptic patients. PATIENTS AND METHODS: The study group comprised 596 consecutive H. pylori-positive dyspeptic patients (334 males and 262 females, mean age 50.6, range 12-81 years). Following upper gastrointestinal endoscopy, patients were subdivided by diagnosis as follows: Non-ulcer patient group (n = 312: gastritis 193, duodenitis 119), gastric ulcer (n = 19), and duodenal ulcer (n = 265). H. pylori infection was confirmed by histology and/or rapid urease test. In addition, 244 patients had a positive 14C-urea breath test prior to antimicrobial treatment. The patients' medical history and smoking habits were obtained using a detailed questionnaire completed by the patients and their referring physicians. RESULTS: There were 337 non-smoking patients, 148 current smokers and 111 past smokers. Gastric and duodenal ulcers were significantly less prevalent in non-smokers than in current or past smokers (gastric 1.8%, 4.1%, 6.3%; duodenal 39.8%, 50%, 51.4%, respectively) (P < 0.05). The incidence of gastrointestinal bleeding was significantly lower in non-smokers than in current or past smokers (7.1%, 8.1% and 20.7%, respectively) (P < 0.05). Bacterial density, as assessed by the UBT value in 244 patients, was higher in non-smokers (mean 352.3 +/- 273 units) than in past smokers (mean 320.8 +/- 199) or current-smokers (mean 229.9 +/- 162) (P < 0.05). Logistic regression analysis revealed that male gender, current smoking, and immigration from developing countries were all significant independent risks for developing duodenal ulcer, while only past smoking was associated with a higher rate of upper gastrointestinal bleeding in the past. CONCLUSIONS: In H. pylori-positive dyspeptic patients, current smoking as well as male gender and immigration from developing countries are associated with an increased risk for duodenal ulcer. This effect does not seem to be related to the bacterial density or increased urease activity of H. pylori organisms.
Adolescent↗
The status of serum iron and transferrin saturation in acute non-hepatotrophic viral infections.
Elevation of serum iron is frequently observed in patients' with chronic Hepatitis C virus infection and was found to be a negative predictive factor for treatment response. We prospectively evaluated the iron status of 112 patients with acute viral infection not due to hepatitis viruses. The virus infections included Epstein-Barr virus (57%), cytomegalovirus (22.3%) and others (20.7%). Increased serum iron was documented in two patients only. Out of nine patients who were evaluated twice, seven had increased serum iron but the level remained well within the normal range. Transferrin saturation was normal in all patients. Disturbed liver function tests were documented in 30-40% of patients. We conclude that serum iron is not significantly increased during acute non (A-E) hepatitis viral infections with or without liver involvement.
Adolescent↗
Amphiregulin and hepatocyte-derived extracellular matrix regulate proliferation and autocrine growth factor expression in colon cancer cell lines of varying liver-colonizing capability.
We studied the effect of two members of the epidermal growth factor (EGF) family--amphiregulin and heparin-binding EGF-like growth factor (HB-EGF)-on cell proliferation, growth factor and growth factor receptor expression, and cell differentiation in two human colon cell lines of varying liver-colonizing potential. The effect of amphiregulin and HB-EGF was assessed both in cells grown on plastic, as well as on cells grown on hepatocyte-derived extracellular matrix (ECM). We found that both colon cell lines were sensitive to HB-EGF stimulation of cell proliferation. Amphiregulin inhibited cell proliferation in KM12 cells and stimulated the strongly metastatic cell line KM12SM to a slight extent. When the cells were cultured on hepatocyte-derived ECM, amphiregulin inhibited the weakly metastatic KM12 and stimulated the growth of KM12SM. HB-EGF synergistically acted with hepatocyte-derived ECM to enhance cell proliferation in both colon cell lines. Expression of ligands of the EGF family, such as transforming growth factor-alpha (TGF-alpha) and amphiregulin, was decreased in both cell lines when cultured on ECM. Hepatocyte-derived ECM decreased expression of cripto in KM12 and increased it in KM12SM cells. Neither cripto nor TGF-alpha mRNA levels was affected by growing the cells in the presence of amphiregulin. However, amphiregulin increased expression of its own mRNA in the weakly metastatic KM12 and decreased it in the strongly metastatic KM12SM when the cells were cultured on plastic. Amphiregulin and HB-EGF stimulated expression of erb-B2 in both cell lines cultured on plastic. Surprisingly, when the cells were grown on hepatocyte-derived ECM, amphiregulin inhibited erb-B2 expression in both cell lines. We observed no effect of amphiregulin on cell differentiation as assessed by alkaline phosphatase expression. Our studies demonstrate one mechanism that could play a role in site-specific metastasis. We found an inhibitory response to an autocrine growth factor in the context of hepatocyte-derived ECM in a weakly metastatic cell and a stimulatory effect of the same growth factor when strongly metastatic cells were cultured on the same ECM.
Amphiregulin↗
Intranasal salbutamol instillation in asthma attack.
Beta-two sympathomimetic drugs are the treatment of choice for asthmatic attack. Their main effect is to dilate the bronchi by a direct action on beta-two adrenoreceptors on the smooth muscle, and also by mediator release inhibition from mast cells. Salbutamol is widely used in the treatment of bronchial asthma, and is usually administered either by inhalation, orally, or parenterally. The nasal route seems to afford an effective way to administer medications, since the nasal mucosa has a relatively large surface area, and there is no gastrointestinal-hepatic first pass-effect, thus avoiding extensive loss of the administered drug. We describe herein the use of nasal salbutamol in 3 patients with severe asthma attacks who were refractory to conventional therapy, with favorable responses and without significant undesirable effects.
Acute Disease↗
Expansion conditions for early hepatic progenitor cells from embryonal and neonatal rat livers.
Long-term primary cultures were established from fetal or neonatal livers by using cell suspensions depleted of red blood cells and by culturing the cells in hormonally defined medium containing dimethyl sulfoxide. Two distinct populations of hepatic progenitor cells were evident in the cultures, based on morphology, proliferative ability, and liver-specific gene expression. Most colonies consisted of immature hepatic progenitors: small, blastlike cells, weakly expressing alpha-fetoprotein, albumin, and gamma-glutamyltranspeptidase, and showing evidence of proliferation as measured by bromodeoxyuridine incorporation. At the perimeter of these colonies of immature cells and forming some colonies by themselves were more mature hepatic progenitor cells: larger cells, with increased cytoplasmic to nuclear ratios, little proliferation, and strongly expressing albumin, alpha-fetoprotein, and gamma-glutamyltranspeptidase. The latter two proteins were localized to the bile canalicular membranes of these cells. Glycogen deposits were present in the mature cells from day 14 embryos after eight days of culture. Thus, DMSO treatment of hepatic parenchymal progenitors provides a novel system for studies of liver development.
Albumins↗
Altered thyroid status modulates portal pressure in normal rats.
BACKGROUND & AIMS: Disturbances in thyroid function in humans and experimental animal models have been associated with alterations in liver function and portal circulation. We have previously shown that hypothyroidism can significantly reduce portal pressure in portal vein ligated rats as well as inhibit the development of cirrhosis and fulminant hepatic failure following toxic liver injury. The aim of this study was to determine the effects of increased and decreased thyroid function on portal pressure in rats with normal liver histology and portal circulation. METHODS: Three groups of 12 Wistar rats each were studied over a 30 day period: euthyroid (Group 1), hyperthyroid (Group 2) and hypothyroid (Group 3). Hyperthyroidism was induced by subcutaneous injection of triiodothyronine (400 microg/100g body weight) every ten days during the study period. Hypothyroidism was induced by methimazole (0.04% in drinking water) from 2 weeks prior to and throughout the 30 day study. Serum triiodothyronine (T3) and thyroid stimulating hormone (TSH) levels were determined to confirm the induction of hyper- and hypothyroidism. Portal pressure was assessed by direct catheterization of the portal vein prior to sacrifice. Indirect confirmation of changes in portal circulation was obtained by determining splenic weight at the time of sacrificing the animals. Animals were sacrificed at 10 day intervals throughout the 30 day study. RESULTS: Triiodothyronine treated rats were hyperthyroid compared to controls, with an elevation in serum T3 levels (3.8+/-0.9 mmol/L vs 1.3+/-0.4 mmol/L, p<0.05). In rats treated with methimazole, hypothyroidism was confirmed by a 7-fold increase in serum TSH compared to controls (1.8+/-0.4 vs 0.24+/-0.04 mmol/L, p<0.01). Portal pressure was significantly higher in the triiodothyronine treated rats compared to controls (12.8+/-1.7 and 9.6+/-0.75 cm H2O, p<0.001). Splenic weights in hyperthyroid rats were significantly higher than in controls (579+/-44 vs 478+/-46 mg, p<0.01). Portal pressure was significantly lower in the methimazole treated group compared to the control group (8.13+/-0.68 vs 9.6+/-0.75 cm H2O, p<0.01) as were splenic weights (400+/-33 vs 478+/-46 mg, p<0.01). CONCLUSION: These studies demonstrate that disturbed thyroid function exerts significant hemodynamic effects on the portal circulation in normal rats and complements results from previous similar studies in cirrhotic animals.
Administration, Oral↗
The efficacy of omeprazole-based short-term triple therapy in Helicobacter pylori-positive older patients with dyspepsia.
OBJECTIVE: To evaluate the efficacy of 1-week triple therapy with omeprazole, clarithromycin,and tinidazole (OCT) in Helicobacter pylori-positive older patients with dyspepsia. DESIGN: A prospective, nonrandomized therapeutic study. SETTING: The primary care and referral center of a gastroenterological outpatient clinic at a central university hospital serving an urban population (>1 million) in Israel. PARTICIPANTS: The study group consisted of 134 patients (71 men, and 63 women) more than 60 years old who were referred for evaluation of symptoms of dyspepsia and were endoscopically diagnosed as H. pylori positive. The patients were divided into two groups: those who received their first course of anti-H. Pylori therapy during this study (Group 1) and those who had previously received standard metronidazole and bismuth combination therapies that failed to eradicate the H. pylori (Group 2). MEASUREMENTS: All the patients underwent upper gastrointestinal endoscopy, and H. pylori infection was confirmed by a rapid urease test (CUTest) and/or histological staining. Therapeutic efficacy was assessed by a 13C-urea breath test 4 weeks after completion of treatment. RESULTS: The mean age of the study population was 68.8 years (range 60-87). There were 112 patients in Group 1 and 22 patients in Group 2. Endoscopic findings were: gastritis (in 46), gastric ulcer (8), duodenal ulcer (52), and duodenitis (28). The H. pylori eradication rate was significantly higher in Group 1 patients (104/112, 92.9%) than in patients of Group 2 (15/22, 68.2%). There was no difference in the eradication rate in relation to gender, endoscopic diagnosis, more advanced age, place of birth, or smoking habits. The compliance in both groups was equally good, and no major side effects were recorded. CONCLUSIONS: A 1-week OCT triple therapy is well tolerated and effective as first line therapy for H. pylori among older people. It is less effective in patients previously treated.
Aged↗
Removal of unexploded ordnance from patients: a 50-year military experience and current recommendations.
BACKGROUND: Retained unexploded ordnance in a patient presents the surgeon with unique emotional and technical challenges. This report is a compilation of data to determine management strategies for these potentially catastrophic injuries. METHODS: All identified military cases from World War II to the present were reviewed. Cases were reviewed for site of injury, type of munition, personnel and equipment precautions, and outcome. Interviews were conducted with available involved surgeons. RESULTS: Thirty-six patients were identified with retained ordnance. Four were moribund upon arrival and died before operation. All of the remaining 32 patients survived the removal of the unexploded ordnance. Thirteen injuries involved the trunk, 4 involved the head and neck, and 18 involved extremities. The majority of missiles (51%) were 40-mm projectiles. No incident was identified in which a round exploded during transportation, preparation, or removal. Explosive Ordnance Disposal assistance was available to the surgical team for all but one patient during and after the Vietnam War. Measures used to reduce the chance of premature explosion are discussed. CONCLUSIONS: Isolation of the operating room and protection of personnel and equipment are essential. Patients should be triaged in the delayed category, because most are not morbund on arrival and all patients operated on survived. Explosive Ordnance Disposal expertise should be used. Knowledge of and adherence to several basic principles will protect personnel and equipment while permitting optimal patient care.
Explosions↗
Pregnancy from a new perspective.
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Adaptation, Psychological↗
Hepatocyte extracellular matrix modulates expression of growth factors and growth factor receptors in human colon cancer cells.
We investigated the role of hepatocyte extracellular matrix (ECM) on the growth of human colon cancer cell lines. We cultured four cell lines with different liver-colonizing potential on ECM derived from primary rat hepatocyte cultures. We investigated the effect of ECM on cell proliferation, clonal growth, and expression of growth factors and growth factor receptors. The highly metastatic cells showed better clonal growth and produced larger colonies on ECM. The proliferation of all colon cancer cell lines was enhanced on hepatocyte ECM, yet inhibited on fibroblast ECM. Screening of autocrine growth factors and receptors showed that the cells expressed growth factors and receptors of the EGF family: EGF receptor, erb-B2, amphiregulin, and cripto. The expression of cripto mRNA, but not of amphiregulin, was induced in KM12SM cells grown on ECM. All colon cancer cell lines grown on ECM showed increased expression of erb-B2. The effect of ECM on erb-B2 expression was mediated by the heparin chains of heparin proteoglycan. ECM from hepatocytes grown in the presence of nitrophenyl-beta-D-xylopyrannoside or sodium chlorate, which prevent formation of heparin proteoglycan, as well as ECM treated with heparinase, had no effect on erb-B2 expression. Our studies suggest a role for liver ECM as a determinant of colon cancer metastasis. Liver ECM acts, in part, via induction of members of the EGF family of growth factors and their receptors.
Animals↗
Restricted tissue expression pattern of a novel human rasGAP-related gene and its murine ortholog.
The mammalian rasGAPs constitute a group of widely expressed proteins involved in the negative regulation of ras-mediated signaling. In this study we have isolated a novel human gene, RASAL (Ras GTPase-activating-like) and its murine ortholog, MRASAL which are most similar to the GAP1 family of rasGAP proteins, based upon the presence and organization of specific conserved domains. Full-length human and murine mRNA sequences are predicted to encode 804 and 799 amino acid polypeptides, respectively. Sequence analysis of these two proteins revealed the presence of two N-terminal calcium-dependent phospholipid binding C2 domains, a conserved GAP related domain (GRD) and a C-terminal pleckstrin homology (PH) domain. Northern blot and mRNA in situ hybridization analyses indicate that RASAL, in contrast to other mammalian rasGAP proteins, has a limited expression pattern; RASAL is highly expressed in the follicular cells of the thyroid and the adrenal medulla and expressed at lower levels in brain, spinal cord and trachea. Human RASAL has been localized by radiation hybrid mapping to chromosome 12q23-24.
Amino Acid Sequence↗
Thyroxine accelerates proliferation of injured liver cells.
BACKGROUND/AIMS: Long-term gene transfer into hepatocytes requires DNA synthesis. Although this can be achieved in vitro, using various hepatic mitogens, marked proliferative response is not seen in vivo in the quiescent liver. We have speculated that controlled reversible liver damage might change the steady state of the liver, and thus render it susceptible to manipulations by growth factors and cytokines. Therefore, the influence of thyroxine on proliferation of hepatocytes and of bile duct epithelial cells was investigated, using an in vivo model of thioacetamide-induced liver insult. METHODS: Five groups of ten rats each were studied: normal rats, thioacetamide-treated, thyroxine-treated, both thioacetamide and thyroxine-treated, and a 70% partial hepatectomy group. DNA synthesis was looked at by PCNA labeling. RESULTS: The PCNA labeling indexes of hepatocytes and of bile duct epithelial cells in rats treated with both thioacetamide and thyroxine (9.5+/-1.2 and 33.8+/-5.7% respectively) were significantly (p<0.0002) higher than those of the normal (0.84+/-0.2 and 4.4+/-0.50%), thioacetamide-treated (2.1+/-0.3 and 7.1+/-2.3%) and thyroxine-treated animals (0.6+/-0.3 and 11+/-5.6%). The labeling index in the hepatectomized animals was significantly higher for hepatocytes (18.3+/-1.2%, p<0.003), but lower for biliary cells (15+/-2.6, p<0.05) than that observed in thioacetamide and thyroxine-treated rats. Hypothyroid rats had significantly lower PCNA labeling index, as compared to the thioacetamide-thyroxine-treated group or the partial hepatectomy group. CONCLUSIONS: Following controlled liver damage, thyroxine is a potent mitogen for both hepatocytes and bile duct epithelial cells.
Animals↗
Liver function in cirrhotic patients in the euthyroid versus the hypothyroid state.
We recently showed that some decrease in thyroid hormone blood levels can effectively and significantly prevent the development of cirrhosis and fulminant hepatic failure and decrease portal pressure in three different rat models. This study was conducted to determine whether hypothyroidism has a beneficial effect over euthyroidism on patients with active liver cirrhosis of different etiologies. The medical files of hypothyroid patients with cirrhosis who were referred to the Tel-Aviv Medical Center between the years 1980 and 1995 were retrospectively evaluated. Of 3,528 patients with biopsy-proven cirrhosis and 4,738 hypothyroid patients who were identified, only 46 (25 female, 54%; mean age, 52.3 +/- 9.1) met the eligibility criteria. The patients suffered from cirrhosis (mean, 9.5 +/- 4.3 years; range, 4-23) and had hypothyroidism (mean, 12 +/- 6 years; range, 4-31). Most patients suffered from hypothyroidism of unknown etiology (85%), whereas the rest had hypothyroidism after surgical/iodine ablation of the gland. In the hypothyroid versus the euthyroid state, a significant negative correlation was found between thyroid-stimulating hormone blood levels and both functional and synthetic liver function tests (p < 0.001). A significant negative correlation was also found between thyroid-stimulating hormone blood levels and clinical deterioration manifested as bleeding varices, the development of ascites, and episodes of encephalopathy. We conclude that in patients with liver cirrhosis, the liver function in the hypothyroid state tend to be better than in the euthyroid state. A mild controlled decreased thyroid function may be beneficial for euthyroid cirrhotic patients.
Acute Disease↗
Phenotypic characterization of rat hepatoma cell lines and lineage-specific regulation of gene expression by differentiation agents.
Hepatoma cell lines can be characterized by their expression of hepatocyte- and biliary-specific genes and by their response to differentiating agents in a lineage-dependent manner. These characteristics can be used to map the maturational lineage position of the cell lines. Tissue-specific gene expression and regulation by heparin, dimethylsulfoxide (DMSO), and sodium butyrate (SB) were examined in three rat hepatoma cell lines and two rat liver epithelial cell lines. Based on antigenic profiles and gene expression in serum-supplemented medium, the hepatoma cell lines could be organized in distinct categories of hepatic differentiation. All three hepatomas expressed the following five genes: gamma-glutamyl transpeptidase (GGT), glutathione-S-transferase pi (Yp), glutamine synthetase, and alpha 5 and beta 1 integrin. Cell line H4AzC2 also expressed alpha-fetoprotein (AFP), albumin. IGF II receptor, and the biliary/oval cell antigens OC.2 and OC.3, a phenotype characteristic of fetal hepatocytes. FTO-2B cells lacked AFP, OC.2, and OC.3 but expressed albumin and IGF II receptor in addition to the five commonly expressed genes, consistent with a more hepatocyte-like phenotype. Cell line H5D-7 expressed neither albumin nor the IGF II receptor, but did express OC.2, OC.3, and alpha 3 integrin in addition to the five commonly expressed genes, characteristic of biliary epithelial cells. Regulation of gene expression by heparin, DMSO, and SB was examined in cells cultured in hormonally defined medium. The patterns of regulation of AFP, albumin, GGT, and Yp were dependent upon the state of differentiation of the cell. FTO-2B cells regulated genes in a manner similar to that of E16 fetal hepatocytes, H4AzC2 regulated genes characteristic of both hepatocytic and biliary lineages, and H5D.7 regulated only biliary genes. Suppression of GGT by DMSO was uniformly observed. The three cell lines expressed equal amounts of HNF-4, but FTO-2B cells expressed more HNF-3 beta and less HNF-3 alpha, while the reverse was true of H4AzC2 and H5D.7 cells.
Animals↗