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Biomedical subjects

R Oren

Publications and source records attributed to R Oren.

At least 19 recordsLinked to original sources

Methotrexate in chronic active ulcerative colitis: a double-blind, randomized, Israeli multicenter trial.

BACKGROUND & AIMS: Uncontrolled studies have suggested that methotrexate may be effective in patients with active ulcerative colitis. The aim of this study was to evaluate the effectiveness of oral methotrexate in chronic steroid-dependent ulcerative colitis in a randomized, double-blind multicenter trial. METHODS: Patients with active ulcerative colitis who have received steroids and/or immunosuppressives for at least 4 months during the preceding 12 months with a current Mayo Clinic score of > or = 7 were included in the study. Methotrexate (12.5 mg) or placebo was added to their treatment once weekly for 9 months. RESULTS: Sixty-seven patients were included (methotrexate, 30 patients, placebo, 37 patients). The proportion of patients entering first remission (methotrexate, 46.7%; placebo, 48.6%), the time to reach first remission (methotrexate, 4.1 +/- 1.9 months; placebo, 3.4 +/- 1.7 months), as well as the proportions of patients having a relapse after first remission (methotrexate, 64.3%; placebo, 44.4%) were not significantly different between the two groups. The mean Mayo Clinic score, the mean monthly steroid dose, and the proportion of abnormal laboratory results during the study were also similar. CONCLUSIONS: Methotrexate at a weekly oral dose of 12.5 mg was not found to be better than placebo in the induction or maintenance of remission in patients with chronic active ulcerative colitis.

Administration, Oral

Inhibition of experimentally induced cirrhosis in rats by hypothyroidism.

The coexistence of hyperkinetic circulation, hypermetabolism, and hyperactivity of the sympathetic nervous system is encountered in both cirrhosis and hyperthyroidism. Several drugs, such as propylthiouracil and propranolol, that are beneficial for treating some patients with chronic liver diseases are also prescribed for the treatment of thyrotoxicosis. We investigated the effects of experimentally induced hypo- and hyperthyroidism on the development of cirrhosis induced in rats by thioacetamide (TAA). We specifically examined whether hypothyroidism could prevent and hyperthyroidism could aggravate liver damage. Hypothyroidism induced by methimazole (MMI, 0.04%), propylthiouracil (PTU 0.05%), and by thyroidectomy was confirmed by a significant elevation of thyroid-stimulating hormone (TSH) levels. Hyperthyroidism (decreased TSH levels) was induced by eltroxin (ELT:50 micrograms/kg). Thirteen groups of 10 rats each were studied: euthyroid controls (3 groups: water, TAA 1.5 months, and TAA 3 months), hypothyroid (6 groups: MMI, PTU, surgical, MMI-TAA, PTU-TAA, surgical-TAA), and hyperthyroid (4 groups:ELT 1.5 months and 3 months, and ELT-TAA for 1.5 months and 3 months). Hepatic fibrosis (scored from 0 to 3) was significantly reduced (P < .0001) in hypothyroid rats as compared with euthyroid controls, and was aggravated in TAA-treated hyperthyroid rats (P < .0001). Quantitative microscopic analysis of liver biopsy specimens from all groups confirmed the semiquantitative histopathological scores (P < .001). Direct intrasplenic pressure measurement revealed a significant portal pressure elevation in the TAA and the ELT-treated rats (from 4.7 +/- 0.1 in the euthyroid group to 8.1 +/- 2.3 and 10.2 +/- 2.1 and 12.5 +/- 1.6 in the TAA, ELT and ELT-TAA groups, respectively). However, in the hypothyroid-TAA groups, the portal pressure was found to be within the euthyroid normal range (4.6 +/- 1.2 and 5.8 +/- 0.6 in the PTU-TAA and surgical-TAA, respectively). After 12 weeks, the mean spleen weight of rats receiving only TAA was significantly higher than the TAA-treated hypothyroid rats (P < .0001), indicating that the hypothyroid TAA-treated rats were less portal hypertensive. These results suggest that induced hypothyroidism can inhibit, whereas hyperthyroidism can aggravate, the development of cirrhosis in a rat model.

Animals

Hemodynamic effects of hypothyroidism induced by methimazole in normal and portal hypertensive rats.

Portal hypertension is accompanied by a hyperdynamic circulatory state that shares some similarities with thyrotoxicosis. This study was conducted in order to investigate the hemodynamic effects of hypothyroidism in a rat model with portal hypertension induced by partial portal vein ligation (PVL). Four groups of 10 rats each were studied: normal control and hypothyroid rats, and PVL control and hypothyroid rats. Hypothyroidism was induced by methimazole 0.04% in drinking water. Hemodynamic measurements were performed using the radioactive microsphere technique. Induction of hypothyroidism was confirmed by elevated TSH levels. In the PVL groups, hypothyroidism ameliorated the hyperdynamic circulation. Portal venous inflow and portal pressure dropped significantly: 7.1 +/- 0.2 vs 4.8 +/- 0.3 ml/min/100 g body wt (P < 0.01) and 13.4 +/- 0.9 vs 10.9 +/- 0.8 mm Hg; (P < 0.01), respectively. In normal rats, hypothyroidism was manifested by a hypodynamic circulatory state. These results demonstrate that hypothyroidism induced by methimazole is followed by amelioration of the hyperdynamic circulation, normalization of portal venous inflow, and reduction of portal pressure.

Animals

C3, C4, factor B and HLA-DR alpha mRNA expression in renal biopsy specimens from patients with IgA nephropathy.

The deposition of complement in the kidney mesangium is a constant finding associated with renal injury in IgA nephropathy, even though IgA does not bind complement. We have previously reported that complement gene expression in the kidney increases concurrently with the progression of immune complex disease in murine lupus nephritis. We have now studied the expression of C3, C4, factor B and HLA-DR alpha mRNA by in situ hybridization in renal biopsy specimens of patients with IgA nephropathy and compared these findings to those in patients with other immune-mediated diseases of the kidney, hereditary nephritis and normal kidney. In IgA nephropathy, C3 and factor B mRNA were expressed in the renal tubular epithelial cells, while no expression of either C3 or factor B mRNA was apparent in the glomerulus. Specimens from patients with other immune-mediated forms of chronic glomerulonephritis also showed a similar pattern of expression of C3 and factor B mRNA only in the tubules, but not in the glomerules. However, C3 and factor B mRNA were not found in normal kidney tissue or biopsy specimens from patients with hereditary nephritis. C4 mRNA was expressed in the tubular epithelial cells in all specimens examined, indicating that C4 mRNA is constitutively expressed in the human kidney. In IgA nephropathy HLA-DR alpha mRNA was observed in the interstitium, but not the tubules or glomerular cells. In contrast, HLA-DR alpha mRNA was present in the glomerulus and scattered in the interstitium in other immune-mediated kidney diseases. There was no expression of HLA-DR alpha mRNA in hereditary nephritis or normal kidney. Our findings, which reflect the immunopathogenic events in vivo, provide new insights as to the interpretation of the molecular immunology of this immune complex disease.

Adolescent

New mollusc-specific alpha-conotoxins block Aplysia neuronal acetylcholine receptors.

Two mollusc-specific neurotoxic peptides from the venom of the molluscivorous snail Conus pennaceus are described. These new toxins block acetylcholine receptors (AChR) of cultured Aplysia neurons. Bath application of 0.5-1 microM toxin induces 5-10-mV membrane depolarization, which recovers to the control level within 1-3 min in the presence of the toxin. This response is blocked by 1 mM hexamethonium. Concomitantly with the transient depolarization, the toxins block approximately 90% of the depolarizing responses evoked by brief iontophoretic application of acetylcholine. The pharmacology and amino acid sequences of the toxins (alpha PnIA, GCCSLPPCAANNPDYC-NH2; alpha PnIB, GCCSLPPCALSNPDYC-NH2) enable their classification as novel alpha-conotoxins. The sequences differ from those of previously described alpha-conotoxins in a number of features, the most striking of which is the presence of a single negatively charged residue in the C-terminal loop. This loop contains a positively charged residue in piscivorous venom alpha-conotoxins. In contrast to other alpha-conotoxins, which are selective for vertebrate skeletal muscle nicotinic ACh receptors, these Conus pennaceus toxins block neuronal ACh receptors in molluscs. As such they are new probes which can be used to define subtypes of ACh receptors, and they should be useful tools in the study of structure-function relationships in ACh receptors.

Amino Acid Sequence

Colchicine induced remission in amyloid nephrotic syndrome.

An unusual case of reversible reactive amyloidosis (AA) is described. A patient in the course of lobar pneumonia developed acute transient nephrotic syndrome and renal failure. Renal and liver biopsy showed amyloidosis and positive immunohistochemistry stains for amyloid A protein. The nephrotic syndrome resolved completely following 6 months of colchicine treatment and the urine is protein free after 6 years of follow-up.

Aged

Thrombocytopenic purpura as a manifestation of acute hepatitis A.

Extrahepatic autoimmune manifestations are rare in patients with acute hepatitis A infection. We describe a 34-year-old man in whom severe autoimmune thrombocytopenic purpura developed as the manifestation of acute hepatitis A infection. Thrombocytopenic purpura is rarely described in association with hepatitis A, but to our knowledge has never been reported as a manifestation of acute hepatitis A.

Acute Disease

Gastro-duodenal injury associated with intake of 100-325 mg aspirin daily.

During the year 1991, 43 patients with upper gastrointestinal bleeding and one with severe epigastric pain associated with intake of non-steroidal anti-inflammatory drugs were admitted for emergency endoscopy to our unit. Fourteen patients (33%) had been treated with 100-325 mg aspirin daily, 11 of them for at least one year. The mean age of this group was 71. Only two patients had a previous history of peptic ulcer. Five patients used anticoagulants or antiplatelet drugs concomitantly with aspirin. The endoscopic diagnosis of the sources of bleeding was erosive gastritis in eight patients, gastric ulcer in four, duodenal ulcer in five and oesophageal ulcer in one. Our results support findings by other groups, showing that doses of aspirin as low as 75 mg daily should be used in the management of elderly patients with thrombo-embolic disease.

Acute Disease

Recurrent infective endocarditis.

Infective endocarditis is a serious disease associated with high mortality. Patients surviving recurrent bouts of infective endocarditis are reported infrequently. We report on a non-drug abuser patient who experienced seven episodes of infective endocarditis--the largest number reported to our knowledge in a single non-drug abuser patient.

Aged

Preoperative clues to Crohn's disease in suspected, acute appendicitis. Report of 12 cases and review of the literature.

Twelve patients who underwent laparotomy for suspected acute appendicitis were found to have Crohn's disease of the terminal ileum. Appendectomy was performed in all although in only four patients was the appendix grossly inflamed. Postoperative complications, either abscess or fistula, developed in four patients (33%). Careful investigation of the records revealed some preoperative diagnostic clues: a history of recurrent abdominal pain and/or diarrhea (83%), physical examination revealing normal temperature (50%), and laboratory results compatible with a chronic process such as microcytic anemia (33%) and hypoproteinemia/hypoalbuminemia/hypocholesterolemia (50%). As the differential diagnosis between Crohn's disease and appendicitis is difficult and the surgical approach to the appendix in the presence of Crohn's disease is controversial, we illuminate some practical points in the preoperative evaluation of these patients and deal with the question of whether appendectomy should be performed in these patients.

Acute Disease

Relapsing hepatitis A. Review of 14 cases and literature survey.

We have reviewed our experience with 14 cases of relapsing hepatitis A (RH-A), as well as 68 cases reported in the literature. Relapse occurs in 3 to 20% of patients with acute hepatitis A, and rarely takes the form of a polyphasic disease (multiple relapses). After a stage of typical hepatitis A, remission phase ensues, with partial or complete resolution of clinical and biochemical manifestations. Relapse usually occurs after a short period (usually less than 3 weeks). Relapse is usually clinically milder than the first phase, with variable liver function abnormalities and a tendency toward more marked cholestatic features. Not uncommonly, immune manifestations occur during this phase, including purpura, nephritis, and arthralgia, with common laboratory findings of rheumatoid factor as well as false-positive reaction to HCV-EIA tests. The clinical course in relapsing hepatitis A is almost always benign, and uneventful recovery is the rule with few exceptions. Steroid treatment, first reported in the present series, resulted in marked clinical improvement. Preliminary results suggest that R-HA is associated with a continuing viremia as well as shedding of virus in stools during the relapse phase. The pathogenesis of R-HA probably involves an interaction between persistent viral infection and immune mechanisms responding to the continuing antigenic stimulation.

Adult

[Kaposi's sarcoma following liver transplantation].

A 54-year-old man developed Kaposi's sarcoma 2 months following orthotopic liver transplantation for hepatitis B-associated liver cirrhosis. At that time he was on combined immunosuppressive therapy (azathioprine, prednisone and cyclosporine A). The disease is very prevalent among immunosuppressed patients following renal transplantation, but is considered to be relatively rare following liver transplantation. The patient ran a relatively benign course without organ involvement and with only the skin disease. This is the first case of Kaposi's sarcoma following liver transplantation reported in Israel.

Humans