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Biomedical subjects

D Kershenobich

Publications and source records attributed to D Kershenobich.

18 recordsLinked to original sources
PubMed1992

Phase II study of the safety and efficacy of a 5-lipoxygenase inhibitor in patients with ulcerative colitis.

We examined the effects of an inhibitor of 5-lipoxygenase (A-64077) in 11 patients with mild to moderately active ulcerative colitis (UC). Treatment was a daily oral dose of 800 mg for 28 days. Physicians global rating (scale 1-50) included stool characteristics, rectal bleeding, abdominal and rectal pain, urgency, and general well being; sigmoidoscopic evaluation (scale 1-15) included mucosal vascular pattern, erythema, granularity/ulcerations, friability, and exudate. All of the patients experienced a decrease in discomfort of their disease, and the gross appearance in the sigmoidoscopy improved in eight of them, but were not accompanied by histologic improvement. No significant side effects occurred. A long-term controlled double-blind and dose-effect trial using 5-lipoxygenase inhibitors is needed which may lead to a new therapeutic approach in UC.

Administration, Oral↗
PubMed1990

Effect of colchicine on lymphocyte and monocyte function and its relation to fibroblast proliferation in primary biliary cirrhosis.

Lymphocyte and monocyte function was investigated in eight patients with primary biliary cirrhosis and in age-matched and sex-matched controls. In three of the eight cirrhotic patients, two were in the late stage of the disease (stage III) and concanavalin A-induced suppressor cell function was markedly decreased; it returned to normal levels after 1 mo of treatment consisting of 5 mg per week of orally administered colchicine. The relative percentage of T cell subsets (CD3, CD4 and CD8) and the mean percentage of the helper and the suppressor phenotype were similar in cirrhotic patients and in controls. Basal production of interleukin-1 activity by a monocyte-enriched fraction of peripheral blood mononuclear cells of cirrhotic patients was three-fold above control values: after stimulation with endotoxin, interleukin-1 values increased tenfold above basal levels in monocyte-enriched fraction of peripheral blood mononuclear cells of both normal and cirrhotic patients. Colchicine normalized the basal production of interleukin-1 and inhibited its stimulation by endotoxin by 50%. Culture supernatants of endotoxin-stimulated monocyte-enriched fraction of peripheral blood mononuclear cells increased the proliferation of cultured human skin fibroblasts by 50%. In contrast, supernatants from stimulated monocyte-enriched fraction of peripheral blood mononuclear cells obtained from colchicine-treated patients significantly inhibited fibroblast proliferation. These findings suggest that stimulated chronic inflammatory cells may play an important role in liver fibrosis. Some of the actions of colchicine could be related to its effects on lymphocyte and monocyte function.

Adult↗
PubMed1988

Colchicine in the treatment of cirrhosis of the liver.

There is preliminary evidence that colchicine, an inhibitor of collagen synthesis, may be beneficial in the treatment of cirrhosis of the liver. To evaluate the use of colchicine (1 mg per day, five days per week) in the treatment of hepatic cirrhosis, we performed a randomized, double-blind, placebo-controlled trial in which 100 patients were followed for up to 14 years. Forty-five patients had alcoholic cirrhosis, 41 had posthepatitic cirrhosis, and the remaining 14 had cirrhosis with various other causes. Histologic studies were available for 92 percent of patients. Seventy-three patients were in Child-Turcotte class A, 26 were in class B, and one was in class C. Fifty-four patients received colchicine, and 46 received placebo. The overall survival in the colchicine group was markedly better than in the placebo group (median survival, 11 and 3.5 years, respectively; P less than 0.001). The cumulative 5-year survival rates were 75 percent in the colchicine group and 34 percent in the placebo group; the corresponding 10-year survival rates were 56 percent and 20 percent. Among the 30 patients treated with colchicine who underwent repeated liver biopsies, histologic improvement was seen in 9; the liver appeared normal in 2, and 7 had minimal portal fibrosis. No histologic improvement was observed in the 14 members of the placebo group who had two or more biopsies. Few side effects were observed in either group.

Clinical Trials as Topic↗
PubMed1979

Treatment of cirrhosis with colchicine. A double-blind randomized trial.

As part of a double-blind, randomized, controlled trial to evaluate the effect of colchicine on liver cirrhosis, 43 cirrhotic patients were assigned to either a placebo (20 patients) or a colchicine (23 patients) treatment group. Colchicine 1 mg and an indistinguishable placebo were administered orally on a daily dose 5 days a week. In the colchicine group, 12 were males and 11 females, while in the control group 13 were males and 7 females. The time elapsed between diagnosis and inclusion in the study was 14.1 mo for the controls and 14.5 mo for the patients on colchicine. Mortality related to the liver disease occurred in 4 patients on colchicine and 8 patients on placebo. Although the probability of surviving in the colchicine group was greater than that of the placebo, the difference did not reach statistically significant levels. Of the colchicine-treated patients, in three a remarkable decrease in liver fibrosis was observed in serial biopsies. In two other patients, carcinoma of the liver developed. Six of the survivors on colchicine have improved clinically, noticing disappearance of ascites and edema, as well as a decrease in the size of the spleen. All the survivors on placebo continue to show clinical deterioration. In contrast to the usual drop of serum albumin seen in the cirrhotic patients, those receiving colchicine increased and maintained their serum albumin levels throughout the study. Serum proline values were elevated only in the alcohol cirrhotic patients. Serum alkaline phosphatase increased only in those patients receiving colchicine. The results indicate that in some cases, liver fibrosis could be modified by treatment with antifibrotic drugs. The use of colchicine at present should remain within controlled studies.

Adult↗
PubMed1976

Hepatic fibrosis.

Explore the source record for details and available documents.

Amino Acids↗
PubMed1975

Effect of colchicine on collagen, albumin and transferrin synthesis by cirrhotic rat liver slices.

Collagen synthesis was found to be increased in liver slices of rats made cirrhotic by chronic administration of CCl4. The liver function was impaired, as determined by an increased retention of conjugated bilirubin and low serum albumin values. However, when animals received colchicine simultaneously with CCl4, collagen synthesis and deposition were inhibited, and the liver function appeared normal. When a group of rats was made cirrhotic by chronic administration of CCl4, and then kept for 30 days without further treatment, fibrosis persisted and collagen synthesis was very low. However, the liver function was severely impaired. When similar rats received L-azetidine-2-carboxylic acid during the 30-days period following CCl4 administration, there was a slight but not significant improvement in liver function. The collagen synthesis and the extent of fibrosis were similar to the controls. However, if similar rats received colchicine during the 30 days period, collagen synthesis was almost negligible, there was a slight decrease in fibrosis and there was a great improvement in liver function. In all the cirrhotic animals studied, transferrin biosynthesis remained constant.

Animals↗
PubMed1975

Serum free proline and free hydroxyproline in patients with chronic liver disease.

Serum free proline and free hydroxyproline were determined in 71 patients with liver disease and in 62 control subjects. The group with liver disease included 60 patients with liver cirrhosis and 11 with chronic active liver disease. Forty-five of the cirrhotic patients were alcoholics, 9 of which were studied during an episode of alcoholic hepatitis. The control group consisted of 24 healthy volunteers, 19 primary malnourished patients, and 19 severely ill patients without liver disease. The values obtained in normal subjects were quite constant; no differences related to sex or age were detected. In patients with malnutrition, and especially in severely ill patients, the proline values were always below the normal limit. Patients with nonalcoholic cirrhosis or chronic active liver disease had serum proline and hydroxyproline values similar to those of normal subjects. However, the patients with alcoholic liver cirrhosis had proline and hydroxyproline values significantly higher than the normal group. Furthermore, in patients with alcoholic hepatitis the serum free proline values were significantly higher than in the other groups. The results suggest that alcohol might have a direct effect on proline metabolism or facilitate its release from the liver cell.

Adolescent↗
PubMedDate not supplied

[Liver transplantation in Mexico. Report of the first successful case].

This article reports the first successful human orthotopic liver transplantation performed in Mexico. The recipient was a 41 year old white male, with a history of essential hypertension and hepatitis in 1975. The diagnosis of postnecrotic cirrhosis was made in 1985 by liver biopsy. The HBsAg was negative and the functional reserve of the liver was limited (Stage "C" of the Child-Pugh classification). A liver graft was obtained through the National Cadaver Organ Transplant Program on May 2, 1988 and an orthotopic liver transplantation was performed without incidents, using the portosystemic veno-venous bypass. Inmunosuppression was carried out with triple drug therapy, cyclosporine, azathioprine, and prednisone. His postoperative course was characterized by idiopathic cholestasis, one episode of acute rejerction, arterial hypertension, renal dysfunction, esophageal herpes and inguinal lymphocele, all of which resolved. Currently the patient is alive 22 months postransplantation with normal liver function and adequate quality of life.

Adult↗
PubMedDate not supplied

[Seroprevalence of viral markers of hepatitis B among health professionals. Multicenter study in Mexico].

To determine the prevalence of serological markers for hepatitis B infection among health care workers (HCW) in Mexico we surveyed 1072 volunteers from 26 hospitals in 12 states, from which only 1017 fulfilled the inclusion criteria: 82 patients (8.1%) were excluded because of lipemic and/or hemolyzed serum, leaving 935 persons in the study. The study population consisted of physicians, nurses, laboratory chemists, health laboratory technicians and odontologists. All of them had been working in their respective fields and in contact with biological materials for at least 12 months. None of them had been vaccinated for hepatitis B. We determined the presence of HBsAg and anti-HBs by the ELISA method. The participants' mean age was 31.4 years (range: 18-72) and their mean working time was 7.8 years. 615 were female and 320 male. The HBsAg was positive in 11 (1.2%) and the anti-HBs in 91 cases (9.7%). These results suggest that HCW in Mexico have a greater relative risk of becoming infected with the HB virus than the general population. Relative risks were particularly higher for the health laboratory technicians and the physicians. These results confirm that biohazard measures must be reinforced and that the application of HB virus vaccine could be recommended for health care workers.

Adolescent↗
PubMedDate not supplied

[Endotoxins and liver].

Endotoxins are macromolecules containing lipopolysacharides that form part of the bacteria wall. They are released only when the cell integrity is lost. They are suceptible to be absorved and pass to the portal circulation. However, in normal individuals endotoxins are not detected in peripheral blood, due to a filter effect of the liver. The possibility that liver failure could produce alterations in the detoxification of endotoxins is analyzed as well as the role of endotoxins to initiate or perpetuate liver damage. The biological effects of endotoxins on bile secretion, liver circulation, energy and carbohydrate metabolism in the liver are described.

Bile↗