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Biomedical subjects

W D Warren

Publications and source records attributed to W D Warren.

At least 109 records · Page 6Linked to original sources

The rate of synthesis of glycosaminoglycans and collagen by fibroblasts cultured from adult human liver biopsies.

Adult human liver biopsies were cultured from normal, alcoholic hepatitis, chronic active hepatitis, fibrosis plus alcoholic hepatitis (active cirrhosis), inactive cirrhosis, and drug hepatitis. The synthesis of collagen was estimated in cultures from 58 livers by measuring the conversion of [(14)C]proline to the [(14)C]hydroxyproline of collagen; that of glycosaminoglycans in cultures from 57 livers by the incorporation of [(3)H]acetate and (35)SO(4) into glycosaminoglycans (GAG). The synthesis of procollagen was increased only in cultures from alcoholic hepatitis, both in the pulse medium (P < 0.05) and in the chase medium (P < 0.02). The synthesis of insoluble collagen was increased in cultures from chronic (active) hepatitis (P < 0.01), fibrosis plus alcoholic hepatitis (active cirrhosis) (P < 0.001), and inactive cirrhosis (P < 0.05). Essentially all radioactive GAG was soluble in culture media. The predominant GAG were chondroitin-4 or -6-SO(4). The synthesis of GAG was increased only in cultures from fibrosis plus alcoholic hepatitis (active cirrhosis) both in the pulse medium (P < 0.01) and chase medium (P < 0.001). The data indicate that in the absence of immuno-competent cells or their secretory products, tissue cultures from livers showing biopsy evidence of active fibrosis in vivo may demonstrate increased synthesis of collagen and GAG in vitro. Increased (soluble) procollagen synthesis in cultures from alcoholic hepatitis was not associated with histologically demonstrable overt hepatic fibrosis in vivo, nor was it associated with increased GAG synthesis in vitro. No significant difference was demonstrable in collagen or GAG synthesis in paired cultures which contained either 300 mg/dl ethanol or 3.75 mg/dl methylprednisolone compared to their respective controls.

Alcoholism↗

Selective and total shunts in the treatment of bleeding varices. A randomized controlled trial.

Two types of surgical therapy of bleeding esophageal varices were evaluated in 48 patients by a randomized controlled trial: 24 were randomized for a total shunt and 24 for the selective shunt. In two of the latter, a total shunt had to be performed for technical reasons. The fatality rates (six in the 24 total, and six in 22 selective [performed], and seven in 24 selective [randomized]), the frequency of shunt occlusion (two in each group), and of recurrent gastronintestinal bleeding (three in each group) were similar. Encephalopathy developed more often after a total shunt -- 10 of 24, or one per 58 patient-months -- than after selective (performed) -- one of 22, or one per 593 patient-months (P less than 0.005). Total shunts consistently diverted the hepatopetal mesenteric-portal flow from the liver. Deterioration of hepatic function (maximum rate of urea synthesis) was greater after total than selective shunt (P less than 0.05).

Adult↗

Portal hypertension. A new beginning for an old problem.

There are two types of shunts for the treatment of esophageal varices: total shunts or selective shunts. The various total shunts are designed to "decompress" both the portal and the variceal venous systems. In contrast, a selective shunt decompresses the varices only, and the portal pressure and presumably portal flow are not affected. The very purpose of the total shunt is the total or partial diversion of portal flow. This is the case no matter which branches of the portal and systemic venous systems are connected and whether the anastomosis is a direct one or is through a graft. In an ongoing prospective, randomized clinical trial, which now includes 46 patients, a total shunt (mesorenal H graft) and the selective distal splenorenal (Warren) shunt are compared. The operative mortality rate and the frequency of postoperative bleeding are the same. However, encephalopathy is more frequent after the total shunt (P less than 0.05), and a trend is developing which suggests a better long-term survival rate after the Warren shunt. If these trends continue, then the superiority of the Warren shunt is established in a selected group of patients who have bled at least once from their varices. If these patients continue to remain free of encephalopathy and hemorrhage will not recur, then it is probable that the Warren shunt could improve the chances of survival of cirrhotic patients with esophageal varices who did not bleed yet. The "prophylactic" value of the Warren shunt will require a multicenter, cooperative, controlled clinical trial.

Esophageal and Gastric Varices↗

Genetic and morphological study of aggregation in the cellular slime mold Polysphondylium violaceum.

A system for genetic analysis in the cellular slime mold P. violaceum has been developed. Two growth-temperature-sensitive mutants were isolated in a haploid strain and used to select rare diploid heterozygotes arising by spontaneous fusion of the haploid cells. A recessive mutation to cycloheximide resistance in one stain enables selection of segregants, which often appear to be aneuploid.-Aggregation-defective (ag-) mutants having a wide range of phenotypes were isolated in both temperature-sensitive strains after nitrosoguanidine treatment, and complementation tests were performed between pairs of these mutants. Of 380 diploids isolated, 32 showed defective aggregation and were considered to contain 2 noncomplenting ag- mutations. Among noncomplementing mutants interallelic complentation is common. Noncomplementing mutants fall into 4 complementation groups, and those within each complementation group are phenotypically similar. Statistical analysis of the results suggests that the number of complementation units involved in aggregation is about 50.

Alleles↗

Selective distal splenorenal shunt for bleeding esophageal varices.

The selective distal splenorenal shunt has been shown to be equally as effective as total portal-systemic shunting procedures in the control of variceal hemorrhage and it can now be performed with an equivalent operative mortality. It is superior to other shunts in metabolic aspects and results in a markedly decreased incidence of postoperative hepatic encephalopathy. Massive ascites constitutes a definite contraindication to the selective distal splenorenal anastomosis, but for all other suitable patients this procedure appears to be the optimal method of surgical management at this time.

Angiography↗

The metabolic basis of portasystemic encephalopathy and the effect of selective vs nonselective shunts.

Portasystemic encephalopathy has been a major deterent to the utilization of total or non-selective shunts. A procedure to determine the maximum rate of urea synthesis (MRUS) has been developed and a depression in the ability to synthesize urea has been shown to correlate closely with the development of encephalopathy. Utilizing this procedure and a modified ammonium tolerance curve, a controlled comparison was instituted between selective and non-selective shunts. Following a non-selective or total shunt, there was a definite deterioration in both the MRUS and the ammonium chloride tolerance curve which was accompanied by a high rate of clinical encephalopathy. In marked contrast, the selective shunt, which maintains portal venous perfusion of the liver, showed little or no change in the MRUS and the ammonium chloride tolerance curve following the selective shunt and there was a very low incidence of encephalopathy. The difference between the non-selective and selective shunt in maintenance of urea synthesis, metabolism of ammonium chloride, and the development of clinical encephalopathy show the selective shunt procedure to be definitively superior in this regard.

Ammonium Chloride↗