Fournier gangrene associated with Crohn disease.

A 17-year-old boy presented with Fournier gangrene associated with previously undiagnosed Crohn ileocolitis. Fournier gangrene was managed by débridement, broad-spectrum antibiotics, and hyperbaric oxygen. A diverting ileostomy was performed before skin grafting and scrotal reconstruction. Microscopy of a full-layer surgical sample from the terminal ileum revealed granulomas with multinucleated histiocytes, consistent with Crohn disease. Crohn disease was treated with mesalamine, metronidazole, 6-mercaptopurine, and infliximab. The patient was discharged on hospital day 32. At 6-month follow-up, reconstruction of his scrotum had completely healed. Ostomy output was normal.

Regulation of biliary protein secretion in dogs.

The biliary secretion of protein in response to bile acids and other agents known to increase bile flow was examined in a chronic bile fistula dog model. Infusion of 25, 50, or 75 mumole/kg/hr sodium taurocholate after 3 hr of bile fistulization increased biliary protein output significantly by 52, 86, and 108% respectively compared to preinfusion values. A proportionate increase in biliary albumin output during taurocholate choleresis was demonstrated. Protein outputs during bile fistulization without taurocholate replacement were unchanged. The non-micelle-forming bile acid dehydrocholate markedly increased bile flow but did not change protein output. Similarly, the hormonal choleretics glucagon and secretin caused significant decreases in biliary protein concentration but no change in protein output. These data indicate a correlation between biliary protein secretion and bile acid-dependent bile flow. It is likely that regulation of certain proteins is dependent on the micelle-forming properties of bile acids.

Influence of apolipoprotein E on soluble and heparin-immobilized hepatic lipase.

The effect of human apolipoprotein E (apoE), either alone or in combination with apoC, on the lipolysis of a radiolabeled triglyceride emulsion was studied with hepatic lipase in solution and immobilized on heparin-Sepharose. The soluble hepatic lipase was inhibited, whereas the heparin-immobilized lipase was stimulated by apoE. This stimulation was attenuated by combining apoE with either apoC-II or C-III. The heparin-immobilized lipase demonstrated much less lipolysis of the zwitterionic phosphatidylcholine-stabilized triglyceride emulsion than did the soluble enzyme. This difference was less when the emulsion was stabilized by a nonionic detergent. apoE inhibited lipase activity when assayed under conditions (0.4 M NaCl) of bound enzyme and unbound substrate. Increasing the emulsion apoE content beyond optimum inhibited lipolysis by the immobilized enzyme. Kinetic analysis of phosphatidylcholine-stabilized triglyceride emulsions revealed a significant decrease in immobilized enzyme Km and an increase in Vmax when the emulsion was supplemented with apoE. Distributing the immobilized lipase in clustered aggregates produced more lipolysis than when the same enzyme content was uniformly bound.

Bile flow--an index of ischemic injury.

Bile formation is an active secretory process involving bile salt-dependent and -"independent" mechanisms. This study was performed to determine the effect of selected periods of warm ischemia on biliary secretion. Rats were studied using an in situ liver perfusion system after stabilization of bile flow with intravenous sodium taurocholate. Bile flow remained stable in control livers and ceased during ischemic periods of 15 or 25 min. After reperfusion of 15-min ischemic livers, bile flow was depressed but returned to normal by 45 min of reperfusion. After 25 min of ischemia, bile flow remained depressed. A similar depression in bile salt secretion was observed. These studies indicate that both bile flow and bile salt secretion reflect the degree of ischemia in this isolated perfused system, and further use of this model for the investigation of biliary flow as an index of ischemic injury is warranted.

Adenocarcinoma of the stomach. Changing patterns over the last 4 decades.

A retrospective study was performed on 255 consecutive patients admitted to a single hospital from 1953-1983 with a follow-up of 100%. The number of proximal esophagogastric junction and fundus tumors increased significantly over the last 4 decades from 21% to 44% (p less than 0.001), accompanied by a significant decrease in antral carcinomas from 60% to 33% (p less than 0.01). Patients with proximal neoplasms were significantly more likely to be white (71% vs. 29%, p less than 0.001), whereas patients with antral cancer were significantly more likely to be black (64% vs. 36%, p less than 0.001). There were no significant differences in nodal status, presence of distant metastases, or the overall 5-year survival rate between these two sites. The 5-year survival rate for the entire group was 6%. Sixty-five patients (30%) underwent curative resection, and the 5-year survival rate in this group was 24%, which was significantly better than palliative procedures. The 5-year survival rate was strongly influenced by TNM stage, local invasiveness, nodal status, and presence or absence of distal metastases (p less than 0.001). Although the overall survival rate has not changed over the past 30 years, there were definite epidemiologic differences between proximal and antral lesions, which suggest that new treatment protocols should be designed to include the location of the neoplasm.

Effect of cyclosporine on bile secretion in rats.

Short-term effects of cyclosporine were studied in the isolated perfused rat liver model. Bile flow was inhibited by cyclosporine in 2 mg/kg and 20 mg/kg doses but not by a 0.2 mg/kg dose. Cholestasis was accompanied by a decrease in bile acid secretion, indicating an inhibitory effect on the bile acid-dependent fraction of bile flow. Perfusate bilirubin levels increased threefold in rat livers given 20 mg/kg of cyclosporine, but did not change in control animals. Alkaline phosphatase and transaminase levels did not differ from those of control animals. The isolated perfused rat liver was able to excrete cyclosporine, as demonstrated by a continual decrease in perfusate cyclosporine levels. No light microscopic evidence of cholestasis or hepatocellular damage was demonstrated on histologic staining. Our model appears to be a good one for the study of altered hepatic physiologic characteristics caused by administration of cyclosporine.

Inhibition of bile flow by intravenous arginine hydrochloride.

One proposed mechanism for the cholestasis associated with total parenteral nutrition is infusion of amino acids. Arginine, 19 mumol/kg/min, was infused for a short time in healthy dogs with a biliary fistula to test the effect of endogenous hormone release on bile flow and composition. Both plasma glucagon and blood glucose levels increased. Despite the release of the choleretic hormone, glucagon, bile flow decreased 30%. The suppression of bile flow was attributed to a decrease in the bile acid-dependent fraction of bile flow. Bile acid, cholesterol, and phospholipid output were all depressed.

Successful management of late-onset primary lymphatic hypoplasia.

Primary lymphedema of the extremities, abdomen, or chest is an unusual and difficult clinical problem with few guidelines for management. A case is reported of lymphedema acquired at the age of 61 years, with associated massive chylous ascites and chylothorax. No underlying condition was discovered and the patient was found to have hypoplastic lymphatics by lymphangiography. Initial management consisted of extremity elevation, diuresis, and repeated paracenteses and thoracenteses. A peritoneojugular shunt provided temporary relief. Surgical pleurodesis combined with intensive diuresis has given prolonged relief of his symptoms allowing him to return to a functional life. Diagnostic and therapeutic guidelines for the management of this unusual condition are suggested.

Semiquantitative computerized image analysis of fetal hemoglobin distribution patterns in sickle cell anemia and its variants.

Computerized, semiquantitative image analysis of 2913 erythrocytes from 29 young patients with sickle cell anemia and its variants was conducted utilizing a modified method for determination of fetal hemoglobin distribution by an acid elution procedure. Histograms of eight arbitrary levels of staining intensity, proportional to fetal hemoglobin levels, were analyzed in relationship to both computer-generated, mathematical parameters of erythrocytic shape abnormalities and clinical parameters of disease severity. Shifts in fetal hemoglobin distribution were observed in analysis of sequential specimens. An inverse correlation was observed between angularity of erythrocytes and their individual fetal hemoglobin content (p less than or equal to 0.05). A positive correlation was noted between growth percentiles and percentage erythrocyte ghosts by acid elution (p less than or equal to 0.01).