Effect of pH on the stability of methacholine chloride in solution.

Methacholine chloride bronchoprovocation challenges are performed for the diagnosis and investigation of hyperreactive airways. Over the last 20 yrs various formulations and pH values for the preparation of solutions of methacholine have been described. To determine the stability of methacholine chloride solutions prepared in a variety of buffers with differing pH values and under varying storage temperatures, we measured methacholine concentrations at intervals from 1 to 5 weeks. It was found that methacholine chloride solutions rapidly decompose if the pH is greater than 6 and that decomposition is more rapid as the pH is raised; solutions at pH 9, i.e. bicarbonate buffer, and stored at 27 degrees C have degradation up to 36% after only one week. Solutions of the same pH but prepared in different buffers can have both varied rates of deterioration and different absolute amounts of methacholine hydrolysed, e.g. solutions prepared in pH 9 borate buffer and stored at 27 degrees C have up to 60% degradation after 1 week. Solutions prepared in saline are stable probably because methacholine solutions are weakly acidic. The results emphasise the importance of preparing methacholine chloride in the proper buffers for use in the accurate assessment of airway responsiveness.

Shunt surgery versus endoscopic sclerotherapy for variceal hemorrhage: late results of a randomized trial.

Between September 1982 and April 1988, 60 cirrhotic patients with prior variceal hemorrhage were randomized to undergo the placement of an elective shunt (distal splenorenal: 26; nonselective: 4) or long-term endoscopic sclerotherapy (n = 30). Eighty-six percent of patients had alcoholic cirrhosis, and 33% were classified as Child's class C. After a mean follow-up of 87 months, 60% of patients undergoing sclerotherapy and 17% of shunt patients experienced rebleeding (p < 0.001). Shunt patients have survived longer than those who had sclerotherapy (6-year survival rates of 53% and 26%, respectively; p < 0.05). In part because of the wide geographic distribution of patients, only 4 of 13 patients in whom sclerotherapy failed (31%) could undergo salvage by shunt surgery. Although hepatic portal perfusion was better maintained after sclerotherapy, there were no major differences between the groups in terms of post-therapy hepatic or psychoneurologic function. In a predominantly alcoholic cirrhotic patient population (half non-urban), the results of elective shunt surgery were superior to those of chronic endoscopic sclerotherapy with respect to the prevention of recurrent variceal hemorrhage and survival.

Changing patterns in surgery for chronic renal artery occlusive diseases.

We report 66 patients undergoing 69 operations for chronic renal artery occlusive diseases operated on at two institutions between January 1985 and June 1990. Etiology was atherosclerosis in 59 patients (90%); fibromuscular disease in four (6%), and three children with nonfibromuscular disease stenosis (4%). Atherosclerosis was local in 10 and generalized in 49 (83% of all patients). Fifty operations (72%) were for salvage of renal function. Average serum creatinine was 2.3 mg/dl and was elevated in 46 patients (70%). Donor arteries for reconstruction were aorta 20 (29%), aortic graft 16 (23%), and other abdominal arteries 33 (48%). Twenty-one patients had concomitant vascular procedures including 16 aortic replacements. The two operative deaths (3%) followed aortic replacements. Three grafts (4%) occluded before discharge from the hospital. Eighty-six percent of patients undergoing renal salvage avoided long-term dialysis. In past decades fibromuscular disease and localized atherosclerosis were the most frequent renal artery occlusive diseases undergoing surgery, hypertension was the predominant indication, and the most frequent operation was aortorenal bypass. As a result of improved pharmacologic management of hypertension and the development of percutaneous transluminal dilation, most patients in this series had far advanced generalized atherosclerosis, and renal salvage was the most frequent indication for operation. As a consequence of the severity of the atherosclerosis, 48% of operations avoided the aorta, 23% replaced the aorta, and aortorenal bypass was used in only 29%.

Plasma postheparin diamine oxidase activity. Development of a simple technique of assessing Crohn's disease.

Plasma diamine oxidase (DAO) activity may reflect intestinal involvement in Crohn's disease. The purpose of this study was to develop a simple heparin stimulation test for assessing postheparin plasma diamine oxidase activity in Crohn's disease. Ten volunteers and five patients with Crohn's disease received 1000 units and 3000 units of heparin intravenously and plasma samples were obtained at timed intervals. Plasma DAO activity increased significantly, compared with basal values, 30 minutes after 3000 units of heparin in both volunteers (26.2 +/- 5.0 vs. 4.5 +/- 0.5 units/ml) and patients with Crohn's disease (14.6 +/- 2.0 vs. 4.0 +/- 1.1 units/ml, P less than .05) and was significantly greater in the volunteers. There was no significant increase in DAO activity after 1000 units of heparin. Plasma DAO activity increased significantly within 15 minutes after 3000 units of heparin and remained at this high level at 60 minutes. Postheparin DAO activity correlated with the integrated area under the DAO activity curve. Plasma DAO activity correlated with the Crohn's Disease Activity Index in the patients with Crohn's disease. Plasma DAO activity, 30 minutes after the intravenous administration of 3000 units of heparin, should reflect intestinal involvement in Crohn's disease.

Shunt surgery versus endoscopic sclerotherapy for long-term treatment of variceal bleeding. Early results of a randomized trial.

In September 1982, a prospective randomized trial comparing shunt surgery and endoscopic sclerotherapy for the elective management of variceal hemorrhage in patients with cirrhosis was initiated. Twenty-seven patients have received shunts (distal splenorenal = 23, nonselective = 4) and 30 patients have had chronic sclerotherapy. Eighty-six per cent of patients had alcoholic cirrhosis and 33% were Child's class C. After a mean follow-up of 25 months, 19% of shunt and 57% of sclerotherapy patients have had rebleeding (p = 0.003). Kaplan-Meier survival analysis reveals similar 2-year survival rates for shunt (65%) and sclerotherapy (61%) groups. Only two of 10 sclerotherapy failures have been salvaged by surgery. Posttherapy quantitative hepatic function, frequency of encephalopathy, and cumulative medical costs were similar for both groups. Hepatic portal perfusion and portal pressure at 1 year were better maintained by sclerotherapy than by distal splenorenal shunt. In conclusion, endoscopic sclerotherapy and shunt surgery provide similar results with respect to survival, hepatic function, frequency of encephalopathy, and costs. Sclerotherapy is an acceptable, but not superior, alternative to shunt surgery for treatment of variceal hemorrhage.

Effects of altered portal hemodynamics after distal splenorenal shunts.

Patients with cirrhosis who had undergone the distal splenorenal shunt were grouped based on preoperative to early postoperative changes in hepatic portal perfusion and corrected sinusoidal pressure. Early and late postoperative morbidity and mortality rates were determined for each hemodynamic group. Morbidity was least when both hepatic portal perfusion and sinusoidal pressure were maintained near preoperative levels (Group 1). Survival for this group was significantly better than for patients who lost portal flow to the liver during the early postoperative interval (Group 4). Patients with absent hepatic portal perfusion had the worst survival and greatest morbidity. Intermediate results were achieved for the two groups of patients that had postoperative preservation of portal perfusion but significant preoperative to postoperative alterations in sinusoidal pressure. Although survival curves for these two groups were not significantly different from Group 1, morbidity was greater, especially for patients with an increase in sinusoidal pressure (Group 2).

Selective operative approach for variceal hemorrhage.

Since 1978, the operation chosen for patients with variceal hemorrhage has been based on preoperative hemodynamic and clinical factors. One hundred sixteen consecutive patients were managed with the following operations: distal splenorenal shunt (75 patients), nonselective shunts (33 patients), and nonshunting operation (8 patients). Emergency surgery was required in 19 percent of patients. The selection criteria used resulted in the majority of high risk patients receiving nonselective shunts. This selective operative approach resulted in an overall operative mortality of 12 percent, a median survival of 3 years, and postoperative encephalopathy, ascites, and recurrent variceal hemorrhage in 20, 23, and 11 percent of patients, respectively. Operative mortality for the total group was closely related to Child's class. Whereas encephalopathy was most frequent after nonselective shunts, ascites was more common after the distal splenorenal shunt. Recurrent hemorrhage rarely occurred after a shunting procedure, but was a frequent complication of nonshunting operations. Neither the type of procedure selected nor the cause of liver disease influenced long-term survival.