Significance of megamitochondria in alcoholic liver disease.

The significance of megamitochondria in the alcoholic liver injury of humans was investigated as part of a large Veterans Administration cooperative study of the natural history of alcoholic hepatitis. Two hundred twenty patients were clinically stratified into the following three groups according to disease severity using serum bilirubin and prothrombin time as indicators: Group 1 (mild disease), serum bilirubin levels less than 5 mg/dl and prothrombin time prolonged for less than 4 s; group 2 (moderate disease), serum bilirubin levels greater than 5 mg/dl but prothrombin time prolonged for less than 4 s; and group 3 (severe disease), serum bilirubin levels greater than 5 mg/dl and prothrombin time prolonged for greater than 4 s. Megamitochondria were observed in 20% of the patients (45 of 220). Of these, 43 patients were in groups 1 and 2 of severity and only 1 patient belonged in group 3. The association of megamitochondria with cirrhosis was infrequent (33%, 15 of 45 patients). The differences in severity correlated with the differences in mortality: in patients with megamitochondria, only 1 had died at 6 mo compared with 40 deaths in patients without megamitochondria. By 12 mo, there were two deaths in patients with megamitochondria versus 51 deaths in those patients without. No complications were present in 72% of patients with megamitochondria versus 39% for those without. Infection, gastrointestinal bleeding, pancreatitis, hyperglycemia, azotemia, delirium tremens, seizures, and hepatic encephalopathy were all more common in patients without megamitochondria. The patients with megamitochondria appear to represent a subcategory of alcoholic hepatitis with a milder degree of clinical severity, lower incidence of cirrhosis, fewer complications, and good long-term survival.

VA cooperative study on alcoholic hepatitis. II: Prognostic significance of protein-calorie malnutrition.

Three hundred and fifty-two patients with alcoholic hepatitis were evaluated for protein-calorie malnutrition (PCM). In order to facilitate data analysis of nutritional status, a PCM score was calculated for each patient using eight nutritional parameters. The PCM score correlated significantly with mortality, clinical severity of the liver disease, and biochemical liver dysfunction. When 30 day changes in the PCM scores were compared with 30 day caloric intake (expressed as percent basal energy expenditure (BEE], a marginally significant correlation was observed (p = 0.05). However, those patients who showed improvement in their PCM score over 30 days of hospitalization also improved their 6-mo and 1-yr survival. These data indicate that nutrition, as determined by the PCM score, has prognostic significance. Additional studies are needed to establish the beneficial role for vigorous protein-calorie nutritional therapy in the management of alcoholic hepatitis.

VA Cooperative Study on Alcoholic Hepatitis. III: Changes in protein-calorie malnutrition associated with 30 days of hospitalization with and without enteral nutritional therapy.

Patients with moderate to severe alcoholic hepatitis and features of protein-calorie malnutrition were studied with respect to changes in their nutritional status during 30 days of hospitalization. Thirty-four patients served as controls, were given a 2500 kcal hospital diet and allowed to eat ad libitum. Twenty-three patients were given, in addition to the hospital diet, a nutrition supplement high in calories, protein, and branched-chain amino acids (Hepatic Aid). Because of anorexia, the controls consumed lesser amounts of both calories and protein while those given the nutritional therapy exceeded their estimated energy requirements (116.1%) and consumed a mean of 98.3 g of protein per day. This was well tolerated despite the fact that portal systemic encephalopathy was present in 72% of the patients. Mortality associated with the liver disease was comparable in both groups, 16.7% in the treated vs 20.6% in the controls. In those patients that survived the 30 days of hospitalization, clinical and biochemical tests of liver injury improved in both groups. With respect to their nutritional status, those given nutritional therapy showed significant improvement in six of the nine parameters (67%) used to assess nutrition. In the controls significant improvement was observed in only two nutritional parameters (22%) while three parameters (33%) deteriorated further. These three were all associated with calorie deprivation (marasmus). This study suggests that patients with acute alcoholic hepatitis require additional nutritional therapy to maintain and improve their nutrition parameters, especially those related to marasmus; and that Hepatic Aid is well tolerated for this purpose.

National survey of pharmacy-coordinated investigational drug services.

A national survey of 703 pharmacy departments was conducted to obtain information on the status and scope of investigational drug services (IDS). Questionnaires were mailed to the directors of pharmacy departments of general medical and surgical hospitals with 300 or more beds and a university affiliation. The survey consisted of 27 questions that were primarily based on the ASHP guidelines for the use of investigational drugs in institutions. A total of 403 questionnaires were returned, 386 of which could be evaluated, 386 of which could be evaluated. Only 33% of the pharmacy departments adopted a minimal subset (7 of 11) of the recommended procedures based on the ASHP guidelines. All pharmacy departments with more than 40 protocols reported having a research pharmacist or a need for one. Of all of the protocols, 43% were sponsored by the National Institutes of Health, 34% by pharmaceutical companies, 16% by investigators and physicians, and 7% by various other sponsors. Drug information, monetary reimbursement for services,a dn coordination and communication were the most frequently cited areas in need of improvement by the drug sponsors. The most common types of protocols involved cancer research (56%) and infectious disease and cardiovascular studies (12% and 13%, respectively). Directors of pharmacy departments should review their investigational drug policies and procedures for compliance with ASHP guidelines as the first step in developing the IDS concept.

Periductal elastic tissue of breast cancer. Quantitative histologic study.

Using techniques of stereology, we estimated the relative volume of periductal elastic tissue in 60 infiltrating ductal carcinomas of the breast. Volume density of periductal elastic tissue in the neoplasm correlated with our own subjective histologic estimates of the amount of elastic tissue. Periductal elastic tissue had a significantly higher volume density in the neoplasm than in nonneoplastic breast, but the two estimates did not correlate with each other. Similarly, the volume density of elastic tissue in the neoplasm did not correlate with that of neoplastic cells or of stromal collagen in the neoplasm, degree of lymphocytic infiltration, lymph node metastasis, mortality, menstrual status, age, parity, or presence or levels of estrogen receptor protein in the neoplasm. On the other hand, parity correlated with the volume density of periductal elastic tissue in the nonneoplastic parenchyma of the breast. Our findings indicate that there are at least two separate elastogenic effects in infiltrating ductal carcinoma of the breast: that exerted by parity on nonneoplastic tissue and that exerted by cancer itself on the neoplasm.