Judith S. Gavaler

Blood ethanol levels in sober alcohol users seen in an emergency room

Abstract During the course of two years, 76 representative subjects seen in a community hospital emergency room who admitted to having recently used alcohol while still appearing sober had their blood alcohol levels measured to determine the levels of blood alcohol present in ambulatory sober alcohol users. As a group the mean blood alcohol level obtained in those who had measurable levels was 268 ± 10 mg/dl mean ± SEM). More men (47) than women (18) admitted to having used ethanol and had measurable blood ethanol levels and therefore were studied. Moreover, the mean blood alcohol level in the men studied was arithmetically greater (272 ± 13 mg/d1) than that present in the women (260 ± 13mg/d1). The range of alcohol levels seen in the two sexes, however, were quite similar. Using a blood alcohol level > 200 mg/dl in a clinically “non-intoxicated” individual as the cut-off level for defining one as a suspect chronic alcohol user, our data would suggest that such individuals not uncommonly have blood alcohol levels as high as 290 ± 9 mg/dl.

Response to interferon α therapy is influenced by the iron content of the liver

Seventy-nine subjects (19 women and 60 men) with chronic viral hepatitis were studied to determine the role of hepatic iron and its biochemical correlates in determining response to interferon α therapy. Each subject was treated for 6 months with interferon α . A total of 45 (57%) subjects achieved either a full or partial response. No differences between responders and non-responders were evident for the type of hepatitis, age, initial alanine aminotransferase, serum iron, total iron binding capacity, %sat, or ferritin. In contrast, the hepatic iron content of non-responders was almost twice that of responders (1156±283 μ g/g dry weight vs. 638±118; p

Nonalcoholic Cirrhosis Associated With Neuropsychological Dysfunction in the Absence of Overt Evidence of Hepatic Encephalopathy

Although much is known about the neuropsychological functioning of cirrhotic individuals with Laennecs (alcohol associated) cirrhosis, little is known about the neuropsychological functioning of individuals with nonalcoholic cirrhosis. In the present investigation, we have determined that individuals suffering from chronic nonalcoholic cirrhosis, despite the absence of clinical signs of hepatic encephalopathy, are impaired on neuropsychological tests that measure visuopractic capacity, visual scanning, and perceptual-motor speed. In contrast, intellectual, language, memory, attentional, motor, and learning abilities are intact. In comparison with a chronically ill control group of patients suffering from Crohns disease, individuals with advanced nonalcoholic cirrhosis exhibit less emotional disturbance, but are more impaired in their daily activities. These findings indicate that individuals with nonalcoholic cirrhosis, even in the absence of overt clinical signs of encephalopathy, manifest neuropsychological impairments and experience significant disruption in the routines of everyday living.

Ethanol Inhibition of Vitamin A Metabolism in the Testes: Possible Mechanism for Sterility in Alcoholics

Vitanin A (retinol) is essential for spermatogenesis. Alcohol dehydrogenase, the enzyme responsible for ethanol metabolism, is also required for the conversion of retinol to bioactive retinal at the end organ site. Ethanol inhibits the oxidation of retinol by testicular homogenates containing alcohol dehydrogenase. Thus, a possible biochemnical mechanism for the sterility of chronic alcoholics is identified.

Effects of renal impairment on liver transplantation

To determine the incidence, prevalence, and prognostic value of preoperative and postoperative renal dysfunction occurring in adults undergoing orthotopic liver transplantation, the records of 102 consecutive adults who underwent orthotopic liver transplantation using cyclosporin A were reviewed. Renal dysfunction was defined arbitrarily as an increase in creatinine or blood urea nitrogen, or both, to 1.5 and 50 mg/dl, respectively, in patients previously having normal renal function or a 50% increase in either creatinine or blood urea nitrogen in patients with preexisting renal dysfunction. Twenty-six of the 102 patients had renal dysfunction before orthotopic liver transplantation. Sixty-eight of the 102 patients studied experienced an episode of renal impairment after orthotopic liver transplantation. Forty-nine of these episodes developed early, having occurred within the first 6 days. Late renal impairment occurred in 36 cases at 32 +/- 6 days after orthotopic liver transplantation. Using multivariate analysis, cirrhosis of a noncholestatic nature was found to be an independent predictor of early renal impairment. Trough blood cyclosporin A levels measured by radioimmunoassay were higher in those who experienced early renal impairment or late renal impairment than in those who did not (p less than 0.05). Several factors capable of adversely influencing renal function (nephrotoxic drugs, shock, and graft failure) other than cyclosporin A were present also in half of the patients who developed late renal impairment. Overall, 25 patients died. Multivariate analyses identified serious postoperative infection, graft failure, and preoperative renal dysfunction to be independent predictors of mortality.

Effect of pregnancy on gastrointestinal transit.

In order to evaluate the possible effects of pregnancy-associated sex steroids on gastrointestinal function, we determined gastrointestinal transit times and sex steroid levels in 15 women during the third trimester of their pregnancies and again 4–6 weeks following delivery when gastrointestinal function had symptomatically returned to normal. Gastrointestinal transit time from ingestion of a liquid lactulose meal to its delivery to the cecum was determined by monitoring breath hydrogen concentrations at 10-min intervals. Gastrointestinal transit times were significantly prolonged in the third trimester of pregnancy, when progesterone and estradiol levels were increased, compared to the postpartum period. This study supports previous findings which suggest that increasing levels of progesterone and estradiol affect gastrointestinal function and therefore may contribute to gastrointestinal symptoms that often occur in pregnant women.

Colonie Polyps in Patients with Acromegaly

Seventeen patients with acromegaly were prospectively studied with barium enemas and colonoscopy to investigate the possibility that acromegaly is associated with an increased frequency of colonic polyps and colon cancer. Polyps were identified in nine patients and were removed and examined in eight. In five patients the polyps were adenomatous, and in four of the five there were multiple polyps. The presence of polyps closely correlated with the presence of skin tags (p = 0.041) and also with the age of the patient (p less than 0.01). No new cases of colonic cancer were discovered; however, reviewing the records of 44 patients with acromegaly, four cases were previously diagnosed with colon carcinoma. This study identifies a unique group of patients that are at risk for the development of colonic polyps and perhaps colon cancer.

Plasma estrone, prolactin, neurophysin, and sex steroid-binding globulin in chronic alcoholic men.

The feminization frequently observed in men with alcoholic liver disease has not been satisfactorily explained by existing reports. We have measured plasma estrone, prolactin, estrogen-stimulated neuorphysin, and sex steroid-binding globulin concentrations in 50 men with chronic alcoholism and varying degrees of alcoholic liver disease in an effort to further elucidate possible hormonal mechanisms responsible for the observed feminization. Plasma concentrations of each of these parameters were at least two-fold elevated (p smaller than or equal to 0.01) when compared to values obtained for the same steroid or protein in plasma obtained from normal men. The plasma concentrations of estrone and prolactin in men studied with synecomastia were significantly greater (p smaller than or equal to 0.01 and p smaller than or equal to 0.05, respectively) than were the concentrations of these two hormones in those without this physical sign. Similarly, those men with spider angiomata had significantly greater (p smaller than or equal to 0.01) plasma estrone levels than did the men without this cutaneous vascular abnormality. These significant hormone elevations may contribute to the pathogenesis of feminization so frequently observed in chronic alcoholic men.

Alcohol-Induced Ovarian Failure in the Rat

The effect of ethanol feeding on ovarian function and structure in female rats was studied in alcohol-fed animals, isocalorically fed controls, and two ad libitum-fed control groups. Ovarian weight was reduced by 60% in alcohol-fed animals compared with the control groups. Gross disruption of ovarian architecture was noted, characterized by the absence of any corpus hemorrhagicum and corpus albicans. Moreover, plasma levels of estradiol were significantly reduced in the alcohol-fed animals (P < 0.01) compared with the levels found in isocaloric controls. Plasma levels of estrone and corticosterone were increased in alcoholfed and isocaloric control animals relative to those of ad libitum-fed animals suggesting a primarily adrenal, rather than ovarian, origin for these two steroids. Despite the increase in estrone, the secondary sex organs (uterus and fallopian tubes) reflected marked estrogen deprivation presumably as a result of estradiol insufficiency. Progesterone levels in the alcohol-fed animals were significantly less than levels in the isocaloric and intact ad libitum-fed controls but were not significantly different compared to oophorectomized animals. Plasma follicle-stimulating hormone levels were similar in alcohol-fed, isocaloric controls, and ad libitum-intact controls. They were, however, one-third the level of oophorectomized controls. Both alcohol-fed and isocaloric controls had increased levels of plasma luteinizing hormone, although levels were below those seen in oophorectomized controls (P < 0.01). The results establish that ingestion of a diet containing 5% ethanol for periods as short as 6 wk produces functional and histologic ovarian failure in the female rat.

Impairment of gallbladder emptying in diabetes mellitus.

Individuals with diabetes mellitus are reported to have a twofold to threefold increase in the incidence of cholesterol gallstones. A frequently cited but unproven pathophysiologic mechanism for this phenomenon is reduced gallbladder muscle function, which results in stasis and allows for cholesterol gallstone crystal formation and gallstone growth. To date, gallbladder motor function has not been investigated in a well-characterized diabetic population. Therefore, using radionuclide cholescintigraphy, gallbladder filling and subsequent emptying produced in response to an infusion of the octapeptide of cholecystokinin in 30 diabetic patients and 20 control individuals were studied. No difference in any parameter used to assess gallbladder filling was demonstrated in the diabetics when compared with controls. In contrast, gallbladder emptying induced with cholecystokinin-octapeptide (20 ng/kg body wt . h) was reduced in diabetics compared with controls (55% +/- 5% vs. 74% +/- 4%, p less than 0.01). The peak emptying rate in the diabetics was also decreased (5.0% +/- 0.5% per minute) compared with the controls (7.0% +/- 0.6% per minute, p less than 0.02). The observed decreased gallbladder emptying found in diabetics was not related to obesity, type of diabetes, diabetic control, or presence or absence of peripheral neuropathy. The most severe impairment of gallbladder emptying occurred, however, in diabetics with an associated autonomic neuropathy. This subgroup demonstrated a significant reduction in the percentage of gallbladder emptying (40% +/- 8% vs. 62% +/- 5%, p less than 0.04) and the peak ejection rate (3.5% +/- 0.5% per minute vs. 5.6% +/- 0.6%, p less than 0.02) compared with the diabetics without autonomic neuropathy.