Ceruloplasmin in Wilson's disease.

Ceruloplasmin was highly purified from one patient with Wilson's disease and partially purified from a second unrelated patient. The highly purified ceruloplasmin was indistinguishable from normal ceruloplasmin by electrophoresis, tryptic peptide map, oxidase activity, and copper, amino acid, and sugar composition. The partially purified ceruloplasmin was indistinguishable electrophoretically from normal ceruloplasmin. With penicillamine therapy, ceruloplasmin disappeared from the serum of the first patient; it reappeared after the drug was discontinued. The significance of this observation in regard to the basic defect in Wilson's disease is discussed.

Drug metabolism in heavy consumers of ethyl alcohol.

Data are presented on the rate of removal of tolbutamide from the blood from studies in heavy drinking, unemployed, male alcoholic subjects. In such subjects tolbutamide was removed faster than it was in normal subjects and faster than in patients with cirrhosis who are not drinking. This rapid removal rate persists for 4 to 9 wk after hospitalization and is reproduced with 400 gm of pure ethanol in 2 or 3 wk but cannot be reproduced with lesser amounts of beverage alcohol taken outside of the experimental study. Similar acceleration of the clearance rates was observed for warfarin and for phenytoin but could not be demonstrated for aminopyrine.

Increased rate of alcohol removal from blood with oral fructose and sucrose.

The effect of oral glucose, fructose and sucrose on the disappearance rate for intravenously administered alcohol was studied in eight abstinent alcoholic subjects. The three sugars were ingested on separate days in random sequence. alcohol levels were determined at hourly intervals. During sugar ingestion, the mean rates of alcohol disappearance were: 19 plus or minus 1.4 mg/100 ml per hour (plus or minus SE), with glucose, 23.9 or minus 1.4 mg/100 ml per hour with sucrose, and 25.4 plus or minus 1.4 mg/100 ml per hour with fructose. Compared to glucose both fructose and sucrose increased the rate of alcohol from the blood. The blood levels of fructose were similar after the oral dose of 2 g/kg of fructose or 4 g/kg of sucrose.

Jejunoileal bypass for the treatment of massive obesity. Prevalence, morbidity, and short- and long-term consequences.

The jejunoileal bypass for patients 125 lb or more above their ideal body weight as an experimental procedure exchnages almost certain weight loss for many known and many yet undescribed problems. Study of the known complications has led to altered operative procedures and management techniques that lessen the impact of nearly all of the complications. All patients need occasional advice on potential complications, and most experience episodes of depletions or diarrhea that require hospital intervention. The improved versions of this surgery have not been present sufficiently long to indicate the real nature of long term changes, and careful evaluation is essential for at least small groups of these patients in order for all interested physicians to provide proper advice to the 10,000 or so patients who have already had this procedure. Careful selection of patients to identify those who will accept follow-up and seek help when needed, and to identify those with sufficient social adaptability to adjust to a change in body image, and a competent, experienced acute and chronic team for management lead to the majority of patients having a very satisfactory result. Many specific complications of massive obesity are specifically helped by this procedure. In America, this is the only treatment effective more than half of the time in the massively obese.

Intestinal-transit and lactose intolerance in chronic alcoholics.

Intestinal transit time of lactulose and malabsorption of lactose were measured by hydrogen excretion in breath following ingestion of 20 g lactulose or 25 g lactose. Patients were 20 recently drinking, adequately nourished, chronic, male alcoholics. Many (65%) complained of diarrhea while drinking actively. Small bowel transit was significantly shorter in alcoholics with diarrhea (62 +/- 8.6 min) than in normal controls (93 +/- 10.4 min, p less than 0.05). It increased significantly after 8-10 days abstinence, to a value of 101.5 +/- 11 min, not significantly different from normal controls. Following lactulose 75% of alcoholics developed diarrhea after 1-2 days compared with only 15% after 8-10 days of abstinence; 40% had diarrhea after lactose in the initial study, whereas no subjects had diarrhea from the same dose after a period of sobriety. These data suggest that drinking alcoholics have an increased sensitivity to osmotic loads, which is associated with diarrhea, shortened transit time, and lactose intolerance. Abnormalities disappeared 8-10 days following cessation of drinking and normal diet.

Thiamin in the elderly--relation to alcoholism and to neurological degenerative disease.

Status of thiamin in the elderly North American population is reviewed. Most Americans eat sufficient thiamin but about 5% of those over 60 yr old show impaired thiamin status. This is more marked in the poor, those confined in institutions, or those with illness. Thiamin responsive heart disease and Wernicke Korsakoff CNS syndromes occur in the elderly but there is no increased prevalence. Minor heart or neurological syndromes related to thiamin deficiency cannot be identified. The Recommended Dietary Allowance of thiamin provides at least 50% excess thiamin for those over 60 yr old--this amount is adequate. There is no known toxicity for thiamin.

Deficiency of fat soluble vitamins after jejunoileal bypass surgery for morbid obesity.

Significant vitamin A, E, or 25-hydroxy D deficiency occurred in 76% of 40 patients studied up to 6 years after jejunoileal bypass surgery for morbid obesity. Vitamin A was significantly lower in those who had lost 30% of their initial weight than in those who had lost less weight; however, there was no correlation of vitamin A, E, or D levels, time elapsed since surgery, or with daily intake of vitamins as subnormal values were found despite multivitamin supplementation and consumption of twice the recommended daily allowance of vitamin A. Functional derangement of retinal adaptation to darkness secondary to vitamin A deficiency was found in four of nine stable, healthy patients studied at least 18 months after surgery. There was no linear relationship between vitamin A levels and dark adapted final thresholds or with serum albumin, prothrombin time, or degree of steatorrhea. Three patients with abnormal adapted final thresholds were treated with vitamin A. Total daily intake of up to 65,000 IU of vitamin A daily for several months resulted in normalization of function in all.

Increased urinary excretion and prolonged turnover time of folic acid during ethanol ingestion.

The effect of ethanol on the kinetics of folic acid urinary excretion was studied in five chronic alcoholic patients who were maintained in a folate replete state. For 17 days, 95% ethanol was administered orally at 2-h intervals (X9). The folate pool(s) were labeled with the tritium labeled pteroyl glutamic acid at the start of the period of ethanol ingestion and at the start of a control abstinent period. The 24-h urine volume did not change with consumption of ethanol. Total urinary folate excretion was significantly greater by 20 to 40% in four of five patients during the ethanol administration period (p less than 0.05). The fall-off in urinary radioactivity corrected for total folate excretion (dpm/microgram Lactobacillus casei folate) was resolved into a biexponential decay with two distinct slopes. Ethanol caused the slope of the second component to flatten significantly with mean t1/2 of 63.7 days on ethanol versus 9.6 days off (p less than 0.05). These kinetic results are consistent with the known interference by ethanol of folate utilization in a functional tissue pool.

Bumetanide in refractory ascites of cirrhosis of the liver: a comparison with furosemide.

Bumetanide and furosemide were compared in the treatment of resistant ascites in patients with liver disease of alcoholic origin. In a prospective randomized trial, no significant difference was found in the ability of these two agents to promote natriuresis or diuresis. The duration of action was 12 hours for bumetanide and 6 hours for furosemide, but this difference was of no clinical significance.

The effect of bumetanide on the serum disappearance of warfarin sodium.

Ten normal subjects were given 0.8 mg/kg warfarin orally, and daily blood samples were taken for one week to test for prothrombin activity and warfarin levels, the latter determined specifically by a high-performance liquid chromatography method. Bumetanide at a dose of 1 mg/day was then administered for 14 days. A second dose of warfarin was given on the eighth day of bumetanide administration. The curves showing disappearance of warfarin from the blood were identical before and during bumetanide administration. The prothrombin times were similar in both studies. It is concluded that bumetanide does not influence anticoagulant activity or its duration when warfarin and bumetanide are given simultaneously.

Influence of alcohol on the pharmacokinetics of diazepam controlled-release formulation in healthy volunteers.

Twelve normal volunteers were empanelled in an open-label, three-way crossover study to evaluate the influence of alcohol on the pharmacokinetics of controlled-release diazepam capsules. Each volunteer received one 15-mg diazepam controlled-release capsule alone, concomitantly with alcohol or followed by alcohol 2 hours later. The mean plasma concentration-time profiles following both alcohol treatments were superimposable on the profile from the control. The mean plateau concentrations were observed to endure from 2 through 12 hours in all cases. The mean +/- S.D. areas under the plasma concentration-time curves from time zero to infinity were similar indicating no difference in the extent of absorption of diazepam in the presence of alcohol. The harmonic mean elimination half-lives were also similar. Overall, the pharmacokinetics and the release properties of controlled-release diazepam capsule were not influenced by alcohol in normal volunteers.

Age-related changes in the gastrointestinal system. Effects on drug therapy.

Although there are many changes in the gastrointestinal tract with aging, only those in the liver substantially influence blood concentrations and clearance of drugs. The liver mass, overall function, and blood flow decrease approximately 1% per year after age 40 to 50 years, and accordingly, the hepatic metabolism or clearance of drugs decreases in this proportion. The sensitivity of the gastrointestinal tract to usual concentrations of drugs is increased, and this, in part, accounts for the increased frequency of adverse drug reactions in elderly patients.

Internal locus of control and social support associated with some dietary changes by elderly participants in a diet intervention trial.

OBJECTIVE: Measure relationships of locus of control and social support to diet changes in an intervention trial. DESIGN: Participants in the Polyp Prevention Trial (PPT) completed Multidimensional Health Locus of Control (MHLC) and Norbeck Social Support Questionnaires (NSSQ) and modified Block food frequency questionnaires. Data were collected at baseline and 1 year later. SUBJECTS/SETTING: A convenience sample of PPT intervention (N = 68) and control (n = 43) participants at 1 clinical center participated in this ancillary study. MAIN OUTCOME MEASURES: Mean daily dietary intakes after 1 year were compared with baseline values. Intervention participants' scores for MHLC internal locus of control and NSSQ total functional network were correlated with diet changes. STATISTICAL ANALYSES PERFORMED: Group percentages were compared using the Fisher exact test; means were compared by t test. RESULTS: Groups were comparable in demographics, baseline diet, and scores for internal locus of control and total functional network. Intervention group participants made greater diet changes than control participants in intake of fat (-27 g vs -8 g), fat as a percentage of kilocalories (-8% vs -2%), fiber as grams per 1,000 kcal (7 g vs 0.3 g), and daily fruit/vegetable servings (2.0 vs 0.2). Pearson correlations of diet changes with internal locus of control scores (all P > .05) were fat grams, r = 0.031; fat as percentage of kilocalories, r = 0.023; fiber grams per 1,000 kcal; r = 0.230; and fruit/vegetable servings, r = 0.186. Correlations with total functional network scores were: fat grams, r = 0.022 (P > .05); fat as percentage of kilocalories, r = -0.108 (P > .05); fiber grams per 1,000 kcal, r = 0.276, P < .05; and daily fruit/vegetable servings, r = 0.326, P < .05. APPLICATIONS/CONCLUSIONS: Intensive and skillful dietary intervention can succeed whether or not clients bring strong internal locus of control or social support to the diet change program.

Alcoholism and associated malnutrition in the elderly.

Although most free-living people over age 55 yr use alcohol occasionally, both the fraction of people drinking and the magnitude of individual alcohol consumption decrease with every decade of age. Overall, approximately 5% of drinkers over age 55 yr use alcohol at excessive levels, i.e., sufficient to interfere with health or social functioning. As age increases, the fraction of drinkers with alcohol-caused central nervous system disease and cirrhosis increases, indicating increased sensitivity to alcohol injury. Beyond age 70 yr, new-onset alcoholism is more common than long-standing alcoholism. Malnutrition in the elderly alcoholic person is rare; it usually is caused by multiple factors, including alcohol displacing nutrient-rich diet factors, disease, limited availability of food, or altered metabolism increasing nutrient requirement. The recognition of alcohol and malnutrition problems in the elderly is more difficult than in younger people.

Oral Candida colonizes the stomach and gastrostomy feeding tubes.

The lumen of gastrostomy tubes is frequently colonized with Candida. To investigate the source of this contamination, 20 consecutive malnourished patients undergoing placement of a percutaneous endoscopic gastrostomy tube and ten ambulatory controls having routine upper endoscopy performed had both their oral cavity and gastric antrum swabbed and cultured. Percutaneous endoscopic gastrostomy tube recipients who after several weeks were still under our care (9 of 20) had the lumen of their tubes cultured. Fungi were isolated from the stomach in 13 (65%) of 20 patients undergoing percutaneous endoscopic gastrostomy tube placement but in only 1 of 10 ambulatory patients (p < .01). The species isolated from the oral cavity, the stomach, and later the gastrostomy tube were identical in most cases. We conclude that gastrostomy tubes are probably colonized by oral organisms that have made their way into the stomach.

Comparison of outcome in a 9-day and 30-day alcoholism treatment program.

At 3 and 6 months after discharge no differences in abstinence rates were found between patients who completed a 9-day inpatient alcoholism treatment program and those who participated in a 21-day treatment program.

Failure of a 2-hour motivational intervention to alter recurrent drinking behavior in alcoholics with gastrointestinal disease.

Patients (N = 114) consecutively entering a medical service with ulcer, cirrhosis or pancreatitis, currently drinking and not currently active in alcoholism treatment were randomly assigned to motivational intervention (MI) or to a control group. Increased utilization of alcoholism programs and self-reported sobriety at 10 weeks were assessed. MI consisted of three separate discussions of the relationship of the patient's disease to continued drinking and the compassionate offer of treatment. Two persons skilled in treatment also met with each MI subject and discussed treatment possibilities for them, facilitating entrance if desired. Patients in both the MI and control group were treated for their medical condition by a medical team and alcoholism treatment was always recommended. Outcome was evaluated for the period from the 10th to the 16th week after return to the community by interview of patient and household contacts and by the keeping of appointments. There were no differences between the control and MI groups, with at least 38% remaining sober for the 10-week interval; the study size was sufficient to detect reliably a 30% improvement. We conclude that additional motivational intervention to this level was not beneficial to the hospitalized alcoholic with disease. There was a statistically significant increase in sobriety among patients who either undertook alcoholism therapy, accepted all parts of the study or kept clinical appointments.

Colon polyps in the elderly: appropriate primary care follow-up.

The presence of adenomatous polyps in the colon identifies patients at increased risk of colon cancer. Removal of such polyps and undertaking repeated future examinations is proven to diminish subsequent development of the disease. Discussing with the patient, at the time of index colonoscopy, the need for repeat examination and including a note in the patient's medical record are not by themselves adequate measures of obtaining follow-up. A reminder letter mailed directly to the patient shortly before the desired appointment is a highly effective method of obtaining follow-up, when accompanied by information on the importance of repeat colonoscopy.