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Biomedical subjects

R K Fuller

Publications and source records attributed to R K Fuller.

33 records · Page 2Linked to original sources

Immune complexes and complement abnormalities in patients with cystic fibrosis. Increased mortality associated with circulating immune complexes and decreased function of the alternative complement pathway.

Serum samples from 139 patients with cystic fibrosis (CF) were tested for complement abnormalities and circulating immune complexes (CIC). We found no consistent changes in whole complement activity. However, we found CIC in 29% of these patients and decreased activity of the alternative complement pathway (ACP) in 36%. During 5 yr of observation, mortality was much higher in patients whose sera contained CIC (p less than 0.001) or decreased ACP activity (p less than 0.01). Of patients with both abnormalities, 31% died; however, no deaths occurred in patients with normal ACP activity and negative tests for CIC (p less than 0.001). During a subsequent 2.5-yr period, 55% of patients greater than or equal to 21 yr old with both findings died. In contrast, no deaths occurred in older patients lacking this combination (p = 0.0062). Circulating immune complexes but not decreased ACP activity were an independent risk factor for death. Our findings support the hypothesis that humoral immune mechanisms may contribute to morbidity and mortality in CF.

Adolescent↗

Veterans Administration cooperative study of disulfiram in the treatment of alcoholism: study design and methodological considerations.

Disulfiram treatment of alcoholism has been difficult to evaluate in controlled studies because the study design must contend with problems unique to this drug. The therapeutic effect may be a result of the patient's fear of the disulfiram-ethanol reaction rather than a direct pharmacological effect on the craving for alcohol. Good outcome may not be directly related to compliance with the drug regimen; a patient may remain abstinent even if he does not take his medication. The Veterans Administration Cooperative Study "Disulfiram in the Treatment of Alcoholism," is a multicenter, randomized, blinded, controlled clinical trial designed to evaluate the efficacy of disulfiram while addressing these issues. Two control groups are used. The members of one control group will not receive disulfiram and will be told they are not receiving disulfiram. The members of the other control group will be given disulfiram and will be told they are receiving disulfiram; however, the dose of their disulfiram will be measured by doing pill counts and obtaining urine specimens at each clinic visit and measuring urinary diethylamine, a metabolite of disulfiram, and riboflavin (a medication marker).

Adolescent↗

The metabolic fate of double-labeled disulfiram.

The metabolic fate of disulfiram labeled with both 14C and 35S was studied in the rat. After administration of 50 mg of 14C, 35S-disulfiram dissolved in corn oil to rats by stomach tube, 95% of the radioactivity was recovered in urine, feces, and expired air at 144 hr. The major portion of the excreted radioactivity was in urine (75 +/- 6%). Feces and expired air contained 13 +/- 2% and 6 +/- 5% of the body organs or carcass. Pretreatment of rats with unlabeled disulfiram for 20 days prior to administration of 14C, 35S-disulfiram led to more rapid catabolism of the drug and more rapid excretion of radioactivity in the urine during the first 12 hr after dosing.

Animals↗

An evaluation of the efficacy of nasogastric suction treatment in alcoholic pancreatitis.

We evaluated the efficacy of nasogastric suction for alcohol-related pancreatitis by performing a randomized, controlled study. Twenty-one patients with pancreatitis associated with alcohol ingestion received either nasogastric suction or nothing by mouth in addition to intravenous fluids and meperidine as needed. Twenty patients completed the treatment to which they were assigned. There were no statistically significant differences between the group that received nasogastric suction and the group that did not in duration of abdominal pain, anorexia, abdominal tenderness, ileus, presence of abdominal masses, or elevated serum amylase and lipase activities and the ratio of the renal clearance of amylase to creatinine; or the number of meperidine injections requested per subject. Patients receiving nasogastric suction complained of significantly longer duration of nausea and vomiting. We conclude that nasogastric suction is not effective in the treatment of uncomplicated alcoholic pancreatitis.

Abdomen↗

The metabolism of 14C-disulfiram by the rat.

After administration of 14C-disulfiram to rats by stomach tube, we found that 87% of the radioactivity was excreted in urine and 7% in feces. Greater than 80% of the radioactivity was excreted by 48 hr. Small but measurable radioactivity was excreted in urine up to 144 hr after administration. Total recovery of radioactivity at 144 hr was 95% of the ingested dose with less than 1% in organs, blood, and carcass; the remainder was in urine and feces. Studies on specific radioactivity showed that diethylamine, a major urinary metabolite of disulfiram, is excreted in the urine undiluted with endogenous diethylamine. Pretreatment of rats with unlabeled disulfiram leads to a more rapid catabolism of the radioactive drug and more rapid excretion of radioactivity in the urine. Further, pretreatment appears to induce formation of a glucuronide conjugate of a disulfiram metabolite.

Animals↗

Life-table analysis of abstinence in a study evaluating the efficacy of disulfiram.

Data from a study evaluating the efficacy of disulfiram for the treatment of alcoholism were analyzed by life-table methods. Previous analysis by more commonly used statistical tests showed a trend favoring disulfiram treatment, but the results were not statistically significant. Life-table methods are the appropriate techniques for analyzing longitudinal studies because they evaluate response to treatment over time rather than at one point in time. Analysis of our data using these methods revealed that disulfiram, combined with medical care and counseling, was superior to medical care and counseling alone in 128 men followed for 1 yr. This report demonstrates: (A) the advantage of life-table methods for evaluating treatment outcome data in alcoholism studies; and (B) the importance of disulfiram treatment in alcoholic patients similar to those we studied.

Actuarial Analysis↗

Disulfiram for the treatment of alcoholism. An evaluation in 128 men.

One hundred twenty-eight alcoholic men were assigned randomly to receive either a regular dose of disulfiram (250 mg), a pharmacologically inactive dose (1 mg), or no disulfiram. There were no statistically significant differences among the three treatment groups in total abstinence, percentage of drinking days, days worked, family stability (living with same relative), or percent of scheduled appointments kept. However, 21% of those who received the regular dose of disulfiram and 25% who received the pharmacologically inactive dose remained abstinent, whereas only 12% of those who received no disulfiram did so. These results indicate that disulfiram may be of limited value in the treatment of alcoholism, fear of the disulfiram-ethanol reaction is important in preventing drinking, and patients willing to take disulfiram are more likely to be abstinent if given the drug. We also found that complete abstinence correlated significantly with compliance and obtaining employment.

Adult↗

An optimal diuretic regimen for cirrhotic ascites. A controlled trial evaluating safety and efficacy of spironolactone and furosemide.

Previous studies demonstrated the effectiveness of diuretics in mobilizing fluid, but frequent complications occur with their use in treating ascites. To develop an effective but safe regimen for treatment of cirrhotic ascites, a two-part crossover study was done. Subjects with life-threatening complications of cirrhosis were excluded. In part one it was demonstrated that a six-day diuretic regimen with dietary sodium restriction of 10 mEq/day is safe and more effective than sodium restriction alone. In part two the duration of diuretic therapy was safely extended from six to nine days with mobilization of significantly more fluid. Careful selection of subjects, use of diuretics in modest dosages for brief periods of time, and daily monitoring of subjects were important for the success of this study.

Ascites↗

Method for the detection of diethylamine, a metabolite of disulfiram, in urine.

Disulfiram is a drug used in the treatment of chronic alcoholism in man. Accurate assessment of patient compliance is important in this treatment. This paper describes a method for the detection and quantitative analysis of diethylamine, a metabolite of disulfiram, in urine. The method involves conversion of the water-soluble diethylamine in the urine to a derivative, N,N-diethyl-3,5-dinitrobenzamide, that is soluble in an organic solvent. This derivative is extracted from urine with diethyl ether and then subjected to thin-layer chromatography. A spectrophotometric procedure is used for quantification. This method provides a means of determining whether or not a patient is taking his prescribed disulfiram.

Benzamides↗

Elevated plasma carnitine in hepatic cirrhosis.

Carnitine is essential for the oxidation of fatty acids. The liver is a major site of fatty oxidation. To determine if there are alterations in plasma carnitine in patients with alcoholic cirrhosis, we measured plasma carnitine and its metabolites by a specific radioenzymatic method in 20 men with hepatic cirrhosis and 30 healthy volunteers. We found total carnitine, free carnitine, short-chain acylcarnitines, and long-chain acylcarnitines to be significantly elevated in the cirrhotic subjects. The mean values for total carnitine, free carnitine, short-chain acycarnitines, and long-chain acylcarnitines for the cirrhotic patients and the control subjects were 73.1 vs. 46.1, 47.0 vs. 36.7, 17.9 vs. 5.7 and 8.2 vs. 3.7 microM, respectively. The greatest increases were noted in the acylcarnitines; 3-fold for short-chain acylcarnitines and over 2-fold for long-chain acylcarnitines. We conclude that alcoholic cirrhosis is a hypercarnitinemic condition.

Adult↗