Biomedical subjects

J P Kromhout

Publications and source records attributed to J P Kromhout.

5 recordsLinked to original sources

PubMed1984

The effect of lactulose on psychomotor performance tests in alcoholic cirrhotics without overt hepatic encephalopathy.

Thirty-two alcoholic cirrhotics without clinical evidence of encephalopathy were randomized to lactulose or sucrose treatment in order to evaluate the effects of chronic lactulose therapy on five psychomotor performance tests. Statistically significant improvement was seen in three of the five tests in the lactulose-treated group, while no significant improvement in any test was noted in the sucrose group. However, because of the limited extent of improvement in the lactulose treated group, problems with medication intolerance, and lack of improvement in complex psychosocial behavior, the impact of chronic lactulose therapy on mental function in cirrhotics without overt encephalopathy appears to be limited.

Adult↗

PubMed1981

Hyperprolactinemia in portal systemic encephalopathy.

The accumulation of false neurotransmitters such as octopamine and depletion of true neurotransmitters such as dopamine have been purported to play a pathogenetic role in portal systemic encephalopathy (PSE). Therefore, we measured plasma prolactin, a known sensitive indicator of functional dopamine activity in man, in an attempt to evaluate dopaminergic function in 21 patients with alcoholic liver disease and PSE and several control groups. Subjects with PSE had markedly elevated prolactin levels (P less than 0.01) when compared to all control groups. Moreover, patients with PSE were divisible into two groups, 12 having mildly increased prolactin levels and 9 having markedly elevated levels. Although the degree of PSE was similar in both groups, those PSE patients with the higher prolactin values had significantly greater derangement of serum albumin, bilirubin, prothrombin time, and also had a higher mortality (100%). These data: (1) provide evidence consistent with the hypothesis of altered neurotransmitter function in individuals with chronic alcoholic liver disease, particularly those manifesting evidence of PSE; (2) suggest that altered dopamine function in chronic liver disease may have pathophysiologic significance as judged by altered hormone release; (3) demonstrate that a markedly elevated plasma prolactin level in individuals with PSE carries an ominous prognosis; and (4) suggest a possible role for the plasma prolactin in the selection and monitoring of PSE patients who are to be treated with agents aimed at correcting neurotransmitter abnormalities.

Dopamine↗

PubMed1981

Effect of sorbitol on psychomotor function: its use in alcoholic cirrhosis.

Sorbitol solution has been used to a control substance of evaluating the efficacy of lactulose therapy for hepatic encephalopathy (HE). However, recent in vitro studies suggested that sorbitol may be an inert placebo and may have therapeutic relevance. We evaluated in vivo metabolism of sorbitol in healthy volunteers and alcoholic cirrhotic patients and found that sorbitol was metabolized by gut bacteria in a similar manner to lactulose. We next evaluated the effect of sorbitol treatment on five psychomotor performances tests in cirrhotic patients. Patients receiving sorbitol demonstrated improvement in all psychomotor tests, whereas similar patients not receiving sorbitol showed no improvement. We conclude the following: sorbitol is metabolized by gut bacteria in man, sorbitol therapy improved psychomotor performance in cirrhotic patients, and previous studies using sorbitol as a control underestimated the beneficial effects of lactulose.

Humans↗

PubMed1980

Potentiation of acetaminophen hepatotoxicity by alcohol.

Severe liver failure developed in three chronic alcoholics after they ingested acetaminophen for therapeutic reasons. The clinical course was characterized by SGOT levels of 5,000 to 10,000 IU. Concomitant renal failure developed in two of these patients, and one died in hepatic coma. To determine whether alcohol enhances acetaminophen hepatotoxicity, a lethal dose for 50% survival of a test group (LD50) was performed for mice fed 10% alcohol in their water supply for three weeks and for mice receiving a normal diet only. A significant reduction in the LD50 was seen in the alcohol-pretreated mice, and correlations were noted between histological findings in the liver and the LD50 data. These findings suggest that alcohol enhances acetaminophen hepatotoxicity in mice and provides supportive evidence that these three alcoholic patients probably had a similar pathophysiological basis for their liver disease.

Acetaminophen↗

PubMed1976

Antibiotic penetrance of ascitic fluid in dogs.

Antibiotic concentrations in ascitic fluid after parenteral therapy may be important in the treatment of peritonitis. We have created ascites in dogs by partial ligation of the inferior vena cava. Ascitic fluid volume was measured at the time each antibiotic was administered. Nine antibiotics were studied in the same three dogs. Antibiotic concentration in ascitic fluid was found to vary inversely with ascites volume. Percentage of penetration (ratio of ascites peak to serum peak x100) ranged from 5.8 to 65% among the drugs studied. Only metronidazole showed a statistically significant higher percentage of penetration than other antimicrobials. Concentrations in ascitic fluid after single doses of cephalothin (15 mg/kg) and the aminoglycosides (2 mg/kg, gentamicin and tobramycin; 7.5 mg/kg, amikacin and kanamycin) did not exceed the minimum inhibitory concentration of many gram-negative rods and may justify the use of higher than usual initial parenteral doses, or possibly initial intraperitoneal administration in seriously ill patients.

Aminoglycosides↗