Daño hepático por fármacos: características clínicas e histológicas en 33 casos / Drug induced liver disease: clinical and pathological patterns in 33 cases

BACKGROUND: Drug induced liver disease (DILD) is common and of difficult diagnosis. AIM: To report the clinical, laboratory and pathological findings in 33 patients with DILD. PATIENTS AND METHODS: We revised 1,164 liver biopsies and 57 were selected as suspicious of DILD. In these, the scale proposed by Maria et al was applied to assess the possibility of hepatotoxicity reactions and 33 were selected. RESULTS: The 33 cases had a mean age of 48 +/- 18 years and 14 were male. Forty eight medications were involved, with an average of 1.4 drugs per patient. The main drugs were antimicrobials, antineoplastics-immunosuppressives and non-steroidal antiinflammatory drugs. The clinical presentations in order of frequency were cholestasis, hepatitis, asymptomatic, fulminant hepatitis and cirrhosis. The laboratory alterations observed in cases with hepatitis were 20 fold transaminase and bilirubin elevation. In cholestasis, moderate elevations of alkaline phosphatases and gamma glytamyl transferase were observed. Pathology showed hepatocellular damage, cholestasis and mixed damage, but also submassive necrosis and cirrhosis in one case. CONCLUSIONS: The present study confirms that DILD is frequently unpredictable and that it can cause a wide variety of clinical and pathological presentations, that can even evolve to chronicity.

Intravenous gammaglobulin therapy for neonatal alloimmune thrombocytopenia.

A clinical experience with the combined use of intravenous gammaglobulin and platelet transfusions in a neonate with alloimmune thrombocytopenia secondary to PLA1 incompatibility is described and compared to a previously affected sibling treated with a conventional regimen of corticosteroids, random donor platelet transfusions, and exchange transfusion for neonatal alloimmune thrombocytopenia.

Necrotizing enterocolitis in the first 24 hours of life.

Necrotizing enterocolitis (NEC) is commonly thought of as occurring in the sick premature infant, usually in the first one to two weeks of life. A review of NEC at the Children's Hospital of Denver over a 5-year period, found that 13 of 79 infants (16.1%) had onset of NEC during the first day of life. These infants were larger (mean birth weight 2,624 +/- 849 g), more mature (mean gestational age 37.9 +/- 2.5 weeks), and less asphyxiated as judged by Apgar scores (mean five-minute score 8.15 +/- 1.07) than infants with onset of NEC after the first day of life (mean birth weight 1,519 +/- 586 g, mean gestational age 32.0 +/- 3.5 weeks, P less than .001, and mean five-minute Apgar score 6.81 +/- 1.84, P less than .05). Despite their large size and degree of maturity, eight of these infants (62%) showed signs of respiratory distress; four (31%) were polycythemic; four (31%) had either a partial or double-volume exchange transfusion performed; and 11 (85%) were fed prior to developing NEC. Presenting signs of disease, occurrence of sepsis (31%), requirement for surgical intervention (62%), and mortality (30%) were similar for the two groups of infants. It is suggested that term and near-term infants who have significant illness after delivery be treated more like their premature counterparts with cautious introduction of feedings after an adequate period of stabilization.

Effects of cimetidine on theophylline, acetaminophen, and zoxazolamine toxicity in the intact mouse.

3-Methylcholanthrene treatment of C57BL/6N mice induces significant amounts of cytochromes P1-450, whereas P1-450 levels in 3-methylcholanthrene-treated DBA/2N mice are no different from those in control C57BL/6N or DBA/2N mice. Comparison of 3-methylcholanthrene-treated C57BL/6N and DBA/2N mice thus provides a convenient means of determining the role of P1-450 metabolism in two strains of mice following identical drug treatment regimens. 3-Methylcholanthrene-induced P1-450 is shown to be more effective than other forms of P-450 in detoxifying theophylline and zoxazolamine and in enhancing the toxicity of acetaminophen. Cimetidine in vivo blocks these metabolic pathways, resulting in increased toxicity of theophylline and zoxazolamine and protection against acetaminophen toxicity. These data illustrate the double-edged sword nature of P1-450 metabolism and the possibility of a paradoxical effect of cimetidine during drug-drug interactions in vivo. Cimetidine is shown to inhibit in vivo and in vitro the metabolism by both 3-methylcholanthrene-induced P1-450 and control forms of P-450; these data suggest that cimetidine may be acting at the level of P-450 reduction by NADPH-P-450 oxidoreductase. This same mechanism of action has been previously suggested for ellipticine.