Hepatotoxicity in HIV-infected children and adolescents on antiretroviral therapy.

CONTEXT AND OBJECTIVE: Adverse drug reactions are a significant problem in patients on antiretroviral therapy (ART). We determined liver enzyme elevation frequencies in HIV-infected children and adolescents receiving ART, and their association with risk factors. DESIGN AND SETTING: Cross-sectional study, at the Pediatrics Immunodeficiency Division, University Hospital, Universidade Estadual de Campinas. METHODS: Medical records of 152 children and adolescents (54.6% male; median age 7.48 years) were analyzed, with a mean of 2.6 liver enzyme determinations per patient. Clinically, patients were classified in categories N (6), A (29), B (78) and C (39). Serum levels of aspartate aminotransferase and alanine aminotransferase were evaluated. Hepatotoxicity was scored as grade 1 (1.1-4.9 times upper limit of normality, ULN), grade 2 (5.0-9.9 times ULN), grade 3 (10.0-15.0 times ULN) and grade 4 (> 15.0 times ULN). To assess hepatotoxicity risk factors, odds ratios (OR) and adjusted odds ratios (aOR) for age, gender, TCD4+ cell count, viral load and medication usage were calculated. RESULTS: We observed grade 1 hepatotoxicity in 19.7 % (30/152) patients. No cases of grade 2, 3 or 4 were detected. There was a significant association between hepatotoxicity and use of sulfonamides (OR, 3.61; 95% confidence interval (CI), 1.50-8.70; aOR, 3.58; 95% CI, 1.44-8.85) and antituberculous agents (OR, 9.23; 95% CI, 1.60-53.08; aOR, 9.05; 95% CI, 1.48-55.25). No toxicity was associated with ART. CONCLUSIONS: One fifth of patients experienced mild hepatotoxicity, attributed to antituberculous agents and sulfonamides. Our results suggest that ART was well tolerated.     

Postpartum acute myocardial infarction

We report a postpartum acute myocardial infarction that occurred during the first week after cesarean section delivery. We also calculated the rate of postpartum myocardial infarction as related to all women with myocardial infarctions seen in our hospital.(Am J Obstet Gynecol 1997;177:1553-5.)     

Heterogeneity of congenital primary hypothyroidism: the importance of thyroid scintigraphy

Current newborn screening programs in California and most of the U.S. depend for diagnosis of congenital primary hypothyroidism on demonstrating an elevated thyrotropin (TSH) level in infants with the lowest 5% to 10% of thyroxine (T4) levels by filter-paper bloodspot test. The diagnosis of primary congenital hypothyroidism based on low T4 with high TSH fails to distinguish between transient hypothyroidism, ectopic or hypoplastic thyroid, athyrosis, dyshormonogenesis, and transient hyperthyrotropinemia. We screened 166,300 newborn infants for primary congenital hypothyroidism for 6.5 years and confirmed the diagnosis in 46 cases; none of these patients had a goiter. Thyroid scintigraphy was performed in 40 with technetium-99m (Tc-99m) in the first eight cases tested and iodine-123 (I-123) in 29 of the last 32 cases. Fifteen infants were athyroid and seven had ectopic or hypoplastic glands; in 18 the thyroid gland appeared normal (present, normal location). Congenital hypothyroidism represents a spectrum of diseases from transient underactivity to complete absence of the thyroid gland. We recommend that, before starting treatment, a specific anatomic and functional diagnosis be confirmed by thyroid scintigraphy and other thyroid function tests.     

Lymphocyte T helper-specific reactivity in sustained responders to interferon and ribavirin with negativation (seroreversion) of anti-hepatitis C virus.

BACKGROUND: Seroreversion, negativation of anti-hepatitis C virus previously positive, is sometimes found in some chronic hepatitis C-sustained responders (SRs) to antiviral therapy. AIMS: To determine the probability of seroreversion in SR treatment with Interferon and Ribavirin, and lymphocyte T helper (CD4+) reactivity to HCV antigens. METHODS: Thirty SR were followed on average for 54.8 months. Anti-HCV was tested by third generation test. Peripheral blood mononuclear cells (PBMCs) were isolated from venous blood and cultured to evaluate CD4+ proliferation in response to 2 microg/ml of eight HCV recombinant antigens from core, NS3, NS4, NS5 regions. RESULTS: Seroreversion was verified in 23% of patients (7/30), appearing at 47.5+/-24.0 months. The probability of anti-HCV loss in this group was 25% at 56 months after ending therapy. In 57% (4/7), anti-HCV returned to positive. These 7 SR patients with seroreversion also showed weaker CD4+ reactivity in 5% of tests (3/56) than the remaining 23 anti-HCV-positive SRs who showed stronger reactivity in 18% of tests (33/184), P=0.036. CONCLUSIONS: One-quarter of the SR showed seroreversion of anti-HCV and weaker CD4+ specific HCV proliferation than those who remained anti-HCV positive. The data suggest that complete viral eradication is a possible and achievable clinical objective.     

Carvedilol protects ischemic cardiac mitochondria by preventing oxidative stress.

Ischemia negatively affects mitochondrial function by inducing the mitochondrial permeability transition (MPT). The MPT is triggered by oxidative stress, which occurs in mitochondria during ischemia as a result of diminished antioxidant defenses and increased reactive oxygen species production. It causes mitochondrial dysfunction and can ultimately lead to cell death. Therefore, drugs able to minimize mitochondrial damage induced by ischemia may prove to be clinically effective. We analyzed the effect of carvedilol, a beta-blocker with antioxidant properties, on mitochondrial dysfunction. Carvedilol decreased levels of TBARS (thiobarbituric acid reactive substances), an indicator of oxidative stress, which is consistent with its antioxidant properties. Regarding cell death by apoptosis, although ischemia did increase caspase-8-like activity, there were no changes in caspase-3-like activity, which is activated downstream of caspase-8; this may indicate that the apoptotic cascade is not activated by 60 minutes of ischemia. We conclude that carvedilol protects ischemic mitochondria by preventing oxidative mitochondrial damage, and, by so doing, it may also inhibit the formation of the MPT pore.     

Intergenerational studies of human birthweight from the 1958 birth cohort. II. Do parents who were twins have babies as heavy as those born to singletons?

OBJECTIVE: To ascertain whether maternal twinning influences the previously described association between the birthweight of singleton mothers and their infants. DESIGN AND SUBJECTS: The association between the birthweight of singleton parents and their offspring and that between twin parents and their offspring was compared using data from the 23-year-old sample of the 1958 British national birth cohort. The numbers available for full comparison were 1027 female and 611 male singleton cohort members, and 26 female and 17 male twin cohort members and their first singleton livebirths. RESULTS: Of the mothers who had been twins, half had been of low birthweight, and overall their mean weight was 700 g less than that of their singleton counterparts. Nevertheless, the mean birthweight of babies of twin mothers was 133 g, and of twin fathers 94 g, greater than of babies of corresponding singletons. For female, but not male, parents this difference persisted after adjustment for confounding variables. CONCLUSIONS: We suggest two possible reasons for the difference between the weight of babies of twin and singleton mothers. Firstly, the growth of twins becomes retarded late in pregnancy, possibly after a period critical in determining long-term reproductive effects. Secondly, the twin survivors were of higher birthweight than the original twin cohort, whilst the singleton survivors were more representative of all singleton births, thus introducing a possible bias.     

Myeloradiculopathy associated with wasp sting

A 12-year-old girl developed a reversible myeloradiculopathy 1 week after a wasp sting. Delayed neurologic hypersensitivity reactions to Hymenopteran stings occur primarily in adults. Reactions involving both the peripheral and central nervous systems are extremely rare and have never been reported in a child. The mechanisms underlying this uncommon reaction may be related to age-dependent differences in immunologic responses.