CONTEXT: Adefovir dipivoxil is a nucleotide analog that has demonstrated effective antiretroviral activity against human immunodeficiency virus (HIV) with once-daily administration. OBJECTIVE: To determine if adefovir confers antiretroviral or immunologic benefit when added to stable antiretroviral therapy. DESIGN: Multicenter, 24-week, randomized, double-blind, placebo-controlled study. Enrollment was conducted from June 3, 1996, through May 6, 1997. SETTING: Thirty-three US HIV treatment centers. PARTICIPANTS: Of 1171 patients screened, 442 patients infected with HIV receiving stable antiretroviral therapy for at least 8 weeks with plasma HIV RNA greater than 2500 copies/mL and CD4+ cell count above 0.20 x 10(9)/L were randomized. INTERVENTION: Patients were randomized to receive either a single 120-mg/d dose of adefovir dipivoxil (n = 219) or an indistinguishable placebo (n = 223). All patients received L-carnitine, 500 mg/d. Open-label adefovir was offered after 24 weeks and was continued until the end of the study. MAIN OUTCOME MEASURES: Changes in HIV RNA from baseline, based on area under the curve and CD4+ cell levels, adverse events, and effect of baseline genotypic resistance on response to adefovir. RESULTS: Patients assigned to adefovir demonstrated a 0.4-log10 decline from baseline in HIV RNA compared with no change in the placebo group (P<.001), which continued through 48 weeks. CD4+ cell counts did not change. During the initial 24 weeks, elevated hepatic enzyme levels (P<.001), gastrointestinal tract complaints (P<.001), and weight loss (P<.001) were associated with use of adefovir. Between 24 weeks and 48 weeks elevations in serum creatinine occurred in 60% of patients, usually returning to baseline after discontinuation of adefovir. Patients with lamivudine or lamivudine and zidovudine resistance mutations demonstrated anti-HIV effects with adefovir (P< or =.01 vs placebo group). CONCLUSIONS: This study suggests that once-daily adefovir therapy reduces HIV RNA and is active against isolates resistant to lamivudine or lamivudine and zidovudine. Nephrotoxicity occurred when treatment extended beyond 24 weeks but was reversible.

Adenine↗

PubMedDate not supplied

Congenital anomalies and the diabetic and prediabetic pregnancy.

Congenital anomalies are two to four times more frequent in the offspring of diabetic mothers than in those of non-diabetic mothers, and represent an increasingly important cause of perinatal mortality. These anomalies involve multiple organ systems more often than those found in the children of non-diabetic mothers. The excess of anomalies associated with maternal diabetes occurs in many organ systems. Anomalies are no more frequent in the offspring of diabetic fathers and pre-diabetic mothers than among those of non-diabetics, suggesting that non-genetic factors are the important determinants. Anomalies are most frequent in the offspring of mothers who have developed diabetes at an early age, many of whom have diabetes of long duration, are insulin-treated, and may have vascular complications. The relative importance of each of these factors in the pathogenesis of anomalies is unknown, but present evidence is consistent with a hypothesis that anomalies are the result of metabolic disturbances in the intrauterine environment during the first trimester of pregnancy. Whether or not their incidence can be reduced by optimum metabolic control of maternal diabetes during this period is unknown.

Congenital Abnormalities↗

PubMedDate not supplied

Gas chromatographic determination of vapor-phase biomarkers formed from rats dosed with CCl4.

Sprague-Dawley rats dosed with CCl4 (3 ml kg-1) were placed in a glass chamber through which air was passed continuously at a rate of 60 ml min-1. Volatile aldehydes and ketones in expired air from rats were derivatized to thiazolidines by passing the effluent gas stream through an aqueous cysteamine solution. The thiazolidine derivatives were then extracted and analyzed by gas chromatography with a nitrogen-phosphorus detector and gas chromatography/mass spectrometry. The compounds identified were formaldehyde, acetaldehyde, acetone and formyl chloride. There were no appreciable differences in levels of formaldehyde and acetaldehyde between CCl4-dosed rats and control rats, whereas the levels of acetone in CCl4-dosed rats showed an increase compared to those in control rats. Results suggest that acetone is the major volatile carbonyl compound produced following acute doses of CCl4. Results of thiobarbituric acid assay on the livers from a control rat and a CCl4-dosed rat did not show any appreciable differences.

Acetaldehyde↗

PubMedDate not supplied

An observational study of attending rounds.

The authors conducted an observational study of attending rounds to determine the current status of this form of clinical teaching in a university-based internal medicine department. Using two forms of measurement, questionnaires and timed observations, we found that 63% of attending physician time was spent in the conference room, 26% in hallways, and only 11% at the bedside. Significant differences were found between estimated and actual times, particularly in discussing previously admitted patients, patient interactions, data reviews, topic presentations, and the category of "other" activities. These results provide a framework for appraising attending rounds and identifying areas that may be improved with a teaching workshop intervention.

Arizona↗

PubMedDate not supplied

Ocular teratology.

The principles of teratology are described, and animal models for research in abnormal ocular development and clinical studies of human teratogens are surveyed. A review is made of presumed ocular teratogenic agents: radiation; external environmental teratogens; maternal conditions such as infections, diabetes, and epilepsy; alcohol and drugs such as thalidomide, retinoic acid, and coumarin anticoagulants; and other agents, such as cigarettes.

Abnormalities, Drug-Induced↗

PubMedDate not supplied

Effects of growth hormone on brain biogenic amine levels.

The effects of IP administered bovine growth hormone (GH) on regional brain serotonin, 5-hydroxyindoleacetic acid (5-HIAA) and norepinephrine levels in rats were examined. GH decreased the levels of both monoamines and 5-HIAA in the diencephalon and brainstem while not affecting telencephalic concentrations. In hypophysectomized rats, however GH produced significant elevations of monoamine and 5-HIAA levels in all brain regions. In normal rats the decreases in norepinephrine content produced by GH were correlated with a reduction in the stimulatory action of d-amphetamine on general activity levels. These results demonstrate that GH can affect brain biogenic amines and that these effects have behavioral consequences.

Animals↗

PubMedDate not supplied

Behavioral differences between vasopressin-deficient (Brattleboro) and normal Long-Evans rats.

Behavioral comparisons were made between rats of the Brattleboro strain with hereditary hypothalamic diabetes insipidus (DI) and normal Long-Evans rats. Measurements were made of activity behavior in a lighted open field and in a darkened activity chamber. Subtle measurement specific differences in the activity behavior of DI rats were found which suggested altered emotion, motivation and/or attention in the DI rats. In terms of learned behavior, DI and normal rats displayed a similar degree of habituation to all within-session activity measures in both the open field and darkened activity chamber. In a passive avoidance test, DI rats exhibited a degree of avoidance behavior equivalent to that of normal animals. Thus, these studies provide evidence that the vasopressin-deficient rat is not defective in learning and memory processes. The data can be interpreted as suggesting that vasopressin may influence memory tasks by extrinsic modulation of related states of emotionality, motivation and/or attention rather than by direct involvement in the retrieval and consolidation of information.

Aging↗

PubMedDate not supplied

Effect of vasopressin on open field and activity behavior of the vasopressin-deficient (Brattleboro) rat.

The effect of 1 and 5 micrograms AVP injections on open field and photoactivity chamber behavior of D.I. and normal Long-Evans animals was studied. Administration of 5 micrograms AVP (SC) resulted in a statistically significant depression of both open field and photochamber activity in the D.I. rat, but had a less pronounced effect on normal animals. However, 1 microgram AVP resulted in only minor alterations of activity in both D.I. and normal animals. In terms of learned behavior, D.I. and normal animals displayed similar within-session habituation when comparisons were made following the same treatment conditions. Thus, this study supports the hypothesis that vasopressin may influence memory tasks by modulation of related states of emotionality, motivation, and/or attention rather than by direct involvement in the retrieval and/or consolidation of information.

Animals↗