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Dunn v. White.

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AIDS Serodiagnosis↗

Social milieu of a residential treatment center for severely or profoundly handicapped young children.

Severely or profoundly handicapped young children who lived in a residential treatment center were subjects in a modified time-sampled observation study of social behavior, state, and physical context. The study was conducted for 3 successive years. Although system-level changes in the ecology of the institution over the 3 years did not appear to affect the social-interaction indices, the developmental ages of the children were positively related to social opportunities and social behavior.

Child Development↗

Hematoporphyrin derivative photoradiation induced damage to normal and tumor tissue of the pigmented rabbit eye.

Cytotoxicity induced by hematoporphyrin derivative (HpD) photoradiation in both normal and experimental tumor tissue of pigmented rabbit eyes has been examined. In addition, documentation of HpD induced fluorescence in ocular structures has also been obtained. Acute normal ocular tissue toxicity studies demonstrated that HpD (1-10 mg HpD/kg) followed 48 hours later by a transpupil irradiation of red light (635 nm, 36-90 J/cm2) resulted in demarcated areas of retinal damage. Long term (chronic) toxicity studies have shown that the initial damage to the retina was permanent but that no damage to the cornea, lens or vitreous could be observed during a 16 month follow-up. Visual and histological documentation have been obtained, following HpD photoradiation therapy (PRT), in rabbit eyes having heterotransplanted single nodule amelanotic melanomas. A toxic effect characterized by tumor blanching, edema and hemorrhage was observed within 24 hours of treatment. Histological examination obtained 24 hours following HpD PRT illustrated massive tumor tissue necrosis and vascular disruption. HpD PRT at clinically relevant doses was also shown to be effective in selectively curing the highly malignant amelanotic iris melanoma. It is concluded that HpD PRT may prove to be an effective modality for treating certain ocular tumors.

Animals↗

An experimental evaluation of alternative communication systems as used for medical diagnosis.

While the problem of providing adequate health care to remote populations has been widely recognized, little research has been undertaken to evaluate alternative systems designed to provide such care. An essential part of such a system is the communications link between the doctor and the community he is serving. Studying this two-way subsystem is the context of primary diagnosis and patient management, efficiency and effectiveness of color television, black and white television and hands-free telephone were compared with physical presence consultation. No significant differences in performance were found among the three systems using telecommunications. Physical presence consultation was found superior only for detecting secondary medical problems. Significant rank order correlations were found, however, between the years of experience of the consulting physician and both diagnostic accuracy and appropriate patient management. Also, the attitudes of the patients, doctors and nurses alike ranked physical presence over color television over black and white television over hands-free telephone for medical consultations.

Attitude↗

Emergence of vancomycin resistance in Staphylococcus aureus. Glycopeptide-Intermediate Staphylococcus aureus Working Group.

BACKGROUND: Since the emergence of methicillin-resistant Staphylococcus aureus, the glycopeptide vancomycin has been the only uniformly effective treatment for staphylococcal infections. In 1997, two infections due to S. aureus with reduced susceptibility to vancomycin were identified in the United States. METHODS: We investigated the two patients with infections due to S. aureus with intermediate resistance to glycopeptides, as defined by a minimal inhibitory concentration of vancomycin of 8 to 16 microg per milliliter. To assess the carriage and transmission of these strains of S. aureus, we cultured samples from the patients and their contacts and evaluated the isolates. RESULTS: The first patient was a 59-year-old man in Michigan with diabetes mellitus and chronic renal failure. Peritonitis due to S. aureus with intermediate resistance to glycopeptides developed after 18 weeks of vancomycin treatment for recurrent methicillin-resistant S. aureus peritonitis associated with dialysis. The removal of the peritoneal catheter plus treatment with rifampin and trimethoprim-sulfamethoxazole eradicated the infection. The second patient was a 66-year-old man with diabetes in New Jersey. A bloodstream infection due to S. aureus with intermediate resistance to glycopeptides developed after 18 weeks of vancomycin treatment for recurrent methicillin-resistant S. aureus bacteremia. This infection was eradicated with vancomycin, gentamicin, and rifampin. Both patients died. The glycopeptide-intermediate S. aureus isolates differed by two bands on pulsed-field gel electrophoresis. On electron microscopy, the isolates from the infected patients had thicker extracellular matrixes than control methicillin-resistant S. aureus isolates. No carriage was documented among 177 contacts of the two patients. CONCLUSIONS: The emergence of S. aureus with intermediate resistance to glycopeptides emphasizes the importance of the prudent use of antibiotics, the laboratory capacity to identify resistant strains, and the use of infection-control precautions to prevent transmission.

Aged↗

N-alkyl urea hydroxamic acids as a new class of peptide deformylase inhibitors with antibacterial activity.

Peptide deformylase (PDF) is a prokaryotic metalloenzyme that is essential for bacterial growth and is a new target for the development of antibacterial agents. All previously reported PDF inhibitors with sufficient antibacterial activity share the structural feature of a 2-substituted alkanoyl at the P(1)' site. Using a combination of iterative parallel synthesis and traditional medicinal chemistry, we have identified a new class of PDF inhibitors with N-alkyl urea at the P(1)' site. Compounds with MICs of 200 micro M for matrilysin and other mammalian metalloproteases. Structure-activity relationship analysis identified preferred substitutions resulting in improved potency and decreased cytotoxity. One of the compounds (VRC4307) was cocrystallized with PDF, and the enzyme-inhibitor structure was determined at a resolution of 1.7 A. This structural information indicated that the urea compounds adopt a binding position similar to that previously determined for succinate hydroxamates. Two compounds, VRC4232 and VRC4307, displayed in vivo efficacy in a mouse protection assay, with 50% protective doses of 30.8 and 17.9 mg/kg of body weight, respectively. These N-alkyl urea hydroxamic acids provide a starting point for identifying new PDF inhibitors that can serve as antimicrobial agents.

Amidohydrolases↗

Prophylaxis against disseminated Mycobacterium avium complex with weekly azithromycin, daily rifabutin, or both. California Collaborative Treatment Group.

BACKGROUND: Azithromycin is active in treating Mycobacterium avium complex disease, but it has not been evaluated as primary prophylaxis in patients with human immunodeficiency virus (HIV) infection. Because the drug is concentrated in macrophages and has a long half-life in tissue, there is a rationale for once-weekly dosing. METHODS: We compared three prophylactic regimens in a multicenter, double-blind, randomized trial involving 693 HIV-infected patients with fewer than 100 CD4 cells per cubic millimeter. The patients were assigned to receive rifabutin (300 mg daily), azithromycin (1200 mg weekly), or both drugs. They were monitored monthly with blood cultures for M. avium complex. RESULTS: In an intention-to-treat analysis, the incidence of disseminated M. avium complex infection at one year was 15.3 percent with rifabutin, 7.6 percent with azithromycin, and 2.8 percent with both drugs. The risk of the infection in the azithromycin group was half that in the rifabutin group (hazard ratio, 0.53; P = 0.008). The risk was even lower when two-drug prophylaxis was compared with rifabutin alone (hazard ratio, 0.28; P<0.001) or azithromycin alone (hazard ratio, 0.53; P = 0.03). Among the patients in whom azithromycin prophylaxis was not successful, 11 percent of M. avium complex isolates were resistant to azithromycin. Dose-limiting toxic effects were more common with the two-drug combination than with azithromycin alone (hazard ratio, 1.67; P=0.03). Survival was similar in all three groups. CONCLUSIONS: For protection against disseminated M. avium complex infection, once-weekly azithromycin is more effective than daily rifabutin and infrequently selects for resistant isolates. Rifabutin plus azithromycin is even more effective but is not as well tolerated.

AIDS-Related Opportunistic Infections↗

Prophylaxis with weekly versus daily fluconazole for fungal infections in patients with AIDS.

We compared the efficacy of a 400-mg once-weekly dosage versus a 200-mg daily dosage of fluconazole for the prevention of deep fungal infections in a multicenter, randomized, double-blind trial of 636 human immunodeficiency virus-infected patients to determine if a less intensive fluconazole regimen could prevent these serious but relatively infrequent complications of AIDS. In the intent-to-treat analysis, a deep fungal infection developed in 17 subjects (5.5%) randomly assigned to daily fluconazole treatment and in 24 (7.7%) given weekly fluconazole during 74 weeks of follow-up (risk difference, 2.2%; 95% confidence interval [CI], -1.7% to 6.1%). Thrush occurred twice as frequently in the weekly versus daily fluconazole recipients (hazard ratio, 0.59; 95% CI, 0.40-0.89), and in a subset of patients evaluated, fluconazole resistance was infrequent. Fluconazole administered once weekly is effective in reducing deep fungal infections in patients with AIDS, but this dosage is less effective than the 200-mg-daily dosage in preventing thrush.

AIDS-Related Opportunistic Infections↗

Adolescents' perceptions of relative weight and self-reported weight-loss activities: analysis of 1990 YRBS (Youth Risk behavior Survey) national data.

PURPOSE: The purpose of the study was to examine, among public high school students across the United States, perceptions of relative weight-loss and its relationship to physical activity levels, time spent viewing television, and efforts to lose weight. METHODS: Self-reported data from the 1990 Youth Risk Behavior Survey (YRBS) were used to analyze these relationships. The YRBS was developed and administered by the Division of Adolescent and School Health (DASH), Centers for Disease Control and Prevention (CDC), to assess important health behaviors which contribute significantly to adverse health outcomes among American youth. A total of 10,870 black, Hispanic, and white respondents were included in this analysis. RESULTS: From this sample, 24.8% perceived themselves as being "too fat." Of that group, 76.4% were trying to lose weight. Females comprised 74.4% of those reporting that they were "too fat" and trying to lose weight. Gender differences in weight perceptions were significant (p < .001), with females (34.6%) being more likely than males (14.4%) to report being "too fat." Whites (26.0%) reported being "too fat" more often than did Hispanics (23.9%) and blacks (17.2%) (p < .001). Skipping meals and exercise were the most commonly reported weight loss strategies. Hispanics were most likely to skip meals, followed by whites and blacks. Whites were more likely than the other groups to use exercise as a means of losing weight. Adolescents who perceived themselves as "too fat" reported fewer days of strenuous activity (p < .001), fewer hours of strenuous exercise in physical education class (p < .001), and more hours spent viewing television on school days (p < .001) than others. CONCLUSIONS: One quarter of U.S. high school students perceive themselves as overweight; three-quarters of these students are trying to lose weight. Adolescents who perceive themselves as overweight are less physically active and spend more time viewing television than those who do not perceive themselves as overweight.

Adolescent↗

Oncocytic cardiomyopathy of infancy with Wolff-Parkinson-White syndrome and ectopic foci causing tachydysrhythmias in children.

Two female infants, ages 6 months and 13 months, were first seen in the newborn period with supraventricular tachycardia associated with Wolff-Parkinson-White syndrome. One infant had echocardiographic and angiographic evidence of diffuse cardiomyopathy and died suddenly at home. The other infant was seen initially at 13 months of age with refractory ventricular tachycardia and died following surgical resection of arrhythmogenic foci on the left and right ventricles. Autopsy showed diffuse patchy oncocytic cardiomyopathy in both instances. Serial histologic sections of the cardiac conduction system showed oncocytic involvement of the atrioventricular (AV) node, His bundle, and bundle branches. Both infants had interruption of the anulus fibrosus by oncocytic cells at several sites, resulting in multiple accessory AV and nodoventricular connections. Additionally, patient No. 1 had an accessory AV connection by oncocytic cells in the fatty fibrous tissue of the left AV sulcus. To our knowledge, this is the first report of multiple accessory AV connections of oncocytic cells seen during histologic study. In addition, both infants had oncocytic involvement of the exocrine and endocrine glands. This report discusses the clinicopathologic correlations in these two patients, the literature on oncocytic cardiomyopathy, and the types of dysrhythmias found in these patients and their management.

Cardiomyopathies↗

Role of factor V Leiden mutation in patients with angiographically demonstrated coronary artery disease.

The study sought to determine whether coagulation factor V Leiden (FV Leiden) plays a role in the pathogenesis of coronary artery disease and/or myocardial infarction. Association of FV Leiden with venous thromboembolism is well established in the literature, but the role of the mutation in arterial thrombotic events is controversial. Some studies have documented an association between the mutation and myocardial infarction and stroke in juveniles. Few studies have explored its possible contribution to coronary atherosclerosis. We screened FV genotype in 850 predominantly white coronary angiography patients. Coronary artery disease risk factors and history of myocardial infarction were then analyzed by genotype. The FV Leiden mutation occurred in 54 (6.4%) patients. There was one homozygote; a 37-year-old, white male smoker with a history of myocardial infarction. Gene frequencies for white males and females were similar: 0.965 for the normal allele and 0.035 for FV Leiden. Gene frequencies for both genders were in Hardy-Weinberg equilibrium. FV Leiden was not a useful predictor (p=0.23) of the presence of clinically defined atherosclerosis (> or = 50% stenosis) in a logistic regression model adjusting for age, lipoprotein (a), total cholesterol, triglycerides, high density lipoprotein cholesterol, and fibrinogen. In addition, there was no difference in frequency of FV Leiden among those with and without medical histories of myocardial infarction (p=0.51). Allelic frequencies of FV Leiden in this patient group do not differ significantly from those reported for white populations. The FV Leiden mutation in its heterozygous state is not independently associated with coronary artery disease or myocardial infarction.

Coronary Angiography↗

Comparison of lower urinary tract symptom severity and associated bother between community-dwelling black and white men: the Olmsted County Study of Urinary Symptoms and Health Status and the Flint Men's Health Study.

OBJECTIVES: To determine the magnitude of racial disparity in lower urinary tract symptom (LUTS) severity and bother by combining two large comparable epidemiologic studies of community-dwelling white and black men, thereby avoiding many of the referral biases present in previous studies. Prior studies evaluating racial differences in benign prostatic hyperplasia have been hampered by selection bias, because nearly all have used surgical treatment as a marker for benign prostatic hyperplasia. METHODS: Data from the Olmsted County Study of Urinary Symptoms and Health Status and the Flint Men's Health Study were combined for a total study sample of 2480 men. We examined LUTS severity and associated bother as measured by the self-administered American Urological Association Symptom Index and Symptom Problem Index. RESULTS: Overall 34% of white men reported moderate/severe LUTS compared with 41% of black men (P <0.001). These patterns were consistent across age and persisted after adjustment for age and other sociodemographic factors. The relationship between LUTS severity and bother differed by race in that black men reported less bother for each unit increase in LUTS (P <0.001). CONCLUSIONS: In contrast to studies based on clinical populations, our community-based study demonstrated greater LUTS severity in black men compared with white men but black men reported less bother for any given level of LUTS severity. Although these findings suggest a racial disparity in benign prostatic hyperplasia, additional studies of anatomic, physiologic, and molecular factors may clarify whether these racial differences are real or due to sociocultural differences in reporting symptom morbidity.

Adult↗

Magnetic resonance imaging in childhood disseminated encephalomyelitis.

We report the magnetic resonance imaging features in two children with post-infectious disseminated encephalomyelitis. Magnetic resonance imaging dramatically demonstrated multiple white matter lesions in both children and resolution of lesions in conjunction with clinical recovery. These cases indicate that magnetic resonance imaging has considerable diagnostic utility in disseminated encephalomyelitis of childhood.

Brain↗

Maternal ethnicity and birthweight among blacks.

This paper examines the association of ethnicity and birthweight, adjusted for other maternal and infant characteristics, among black women who gave birth in Massachusetts from 1987 through 1989. Data are drawn from the standard certificate of live birth, which includes questions on race and ethnicity/ancestry as well as birthweight; maternal sociodemographic and biological characteristics; access to prenatal care; and infant characteristics. The study cohort consists of 18,571 black infants and a comparison group of 206,358 non-Hispanic white infants. Infants whose mothers reported their race as black were further categorized into six ethnic groups: American, Haitian, West Indian, Cape Verdean, Hispanic, and other black. In addition to descriptive analyses, we used multiple linear regression to measure the association between ethnicity, other characteristics, and birthweight; and we used multiple logistic regression to measure the odds ratio of low birthweight (ranging from 500 g to 2499 g) for the six black ethnic groups, adjusted for other characteristics. Results indicate that Americans have lower mean birthweight and generally higher levels of risk than other black ethnic groups. Compared to the reference group of non-Hispanic whites, Americans (OR = 1.49), other blacks (OR = 1.41), and West Indians (OR = 1.37) have significantly elevated relative risks of low birthweight.

Adult↗

The relationship of sex hormones to hyperinsulinemia and hyperglycemia.

Mexican-Americans, a high-risk population for non-insulin-dependent diabetes mellitus (NIDDM), have been previously reported to have decreased levels of sex-hormone-binding globulin (SHBG). We measured total testosterone, total estradiol and SHBG, glucose and insulin in premenopausal women (58 Mexican-Americans and 38 non-Hispanic whites) as part of the San Antonio Heart Study, a population-based study of cardiovascular risk factors. Although total estradiol and total testosterone were, in general, not correlated with metabolic variables, SHBG was negatively correlated with glucose and insulin. After adjustment for body mass index (BMI), ratio of waist-to-hip circumference (WHR) and ratio of subscapular-to-triceps skinfold (Centrality Index), SHBG was still significantly correlated with insulin concentrations (P less than .001). Since Mexican-Americans were previously reported to be more hyperinsulinemic than non-Hispanic whites, we examined the effect of adjusting for SHBG on insulin levels in this small population. While unadjusted insulin concentrations in Mexican-Americans were higher than in non-Hispanic whites (354 microU/mL v 236 microU/mL, respectively, P = .009), adjustment for BMI, WHR, and centrality index reduced the ethnic difference in insulin levels considerably (P = .014). However, only after adjusting for SHBG as well, did the ethnic difference in insulin levels became nonsignificant. Our data suggest that alterations in sex hormones and SHBG in particular may be related to the hyperinsulinemia and the high rates of NIDDM in Mexican-Americans.

Adult↗