Atopic dermatitis complicated by eczema herpeticum is associated with HLA B7 and reduced interferon-γ-producing CD8+ T cells.

BACKGROUND: The increased susceptibility of patients with atopic dermatitis (AD) to disseminated viral skin infections such as eczema herpeticum (ADEH+) is poorly understood. OBJECTIVES: The primary goal of the current study was to determine whether ADEH+ subjects have identifiable defects in cell-mediated immunity that reduce their ability to control viral infections. MATERIALS AND METHODS: In this study, we evaluated cytokine expression by various subsets of peripheral blood mononuclear cells from ADEH+ (n = 24) compared with AD without a history of viral infections (ADEH-) (n = 20) before and after treatment with herpes simplex virus (HSV). RESULTS: We found that interferon (IFN)-γ expression after HSV treatment was lower in the CD8+ T cells and monocytes from patients with ADEH+ compared with patients who are ADEH- or nonatopic. Given the induction of CD8+ T cells as the result of antigen presentation by human leucocyte antigen (HLA) class I, consistent with the findings described above we also found that the HLA B7 allele was significantly associated with risk of the ADEH+ phenotype (odds ratio = 1·91, P = 0·02, 125 ADEH+ and 161 ADEH- subjects). CONCLUSIONS: These data suggest that defects in viral-induced IFN-γ from CD8+ T cells contribute to the ADEH+ phenotype.

Atopic dermo-respiratory syndrome is a correlate of eczema herpeticum.

BACKGROUND: Factors favoring the emergence of eczema herpeticum (EH) in patients with atopic dermatitis (AD) remain elusive. The aim of this work was to identify changes in clinical and laboratory parameters in acute EH patients, before and after 6 weeks of treatment, as well as differences between AD patients with and without a history of EH. METHODS: A total of 235 adult subjects were included and subdivided into six groups: (i) AD patients with acute EH, (ii) AD patients with history of EH, (iii) AD without EH but with recurrent herpes simplex virus (HSV) infections, (iv) AD without EH or recurrent HSV infections and healthy non-AD controls (v) with and (vi) without recurrent HSV infections. Clinical examination of AD, assessment of atopic status and severity were performed. Total IgE, allergen-specific IgE and differential blood count were analyzed. Clinical diagnosis of acute EH was confirmed by PCR. RESULTS: More male patients with AD were affected by EH than female patients. Acute episodes of EH are characterized by lower levels of lymphocytes and higher levels of monocytes. AD patients with history of EH display higher total IgE serum levels (ADEH(+) HSV(+) vs ADEH(-) HSV(+) , P < 0.001) and higher sensitization profiles and stronger severity of AD (EASI and SCORAD; ADEH(+) HSV(+) vs ADEH(-) HSV(+) , P < 0.001). Concomitant asthma and rhinitis were identified as correlates of EH. CONCLUSION: From these data, we conclude that AD patients with EH display a distinct clinical and biological phenotype.

A framework for One Health research.

The need for multidisciplinary research to address today's complex health and environmental challenges has never been greater. The One Health (OH) approach to research ensures that human, animal, and environmental health questions are evaluated in an integrated and holistic manner to provide a more comprehensive understanding of the problem and potential solutions than would be possible with siloed approaches. However, the OH approach is complex, and there is limited guidance available for investigators regarding the practical design and implementation of OH research. In this paper we provide a framework to guide researchers through conceptualizing and planning an OH study. We discuss key steps in designing an OH study, including conceptualization of hypotheses and study aims, identification of collaborators for a multi-disciplinary research team, study design options, data sources and collection methods, and analytical methods. We illustrate these concepts through the presentation of a case study of health impacts associated with land application of biosolids. Finally, we discuss opportunities for applying an OH approach to identify solutions to current global health issues, and the need for cross-disciplinary funding sources to foster an OH approach to research.

Microalbuminuria is associated with insulin resistance in nondiabetic subjects: the insulin resistance atherosclerosis study.

Microalbuminuria is associated with excess cardiovascular mortality in both diabetic and nondiabetic subjects. Patients with NIDDM and microalbuminuria are more insulin resistant than those without microalbuminuria. However, the relationship between insulin resistance and microalbuminuria in patients with NIDDM could be due to hyperglycemia, which can cause both insulin resistance and an increase in albumin excretion rate. Little is known about microalbuminuria and insulin resistance in nondiabetic subjects. Therefore, we examined, cross-sectionally, the relationship of insulin sensitivity (S(I) x 10(-4) min x microU(-1) x ml(-1)), estimated by a frequently sampled intravenous glucose tolerance test and the minimal model and fasting plasma insulin concentration, to microalbuminuria (albumin-to-creatinine ratio > or = 2 mg/mmol) in 982 nondiabetic subjects aged 40-69 years. Altogether, 15% of the subjects had microalbuminuria, and 32% had hypertension. Subjects with microalbuminuria had a lower degree of insulin sensitivity (means +/- SE, 1.70 +/- 0.11 vs. 2.25 +/- 0.07, P = 0.003) and higher fasting insulin concentrations (17.4 +/- 1.1 vs. 15.7 +/- 0.5 mU/l, P = 0.059) compared with subjects without microalbuminuria. In logistic regression analysis, an increasing degree of insulin sensitivity was related to a decreasing prevalence of microalbuminuria (odds ratio = 0.86, 95% CI: 0.79-0.94, P < 0.001). Although this relationship attenuated after adjustment for age, sex, ethnicity, hypertension, fasting glucose, and BMI, it still remained significant. The association between insulin sensitivity and microalbuminuria was shown not to be different between normotensive and hypertensive subjects. Our results suggest a relationship between insulin resistance and microalbuminuria in nondiabetic subjects that is partially dependent on blood pressure, glucose levels, and obesity.

Glycemic control in early IDDM. The Wisconsin Diabetes Registry.

OBJECTIVE: A cohort (n = 277) was followed from diabetes diagnosis to evaluate longitudinal glycemic control, urinary C-peptide levels, and certain features of diabetes self-management. RESEARCH DESIGN AND METHODS: Unselected cases with IDDM, who were less than 30 yr of age, were identified at diagnosis from a 28-county area in Wisconsin. Subjects were asked to submit blood every 4 mo for GHb testing, to report aspects of diabetes self-management every 6 mo, and to collect a 24-h urine specimen 4 mo after diagnosis. RESULTS: In the 1st yr of diabetes, the rate of increase (0.23%/mo) in GHb was significant for the cohort (P less than 0.001) and for almost all age and sex subgroups. In the 2nd yr, there was no significant rate of increase for the cohort as a whole (P greater than 0.10). Adolescent males (10-19 yr of age) had a mean GHb level for year 2 higher than males of other age-groups and higher than female adolescents (P less than 0.001). Adolescent males had a significant rate of increase in GHb for year 2 (P = 0.02), unlike all other age and sex subgroups. Adolescents had higher initial 24-h urine C-peptide levels than children less than 10 yr of age (P less than 0.01). During the 2nd yr of diabetes, the percentage of adolescent males reporting three or more insulin injections/day was lower than any other subgroup. CONCLUSIONS: These data-suggest that glycemic control stabilizes during the 2nd yr of IDDM, except in adolescent males, and that this may be due partly to aspects of self-management.

Insulin-like growth factor-I is related to glycemic control in children and adolescents with newly diagnosed insulin-dependent diabetes.

To address the relationship of insulin-like growth factor-I (IGF-I) to diabetes control, we determined IGF-I levels in 137 subjects age 17 yr and younger with recently diagnosed insulin-dependent diabetes mellitus in a population-based cohort study between 3 and 11 months after diagnosis (mean 4.9 months). Initial determinations of IGF-I, 24-h urine C-peptide and microalbuminuria, age, sex, height, weight, body mass index, pubertal stage, and glycosylated hemoglobin (GHb) were obtained. IGF-I levels ranged from 11-439 ng/mL, were strongly related to age (r = 0.74, P < 0.001), and were higher in females than males at any given age (P < 0.01). IGF-I was inversely related to GHb (partial r = -0.43, P < 0.001) after adjustment for sex and age. The relationship between IGF-I and GHb did not change between age groups (< 6, 6-9, > or = 10 yr of age; P = 0.50), and it did not change between prepubertal and pubertal subjects (P = 0.95). IGF-I was not related to 24-h urine C-peptide or microalbuminuria. These results suggest that lower IGF-I levels are related to poorer metabolic control of diabetes in the period following insulin-dependent diabetes mellitus diagnosis in all young persons regardless of age or pubertal status.

Caloric restriction lowers plasma lipoprotein (a) in male but not female rhesus monkeys.

Many age-associated pathophysiological changes are retarded by caloric restriction (CR). The present study has investigated the effect of CR on plasma lipoprotein (a) [Lp(a)], an independent risk factor for the age-associated process of atherosclerosis. Rhesus monkeys were fed a control diet (n=19 males, 12 females) or subjected to CR (n=20 males, 11 females fed 30% less calories) for >2 years. All female animals were premenopausal. Plasma Lp(a) levels in control animals were almost two fold higher for males than females (47+/-9 vs 25+/-5mg/dl mean+/-SEM, p=0.05). CR resulted in a reduction in circulating Lp(a) in males to levels similar to those measured in calorie-restricted females, (27+/-5 vs 24+/-4 mg/dl mean+/-SEM). For all animals, plasma Lp(a) was correlated with total cholesterol (r=0.27, p=0.03) and LDL cholesterol (r=0.50, p=0.0001) whether unadjusted or after adjustment for treatment, gender or group. These studies introduce a new mechanism whereby CR may have a beneficial effect on risk factors for the development of atherosclerosis in primates.

Cigarette smoking, environmental tobacco smoke exposure and insulin sensitivity: the Insulin Resistance Atherosclerosis Study.

PURPOSE: To investigate whether active smoking and/or exposure to environmental tobacco smoke (ETS) is associated with insulin sensitivity. METHODS: Insulin sensitivity and tobacco use history were measured in 1481 participants in the Insulin Resistance Atherosclerosis Study (IRAS). IRAS is a large mulitcenter epidemiologic study designed to explore the cross-sectional relationships among insulin resistance, cardiovascular disease risk factors and behaviors, and disease in African-American, Hispanic, and non-Hispanic white men and women, aged 40-69 years, selected to represent a broad range of glucose tolerance. Multiple linear regression models and linear contrasts were employed to describe the association between smoking history, as assessed via structured interview, and insulin sensitivity, as assessed by an insulin modified frequently sampled intravenous glucose tolerance test (FSIGT) with minimal model analysis. RESULTS: Active smoking was not associated with insulin sensitivity. Exposure to ETS was associated with lower insulin sensitivity. Specifically, for all participants combined, levels of SI were lower, indicating reduced insulin sensitivity, for those exposed to ETS when compared to those who were not exposed (p = 0.019). This association persisted for female participants (p = 0.013) and exhibited the same trend for males but failed to achieve statistical significance (p = 0.264). CONCLUSIONS: Our study did not reveal an association between active smoking and insulin sensitivity, as has been shown previously. The association between ETS exposure and insulin sensitivity is a puzzling finding which deserves further investigation in the longitudinal data from IRAS as well as in other populations.

Gender moderates the effects of exercise therapy on health-related quality of life among COPD patients.

STUDY OBJECTIVES: To determine whether long-term treatment with exercise therapy results in more favorable, disease-specific, health-related quality of life (HRQL) compared with short-term treatment with exercise therapy; and to determine whether there are gender differences in disease-specific HRQL among individuals randomized into the two treatment groups. DESIGN: Randomized clinical trial. SETTING: Center-based exercise therapy unit at a university. PARTICIPANTS: One hundred forty patients with COPD; 118 completed trial. INTERVENTIONS: Short-term exercise therapy (3 months); long-term exercise therapy (18 months). MEASUREMENTS: Chronic Disease Respiratory Questionnaire (CRQ). RESULTS: After 3 months of treatment, there were significant improvements in all CRQ scores for men and women (p < 0.01), and for the total sample (p < 0.01). At 18 months, individuals randomized into the long-term group had significantly more favorable scores than the short-term group for dyspnea (p = 0.03), fatigue (p < 0.01), emotional function (p = 0.04), and mastery (p = 0.04). However, these effects were moderated by gender. That is, men in the long-term group reported significantly more favorable scores than men in the short-term group for dyspnea (0.04), fatigue (p < 0.001), emotional function (p = 0.02), and mastery (p = 0.02). At the 18-month assessment, there were no differences between long-term and short-term exercise therapy for women on any of the subscales of the CRQ. CONCLUSIONS: Taken collectively, the CRQ data demonstrate that long-term exercise therapy has little added benefit for women over short-term exercise therapy; however, men derive significant benefits from extended training.

Relationships between insulin resistance and lipoproteins in nondiabetic African Americans, Hispanics, and non-Hispanic whites: the Insulin Resistance Atherosclerosis Study.

The study purpose was to explore the association between dyslipidemia and insulin resistance in three ethnic groups. The Insulin Resistance Atherosclerosis Study (IRAS) is a multicenter epidemiologic study conducted at four clinical centers in California, Texas, and Colorado. The study population for this analysis consisted of 931 non-Hispanic white, African American, and Hispanic men and women (aged 45 to 64 years) without diabetes. The IRAS clinical examinations included lipoprotein measures, a 75-g glucose tolerance test, and the frequently sampled intravenous glucose tolerance (FSIGT) test. The results show a consistent relationship between insulin-mediated glucose disposal and dyslipidemia in African American, Hispanic, and non-Hispanic white men and women. Further, LDL size was inversely associated with insulin resistance in all three ethnic groups. These findings indicate that dyslipidemia is a fundamental part of the insulin resistance syndrome in all of the ethnic groups studied.

A randomized trial of nurse intervention to reduce preterm and low birth weight births.

OBJECTIVE: To test the effect of telephone calls from registered nurses to low-income pregnant women on the rates of low birth weight (LBW) and preterm births. METHODS: A total of 1554 women receiving prenatal care in a public clinic who met study criteria and who consented were assigned randomly to intervention and control groups. Women in the intervention group received telephone calls from a registered nurse, one or two times weekly from 24 weeks' through 37 weeks' gestation. Relative risks (RRs) and 95% confidence intervals (CIs) were calculated. RESULTS: Low birth weight rates were 10.9% in the intervention group and 14.0% in the control group (RR 0.75; 95% CI 0.55, 1.03; P = .072). For gestational age less than 37 weeks, rates were 9.7 in the intervention group and 11.0 in the control group (RR .87; 95% CI 0.62, 1.22; P = .415). In the subgroup of low-income black women 19 years of age and older, a statistically significant difference was found in preterm birth rates before 37 weeks (8.7% in the intervention group versus 15.4% in the controls [RR 0.56; 95% CI 0.38, 0.84; P = .004]). CONCLUSION: There was no difference in LBW or preterm births between intervention and control groups in the total sample. In a secondary analysis of black subjects 19 years of age and older, there was a significant difference in preterm birth rates.

Maternal right hypogastric artery blood flow during normal pregnancy and 6 weeks postpartum.

OBJECTIVE: To document and quantify the temporal hemodynamic changes occurring in the pelvic circulation in normal human pregnancy, and to compare these changes with those found 6 weeks postpartum. METHODS: Thirty-three patients had color pulsed Doppler evaluation of the right hypogastric artery six times during pregnancy and once 6 weeks postpartum. Pulsed Doppler waveforms were digitized to assess the time velocity integral (area under the Doppler curve = TVI) and the peak flow velocity (maximum velocity = PFV). The diameter of the vessel was determined during systole using high-resolution two-dimensional ultrasound from a longitudinal plane. A quantitative estimate of the blood flow through this vessel was calculated by multiplying the TVI by the calculated cross-sectional area of the vessel. RESULTS: The cross-sectional area and the indexed volume of blood flow per minute of the hypogastric artery were significantly greater during pregnancy compared with the postpartum value. The estimated vascular resistance index was significantly decreased during pregnancy. Time velocity integral was significantly lower at the initial study compared with the postpartum value. CONCLUSION: The hypogastric artery undergoes significant hemodynamic changes during pregnancy when compared to the postpartum period. Furthermore, the pelvic circulation displays these changes early in gestation.

Hyperemic response of the brachial artery during the second half of pregnancy.

OBJECTIVE: To determine if women who developed preeclampsia had measurable differences in the vascular response postrelease of a 1-minute blood flow occlusion. METHODS: A total of 33 nulliparous patients were enrolled in this study during the second half of the pregnancy. All had baseline Doppler flow velocities while resting in the left lateral decubitus. Subsequently, a blood pressure cuff was inflated for 60 seconds in the forearm so as to occlude blood flow. Doppler waveforms were analyzed immediately after the release of the blood pressure cuff and on a single beat occurring at 15 second intervals for a total of five readings. After a rest period, patients were asked to squeeze a handheld manometer at maximum strength as long as possible. Doppler waveforms were analyzed as above. The Doppler waveforms of all enrolled patients who subsequently developed preeclampsia any time after the study were compared to those who remained normotensive. RESULTS: 1) The "hyperemic response" that occurred immediately after release of the blood pressure occlusion of the forearm was significantly different between patients who subsequently developed preeclampsia compared with those who remained normotensive, 2) the hyperemic response that occurred after the isometric handgrip exercise was not significantly different between the two groups, and 3) sensitivity, specificity, and negative predictive values were high, but positive predictive values were low. CONCLUSION: There was a significant difference in the hyperemic response of the brachial artery to a short period of ischemia of the forearm (blood pressure occlusion) between normotensive patients and a group of patients who subsequently developed preeclampsia.

Ratings of students' performances in a third-year internal medicine clerkship: a comparison between problem-based and lecture-based curricula.

PURPOSE: To compare clinical performances in a third-year medicine clerkship between studies from a problem-based learning (PBL) curriculum and students from a traditional, lecture-based learning (LBL) curriculum. METHOD: The study participants were 88 PBL students and 364 LBL students rotating through a common third-year internal medicine clerkship at the Bowman Gray School of Medicine at Wake Forest University, classes of 1991-1995. Faculty and housestaff assessed the students' performances using four clinical rating scales. The student also completed the medicine student ("shelf") test of the National Board of Medical Examiners (NBME). RESULTS: On average, the PBL students received significantly higher ratings from housestaff and faculty on all four rating scales. No difference in scores on the NBME medicine shelf test was observed. CONCLUSION: The results support the hypothesis that preclinical PBL curricula as found at the Bowman Gray School of Medicine may enhance third-year students' clinical performances.

Cigarette smoking, low birth weight, and preterm births in low-income African American women.

OBJECTIVE: To examine effects of light and heavy cigarette smoking on the incidence of low birth weight (LBW) and preterm births in African American women. DESIGN: A total of 1146 low-income African American women participated in a randomized trial to test the effectiveness of nursing intervention in the reduction of preterm and LBW births. This secondary analysis focused on the effects of cigarette smoking on LBW (< 2500 gm) and preterm (< 37 weeks' gestation) births. RESULTS: Cigarette smoking had a significant effect on both LBW and preterm births. When light smokers were compared with nonsmokers, odds ratios were 1.89 (confidence interval (CI) 1.15, 3.13; p = 0.0127) for LBW births and 1.74 (CI 1.00; 3.02; p = 0.0499) for preterm births. When heavy smokers were compared with nonsmokers, odds ratios were 3.03 (CI 1.90, 4.86; p = 0.001) for LBW births and 2.60 (CI 1.55, 4.35; p = 0.0003) for preterm births. CONCLUSION: Cigarette smoking was associated with significantly higher rates of both LBW and preterm births in this sample of African American women.

Effect of trichloroethylene on the exploratory and locomotor activity of rats exposed during development.

Trichloroethylene (TCE) is a common contaminant of underground water supplies. To examine the effect of TCE on the developing central nervous system, rats were exposed to TCE throughout gestation until 21 days postpartum via their dams' drinking water. TCE concentrations of 312 mg/l, 625 mg/l and 1250 mg/l were tested. Exploratory behavior was higher in 60- and 90-day old male rats which were exposed to any level of TCE. The effect of TCE-exposure on locomotor activity (running wheel) was also examined in 60-day old males (625 and 1250 ppm exposure groups). Locomotor activity was significantly higher in rats exposed to 1250 ppm TCE. These data suggest that TCE has long-term effects on behaviour.

Antibiotic resistance in staphylococci adherent to cortical bone.

The surface-adherent mode of bacterial growth has been shown to play a pivotal role in the persistent nature of infections involving retained foreign bodies, biomaterials, or dead bone (e.g., osteomyelitis). The hypothesis tested herein is that bone and implant materials--polytetrafluoroethylene (PTFE), and polymethylmethacrylate (PMMA)--provide a surface environment that promotes a type of bacterial growth characterized by an enhanced antibiotic resistance. The antibiotic resistance estimates of three staphylococcal subtypes were determined for organisms grown in an adherent state on the aforementioned surfaces as well as in their nonadherent or suspended state. Antibiotic resistance was found to vary with mode of bacterial growth. Secondly, for the staphylococcal subtypes, antibiotics and modes of growth studied herein, adherent growth on bone was associated with the most antibiotic resistance.

Blood lead levels in North Carolina painters.

1. Blood lead levels were examined in 127 housepainters in North Carolina between April and September, 1993. Each participant filled out a questionnaire and gave a blood sample. The questionnaire covered the individual's work history, concentrating on paint-removal activities and personal protection, and also covered potential nonoccupational sources of lead exposure. Blood samples were analysed for lead content using atomic absorption spectroscopy. 2. The geometric mean blood lead level was 0.33 mumol L-1 (6.8 micrograms dL-1). No blood lead samples were found to exceed the occupational standard of 1.93 mumol L-1 (40 micrograms dL-1). The three highest samples had levels between 0.97 and 1.45 mumol L-1 (20 and 30 micrograms dL-1); this represented 2.4% of the study sample. 3. No statistical association was found between blood lead levels in these painters and their painting activities, including using dust masks for personal protection. 4. Current painting practices in this group of North Carolina painters do not appear to elevate blood lead levels above the occupational standard.

Attitudes and practices of registered nurses toward women who have experienced abuse/domestic violence.

OBJECTIVE: To compare the education, attitudes, and practices related to domestic violence of perinatal nurses from three types of practice sites. DESIGN: A descriptive study of responses to a questionnaire administered to a convenience sample and through a mailing. SETTING: Education conferences and responses to a mailing. PARTICIPANTS: Two hundred seventy-five nurses in perinatal practice (87 public health, 71 hospital, 117 private office). MAIN OUTCOME MEASURES: Primary outcomes were attitudes and beliefs about domestic violence and nursing behavior when domestic violence was identified. The effects of education about domestic violence on practice and the effect of a personal/family history of domestic violence on practice were examined. RESULTS: Some differences were found in the attitudes and beliefs of nurses from different practice sites, but more differences were found in their behaviors. Only 54% of the total sample reported having education about domestic violence, received in formal or continuing education programs. Public health nurses were the most likely to have such education. Education affected both attitudes and behavior. In the total sample, 31% of nurses reported abuse of themselves or family members. CONCLUSIONS: Nursing care for women who have experienced domestic violence includes assessment and appropriate counseling. Many nurses in this study lacked education about domestic violence. The provision of education about abuse and domestic violence is a first step toward a change in nursing practice.