Antipolymer antibodies in Danish women with silicone breast implants

OBJECTIVE: To use a new immunologic assay to evaluate antipolymer antibody (APA) levels among women with silicone breast implants (SBIs). METHODS: Women (n = 186) were identified through Danish population-based registers and categorized into six groups defined by prior breast surgery (silicone breast implantation/breast reduction/no breast surgery) and by the presence or absence of a prior hospital diagnosis of soft-tissue rheumatism (muscular rheumatism, ICD-8 codes 717.90 and 717.99). The women underwent blood tests, including an APA test, a clinical examination, and an interview focusing on rheumatic complaints. Blood samples were tested blindly. The severity of rheumatic symptoms/signs was scored from 1 (none) to 5 (severe) based on the clinical examination and interview. RESULTS: Women with SBIs did not have higher levels of APA than women without SBIs. The majority of women with SBIs had mild rheumatic complaints, and the severity of their symptoms was not related to APA levels. Among women who had previously been hospitalized because of soft-tissue rheumatism, there were more fibromyalgia cases, and their symptoms were more severe compared with those women without prior soft-tissue rheumatism; however, APA levels were not higher among these women. There was a significant difference in APA measurements resulting from between-kit variation (p less 0.01). CONCLUSIONS: Our data did not demonstrate higher APA levels among women with SBIs compared with controls. The large variation observed between the individual plates in the APA test should be evaluated in future studies.     

Effect of multimicronutrient supplementation on gestational length and birth size: a randomized, placebo-controlled, double-blind effectiveness trial in Zimbabwe

BACKGROUND: Multiple micronutrient deficiencies may contribute to low birth weight, which is a major global determinant of mortality. OBJECTIVE: We assessed the effect of prenatal multimicronutrient supplementation on gestational length and birth size. DESIGN: We conducted a randomized, placebo-controlled, double-blind effectiveness trial among antenatal care attendees in Harare, Zimbabwe. Pregnant women (22-35 wk of gestation) were randomly allocated to receive a multimicronutrient or placebo supplement daily until delivery. Supplementation with iron and folic acid was part of antenatal care. RESULTS: Of 1669 women, birth data were available from 1106 (66%), of whom 360 (33%) had HIV infection. The mean gestational length was 39.1 wk, and 16.6% of the women had a gestational length < 37 wk. The mean birth weight was 3030 g, and 10.5% of the infants had a birth weight < 2500 g. Multimicronutrient supplementation was associated with tendencies for increased gestational length (0.3 wk; 95% CI: -0.04, 0.6 wk; P = 0.06), birth weight (49 g; -6, 104 g; P = 0.08), and head circumference (0.2 cm; -0.02, 0.4 cm; P = 0.07) but was not associated with low birth weight (birth weight < 2500 g) (relative risk: 0.84; 0.59, 1.18; P = 0.31). The effect of multimicronutrient supplementation on birth weight was not significantly different between HIV-uninfected (26 g; -38, 91 g) and HIV-infected (101 g; -3, 205 g) subjects (interaction, P > 0.10). CONCLUSION: Antenatal multimicronutrient supplementation may be one strategy to increase birth size.     

Predictors and reference values of CD4 and CD8 T lymphocyte counts in pregnancy: a cross sectional study among HIV negative women in Zimbabwe

OBJECTIVE: To identify predictors and define reference values for T lymphocyte subsets in HIV negative pregnant black women. DESIGN: Cross sectional study. SETTING: Edith Opperman Martenity Hospital, Harare, Zimbabwe. STUDY POPULATION: 1113 HIV negative women 22 to 35 weeks pregnant registering for routine antenatal care. METHODS: A questionnaire was used to collect demographic and obstetric data. CD4 and CD8 T lymphocyte counts were determined by manual immunocytochemistry. Concentrations in serum, of retinol, beta-carotene, ferritin, folate and 1-antichymotrypsin were also measured. Multiple linear regression analysis was employed to identify and estimate effects of potential predictors. MAIN OUTCOME MEASURES: CD4 and CD8 T lymphocyte levels, demographic, obstetric data and micronutrient status. RESULTS: Predictors of CD4 counts were gestational age, serum retinol and season. CD4 counts declined by 25 (95% confidence interval [CI]; 11 to 40; p = 0.001) cells/L for each week's increase in gestation among women with low serum retinol, while low serum retinol was independently associated with lower CD4 counts (-127; 95% CI, -233 to 20 cells/L; p = 0.02) at 35 weeks gestation. The late rainy season was associated with higher CD4 counts (137; 95% CI, 67 to 207 cells/L; p < 0.001). CD8 counts were higher in women with low serum folate (87; 95% CI, 6 to 166 cells/L; p = 0.036) and were slightly higher in gravida 4+ compared to gravida one to three. Reference values of CD4 but not CD8 count and percentage markedly differed from flow cytometry values of pregnant and non-pregnant women in developed and developing countries reported in the literature, even after controlling for the differences in methods of T lymphocyte subset immunophenotyping. CONCLUSION: Gestational age, gravidity, micronutrient status and season influence T lymphocyte subset levels and need to be considered when designing clinical management and intervention strategies for pregnant women. The data underscores the need for local reference values.     

Good clinical practice is now obligatory in academic clinical drug research in the European Union

By May 2004, all clinical trials in the European Union (EU) on medicinal products have to be initiated and conducted in compliance with the principles in the new directive on Good Clinical Practice (GCP). This requirement will also apply to non-commercial trials involving registered drugs and may therefore restrain the academic clinical drug research. In Denmark, three public GCP units connected in a national network and associated with the university hospitals in Copenhagen, Odense and Aarhus have been established. The GCP units offer academic researchers the necessary quality assurance and quality control systems to ensure that clinical drug research can be performed according to GCP. The Danish initiative is presented here as a contribution to the future work with implementation of the principles of GCP in academic clinical drug research in the European Union.     

Reducing the duration of untreated first-episode psychosis: effects on clinical presentation

CONTEXT: Most studies on first-episode psychosis show an association between a long duration of untreated psychosis (DUP) and poorer short-term outcome, but the mechanisms of this relationship are poorly understood. OBJECTIVE: To determine whether it is possible to reduce the DUP for first-episode patients in a defined health care area through the introduction of an early detection (ED) program, compared with parallel health care areas without an ED program (No-ED). SETTING AND PATIENTS: We included consecutive patients with a DSM-IV diagnosis of nonorganic, nonaffective psychosis coming to their first treatment in the study health care areas between January 1, 1997, and December 31, 2000. A total of 281 patients (76% of the total) gave informed consent. INTERVENTIONS: The ED and No-ED health care areas offered an equivalent assessment and treatment program for first-episode psychosis. The ED area also carried out an intensive ED program. RESULTS: The DUP was significantly shorter for the group of patients coming from the ED area, compared with patients from the No-ED areas (median, 5 weeks [range, 0-1196 weeks] vs 16 weeks [range, 0-966 weeks]). Clinical status measured by the Positive and Negative Syndrome Scale and the Global Assessment of Functioning Scale was significantly better for patients from the ED area at start of treatment and, with the exception of Positive and Negative Syndrome Scale positive subscale, at 3 months. Multiple linear regression analyses gave no indication that confounders were responsible for these differences. CONCLUSIONS: It is possible to reduce the DUP through an ED program. The reduction in DUP is associated with better clinical status at baseline that is maintained after 3 months.     

Iron,haptoglobin phenotype,and HIV-1 viral load: a cross-sectional study among pregnant Zimbabwean women

BACKGROUND: Viral load is a determinant of HIV-1 progression and transmission. Iron status and the phenotype of haptoglobin, a heme-binding acute phase reactant, may be determinants of viral load. We aimed to describe the effect of iron status, haptoglobin phenotype (Hp), and other predictors on HIV-1 viral load. METHODS: Based on a cross-sectional study among 1669 antenatal care attenders (22-35 weeks) in Zimbabwe, 526 (31.5%) were found to be HIV infected. The role of season, age, gravidity, gestational age, malaria parasitemia, Hp, and elevated serum alpha(1)-antichymotrypsin (ACT) as well as serum ferritin, folate, retinol, and beta-carotene on HIV viral load among the 526 HIV-infected women was assessed using multiple linear regression analysis. RESULTS: The distribution of Hp 1-1 (32%), Hp 2-1 (48%), and Hp 2-2 (20%) was not different from that of 53 uninfected women. Mean viral load was 3.85 log(10) (95% CI: 3.77-3.93) genome equivalents (geq)/mL, ranging from 3.77 (95% CI: 3.64-3.90) geq/mL in women with Hp 1-1 to 4.05 (95% CI: 3.81-4.21) geq/mL in women with Hp 2-2. With elevated serum ACT controlled for, women with Hp 2-2 had viral loads twice (95% CI: 1.4-4.0, p =.002) that of women with Hp 1-1, whereas those with serum ferritin <6 micro g/L had viral loads less than one third (95% CI: 0.13-0.53, p =.013) that of women with serum ferritin >24 micro g/L. Viral loads were also higher in women enrolled in the early rainy season compared with the dry season, in gravidae 4+ compared with gravidae 1 through 3, and in those with moderately elevated compared with low serum alpha(1)-antichymotrypsin, but neither age, gestational age, serum folate, serum retinol, nor serum beta-carotene were predictors. CONCLUSION: Storage iron, Hp 2-2, and elevated ACT are independent positive predictors of HIV-1 viral load. The positive relationship between serum ferritin and viral load was not the result of an acute phase response or iron accumulation with advanced HIV infection. A possible detrimental role of iron in HIV infection would have serious public health implications.     

Predicting Oral Absorption of Drugs: A Case Study with a Novel Class of Antimicrobial Agents

Purpose. The purpose of this work was to evaluate an oral absorption prediction model, maximum absorbable dose (MAD), which predicts a theoretical dose of drug that could be absorbed across rat intestine based on consideration of intestinal permeability, solute solubility, intestinal volume, and residence time. Methods. In the present study, Caco-2 cell permeability, as a surrogate for rat intestinal permeability, and aqueous solubility were measured for 27 oxazolidinones. The oxazolidinones are a novel class of potential antibacterial agents currently under investigation. These values were used to estimate MAD for each of the compounds. Finally, these predicted values were compared to previously measured bioavailability data in the rat in order to estimate oral absorption properties. Results. A reasonably good correlation between predicted dose absorbed and bioavailability was observed for most of the compounds. In a few cases involving relatively insoluble compounds, absorption was underestimated. For these compounds while aqueous solubility was low, solubility in 5% polysorbate 80 was significantly higher, a solvent possibly more representative of the small intestinal lumen. Conclusions. These results suggest that MAD may be useful for prioritizing early discovery candidates with respect to oral absorption potential. In the case of compounds with poor aqueous solubility, additional factors may have to be considered such as solubility in the intestinal lumen.     

Effects of multimicronutrient supplementation on helminth reinfection: a randomized,controlled trial in Kenyan schoolchildren

A randomized, placebo-controlled, double-blind, two-by-two factorial trial was carried out among 977 schoolchildren from 19 primary schools in Nyanza Province, Kenya from February 1995 to February 1996. The interventions were multimicronutrient supplementation (vitamin A, 1000 micrograms; vitamin B1, 1.4 mg; vitamin B2, 1.6 mg; vitamin B6, 1.7 mg; vitamin B12, 2.0 micrograms; folate, 150 micrograms; niacin, 16 mg; vitamin C, 50 mg; vitamin D, 5 micrograms; vitamin E, 8 mg; iron, 18 mg; zinc, 20 mg; copper, 2.0 mg; iodine, 150 micrograms; selenium, 40 micrograms) and multihelminth chemotherapy (albendazole 600 mg in a single dose and/or praziquantel 40 mg/kg in a single dose). This paper reports the effects of the supplementation given on all school days on reinfection with hookworm, Ascaris lumbricoides, Trichuris trichiura and Schistosoma mansoni after 11 months. Baseline prevalence and geometric mean intensity for hookworm, A. lumbricoides, T. trichiura and S. mansoni in all children investigated were 54.7%, 13.8%, 45.6% and 70.0%, respectively and 8.6, 2.7, 5.9 and 19.4 eggs per gram (epg), respectively. Children received a mean of 2.3 multimicronutrient/placebo tablets per school week, giving a compliance rate of 46%. Children given multimicronutrients had a slightly, but significantly, lower intensity of S. mansoni reinfection compared with children given placebo (5.5 epg vs. 7.7 epg, P = 0.047). Multiple linear regression analyses controlling for baseline infection status confirmed this, as children who received micronutrients were reinfected with S. mansoni at only 69% of the intensity of those who received placebo. Multiple logistic regression analyses revealed that micronutrient supplementation was associated with a lower S. mansoni reinfection rate (odds ratio = 0.7) although this was only of borderline significance (P = 0.090). There were no significant differences in reinfection rates or intensities of hookworm, A. lumbricoides and T. trichiura. The effect on S. mansoni infection intensity is particularly interesting given the low compliance, suggesting that full micronutrient supplementation might have a role to play in S. mansoni control programmes.