Lower Mean Body Weight Research Articles

A mutation of the Col2a1 gene (G1170S) alters the transgenic murine phenotype and cartilage matrix homeostasis

Genomic studies have revealed that there is a significant association between a point mutation of the human Col2A1 gene (G1170S) and several hip disorders. The purpose of the study was to explore the phenotype and altered cartilage matrix homeostasis of transgenic mice carrying this mutated Col2a1 gene. Wild-type and transgenic mice were used as the control and study groups, respectively. Body weight measurement, radiographic analysis, and histological analysis of the mice were carried out to describe differences between the wild-type and transgenic mice at different ages. Cartilage metabolism studies were also carried out, including an MTT assay of cellular proliferation and nitric oxide and glycosaminoglycan assays. Allelic expression levels of the mutant A allele and the normal G allele were established by TaqMan assay. Cytokine and protease gene expression were measured. Transgenic mice had a lower mean body weight, a deformed skeletal structure, and abnormal cartilage histomorphology. Chondrocyte proliferation was significantly compromised and this was linked to significantly higher NO secretion and less soluble glycosaminoglycan formation. TNF-α and IL-1β gene expression was significantly upregulated, while MMP-13 gene expression was significantly downregulated. The mutant G1170S Col2a1 gene in mice clearly alters the transgenic murine phenotype and cartilage matrix homeostasis.

A dietary embryo/fetal developmental toxicity study of arruva, an R,R-monatin salt isomer, in Crl:CD(SD) rats

R,R-Monatin is an intensely sweet substance originally identified in the root bark of Sclerochiton ilicifolius. R,R-Monatin salt, commonly known as "arruva", has potential for use as a high-potency sweetener food ingredient. Previously, arruva was concluded to present no toxicologically relevant effects to Crl:CD(SD) rats and Crl:CD-1(ICR) mice fed up to 35,000 ppm arruva in the diet for 90 days. In the present study, groups of mated Sprague-Dawley rats (25 Crl:CD(SD) females/group) were exposed continuously to 0 (control), 15,000, 30,000, or 50,000 ppm arruva in the diet during gestation days 6-21. There were no fetal malformations or developmental variations that were attributable to arruva at any exposure level, nor were there any test article-related effects on intrauterine survival. Maternal toxicity, evidenced by lower mean body weights, body weight gains and feed efficiency, was observed at 50,000 ppm. A developmental effect, in the form of lower mean fetal body weight, was noted in the 50,000 ppm group in the presence of maternal toxicity. Therefore, the dietary no-observed-adverse-effect level (NOAEL) for maternal and embryo/fetal developmental toxicity of arruva in pregnant rats during gestation days 6-21 was 30,000 ppm (equivalent to 2564 mg/kg bw/day) based on reductions in maternal and fetal body weights.

Pregabalin Treatment for Peripheral Neuropathic Pain

Two well-studied conditions of peripheral neuropathic pain are postherpetic neuralgia (PHN) and painful diabetic peripheral neuropathy (DPN). Several pregabalin trials for peripheral neuropathic pain have been conducted in the West, but limited data are available for Japan. As ethnicity may influence health risks, differences may be evident in safety data from pregabalin trials in Japan and in the West. The objectives of this review were to compare large pooled safety data from randomized controlled trials evaluating pregabalin for the treatment of PHN or DPN in the West with data from two (one PHN, N = 371; one DPN, N = 314) similar trials in Japan. Longer-term safety data from Japanese open-label extension studies were also reviewed in these neuropathic pain populations. Published and unpublished Pfizer-supported pregabalin trials were identified and sourced from internal Pfizer records. A PubMed search to check for inclusiveness was conducted on 2 November 2011 using the following criteria: 'diabetic peripheral neuropathy' OR 'postherpetic neuralgia' OR 'neuropathic pain' AND 'pregabalin', with limits set for clinical and randomized controlled trials published in English. Five PHN trials (N = 1250) and nine DPN trials (N = 2554) were identified as suitable for inclusion based on methodological comparability. Descriptive safety data from the original trials were reviewed and the most commonly reported adverse events (AEs; dizziness, somnolence, peripheral oedema and weight gain) were identified to be of primary interest. The majority of AEs were of mild to moderate severity in Japanese and Western populations. The most commonly reported AE data (all-causality) with pregabalin (regardless of dose) in Japan (dizziness: PHN = 31.1%; DPN = 24.6%, and somnolence: PHN = 28.6%; DPN = 25.7%) were compared with pooled data from the Western trials (dizziness: PHN = 24.9%; DPN = 23.0%, and somnolence: PHN = 15.1%; DPN = 13.4%). Further assessment of these pooled AE (all-causality) data showed that dizziness and somnolence appeared early in the course of pregabalin treatment, but resolved before the end of the treatment in the majority of PHN and DPN patients (maximum duration of trials was 13 weeks). The slightly higher incidence of dizziness and somnolence in the two Japanese trials than that seen in the Western trials may reflect an increased exposure to pregabalin per fixed dose due to the lower mean bodyweight of the Japanese versus Western populations (on a mg/kg basis). However, of the participants who experienced these AEs (all-causality), the proportion who withdrew from the trials in Japan (dizziness: PHN = 23.5%; DPN = 18.2%, and somnolence: PHN = 10.3%; DPN = 10.9%) were comparable with the proportion who withdrew from trials in the West (dizziness: PHN = 16.0%; DPN = 29.3%, and somnolence: PHN = 19.4%; DPN = 34.2%). In Japan, 12.5% (PHN) and 15.1% (DPN) of patients experienced peripheral oedema as an AE (all-causality) compared with 8.8% (PHN) and 10.3% (DPN) in the West. Weight gain as an AE (all-causality) was experienced in 11.7% (PHN) and 13.4% (DPN) of patients in Japan compared with 3.8% (PHN) and 7.0% (DPN) in the West, but stabilized with continued treatment. Despite the lower mean bodyweight in Japanese versus Western patients, the PHN and DPN patients in Japan had stable blood glucose and HbA(1c) levels throughout the trials. The results of this review indicate safety outcomes in pregabalin trials are comparable between patients in Japan and those in the West. While managing peripheral neuropathic pain with pregabalin treatment, all patients should be observed closely for the incidence of dizziness and somnolence, especially at the beginning of treatment. These patients should also be monitored for evidence of peripheral oedema and weight gain during stable treatment, regardless of the source of neuropathic pain.

A 90-day oral (dietary) toxicity study of arruva, an R, R-monatin salt isomer, in Crl:CD-1(ICR) mice

R,R-Monatin [2R,4R- isomer of 2-hydroxy-2-(indol-3-ylmethyl)-4-aminoglutaric acid] is one of four natural constituent isomers in the root bark of Sclerochitin ilicifolius; and "arruva" is the common/usual name that is proposed to represent R,R-monatin salt forms, which have potential use as high potency sweetener food ingredients. In the present study, groups of male and female Crl:CD-1(ICR) mice were exposed to 0 (control), 5000, 10,000, 20,000, or 35,000ppm of arruva in the diet for 90days. There were no toxicologically relevant clinical or histopathological findings in any of the test article-treated groups. Significantly lower mean body weights and cumulative body weight gains were noted in the 35,000ppm group when compared to the control group. Mean body weights in the 35,000ppm group males and females were 9% and 7% less than the control group, respectively, at week 13. In the absence of observations associated with systemic toxicity and in consideration of the magnitude of body weight difference, these effects were not considered toxicologically significant. Based on the results of this study, the dietary no-observed-adverse-effect level (NOAEL) of arruva for 90days in male and female mice was 35,000ppm (equivalent to an exposure level of 5764 and 8013mg/kg bw/day, respectively).

Certoparin versus UFH to prevent venous thromboembolic events in the very elderly patient: An analysis of the CERTIFY study

Introduction There is an exponential rise of thromboembolic risk with age because of co-morbidities, immobility and pharmacotherapy. We aimed to investigate the benefits and risks of heparin prophylaxis in very elderly patients ≥ 80 years and the type of heparin used in a subgroup analysis of the CERTIFY trial. Patients/methods 3,239 patients were randomized to 3,000 U aXa o.d. certoparin or 5,000 IU t.i.d. unfractionated heparin (UFH) for 8–20 days. Results Patients ≥ 80 years (n = 1,365) were more likely to be female, had a lower mean bodyweight, were more frequently using antiplatelets and had a GFR below 30 ml/min/1.73 m 2 more often than patients < 80 years (n = 1,875). The combined endpoint of proximal DVT, symptomatic non-fatal PE and VTE related death was experience by 5.26% of patients ≥ 80 years versus 3.51% in younger patients (OR 1.53; 95%CI 1.05-2.21; p = 0.03). There were no significant differences in both minor (OR 1.11; 95%CI 0.75-1.62) and major (OR 2.53; 95%CI 0.93-6.86) bleeding risks. Certoparin and UFH were equally effective in reducing thromboembolic risk in either age group. The risk of any (OR 0.45; 95%CI 0.26-0.79) and minor bleeding (OR 0.42; 95%CI 0.23-0.78) was reduced with certoparin in the very elderly only. There were more adverse events in elderly patients (OR 1.26; 95%CI 1.1-1.46), but rates were otherwise comparable. Conclusions The analysis confirmed the increased thromboembolic risk in very elderly patients, but demonstrated no increased bleeding risk. Certoparin and UFH were equally effective and safe with a reduced risk of minor bleeding complications with certoparin in the very elderly.

Determination of the optimum transfer time of kutum (Rutilus frisii kutum) larvae from live food to artificial dry feed

Kutum Rutilus frisii kutum is known as a valuable commercial species in the southern part of Caspian Sea. Artificial rearing of fry has been introduced as an alternative to supply kutum fry in order to restock the kutum population in the Caspian Sea. The aim of this study was to find the suitable time to transfer kutum larvae from live food to artificial feed. The experiment began on day 3 post- hatching and lasted for 21 days. Mean initial weight of larvae was 4.5 mg. Five experimental groups including Group A (zooplankton alone for 21 days), Group B (12 days zooplankton + 9 days artificial feed), Group C (8 days zooplankton + 13 days artificial feed), Group D (4 days zooplankton + 17 days artificial feed) and Group E (artificial feed alone for 21 days) were considered for this experiment. According to the obtained results, the specific growth rate of kutum larvae varied from 8.01 to 13.58% day−1, and the highest and lowest specific growth rate were found in A and E treatments, respectively. The lowest mean body weight (24.6 mg) was found in larvae fed on artificial feed for 21 days. However, survival rates of kutum larvae fed mixed zooplankton for 8 and 12 days (85.83 and 89.33%, respectively) were comparable with those of larvae fed live food during the entire experiment (91.6%). The lowest survival rate (69.16%) was found in larvae fed artificial feed during the entire experiment.

Ambulatory-Based Standardized Therapy for Multi-Drug Resistant Tuberculosis: Experience from Nepal, 2005–2006

ObjectiveThe aim of this study was to describe treatment outcomes for multi-drug resistant tuberculosis (MDR-TB) outpatients on a standardized regimen in Nepal.MethodologyData on pulmonary MDR-TB patients enrolled for treatment in the Green Light Committee-approved National Programme between 15 September 2005 and 15 September 2006 were studied. Standardized regimen was used (8Z-Km-Ofx-Eto-Cs/16Z-Ofx-Eto-Cs) for a maximum of 32 months and follow-up was by smear and culture. Drug susceptibility testing (DST) results were not used to modify the treatment regimen. MDR-TB therapy was delivered in outpatient facilities for the whole course of treatment. Multivariable analysis was used to explain bacteriological cure as a function of sex, age, initial body weight, history of previous treatment and the region of report.Principal FindingsIn the first 12-months, 175 laboratory-confirmed MDR-TB cases (62% males) had outcomes reported. Most cases had failed a Category 2 first-line regimen (87%) or a Category 1 regimen (6%), 2% were previously untreated contacts of MDR-TB cases and 5% were unspecified. Cure was reported among 70% of patients (range 38%–93% by Region), 8% died, 5% failed treatment, and 17% defaulted. Unfavorable outcomes were not correlated to the number of resistant drugs at baseline DST. Cases who died had a lower mean body weight than those surviving (40.3 kg vs 47.2 kg, p<0.05). Default was significantly higher in two regions [Eastern OR = 6.2; 95%CL2.0-18.9; Far West OR = 5.0; 95%CL1.0-24.3]. At logistic regression, cure was inversely associated with body weight <36 kg [Adj.OR = 0.1; 95%CL0.0-0.3; ref. 55–75 kg] and treatment in the Eastern region [Adj.OR = 0.1; 95%CL0.0-0.4; ref. Central region].ConclusionsThe implementation of an ambulatory-based treatment programme for MDR-TB based on a fully standardized regimen can yield high cure rates even in resource-limited settings. The determinants of unfavorable outcome should be investigated thoroughly to maximize likelihood of successful treatment.

Evaluation Of Clinical Outcomes Of Female Participants In The UMDNJ Worksite Wellness Program

PURPOSE: To measure the effect of a university based worksite wellness program on clinical outcomes in female participants from baseline to 12 weeks, and at follow-up; and to examine differences in week 12 outcomes between those who did and did not return for follow-up METHODS: Female subjects (N=78; age = 47.96 + 8.75) participated in a 12-week, university-based wellness program that consisted of 12 weekly group sessions and three individual sessions on topics related to nutrition, physical activity, and behavior modification. Body weight, BMI, waist (WC) and hip (HC) circumferences, systolic and diastolic blood pressures (SBP, DBP), percent body fat, total cholesterol (TC) and non-fasting glucose were measured at baseline, week 12 and follow-up. Follow-up was done at one point in time which represented six, nine, or 12 months after intervention; 54 subjects returned compared with 24 who did not return. Univariate analyses were used for each of the clinical outcome measures. RESULTS:: All subjects improved at the end of the 12-week intervention with reductions in: body weight (1.70 + 2.44 kg, p < 0.001), BMI (0.63 + 0.90, p = 0.000), SBP (2.33 + 8.80 mm/Hg, p =0.005), DBP (1.70 + 7.76 mm/Hg, p = 0.016), WC (2.87 + 3.15 cm, p < 0.001), HC (2.20 + 2.68 cm, p<0.001) and percent body fat 0.55 + 2.02, p = 0.006). Weight reduction at week 12 was positively correlated with BMI (r=0.997 p=0.01), WC (r=0.388, p = 0.01), and HC (r=0.522, p=0.01). Those that returned for follow-up had a lower mean body weight at baseline (190.8 lbs + 44.7) and week-12 (187.7 lbs + 44.6). There was a significant interaction for HC in those that returned for follow-up compared to those who did not return (p=0.002). Those that returned for follow-up (n=57) had a decrease in HC from week 1 to 12 of 1.61 cm (+2.25 cm) compared to a greater decrease of 3.58cm (+ 3.11 cm) for those who did not return. CONCLUSIONS: The worksite wellness program had a positive impact on improving clinical outcome measures in females after the 12-week intervention. For those who returned for post-intervention follow-up, there was maintenance of the improvements from the end of the program. For those who did not return for follow-up, they may have experienced recidivism.

Metabolic assessment of menstruating and nonmenstruating normal weight adolescents

Resumption of menses (ROM) is a key indicator of recovery in AN, but patients may remain amenorrheic despite weight restoration. The objective of this study is to better understand the mechanism of amenorrhea in patients with eating disorders. A retrospective chart review was conducted of 382 normal weight adolescents with a history of anorexia nervosa, bulimia nervosa, or eating disorder not otherwise specified, who had been referred for indirect calorimetry tests. Resting energy expenditure (REE) was compared between amenorrheic (n = 60) and regularly menstruating females (n = 121). Participants with amenorrhea had a mean REE of 1,103 kcal/24 h (79% predicted), whereas participants who were menstruating regularly had a mean REE of 1,217 kcal/24 h (85% predicted; p = 0.001). The amenorrheic group was found to be at a lower mean body weight (53.7 +/- 5.6 kg vs. 57.5 +/- 7.4 kg; p < or = 0.001), at a lower percent ideal body weight (98.5 +/- 8.3% vs. 102.8 +/- 10.2%; p = 0.005), and at a lower BMI (20.5 +/- 1.7 vs. 21.5 +/- 2.2; p = 0.002). This study highlights that amenorrheic participants with a history of eating disorders who are at normal body weight are hypometabolic, suggesting an adaptive response to dietary restriction.

Effect of pregrazing herbage mass and pasture allowance on the lactation performance of Holstein-Friesian dairy cows

The objective of this study was to investigate the effect of pregrazing herbage mass (HM) and pasture allowance (PA) on the grazing management and lactation performance of spring-calving dairy cows. Sixty-eight Holstein-Friesian dairy cows (mean calving date, February 6) were randomly assigned across 4 treatments (n=17) in a 2×2 factorial arrangement. The 4 treatments consisted of 2 pregrazing HM (>4cm) and 2 PA (>4cm): 1,700kg of dry matter (DM)/ha (medium, M) or 2,200kg of DM/ha (high, H), and 16 or 20kg of pasture DM/cow per day. The experimental period lasted 30 wk. The experimental area was divided into 4 farmlets, with 1 farmlet per treatment. Mean HM throughout the experimental period was 1,767kg of DM/ha (M HM) compared with 2,358kg of DM/ha (H HM). Offering an M HM sward resulted in significantly greater milk protein yield (+31.7g/d) and lower mean body weight (−12.8kg). The body condition score change was significantly smaller (−0.21) with the M HM treatments compared with the H HM treatment (−0.34). Milk solids output per hectare was 6% greater on the M HM treatments compared with the H HM treatments. Increasing PA significantly increased milk (+0.9kg/d), solids-corrected milk (+0.7kg/d), protein (+43.9 g/d), and lactose (+52.7g/d) yields. Mean body weight was also significantly greater for cows offered 20kg of PA (+11.4kg/cow). It was concluded that in rotational grazing systems, adapting the concept of grazing M HM pastures (1,700kg of DM/ha) will result in increased sward quality and increased milk solids output per hectare. At medium levels of pregrazing HM, offering animals 20kg of DM PA will result in increased milk yield per cow.

Factors Associated with Bleeding in Elderly Hospitalized Patients Treated with Enoxaparin Sodium

Despite a lack of clear recommendations to guide decision-making, reductions in enoxaparin sodium dosage in the elderly and in patients with mild and moderate renal dysfunction are common in patients with acute coronary syndrome. To evaluate whether weight, age and renal function are associated with anti-factor Xa activity and with bleeding in elderly patients treated with enoxaparin sodium. This was a prospective observational study of 156 elderly patients admitted consecutively to a general internal medicine ward with creatinine clearance >30 mL/min who were treated with enoxaparin sodium twice daily. Anti-factor Xa activity and bleeding events were documented in all patients. Statistical analyses were conducted to determine the effects of clinical characteristics such as renal dysfunction, age and bodyweight on these parameters. 156 patients (60% males, mean age 71.0 +/- 15.98 years) were studied. Therapeutic anti-factor Xa was observed in 85.3% of patients treated with enoxaparin sodium 0.61-0.8 mg/kg/12h, and in 82.6% of patients treated with enoxaparin sodium 0.81-1.1 mg/kg/12h. Minor or major bleeding was observed in 5.8% of patients, and was associated with a lower mean bodyweight (61.89 +/- 13.35 vs 74.30 +/- 13.24 kg for patients with no bleeding; p = 0.014). Bodyweight < or =55 kg was associated with bleeding with an odds ratio of 5.63 (95% CI 1.2, 25, p = 0.025). Low bodyweight is associated with a greater risk of bleeding despite a reduction in enoxaparin sodium dose according to weight. This finding supports the possibility that low bodyweight is an independent risk factor for enoxaparin sodium-related bleeding.

Growth performance and osmoregulation in the shi drum ( Umbrina cirrosa) adapted to different environmental salinities

In order to investigate the ability of shi drum ( Umbrina cirrosa) to be reared at diverse locations, growth and osmoregulatory performance were assessed at full-strength seawater (40 psu), nearly iso-osmotic water (10 psu) and low salinity water (4 psu). At the end of the 84-day experimental period, fish reared at 4 psu displayed shorter mean fork length, lower mean body weight, lower specific growth rate and higher food conversion efficiency than fish reared at 10 or 40 psu. The effect of salinity on growth performance was also reflected by changes in plasma triglycerides and cholesterol, with fish reared at 4 psu exhibiting the lowest mean concentrations, while there was no significant difference in mean plasma glucose concentrations among treatments. Plasma osmolality was lower at 4 psu from day 42 onwards, while there was no significant difference in mean plasma K + and Cl − concentrations. Plasma sodium and gill Na +/K +-ATPase activity showed minimum values on day 42 at 4 psu, but at the end of the experiment there was no difference among groups. Pavement cells, mucus cells and chloride cells were identified by histology on the gill epithelium. In shi drum reared at full seawater, mucus cells contained a mixture of acid and neutral mucins, whereas in fish adapted to hypo-osmotic environment neutral mucins were mainly observed. There was a significant increase in chloride cell number over the course of the study in all fish, but there was no difference among the three experimental salinities. Finally, in fish reared at 40 psu salinity, chloride cells increased in size significantly compared to fish adapted to 4 psu, whereas at 10 psu after 42 d there was a significant reduction in chloride cell size. These results indicate that shi drum reared from full-strength seawater to iso-osmotic salinity do not face any osmoregulatory imbalance, while fish reared in hypo-osmotic water displayed osmoregulatory impairment and low growth performance.

An oral two-generation reproductive toxicity study of S-111-S-WB in rats

S-111-S-WB (CAS No. 72968-38-8), a mixture of perfluoro fatty acid ammonium salts, was administered daily via oral gavage to 30 Crl:CD(SD) rats/sex/group at 0.025, 0.125 and 0.6 mg/(kg day) over two generations to assess potential reproductive toxicity. Reproductive performance, mean litter size, pup survival and pup weights were unaffected. Lower mean body weights were observed in 0.6 mg/(kg day) group F 0 and F 1 males. Higher liver weights, correlating to hepatocellular hypertrophy in the 0.6 mg/kg group, were noted for parental males in the 0.125 and 0.6 mg/(kg day) groups, parental females in the 0.6 mg/(kg day) group and F 1 pups in the 0.125 and 0.6 mg/(kg day) groups. Higher kidney weights, correlating to renal tubule hypertrophy in the 0.6 mg/kg group, were observed for parental males and females in the 0.125 and 0.6 mg/(kg day) groups. Systemic exposure (measured only in females) to total S-111-S-WB was proportional to dose following 9 weeks of daily administration on the gestation day 19. Total S-111-S-WB concentration in the serum of male and female pups was 1.2–1.4-fold higher than in the dams 2 h following administration to the dams on lactation day 13. A dosage level of 0.6 mg/(kg day) was considered to be the no-observed-adverse-effect level (NOAEL) for reproductive function. A dosage level of less than 0.025 mg/(kg day) was considered to be the NOAEL for F 0 and F 1 parental systemic toxicity based on microscopic hepatic findings in the males of all test article groups, and a dosage level of 0.025 mg/(kg day) was considered to be the NOAEL for neonatal toxicity based on higher liver weights in the F 1 and F 2 pups at 0.125 mg/(kg day) and higher.

Re: Dietary Fat Reduction and Breast Cancer Outcome: Interim Efficacy Results From the Women's Intervention Nutrition Study

Background: Preclinical and observational studies suggest a relationship between dietary fat intake and breast cancer, but the association remains controversial. We carried out a randomized, prospective, multicenter clinical trial to test the effect of a dietary intervention designed to reduce fat intake in women with resected, early-stage breast cancer receiving conventional cancer management. Methods: A total of 2437 women were randomly assigned between February 1994 and January 2001 in a ratio of 40 : 60 to dietary intervention (n = 975) or control (n = 1462) groups. An interim analysis was performed after a median follow-up of 60 months when funding for the intervention ceased. Mean differences between dietary intervention and control groups in nutrient intakes and anthropometric variables were compared with t tests. Relapse-free survival was examined using Kaplan-Meier analysis, stratified log-rank tests, and Cox proportional hazards models. Statistical tests were two-sided. Results: Dietary fat intake was lower in the intervention than in the control group (fat grams/day at 12 months, 33.3 [95% confidence interval {CI} = 32.2 to 34.5] versus 51.3 [95% CI = 50.0 to 52.7], respectively; P<.001), corresponding to a statistically significant (P =.005), 6-pound lower mean body weight in the intervention group. A total of 277 relapse events (local, regional, distant, or ipsilateral breast cancer recurrence or new contralateral breast cancer) have been reported in 96 of 975 (9.8%) women in the dietary group and 181 of 1462 (12.4%) women in the control group. The hazard ratio of relapse events in the intervention group compared with the control group was 0.76 (95% CI = 0.60 to 0.98, P =.077 for stratified log rank and P =.034 for adjusted Cox model analysis). Exploratory analyses suggested a differential effect of the dietary intervention based on hormonal receptor status. Conclusions: A lifestyle intervention reducing dietary fat intake, with modest influence on body weight, may improve relapse-free survival of breast cancer patients receiving conventional cancer management. Longer, ongoing nonintervention follow-up will address original protocol design plans, which called for 3 years of follow-up after completion of recruitment.

Comparison of three multiple injection regimens for Type 1 diabetes: morning plus dinner or bedtime administration of insulin detemir vs. morning plus bedtime NPH insulin

This trial investigated the efficacy and safety of two different administration-time regimens with insulin detemir (IDet) to that of a conventional basal insulin regimen with NPH insulin (NPH). This multinational, 16-week, open, parallel group trial included 400 people with Type 1 diabetes mellitus (DM) randomized to IDet either morning and before dinner (IDetmorn+din) or morning and bedtime (IDetmorn+bed), or to NPH morning and bedtime (NPHmorn+bed), all in combination with mealtime insulin aspart (IAsp). HbA1c was comparable between the three groups after 16 weeks (P = 0.64), with reductions of 0.39-0.49% points. Lower fasting plasma glucose (FPG) was observed with IDetmorn+din and IDetmorn+bed compared with NPHmorn+bed (9.8 and 9.1 vs. 11.1 mmol/l, P = 0.006), whereas the IDet groups did not differ (P = 0.15). Within-person variation in self-measured FPG was significantly lower for both IDet regimens (sd IDetmorn+din 2.5, IDetmorn+bed 2.6 mmol/l) than for NPHmorn+bed (sd 3.1 mmol/l, P < 0.001), but was comparable between the IDet groups (P = 0.48). Ten-point plasma glucose profiles were lower between dinner and breakfast in the IDetmorn+din group (P = 0.043), compared with the two other groups. Risk of overall and nocturnal hypoglycaemia was similar for the three groups. Lower mean bodyweight was observed with IDet compared with NPH after 16 weeks (difference: (IDetmorn+din)-1.3 kg, P < 0.001, (IDetmorn+bed)-0.6 kg, P = 0.050). Both IDet regimens were well tolerated and provided lower and less variable glucose levels with no, or less, weight gain than NPH at comparable HbA1c. IDet can be administered either at dinner or bedtime, with similar glycaemic control according to the need of the individual person.

HIV-1 Viral Load and Elevated Serum α1-Antichymotrypsin Are Independent Predictors of Body Composition in Pregnant Zimbabwean Women

Human immunodeficiency virus (HIV) infection affects body composition, but their relationship has not been studied in pregnant women. We conducted a cross-sectional study among 1669 women receiving antenatal care between 22 and 35 wk of gestation in Harare, Zimbabwe. The role of HIV-1 status and viral load, malaria and elevated serum alpha(1)-antichymotrypsin (ACT, an acute phase protein) in weight, body mass index (BMI), arm circumference (AC), triceps skinfold thickness (TSF), and arm muscle (AMA) and fat (AFA) area were assessed using multiple linear regression analysis. The mean (range) age was 24.4 (14-45) y and gestational age 29 (22-35) wk. HIV infection was present in 31.5% of the women, malaria parasitemia in 0.4% and 11.4% had serum ACT >0.4 g/L. There was no difference in any anthropometric variable between HIV-infected and uninfected women. However, women with viral loads (genome equivalents/mL) between 4 and 5 and >5 log(10) had 1.1 [95% confidence interval (CI): -0.3, 2.3] and 2.5 (95% CI: 0.1, 5.1) kg lower weights compared with uninfected women; this was explained by losses of both AFA and AMA. Malaria parasitemia was associated with 6 cm(2) (95% CI: 0.4; 11.8) or 25% lower AMA. Elevated serum ACT was a negative predictor of all anthropometric variables, i.e., levels between 0.3 and 0.4, 0.4 and 0.5 and >0.5 g/L were associated with 1, 2 and 6 kg lower mean body weights, respectively. Despite the limitations of a cross-sectional design, we conclude that arm fat and muscle areas, reflecting body fat and lean body mass, seem to be unaffected in the majority of HIV-infected pregnant women, but decline with increasing viral loads. The effects of viral load are not explained by elevated serum ACT, which is a strong independent predictor of all anthropometric variables.

Studies of 50 Hz circularly polarized magnetic fields of up to 350 μT on reproduction and embryo‐fetal development in rats: Exposure during organogenesis or during preimplantation

Groups of mated female Sprague-Dawley rats were simultaneously exposed to 0 (sham exposed), 7, 70, or 350 microT (rms) circularly polarized 50 Hz magnetic fields (MF) for 22 h/day on gestational day 8-15, the period of rat fetal organogenesis (organogenesis study) or from day 0 to day 7 of gestation, the rat preimplantation period (preimplantation study). Developmental toxicity was assessed on gestational day 20. Identical experiments were repeated to confirm reproducibility of both studies. In both studies, statistically significant differences between exposed and sham exposed animals were observed in several measured parameters; however, these differences only appeared in one, but not both replicate experiments and generally at only an isolated exposure level. Because these differences were not reproducible and did not show a dose response relationship, they were not considered related to MF exposure. In the organogenesis study, lower kidney weights of dams were seen at 70 and 350 microT in Experiment 1. Lower dam liver weights and lower mean body weights of viable female and male fetuses were seen at 70 microT in Experiment 2. Otherwise, there were no differences in these parameters or in group means for fetal loss after implantation, number of viable fetuses, fetal body weight and sex ratio, incidences of external, visceral, and skeletal abnormalities or variations, or tissue abnormalities after histopathological examination. In the preimplantation study, dam health and indices for reproduction and embryo-fetal development, including pre or postimplantation loss, number and body weight of live fetuses, and sex ratio, external, skeletal abnormalities and variations, and skeletal ossification did not differ. Dam inorganic phosphorous concentration at 350 microT was elevated in one experiment and depressed in another. In one experiment, visceral abnormalities, primarily thymic remnant in neck and accessory liver lobe, were increased in the 7 microT group. Based on these results from two studies, we conclude that circularly polarized 50 Hz MF exposure of up to 350 microT during the fetal organogenesis or during the preimplantation period does not affect reproduction and embryo-fetal development in Sprague-Dawley rats.

Subchronic inhalation toxicity of the chlorinated propane 1,1,1,3,3,3-hexachloropropane (HCC-230fa).

Male and female rats were exposed by inhalation (whole body) to HCC-230fa (1,1,1,3,3,3-hexachloropropane) for 6 h/day, 5 days/week over a 15-week period. Concentrations of 0, 0.50, 2.5, and 25 ppm were studied. A total of eight groups/sex were exposed. Four groups of male and four groups of female rats were used to measure clinical signs and growth, clinical pathology, and tissue pathology. The remaining four groups of male rats were used for immunotoxicological and sperm assessment evaluations, and the remaining four groups of female rats were used for immunotoxicological evaluation. Following the exposure period, surviving male rats were kept for a 1- or 3-month recovery period. Male and female rats exposed to 25 ppm had lower mean body weights, mean body weight gains, and food consumption during the exposure period. Male and female rats exposed to 25 ppm and sacrificed immediately after the exposure period had minimally decreased total leukocyte and lymphocyte counts. These changes were considered to be marginally adverse. Pathologic examination revealed hepatocellular hypertrophy in 0-day recovery males and an increased incidence and/or severity in chronic progressive nephropathy in 0-day, 1-month recovery, and 3-month recovery males at 25 ppm. No other pathological changes, including the testis, epididymis, and other accessory sex organs, were noted in rats during the study. Evaluation of sperm parameters at the end of the exposure period showed statistically significant decreases in epididymal sperm number per cauda epididymis, percent motile sperm, and percent normal sperm morphology at 25 ppm. The biological significance of the slight changes observed in the sperm parameters in the absence of histopathological changes is unclear. After a 1-month recovery period, no biologically significant differences in sperm parameters were noted at 25 ppm compared with controls. Exposure to HCC-230fa did not significantly alter the primary humoral immune response to sheep red blood cell (SRBC). Under the conditions of this study, the no-observed-adverse-effect level (NOAEL) was considered to be 2.5 ppm.

Incidence of acquired immune deficiency syndrome (AIDS)-related disorders at laparotomy in patients with AIDS.

Patients with acquired immune deficiency syndrome (AIDS) present for surgical management of abdominal conditions that are complications of advanced human immunodeficiency virus (HIV) infection or that are caused by other disease not related to AIDS. This study compared the clinical details and postoperative outcomes of patients with AIDS-related diseases found at laparotomy with those of patients with non-AIDS-related disorders. The medical records of 30 consecutive patients with AIDS who underwent laparotomy were examined retrospectively. Fourteen patients had AIDS-related pathologies found at laparotomy, 13 had disease processes that were not AIDS related and three had no abnormal findings at laparotomy. Patients with AIDS-related conditions at laparotomy had lower mean body-weight, serum albumin concentration and CD4 lymphocyte count, and required a longer hospital admission than those who had non-AIDS-related disease. The duration of HIV infection and the number of complications and deaths were similar in the two groups. Complications occurred in 21 patients and there were five deaths (30-day mortality rate 17 per cent). AIDS-related pathologies are commonly found at laparotomy in patients with HIV/AIDS. An AIDS-related diagnosis does not confer a greater risk of complication or postoperative death than other conditions.

Efficacy of Narasin in the Prevention of Necrotic Enteritis in Broiler Chickens

The efficacy of narasin in the control of necrotic enteritis (NE) was investigated in a floor pen study of 2000 broiler chickens using a Clostridium perfringens feed inoculum challenge model. Treatments were 1) nonmedicated, nonchallenged; 2) nonmedicated, challenged; 3) narasin, nonchallenged; 4) narasin, challenged. Narasin was administered at 70 ppm in the feed from day 0 to trial termination on day 41. Challenge inoculum contained approximately 1 x 10(8) colony-forming units CP/ml and was administered from day 14 to day 16. In the unmedicated groups, challenged birds had significantly (P < 0.05) lower mean body weight and reduced feed efficiency at day 21 and significantly (P < 0.01) higher cumulative NE mortality at day 41 compared with unchallenged. Similarly, among unmedicated birds, those challenged had a significantly (P < 0.01) higher mean NE score on day 17 and significantly (P < 0.05) higher mean huddling scores on days 15-17 than unchallenged. Among challenged birds, those fed narasin had significantly (P < 0.05) higher mean body weight and improved feed efficiency at days 21 and 41 and significantly (P < 0.01) lower cumulative NE mortality at day 41 than unmedicated. Similarly, among challenged birds, those receiving narasin had a lower mean NE score on day 17 (P > 0.05) and significantly (P < 0.05) lower huddling scores on days 16 and 17 than unmedicated. Coccidiosis lesion scores were zero for birds euthanatized from all treatment groups on day 17, suggesting that the beneficial effects of narasin were not due to prevention of coccidiosis. This study thus provides evidence that narasin is effective in the prevention of necrotic enteritis in broiler chickens.