Acute effects of rapamycin on glomerular dynamics: a micropuncture study in the rat

The acute effects of cyclosporin (CsA, 20 mg(kg i.v.) and rapamycin (RAPA, 5 mg(kg i.v.) on glomerular dynamics were separately investigated by renal micropuncture in two groups of intact rats (group CsA and RAPA, respectively) and compared with vehicle-treated rats, used as controls (group CON). Left kidney glomerular filtration rate (GFR) was decreased by CSA (-35% vs. CON, P<0.05), but was not affected by RAPA (-14% vs. CON, NS), whereas the single-nephron GFR (SNGFR) was significantly decreased in both groups (-40% in CsA, P<0.01 and -26% in RAPA, P<0.05 vs. CON). In both groups glomerular plasma flow (GPF) was significantly reduced vs. CON (CsA: -48%, and RAPA: -25%) due to the increase in both afferent (Ra) and efferent (Re) glomerular resistances: group CSA showed a prevalent rise in Re (+98% vs. CON, P<0.001) than in Ra (+66%, P<0.001); in group RAPA the increment was modest and similar in Ra and Re (+33 and +32%, respectively, NS versus CON). A further group of rats was studied in which L-Arginine (ARG), the precursor of nitric oxide (NO), was administered (2.5 mg/Kg/min iv) with RAPA (group ARG). ARG limited the rise in Ra and Re, thereby preserving GPF; nevertheless, SNGFR remained low (-26% vs. CON, P<0.05) due to the decrease in the effective filtration pressure (-26% vs. CON). These data demonstrate that: (1) CsA is nephrotoxic at immunosuppressive doses; (2) RAPA, even at huge doses, has marginal effects on renal and glomerular dynamics; (3) the ARG-NO pathway is only partially involved in the vasoconstriction of superficial nephrons after RAPA administration.     

Prognostic value of CD40 in adult soft tissue sarcomas.

PURPOSE: The purpose is to evaluate the expression of CD40, a membrane protein predominantly expressed on B cells, dendritic cells, and macrophages, in a series of adult soft tissue sarcomas and to test its possible prognostic value. EXPERIMENTAL DESIGN: CD40 expression was studied by immunohistochemistry. Correlations with other baseline characteristics of patients and tumors were analyzed with chi(2) test. The prognostic value was studied with univariable and multivariable analysis adjusted by age, sex, tumor size, grade, location, and distant metastases. RESULTS: Eighty-two patients, between January 1994 and May 2001, were analyzed. Membrane or cytoplasmic staining for CD40 protein was absent in 30% of the tumors but present in <10% of cells in 22 (27%), in 10% to 50% in 23 (28%), and in >50% of cells in 12 (15%) tumors. There was no correlation between CD40 expression and age, sex, size, grade, and location of the primary tumor and distant metastases. With 61 patients (74.4%) progressed and 31 (37.8%) dead, CD40 expression was a significant prognostic factor for disease-free and overall survival at univariable and multivariable analysis. Patients with tumors expressing CD40 in >50% of cells had a dramatically unfavorable prognosis with median disease-free and overall survival of 7 and 17 months, respectively, and hazard ratios of relapse and death as compared with patients with CD40-negative tumors of 2.89 (95% confidence interval: 1.26-6.60) and 6.92 (95% confidence interval: 2.18-22.0), respectively. CONCLUSIONS: These data suggest that expression of CD40 protein in >50% of cells might indicate an unfavorable prognosis in adult soft tissue sarcomas.     

A comparison in cosmetic outcome between per-operative interstitial breast implants and delayed interstitial breast implants after external beam radiotherapy.

BACKGROUND AND PURPOSE: Interstitial implants for brachytherapy boost in the breast conserving therapy of breast cancer can be performed in two ways; implants during the tumor excision (per-operative implants) or after the external beam therapy (delayed interstitial implants). Differences in cosmetic outcome were investigated. PATIENTS AND METHODS: Cosmetic results in 47 patients having a per-operative implant were compared to 123 patients having a delayed interstitial implant in a matched case-control study. Cosmesis was scored on a four-point-scale varying from 0 (excellent) to 3 (poor). RESULTS: After mean follow-up of 63 months, three observers found no difference in cosmetic outcome between the two groups after adjustment for variables found to be related with cosmesis (difference in mean score 0.50, P=0.26). Implant volume at 100% isodose was not found to differ (P=0.084) between the per-operative group (mean 102 cm3, S.D. 34 cm3) and the delayed group (mean 93 cm3, S.D. 29 cm3). CONCLUSIONS: Performing per-operative implants has not led to smaller implants. The method of performing brachytherapy does not result in marked differences in cosmetic outcome.     

Social difficulties and victimization in children with SLI at 11 years of age.

Specific language impairment is sometimes thought to be associated with concurrent difficulties in the area of social and behavioral development (N. Botting and G. Conti-Ramsden, 2000; D. P. Cantwell and L. Baker, 1987; M. Fujiki, B. Brinton, and C. Todd, 1996; S. Redmond and M. Rice, 1998). The present study follows a group of 242 children, initially studied at age 7 years when they attended language units in England, and assesses their social and behavioral status at age 11 years. In total, 64% of the children were found to have scores on the Rutter behavioral questionnaire (M. Rutter, 1967) of 9 or above (clinical threshold); 34% scored over the threshold for the Strengths and Difficulties questionnaire (R. Goodman, 1997); and 39% scored below average on the Peer Competence subscale of the Harter Perceived Competence Scale (S. Harter and R. Pike, 1984). On further analysis, these generalized difficulties were characterized mainly by poor social competence. In addition, 36% of the cohort were at risk of being regular targets for victimization compared to 12% of a comparison sample of typically developing peers. Few associations were found between social outcome and other measures, including nonverbal intelligence, overall linguistic skill, gender, and longitudinal measures taken previously. Importantly, however, pragmatic language difficulties measured on the Children's Communication Checklist (D. V. M. Bishop, 1998) were most strongly related to poor social outcome and to expressive language related to victimization.     

School vision screening, ages 5–16 years: the evidence-base for content, provision and efficacy

The optometric profession in the UK has a major role in the detection, assessment and management of ocular anomalies in children between 5 and 16 years of age. The role complements a variety of associated screening services provided across several health care sectors. The review examines the evidence-base for the content, provision and efficacy of these screening services in terms of the prevalence of anomalies such as refractive error, amblyopia, binocular vision and colour vision and considers the consequences of their curtailment. Vision screening must focus on pre-school children if the aim of the screening is to detect and treat conditions that may lead to amblyopia, whereas if the aim is to detect and correct significant refractive errors (not likely to lead to amblyopia) then it would be expedient for the optometric profession to act as the major provider of refractive (and colour vision) screening at 5-6 years of age. Myopia is the refractive error most likely to develop during primary school presenting typically between 8 and 12 years of age, thus screening at entry to secondary school is warranted. Given the inevitable restriction on resources for health care, establishing screening at 5 and 11 years of age, with exclusion of any subsequent screening, is the preferred option.     

A realist qualitative study to explore how low‐income pregnant women use Healthy Start food vouchers

Healthy Start is the UK government's food voucher programme for low‐income pregnant women and young children. It was introduced in 2006, but the impact of the programme on nutritional outcomes remains understudied. This study sought to explore potential outcomes of the Healthy Start programme (including intended and unintended outcomes) and develop explanations for how and why these outcomes might occur. A realist review preceded this study, in which programme theories were developed and tested using existing evidence. This qualitative study aimed to further refine and consolidate the programme theories from the realist review while remaining open to new and emerging theories (or hypotheses) about how low‐income pregnant women use Healthy Start vouchers. Semistructured interviews were conducted with 11 low‐income women from North West England, who received Healthy Start vouchers during pregnancy. A realist logic of analysis was applied to generate clear and transparent linkages between outcomes and explanations. The findings suggested that some women used the vouchers to improve their diets during pregnancy (intended outcome), whereas some women were diverted towards alternative or unintended outcomes. Women's circumstances, values, beliefs, and motivations influenced how they perceived and responded to the vouchers. This paper presents four evidence‐based programme theories to explain four contrasting (and potentially overlapping) outcomes: dietary improvements (theory refined from review), shared benefits (new theory), financial assistance (theory refined from review), and stockpiling formula (new theory). It considers how the Healthy Start programme could be improved, to increase the possibilities for low‐income women to experience the intended outcome of dietary improvements.     

Effects of quercetin on the gastrointestinal tract in rats and mice

Intraperitoneal administration of quercetin (6.25–50 mg/kg) significantly (p<0.5-0.01) reduced intestinal transit in mice and this effect was antagonized by yohimbine and phentolamine but not by atropine or naloxone. Quercetin (12.5–50 mg/kg) reduced also (p<0.05-0.01) intraluminal accumulation of fluid and diarrhoea induced by castor oil and these effects were antagonized by yohimbine. Finally quercetin (12.5–50 mg/kg) reduced the area of gastric ulcer but not the number. It is suggested that α2-adrenergic receptors mediate the effect of quercetin on intestinal motility and secretion.