BRAF and NRAS Mutations Are Frequent in Nodular Melanoma but Are not Associated with Tumor Cell Proliferation or Patient Survival

Previous studies have shown frequent mutations in the BRAF (V-raf murine sarcoma viral oncogene homolog B1) or NRAS (neuroblastoma RAS viral [V-ras] oncogene homolog) genes in cutaneous melanoma, but the relationship between these alterations and tumor cell proliferation has not been examined in human melanoma. In our study of 51 primary nodular melanomas and 18 paired metastases, we found mutations in BRAF (codon 600, previously denoted 599) in 15 primary tumors (29%) and eight metastases (44%). The figures for NRAS mutations were 27% and 22%, respectively. Mutations in BRAF and NRAS genes were mutually exclusive in all but one case, and were maintained from primary tumors through their metastases. Mutations, however, were not associated with tumor cell proliferation by Ki-67 expression, tumor thickness, microvessel density, or vascular invasion, and there were no differences in patient survival. Although BRAF and NRAS mutations are likely to be important for the initiation and maintenance of some melanomas, other factors might be more significant for proliferation and prognosis in subgroups of aggressive melanoma.     

A mitochondrial myopathy in an infant with lactic acidosis

We describe a girl with mitochondrial myopathy, who presented with general muscle weakness, muscle hypotonia and motor retardation. The level of blood lactate and pyruvate was consistently increased. Enzymatic studies showed impairment of NADH-dehydrogenase activity (complex I of the respiratory chain) in skeletal muscle. Electron-microscopy of a muscle biopsy showed abnormalities of a mitochondrial myopathy. The girl, now aged 30 months, has been treated with riboflavine (vitamin B2) since the age of 14 months, and lactate and pyruvate levels have decreased to normal. The patient still shows mild muscle hypotonia and weakness, but good motor progress and normal cognitive development.     

Service quality in hospital wards with different nursing organization: nurses' ratings

Title. Service quality in hospital wards with different nursing organization: nurses’ ratings. Aim. This paper is a report of a study to assess: (1) the relations between nursing organization models in hospital wards and nurses’ perception of the quality of patient care and dimensions of the practice environment, and (2) if these relations were modified by variations in local conditions at the ward level. Background. Previous literature is inconclusive concerning what model of nursing organization maximizes the quality of nursing services. Method. A cross‐sectional survey was carried out in a representative sample of Norwegian hospital wards in 2005. Intra‐ward organization models were classified as: (1) Team leader (n = 30), characterized by extensive responsibilities for team leaders, (2) Primary nurse (n = 18), with extensive responsibilities for named nurses, and (3) Hybrid (n = 37), (1) and (2) combined. We prepared multilevel regression models using scales describing quality of patient care, learning climate, job satisfaction, and relationships with physicians as dependent variables. As independent variables, we used variables representing local ward conditions. Results. Eighty‐seven wards and 1137 nurses (55% response rate) provided complete data. The ward level proportion of variance ranged from 0·10 (job satisfaction) to 0·22 (relationships with physicians). The univariate effect of organization models on quality ratings was not statistically significant. Introducing local ward conditions led to a statistically significant effect of primary nurse organization on relationships with physicians, and to a substantial proportional reduction in ward level variance, ranging from 32% (quality of patient care) to 24% (learning climate). Conclusion. Caution is needed about using service quality arguments when considering the possible benefits and drawbacks of different organizational models.     

Correlation between ocular pulse amplitude measured by dynamic contour tonometer and visual field defects

Purpose To investigate the correlation between ocular pulse amplitude and visual field defects in patients with glaucoma, ocular hypertension, and glaucoma suspicion when measured with the Pascal Dynamic Contour Tonometer, and to verify if the ocular pulse amplitude is an independent predictor for visual field parameters. Methods Seventy-seven eyes (42 patients) with glaucoma, ocular hypertension or glaucoma suspicion were examined. Ocular pulse amplitude was measured with the dynamic contour tonometer by one investigator masked to the visual field data. Visual fields were performed within three months of ocular pulse amplitude measurement by the Octopus or Humphrey Field Analyser, and were analysed with Peridata Software. Mean defect, pattern standard deviation (√ Loss Variance) and regression analysis of those parameters (Trend Indices) were correlated with the ocular pulse amplitude for each eye. Results Forty-nine eyes had glaucoma, 14 had ocular hypertension, and 14 were glaucoma suspects. The mean follow-up was 46.5 (range 6–96) months. There was a significant correlation between OPA and MD and OPA and PSD, even after correction for IOP (and diagnostic group and eye): the estimated slope equals 2.68 (S.E. = 0.82, p = 0.003) and −0.86 (S.E. = 0.33, p = 0.014), respectively. There was even a weak correlation between OPA and the evolution of MD (dB/year). The slope estimate for OPA equals 0.070 (S.E. = 0.033), p = 0.037. However, after correction for IOP (and diagnostic group and eye), the strength of the relationship is reduced and the evidence disappears: the slope estimate for OPA now equals 0.039 (S.E. = 0.041), p = 0.34. There is no evidence for an association between OPA and the evolution of Trend-PSD. Conclusion A small ocular pulse amplitude, as measured with a dynamic contour tonometer, is correlated with moderate to severe glaucomatous visual field loss and might be a risk factor for the development of glaucomatous visual field defects.     

Treatment of hypercholesterolemia in children and adolescents

In patients with severe genetic hypercholesterolemia, therapeutic reduction of elevated serum total cholesterol and LDL cholesterol should begin in early childhood to lower the risks of cardiovascular disease later in life. We evaluated the effects of outpatient therapy with diet alone and with combined diet and drug therapy in children and adolescents with hypercholesterolemia of apparent dominant inheritance. Serum lipid values before and during dietary treatment were available in 35 patients (mean age at start of treatment 7.9 years, range 2.0-17.6 years) followed for an average duration of 17.5 months (range 4-70 months). A comparison between untreated state and combined therapy with diet and cholestyramine was possible in 14 patients (mean age 8.6 years, range 2.4-17.0 years) followed for 27.9 months (range 4-97 months). Dietary modification achieved by repeated counseling and training lowered serum total cholesterol by mean (+/- SE) 11.7 +/- 1.9% (p < 0.0001) and LDL cholesterol by 17.3 +/- 3.5% (p < 0.0001). However, five of 35 patients did not show an appreciable effect of therapy (cholesterol reduction < 5%), possibly because of non-compliance. Diet combined with cholestyramine in an average dose of 0.36 g/kg body weight/day reduced total cholesterol by 33.0 +/- 2.4% (p < 0.0001) and LDL cholesterol by 37.5 +/- 4.3% (p < 0.0001) and was effective in all patients. Both forms of treatment had no effect on serum triglycerides and HLD cholesterol. No serious side effects were noted, and percentile values for weight and height remained unchanged in all but three obese children.(ABSTRACT TRUNCATED AT 250 WORDS)