Associations between two common variants C677T and A1298C in the methylenetetrahydrofolate reductase gene and measures of folate metabolism and DNA stability (strand breaks, misincorporated uracil, and DNA methylation status) in human lymphocytes in vivo.

OBJECTIVE: Homozygosity for variants of the methylenetetrahydrofolate reductase (MTHFR) gene is associated with decreased risk for colorectal cancer. We have investigated the relationships between two variants of the MTHFR gene (C677T and A1298C) and blood folate, homocysteine, and genomic stability (strand breakage, misincorporated uracil, and global cytosine methylation in lymphocytes) in a study of 199 subjects. RESULTS: The frequencies of homozygosity for the C677T and A1298C variants of the MTHFR gene were 12.6% and 14.6%, respectively. Plasma homocysteine, folate, vitamin B12, 5-methyltetrahydrofolate, and RBC folate were determined in the C677T genotypes. Plasma folate was significantly lower (P < 0.001) in the homozygous variants (6.7 +/- 0.6 ng/mL) compared with wild-types (8.8 +/- 0.4 ng/mL) and heterozygotes (9.1 +/- 0.5 ng/mL). Homocysteine was significantly higher (P < 0.05) in homozygous variants (13.2 +/- 1.1 micromol/L) compared with homozygous subjects (10.9 +/- 0.4 micromol/L). Homozygous variants had significantly lower (P < 0.05) RBC folate (84.7 +/- 6.3 ng/mL) compared with wild-types (112.2 +/- 5.2 ng/mL) and heterozygous individuals (125.1 +/- 6.6 ng/mL). No significant difference in RBC folate was observed between wild-types and heterozygotes. The A1298C variant did not influence plasma homocysteine, folate, 5-methyltetrahydrofolate, vitamin B12, or RBC folate. Lymphocyte DNA stability biomarkers (strand breaks, misincorporated uracil, and global DNA methylation) were similar for all MTHFR C677T or A1298C variants. CONCLUSION: Data from this study do not support the hypothesis that polymorphisms in the MTHFR gene increase DNA stability by sequestering 5,10-methylenetetrahydrofolate for thymidine synthesis and reducing uracil misincorporation into DNA.     

Spontaneous Splenic Rupture in a Patient with Acute Lymphoblastic Leukemia of Burkitt Type

We describe a case of spontaneous splenic rupture occurred in a patient with acute lymphoblastic leukemia of Burkitt type before starting cytotoxic chemotherapy. Left hypochondrial pain radiating to the homolateral shoulder was the only clinical symptom. Emergency computed tomography showed splenic laceration and hemoperitoneum. The patient underwent immediate laparotomy with splenectomy and experienced an uneventful postoperative recovery. Eight days after surgery, chemotherapy could be administered and complete remission was achieved. Although spontaneous rupture of the spleen is rare in leukemia and related disorders, this diagnosis should be taken in account also when clinical symptoms are mild. Following immediate operative management, patients may completely recover and receive cytotoxic chemotherapy with substantial possibilities of achieving complete remission.     

Donor agencies' involvement in reproductive health: saying one thing and doing another?

The debates about what services constitute reproductive health, how these services should be organized, managed, and delivered, and what the role of donor agencies' support should be mirror the long-standing debates on how best to implement primary health care. After briefly reviewing the development of the discourse on primary health care and reproductive health, the authors present results of qualitative research in Ghana, Kenya, and Zambia that indicate a range of factors influencing and explaining the way donors operate in these countries and consider the implications of these results for the delivery of comprehensive reproductive health services. These findings are compared with South Africa, a country with limited donor activity. In the light of the complex interplay of factors, the authors suggest that donors' words and actions frequently do not correlate. Conclusions are drawn as to the potential for donor support for integrated reproductive health service delivery in sub-Saharan Africa, drawing on the research to provide lessons and a reappraisal of the role of donors in health sector aid.     

Consumer assessment of the quality of interpersonal processes of prenatal care among ethnically diverse low-income women: development of a new measure.

PURPOSE: Consumer assessments of interpersonal processes of care during prenatal care provide important information about how well clinicians satisfy the perceived needs of the women they serve, but few measures are available that tap the various components of these processes. The purpose of this study is to develop a multidimensional measure of prenatal interpersonal processes of care (PIPC) that demonstrates reliability and validity in ethnically diverse women in Medicaid managed care plans. METHODS: A telephone survey of African American, Latino (U.S. and foreign born) and Caucasian pregnant women in four Medicaid managed care plans in California was conducted in English and Spanish in 2001. Factor analytic methods were used to test the PIPC measures. A psychometric evaluation, including reliability, variability, and construct validity, was conducted with the final scales for the total sample and for each racial/ethnic group. RESULTS: Three dimensions, Communication, Patient-Centered Decision Making, and Interpersonal Style, with seven scales were supported with 30 items. The scales for each dimension exhibit acceptable reliability for the total sample (Internal Consistency Reliability ranged from 0.66 to 0.85) and for all racial/ethnic groups. All scales had significant associations with satisfaction with prenatal care and explained considerable variation in satisfaction (19-43%). The scale qualities and validity associations held for all scales and ethnic groups except some scales for U.S.-born Latinas. CONCLUSIONS: The multidimensional PIPC measure for assessing what actually happens between providers and low-income pregnant women of diverse ethnic groups demonstrates acceptable reliability and construct validity.     

mGluR5 antagonist MPEP reduces ethanol-seeking and relapse behavior.

The glutamatergic system plays an important role in mediating neurobehavioral effects of ethanol. Metabotropic glutamate receptors subtype 5 (mGluR5) are modulators of glutamatergic neurotransmission and are abundant in brain regions known to be involved in ethanol self-administration. Here, we studied the effects of 2-methyl-6-(phenylethynyl)-pyridine (MPEP), a highly potent, noncompetitive mGlu5 receptor antagonist, on voluntary ethanol consumption and relapse behavior. For this purpose, we used two models for the measurement of relapse behavior: (i) reinstatement of ethanol-seeking behavior by drug-associated cues and (ii) the alcohol deprivation effect in long-term ethanol-consuming rats. In the first set of experiments, rats were trained to lever press for ethanol in the presence of a distinct set of cues. After extinction, the animals were exposed to the respective cues that initiated reinstatement of responding. A response-contingent ethanol prime further enhanced responding compared to the conditioned cues alone. Under these conditions, MPEP (0, 1, 3, and 10 mg/kg) attenuated ethanol seeking significantly and in a dose-related manner. However, at the highest dose, MPEP also decreased the number of inactive lever responses. In the second set of experiments, rats with 1 year of ethanol experience and repeated deprivation phases were used. A subchronic treatment with MPEP (twice daily; 0, 3, and 10 mg/kg) resulted in a significant and dose-dependent reduction of the alcohol deprivation effect (ADE). Although the same MPEP treatment regimen decreased baseline drinking, this effect was not as pronounced as on the ADE. These results show in two commonly used models of relapse to ethanol that pharmacological targeting of mGlu5 receptors may be a promising approach for the treatment of alcoholism.     

The challenge of pain assessment in children with cognitive disabilities: Features and clinical applicability of different observational tools

Children with cognitive disabilities are at greater risk of experiencing pain. It has been shown that this paediatric population often receive inadequate pain management. Pain may be very difficult to assess, especially in a defined subgroup with non‐communicating intellectual disability or severe cognitive disability. Accordingly, several observational pain assessment tools have been proposed to overcome this issue. Due to the absence of an ideal measurement tool, accurate pain assessment requires, after a case‐by‐case analysis, selecting the more appropriate tool or a variety of combined instruments. The aim of this work is to provide a comprehensive review of the pain assessment tools commonly used in cognitively impaired children. Critical discussion on features and clinical applicability may suggest how to overcome this difficult challenge. Furthermore, this review will help further research aiming to design new instruments and to improve already‐in‐use tools.     

Cognition and functional performance in daily activities before and after pontine and extrapontine myelinolysis: A case study

Central pontine and extrapontine myelinolysis (CPEM) is a rare neurological condition usually due to rapid correction of hyponatremia. CPEM is mainly characterized by motor deficits (typically quadraparesis or extrapyramidal features) but neurobehavioral symptoms were also reported in the literature. However, very few studies on the neuropsychological and functional performance in daily activities have been performed in this population. In this case study, a 55-year-old woman had neuropsychology and functional evaluations prior and after the first manifestations of CPEM. The patient presented motor impairments characterized by parkinsonism symptoms and decreased dexterity. Several neurobehavioral deficits were observed including emotional lability, impulsivity, altered judgment, and disinhibition. Executive dysfunctions and impulsivity were observed during neuropsychological and functional evaluations, limiting the patient's autonomy in complex activities of daily living. The patient recovered progressively from most motor, neurobehavioral and cognitive deficits.     

Standardized Ultrasound Measurement of Subcutaneous Fat Patterning: High Reliability and Accuracy in Groups Ranging from Lean to Obese

A recently standardized ultrasound technique for measuring subcutaneous adipose tissue (SAT) was applied to normal-weight, overweight and obese persons. Eight measurement sites were used: upper abdomen, lower abdomen, erector spinae, distal triceps, brachioradialis, lateral thigh, front thigh and medial calf. Fat compression was avoided. Fat patterning in 38 participants (body mass index: 18.6–40.3 kgm^?2; SAT thickness sums from eight sites: 12–245 mm) was evaluated using a software specifically designed for semi-automatic multiple thickness measurements in SAT (sound speed: 1450 m/s) that also quantifies embedded fibrous structures. With respect to ultrasound intra-observer results, the correlation coefficient ρ = 0.999 (p < 0.01), standard error of the estimate = 1.1 mm and 95% of measurements were within ±2.2 mm. For the normal-weight subgroup, the median measurement deviation was 0.43 mm (1.1% of mean thickness), and for the obese/overweight subgroup it was 0.89 mm (0.5%). The eight sites used here are suggested to represent inter-individual differences in SAT patterning. High measurement accuracy and reliability can be obtained in all groups, from lean to overweight and obese, provided that measurers are trained appropriately.