The 'intestinal-renal' arginine biosynthetic axis in the aging rat

It has been suggested that L-arginine availability declines with advanced age, which could contribute to the endothelial dysfunction and decreased nitric oxide (NO) production that are features of aging. L-Arginine is made in the kidney and since the aging kidney develops progressive injury there may be decreased synthesis limiting availability. In this study we investigated the impact of aging on the regulation, at the gene level, of the various enzymes that synthesize L-arginine in the kidney (argininosuccinate synthetase and argininosuccinate lyase) and citrulline, the precursor of L-arginine made in the small intestine (phosphate-dependent glutaminase, carbamyl phosphate synthetase-1 and ornithine transcarbamylase). Studies were in young (3-5 months), middle-aged (11-13 months) and old (18-22 months) male and female Sprague-Dawley rats aged under barrier conditions. The plasma, renal cortical and brain cerebellar levels of L-arginine are unchanged in the old male rat, and expression of the genes involved in renal arginine synthesis and small intestinal citrulline synthesis is unchanged or upregulated with age in both males and females. This study shows that the synthesis of L-arginine is maintained with aging despite developing kidney damage. Therefore, the reduced NO generating capacity that occurs in aging must be due to downstream changes in the NO biosynthesis pathway, such as reduced abundance of NO biosynthetic enzymes.     

Mammographic breast density and family history of breast cancer

The association between mammographic breast density and breast cancer risk may be the result of genetic and/or environmental factors that determine breast density. We reasoned that if the genetic factors that underlie breast density increase breast cancer risk, then breast density should be associated with family history of breast cancer. Therefore, we determined the association between mammographic density and family history of breast cancer among women in the San Francisco Mammography Registry. Mammographic density was classified using the four BI-RADS criteria: 1 = almost entirely fatty, 2 = scattered fibroglandular tissue, 3 = heterogeneously dense, and 4 = extremely dense. We adjusted for age, body mass index, hormone replacement therapy use, menopause status, and personal history of breast cancer. Compared with women with BI-RADS 1 readings, women with higher breast density were more likely to have first-degree relatives with breast cancer (BI-RADS 2, odds ratio [OR] = 1.37, 95% confidence interval [CI] = 0.96 to 1.89; BI-RADS 3, OR = 1.70, 95% CI = 1.19 to 2.40; BI-RADS 4, OR = 1.70, 95% CI = 1.05 to 2.71). Thus, the genetic factors that determine breast density may determine breast cancer risk.     

Prognostic value of global myocardial performance indices in acute myocardial infarction: comparison to measures of systolic and diastolic left ventricular function

STUDY OBJECTIVES: Assessment of global myocardial performance by a single index (ie, the myocardial performance index [MPI]) has been suggested as an appealing alternative to the individual assessment of systolic and diastolic left ventricular (LV) function We sought to test the prognostic value of MPI in comparison to clinical characteristics and echocardiographic parameters of LV filling and ejection in acute myocardial infarction (AMI). PATIENTS: Four hundred seventeen consecutive patients with AMI were examined within 24 h of hospital admission. INTERVENTIONS: Doppler echocardiographic measures of systolic, diastolic, and global myocardial performance were assessed within 24 h of hospital admission. In addition to MPI (ie, the sum of the isovolumic time intervals divided by ejection time), we determined the isovolumic/heterovolumic time ratio, which expresses the time "wasted" by the myocardium to generate and decrease LV pressure without moving blood. RESULTS: The end points of the study at 30 days were death (4.7%), congestive heart failure (23%), and recurrent infarction (4.8%), and occurred in 109 patients, who were compared as group B to 314 patients without an event (group A). Multivariate analysis identified only age (odds ratio [OR], 1.04; 95% confidence interval [CI], 1.02 to 1.07), LV ejection fraction (LVEF) < or = 40% (OR, 3.82; 95% CI, 2.15 to 6.87), and E-wave deceleration time (EDT) of < or = 130 ms (OR, 2.29; 95% CI, 1.0 to 5.21) as independent predictors of adverse events. CONCLUSION: LVEF and EDT are powerful and independent echocardiographic predictors of poor outcome following AMI, and are superior to indexes of global LV performance. Both parameters should be taken into consideration when deciding about the management of these patients.     

Quality of life following surgery for anterior skull base tumors

OBJECTIVES: To evaluate patients' quality of life (QOL) after surgical extirpation of anterior skull base tumors, to elucidate different QOL domains, and to define possible predictors of functional outcome postoperatively. DESIGN: Retrospective survey. SETTING: University-affiliated medical center. PARTICIPANTS: Sixty-nine patients (76 consecutive cases) who underwent subcranial surgery between 1994 and 2002 for extirpation of anterior skull base tumors. MAIN OUTCOME MEASURE: A multidimensional, disease-specific questionnaire with 39 items was used. Six relevant domains of QOL were assessed: role of performance, physical functioning, vitality, pain, specific symptoms, and impact on emotions. RESULTS: The response rate for completing the questionnaire was 98% (40/41) after excluding patients who died (n = 13), were lost to follow-up (n = 10), and were operated on within 3 months of commencement of the study (n = 5). Thirty patients (74%) reported a significant improvement or no change in overall QOL within 6 months after surgery. The worst impact of surgery on the patients' QOL was on their financial status and emotional state. The most influential factor on QOL was malignancy leading to a significant decrease in the overall score. Radiotherapy, old age, comorbidity, and wide resection also significantly worsened QOL scores of specific domains. CONCLUSION: After subcranial extirpation of anterior skull base tumors, the overall outcome of the patients is good. Old age, malignancy, comorbidity, wide resection, and radiotherapy are negative prognostic factors for these patients' QOL.     

Early therapy for latent tuberculosis infection

The risk of developing active tuberculosis is highest within the first 2 years of infection. Therefore, an intervention that targets persons with recent infection, such as identifying contacts of active cases, could be particularly effective as an epidemic control measure. A mathematical model of a tuberculosis epidemic is formulated and used to evaluate the strategy of targeting therapy to persons with recently acquired latent tuberculosis infection. The model is used to quantify the effectiveness of therapy for early latent tuberculosis infection in reducing the prevalence of active tuberculosis. The model is also used to demonstrate how effective therapy for early latent tuberculosis infection has to be to eliminate tuberculosis, when used in conjunction with therapy for active tuberculosis. Analysis of the model suggests that programs such as contact investigations, which identify and treat persons recently infected with Mycobacterium tuberculosis, may have a substantial effect on controlling tuberculosis epidemics.     

Postpartum depression in an Israeli cohort: demographic, psychosocial and medical risk factors

Demographic, psychosocial and medical risk factors for postpartum depression (PPD) were studied prospectively in a community cohort of 288 Israeli women. An Edinburgh Postnatal Depression Scale score of > or = 10 at 6 weeks postpartum was the criterion for PPD. Psychosocial risk factors were found to be the most potent. Lack of social support, marital disharmony, depressive symptoms during pregnancy, history of emotional problems and prolonged infant health problems were most predictive of PPD. The major role of psychosocial factors in PPD was similar to that found in other countries. The results were somewhat different for new Russian immigrants. These findings indicate that early identification of women at risk for PPD is feasible, and that consideration should be taken of subgroups that may be at heightened risk, or for whom risk factors play different roles.