Nocturnal blood pressure and 24-hour pulse pressure are potent indicators of mortality in hemodialysis patients

BACKGROUND: Cardiovascular (CV) complications are the leading cause of mortality in hemodialysis patients. The role of arterial hypertension on the prognosis of CV in hemodialysis patients is not as clear as in the general population. The purpose of this study was to investigate the prognostic role of ambulatory blood pressure (BP) on CV mortality in treated hypertensive hemodialysis patients. METHODS: Fifty-seven treated hypertensive hemodialysis patients (56.87 +/- 16.22 years, 30 men) were prospectively studied. All patients initially underwent an ambulatory BP monitoring between two dialysis sessions. The outcome event studied was CV death; kidney transplantation and deaths not related to CV disease were censored. RESULTS: The duration of follow-up was 34.4 +/- 20.39 months, during which 10 CV and 8 non-CV fatal events occurred. In the 10 patients who died from CV complications, age, previous CV events, ambulatory systolic BP, ambulatory pulse pressure (PP), and life-long smoking level were significantly higher, and the office diastolic BP was lower at the time of inclusion than in those who did not die from CV complications (N = 47). Based on Cox analysis and after adjustment for age, sex, and previous CV events, a low office diastolic BP [relative risk (RR) 0.49, 95% CI, 0.25 to 0.93, P = 0.03], an elevated 24-hour PP (RR 1.85, 95% CI, 1.28 to 2.65, P = 0.009), and an elevated nocturnal systolic BP (RR 1.41, 95% CI, 1.08 to 1.84, P = 0.01) were predictors of CV mortality (RR associated with a 10 mm Hg increase in BP and in PP). CONCLUSION: This study demonstrates that nocturnal BP and 24-hour PP are independent predictors of CV mortality in treated hypertensive hemodialysis patients. Randomized trials are needed to investigate whether nocturnal BP and 24-hour PP are superior to office BP as targets for antihypertensive therapy in this high-risk group.     

[18F] FDG PET in Gastric Non-Hodgkin's Lymphoma

The possibility of using [¹⁸F] FDG PET for assessment of tumor extension in primary gastric non-Hodgkin's lymphoma (NHL) was studied in 8 patients (6 high-grade and 2 Iow-grade, one of the MALT type) and in a control group of 7 patients (5 patients with NHL without clinical signs of gastric involvement, 1 patient with NHL and benign gastric ulcer and 1 patient with adenocarcinoma of the stomach). All patients with gastric NHL and the two with benign gastric ulcer and adenocarcinoma, respectively, underwent endoscopy including multiple biopsies for histopathological diagnosis. All patients with high-grade and one of the two with low-grade NHL and the patient with adenocarcinoma displayed high gastric uptake of [¹⁸F] FDG corresponding to the pathological findings at endoscopy and/or CT. No pathological tracer uptake was seen in the patient with low-grade gastric NHL of the MALT type. In 6/8 patients with gastric NHL, [¹⁸F] FDG PET demonstrated larger tumor extension in the stomach than was found at endoscopy, and there was high tracer uptake in the stomach in two patients who were evaluated as normal on CT. [¹⁸F] FDG PET correctly excluded gastric NHL in the patient with a benign gastric ulcer and in the patients with NHL without clinical signs of gastric involvement. Although the experience is as yet limited, [¹⁸F] FDG PET affords a novel possibility for evaluation of gastric NHL and would seem valuable as a complement to endoscopy and CT in selected patients, where the technique can yield additional information decisive for the choice of therapy.     

The epidemiology of rotavirus diarrhea in Latin America. Anticipating rotavirus vaccines.

OBJECTIVE: To assess the disease burden and characterize the epidemiology of rotavirus diarrhea in Latin America. METHODS: We conducted a literature review of studies of children < 5 years of age who were hospitalized or seen as outpatients for diarrhea and for whom rotavirus was sought as the etiologic agent of the diarrhea. This review included inpatient and outpatient studies published since 1998 that included at least 100 children and reported surveillance activities lasting at least 12 consecutive months. RESULTS: A total of 18 inpatient and 10 outpatient studies met the criteria for inclusion in this review. Rotavirus was detected in a median of 31% of inpatients (range, 16%-52%) and 30.5% of outpatients (range, 4%-42%). The median detection rate was higher in studies that used an enzyme-linked immunosorbent assay (ELISA) (inpatients 38%, outpatients 33%) versus less sensitive methods of detection. The age distribution of rotavirus disease varied among countries, with 65%-85% of children hospitalized in the first year of life. Most countries had rotavirus admissions year round, and rotavirus generally exhibited a winter seasonal peak in both temperate and tropical climates. CONCLUSIONS: The heavy burden of disease attributable to rotavirus in Latin America suggests that vaccines currently being tested could have considerable impact in preventing hospitalizations, clinic visits, and deaths. The findings of the young age distribution of patients highlight the importance of early immunization for the success of a vaccine program. The data suggest that future surveillance for rotavirus diarrhea in Latin America should use a standardized surveillance protocol with an ELISA for detection. Data from surveillance studies will be critical to monitor the impact of the future introduction of vaccines.     

Spectacle use and reduced unaided vision in third grade students: a comparative study in different educational settings

Background: The development of myopia is influenced by hereditary factors, environmental factors and geneenvironment interaction. Reading and near‐work activity are associated with myopia and myopic progression. This study sought to determine and compare the prevalence of reduced unaided vision and spectacle use among third grade Israeli students from three different educational settings. Method: A sample of 917 students (mean age 8.5 years, range seven to 10 years) was drawn from the three Israeli educational streams: secular, Orthodox and ultra‐Orthodox. Children in the ultra‐Orthodox education pathway begin studying at the age of three years and their daily reading involves sustained near work with increased accommodative effort accompanied by head‐rocking movements. Reduced distance vision was used to indicate the likely development of or an increase in the amount of myopia. Spectacle lenses were measured to determine the prevalence of myopia. Results: Of the 917 students studied, 103 (11.2 per cent) wore spectacles (14.2 per cent of the males and eight per cent of the females); 82.5 per cent of those who wore spectacles were myopic. Males from ultra‐Orthodox schools had the highest rate of reduced unaided vision (72.5 per cent) compared with males from secular schools (27.3 per cent), males from Orthodox schools (59.3 per cent) or with females from all three groups (average of 34.8 per cent, p < 0.0001, chi squared). Males had a higher rate of reduced unaided vision, especially in the Orthodox and ultra‐Orthodox schools. Conclusions: Our study suggests that Jewish ultra‐Orthodox males have a higher prevalence and degree of myopia. The study habits of young children, including exposure to prolonged near tasks, high accommodative demands and possibly optical defocus induced by body sway, may contribute to the development of myopia.     

Interactions of chronic lead exposure and intermittent stress: consequences for brain catecholamine systems and associated behaviors and HPA axis function.

Elevated lead (Pb) burden and high stress levels are co-occurring risk factors in low socioeconomic status (SES) children. Our previous work demonstrated that maternal Pb exposure can permanently alter hypothalamic-pituitary-adrenal (HPA) axis function and responsivity to stress challenges in offspring. The current study sought to determine the consequences of chronic Pb exposures initiated later in development combined with variable intermittent stress challenges. Male rats were exposed chronically from weaning to 0, 50, or 150 ppm Pb acetate drinking solutions (producing blood Pb levels of <5, 9-15, and 23-27 mug/dl, respectively). Pb itself decreased basal plasma corticosterone, with greater effects at 50 than 150 ppm; 150 ppm reduced both cytosolic and nuclear glucocorticoid receptor binding. Responsivity to stress challenges including novelty, cold, and restraint, was measured as changes in Fixed Interval (FI) schedule-controlled behavior in a subset of rats within each group. FI performance was modified by novelty stress only in Pb-treated rats, whereas cold and restraint stress effects were comparable across groups. Novelty elevated corticosterone equivalently across groups, but cold stress markedly increased corticosterone only in Pb-treated groups. The pattern of Pb-induced changes in serotonin (5-HT) or its metabolite 5-HIAA in frontal cortex, nucleus accumbens, striatum, and hypothalamus resembled that observed for basal corticosterone levels indicating a relationship between these variables. In addition to suggesting the potential for HPA axis-mediated effects of Pb on the central nervous system, these findings also raise questions about whether single chemicals studied in isolation from other relevant risk factors can adequately identify neurotoxic hazards.     

Irinotecan plus oxaliplatin and leucovorin-modulated fluorouracil in advanced pancreatic cancer--a Groupe Tumeurs Digestives of the Federation Nationale des Centres de Lutte Contre le Cancer study.

PURPOSE: To evaluate response rate and toxicity of irinotecan and oxaliplatin plus fluorouracil (FU) and leucovorin (Folfirinox) in advanced pancreatic adenocarcinoma (APA). PATIENTS AND METHODS: Chemotherapy-naive patients with histologically proven APA and bidimensionally measurable disease were treated with Folfirinox therapy every 2 weeks, which comprised oxaliplatin 85 mg/m(2) and irinotecan 180 mg/m(2) plus leucovorin 400 mg/m(2) followed by bolus FU 400 mg/m(2) on day 1, then FU 2,400 mg/m(2) as a 46-hour continuous infusion. Quality of life (QOL) was assessed using European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire C30 (EORTC QLQ-C30). RESULTS: Forty-seven patients were entered, and 46 received treatment. Thirty-five patients (76%) had metastatic disease. A total of 356 cycles were delivered, with a median of eight cycles per patient (range, one to 24 cycles). All patients were assessable for safety. No toxic death occurred. Grade 3 to 4 neutropenia occurred in 52% of patients, including two patients with febrile neutropenia. Other relevant toxicities included grade 3 to 4 nausea (20%), vomiting (17%), and diarrhea (17%) and grade 3 neuropathy (15%; Levi's scale). The confirmed response rate was 26% (95% CI, 13% to 39%), including 4% complete responses. Median time to progression was 8.2 months (95% CI, 5.3 to 11.6 months), and median overall survival was 10.2 months (95% CI, 8.1 to 14.4 months). Between baseline and end of treatment, patients had improvement in all functional scales of the EORTC QLQ-C30, except cognitive functioning. Responders had major improvement in global QOL. CONCLUSION: With a good safety profile, a promising response rate, and an improvement in QOL, Folfirinox will be further assessed in a phase III trial.     

Análisis de la concentración sérica del ADN tumoral en el cáncer de pulmón no microcítico y avanzado: ¿es útil como factor pronóstico?

INTRODUCTION: Presence of circulating DNA in the serum of patients with cancer makes detection of tumour-specific genetic alterations feasible. OBJECTIVE: To study serum DNA concentration in patients diagnosed as having advanced Non-Small Cell Lung Cancer (NSCLC) and to evaluate its relationship with age, histology, stage, response, time-to-progression (TTP), and survival. METHODS: Serum DNA from 78 patients was purified and spectrophotometrically quantified. RESULTS: No significant correlations were found between serum DNA concentration and age, histology, response and survival. There was a significant correlation with respect to stage (IIIB = 408.75 ng/ml; IV = 478.74 ng/ml; p = 0.02). When patients were grouped according to DNA concentration, significant correlation with TTP was found; establishing a cut-off point at 500 ng/ml ([DNA] < 500 ng/ml TTP = 7.25 months, 95%CI: 3.5-5.25; [DNA ] > or = 500 ng/ml TTP = 4.25 months, 95%CI: 2-6.5; p = 0.05). CONCLUSIONS: Using the present method, DNA concentration quantification appears to be simple, but with certain deficiencies due to inter-sample variability and low specificity. This is because total DNA concentration is measured without distinguishing as to whether it is tumour-related. We suggest that there is a correlation between DNA concentration and prognosis which enables an analysis of the natural history of the disease.     

Vascular modulation through exercise improves chemotherapy efficacy in Ewing sarcoma

Recent studies in mouse models of cancer have shown that exercise improves tumor vascular function, thereby improving chemotherapy delivery and efficacy. However, the mechanisms underlying this improvement remain unclear and the effect of exercise on Ewing sarcoma (ES), a pediatric bone and soft tissue cancer, is unknown. The effect of exercise on tumor vascular hyperpermeability, which inversely correlates with drug delivery to the tumor, has also not been evaluated. We hypothesized that exercise improves chemotherapy efficacy by enhancing its delivery through improving tumor vascular permeability. We treated ES‐bearing mice with doxorubicin with or without moderate treadmill exercise. Exercise did not significantly alter ES tumor vessel morphology. However, compared to control mice, tumors of exercised mice had significantly reduced hyperpermeability, significantly decreased hypoxia, and higher doxorubicin penetration. Compared to doxorubicin alone, doxorubicin plus exercise inhibited tumor growth more efficiently. We evaluated endothelial cell sphingosine‐1‐phosphate receptors 1 and 2 (S1PR1 and S1PR2) as potential mediators of the improved vascular permeability and increased function afforded by exercise. Relative to tumors from control mice, vessels in tumors from exercised mice had increased S1PR1 and decreased S1PR2 expression. Our results support a model in which exercise remodels ES vasculature to reduce vessel hyperpermeability, potentially via modulation of S1PR1 and S1PR2, thereby improving doxorubicin delivery and inhibiting tumor growth more than doxorubicin alone does. Our data suggest moderate aerobic exercise should be tested in clinical trials as a potentially useful adjuvant to standard chemotherapy for patients with ES.     

Shoulder dystocia: a comparison of patients with and without diabetes mellitus

Background: The study was aimed to compare pregnancies complicated with shoulder dystocia, of patients with and without diabetes mellitus. Methods: A comparison of all singleton, vertex, term deliveries between the years 1988–1999, complicated with shoulder dystocia with and without diabetes mellitus was performed. Statistical analysis was done using receiver operating characteristic curve analysis. Results: Using a receiver operating characteristic curve analysis, the area under the curve for birth weight was 0.92 (95% CI 0.90–0.93). However, for birth weight of 4,000 g the sensitivity was only 56% with specificity of 95%. While comparing shoulder dystocia between patients with (n=38) and without diabetes mellitus (n=207), neonates of the diabetic patients were significantly heavier (mean birth weight 4,244.2±515.1 vs. 4,051.6±389.5; P=0.008) and had higher rate of Apgar scores lower than 7 at 1 min (50.0% vs. 25.9%; P=0.030), but not at 5 min (2.6% vs. 2.0%; P=0.083) when compared to the non-diabetic group. No significant differences were noted regarding perinatal mortality between the groups (0% vs. 4.3%; P=0.362). Conclusions: The newborn of the diabetic mother complicated with shoulder dystocia does not appear to be at an increased risk for perinatal morbidity compared with the newborn of the non-diabetic mother. Presented in part at the Society for Gynecologic Investigation 50th Annual Scientific Meeting, Washington, DC, 27–30 March 2003.