Capillary whole blood measurement of islet autoantibodies.
(41/3987)
OBJECTIVE: Islet cell antibody (ICA) measurements in serum are used for large-scale screening to identify subjects who are at high risk of developing type 1 diabetes. The aim of this study was to adapt measurements to capillary whole blood samples to facilitate and reduce screening costs. RESEARCH DESIGN AND METHODS: GAD65, IA-2, and combined GAD65/IA-2 antibody tests were performed on patients with type 1 diabetes, first-degree relatives of patients, and control subjects, and results from serum, plasma, whole venous blood, and capillary whole blood lysates were compared. Measurements obtained in serum and eluates from dried capillary blood spots from 36 ICA+ first-degree relatives were also compared. RESULTS: GAD65, IA-2, and combined GAD65/IA-2 antibody levels were completely concordant with measurements obtained from serum, plasma, whole venous blood, and capillary whole blood lysates. Antibody levels obtained in eluates from dried capillary blood spots were lower than corresponding serum samples, and weak antibodies were not detected. CONCLUSIONS: Initial screening for diabetes risk can be performed using one drop of capillary whole blood without further processing to separate serum. This method should be considered as a way to simplify and reduce costs of screening programs. (+info)
Astrocytes enhance radical defence in capillary endothelial cells constituting the blood-brain barrier.
(42/3987)
Astrocytes (AC) induce blood-brain barrier (BBB) properties in brain endothelial cells (EC). As antioxidative activity (AOA) is assumed to be a BBB characteristic, we tested whether AC improve AOA of EC. Monocultivated AC showed higher AOA [manganese superoxide dismutase (SOD), catalase (Cat), glutathione peroxidase (GPx)] than EC. Cocultivation elevated AOA in EC (MnSOD, CuZnSOD, Cat, GPx), and AC (MnSOD, CuZnSOD, GPx). Hypoxia increased radical-induced membrane lipid peroxidation in monocultivated, but not in cocultivated EC. Thus, EC/AC cocultivation intensifies AOA in both cell types, protects the EC, and therefore, the BBB against oxidative stress. The high AOA is regarded as an essential property of the BBB, which is induced by AC. (+info)
Endothelial cell nitric oxide synthase in peritumoral microvessels is a favorable prognostic indicator in premenopausal breast cancer patients.
(43/3987)
Nitric oxide (NO) is involved in tumor cell apoptosis and has additional effects on tumor blood flow, immune responses, and angiogenesis. We, therefore, studied endothelial cell NO synthase (ecNOS) protein expression in a retrospective series of 118 patients with primary invasive breast cancer. Immunocytochemically stained paraffin sections were used for determining the frequency of (a) tumor cells, (b) intratumoral microvessels, and (c) peritumoral microvessels that were positive for ecNOS. A high density of ecNOS positive microvessels in the normal tissue surrounding the tumor (measured by the variable PEMVD) was associated with significantly better recurrence-free and overall survival. The prognostic significance was observed in a representative series of premenopausal patients and was independent of other factors, including lymph node status. The counting procedure was highly reproducible and correlated to stereological measurements but was influenced by heterogeneity of the tissue samples. Analyzing two sections per patient improved the discriminative power by reducing the influence of tissue heterogeneity and produced highly significant results (recurrence-free survival, P < 0.001; overall survival, P < 0.0001). Immunoreactive ecNOS in microvessels is an independent prognostic factor in breast cancer and may reflect a mechanism of endothelial defense against invasion by tumor cells. Individual variations in ecNOS may be related to environmental, hormonal, and genetic factors and could represent a therapeutic target. (+info)
Precision, accuracy, and reliability of hemoglobin assessment with use of capillary blood.
(44/3987)
BACKGROUND: Previous research has suggested that there may be significant within-subject variability, both site-to-site and over time, in hemoglobin concentrations in capillary blood. OBJECTIVE: This study examined the reliability of the portable hemoglobinometer (PHM) system with use of capillary blood and the implications of errors of the magnitude found for the classification of anemia status in individuals and population groups. The precision and accuracy of the method with use of venous blood were also tested. DESIGN: Three empirical data sets were used to measure reliability, precision, and accuracy of the PHM system [2 from Honduras (n = 87 and 141); 1 from Bangladesh (n = 73)]. Simulation data were used to assess the implications of errors for screening individuals for anemia and to estimate anemia prevalence. RESULTS: High within-subject variability (unreliability) was identified when capillary blood from the left hand was compared with that from the right hand (CV: 6.3%) and when measurements were taken on 4 consecutive days (CV: 7.0%). Reliability was only 69% and 50%, respectively. Precision and accuracy, however, were very high (concordance coefficients of 0.99 and 0.98 and CV < 1%). CONCLUSIONS: The simulation data showed that errors of the magnitude found due to unreliability can lead to misclassification of anemia status in individuals and small biases in anemia prevalence estimates. We recommend replicate sampling to reduce the influence of unreliability in the use of the PHM system with capillary blood. (+info)
School-administered weekly iron-folate supplements improve hemoglobin and ferritin concentrations in Malaysian adolescent girls.
(45/3987)
BACKGROUND: Iron deficiency and its consequent anemia constitute the commonest micronutrient deficiency in the world. OBJECTIVE: We investigated whether long-term, weekly iron-folate supplements administered at school would improve hemoglobin and ferritin concentrations in adolescent girls, including those with mild-to-moderate anemia and hemoglobin concentrations indicating borderline anemia. DESIGN: Subjects were 266 girls with hemoglobin concentrations of 80-119.9 g/L (group A) and 358 girls with hemoglobin concentrations of 120-130 g/L (group B) who were otherwise healthy. Two hundred sixty-six girls in group A and 268 girls in group B were randomly assigned to receive either 60 or 120 mg Fe plus 3.5 mg folic acid weekly for 22 wk. Ninety of the girls in group B were randomly assigned to receive only 5 mg folic acid weekly. Capillary hemoglobin and plasma ferritin were measured at baseline and after 12 and 22 wk of supplementation. RESULTS: By the end of the study, 2% of the girls had dropped out and > 96% had taken > or = 20 of the 22 tablets; side effects were minimal. Mean plasma ferritin increased significantly in all iron-supplemented groups, independently of initial hemoglobin values and iron doses. Ferritin concentrations decreased in the girls supplemented with folic acid only. As expected, hemoglobin responses to iron were higher in group A than in group B and increases were positively correlated with initial plasma ferritin. Hemoglobin failed to respond to folate supplementation if initial plasma ferritin concentrations were low. Mean hemoglobin increased significantly and consistently in relation to the length of treatment. CONCLUSION: Long-term, weekly iron-folate supplementation was found to be a practical, safe, effective, and inexpensive method for improving iron nutrition in adolescent schoolgirls. (+info)
Inhibition of choriocapillaris regeneration with genistein.
(46/3987)
PURPOSE: To test the effects of genistein on choriocapillaris regeneration and retinal pigment epithelial (RPE) wound healing in a surgical model in the rabbit. METHODS: Intravitreal injections of either 0.1 ml of a 90-microM concentration of genistein, dimethyl sulfoxide (DMSO; negative control), or 2 microg cycloheximide (positive control) were given 24 hours before surgical debridement of RPE in rabbits. Scanning electron microscopy (EM) of choroidal vascular casts and the RPE wounds and histologic evaluation by light microscopy and EM of the disturbed areas were performed at days 1, 7, and 30 after surgery. Quantitative analysis of the area of the choriocapillaris bed and RPE was performed by automated image analysis, and the results were analyzed by paired Student's t-test. RESULTS: Loss of RPE caused a rapid initial atrophy followed by slower subsequent revascularization of the choriocapillaris, which paralleled the RPE wound healing. Choriocapillaris regeneration appeared nearly normal by day 30 in the DMSO group. Inhibition of choriocapillaris revascularization by genistein was significant at day 30 when compared with the DMSO-treated negative control (P = 0.013). There was a strong trend toward inhibition in the cycloheximide-treated positive control group (P = 0.062), which reached significance at day 7 compared with the DMSO group (P = 0.02). RPE covered the wound area by day 7 in all groups. CONCLUSIONS: Intravitreal injection of genistein was found to cause significant inhibition of choriocapillaris regeneration without apparent effect on RPE wound healing. Tyrosine kinase inhibitors such as genistein may be useful as a pharmacologic approach in the treatment of choroidal neovascularization. (+info)
Capillary density of skeletal muscle: a contributing mechanism for exercise intolerance in class II-III chronic heart failure independent of other peripheral alterations.
(47/3987)
OBJECTIVES: The study was conducted to determine if the capillary density of skeletal muscle is a potential contributor to exercise intolerance in class II-III chronic heart failure (CHF). BACKGROUND: Previous studies suggest that abnormalities in skeletal muscle histology, contractile protein content and enzymology contribute to exercise intolerance in CHF. METHODS: The present study examined skeletal muscle biopsies from 22 male patients with CHF compared with 10 age-matched normal male control patients. Aerobic capacities, myosin heavy chain (MHC) isoforms, enzymes, and capillary density were measured. RESULTS: The patients with CHF demonstrated a reduced peak oxygen consumption when compared to controls (15.0+/-2.5 vs. 19.8+/-5.0 ml x kg(-1) x min(-1), p <0.05). Using cell-specific antibodies to directly assess vascular density, there was a reduction in capillary density in CHF measured as the number of endothelial cells/fiber (1.42+/-0.28 vs. 1.74+/-0.35, p = 0.02). In CHF, capillary density was inversely related to maximal oxygen consumption (r = 0.479, p = 0.02). The MHC IIx isoform was found to be higher in patients with CHF versus normal subjects (28.5+/-13.6 vs. 19.5+/-9.4, p <0.05). CONCLUSIONS: There was a significant reduction in microvascular density in patients with CHF compared with the control group, without major differences in other usual histologic and biochemical aerobic markers. The inverse relationship with peak oxygen consumption seen in the CHF group suggests that a reduction in microvascular density of skeletal muscle may precede other skeletal muscle alterations and play a critical role in the exercise intolerance characteristic of patients with CHF. (+info)
Systemic and microcirculatory effects of autologous whole blood resuscitation in severe hemorrhagic shock.
(48/3987)
Systemic and microcirculatory effects of autologous whole blood resuscitation after 4-h hemorrhagic shock with a mean arterial pressure (MAP) level of 40 mmHg were investigated in 63 conscious Syrian golden hamsters. Microcirculation of skeletal skin muscle and subcutaneous connective tissue was visualized in a dorsal skinfold. Shed blood was retransfused within 30 min after 4 h. Animals were grouped into survivors in good (SG) and poor condition (SP) and nonsurvivors (NS) according to 24-h outcome after resuscitation and studied before shock, during shock (60, 120, and 240 min), and 30 min and 24 h after resuscitation. Microvascular and interstitial PO2 values were determined by phosphorescence decay. Shock caused a significant increase of arterial PO2 and decrease of PCO2, pH, and base excess. In the microcirculation, there was a significant decrease in blood flow (QB), functional capillary density (FCD; capillaries with red blood cell flow), and interstitial PO2 [1.8 +/- 0.8 mmHg (SG), 1.3 +/- 1.3 mmHg (SP), and 0.9 +/- 1.1 mmHg (NS) vs. 23.0 +/- 6.1 mmHg at control]. Blood resuscitation caused immediate MAP recompensation in all animals, whereas metabolic acidosis, hyperventilation, and a significant interstitial PO2 decrease (40-60% of control) persisted. In NS (44.4% of the animals), systemic and microcirculatory alterations were significantly more severe both in shock and after resuscitation than in survivors. Whereas in SG (31.8% of the animals) there was only a slight (15-30%) but still significant impairment of microscopic tissue perfusion (QB, FCD) and oxygenation at 24 h, SP (23.8% of the animals) showed severe metabolic acidosis and substantial decreases (>/=50%) of FCD and interstitial PO2. FCD, interstitial PO2, and metabolic state were the main determinants of shock outcome. (+info)