Evidence for the presence of CFU-E with increased in vitro sensitivity to erythropoietin in sickle cell anemia

To investigate the cellular events that accompany erythroid hyperplasia, we studied several effects of erythropoietin (Epo) on marrow CFU-E in sickle cell anemia (SCA). We measured CFU-E number, CFU- E growth as a function both of Epo exposure time and of Epo concentration, and suppression of Epo-induced CFU-E formation by anti- Epo antiserum. With 0.5 U Epo/ml, the number of CFU-E was elevated in SCA (1,087 +/- 520) compared to normal (430 +/- 130). CFU-E were formed even when Epo was immediately neutralized by a 1/150 dilution of anti- Epo. After 40 hr of Epo exposure, only 2% of total CFU-E were expressed in normal marrow, whereas 12%-40% of CFU-E were expressed in SCA. Inhibition of CFU-E growth required at least 1/50 dilution of anti-Epo in SCA and a 1/300 dilution in normal marrow. In contrast to normal, a small number (5%-20%) of CFU-E were expressed in the absence of added Epo in SCA, and this pool required a 1/150 dilution of anti-Epo for inhibition. The Epo dose-response curve in SCA revealed a peak in colony formation around 0.1 U Epo/ml and 0.5 U Epo/ml, whereas only one peak at 0.5 U Epo/ml was seen in normals. These data strongly suggest that, in response to the demands of chronic erythroid hyperplasia in SCA, a pool of CFU-E is present characterized by increased in vitro sensitivity to Epo.     

Epidemiology of suicide in Israel: a nationwide population study

BACKGROUND: In Israel, some population characteristics and lifestyle patterns make epidemiological research on suicide of particular interest. The Israeli population is characterized by ethnic diversity, with a multi-religious, multi-national mosaic of Jews and Arabs. These subgroups also vary in their suicidal behavior. The aims of the present study were to examine the trends in suicide incidence rates in Israel from 1984 to 1994, to identify sub-populations at high risk for suicide and to identify suicide methods associated with increased risk. METHODS: Suicide rate trends in Israel over the period from 1984 to 1994 were examined for four subgroups: Jewish men and women, and Arab men and women. Cases of undetermined external cause (UEC) of death were also considered. Mortality data were obtained from the computerized data files of the Israeli Central Bureau of Statistics, which includes cause of death and sociodemographic variables. Suicide was classified according to the ICD-9 codes. RESULTS: Suicide rates were higher for Jews than for Arabs, and higher for men than for women. The rates among both population and sex groups increased directly with age. A significant increase over the years studied was found for Jewish men, particularly in the 18- to 21-year-old age group. An increase in the use of firearms was noted, mainly in the groups in which total suicide rates increased. CONCLUSIONS: The findings of this study highlight the need for further studies to identify both sub-populations at high risk for suicide, and societal trends such as lifestyles, immigration, military service, and media exposure to violence, as first steps toward planning of intervention programs to reduce suicide rates.     

Dose-related effects of chronic gestational cocaine treatment on maternal aggression in rats on postpartum days 2, 3, and 5

Gravid Sprague-Dawley rats received subcutaneous injections of saline, 3.5, 7.5 or 15 mg/kg of cocaine, twice daily, throughout gestation. On postpartum days 2, 3, and 5, dams and their litters (surrogate or natural) were videotaped for 10 minutes in the presence of a male rat for assessment of aggression towards the intruder. Oxytocin levels in discrete brain areas were assayed on postpartum day 5. The 30 mg/kg dose group had a significantly greater increase in the frequency of threats from postpartum day2 through postpartum day 5 than the 7.5 mg/kg cocaine and the non-yoke-fed saline control groups. Dams with natural litters exhibited a significantly greater frequency of receptive behavior compared to dams with surrogate litters. There were no significant differences in oxytocin levels between the 30 mg/kg cocaine-treated group and the other treatment or control groups on postpartum day 5. There are very few statistically significant cocaine-induced increases in maternal aggressive behavior and no dose-dependent decreases in amygdaloid OT levels in the early postpartum period.     

Sickle-cell disease not identified by newborn screening because of prior transfusion

Erythrocyte transfusion can impair detection of sickle-cell disease, galactosemia, or biotinidase deficiency with newborn screening. We report on 4 infants with SCD in whom delayed diagnosis was associated with neonatal transfusion. In 2 cases, the initial newborn screening showed no hemoglobin S. In no case was the recommended screening >/=120 days from the last transfusion obtained. Two children had significant SCD-related morbidity before diagnosis.     

Body mass index in 17-year-old Israeli males of different ethnic backgrounds; national or ethnic-specific references?

OBJECTIVE: To evaluate whether a single national reference is appropriate for assessing prevalence of overweight in heterogeneous populations, or whether ethnic-specific references are needed. DESIGN: A population-based study of Israeli Jewish males who underwent routine physical and clinical examinations prior to army recruitment served as the basis for the development of two types of references for body mass index (BMI): a national reference (NR) and an ethnic-specific reference (ER). SUBJECTS: Consecutive cohorts of all 17-y-old Jewish male recruits (n=109, 570). MEASUREMENTS: Weight, height and blood pressure values were obtained. BMI was calculated, and the 85th percentile of BMI was used as a cut-off point for overweight, using both types of references. Prevalence of hypertension among recruits was used as a biomarker to support the reliability of the ER when discrepancy in classification between the two references was found. RESULTS: As compared to the NR, three ethnic groups had a BMI distribution shifted to the left (light sub-population) and five were shifted to the right (heavy sub-population). In the light sub-population, 7% of the inductees who were classified as having normal weight by the NR were considered overweight by the ER and had a hypertension rate similar to that of those defined as overweight by both references (3.1 per 1000). In the heavy sub-population the 4% of subjects who were overweight by NR and normal by ER had hypertension rates similar to those defined as normal weight by both references (2.7/1000), and significantly lower than that of those classified as overweight by both references (10.8/1000). CONCLUSION: In heterogeneous populations, ethnic references should be used to evaluate prevalence of overweight, rather than one national reference. International Journal of Obesity (2000)24, 88-92     

Effect of osmotic lysis and resealing on red cell structure and function.

We have recently modified the dialysis tubing osmotic lysis and resealing method to examine the role of intracellular red blood cell (RBC) antioxidants. However, the potential effect of resealing on the RBC was not fully investigated. This study examined a number of cellular characteristics to determine the effects of physical lysis and resealing on the RBC. Following resealing, RBC exhibited normal morphology and at most only slight alterations in mean cell volume and mean cell hemoglobin concentration. RBC density distribution was significantly affected by resealing with increased populations of both light and dense cells, though the mean cell density was similar to that of control cells. Endogenous enzyme activities and adenosine triphosphate (ATP) concentration were unaffected by the resealing procedure. While reduced glutathione (GSH) concentration was decreased by 15%, RBC oxidant sensitivity was found to be unaltered. Cellular deformability of the resealed RBC was 80% to 90% that of the control cells. Membrane phospholipid and fatty acyl composition of the resealed RBC were unaffected when compared with matched control samples. Membrane transport, permeability, and Ca2(+)-mediated cellular vesiculation were minimally altered by resealing. Finally, entrapment of fluorescent compounds demonstrated that greater than 95% of the resealed RBC had incorporated exogenous agents. In summary, the osmotic lysis and resealing method described resulted in only minor changes in cellular characteristics while allowing for the efficient loading of compounds to which the RBC membrane is normally impermeable. Consequently, this method provides great potential for the selective modification of erythrocyte constituents in order to further define their roles within the RBC.     

Sickled erythrocytes accelerate clotting in vitro: an effect of abnormal membrane lipid asymmetry

A membrane lipid abnormality induced by sickling and found as a permanent alteration in the irreversibly sickled cell (ISC) is the rearrangement of phosphatidyl ethanolamine (PE) and phosphatidyl serine (PS) from the inner to the exterior side of the lipid bilayer. Since PS can provide a catalytic surface for the binding of blood coagulation factors and thus can exhibit procoagulant activity, we investigated the influence of oxy and deoxy reversibly sickled cells (RSC) ass well as ISC on clotting in vitro. Red blood cells (RBC), as the source of phospholipid, were added to platelet-poor citrated plasma containing Russell's viper venom (RVV) and clotting time was measured after recalcification. The clotting time after addition of normal RBC and oxy- RSC was similar to the saline blank (100 sec). In contrast, both oxy- ISC and deoxy completely sickled RSC shortened clotting time by 30%. Using liposomes prepared with identical phospholipid composition to the outer lipid leaflet of either normal RBC, RSC or ISC clotting times similar to those with intact cells were achieved. Since the liposomes did not contain protein, accentuation of clotting appears to be related to abnormal phospholipid organization, in particular to the abnormal exposure to aminophospholipids on the outer surface of the membrane. This abnormality may contribute to the pathogenesis of the vaso- occlusive episode in sickle cell anemia.     

Expression of T-helper-associated cytokines in the serum of pituitary adenoma patients preoperatively and postperatively

Pituitary adenomas are benign tumors, However, 30% of them may develop into invasive tumors by invading the surrounding tissues. The studies have shown that several cytokines were expressed in human anterior pituitary adenomas, therefore, we speculate that the cytokines are important in human anterior pituitary tumorigenesis. The current study is designed to investigate expression profiles of cytokines in the serum of patients with pituitary adenomas. This was done by selecting 75 cases with pituitary adenoma, including invasive and non-invasive pituitary adenomas and collected blood samples of preoperative, 1 month, 3 months, and 6 months after surgery, respectively. We used the cell flow instrument to detect the level of Lymphocytes and subsets and immunoglobulin and complement in the peripheral blood, and by ELISA detecting the content of cytokines (IL-17, IL-4, IL-5, TNF-α, INF-γ) in the serum of pituitary adenoma patients. The results show that the level of IL-4, IL-5 and IL-17 was increased substantially before surgery but they decreased substantially after surgery, IFN-γ, TNF-a was increased after surgery, the ratio of Th1/Th2 (IFN-γ/IL-4) was significantly lower before surgery and increased distinctly post-operation. These data indicated that there is some cross-regulation among Th1, Th2 and Th17 subsets and that cytokines are important in tissue inflammatory lesions of pituitary adenomas and promoting invasive development.     

The effect of gestational age on neonatal outcome in low-risk singleton term deliveries

Objective: To assess the association between gestational age at delivery and adverse neonatal outcome among term low-risk singleton neonates.

Methods: A retrospective cohort study design was used. The study group included all low-risk singleton term (37?+?0 to 41?+?6 weeks) newborns delivered in a single tertiary university-affiliated medical center over a 5-year period. Outcome of neonates delivered at 37?+?0 to 37?+?6 weeks of gestation (early term) and 41?+?0 to 41?+?6 weeks of gestation (late term) was compared to that of neonates delivered at 39?+?0–39?+?6 weeks of gestation (control).

Results: Overall, the outcome of 30?229 neonates was analyzed. The incidence of neonatal mortality was 1.0 per 1000 live-born neonates, with no significant difference between the various gestational age groups. Early term newborns were at higher risk for respiratory morbidity, hypoglycemia, hypocalcemia, thrombocytopenia and unexplained jaundice, and had higher rates of prolonged hospital stay, NICU admission, sepsis workup and antibiotic treatment. On multivariate analysis, early term delivery was an independent predictor for composite respiratory morbidity (OR=2.4, 95% CI 1.6–3.8, p?p?p?p?Conclusion: Even in low-risk singleton deliveries, early term is associated with an increased risk of neonatal morbidity.     

Pre-illness dietary factors in inflammatory bowel disease.

BACKGROUND: The effect of environmental factors has been demonstrated in the pathogenesis of inflammatory bowel disease (IBD). Nutrition may be one of them. AIM: To investigate the pre-illness diet in patients with recent IBD in comparison with matched population and clinic controls. METHODS: Quantified dietary histories were obtained from 87 patients with recent IBD (54 ulcerative colitis (UC) and 33 Crohn's disease (CD)) and 144 controls. Odds ratios (OR) for IBD were derived for intake levels of various foods. RESULTS: A high sucrose consumption was associated with an increased risk for IBD (OR 2.85 (p = 0.03) against population controls and 5.3 (p = 0.00) against clinic controls). Lactose consumption showed no effect while fructose intake was negatively associated with risk for IBD (NS). Similar trends were noted in UC and CD. A high fat intake was associated with an increased risk for UC; this was particularly marked for animal fat (OR 4.09, p = 0.02) and cholesterol (OR 4.57, p = 0.02). A high intake of fluids (p = 0.04), magnesium (p = 0.04), vitamin C, and fruits (NS) was negatively associated with the risk for IBD, while a positive association was found for retinol (p = 0.01). Most of the findings were similar in UC and CD except for potassium and vegetable consumption which showed a negative association only with risk for CD. CONCLUSIONS: An association was found between pre-illness diet and subsequent development of UC and CD. The effect of dietary components may be primary or modulatory.