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The objective of this study was to examine whether there is a difference in the frequency of fetal erythroblasts in maternal blood in pregnancies with intrauterine growth restriction (IUGR) as compared with normal pregnancies. Nucleated red blood cells (NRBC) were isolated from nine pregnant women with ultrasonically diagnosed IUGR (estimated fetal weight less than the 10th percentile for gestational age) and 11 women with appropriately grown fetuses. The frequency of fetal hemoglobin-expressing NRBC (FHE-NRBC) in maternal blood was evaluated by triple density centrifugation and anti-CD71+ magnetic cell sorting, followed by indirect immunocytochemistry for the detection of gamma-chain fetal hemoglobin. The number of FHE-NRBC in 10 ml maternal blood in the IUGR group was higher than in the control group (454.5 vs 56.7, p

Activity levels of total and placental alkaline phosphatase (AP) were determined in maternal serum and neutrophils of normal and Down syndrome pregnancies. The placental iso-enzyme (PAP) was identified by its relative stability to urea and heat. Significant increase in the activity of all iso-enzymes across gestational stages was observed in maternal sera of 28 normal pregnancies. However, in the neutrophil extracts of the same blood samples no differences were detected between trimesters. Another set of experiments was aimed at finding diagnostic differences of PAP activity in maternal neutrophils of normal and trisomy 21 affected pregnancies. No differences of heat stable AP activity were found in maternal samples of 19 normal and 19 Down syndrome affected pregnancies. Urea resistant AP proportions were also similar when measured after 40 minutes of exposure (13 samples in each group). However, a marginally significant increase was observed in the mean value of the Down syndrome affected samples, after 60 minutes of urea treatment. In view of the above results we conclude that neutrophil AP activity is not as yet a useful marker for the screening of trisomy 21 fetuses.

Objective To ascertain the influence of estrogen replacement therapy (ERT) on blood and urinary zinc in postmenopausal women. Methods Thirty-seven postmenopausal women aged 53.2 ± 3.7 years were examined. All were treated with conjugated estrogens 0.625 mg and medroxyprogesterone acetate 5 mg. Zinc, magnesium, calcium, phosphate, and alkaline phosphatase levels in blood were measured before and after 6 and 12 months of treatment. Urinary excretion of zinc, magnesium, calcium, phosphate, and hydroxyproline were evaluated before and after 3, 6, and 12 months of therapy. Bone mineral density was examined before treatment and after 1.7 ± 0.3 years of ERT. Subjects were classified by 1) initial bone mineral density values (osteoporotics less than 0.850 g/cm 2 ) and 2) zinc excretion as elevated (greater than 600 μg/g creatinine). Results At baseline, the values of most markers of bone turnover were higher in the osteoporotic women (Hotelling test, P = .06). After 1 year of treatment, a higher decrease of most indices was observed in the osteoporotic patients, and no statistical difference was found between the osteoporotic and the normal groups (Hotelling test, P = .31). A consistent negative association was observed between changes in bone mineral density and urinary zinc excretion in the osteoporosis group. Estrogen replacement therapy reduced excretion of zinc, magnesium, and hydroxyproline in the elevated zinc excretion group. Zinc excretion decreased 35% after 3 months and 26% after 1 year of treatment. The serum tests, with the exception of alkaline phosphatase, showed only negligible changes during ERT. Conclusion A significant decrease in zinc excretion was observed after 3 months of ERT. This change was more pronounced in women with osteoporosis and elevated zinc excretion. Because zinc excretion is almost uninfluenced by variation in diet, it may be used as an additional marker of changes in bone metabolism.

Hypertensive disorders in pregnancy are associated with an increase in serum lipid fractions. Fluorescence Polarization (FP) of lipids in the serum of 80 hypertensive pregnant patients at full term was compared to measurements in a control group of 71 healthy pregnant volunteers. In addition, the FP values were correlated with measurements of serum lipid fraction in 34 hypertensive and 17 control patients. Both chronic hypertension and pregnancy induced hypertensive (PIH) subjects had significantly reduced serum FP values compared to the control group. This difference was however present only in the severely hypertensive patients, independent of the etiology of this disorder. Highly significant correlations were present between the FP values and serum level of Triglycerides r = -0.85, Very Low Density Lipoprotein r = -0.76, and Low Density Lipoprotein r = 0.53. Serum FP values appear to reflect the change in the lipoprotein pattern present in pregnant patients with hypertensive disorders. This change appears to reflect the severity of the condition rather than the etiology of the hypertension.

The efficacy of glucocorticoid and intra amniotic thyroxine therapy on fetal lung maturity were compared in a randomized prospective clinical trial. Eighty two patients received either intra amniotic thyroxine (n = 36), or intra muscular Dexamethasone (n = 46). The Fluorescence Polarization (FP) of amniotic fluid measured prior to and one week following treatment were similar in the two groups. The rate of decrease in FP value per unit of time (dFP/dt) was identical in the T4 and corticosteroid treated patients and the proportion of immature FP values obtained was similar in the two groups. The effect of thyroxine therapy was more pronounced in pregnancies above 33 weeks gestation. Intra amniotic thyroxine therapy appeared to be as effective as glucocorticoids for the enhancement of fetal lung maturity. This therapeutic modality may be of particular use on pregnant subjects in whom a relative contra indication for the administration of steroids exists.

BACKGROUND The possibility that hyperinsulinemia may be involved in the etiology of atherosclerotic cardiovascular disease (CVD) was first suggested 20 years ago. During the last decade, this possibility has received support from three large prospective studies. METHODS AND RESULTS In the present study, the association between CVD, glucose intolerance, obesity, and hypertension (the GOH conditions) and hyperinsulinemia was examined cross-sectionally in a representative sample (n = 1,263) of the adult Jewish population aged 40-70 years in Israel. Previously known diabetics were excluded. CVD comprising clinical or ECG evidence of ischemic heart disease, as well as clinical evidence of cerebrovascular or peripheral vascular disease, was identified in 97 men and 39 women. A significant (p less than 0.01) hyperinsulinemia-sex interaction was found for CVD rate, with the adjusted risk ratios (followed by 95% confidence limits), relative to the rate in 298 normoinsulinemic women, being 1.15 (0.68-1.95) in 328 normoinsulinemic men, 0.85 (0.48-1.49) in 277 hyperinsulinemic women, and 2.27 (1.33-3.08) in 360 hyperinsulinemic men. Age-adjusted CVD rates in men versus women were: a) similar and low among all normoinsulinemic normotensives and hyperinsulinemics free of any of the GOH conditions (all rates less than or equal to 6.5%); b) similar and high among normoinsulinemic hypertensives (13.4% versus 10.4%); c) significantly higher in men among hyperinsulinemic normotensives with glucose intolerance and/or obesity (15.2% versus 3.3%; p = 0.02) and all hyperinsulinemic hypertensives (21.5% versus 12.8%; p = 0.04). These trends remained significant after adjusting for age, ethnic group, and blood lipids. CONCLUSIONS Therefore, hyperinsulinemia was associated with excess CVD risk in men but not in women, and all excess CVD risk in men was confined to hyperinsulinemic individuals in the presence of glucose intolerance, obesity, or hypertension.

Responsiveness to antihypertensive medications was investigated cross-sectionally in 559 individuals comprising all treated hypertensive patients identified within a representative sample (n = 3,532, aged 40-70 years) of the Jewish population in Israel. A rate of dosage score (a summed ranking of dosages of all drugs taken) of two or more increased significantly with increasing levels of body mass index (BMI) from 37.5% in levels less than 23, 54.9% in levels 23.0-29.9, and 76.4% in levels of 30 or greater (p less than 0.0001). Multivariate analyses, adjusting for age, gender, arm circumference, and ethnic group, confirmed the independent effect of BMI on dosage score (p less than 0.001). At each level of dosage score, mean blood pressure levels were equivalent at all levels of BMI after adjusting for potential confounders. This indicates that achieved blood pressure level and not BMI itself was the main determinant of the higher dosing regimens prescribed at higher levels of BMI. In representative subgroups, glucose tolerance (n = 372) and hyperinsulinemia (n = 190) were determined and were found to be positively associated with a dosage score of two or more (p less than 0.05) independently of BMI. These effects could not be accounted for by poor compliance or by altered drug absorption or disposition since overnight urinary drug excretion and plasma drug concentrations 2 hours after ingestion, measured in 80 randomly selected patients from the study group, were not different across BMI categories at similar dosages.(ABSTRACT TRUNCATED AT 250 WORDS)

OBJECTIVE: To assess the risk of neoplastic development among persons exposed to scalp irradiation. STUDY DESIGN: Historical cohort study initially; prospective follow-up subsequently. METHOD: Two control groups--population and siblings--matched for age, sex, ethnic origin, and year of immigration. Follow-up from time of irradiation (1950s) until the end of 1991. Linkage with nationwide cancer registry. RESULTS: A 4.5-fold incidence of cancer (P < .01) and a 2.6-fold increase of benign tumors were noted. The mean length of latency period until tumor development was 11 years for malignant tumors and 21.5 years for benign. A clear dose response effect for both cancer and benign tumors was demonstrated. CONCLUSIONS: The study confirms the role of radiation in salivary gland carcinogenesis. It indicates a need for better awareness, a comprehensive examination, and long-term follow-up of patients who have been subjected to head and neck radiation.

Background:Patent ductus arteriosus is a risk factor for the development of necrotizing enterocolitis. The use of indomethacin to treat patent ductus arteriosus in preterm infants may either decrease the incidence of necrotizing enterocolitis by stabilizing or closing the ductus arteriosus or increase its incidence by a direct constricting effect on mesenteric blood vessels. The authors sought to evaluate the interrelationship between patent ductus arteriosus, treatment with indomethacin and the risk of necrotizing enterocolitis in very low birth weight infants. Method:The Israel National database includes prospectively collected data on 99% of all very low birth weight infants in Israel. The study population comprised 6146 infants of 24–34 weeks gestation born between 1995 and 2000. The effect of patent ductus arteriosus on necrotizing enterocolitis was assessed using multiple regression analysis. Results:Necrotizing enterocolitis occurred in 5.5% (n = 343) of all infants, in 9.4% of infants with patent ductus arteriosus and in 8.9% of infants who received indomethacin. The occurrence of necrotizing enterocolitis was independently associated with the presence of patent ductus arteriosus among infants not treated with indomethacin (odds ratio, 1.85) and those who received indomethacin therapy (odds ratio, 1.53). Indomethacin therapy in absence of patent ductus arteriosus was not associated with an increased risk of necrotizing enterocolitis (odds ratio, 0.72). Conclusions:Patent ductus arteriosus is an independent risk factor for the development of necrotizing enterocolitis in very low birth weight infants. Therapy with indomethacin did not have a significant effect on the risk for necrotizing enterocolitis. JPGN 40:184–188, 2005. Key Words: Necrotizing enterocolitis—patent ductus arteriosus—indomethacin—mesenteric blood flow. 2005 Lippincott Williams & Wilkins

BACKGROUND Late-onset sepsis (LOS) is an important cause of mortality among very low birth weight (VLBW) infants, and deaths occurring within 3 days after the onset of sepsis can probably be ascribed to sepsis. We examined the association of sepsis due to specific pathogens with the risk for early mortality after the onset of LOS, adjusted for perinatal and neonatal risk factors. METHODS From 1995 through 2001, information about 10,215 infants was gathered and deposited in the Israel National VLBW Infant Database. The study population was composed of 2644 infants, of which each had >or=1 events of LOS (totalling 3462 events). Logistic regression models were used to calculate the crude and adjusted risk for early mortality. RESULTS Early mortality was associated with 179 LOS events (5.2% of 3,462); the range of pathogens associated with these events included coagulase-negative staphylococci (CoNS), which were the cause of 1.8% of LOS events associated with early mortality, and Pseudomonas species, which were the cause of 22.6% of such events. Early mortality after LOS, adjusted for neonatal risk factors, was significantly associated with sepsis due to certain pathogens: Pseudomonas species (odds ratio [OR], 12.3); Klebsiella species (OR, 6.3); Serratia species (OR, 6.2); Escherichia species (OR, 4.3); Enterobacter species (OR, 4.1); and Candida species (OR, 3.2), compared with sepsis due to CoNS . In addition, lower gestational age, lower chronological age, small size for gestational age, and grade 3-4 intraventricular hemorrhage, each had an independent association with early mortality. CONCLUSIONS Klebsiella sepsis and Pseudomonas sepsis were associated with a 6.3-fold and 12.3-fold increased risk of early mortality, respectively, and accounted for 41.9% of all early deaths associated with LOS. Considering the aggressive nature of sepsis caused by these pathogens, empiric antibiotic therapy active against these organisms is worth consideration for VLBW infants with presumed LOS.

Objectives: The immediate consequences of surgical castration and estrogen replacement therapy (ERT) on left ventricular systolic performance as assessed by Doppler-derived parameters of aortic flow were examined. Methods: A follow up study comprising two groups: eight premenopausal women who underwent hysterectomy and bilateral oophorectomy and started ERT 1 week after surgery – the study group, and a control group consisted of eight premenopausal women who did not start ERT following hysterectomy. Doppler echocardiography was performed before surgery, 1 week and 1 month post surgery. Results: In both groups significant increase in heart rate was observed after 1 week, remaining high after 1 month in the control group only. The early post-operative period in all women was characterized by an increase in aortic flow velocity, but was statistically significant in the study group only. After initiation of ERT a significant decrease in peak flow velocity (PFV) and mean acceleration (MA) was recorded. Conclusions: Changes in estradiol level may be associated with alterations in left ventricular function. The initial and acute effect of estrogen on the heart muscle after surgical castration is towards a decrease in Doppler-derived parameters of aortic flow. Whether these effects represent a depression of left ventricular function, or alternatively, reflect peripheral vasculature reactivity, requires further evaluation.

To determine whether the midtrimester serum lipid profile, as expressed by fluorescence polarization (FP) values, is decreased in patients who subsequently develop pregnancy-induced hypertension (PIH). Stored serum samples of normotensive patients who had undergone midtrimester biochemical screening for Down's syndrome were used in this case-control study. Forty patients who subsequently developed PIH comprised the study group, and were divided into subgroups with proteinuric PIH (P-PIH, n = 18) and those with nonproteinuric PIH (NP-PIH, n = 22). Sixty randomly selected patients who remained normotensive throughout pregnancy comprised the control. Serum total cholesterol (CL) and triglycerides (TG) were determined using enzymatic colorimetric kits. FP values were determined by optical microviscosimeter. Both study subgroups had significantly lower FP values and higher TG concentrations than the control group. Total CL concentrations were slightly higher in the P-PIH subgroup. There were no differences in mean. Total CL or TG concentrations or mean FP values were found between those patients who developed mild and severe PIH. Using FP value cutoff points of 0.250, 0.245, and 0.240 sensitivity was 95%, 90%, and 78%, respectively, in detecting patients who subsequently developed PIH. Midtrimester serum FP values may have some predictive value for the development of P- and NP-PIH.

Alpha track radon detectors were placed in the homes of 35 lung cancer patients and 35 matched controls for a period of 8 to 10 mo. Twenty lung cancer patients had small cell lung carcinoma; 11 had adenocarcinoma, 2 had squamous cell carcinoma, and 2 had unclassified carcinoma among 15 nonsmokers. Mean overall living on ground level was significantly higher in the group with small cell lung carcinoma (50 y +/- 15) than among controls (33 y +/- 19); the adjusted odds ratio for lung cancer was 5.2 (90% confidence interval [90% CI] = 1.1-24.9) per decade of living on the ground floor for the group with small cell lung carcinoma. Radon exposure of more than 1.0 pci/l in the group with small cell lung carcinoma was associated with increased risk of lung cancer, although it did not reach statistical significance [odds ratio = 1.5 (90% CI = 0.4-5.4)], adjusting for differences in smoking habits. Our study supports the presence of a differentially increased risk for small cell lung carcinoma following long-term radon exposure.

Idiopathic hypercalciuria: A familial generalized renal hyperexcretory state. Twenty-two children with idiopathic hypercalciuria (IH) as well as their parents and siblings were compared to 29 control children and their parents and siblings. Urinary calcium excretion following calcium deprivation or calcium loading was significantly higher in parents and siblings of the IH children than in the corresponding controls. Significantly higher rates of glomerular filtration and increased urinary excretion of sodium potassium and phosphate were found in all family members in the IH group as compared to controls. Significant positive correlations of the five variables studied (glomerular filtration and urinary excretion of calcium, phosphate, sodium, and potassium) were noted within individuals and also within families, both in the IH and the control groups, notwithstanding the lower mean levels in the latter. Serum concentrations of calcium, phosphate, potassium, and sodium were similar in the IH and controls. The distributions of all urinary variables in both the IH and control groups were unimodal with considerable overlap of the two groups, suggesting that IH may be a single entity, possibly representing the upper end of normality. Our data seem to indicate that IH is more likely to be due to nutritional than to genetic factors, since maintenance of sodium potassium homeostatis in the face of increased excretion necessitates increased ingestion of these electrolytes, while increased sodium ingestion is known to be associated with increased urinary excretion of calcium, potassium, and phosphate. Hypercalciurie idiopathique: Un etat d'hyperexcretion renale generalisee familiale. Vingt-deux enfants avec une hypercalciurie idiopathique (IH) ainsi que leurs parents et fratrie ont ete compares a 29 enfants controles et leurs parents et fratrie. L'excretion urinaire de calcium apres restriction calcique ou charge calcique etait significativement plus elevee chez les parents et la fratrie des enfants IH que chez les controles correspondants. Des debits de filtration glomerulaire significativement plus eleves, et des elevations de l'excretion urinaire de sodium, de potassium, et de phosphate ont ete trouves chez tous les membres des familles du groupe IH par rapport au controle. Des correlations positives significatives des cinq variables etudiees (filtration glomerulaire et excretion urinaire de calcium, phosphate, sodium, et potassium) ont ete notees chez les individus, et aussi dans les familles chez les groupes IH et controle, malgre des concentrations moyennes plus faibles chez le dernier. Les concentrations seriques de calcium, phosphate, potassium, et sodium etaient identiques chez les IH et les controles. Les distributions de toutes les variables urinaires chez les groupes IH et controles etaient unimodales, avec un chevauchement considerable entre les deux groupes, suggerant que l'IH pourrait etre une entite unique, representant peut-etre la partie superieure de la normale. Nos donnees semblent indiquer que l'IH est probablement due a des facteurs plus nutritionnels que genetiques, puisque le maintien de l'homeostasie du sodium et du potassium en presence d'une augmentation de l'excretion necessite l'augmentation de l'ingestion de ces electrolytes, tandis que l'augmentation accrue de sodium est connue pour etre associee avec l'augmentation de l'excretion urinaire de calcium, de potassium, et de phosphate.

Mean plasma levels of total cholesterol, high density lipoprotein cholesterol, total-to-high density lipoprotein cholesterol ratio, and total triglycerides were determined in a representative sample of the adult Israeli Jewish population, excluding known diabetics and individuals with overt atherosclerotic morbidity (n = 1,153). Levels were compared in normotensive and untreated and treated hypertensive individuals by glucose tolerance category and smoking, after adjustment for sex, age, and body mass index. In the presence of normal glucose tolerance, lipid levels in the nonsmoking normotensive and treated hypertensive groups were similar, whereas in the smoking, treated hypertensive group, lipids were significantly affected, as indicated by the respective adjusted mean levels (mg/dl): total cholesterol, 219, 221, and 240; high density lipoprotein cholesterol, 45.0, 43.6, and 42.0; ratio, 5.2, 5.3, and 6.0; and triglycerides, 114, 107, and 144. In individuals with glucose intolerance, trends were the same with the exception of triglycerides, which were significantly elevated in the nonsmoking, treated hypertensive group also; the respective values were 217, 225, and 257 for total cholesterol; 45.1, 44.9, and 41.4 for high density lipoprotein cholesterol; 5.2, 5.5, and 6.8 for the ratio; and 133, 152, and 187 for triglycerides. Lipid disturbances in treated smokers were not due to heavier smoking or differences in dietary intake. We conclude that disturbance of plasma lipid profile in treated hypertensive individuals may be mainly due to an interaction with smoking, with an additional effect of glucose intolerance.

SummarySixty-six SLE patients were studied for the presence of lupus type circulating anticoagulant. Forty-nine percent of them showed activity of this anticoagulant. The sensitivity of various coagulation tests was compared. Recalcification time was found to be the most sensitive screening test and the kaolin clotting time mixture test, the best for determining the presence of the anticoagulant.Tissue thromboplastin inhibition test detected only half of the patients in whom the anticoagulant was found by recalcification time and kaolin clotting time mixture test.APTT, using 2 different reagents, resulted in 73% and 52% false negatives. A numerical index for determining the presence of the anticoagulant and its quantitative evaluation is suggested.The association between thromboembolic events, recurrent abortions and the different coagulation tests is shown.

Two hundred twenty patients, preferentially those with high-risk conditions, underwent coronary artery bypass grafting without cardiopulmonary bypass. Early unfavorable outcome events included operative mortality (7 patients, 3.2%), nonfatal perioperative myocardial infarction (6 patients, 2.7%), cerebrovascular accident (1 patient, 0.4%), and sternal infection (3 patients, 1.4%). There were two deaths (13%) among 15 patients with calcified aorta and four (12%) in 33 patients who underwent emergency operation. Multivariate analysis revealed these two risk factors to be the only predictors of early mortality (odds ratios, 8.0 and 9.8, respectively). Preoperative risk factors such as left ventricular dysfunction (ejection fractionor = 35%) (40 patients, 18%), congestive heart failure (46 patients, 21%), acute myocardial infarction (59 patients, 27%), cardiogenic shock (7 patients, 3%), age 70 years or older (59 patients, 27%), renal failure (19 patients, 9%), and cerebrovascular accident and carotid disease (11 patients, 5%) were not found to be major predictors of early mortality or unfavorable outcome. During 12 months of follow-up (range 1 to 21 months), there were four cardiac and three noncardiac deaths (1-year actuarial survival 93%) and 17 cases (7.7%) of early return of angina. Calcified aorta, nonuse of the internal mammary artery, reoperation, and diabetes mellitus were independent predictors of unfavorable events. We conclude that coronary artery bypass grafting without cardiopulmonary bypass can be done with relatively low operative mortality, although there seems to be an increased risk for early return of angina. This procedure should therefore be considered for patients with appropriate coronary anatomy, in whom cardiopulmonary bypass poses a high risk. This procedure is still hazardous with calcified aorta or emergency operation.

Association of “senile” cataract (SC) with glucose intolerance (impaired tolerance and diabetes) was assessed by sex and age in a random population sample comprising 930 individuals aged 40–70 yr, who underwent concurrent oral glucose tolerance test and ophthalmoscopy. The eye examination was performed without knowledge of the glucose tolerance status. SC was defined as lens opacification preventing visualization of the eyeground or as surgical aphakia due to SC. To assess the independent effect of hyperglycemia, glycosylated hemoglobin (HbA1) was determined in 769 participants. In men, no association was found between SC, glucose intolerance, and HbA1. In women of all ages, glucose intolerance was associated with an SC risk ratio of 6.1 (95% confidence limits 3.3–11.1; P < 0.001). Furthermore, SC was associated in women with increased HbA1 independently of the effect of glucose intolerance (P < 0.01). These findings confirm the reported association of SC with diabetes (although unlike the Framingham and HANES population studies, the association was confined in women), indicate its presence at all degrees of glucose intolerance, and suggest a possible independent role of nonenzymatic glycosylation in its pathogenesis.

Hypertension and glucose intolerance, determined in a random population sample (n = 2,475), showed a highly significant (P less than 0.001) association from the mildest levels of both conditions, independent of the confounding effects of age, sex, obesity, and antihypertensive medications. Summary rate ratios for hypertension were 1.48 (1.18-1.87) in abnormal tolerance and 2.26 (1.69-2.84) in diabetes compared with normal tolerance. Altogether, 83.4% of the hypertensives were either glucose-intolerant or obese--both established insulin-resistant conditions. Fasting and post-load insulin levels in a representative subgroup (n = 1,241) were significantly elevated in hypertension independent of obesity, glucose intolerance, age, and antihypertensive medications. The mean increment in summed 1- and 2-h insulin levels (milliunits per liter) compared with nonobese normotensives with normal tolerance was 12 for hypertension alone, 47 for obesity alone, 52 for abnormal tolerance alone, and 124 when all three conditions were present. The prevalence of concentrations (milliequivalents per liter) of erythrocyte Na+ greater than or equal to 7.0, K+ less than 92.5, and plasma K+ greater than or equal to 4.5 in a subsample of 59 individuals with all combinations of abnormal tolerance obesity and hypertension was compared with those in 30 individuals free of these conditions. Altogether, 88.1% of the former vs. 40.0% of the latter group presented at least one of these three markers of internal cation imbalance (P less than 0.001). We conclude that insulin resistance and/or hyperinsulinemia (a) are present in the majority of hypertensives, (b) constitute a common pathophysiologic feature of obesity, glucose intolerance, and hypertension, possibly explaining their ubiquitous association, and (c) may be linked to the increased peripheral vascular resistance of hypertension, which is putatively related to elevated intracellular sodium concentration.

A representative sample (n=2140) of the Israeli Jewish population aged 40–70 (excluding known diabetic patients), whose body mass index had been measured 10 years earlier, underwent an oral glucose tolerance test and redetermination of body mass index. Irrespective of weight changes, high concurrent and high past body mass index values (≥ 27) were associated with similarly increased rates of glucose intolerance as compared with body mass index values < 27 at both time-points (rate ratio 1.76, 90% confidence limits 1.56–1.99). Glucose intolerance here includes borderline and impaired tolerance as well as Type 2 diabetes. The rate of Type 2 diabetes increased only with increasing past body mass index, while concurrent body mass index had no effect [rate ratios: 2.36 (1.48–3.75) and 1.99 (1.48–2.68) respectively for the medium-(23–26.9) versus-low (

The significance of high hemoglobin A1 (HbA1) levels (greater than or equal to 8.0%) found in 12.1% of 648 individuals with normal glucose tolerance constituting a part of a representative population sample was examined. Measurement error in HbA1 and/or glucose-tolerance levels was precluded by HbA1 remaining in the same range over 3.5 yr in 89.7% of 29 individuals with initially high and 68.1% of 22 individuals with initially low (less than 6.5%) HbA1. Rate of deterioration to glucose intolerance (6.9%) in the high group during that period resembled the rate (11.8%) in a control group (n = 279). Fasting plasma glucose significantly accounted for only 2.4% of total HbA1-population variance. No correlation of HbA1 was found with other correlates of glucose tolerance or with daily caloric intake and physical activity. A small but significant increment in HbA1 was associated with smoking (7.1 vs. 6.8%, P less than .01) and with clinically overt atherosclerosis (7.3 vs. 6.9%, P less than .01). We conclude that factors unrelated to glucose metabolism are the main determinants of HbA1 level in normal glucose tolerance and play an important role in diabetes as well. These factors have bearing on evaluation of diabetic control by HbA1 and possibly on risk for diabetic complications.

In a representative sample of the adult Jewish population in Israel (n = 1016) excluding known diabetic patients and individuals on antihypertensive medications, serum uric acid showed a positive association with plasma insulin response (sum of 1- and 2-hour post glucose load levels) in both males (r = 0.316, p less than 0.001) and females (r = 0.236, p less than 0.001). This association remained statistically significant in both sexes (p less than 0.001) after accounting by multiple regression analysis for age and major correlates of serum uric acid i.e. body mass index, glucose response (sum of 1- and 2-hour post load levels), systolic blood pressure and total plasma triglycerides. The net portion of the variance of serum uric acid attributable to insulin response was 12% in males and 8% in females, the total variance accountable by all these variables being 17% and 19% respectively. We conclude that elevated serum uric acid is a feature of hyperinsulinaemia/insulin resistance.

Thirty patients with incurable gastrointestinal cancer were treated in a randomized clinical trial, either with combination chemotherapy (5-fluorouracil, vincristine, and methyl-CCNU) or with the same chemotherapy and the thymic extract TP-1. T-lymphocyte counts slowly and steadily, increased in the TP-1-treated patients over a period of 4–5 months, in contrast to decreasing counts in the patients treated by chemotherapy only. The changes in both groups were significantly different from pretreatment counts (P

Five shortcut methods of population screening for glucose intolerance (impaired glucose tolerance and non-insulin-dependent diabetes mellitus) were assessed for effectiveness: 1) glycosylated hemoglobin concentration (HbA1), 2) fasting plasma glucose level, 3) combinations of fasting plasma glucose and HbA1, 4) plasma glucose one hour post oral glucose load, and 5) plasma glucose two hour post oral glucose load. In a sample of the Israeli Jewish population aged 40-70 years, 2040 participants in the Israel Study of Glucose Intolerance, Obesity and Hypertension, who were not known to be diabetic, underwent an oral glucose tolerance test based on three blood samples (fasting, one hour, and two hour post oral glucose load). In 1058 of the subjects, HbA1 was also measured, and was found to increase significantly (P less than 0.001) with increasing glucose intolerance, but with extensive overlap of ranges, even between normals and newly found diabetics. Fasting plasma glucose was more effective than HbA1 in screening for both impaired glucose tolerance and diabetes by its higher specificity and predictive value of a positive test at comparable sensitivity levels. Combinations of HbA1 and fasting plasma glucose did not improve prediction over fasting plasma glucose alone. As observed in other studies, the screening effectiveness of fasting plasma glucose was also unsatisfactory, either post load glucose level being more effective. Plasma glucose level two hour post load was better for detection of diabetes alone. Plasma glucose level one hour post load was more effective at detecting the total group of glucose intolerance, but did not discriminate well between impaired tolerance and diabetes. A cost-risk-benefit evaluation suggests that a full three-sample oral glucose tolerance test is the best method in screening for both intolerance categories.

Plasma very low density lipoprotein (VLDL) cholesterol and triglyceride, low density lipoprotein (LDL) cholesterol and triglyceridea, high density lipoprotein (HDL) cholesterol, glucose and insulin response (sums of 1- and 2-hour postload oral glucose levels), body mass index (BMI), and blood pressure were determined in a representative sample (n = 542) of the adult Israeli Jewish population. Persons with diabetes or on antihypertensive medications were excluded. Total VLDL and LDL fractions were estimated from their cholesterol and triglyceride subfraction levels that were standardized relative to the mean of the reference group (participants free of glucose intolerance, obesity, and hypertension--the GOH conditions). Hyperinsulinemia and disturbed levels of VLDL and LDL were defined as levels equal to or greater than the 75th percentile and those of HDL, equal to or less than the 25th percentile of their respective reference group distributions. When VLDL was disturbed jointly with LDL and HDL, the mean insulin response adjusted for age, gender, glucose response, BMI, blood pressure, and smoking was high compared to the reference group (166.0 vs. 122.5, p less than 0.001). With isolated disturbed VLDL, or disturbed LDL and HDL but normal VLDL, the mean insulin response resembled the reference group. The adjusted risk ratio for this jointly disturbed lipoprotein profile among hyperinsulinemic individuals was 3.4 (95% confidence limits 2.6 to 4.4, p less than 0.001) with no further association with the GOH conditions. We conclude that hyperinsulinemia is characterized by an atherogenic lipoprotein profile.

The effect of cardiomegaly on operative and late mortality in patients with left ventricular dysfunction undergoing coronary bypass operation was investigated. The study group consisted of 178 patients whose left ventricular ejection fraction was below 45% and who were operated on from 1978 through 1985. Forty-five patients (group A) had severe left ventricular dysfunction (ejection fraction30%) and 133 (group B) had moderate dysfunction (30%ejection fraction45%). Twenty-four of group A (53%) and 54 of group B (41%) patients had cardiomegaly (cardiothoracic ratio on chest x-ray films0.5). There were 10 (6%) hospital deaths, four in group A (9%) and six in group B (4.5%). All four deaths in group A and the six deaths in group B were patients who had cardiomegaly. Regardless of the severity of the left ventricular dysfunction, there was no operative death among patients with normal heart size (p0.001). Age over 65, bypass time longer than 2 hours, and incomplete revascularization emerged as risk factors. Follow-up ranged from 5 to 13 years (mean 7.8 years). Overall 5-year actuarial survival, including hospital mortality, was 80% +/- 3%. Reduced 5-year survival was observed in patients with cardiomegaly (67% +/- 5% versus 91% +/- 3%, p0.05). Five- and 10-year survival of patients from group A with cardiomegaly was 53% +/- 7% and 18% +/- 13%, respectively.

We have previously reported on the decrease of the microviscosity after IA T4 treatment suggesting enhancement of lung maturity. In the present study we report on the outcome of non-selected 856 pregnancies in 4 groups of patients. (1) No treatment; (2) intra-amnotic T4 500 ug (1 to 3 injections, a week apart); (3) betamethasone (B) (1 to 4 courses); and (4) combined IA T4 + B. There was no significant difference in the age and weight at birth in the 4 groups. There was no significant difference in the incidence of RDS or the mortality from RDS between the 4 groups; there was a significant difference (p < 0.05) in the overall mortality (*after congenital letal malformation were excluded). These data suggest that: (1) T4 and/or betamethasone therapy may decrease RDS and non-RDS related mortality and (2) the intra-amnotic route of T4 represents a safe, effective method of hormone administration. This approach deserves further investigation as a tool to help us understand and treat fetal abnormalities during the intrauterine period.