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Biomedical subjects

K Berkowitz

Publications and source records attributed to K Berkowitz.

16 recordsLinked to original sources

Independent predictors of cesarean delivery in women with diabetes.

OBJECTIVES: To identify independent risk factors for Cesarean delivery in women with pregnancy complicated by diabetes. METHODS: Retrospective analysis of pregnancies from 5735 diabetic women delivering liveborn infants. Maternal demographic, medical, obstetric historical factors and index pregnancy obstetric, glycemic and neonatal outcome parameters were evaluated for association with Cesarean delivery after a trial of labor. Individual risk factors were analyzed for association by chi2 and ANOVA. Independent predictors of Cesarean delivery and adjusted relative risk (RR) were identified by stepwise logistic regression. RESULTS: Trial of labor was permitted in 90.8% and 59.4% of women without (n = 4643) and with prior Cesarean delivery (n = 1092) and was successful in 85.2% and 56.9%, respectively. Eleven independent predictors were found. Five were related to obstetric history and maternal age: prior Cesarean delivery (RR 5.34, 95% CI 3.94-7.25), no prior live birth (RR 3.17, 95% CI 1.98-5.07), no prior vaginal delivery (RR 2.28, 95% CI 1.50-3.44), prior stillbirth (RR 1.71, 95% CI 1.09-2.68%) and maternal age > or = 35 years (RR 1.53, 95% CI 1.20-1.93). Two were related to the severity of diabetes at entry to diabetes care: requiring insulin (RR 1.53, 95% CI 1.20-1.93) and highest fasting plasma glucose level (RR 1.04, 95% CI 1.01-1.07). Two were related to obstetric factors: pre-eclampsia/hypertension (RR 2.56, 95% CI 2.00-3.27) and labor induction (RR 3.32, 95% CI 2.70-4.10). The remaining two were birth weight (per 250 g, RR 1.12, 95% CI 1.09-1.17) and pre-delivery body mass index (RR, 1.03, 95% CI 1.00-1.05). CONCLUSION: The majority of predictors were not modifiable, relating to obstetric history, maternal age and diabetes severity. Possible modifiable interventions to avoid/improve labor induction, and decrease birth weight and maternal weight gain might decrease risk of Cesarean delivery. Future studies must address these multiple predictors.

Adult↗

Response of pancreatic beta-cells to improved insulin sensitivity in women at high risk for type 2 diabetes.

The purpose of this study was to examine the response of pancreatic beta-cells to changes in insulin sensitivity in women at high risk for type 2 diabetes. Oral glucose tolerance tests (OGTTs) and frequently sampled intravenous glucose tolerance tests (FSIGTs) were conducted on Latino women with impaired glucose tolerance and a history of gestational diabetes before and after 12 weeks of treatment with 400 mg/day troglitazone (n = 13) or placebo (n = 12). Insulin sensitivity was assessed by minimal model analysis, and beta-cell insulin release was assessed as acute insulin responses to glucose (AIRg) and tolbutamide (AIRt) during FSIGTs and as the 30-min incremental insulin response (30-min dINS) during OGTTs. Beta-cell compensation for insulin resistance was assessed as the product (disposition index) of minimal model insulin sensitivity and each of the 3 measures of beta-cell insulin release. In the placebo group, there was no significant change in insulin sensitivity or in any measure of insulin release, beta-cell compensation for insulin resistance, or glucose tolerance. Troglitazone treatment resulted in a significant increase in insulin sensitivity, as reported previously. In response, AIRg did not change significantly, so that the disposition index for AIRg increased significantly from baseline (P = 0.004) and compared with placebo (P = 0.02). AIRt (P = 0.001) and 30-min dINS (P = 0.02) fell with improved insulin sensitivity during troglitazone treatment, so that the disposition index for each of these measures of beta-cell function did not change significantly from baseline (P > 0.20) or compared with placebo (P > 0.3). Minimal model analysis revealed that 89% of the change from baseline in insulin sensitivity during troglitazone treatment was accounted for by lowered plasma insulin concentrations. Neither oral nor intravenous glucose tolerance changed significantly from baseline or compared with placebo during troglitazone treatment. The predominant response of beta-cells to improved insulin sensitivity in women at high risk for type 2 diabetes was a reduction in insulin release to maintain nearly constant glucose tolerance.

Adult↗

TRIPOD (TRoglitazone In the Prevention Of Diabetes): a randomized, placebo-controlled trial of troglitazone in women with prior gestational diabetes mellitus.

The TRoglitazone In the Prevention Of Diabetes (TRIPOD) trial is a single-center, randomized, placebo-controlled, double-masked study. The primary aim of the TRIPOD trial is to test the hypothesis that chronic administration of troglitazone to nondiabetic women with prior gestational diabetes mellitus (GDM) will improve whole-body insulin sensitivity and reduce the incidence of non-insulin-dependent diabetes (NIDDM). Because troglitazone is already known to lower blood glucose concentrations in persons who have developed NIDDM, an additional aim of the project will be to determine whether early intervention with troglitazone will achieve better final glycemic control than can be achieved by later intervention. In addition, since troglitazone treatment is expected to improve insulin sensitivity and may prevent or delay a decline in glucose tolerance, we also plan to determine whether long-term troglitazone treatment alters the development or progression of atherosclerosis. In this article we describe the experiment's design, the study's endpoints and methods for determining those endpoints, methods for assessing quality of life, and proposed methods for statistical analyses. The unique two-phase study design of the TRIPOD trial will permit testing not only of the biological question about reversal of insulin resistance and prevention of diabetes, but also of the clinical question about whether early intervention is superior to late intervention. Results from this trial will have an important impact on the monitoring and treatment of patients at high risk for NIDDM.

Adolescent↗

Utility of fetal measurements in the management of gestational diabetes mellitus.

The metabolic management of gestational diabetes mellitus (GDM) during pregnancy traditionally has focused on maintenance of circulating maternal glucose concentrations in all patients within a range that is associated with a low rate of perinatal morbidity, especially morbidity related to excessive fetal growth and macrosomia. Clinical data reviewed elsewhere in this supplement provide guidelines for glycemic targets that appear to eliminate the excess risk to the fetus. However, because only a minority of infants are at risk for perinatal morbidity over the range of glycemia generally encountered in patients with GDM, attainment of those strict glycemic targets in all women with GDM requires implementation of self-monitoring of glucose and exogenous insulin therapy in many pregnancies that are not at risk. In this article, we review management approaches that take into account not only maternal glycemia, but also fetal growth and metabolic parameters in selecting GDM pregnancies for intensive metabolic therapy. The approaches can reduce the number of women with mild GDM who require self-monitoring of glucose and/or exogenous insulin therapy, thereby providing the potential to improve cost-effectiveness of antepartum management of GDM.

Birth Weight↗

Congenital malformations in offspring of women with hyperglycemia first detected during pregnancy.

OBJECTIVES: Our aim was to determine risk factors for congenital malformations in offspring of women with hyperglycemia first detected during pregnancy (i.e., women with gestational diabetes). STUDY DESIGN: A total of 3743 pregnancies complicated by gestational diabetes mellitus delivered at > 20 weeks of gestation were reviewed for the presence of congenital malformations diagnosed before hospital discharge. Anomalies were categorized as major, minor, or absent. Pregnancies with genetic syndromes and aneuploidies were excluded. In addition to maternal clinical and historic parameters, diagnostic glycemic parameters (fasting and post-glucose-challenge levels from the diagnostic glucose tolerance test, highest fasting serum glucose level, and hemoglobin A1c level before insulin therapy) were examined by logistic regression for predictive risk of major anomalies. RESULTS: One or more major congenital anomalies were present in 108 (2.9%) of the newborns; an additional 91 (2.4%) had only minor anomalies. None of the maternal variables were associated with the risk of minor anomalies. By contrast, parity, a history of gestational diabetes mellitus, and several glycemic parameters were associated with the risk of major anomalies. The highest fasting serum glucose level was the best independent predictor (odds ratio 1.13/10 mg/dl, 95% confidence interval 1.09 to 1.34). The fasting serum glucose level at diagnosis, a parameter that is almost uniformly available to clinicians, gave similar predictive information about the risk of major anomalies (odds ratio 1.13, 95% confidence interval 1.08 to 1.14). Stratification of women into subgroups of fasting serum glucose level at diagnosis revealed the incidence of major anomalies to be as follows: 2.1% with a fasting serum glucose level < 120 mg/dl (2973 pregnancies), 5.2% with a fasting serum glucose level of 121 to 260 mg/dl (747 pregnancies), and 30.4% with a fasting serum glucose level > 260 mg/dl (23 pregnancies). CONCLUSION: In a large population of women without a diagnosis of diabetes before pregnancy, the maternal fasting serum glucose concentration at diagnosis was a useful predictor of the risk of major but not minor anomalies. The rate of major anomalies doubled with a fasting glucose level > 120 mg/dl. Thus a fasting glucose level below that of overt diabetes outside of pregnancy carries an important risk of major anomalies that must be considered in the counseling and management of these patients.

Adult↗

Fetal lung maturation. Comparison of biochemical indices in gestational diabetic and nondiabetic pregnancies.

OBJECTIVE: To compare the biochemical maturation of the components of the lung profile according to gestational age between reliably dated gestational diabetic and nondiabetic pregnancies. STUDY DESIGN: Lung maturation was compared in reliably dated pregnancies in 501 gestational diabetic women and 561 nondiabetic women. Lecithin/sphingomyelin ratio (L/S) and phosphatidylglycerol (PG) were evaluated by analysis of variance according to the presence or absence of diabetes and weeks of gestational age. The effect of gestational diabetes on fetal lung maturation was determined by analysis of variance. RESULTS: The gestational diabetic group had no clinical or statistical differences in L/S ratios as compared to the nondiabetic patients at any gestational age. There were no differences in mean percent PG between the diabetic and nondiabetic groups at any gestational age. By 37 completed weeks, 86% of the L/S ratios and 78% of the PG values were mature in the diabetic group as compared to 80% of the L/S ratios and 78% of the PG values in the control group (P = .33 and .43, respectively). CONCLUSION: In reliably dated gestational diabetic pregnancies, biochemical maturation of the fetal lung strongly correlates with gestational age and does not appear to be significantly delayed when compared to a nondiabetic control group.

Adult↗

Effect of troglitazone on insulin sensitivity and pancreatic beta-cell function in women at high risk for NIDDM.

We conducted a randomized placebo-controlled study to determine the effects of the thiazolidinedione compound troglitazone on whole-body insulin sensitivity (SI), pancreatic beta-cell function, and glucose tolerance in 42 Latino women with impaired glucose tolerance (IGT) and a history of gestational diabetes mellitus (GDM), characteristics that carry an 80% risk of developing NIDDM within 5 years. After baseline oral (OGTT) and intravenous (IVGTT) glucose tolerance testing, subjects were assigned to take placebo or 200 or 400 mg troglitazone daily for 12 weeks (14 subjects per treatment group). An OGTT and IVGTT were repeated during the 12th week of treatment. Five subjects failed to complete the trial for personal reasons, and medication compliance averaged 90% in the remaining subjects, none of whom experienced a serious adverse event. SI, calculated by minimal model analysis of IVGTT results, changed by only 4 +/- 14% during 12 weeks of placebo administration, but increased 40 +/- 22 and 88 +/- 22% above basal during treatment with 200 and 400 mg troglitazone, respectively (P = 0.01 among groups). Troglitazone administration was also associated with a dose-dependent reduction in the total insulin area during IVGTTs, which was highly significant (P < 0.001), and with a reduction during OGTTs, which approached statistical significance (P = 0.09). Glucose tolerance improved slightly in all groups, but the magnitude of change did not differ significantly among groups, whether it was assessed as the number of subjects who continued to manifest IGT at 12 weeks (P = 0.64 among groups), the change in total glucose area during OGTTs (P = 0.58), or the change in fractional glucose disappearance rates during IVGTTs (P = 0.28). Among the women who received troglitazone, the greatest improvement in SI occurred in the women who had the highest diastolic blood pressures and the best IVGTT insulin responses during baseline testing. Our findings indicate that troglitazone improved whole-body insulin sensitivity and lowered circulating insulin concentrations in women with prior GDM who are at very high risk for NIDDM. The lack of improvement in glucose tolerance despite improved insulin sensitivity may be a manifestation of the beta-cell defect that predisposes the women to NIDDM. The overall pattern of response to troglitazone in our high-risk patients indicates that the drug is an ideal agent with which to test whether the amelioration of insulin resistance can delay or prevent diabetes in women with limited beta-cell reserve.

Adult↗

Postpartum osteomyelitis caused by group B streptococcus.

Postpartum infections caused by group B streptococci are generally limited in scope. We report a case of vaginal colonization with group B streptococcus that progressed in the postpartum period to osteomyelitis that necessitated total hip replacement. The patient had no risk factors predisposing to streptococcal osteomyelitis. An altered immune status in pregnancy and intrapartum bacteremia may be involved in the pathogenesis of this infection.

Adult↗

Mitochondrial myopathy and preeclampsia associated with pregnancy.

Mitochondrial myopathy is characterized by weakness, exercise intolerance, and acidosis. Pregnancy has been reported to accelerate the disease process. This report discusses pregnancy and management of labor complicated by mitochondrial myopathy and the therapeutic dilemmas that arise when preeclampsia is diagnosed.

Female↗

False-negative syphilis screening: the prozone phenomenon, nonimmune hydrops, and diagnosis of syphilis during pregnancy.

The prevalence of congenital syphilis is rapidly rising in several areas of the United States. Efforts to control the disease depend on the effectiveness of established screening strategies and treatment of infected pregnant women. False-negative test results hinder these efforts and leave the fetus at risk for acquiring congenital syphilis. Recently we encountered four cases of false-negative syphilis serologic results in women who gave birth to infants with congenital syphilis. The false-negative results were caused by the prozone phenomenon. The prozone phenomenon, seen during primary and secondary syphilis, occurs because a higher than optimal amount of antibody in the tested sera prevents the flocculation reaction typifying a positive result in reagin tests. Serum dilution is necessary to make the correct diagnosis. We recommend that for any pregnant woman with apparently negative syphilis serologic results in whom fetal compromise of unknown etiology exists, particularly nonimmune hydrops, nontreponemal testing should be repeated using serum dilutions to prevent a missed diagnosis of syphilis. We further recommend serum dilution as a routine procedure for all pregnant women in areas of high syphilis prevalence.

Adult↗

Risk factors associated with the increasing prevalence of pneumonia during pregnancy.

A retrospective chart review of 1120 antepartum admissions revealed the prevalence of antepartum pneumonia rose to 1 per 367 deliveries. A total of 26 cases in 9560 deliveries were identified with criteria of fever greater than 39 degrees C, productive cough, and radiologic findings of infiltrates or consolidation. Pregnancy-related outcome variables studied were prevalence of preterm labor or birth, birth weight, and trimester of occurrence. Pneumonia characteristics studied were rate and type of organisms recovered, seasonality, and severity of the illness and radiologic findings. Exposure variables relating to the development of pneumonia studied were underlying medical conditions, hematocrit, human immunodeficiency virus status, and drug use. Birth weight, hematocrit, human immunodeficiency virus status, and drug use were compared with a randomly selected sample of women drawn from the general population delivered of infants during the study time period. One patient experienced preterm delivery, which occurred 1 month after cure of pneumonia. Birth weight was significantly lower in the study group (2770 +/- 224 gm versus 3173 +/- 99 gm, p less than 0.01). The most common organism recovered was Streptococcus pneumoniae. A total of 42% of patients had multilobar involvement and two required intubation. Cocaine use (52% in the study group versus 10% in the general population, p less than 0.01) and human immunodeficiency virus positivity (24% in the study group versus 2% in the general population, p less than 0.01) were significant risk factors for antepartum pneumonia.

Cocaine↗

Antibiotic resistance patterns of group B streptococci in pregnant women.

This study examined the antibiotic resistance patterns of group B streptococci (GBS) isolated from gravid women. A total of 156 vaginal and cervical isolates of GBS were examined for resistance to penicillin, ampicillin, clindamycin, cefoxitin, gentamicin, and erythromicin. No resistance to penicillin or ampicillin was found, nor was penicillinase production demonstrated. A high level of resistance to gentamicin was noted (91%). Of the isolates examined, 9, 9.5, and 15.3% exhibited either resistance or intermediate susceptibility to erythromycin, clindamycin, and cefoxitin, respectively. Thirty strains (19%) exhibited a multiple antibiotic resistance pattern. Given the high penicillin and ampicillin treatment failure rates when attempting to eradicate vaginal GBS colonization and our findings of higher and multiple drug resistance patterns of GBS, the selection of an alternative antibiotic regimen is of considerable clinical importance. We recommend that routine reporting of GBS susceptibilities by clinical laboratories be adopted.

Cervix Uteri↗

Alprazolam decreases isoproterenol induced myocardial damage in the rat.

Myocardial trauma and damage were induced by two doses of isoproterenol 40 mg.kg-1 in rats. Isoproterenol injections alone caused the expected cardiotoxicity. Two doses of alprazolam 0.5 mg.kg-1 decreased the severity of electrocardiographic changes after isoproterenol injection and the amount of myocardial tissue damage. The frequency of ischaemic ST-T changes, flat or inverted T waves, Q wave appearance, and heart block was significantly reduced in the alprazolam group. The alprazolam treated group had a significantly smaller proportion of infarcted tissue in the ventricular section (2.3%) and in the apical sections (1.8%) than the vehicle injected rats (6.5% and 14.7% respectively). There was no difference in wet heart weight or in heart rate between the alprazolam group and the control group. These results show that alprazolam has a cardioprotective effect in rats treated with cardiac damaging doses of isoproterenol.

Alprazolam↗

Rats' preference for earned in comparison with free food.

Rats were trained to eat free food from a dish, then trained to press a lever for similar food. The free food was then presented while subjects were pressing on several reinforcement schedules. Subjects continued to press for reinforcement when one or two presses were required for reinforcement, and ate little free food. When ten presses were required for reinforcement, rats preferred free food and pressed little or not at all. It was concluded that, when work demands are not too high, rats prefer earned food to free food.

Animals↗

Inhibition of methionine transport by methotrexate in mitogen-stimulated human lymphocytes.

Mitogen stimulation of human lymphocytes was used to study the expression of several amino acid transport systems in response to cell growth. Resting lymphocytes possess detectable neutral amino acid transport systems which can be activated by the mitogen, phytohemagglutinin (PHA). Sodium-independent transport of 2-aminobicyclo (2,2,1) heptane 2-carboxylic acid was similar in resting and stimulated lymphocytes. However, sodium-dependent uptake of methyl aminoisobutyric acid and alpha-aminoisobutyric acid increased threefold to eightfold with stimulation by PHA. Methionine uptake was primarily sodium-independent in resting lymphocytes, whereas methionine uptake increased fourfold to eightfold in stimulated cells; most of this increase was attributable to sodium-dependent transport. Uptake of methotrexate (MTX) was minimal in resting lymphocytes but was maximal 72 hrs after stimulation with PHA; this increase in MTX uptake was accompanied by inhibition of sodium-dependent methionine transport. These results suggest that PHA activates sodium-dependent transport of methionine and that this activation is blocked by the folate antagonist, MTX.

Biological Transport↗