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Biomedical subjects

L Jovanovic

Publications and source records attributed to L Jovanovic.

At least 19 recordsLinked to original sources

Significance of umbilical and uterine artery velocimetry in the well-controlled pregnant diabetic.

The measurement of umbilical and uterine artery velocity waveforms was used to study pregnancies complicated by diabetes. Continuous wave Doppler velocimetry was used to identify the umbilical and uterine artery velocity waveforms. A systolic:end diastolic ratio (S:D ratio) was calculated to analyze the obtained velocity waveforms. We treated 33 tightly controlled and monitored diabetic gravidas. The mean blood sugar value for this population was 95 +/- 8 mg/dL, and the mean umbilical artery S:D ratio was 2.5 +/- 0.3. That group of patients was compared to a group on which we reported previously. Statistically significant differences were found between the well-controlled and poorly controlled populations in third-trimester S:D ratios, number of stillbirths and neonatal morbidity. Uterine artery velocimetry allowed the identification of a patient who developed preeclampsia. This study seems to have indicated that umbilical and uterine artery velocimetry may have an adjunctive role in the surveillance of pregnancies complicated by diabetes.

Arteries

Low fetal loss rates after ultrasound-proved viability in early pregnancy.

Once pregnancy is recognized clinically, it is accepted that 12% to 15% undergo spontaneous abortion. However, the actual time of fetal demise has not yet been determined. To address this question, the outcomes of pregnancies identified before 21 days of conception by serum beta-human chorionic gonadotropin assays were studied. All subjects underwent ultrasound examinations at eight and 12 weeks' gestation. Among 220 women who had a viable pregnancy at eight weeks, only seven (3.2%) experienced a fetal loss thereafter. The results of this study suggest that most clinically recognized spontaneous abortions manifested after eight weeks actually represent pregnancies in which fetal demise occurred before eight weeks. These findings have important implications with respect to the safety of chorionic villi sampling and to the identification of exogenous agents that cause fetal wastage.

Abortion, Spontaneous

Simultaneous cloacogenic carcinoma in dizygotic twins.

Dizygotic twins developed cloacogenic carcinoma of the anus almost simultaneously. The patients, although separated from the time they were 20-years-old, had very similar life styles. There are several reports in the medical literature of synchronous tumors in mono and dizygotic twins. It is recommended that if a cancer diagnosis is made in one twin, the other undergo workup to exclude the presence of a tumor with similar histology. The establishment of state or national twin registries would provide valuable information regarding the role of genetic and environmental factors in the development of not only cancer but also of various nonmalignant disorders.

Anus Neoplasms

Linogliride fumarate, representing a new class of oral hypoglycemic agent for diabetes.

This study presents the first multiday therapy trial of linogliride fumarate, a representative of a new class of oral hypoglycemic agents. Linogliride demonstrated a significant hypoglycemic activity in 26 patients with non-insulin-dependent diabetes mellitus receiving 1 week of therapy. In a dose range of 150 to 400 mg b.i.d., fasting glucose levels fell from 237 +/- 52 mg to 199 +/- 59 mg by day 7 (P less than 0.01). Eight-hour glucose AUCs fell from 2121 +/- 617 mg/dl/8 hr baseline to 1781 +/- 631 mg/dl/8 hr on day 7 of treatment (P less than 0.01). This was associated with a significant increase in insulin AUC from 380 +/- 327 to 610 +/- 417 on day 7 (P less than 0.01). Thus its initial action appears to be by an insulin secretagogue mechanism. No patient had any major adverse effect. This initial study indicates that linogliride fumarate is an effective hypoglycemic agent that significantly lowers fasting and postprandial glucose levels with short-term use. Linogliride fumarate represents a new group of hypoglycemic agents that may be shown to have therapeutic utility.

Administration, Oral

Verification of early pregnancy tests in a multicenter trial.

Tests for the diagnosis of early pregnancy have been available since 1974. However, no studies have systematically verified the accuracy of routine clinical laboratories in measuring human chorionic gonadotropin (hCG) prior to the time that pregnancy is clinically evident. We have conducted such a study in association with the NICHD-funded Diabetes in Early Pregnancy Study (DIEP). The purpose of this study was to elucidate the etiology of malformations in pregnancies complicated by diabetes mellitus, which probably occurs within the first few weeks of pregnancy, and therefore uniformity of pregnancy testing was necessary among the five centers to find an association of a teratogen at the time of organogenesis. We confirmed that routine clinical laboratories, in fact, could measure accurately hCG at the time of the missed menses; however, detection was not necessarily possible prior to that time. We conclude that in order to assure accurate diagnosis of early pregnancy, tests should ordinarily be delayed until time of the missed menses. When the test is used at this time, it is a reliable tool for early pregnancy testing and thus can be used to resolve questions relating to early pregnancy pathophysiology.

Chorionic Gonadotropin

The offspring of the female diabetic "nonobese diabetic" (NOD) mouse are large for gestational age and have elevated pancreatic insulin content: a new animal model of human diabetic pregnancy.

Pregnancy in diabetic mothers is associated with intrauterine death, perinatal mortality, and birth weight greater than that of infants born of normal mothers. The use of rodents made diabetic by alloxan or streptozotocin as an animal model for human diabetic pregnancy has been controversial because of the severity of the diabetes as well as the direct effect of diabetogenic drugs on the developing organism. Among our female NOD (nonobese diabetic) mice, insulin-dependent diabetes occurs spontaneously in 9% by 12 weeks and in 80% by 29 weeks of age. Offspring born within 21 days of conception to mildly hyperglycemic NOD pregnant mice between 26 and 52 weeks of age, and prior to the onset of maternal ketonuria are macrosomic with an average of 31% increase in body weight and 44% increase in kidney weight, in comparison to controls. Besides organomegaly, the macrosomic offspring have significantly higher pancreatic insulin content which was elevated 80% when compared with that of controls, and litter sizes are significantly 50% smaller. These results suggest that the mildly hyperglycemic pregnant NOD mouse represents a promising model for the study of pregnancy complicated by diabetes.

Animals

Pregnancy, diabetes, and Jewish dietary law: the challenge for the pregnant diabetic woman who keeps kosher.

One system of management for the pregnant woman with Type I diabetes is to instruct her in the strategies of achieving and maintaining normoglycemia with the use of self blood glucose monitoring, split doses of insulin, and titration of insulin to cover the meal plan. Normoglycemia is achieved only when the meal plan is adhered to in a rigid fashion to facilitate the insulin dose surrounding the meal. A 30 kcal/kg diet is divided into three meals and three snacks, of which 40% is composed of carbohydrate. These frequent small feedings must be perfectly timed to meet the insulin injected. Such systems require 35 hours of intensified training to become skilled in the techniques of diabetes self-care, but still the regimen does not provide much flexibility. When a pregnant woman also wishes to honor her religious beliefs by keeping kosher and so following another set of rigid laws surrounding the meal plan, adherence to both sets of rules becomes a challenge. Specifically, attention to separating milk and meat and eating only kosher foods must be part of the program. This article describes not only the basic diabetes self-care method but also how to adapt the method to the laws of keeping kosher while sustaining normoglycemia.

Blood Glucose

Hypogammaglobulinemia and hemophagocytic syndrome associated with lymphoproliferative disorders.

Four patients with lymphohistiocytic disorders had or subsequently experienced severe hypogammaglobulinemia and pancytopenia due to hemophagocytosis. The percentages of B- and T-lymphocytes and the ratios of helper (OKT4) cells to suppressor (OKT8) cells in the peripheral blood were variably altered. Mitogenic response to pokeweed mitogen and phytohemagglutinin was depressed but could be restored to near normal by the in vitro addition of indomethacin or interleukin-2. The half-life of intravenously administered immunoglobulin was markedly shortened. The data indicate that hyperactive monocytes/histiocytes are capable of simultaneously ingesting apparently normal blood cells and immunoglobulin, leading to pancytopenia and hypogammaglobulinemia. The monocytes with suppressor activity (which could be abrogated with indomethacin or interleukin-2) appeared to additionally contribute to the hypogammaglobulinemia, possibly by interfering with the terminal differentiation of the B-lymphocytes. Hemophagocytosis occurs frequently in histiocytic and occasionally in lymphoproliferative disorders or viral diseases. More frequent and serial determination of serum immunoglobulin levels in such situations may lead to the discovery of additional cases.

Adult

Glycosylated proteins in normal and diabetic pregnancy.

The methods available for and the clinical usefulness of measuring glycosylated proteins in pregnancy complicated by diabetes is reviewed. The need for standardization of reference ranges for pregnancy and for highly accurate and precise methods of measurement is emphasized. Measurement of glycosylated proteins is useful in patients with established diabetes to identify pregnancies at risk for complications known to be associated with significant hyperglycaemia. These include spontaneous abortion and malformations, foetal loss due to premature labour or intrauterine death, and macrosomia and other neonatal morbidities. The use of glycosylated protein measurements as a diagnostic test for gestational diabetes appears limited.

Abortion, Spontaneous

Randomized trial of computer-assisted insulin delivery in patients with type I diabetes beginning pump therapy.

Sixteen patients with type I diabetes were randomly assigned to two groups to evaluate the utility of computer-assisted insulin dosage decision-making. All patients used the same solid-phase reagent strip system for glucose measurement and the same pump. The standard group (n = 9) used standard algorithms for insulin adjustment, whereas the computer group (n = 7) relied on interactive instruction from a small, inexpensive (less than $100) computer. At the beginning of the study, there were no significant differences between groups in C-peptide level, hemoglobin A1c level, age, or duration of diabetes. Mean blood glucose level during the study for the computer group was 121 mg/dl (6.7 mM), which was significantly lower (p less than 0.01) than glucose levels charted by the standard group: 148 mg/dl (8.2 mM). Mean number of blood glucose values charted by the computer group (58 per week) was significantly (p less than 0.01) greater than the number charted by the standard group (51 per week). Hemoglobin A1c values at six weeks correlated with the mean number of blood glucose values charted per week of the study. There was no difference between groups in symptomatic hypoglycemic episodes. Computer-assisted insulin dose decision-making is feasible, safe, and effective in enabling persons with type I diabetes mellitus to achieve lower mean blood glucose values over a six-week period while initiating pump therapy.

Adult

Intensified treatment of pregnant insulin-dependent diabetic women.

Intensified treatment of glycaemic excursions has become the standard of care for all insulin-dependent diabetic women. This paper reviews the rationale for intensified insulin treatment programs and offers the algorithms of one approach to achieve and maintain normoglycaemia throughout pregnancy.

Diet, Reducing

Insulin pump therapy in the very low birth weight infant.

Ten critically ill, very low birth weight infants less than 30 weeks' gestation were treated with exogenous insulin administered through a continuous insulin infusion pump (Betatron II, Cardiac Pacemaker, Inc). Infants were hyperglycemic to dextrose infusions greater than 6 mg/kg/min. The blood glucose concentration became normal in all infants within two to four hours, with varying requirements for continued insulin treatment. Tolerance to intravenous dextrose increased from a mean of 7.4 mg/kg/min to 11.2 mg/kg/min with glycosuria. Energy intake increased from 49.5 calories/kg/d prior to insulin pump therapy to 70.4 calories/kg/d afterward (P less than .01) with weight gain changed from -23 g/d to +13 g/d (P less than .01). One unexpected observation was the apparent normalization of blood glucose homeostasis on higher dextrose doses among some infants after only one three- to six-hour treatment with insulin. The continuous insulin infusion pump is a flexible tool that allows insulin infusion rates to be changed as dictated by blood glucose values without altering other parenteral infusions.

Acute Disease

Antibody to cardiolipin as a predictor of fetal distress or death in pregnant patients with systemic lupus erythematosus.

During a prospective study of pregnancies in women with systemic lupus erythematosus, we examined the relation between antibody to cardiolipin, measured by the enzyme-linked immunosorbent assay, and midpregnancy fetal distress, identified by abnormal results of antepartum fetal heart-rate testing or by fetal death. All of nine patients with lupus and this complication had abnormally high antibody levels (mean, 212.3 +/- 55.3 units), as compared with values in normal nonpregnant women (28.2 +/- 10.1 units). None of 12 pregnant patients with lupus but without this complication had antibody levels above 50 units (mean, 27.5 +/- 3.4 units; P less than 0.005 vs. women with lupus and fetal distress); 4 of 12 pregnant subjects without lupus had antibody levels above 50 units (mean, 42.5 +/- 11.0), and fetal death occurred in the subject with the highest level. The mean antibody level in 12 nonpregnant patients with lupus was 117.4 +/- 35.0 units. Two patients who had lupus anticoagulant but not clinical lupus, both with histories of prior fetal death, also had high antibody levels; fetal death occurred in one, and spontaneous fetal bradycardia in the other. Antibody to cardiolipin was loosely linked to a history, but not the simultaneous presence, of demonstrable lupus anticoagulant or thrombocytopenia, and could be detected as early in pregnancy as either anticoagulant or thrombocytopenia. We conclude that measurement of antibody to cardiolipin is the most sensitive assay to predict fetal distress or death in patients with systemic lupus erythematosus and may be of pathogenetic importance in this syndrome.

Autoantibodies

Human maternal and fetal response to graded exercise.

Six healthy active women in the third trimester of pregnancy participated in a graded exercise protocol to levels of exertion perceived to be equivalent to that of their usual exercise regimen. Fetal heart rate response (FHR) was documented by ultrasound transducer and confirmed (n = 1) by ultrasonic visualization. Resting maternal O2 consumption was 277 +/- 50 (SD) ml/min and rose to 1,132 +/- 202 ml/min at a mean final exercise intensity of 79 +/- 9 W after 12.8 +/- 1.7 min on a cycle ergometer. There was no significant change in maternal serum insulin, growth hormone, glucose, or pH values. Maternal leukocyte count, hemoglobin, and venous lactate levels rose significantly during the exercise (P less than 0.05). FHR prior to exercise was 142 +/- 4 beats/min and decreased to 84 +/- 34 beats/min during exercise. The decrease in FHR was documented within 1 min of initiating exercise in all cases. During exercise, fetal movements were not accompanied by FHR accelerations. Within 1 min following the cessation of exercise, FHR rose to 143 +/- 8 beats/min and fetal movements were accompanied by FHR accelerations. Since the recovery of FHR occurred immediately after cessation of maternal exercise, this level of maternal exercise does not appear to be harmful to the fetus.

Exercise Test

Screening for gestational diabetes. Optimum timing and criteria for retesting.

Because of the morbidity associated with undiagnosed gestational diabetes (GDM), screening programs are advocated in all pregnancy clinics. The purpose of this study was to elucidate the optimum time to test for diabetes during gestation, the indication for retesting, and the predictive value of a positive screening test for a large (greater than 4000 g) infant. Women (N = 300) were screened at three time points: 9-20 wk, 27-31 wk, and 33-36 wk. An additional group of 300 women were screened at two time points: 27-31 wk and 33-36 wk. The prevalence of GDM in this group was 3.2%. The optimum timing for screening for highest yield was 27-31 wk. Retesting at 33-36 wk appeared cost effective if (1) maternal age was greater than or equal to 33 yr, (2) a positive screen was present at 27-31 wk, and (3) the mother was obese (greater than 120% ideal body wt).

Adult

Use of the minor hemoglobin ratio for the determination of gestational age.

Maternal and cord blood hemoglobin A1c were quantitated at the time of delivery by radioimmunoassay. Other cord blood hemoglobins were quantitated by column chromatography using Bio-Rex 70. The minor hemoglobin ratio : formula: (see text),showed an excellent linear correlation (r2 = 0.88) with gestational age. Therefore, the ratio of : formula: (see text), could be a useful test to determine gestational age in the third trimester.

Chromatography

Hormonal profile as a prognostic index of early threatened abortion.

Twelve pregnancies, in which the initial serum hCG titer as measured by RRA was subnormal, were studied to determine if a hormonal profile would serve as a prognostic index of spontaneous abortion. Three of the 12 patients delivered term babies. The hCG titers remained subnormal throughout the pregnancy, however, the serum E2, P, 17alpha-OHP, and PRL remained normal. One of the 12 patients aborted in week 25 of gestation. The serum hCG and PRL were subnormal; however, the serum E2, P, and 17alpha-OHP were normal. Eight of the 12 patients aborted prior to 100 days' gestation. The serum hCG, E2, and PRL were subnormal whereas the P and 17alpha-OHP were normal. Therefore, in patients who have subnormal serum hCG titers, serum E2 and PRL may provide a prognostic index of spontaneous abortion.

Abortion, Threatened