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Biomedical subjects

L Jovanovic

Publications and source records attributed to L Jovanovic.

At least 73 records · Page 4Linked to original sources

A comparative evaluation of glycosylated haemoglobin assays: feasibility of references and standards.

Four assays, high pressure liquid chromatography, colorimetric with thiobarbituric acid, affinity columns, and microcolumn cation exchange were compared for ability to discriminate between samples taken from diabetic and normal subjects; correlation with each other; stability over time at different temperatures; and reproducibility between laboratories. The most discriminatory (10 samples from a diabetic and 10 samples from a normal group) was the microcolumn cation exchange method (t = 5.25; p less than 0.001), but all were significantly different at p less than 0.005. The intra-assay coefficient of variation was 1%-6%, except for the affinity column method which was 13% in normal subjects. High pressure liquid chromatography was used as a reference and the other assays correlated well (r = 0.93-0.99). Storage at -80 degrees C, -20 degrees C, 4 degrees C, and 24 degrees C showed marked differences. The thiobarbituric acid method results were stable except for 24 degrees C. Microcolumn cation exchange was labile under all conditions. Affinity column was stable for up to 15 days, only if samples were stored as whole blood. High pressure liquid chromatography showed an increase in haemoglobin A1a + b and a decrease in the haemoglobin A1c. Haemoglobin A1c was reproducible for 4 days when stored at 4 degrees C and up to 11 days when stored at -80 degrees C. Samples exchanged between centres at 4 degrees C and performed within 5 days by high pressure liquid chromatography for haemoglobin A1 and haemoglobin A1c correlated well (r = 0.98 and 0.99). Samples exchanged between centres after storage (up to 40 days -80 degrees C) correlated (r = 0.99) by the thiobarbituric acid method.(ABSTRACT TRUNCATED AT 250 WORDS)

Chromatography, Affinity↗

Increased fetal activity with low maternal blood glucose levels in pregnancies complicated by diabetes.

Ten diabetic pregnant women were studied during the thirty-sixth to fortieth weeks of gestation to determine whether maternal blood glucose levels influence fetal activity. Maternal blood glucose level was monitored and controlled utilizing an artificial pancreas (Biostator) while fetal activity and heart rate were quantitated by continuous ultrasonic and electrocardiac fetal monitoring. Fetal activity was confirmed independently by a maternal controlled event marker. There was no difference in fetal movement with heart rate accelerations between periods of maternal normoglycemia defined as blood glucose levels between 60 and 140 mg/dl (3.3-7.8 mMol/L) and periods of maternal hyperglycemia (blood glucose level greater than 140 mg/dl or 7.8 mMol/L). Maternal blood glucose levels of less than 60 mg/dl (3.3 mMol/L) were accompanied by a significant (p less than 0.001) increase in fetal activity (19.9 +/- 3.9 SEM episodes of fetal movement per 20-minute observation period versus 8.0 +/- 5 episodes during periods of hyperglycemia). These observations indicate that hyperglycemia does not stimulate fetal activity and that the obstetric practice of beverages with high glucose content administered during antepartum testing (in an attempt to increase fetal movement) should be reevaluated in diabetic women.

Adult↗

Time course of reversibility of accelerated fibrinogen disappearance in diabetes mellitus: association with intravascular volume shifts.

Accelerated fibrinogen disappearance in diabetic patients is reversible with normalization of blood glucose. To define the time course of this reversal, we measured 125I-fibrinogen disappearance in 19 diabetic patients experiencing acute changes in blood glucose, as monitored and controlled by a microprocessor-controlled closed loop insulin infusion system (artificial beta cell). The data were corrected for blood volume dilutional changes and fit to a model describing two sequential exponential functions and a single exponential function. The sequential model provided the best fit for all but one patient. This indicates that there were two distinct rates of fibrinogen disappearance and suggests that the time course of reversal of accelerated fibrinogen disappearance in diabetic patients is very rapid, if not immediate. Rapid fibrinogen turnover during hyperglycemia was temporally associated with vascular volume changes, reflected as dilutional changes of 51Cr-RBC concentrations. These findings were also associated with an increase in pulse pressure during hyperglycemia, suggesting blood volume expansion due to an osmotic mechanism. The results of this study suggest a picture of vascular volume expansion and contraction, perhaps secondary to the osmotic effects of hyperglycemia. Accelerated fibrinogen turnover associated with these events may be related to increased vascular permeability and/or increased fibrin formation. These events, in concert, may contribute to the initiation and/or propagation of diabetic vascular sequelae.

Adolescent↗

Spontaneous hypoglycemic seizures in pregnancy. A manifestation of panhypopituitarism.

A 32-year-old woman had seizures and coma due to severe hypoglycemia (26 mg/dL) in the 32nd week of an otherwise uncomplicated pregnancy. She responded dramatically to the administration of cortisol. Initial endocrine evaluation disclosed prolactin (PRL), corticotropin, and thyrotropin (TSH) deficiencies. The patient recovered completely with cortisol and thyroid hormone therapy and was delivered of a healthy male child at term. Endocrine reevaluations one week and six months postpartum disclosed luteinizing hormone, follicle-stimulating hormone, growth hormone, PRL, corticotropin, and probable TSH deficiencies. The cause of this panhypopituitarism has not been determined. This case suggests that the appropriate initial treatment for spontaneous symptomatic hypoglycemia in pregnancy, while awaiting further endocrine evaluation, is the administration of cortisol.

Adult↗

Insulin and glucose requirements during the first stage of labor in insulin-dependent diabetic women.

Studies utilizing glucose-controlled insulin infusion systems were undertaken to more accurately define the glucose and insulin requirements during the first stage of labor induced by oxytocin in 12 insulin-dependent diabetic women in whom normoglycemia had been maintained before delivery. Insulin requirements decreased to zero during active stage 1 labor, while the glucose infusion rate necessary to maintain a blood glucose level of 70 to 90 mg/dl (or 3.9 to 5.0 mmol/liter) was constant at 2.55 mg/kg per minute. The findings were confirmed in 40 additional studies of oxytocin-induced labor. Studies of six women undergoing spontaneous labor and one nonpregnant woman receiving oxytocin confirmed that the decrement in the insulin requirement during stage 1 labor was not influenced by oxytocin infusion. The changes occurred regardless of whether epidural anesthesia was employed. Insulin requirements returned during the second stage of labor. Active stage 1 labor in diabetic women thus appears to be associated with a predictable decrease in the need for insulin and a constant glucose requirement.

Blood Glucose↗

Surgical cure of hypoglycemia associated with cystosarcoma phyllodes and elevated nonsuppressible insulin-like protein.

A woman with a large, benign cystosarcoma phyllodes of the breast was found to have recurrent, profound hypoglycemia. Plasma levels of nonsuppressible insulin-like protein were increased (15.18 micrograms/ml; normal = 1 to 4 micrograms/ml), whereas levels of insulin and nonsuppressible insulin activity soluble in acid ethanol were normal. Surgical excision of the tumor resulted in immediate and lasting correction of the metabolic abnormalities, although nonsuppressible insulin-like protein levels did not completely return to normal. Surprisingly, preoperative nonsuppressible insulin-like protein levels were highest in blood distant from the tumor site.

Adult↗

Systemic lupus erythematosus in men. Genetic and endocrine features.

Sixteen men with systemic lupus erythematosus (SLE) were examined to assess their genetic and hormonal status. The results of buccal smears in 13 patients examined were normal. Hormonal profiling was done in eight patients receiving no steroid therapy. Four patients had elevated plasma estradiol levels (30, 35, 55, and 103 pg/mL; normal, 12 to 23 pg/mL) and elevated plasma estrone levels (115, 150, 155, and 160 pg/mL; normal, 48 to 100 pg/mL). One patient had a decreased serum testosterone level (134 ng/dL; normal, 300 to 1,000 ng/dL), with an elevated luteinizing hormone (LH) level (4.2 ng/mL; normal, 1.6 to 4.0 ng/mL). One patient had an elevation in both levels of serum follicle-stimulating hormone (17.6 ng/mL; normal, 1 to 5 ng/mL) and LH (10.0 ng/mL). Two patients given infusions of 3H-androstenedione and 14C-testosterone had normal findings from kinetic studies of these hormones. Hyperestrogenemia and hypoandrogenemia observed in some men with SLE suggest that female sex hormones may create an immunologic milieu that facilitates the autoimmune phenomena.

Adolescent↗

The clinical utility of glycosylated hemoglobin.

Measurement of glycosylated hemoglobins in diabetic patients has been available to clinicians for about five years. Such measurements correlate with mean serum glucose determinations over time; therefore, they have stimulated a number of studies to determine (1) if these assays are useful in diagnosing diabetes, (2) the clinical utility of determinations of minor hemoglobins in monitoring diabetic control, and (3) the relationship of glucose "control" (as indicated by concentrations of glycosylated hemoglobins) to abnormalities or "sequelae" of the diabetic state. High concentrations of glycosylated hemoglobins are highly specific for diabetes, and positive findings provide a useful diagnostic test. However, this measurement is less sensitive than a glucose tolerance test. As a clinical tool, these hemoglobins are most useful in labile diabetes, i.e., juvenile-onset diabetes and diabetes in pregnancy. In adult-onset diabetes, the fasting serum glucose concentration is apt to correlate well with the concentration of hemoglobins A1a-c. A correlation between several abnormalities associated with diabetes mellitus and concentrations of hemoglobins A1a-c have been reported. These abnormalities include abnormalities of the erythrocyte, leukocyte, platelet, and coagulation cascade and hormonal profiles in juvenile-onset diabetes and diabetes in pregnancy. In addition, correlation have been reported between certain risk factors or abnormalities, associated with vascular disease and concentrations of minor hemoglobins, including lipid profiles microvascular disease as reflected by retinal changes and quadriceps capillary basement membrane thickening, and macrovascular disease as reflected by pulse volume recordings. These studies have led to a reevaluation of the role of glucose "control" in contributing to diabetic sequelae, and, thus, have stimulated new approaches to the management of diabetes.

Animals↗

Feasibility of maintaining normal glucose profiles in insulin-dependent pregnant diabetic women.

This study was designed to test the feasibility of a patient-monitored glucose determination program to establish and maintain normal blood glucose levels. Ten pregnant women, who were insulin-dependent diabetics prior to becoming pregnant and who were in their eighth week or less of pregnancy, were offered the program. All 10 accepted and continued the program for the duration of their pregnancy. Normal plasma glucose (60 to 140; mean = 80 mg/dl) levels were achieved after one week of the program and were maintained throughout the pregnancy as documented by 5 to 8 blood glucose determinations a day. The hemoglobin A1c level, which was elevated in all 10 patients at the start (9.4 +/- 1.6 per cent) of the program, fell into the normal range (2 to 5.0 per cent) five weeks after glucose values became normal. Serum estradiol (0.8 +/- 0.6 ng/ml), serum prolactin (10 +/- 9 ng/ml) and serum human chorionic gonadotropin (5,500 +/- 1,700 ng/ml), although all abnormal at the start of the program, became normal after glucose control was achieved (program weeks 4, 5 and 6, respectively). The infants showed no signs of macrosomnia (2,988 +/- 959 g), hypoglycemia, hyperbilirubinemia, hypocalcemia, erythremia or respiratory distress. Therefore, a program to maintain normal blood glucose levels during a diabetic patient's pregnancy is not only possible but may also improve the pregnancy and the outcome.

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↗

Screening for twin pregnancy.

A group of 590 women who, 4 to 5 weeks after their last menstrual period, were confirmed to be pregnant, as measured by the human chorionic gonadotropin (hCG) by radioreceptor assay. Nine of these women had serum hCG levels approximately twofold higher than the others and were suspected of having twin pregnancy. When these women were tested at 12 weeks of gestation, pelvic sonography confirmed twin pregnancies in all the nine cases. Serum hCG levels thus provide a simple, rapid, and easy method to detect twin pregnancy.

Chorionic Gonadotropin↗

Medical nutritional therapy in pregnant women with pregestational diabetes mellitus.

OBJECTIVE: Diabetic women now can have the same chances as nondiabetic women to have a healthy infant. The reduction of risk associated with pregnancies complicated by diabetes can only be assured if normoglycemia is achieved before and during pregnancy. This review is intended to provide guidelines and scientific evidence for the optimal diet for the Type 1 or Type 2 diabetic woman. METHODS: The literature over the past 10 years is presented. Those diets which achieved the best outcome of pregnancies complicated by diabetes (as evidenced by term delivery of a healthy, normal weight infant) are then outlined. RESULTS: Diets which provide adequate calories without causing postprandial hyperglycemia or premeal ketosis are found to be based on body weight and gestational week of the pregnancy. Quantity of carbohydrate in the meal plan emerges as the most important component in achieving and maintaining glucose control. CONCLUSIONS: The medical nutritional therapy for the Type 1 and Type 2 diabetic woman is a necessary component of the overall strategy to achieve and maintain normoglycemia and thus achieve the best outcome of pregnancy.

Blood Glucose↗

Teacher as learner.

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Communication↗