Insulin sensitivity as a risk factor for common carotid intima media thickness (IMT): its relation to atherosclerosis.

INTRODUCTION: The relationship between insulin resistance and atherosclerosis (ATH) in non-diabetic hypertensive patients from the Asian Indian population remains poorly understood. To resolve this issue, the present study was designed to analyze whether insulin sensitivity in a non-diabetic individual is related to the development of ATH.(by using IMT as an index) and whether this relationship is dependent on the presence of other cardiovascular disease (CVD) risk factors such as dyslipidemia and hypertension. METHODOLOGY: This study included 68 healthy controls with no diabetes and hypertension and 41 hypertensive patients who underwent four-point oral glucose tolerance test (OGTT) and intravenous glucose tolerance test (IVGTT). A biochemical profile, beta mode ultrasonography for intima media thickness of carotid artery, and ECG determination was carried out. RESULTS: Hypertensive patients in our study exhibited significantly increased abdominal obesity. Blood pressure, fasting and 2 hr plasma glucose (4.62 +/- 0.08 and 5.55 +/- 0.17 mmol/l), and triglyceride (1.47 +/- 0.067 mmol/l) levels were compared to those of control subjects (p < 0.05). The fasting insulin levels and HOMA-IR were also significantly increased and Composite Insulin Sensitivity Index (CISI) reduced compared to controls with p < 0.01. Intima media thickness of the left (0.08 +/- 0.01) and right (0.069 +/- 0.008) CA were both significantly increased in hypertensives (p < 0.01). Correlation analysis showed that IMT of the left carotid artery was significantly associated with triglyceride levels (r = 0.813, p < 0.05) but not with insulin measures such as HOMA-IR and CISI. CONCLUSION: Hyperinsulinemia was observed in our non-diabetic hypertensive patients, but no association was found between IMT and insulin resistance. That IMT of hypertensives was associated with triglyceride levels suggests that high levels of insulin may be related to the development of ATH indirectly through its effects on lipid metabolism in our population.

Experience with intrauterine transfusions for severe Rh alloimmunization in a developing country.

This study reports our experience with 67 intrauterine transfusions (IUTs) carried out for 27 cases of severe Rh alloimmunization, which could be useful to other developing countries with similar situations. Most of the mothers were from sections of India other than Mumbai, their socioeconomic status was low, and they were referred during the second or third trimester. The mean gestation age at first IUT was 27+/-2.9 weeks and maternal anti-D titer ranged from 1:32 to 1:512. Ultrasonography (USG) was normal in eight cases, but showed minimal or gross ascites in 8 and 11 cases, respectively. The mean +/- SD hematocrit (HCT) in three groups defined by USG was 23.5+/-1.7, 15.9+/-4, and 12+/-5.9, respectively. Amniotic fluid analysis, which proved to be an important investigation, indicated IUT in eight cases having normal USG. Six cases were severely anemic (Hb deficit >7 g/dl). By fetal cell staining, the percentage of the donor's red cells in the fetal circulation was determined. Besides Hb, blood group, direct antiglobulin test, and mean cell volume, this parameter was also useful in assessing efficacy of IUT and the need for an exchange transfusion after birth. Of 11 fetuses having gross ascites, eight and one each from the remaining two groups, were stillborn. One death may be procedure related. Two neonates died due to hemorrhagic disorder and prematurity. The overall survival rate was 55.6%. Late referral, severe Rh alloimmunization, volume overload, delay in IUT because of nonavailability of blood and use of nonirradiated blood could be the reasons for the poor outcome. Strategies for improving results are discussed.

Antenatal diagnosis of congenital renal malformations using ultrasound.

Our objectives were to determine the accuracy of antenatal sonography for the detection of congenital renal malformations and to characterize the type of malformations, seen in a 3-year prospective study at a university-affiliated maternity hospital. Participants were 31,217 pregnant women, during the study period, and subjects were 65 fetuses in whom renal malformations were detected on antenatal ultrasound. Pelvic ultrasound scans were performed at least once between 20 and 37 weeks' gestation on all pregnant women attending the antenatal clinic of the hospital for the detection of renal malformations. Fetal urinary sampling, diversion procedures, or termination of pregnancy were carried out as required in those detected to have renal anomalies. Postnatal diagnosis was confirmed by sonography or autopsy. Diagnostic procedures and renal surgery were performed postnatally if indicated. Sixty-five fetuses (0.2 per cent) were diagnosed to have congenital renal malformation antenatally at a mean gestational age of 28.4 weeks. A dilated urinary system was seen in 39, cystic renal disease in 15, agenesis/hypoplasia in six, combined lesions in four, and a horseshoe kidney in one. Oligohydramnios was noted in 20 (31 per cent) pregnancies. Multiple congenital malformations associated with renal anomalies were detected in 12 pregnancies. Termination was carried out at 20 weeks in two pregnancies for lethal malformations; fetal urinary sampling was done in two fetuses with obstructed uropathy, and a vesicoamniotic shunt inserted in one. Postnatal ultrasound confirmed a dilated urinary system in 32, cystic renal dysplasia in 15, renal aplasia/hypoplasia in five, combined lesions in six, and a horseshoe and an ectopic kidney in one each. Five infants were found to be normal. There were seven stillbirths and seven neonatal deaths. Radionuclide scans showed obstruction in nine, decreased renal function in six, and absent renal functions in 10 infants. Micturating cystourethrography demonstrated reflux in 11 and a non-refluxing non-obstructive dilated renal system in five babies. Renal surgery was performed in nine infants. The conclusions drawn from this study were that antenatal detection of renal disease is fairly accurate, even in an extremely busy hospital and certain types of malformations reported in other studies were not observed, despite a large cohort.

Prenatal diagnosis of beta-thalassemia among Indians using denaturing gradient gel electrophoresis.

We have offered first trimester prenatal diagnosis to 55 couples at risk for beta-thalassemia, originating from various parts of India, using polymerase chain reaction and denaturing gradient gel electrophoresis. Apart from the six common mutations, codon 30 (CAG-->CAA), Cap site +1 (A-->C), as well as three uncharacterized mutations were seen among the parents. In the majority of cases, the diagnosis was possible by scanning only one fragment (B) where most of the Indian mutations are situated. In 18 out of 55 cases, framework analysis could also have been used to offer prenatal diagnosis without characterizing the beta-thalassemia mutations. In the two cases where the mutations were uncharacterized, prenatal diagnosis was done only on the basis of the anomalous denaturing gradient gel electrophoresis patterns seen in the parents and in previously affected children. This is the first attempt of prenatal analysis using denaturing gradient gel electrophoresis in the extremely diverse Indian population where the profile of mutations has not yet been fully elucidated.

Rapid mid-trimester prenatal diagnosis of beta-thalassaemia and other haemoglobinopathies using a non-radioactive anion exchange HPLC technique--an Indian experience.

Anion exchange high performance liquid chromatography (AX-HPLC) has been widely used for separating and quantifying various haemoglobin fractions especially in the haemoglobinopathies. We have evaluated the reliability of this technique to measure low concentrations of adult haemoglobin (HbA) in fetal blood to enable differentiation between affected and unaffected fetuses at risk for beta-thalassaemia (85) and other haemoglobinopathies such as delta beta/beta-thalassaemia (1), E-beta-thalassaemia (2), S-beta-thalassaemia (1), and sickle cell anaemia (1). The HbA values obtained ranged between 0 and 9.51 per cent. The HbA for 27 affected fetuses was 0 per cent, while two showed a HbA value of 0.5 per cent. The mean HbA for 61 unaffected fetuses was 4.8 +/- 2.08 per cent. Thirty cord blood samples (cord abortus in cases of affected fetuses and cord full term in cases of unaffected fetuses) were analysed to reconfirm the diagnosis. Ten babies between 8 and 18 months of age could be followed up for confirmation. AX-HPLC was found to be a simple and rapid procedure with high sensitivity and there was a good correlation between the HbA values obtained by AX-HPLC and the diagnosis by carboxymethyl cellulose (CMC) chromatography.

Fetal outcome following intrauterine intravascular transfusion in rhesus alloimmunization.

The outcome of 14 pregnancies with severe rhesus alloimmunization was analyzed over a period of 16 months. Group A consisted of 7 cases who received ultrasound guided intravascular intrauterine packed red blood cell transfusions via the umbilical vein after determining fetal blood group and hematocrit. The outcome of these cases was compared with another 7 cases (Group B), who did not require intrauterine transfusions. The 7 cases in Group A received a total of 25 intrauterine transfusions between 25 to 33 weeks gestation. Procedure related complications encountered were transient fetal bradycardia on 4 occasions, difficulty in cord cannulation due to fetal movements in 2 cases and transient bleeding at puncture site in 2 cases. These complications were not associated with any maternal or fetal consequences. There was no procedure related mortality. Mean cord hemoglobin in Group A (12.52 g/dl) was significantly higher (p < 0.05) than in Group B (8.5 g/dl), and mean cord indirect serum bilirubin was significantly lower (p < 0.1) in Group A (2.5 mg/dl) than in Group B (5.8 mg/dl). Three neonates in Group A required one exchange transfusion each, as compared to all 7 in Group B who required a total of 12 exchange transfusions. All neonates in Group B survived, whereas 2 expired in Group A, one of severe intravascular coagulopathy and the other due to prematurity and hyaline membrane disease. Percutaneous ultrasound guided umbilical blood transfusions directly into the vascular system appears to be safe in experienced hands and has the potential to improve the prognosis of the severely alloimmunized fetus.

Color Doppler evaluation of uteroplacentofetal circulation in management of high risk pregnancies.

The study group consisted of 75 high risk singleton pregnancies in whom color duplex Doppler evaluation of the uteroplacental circulation was determined and correlated with perinatal outcome. Uterine, umbilical and middle cerebral artery flow velocity waveforms (FVW) were analysed and the resistance index (RI), pulsatility index (PI) and the systolic/diastolic (S/D) ratios measured. On the basis of the FVW the uteroplacentofetal blood flow was classified as normal, increased resistance to flow, absent end diastolic flow (AEDF), and reversed end diastolic flow (REDF). Ultrasound biometry was simultaneously performed for all fetuses, while non stress testing was performed as and when indicated. Of the 75 fetuses studied 33 (44%) had abnormal FVWs and only 30.3% of these had an uncomplicated outcome as compared to 81% of those with normal flows. The mortality in cases with abnormal flows was 43% as compared to 7% in those with normal flows. There were 40 growth retarded fetuses in the study group of which 30 (75%) had abnormal umbilical artery FVWs. Of the 18 fetuses with AEDF or REDF, all (n = 7) in whom timely obstetric intervention was not done died in utero, irrespective of fetal weight and gestational age, however 75% of these with weight > 1000 g survived when delivered by cesarean section.