Investigating the Role of Plasma Glucose Concentration as a Phenotypic Marker for CYP2C9 Genetic Variants, in the Diabetic Population of Gujarat.

The present study was aimed to investigate the role of plasma glucose concentration as a phenotypic marker and to study the frequency distribution of CYP2C9 genetic variants in Gujarat state diabetic population. One hundred and nine unrelated diabetes mellitus patients treated with sulfonylureas were genotyped for CYP2C9*2 and CYP2C9*3 alleles. Their pre- and posttreatment postprandial blood glucose levels were recorded and mean glucose drop per milligram of drug values were calculated and further used as an index for phenotypic correlation. The frequencies of CYP2C9*1, CYP2C9*2 and CYP2C9*3 alleles in the Gujarat state diabetic population were 0.84, 0.07 and 0.09, respectively. The distribution of CYP2C9*1/*1, CYP2C9*1/*2, CYP2C9*1/*3, CYP2C9*2/*2, CYP2C9*2/*3 and CYP2C9*3/*3 genotypes were 0.73, 0.08, 0.13, 0.0, 0.06 and 0.0, respectively. Patients with CYP2C9*1/*2 genotype did not show any significant difference in the mean glucose drop per milligram of drug values when compared with wild-type patients in glipizide-treatment group. Patients with CYP2C9*1/*3 genotype showed greater mean glucose drop per milligram of drug values than patients with CYP2C9*1/*1 wild-type genotype for both glipizide and glimepiride while patients with CYP2C9*2/*3 genotype showed greater drop than patients with CYP2C9*1/*1 genotype only in the glipizide-treatment group. The presence of CYP2C9*3 allele significantly affected plasma glucose drop per milligram of drug values in patients taking glipizide and glimepiride, while effects of CYP2C9*2 allele were insignificant. Further studies are needed to confirm the effects of CYP2C9*2 allele on plasma glucose drop per milligram of drug values. However, plasma glucose concentration is a complex physiological marker that cannot be used to establish perfect genotype-phenotype correlation. Hence studies exploring robust phenotypic markers must be initiated.

Quinacrine nonsurgical female sterilization in Baroda, India: 23 years of follow-up of 84 women.

OBJECTIVES: Evaluate the long-term effectiveness and safety of transcervical insertion of quinacrine hydrochloride pellets for nonsurgical female sterilization (QS). METHODS: During the period June 1979 through January 1980, 84 women were admitted to a study at the Baroda Medical College and Hospital, Baroda, India. Our protocol called for three transcervical insertions of 252 mg of quinacrine hydrochloride to be deposited in the uterus of each patient. Follow-up was scheduled at 6, 12 and 48 months after the last administration. RESULTS: These women were 25 to 39 years of age at the time of the QS procedure and now, 23 years later, have completed their reproductive years. There were 4 pregnancies subsequent to the completion of QS, all prior to their 4-year follow-up. Thus, the life-time failure rate for these women was 3.7%. Complaints were minor, especially when compared to surgical sterilization. There were no long-term effects suspected of being attributable to QS. CONCLUSIONS: QS appears to be a reasonably effective method that is much safer than surgical sterilization.

Maternal mortality in India.

Authors worked on maternal mortality in India from 1992-94. This article is a review article on the basis of authors' experience. The article starts with the brilliant sentence, 'Maternal mortality in India is unacceptably high' and ends with the suggested strategies to solve the problem.

Environmental influence on reproductive health.

A rise in industrialization and the consequent environmental pollution, an increase in the use of synthetic chemicals and repeated exposure to hazardous compounds at the workplace and at home adversely affects reproductive health. Biohazardous compounds, some of which act as endocrine disrupters, are being increasingly implicated in infertility, menstrual irregularities, spontaneous abortions, birth defects, endometriosis and breast cancer. In some cases, women are at a greater risk than men, especially with the rise in environmental estrogens. Only a fraction of these chemicals have been adequately examined for toxicity and for synergistic effects due to multiple exposures. There is a need for a greater awareness and vigilance of the effects of environmental pollution on reproductive health.

Domestic violence and substance abuse.

The females and children have been the victims of family violence in most societies and cultures. The use of tobacco, alcohol and narcotic drugs are responsible in aggravating the violence. Incidences of domestic violence is significantly higher in substance abusers than others. It is equally present in countries where the status of women is high. Education level and economic status does not affect the incidence of domestic violence. Therefore we must look at other factors which perpetuate domestic violence. It is time for governments, societies and thinking people to give serious thought on how to reduce domestic violence and bring sanity into the community. Tobacco, alcohol and narcotic drugs are well on their way to the 'road of destruction' and fragmentation of social fabric. The conscience of the world needs to be roused to prevent the march of substance abuse. In the words of the Nobel laureate poet Tagore, I must say, 'into that heaven of freedom my father, let my country awake'.

Camp laparoscopic sterilization deaths in Gujarat State, India, 1978-1980.

An early experience of camp laparoscopic sterilization in Gujarat State, India, resulted in 22 deaths among 106,500 women undergoing the operation during 1979 and 1980. Increased risk of death was seen when larger numbers of procedures were performed by year or month of year. The least experienced surgeons had the highest case-fatality rate. Improvised settings (i.e., school buildings) exacerbated the risk of death, as did advanced age, and, to a lesser extent, high parity. Errors in clinical judgment were identified in some fatal procedures. A system of health audit of large sterilization programs is needed.

PIP: A physician analyzed 1978-80 data on 22 laparoscopic deaths among 106,500 women who underwent sterilization at camps in Gujarat State in India to determine the programmatic and clinical risk factors in these camps. The death rate stood at 20.65/1000,000 procedures compared with 1.5/1000,000 for the US. The laparoscopic sterilization camps were set up in district hospitals, primary health centers, and school buildings. The leading causes of death were peritonitis (9), septicemia (4), and tetanus (2). 5 women also died on the operating table of lignocaine sensitivity (2), cardiac arrest (2), and air embolism (1). The death rate climbed with age (0 deaths for 25 year old, 17 for 26-30 year old, 25.2 for 31-35 year old, and 40.4 for 36-40 year old). It also increased with parity (11.9 for women with 2 living children and 29.8 for those with at least 5 children). 10 of the 22 sterilization deaths were women =or 30 years old with at least 4 children. The number of sterilizations grew 3-fold between 1979-80 and the risk of death grew almost 2-fold. The risk of deaths was especially high during the campaign season (December-March) indicating an increased risk of speedy completions to meet quotas. Surgeons with 6 months experience in laparoscopic sterilization were responsible for most deaths (67%) in camps with 50-100 sterilizations. The case fatality rate for these surgeons was 54.2/1000,000 compared with 8.1 for surgeons with at least 25 months, experience. The same percentage of deaths in these camps occurred to women operated on in school buildings. The case fatality rate for school building operations was 71/1000,000 compared with 15.4 for district hospitals and 13.5 for primary health centers. An unacceptable risk would remain even if school buildings were excluded and laparoscopic sterilization training would not occur at sterilization camps. Improved sterilization of equipment and improved surgical judgment of complications could have prevented many deaths. A medical audit of camps services is justified.

Professional responsibility in maternity care: role of medical audit.

In 1965, Baroda Medical College initiated a process of medical audit of maternal and perinatal deaths occurring at this institution, and consultation in peripheral medical facilities providing antenatal and obstetric care. By 1984 maternal and perinatal mortality had declined and clinical judgment in maternity care had improved.

PIP: In 1965, Baroda (India) Medical College started a medical audit process into maternal and perinatal deaths, and consultation in peripheral medical facilities providing prenatal and obstetric care. Record forms were designed. Weekly departmental meetings of all teaching staff and residents were held. A committee was formed to keep confidential records of all maternal deaths. 6 to 8 meetings of staff and residents were held annually to discuss maternal and perinatal deaths. Data on obstetric cases and maternal deaths were compiled an distributed to staff and residents. The staff and residents visited primary health centers (PHCs) to provide prenatal care. 6 PHCs were selected. Ward nurses held meetings every other week to discuss nursing aspects of complicated cases. The data showed that in 1967-68 the following might have led to maternal deaths. Consultants attended 75% of the maternal deaths. Residents managed 25% of the obstetric emergencies without consulting the attending physician. Common mistakes by residents are listed. In 4% of the maternal deaths, there was a delay in performing cesarean sections. Residents performed more obstetric procedures at night that resulted in maternal deaths than cases that were managed by consultants. Maternal mortality was higher on weekends and holidays as a result of inadequate staffing. In 1983-84 errors in judgment by members of the obstetric department were responsible for 1.5% of maternal mortality as compared to 10% in 1967-68. The main drawbacks in teaching institutions in the developing world include: 1) failure to supervise junior staff; 2) failure of consultants to examine patients before prescribing treatment; and 3) allowing juniors to perform obstetric procedures in high risk cases without monitoring.

Assessment of trace metal intake and status in a Gujerati pregnant Asian population and their influence on the outcome of pregnancy.

Dietary assessments and biochemical indices including plasma zinc and copper were determined in pregnant vegetarian and non-vegetarian Gujerati women in India at 28 weeks gestation, and the results were contrasted with those of a comparable group of Gujerati pregnant women living in Harrow. Even though the dietary intake of energy, protein and zinc was significantly lower in the Indian vegetarian Gujerati group when compared to the equivalent group in Harrow, the birthweights of the babies delivered at term were similar. The intake of zinc in the diet of the Gujerati Indian vegetarian and non-vegetarian groups was only one quarter of the US recommended intake during pregnancy and was approximately one half in the Harrow Indian groups. Even so, the plasma concentrations of zinc were similar in all dietary groups in either India or Harrow. The albumin content in the plasma of both the Gujerati Indian vegetarian and non-vegetarian was significantly reduced when compared to the equivalent Harrow dietary groups. The plasma concentrations of both calcium and sodium were significantly correlated with the albumin concentration but not with the plasma content of zinc. Copper levels were elevated to the normal range in both dietary groups of the Gujerati and were similar to the concentrations found in the Harrow groups.

Liver stores of vitamin A in human fetuses in relation to gestational age, fetal size and maternal nutritional status.

1. Studies were made on liver stores of retinol in aborted human fetuses and stillborn babies in relation to gestational age, fetal size and maternal retinol status. The mothers belonged to low- and high-income groups (LIG and HIG respectively) in urban Baroda. 2. Fetal weights were less than those reported by Widdowson (1968) for similar gestational ages and the deficits were greater in LIG. 3. The combined mean values (microgram/l) for maternal serum retinol for all gestational ages were 193 for LIG and 261 for HIG. They were found to decline in late pregnancy in the former but not significantly in the latter. 4. Fetal liver retinol concentrations were much lower than those reported for healthy Thai subjects by Montreewasuwat & Olson (1979) in early pregnancy but showed complete 'catch up' in late pregnancy for HIG and to a considerable extent for LIG. 5. Significant correlations were found between maternal serum retinol, fetal liver retinol and fetal growth. 6. These findings stress the importance of adequate vitamin A supplies during pregnancy to prevent vitamin A deficiency and intra-uterine growth retardation in the newborn.

Vitamin E status of the newborn in relation to gestational age, birth weight and maternal vitamin E status.

1. Studies were made on the vitamin E status of the newborn as judged by cord serum vitamin E and erythrocyte haemolysis in vitro in relation to gestational age, birth weight and maternal vitamin E status in subjects belonging to low (LIG)- and high (HIG)-income groups in urban Baroda. 2. In the case of full-term infants, the mean values for maternal serum vitamin E (mg/l) for LIG (n 73) and HIG (n 43) were 9.9 (SE 0.4) and 11.6 (SE 0.5). The corresponding values for cord serum vitamin E were 3.6 (SE 0.2) and 4.6 (SE 0.2) mg/l. 3. Serum vitamin E levels (mg/l) were lower in premature infants (2.3 (SE 0.2); n 20) and low-birth-weight full-term infants (2.9 (SE 0.2); n 25) than in full-term normal infants (4.2 (SE 0.1); n 91). This was associated with differences in maternal serum vitamin E levels (7.4 (SE 0.5), 8.2 (SE 0.5) and 11.1 (SE 0.3) respectively). The differences were more marked for LIG. 4. A negative correlation was found between serum vitamin E and erythrocyte haemolysis in vitro in the case of maternal blood but not in cord blood. 5. These results suggest that maternal vitamin E deficiency is one of the features associated with prematurity and intra-uterine growth retardation.

Comparative evaluation of contraceptive efficacy of norethisterone oenanthate (200 mg) injectable contraceptive given every two or three monthly. Indian Council of Medical Research Task Force on Hormonal Contraception.

A total of 2388 subjects, 1181 for 60 +/- 5-day and 1207 for 90 +/- 5-day treatment regimen with norethisterone oenanthate (NET OEN) 200 mg injection, were observed for 24 months, constituting 28,513 woman-months. This clinical trial represents the largest clinical trial undertaken on NET OEN. The observations indicated that NET OEN given at 60 +/- 5-day intervals provides adequate contraceptive protection. However, as compared to the published studies elsewhere, higher method failures were seen during the first six months of NET OEN usage, when all women were receiving the drug at 60 +/- 5-day intervals. The reasons for this discrepant observation in the present study cannot be explained. The higher method failures reported with 90 +/- 5-day regimen were mainly during the third month following the injection, suggesting reduced contraceptive efficacy of the drug during this period. Thin build women (body weight less than or equal to 40 kg) were at higher risk of involuntary pregnancy. Disrupted menstrual pattern was the major reason for discontinuation ranging between 42-43 per 100 users at the end of 24 months. Amongst these, amenorrhoea was the commonest reason for discontinuation. No change in blood pressure was observed during contraceptive usage. The majority of NET OEN users did not show any change in body weight. The overall continuation rates with NET OEN were lower than those observed in similar conditions with Cu-T 200 mm2 IUCD.

A two-year follow-up study of women sterilized in India.

For large-scale program implementation, it is important to document both early and long-term safety and effectiveness of female sterilization methods. The results of this controlled, prospective, two-year study of 2,053 women who underwent sterilization in Baroda, India, show a marked decline in gynecological abnormalities over time; the incidence of gynecological pathology following sterilization was not significantly higher than what might be expected in the general population. The incidence of post-sterilization gynecological surgery was low. Significantly more women had weight gain than weight loss after sterilization. After sterilization, no change in menstrual cycle parameters was reported for the vast majority of women. Both favorable and unfavorable changes in menstrual cycle parameters were noted. The one-year and two-year pregnancy rates were 0.0 and 0.4 percent, respectively. No ectopic pregnancies were reported.

A study of postabortion versus interval sterilization.

PIP: The attempt was made to evaluate and compare postabortion and interval minilaparotomy sterilization procedures. Over the July 1975 to November 1977 period, 149 women underwent postabortion sterilization and 151 women underwent interval sterilization at the Medical College Hospital in Baroda, India. All the procedures were performed by a single operator via minilaparotomy using the tubal ring technique. 100% of the subjects returned to the hospital for the 1st followup visits. Women undergoing postabortion and interval sterilization procedures were similar with respect to age, parity, number of living children, previous child loss and education. Over 90% of the women in both groups had not practiced any form of contraception. There were no technical problems. The incidence of surgical difficulties was higher for the interval (13.2%) than for the postabortion (10.1%) cases. There were no major surgical problems. The most frequently reported difficulty in both groups of patients were related to visualizing and exteriorizing the tubes. No complications attributable to the abortion procedure were reported for patients undergoing postabortion sterilization. The incidence of all sterilization complications was higher for the postabortion cases (43.0%) than for the interval cases (27.8%). The difference was statistically significant for early postoperative complications. There was a higher incidence of complaints among the postabortion (34.9%) than among the interval cases (25.8%).^ieng