Cytogenetic evaluation of traffic policemen occupationally exposed to vehicular exhaust.

Background & objectives: Automobile exhaust consists of many toxic components and is considered to be a major health concern in urban areas. Traffic policemen are occupationally exposed to vehicular exhaust during the traffic control. Hence, the present study was aimed to evaluate genotoxic effects of vehicular exhaust in traffic policemen in Hyderabad, south India. Methods: Analysis of chromosomal aberrations was carried out in 136 traffic policemen, including 78 non smokers and 58 smokers who were exposed to vehicular exhaust for a period of 1-28 yr. For comparison, 115 healthy males including 69 non smokers and 46 smokers of the same age group and socio-economic status (who were not exposed to any chemical or radiation at their workplace) were studied. Results: A significant increase (P<0.05) was observed in the mean frequency of chromosomal aberrations in non smoker and smoker traffic policemen (6.48 and 8.96 respectively) when compared to their respective control groups (3.35 and 4.30). According to the age a significant increase in the frequency of chromosomal aberrations was observed both in control and exposed groups (P<0.05). As the duration of exposure increased in traffic policemen, there was a corresponding increase in the frequency of chromosomal aberrations. Interpretation & conclusions: Cytogenetic damage was more pronounced in smokers when compared to non smokers. Age and duration of exposure also appear to play a vital role in causing cytogenetic damage. Thus the present study suggests that the induction of cytogenetic damage might be due to the cumulative effect of smoking, age and duration of exposure to vehicular exhaust.

Modulating effect of Phyllanthus fruit extract against lead genotoxicity in germ cells of mice.

The objective of the present study was to evaluate the protective effect of Phyllanthus emblica against clastogenicity induced by lead nitrate on the incidence of sperm head abnormalities in the germ cells of mice. At higher concentration of lead, a significant increase in the percentage of sperm head abnormalities was noted but when animals primed with Phyllanthus fruit extract (PFE), a reduction in the frequency of sperm head abnormalities was observed. It can be suggested from the above study that Phyllanthus emblica plays a key role in inhibition of heavy metal mutagenesis in mammals.

Role of intrauterine Rubella infection in the causation of congenital deafness.

Background : Rubella is a contagious viral infection associated with rash. 10-15% of women are susceptible to this infection in their childbearing years and the disease is usually transmitted to the developing fetus causing abortion or stillbirth or congenital Rubella syndrome (CRS). Sensorineural hearing loss is one of the most common abnormalities associated with CRS. Aims : The study was undertaken to determine the prevalence of Rubella induced congenital deafness in south India. Materials and Methods :The present study is carried out on 1076 hearing impaired children below 14 years of age to determine etiological factors for congenital hearing impairment. Various audiometric tests such as PTA, OAE and BERA were carried out to know the type and degree of hearing impairment. Development histories including the prenatal, perinatal and postnatal histories were collected using a standard questionnaire. Results :The results indicated very less percentage (1.57%) of cases with the history of maternal Rubella infection indicating a significant reduction of Rubella-induced deafness in the developing countries. Conclusions : The main reason behind the low percentage of children with rubella- induced hearing impairment may be due to appropriate immunization of mothers to the rubella infection during their child bearing years. The increasing awareness in the developing countries of this infection and its consequences is another important reason behind the low percentage of the affected population.

Detection of L1 (CAM) mutations in X-linked mental retardation: A study from Andhra Pradesh, India.

BACKGROUND : Mental health is an essential ingredient in the quality of life. Recent studies carried out in countries like Germany, USA, France, England and Belgium have provided evidence for the involvement of L1 (CAM) mutations in various X-linked mental retardation syndromes. L1 CAM is a neural cell adhesion molecule belonging to the superfamily of the immunoglobulins and is critical for proper CNS development in humans. AIM: This study was aimed to screen idiopathic mental retardation cases for L1 CAM mutations. MATERIALS AND METHODS : In this study, we screened 15 cases with mental retardation. Genomic DNA from the patients and control subjects was analyzed by polymerase chain reaction using specific primers. RESULTS : In 2 out of 15 patients, mutation was detected between exon 26 and 27. CONCLUSION : It is worthwhile to screen idiopathic mental retardation cases for L1 CAM mutations to reduce genetic morbidity in the population by offering genetic counseling and prenatal diagnosis.

Immunological studies in children with hearing impairment.

An immunological study was carried out on 58 children below 14 years of age with sensorineural hearing loss of unknown aetiology. The observed elevated levels of IgE in 25.86% (n = 15) children and antinuclear antibodies in 10.34% (n = 6) children indicate that auto-immune activity has a role in the causation of hearing impairment.

Facio-auricular vertebral syndrome-a case report.

Facio Auricular Vertebral (FAV) or Goldenhar syndrome is a very rare kind of syndromic deafness and is inherited as autosomal dominant. A study was taken up to understand the prevalence of this syndrome in children below the age of 14 years with hearing loss. Out of 1073 children with hearing impairment, Goldenhar syndrome was observed only in 1 (0.09%) case. The child suffered severe hearing loss. Facial paralysis and hemifacial microsomia were prominent features observed in the child. Facio-Auricular-Vertebral syndrome is therefore synonymously used with Goldenhar syndrome.

Translocation Down syndrome.

Cytogenetic investigations carried out on 1021 cases of Down syndrome revealed translocation in 46 cases. The most frequent was of t(14;21) and t(21;21) types. Most of the translocation DS cases (n = 31) were born to younger mothers (< 25 years), when compared to pure trisomy 21 DS cases. Parental karyotypes, family history and parental ages has helped us greatly in offering genetic counseling, prenatal diagnosis and estimating the risk for the next conception.

Translocation Down syndrome.

Cytogenetic investigations carried on 1021 cases of Down syndrome revealed translocation in 46 cases. The most frequent was of t(14;21) and t(21;21) types. Most of the translocation DS cases (n = 31) were born to younger mother's (< 25 years), when compared to pure trisomy 21 DS cases. Parental karyotypes, family history and parental ages has helped us greatly in offering genetic counseling, prenatal diagnosis and estimating the risk for the next conception.

Beta2-glycoprotein I dependent anticardiolipin antibodies and lupus anticoagulant in patients with recurrent pregnancy loss.

AIM: The present study was aimed to define the incidence of antiphospholipid antibodies of different types lupus anticoagulant (LAC), venereal disease research laboratory test (VDRL) and Beta2-glycoprotein I dependent anticardiolipin antibodies Beta2 I aCL) in our cohort of population experiencing recurrent pregnancy loss (RPL) from Andhra Pradesh, South India. SETTING AND DESIGN: A referral case-control study at a tertiary centre over a period of 5 years. PARTICIPANTS: 150 couples experiencing 3 or more recurrent pregnancy losses with similar number of matched controls. MATERIAL AND METHODS: LAC activity was measured by the activated partial thromboplastin time (aPTT) according to the method of Proctor and Rapaport with relevant modifications. VDRL analysis was performed by the kit method supplied by Ranbaxy Diagnostics Limited and Beta2 Glycoprotein I dependent anticardiolipin antibodies were estimated by ELISA kit (ORGen Tech, GmbH, Germany) with human Beta2 Glycoprotein I as co-factor. STATISTICAL ANALYSIS: Statistical analysis was performed using Student's t test. RESULTS: LAC activity was found positive in 11 women (10.28%). The mean +/- SE Beta2 I aCL concentration in the study group was 14.53 (micro/ml) +/- 1.79 (range 0 to 90.4 micro/ml) which was higher than the control group with a mean +/- SE of 7.26 (micro/ml) +/- 0.40 (range 0 to 18 u/ml). The binding of the antibodies to the antigen was observed in 40.24% (n=33) of the cases compared to 6.09% (n=5) in controls. VDRL test was positive in 7(2.34%) individuals (3 couples and 1 male partner) and none among controls. CONCLUSIONS: The present study indicates the importance of antiphospholipid antibodies in women experiencing RPL and suggests the usefulness of screening for these antibodies as a mandatory routine for instituting efficient therapeutic regimens for a successful outcome of pregnancy.

Cytogenetic studies of 1001 Down syndrome cases from Andhra Pradesh, India.

Cytogenetic data obtained from investigating 1001 patients of Down syndrome (DS) and their parents over a period of 20 years (January 1979-January 1999) are presented. The frequency of pure trisomy, mosaicism and translocation was 87.92, 7.69 and 4.39 per cent respectively. The origin of the extra chromosome 21 due to meiotic non-disjunction was 79.24 per cent maternal and 20.76 per cent paternal. A high frequency of acrocentric chromosome associations was also observed in mothers of children of Down syndrome, this might have predisposed to an enhanced risk for non-disjunction. Birth order of DS showed a higher number of first and second borns. Reproductive performances of the parents indicated a high rate of abortions, compared to controls. Cytogenetic investigations carried out over these years greatly helped in the management of these children and for counseling the affected families.

Serum and erythrocyte magnesium levels in hypertensives and their first degree relatives.

Essential hypertension is an arbitrarily defined disorder to which both genetic and environmental factors contribute. Magnesium and its interactions with other cations may play an important role in the pathogenesis of essential hypertension. Various studies have been carried out on the levels of serum and erythrocyte magnesium in hypertensives and the results are controversial and there is no systematic study in Indian population. In the present study serum and erythrocyte magnesium levels in 86 hypertensives and their 77 first degree relatives as well as in sex and age matched controls were studied. Serum and erythrocyte magnesium levels showed a significant decrease both in the hypertensives and their first degree relatives (p < 0.01). The significantly decreased levels of magnesium in the first degree relatives suggest genetic basis of essential hypertension and may be used as marker to identify those at risk.

Erythrocyte sodium and Na+, K(+)-ATPase activity in untreated hypertensives and their first degree relatives.

In this paper we report the erythrocyte sodium concentration and Na+, K(+)-ATPase activity in 86 untreated hypertensives and their 77 first degree relatives and also in sex and age matched controls. There was significant increase in erythrocyte sodium both in the hypertensives and their first degree relatives (p < 0.01), whereas Na+, K(+)-ATPase activity was significantly reduced in the study group when compared with controls. The possibility of using these parameters as genetic markers is suggested.

Hyperinsulinemia And Polycystic Ovary Syndrome.

Hyperinsulinemia has been reported to be associated with polycystic ovaries. The prevalence of hyperinsulinemia in patients with Polycystic Ovary Syndrome (PCOS) and their female members was studied. The results have indicated that hyperinsulinemia could be a factor amplifying leutinizing hormone (LH) dependent androgen secretion in hyperadrogenised patients with PCOS and their female family members.

Leukocyte glucose 6 phosphate dehydrogenase as prognostic indicator in ANLL and CML.

Glucose 6 phosphate dehydrogenase (G6PD) was estimated in the leucocytes of 35 patients with acute non-lymphocytic leukemia (ANLL) and 10 patients with chronic myeloid leukemia (CML). G6PD levels were found to be significantly decreased in majority of the patients with ANLL while it was increased in all CML patients. Variation in G6PD was found to be dependent on the percentage of myelocytes inANLL. Cytogenetic analysis was also carried out in these patients. Correlation analysis of leucocyte G6PD activity and karyotype with prognostic assessment clearly indicated the association of (s) high percentage of chromosomal abnormalities especially translocations, (b) low survival and remission rates, with patients having decreased G6PD activity when compared to patients with normal activity in ANLL. The studies indicate that leucocyte G6PD may be useful as a diagnostic and prognostic tool.

Glycosylation of hemoglobin and erythrocyte membrane proteins mediated changes in osmotic fragility of erythrocytes.

The increased levels of glycosylated hemoglobin and glycosylated erythrocyte membrane proteins in gestational diabetes could bring about alterations in osmotic fragility in erythrocytes of gestational diabetes during their first trimester. The glycosylated hemoglobin levels in erythrocytes were found to be significantly elevated with a mean of 5.42 +/- 0.77 mg/dl when compared to 3.45 +/- 0.62 mg/ dl in non diabetic pregnant control (where as in non pregnant women the value was 3.4 +/- 0.47 (n = 25)). The mean osmotic fragility (MOF) of control cells was 60.2 + 0.6 mMol/L Nacl and MOF of gestational diabetic cells was 63.93 +/- 0.6 mMol/L Nacl. The mean osmotic fragility, operationally defined as the Nacl concentration for 50% hemolysis, was found significantly higher by 3.9 + 0.01 mMol/L Nacl in gestational diabetes, than in normal cells. The total levels of glycosylated membrane proteins were increased from 50.60 +/- 8.0 in control to 69.14 + 0.47 in gestational diabetes. Therefore it is proposed that the increased levels of glycosylated Hb as well as glycosylated membrane proteins have a role in altering the membrane permeability resulting in increased osmotic fragility of erthrocytes in gestational diabetes.

Red cell enzymopathies in leukemias.

Red cell glucose-6-phosphate dehydrogenase (G6PD) and pyruvate kinase (PK) levels were estimated in patients with leukemias, to see if there was a consistent enzyme defect and correlation of enzyme levels with stage of the disease with prognostic assessment. G6PD levels were found to be significantly increased or decreased in majority of the patients with acute leukemias. Increased activity was seen in majority of the patients with L1 and decreased activity in L2 subtype of acute lymphocytic leukemia (ALL). In chronic myeloid leukemia (CML) G6PD activity was consistently increased, with levels being highly elevated in chronic phase and moderately in blast phase. Variation in G6PD activity was found to be related to the stage of disease and was of prognostic significance. PK was found to be normal or decreased. Fetal haemoglobin levels were also estimated in 30 patients with leukemias and were found to be elevated in most patients. Red cell G6PD may be useful for staging of the disease, as prognostic indicator and predictor of relapse.

Serum alpha-1-antitrypsin in ischemia and rheumatic heart diseases.

Tissue damage, inflammation and necrosis are hallmarks of myocardial infarction. In the present study significant elevations of serum alpha-1-antitrypsin were noted in coronary artery disease and angina cases. Interestingly chronic rheumatic heart disease which is also characterized by tissue injury. Inflammation revealed normal levels of serum alpha-1-antitrypsin. The level in chronic rheumatic heart disease was 3.37 +/- 0.57 mumol/mt/ml (control level was 3.37 +/- 0.54 mumol/mt/ml). The corollary of these observations is that in heart diseases acute phase response in terms of enhanced levels of alpha-1-antitrypsin differ depending on the causative factors. Except chronic rheumatic heart disease, in all other stressful states studied there is (to a certain degree) an altered systemic homeostasis and haemostasis. On the other hand chronic rheumatic heart disease encompass certain amount of acute phase status in terms of tissue damage and inflammation does exist unaccompanied by altered systemic homeostasis and haemostasis. However, bacteriological etiologies predominate the triggered immune responses. It is hypothesised that serum alpha-1-antitrypsin enhancement will not occur even though acute phase state exists if specific immune responses are also a part of the disease manifestation.

Leukocyte glucose 6 phosphate dehydrogenase (G6PD) as prognostic indicator in children with acute lymphocytic leukemia.

G6PD activity, estimated in 37 patients with acute lymphocytic leukemia (ALL) prior to therapy was found to be significantly decreased in 78.37% of the patients with ALL while it was normal in other patients. Variation in G6PD was found to be dependent on the percentage of myelocytes. Correlation analysis of leukocyte G6PD activity with karyotype indicated that patients with normal karyotype with normal G6PD activity had good prognosis while those with abnormal G6PD with abnormal karyotype had poor prognosis. Subjects with normal karyotype and abnormal G6PD and vice versa had intermediate prognosis. Thus the results clearly indicate that leukocyte G6PD may be used as a diagnostic and prognostic tool.