Sister chromatid exchanges and chromosome aberrations in lymphocytes of medical personnel handling cytostatic drugs.

Many anticancer drugs, including cytostatic drugs, are genotoxic. Evidence on human carcinogenicity has been conclusive. Persons handling these drugs might be exposed to an occupational health hazard, as they cause chromosomal damage in the lymphocytes. This study was conducted on 30 Egyptian medical personnel handling cytostatic drugs, working in the Medical Research Institute, Alexandria University and Gamal Abd El Naser Hospital in Alexandria. A control group comprised 30 normal healthy individuals matched for age and sex and had no contact with cytostatic drugs. Also, they were not exposed to any mutagenic agents. The workers and controls were interviewed to exclude exposure to any mutagenic agents other than anticancer drugs in case of medical workers. Cytogenetic methods were done to all subjects to assess chromosomal aberrations (CA) and sister chromatid exchanges (SCE). Significantly increased frequencies of CA and SCEs were found in exposed personnel as compared to the controls. Chromosomal aberrations and SCEs frequencies were not correlated with the age of exposed personnel and duration of exposures to cytostatic drugs. There was no increased risk of malformed children in exposed females and no history of repeated abortion. The results of this study point to the handling of cytostatic drugs as a possible genotoxic hazard. Therefore, effective protection and care in handling must be further emphasized to prevent adverse effects.

Genetic study of epilepsy.

This study comprised 32 patients with epilepsy. They were referred to the Human Genetics Department, Medical Research Institute, Alexandria University, Egypt. They were mentally retarded with the exception of three patients who had normal mentality. Their ages ranged from 2 months to 16 years. Females and males were equally affected (M/F=1). All patients were evaluated to identify the specific etiology of epilepsy. They were classified into symptomatic generalized epilepsy (29 cases) and idiopathic generalized epilepsy (3 cases). After evaluation they were classified according to their diagnosis into those displaying mendelian inheritance, norunendelian inheritance and chromosome disorders. The symptomatic group showed a mendelian inheritance and chromosomal aberrations while the idiopathic group showed a nonmendelian inheritance.

Chromosome anomalies in normal androgenized infertile males.

Chromosome anomalies are known to play a role in human infertility. Chromosome analysis of 103 normal androgenized infertile azoospermic (97.1%) or oligospermic (2.9%) males revealed that the frequency of chromosomal abnormalities was 8.7%. Two patients (1.94%) had a 46,XX chromosome complement, one patient (0.97%) had a 45,X karyotype, two patients (1.94%) had a 45,XY,t(13;14)(p11;q11) karyotype, one patient (0.97%) had a 46,XY,inv(9)(p12;q13) chromosome constitution, two patients (1.94%) had a 46,XY,del(Y)(q12) karyotype, and one patient (0.97%) had a 45X/46,X+marker the nature of which was not clarified.

Down syndrome and maternal age: changes over time and review of risk factors.

During 1987-1996, 292 Egyptian Down syndrome (Trisomy 21) infants were identified in Human Genetics Department in Alexandria. They comprised 139 males and 153 females (sex ratio 0.91). Data on maternal age, paternal age and birth order were analyzed. Maternal ages were examined for transient changes over time and for linear trends. Significant changes in maternal age over the 10 years period of study were observed. First born infants were at greater risk of trisomy 21 than higher order of births, independent of maternal age.

Newborn screening for certain treatable inborn errors of metabolism in Alexandria.

The study was conducted on two groups of newborn infants: Group A; a random sample of 3000 infants attending different Health offices in Alexandria for BCG vaccination. Their ages ranged from 5-120 days with a mean age of 39.9 days. Group B; included all the infants born to high risk families attending the clinic of Human Genetics Department, Medical Research Institute (9 infants; 7 with family history of PKU and 2 with family history of congenital hypothyroidism). Their ages ranged from 7 to 60 days with a mean age of 18 days. The newborn infants of the two groups were screened for three treatable inborn errors of metabolism, phenylketonuria "PKU", galactosemia and congenital hypothyroidism with the aim of early detection and therapy to prevent mental retardation. In group A; one baby with transient hyperphenylalaninemia (HPA) (0.33%) and one presumptive case of galactosemia (0.33%) were found. Initial positive results were found in eleven infants they had high levels of thyroid stimulating hormone (TSH). On reevaluation of nine infants of them they were all euthyroids. In Group B, four infants were detected among the infants of PKU families. After confirmation of these results breast feeding was stopped at once and the infants started their dietary management and were kept on it with follow up and periodic evaluation of the adequacy of treatment.

Cytogenetic study in idiopathic infertile males.

Sex chromatin investigations, including X-chromatin and Y-chromatin, was carried out on one hundred idiopathic infertile males with marked oligospermia or azoospermia. Seven cases (7%) were X-chromatin positive, 18% of the cases had aberrant Y-body (10% big Y, 7% small Y and 1% double Y). Such Y-chromosome abnormalities were frequent among azoospermic than oligospermic males. Chromosomal analysis of patients with positive X-chromatin and/or abnormalities of the Y-chromosome showed chromosomal abnormalities in the seven azoospermic cases (7%) which were X-chromatin positive. These chromosomal abnormalities are varieties of mosaic Klinefelter. Six patients (6%) were 46,XY/47,XXY mosaic and one patient (1%) was 46, XY/47,XXY/48,XXYY mosaic. In conclusion, chromosome analysis as well as sex-chromatin analysis is thus necessary in the investigation of male infertility.

Familial male breast cancer. A case report and review of the literature.

The occurrence of breast cancer in aged male and his paternal uncle is reported. A review of previously reported cases of male breast cancer (M.B.C.) occurring in families and the association with other cancers in the family members is included. Familial or hereditary factors have not been recognized as a major contributing factor in previous reports. Seven families (63.6%) out of eleven families reported had females with breast cancer. It appears that there are some families in which males as well as females have increased risk of developing breast cancer. It is believed that this report supports the genetic predisposition of breast cancer in males. Estrogen affects the growth of breast cancer through estrogen receptor. An approach to subsequent genetic studies of breast cancer may be to focus on steroid hormone receptors.

Genetic study of phenylketonuria.

Among four hundred and eighty mentally retarded patients referred to the Human Genetics clinic, Medical Research Institute, Alexandria University, Egypt; twelve cases were found to have pku, ten cases had classical pku and 2 cases atypical pku. Genetic studies of those patients and their families revealed segregation of autosomal gene(s) that are responsible for the development of the disorder with a recurrence risk of 0.283 +/- (1.96)(0.066). The high average inbreeding Coefficient indicated the important role played by consanguinity. Heterozygote detection is very important to normal sibs of affected patients to provide proper genetic counseling. Dietary management of the young infants in the first three months showed normal growth and development. Behavioral improvement was observed in cases who were treated late despite the fact that they were mentally retarded. Dietary control should be continued for a long life time to obtain good outcome in both sexes and to prevent the risk of fetal damage during child-bearing age in females.