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Biomedical subjects

M Swift

Publications and source records attributed to M Swift.

At least 73 records · Page 4Linked to original sources
PubMed1987

Breast and other cancers in families with ataxia-telangiectasia.

Patients who are homozygous for ataxia-telangiectasia have an exceptionally high incidence of cancer. In a group of families expected to have a high proportion of heterozygotes for ataxia-telangiectasia, we tested the hypothesis that such heterozygotes, estimated to make up 0.68 to 7.7 percent of the U.S. white population, also have an excess cancer risk. Retrospective cancer incidence rates in adult blood relatives of patients with ataxia-telangiectasia in 110 white non-Amish families were significantly elevated over the incidence rates in spouse controls (rate ratios, 1.6 for men [P = 0.032]; 2.0 for women [P = 0.013]). For persons who are heterozygous for ataxia-telangiectasia, the relative risk of cancer was estimated to be 2.3 for men (P = 0.014) and 3.1 for women (P = 0.004). Breast cancer in women was the cancer most clearly associated with heterozygosity for ataxia-telangiectasia (rate ratio, 3.0 [P = 0.028]; heterozygote relative risk, 6.8 [P = 0.006]). On the basis of this estimated relative risk of 6.8 and an estimated heterozygote frequency in the general population of 1.4 percent, 8.8 percent of patients with breast cancer in the U.S. white population would be heterozygous for ataxia-telangiectasia. We conclude that heterozygous carriers of the gene for ataxia-telangiectasia have an excess risk of cancer, particularly breast cancer in women.

Adult↗
PubMed1987

X-linked dilated cardiomyopathy.

To study the inheritance of idiopathic dilated cardiomyopathy, we investigated a large kindred in which 11 young male members had definite or possible evidence of the disorder. The five affected males for whom we had complete clinical data survived for 5 to 12 months after the onset of symptoms, which occurred early in life (ages 15 to 21 years). In six other males, clinical data were incomplete but suggested possible cardiomyopathy. Three mothers of affected males were given a diagnosis of definite, and two of possible, late-onset dilated cardiomyopathy. These women presented in their 40s with atypical chest pain, and progressive congestive heart failure developed gradually over a period of 10 or more years. X-linked inheritance of dilated cardiomyopathy is suggested in this family by the early onset in males, late onset in females, and no evidence of male-to-male transmission. The late onset of the disease in females, in contrast to the early onset in hemizygous males, is compatible with heterozygosity for the mutant allele. Since most cases of genetically lethal X-linked syndromes appear to be sporadic, for every case of "idiopathic" dilated cardiomyopathy in which X-linked inheritance can be confirmed from family information, it is possible that there are several nonfamilial cases due to a mutation at the same locus.

Adult↗
PubMed1987

Early and late results of coronary bypass surgery. Evolution and the influence of cardioplegia.

Comparison of 1085 patients having coronary bypass surgery without cardioplegia from Jan. 1970 to Aug. 8, 1977 with 1060 patients operated upon with cardioplegia from Aug. 9, 1977 to Dec. 31, 1980 suggests that improved myocardial protection afforded by cardioplegia combined with profound topical hypothermia has its principal impact in those patients requiring urgent or emergency operations by reducing the probability of intraoperative left ventricular failure after coronary bypass. The need for postoperative balloon pumping and the risk of intraoperative death were significantly lower in patients operated upon with hypothermia + cardioplegia myocardial protection. In patients who survived 30 days after operation there was no significant improvement in long-term survival, incidence of myocardial infarction, or recurrence of angina pectoris in the cardioplegia group despite a greater average number of grafts per patient and a smaller number of ungrafted but obstructed coronary arteries.

Adult↗
PubMed1987

Cancer in families with severe combined immune deficiency.

Cancer incidence and mortality were analyzed in 1,181 blood relatives and 558 spouse controls in 24 families of severe combined immune deficiency (SCID) patients, to test the hypothesis that heterozygous carriers of a gene for an autosomal recessive form of SCID are predisposed to cancer. Since at least 1 patient in each family was female and there were no cases outside the probands' sibships, the pattern of occurrence of SCID within the families was compatible with autosomal recessive inheritance. The observed numbers of cancer cases and deaths did not exceed the expected numbers derived from population-based rates; and there was no cancer excess when incidence rates in blood relatives were compared directly to those in spouse controls, since the rate ratios were 1.2 and 1.0 for males and females, respectively. In addition, cancer rate ratios were not significantly elevated when calculated separately for the 9 families of adenosine deaminase (ADA)-deficient SCID patients and for the 15 families without evidence of ADA deficiency.

Adenosine Deaminase↗
PubMed1986

Cancer and autoimmune disease in families with common variable immune deficiency.

Twenty-five families including 34 individuals with common variable immune deficiency (CVID), with at least one affected female in each family, were studied. The distribution of cases within families was compatible with autosomal recessive inheritance, making it plausible to test hypotheses about the disease risk of heterozygote carriers of putative CVID genes by comparing the frequency of autoimmune disorders and cancer in 1033 adult blood relatives to that in 566 spouse controls. For cancer, observed numbers of cases or deaths were also compared to expected numbers derived from population rates. No single family had an unusual clustering of autoimmune conditions, and, overall, autoimmune disease was not found more frequently in blood relatives than in spouse controls. Blood relatives did have a modest, although not significant, excess of rheumatic heart disease. For cancer analyses, comparisons with general population rates indicated no heterozygote predisposition, while direct comparisons of blood relatives to spouse controls revealed a significantly elevated cancer rate in females (rate ratio = 2.3, P less than 0.003). The estimated relative risk of cancer for female CVID heterozygotes was most elevated in the 45-69-year-old age group. It is arguable whether comparisons with population or spouse controls are the most appropriate for evaluating the cancer risk of CVID heterozygotes. The hypothesis that the CVID gene predisposes heterozygous female carriers to cancer may be evaluated more easily in the future when the genetic basis for CVID is better understood.

Adolescent↗
PubMed1986

Diabetes mellitus in ataxia-telangiectasia, Fanconi anemia, xeroderma pigmentosum, common variable immune deficiency, and severe combined immune deficiency families.

The hypothesis that heterozygous carriers of genes for certain autosomal recessive syndromes may be predisposed to diabetes was tested by comparing diabetes incidence from age 20 to 69 yr in blood relatives to that in spouse controls among 7999 adult family members of patients with one of five autosomal recessive syndromes: ataxia-telangiectasia (A-T), Fanconi anemia (FA), xeroderma pigmentosum (XP), common variable immune deficiency (CVID), and severe combined immune deficiency (SCID). FA and A-T families were studied because earlier findings in family members and the frequency of diabetes in homozygotes suggested that heterozygotes might also be predisposed to diabetes. The XP, CVID, and SCID families were included to see what analysis of family data would reveal when there was no prior evidence for a gene-diabetes association. The diabetes rate ratios of 2.6 and 4.2 among FA and SCID females, respectively, were significantly elevated. For female FA heterozygotes specifically, the estimated relative risk of 5.1 for developing diabetes was also significantly elevated. Among males, the most pronounced, although not statistically significant, findings were an elevated rate ratio of 2.2 for A-T males and a low-rate ratio of 0.5 for CVID males. The results suggest that heterozygotes for some of the diabetes-associated autosomal recessive syndromes may themselves be predisposed to diabetes.

Adult↗
PubMed1986

Mortality and cancer incidence in 263 patients with ataxia-telangiectasia.

Mortality and cancer incidence were measured retrospectively in 263 ataxia-telangiectasia (A-T) homozygotes. For white and black A-T patients, respectively, all-cause mortality was 50 and 147 times higher than expected based on U.S. mortality rates. There were 52 primary cancers, representing a 61-fold cancer excess for white probands and a 184-fold excess for black probands. The cancer excess was most pronounced for lymphoma, with 252- and 750-fold excesses observed for whites and blacks, respectively. All the age-specific mortality and cancer incidence rates for blacks exceeded those for whites, and overall mortality was 3.0 times higher for black probands than for whites (P less than .001), whereas cancer incidence was 2.2 times higher (P less than .06). Among the white A-T patients, 36% of those who had died had lived at least until 20 years of age, and 33% of those still living were at least 20 years old.

Adolescent↗
PubMed1986

The incidence and gene frequency of ataxia-telangiectasia in the United States.

Ataxia-telangiectasia (A-T) is an autosomal recessive neurological syndrome of considerable interest because homozygotes are highly predisposed to cancer. Vigorous casefinding in the United States in 1970-72 and 1980-84 identified 231 white, 29 black, and three Oriental A-T cases that provide information about the incidence and gene frequency of A-T. White patients identified in this study were born at the rate of 3.0 per million live births in the U.S. in the years 1965-69. The highest observed incidence was in the state of Michigan for 1965-69, where identified white A-T patients were born at the rate of 11.3 per million births. Based on the incidence data, the minimum frequency of a single hypothetical A-T gene in the U.S. white population was estimated to be .0017. Pedigree analysis, which estimates the gene frequency from the proportion of affected close blood relatives of homozygous probands, estimated the most likely gene frequency to be .007 on the assumption that A-T is a single homogeneous genetic syndrome, with 95% confidence limits of .0012-.02. Given that complementation analysis has demonstrated the genetic heterogeneity of A-T, the A-T heterozygote frequency will probably fall between 0.68% and 7.7%, with 2.8% being the most likely estimate.

Ataxia Telangiectasia↗
PubMed1985

Genetics and epidemiology of ataxia-telangiectasia.

According to the Hardy-Weinberg principle, the frequency in the general population of heterozygous carriers of a gene causing an autosomal recessive syndrome in homozygotes is likely to be between 0.1% and 5%. It is thus important to know whether carriers of the AT gene have a risk of cancer or diabetes greater than comparable noncarriers. A retrospective study of blood relatives in 26 AT families, and follow-up of the obligatory heterozygotes in those families, demonstrated an excess of diabetes, deaths from cancer, and deaths from ischemic heart disease among obligatory or probable AT heterozygotes. Hypotheses about the disease-predisposing effects of the AT gene in the heterozygote are now being reexamined, retrospectively and prospectively, in almost 150 newly identified AT families. Specific tests for the AT gene will permit even more rigorous tests of these hypotheses.

Adolescent↗
PubMed1984

Evaluation of a rapid method for the detection of vaginal group B streptococci in women in labor.

Group B streptococci infection is an important cause of neonatal morbidity and mortality. Effective therapeutic intervention has been prevented to date by our inability to rapidly detect vaginal colonization. Material obtained from the lower vagina of 414 women in labor was cultured, incubated in modified Islam serum starch broth and observed on the ward for the production of orange carotenoid pigment specific for group B streptococci. Subcultures yielded 48 true group B streptococci-positive results. For the Islam broth, the pigment appeared in 2 to 22.5 hours (median, 12.5 hours). The test was shown to have a sensitivity of 96% and a specificity of 100% for group B streptococci. This study demonstrated a simple inexpensive method of detecting vaginal group B streptococci colonization which does not require sophisticated 24-hour laboratory facilities. The method holds promise as a screening test for future intervention studies.

Bacteriological Techniques↗
PubMed1984

Evaluations of wasted mouse fibroblasts and SV-40 transformed human fibroblasts as models of ataxia telangiectasia in vitro.

Fibroblast cultures from wasted mice have been derived and the responses of these cultures to bleomycin treatment or gamma-irradiation have been examined. No differences were observed between wasted fibroblasts and littermate controls in the post-treatment inhibition of DNA replication. In contrast, a human SV-40 transformed ataxia telangiectasia fibroblast line mimicked the abnormal response of primary ataxia telangiectasia fibroblasts to gamma-rays or bleomycin and thus appears to be a useful in vitro model of ataxia telangiectasia.

Animals↗
PubMed1983

Alzheimer's disease: genetic aspects and associated clinical disorders.

Genetic aspects and associated clinical disorders were studied in a consecutive series of 68 men and women in whom Alzheimer's disease appeared at or before age 70. Secondary cases of dementia were found in 17 (25%) of the families, affecting 22 of the probands' siblings and parents. The cumulative incidence of Alzheimer's disease in these relatives was approximately 14% at age 75. An increased frequency of Down's syndrome was observed among relatives of the probands: a rate of 3.6 per 1,000, as compared with an expected rate of 1.3 per 1,000. A history of thyroid disease was established in 9 (19.6%) of the 46 female probands, a frequency greater than that reported in the general population. There was no excess of hematological malignancies among the blood relatives, and parental age at the time of birth of the probands did not differ from the norm. The results of this study indicate that early-onset Alzheimer's disease is associated with a genetic factor manifested in a substantial familial aggregation of dementia, a probable excess of Down's syndrome in the probands' relatives, and a possible association with thyroid dysfunction in women with this form of dementia.

Aged↗
PubMed1982

Congenital malformations and developmental disabilities in ataxia-telangiectasia, Fanconi anemia, and xeroderma pigmentosum families.

Heterozygous carriers of an ataxia-telangiectasia (A-T), Fanconi anemia (FA), or xeroderma pigmentosum (XP) gene may be predisposed to some of the same congenital malformations or developmental disabilities that are common among homozygotes. To test this hypothesis, medical records, death certificates, and questionnaires from 27 A-T families, 25 FA families, and 31 XP families were reviewed. Eleven XP blood relatives (out of 1,100) were found with moderate or severe unexplained mental retardation, a significant excess compared to the FA and A-T families (3/1,439). There were four microcephalic XP blood relatives and none in the FA or A-T families. In the A-T families, idiopathic scoliosis and vertebral anomalies were in excess, while genitourinary and distal limb malformations were found in the FA families. A-T, FA, or XP heterozygotes may constitute an important proportion of individuals at risk for specific malformations or developmental abnormalities.

Adolescent↗
PubMed1981

Responses of Fanconi anemia fibroblasts to adenine and purine analogues.

Fanconi anemia (FA) fibroblasts are known to be exceptionally sensitive to the cytotoxic action of mitomycin C (MMC). The survival of FA cells was enhanced significantly when 0.5 mM caffeine or 0.5 mM adenine was added for 72 h after the cells were exposed to MMC. In other experiments in which MMC was not used, FA fibroblasts were shown to be significantly more sensitive than control cells to 6-mercaptopurine (6-MP), 6-thioguanine (6-TG), and 6-azauridine (6-AU). These observations offer a new approach to defining the basic biochemical defect in FA.

Anemia, Aplastic↗