Search PubMed⌕ Search

Biomedical subjects

D Morrell

Publications and source records attributed to D Morrell.

At least 37 records · Page 2Linked 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

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

A feasibility study of a new approach to clinical radiosensitisation: hypothermia and hyperbaric oxygen in combination with pharmacological vasodilatation.

It is proposed that hyperbaric oxygen fails in the clinical situation due to a high proportion (greater than 33%) of hypoxic cells in human tumours. The means of overcoming this problem are reviewed. Additional to hyperbaric oxygenation, moderate hypothermia (30 degrees C) to allow redistribution of oxygen in the tumour is proposed. A system of externally controlled intravenous anaesthesia has been developed for the single-subject hyperbaric cylinder. Pharmacological vasodilatation is induced in the anaesthetised patient who is then fluid loaded and cooled. Initial single-sensitising treatments are advocated. Twenty-nine patients with advanced mouth cancer have completed a course of this treatment, of whom five of nine were free of disease after 2 years and 10 of 21 at 1 year, with three intercurrent deaths. Fifteen have experienced local failure. This approach would appear to be practical, safe and promising.

Anesthesia, Intravenous↗
PubMed1986

Single-dose relative biological effectiveness and toxicity studies under conditions of hypothermia and hyperbaric oxygen.

An approach to using hyperbaric oxygen with radiation in a clinical situation has been described in the preceding paper in this issue. To ascertain whether there might be a change in the relative biological effectiveness of radiation on normal mammalian tissue treated under conditions of hypothermia and hyperbaric oxygen, the acute reaction to radiation of pig skin was studied. A single dose enhancement ratio at the erythema reaction level of 1.4 +/- 0.08 was obtained when compared with irradiation at normal body temperature in air. We studied also a series of antioxidant enzymes in rat liver and lung after exposure to hypothermia and hyperbaric oxygen. Enzyme changes were such as to combat oxygen toxicity which might develop as a result of the pre-treatment.

Animals↗
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

Fetal rat myoblasts release both rat somatomedin-C (SM-C)/insulin-like growth factor I (IGF I) and multiplication-stimulating activity in vitro: partial characterization and biological activity of myoblast-derived SM-C/IGF I.

The relative release of rat somatomedin-C (SM-C)/insulin-like growth factor I (IGF I) and multiplication-stimulating activity (MSA) immunoreactivity and bioactivity from isolated fetal rat myoblasts was assessed by a partial characterization of the SM peptides present in concentrated myoblast-conditioned culture medium (MCM). The SM bioactivity of MCM, measured by [3H]thymidine or [35S]sulfate uptake by fetal rat cartilage explants, eluted with an apparent size of 50-80K on Sephadex G-200 at pH 7.5, and was associated with SM-C/IGF I immunoreactivity. Chromatography of MCM on Bio-Gel P-10 or Sephadex G-75 at acidic pH resulted in a peak of SM bioactivity associated with both SM-C/IGF I and MSA immunoreactivity in the 6-9K region. SM-binding activity, measured by competition with activated charcoal for [125I]SM-C or MSA, eluted in the void volume. When these fractions were incubated with [125I]SM-C and chromatographed on Sephadex G-200 at neutral pH, a heterogeneous pattern of binding proteins was seen, with a major component of 50-80K. After chromatofocusing of proteins in the 6-9K region from Bio-Gel P-10, three peaks of SM bioactivity were recovered, each associated with SM-C immunoreactivity, with pI values of 8.5, 7.1, and 6.5. Although both the basic and neutral peaks enhanced [3H]thymidine uptake by growth-restricted fetal rat myoblasts in vitro, only the bioactivity of the former could be blocked by incubation with a monoclonal antibody to human SM-C. Both human SM-C/IGF I and MSA purified from Buffalo rat liver cell-conditioned medium enhanced thymidine incorporation by growth-restricted fetal rat myoblasts. The results suggest that unlike reports of other fetal rat tissues, fetal rat myoblasts released approximately equal amounts of rat SM-C/IGF I and MSA during culture. The myoblast-derived SM-C/IGF I was biologically active on the cell type of origin and may play a paracrine role in muscle development.

Animals↗
PubMedDate not supplied

Characteristics and quality of Papanicolaou smears obtained by primary care clinicians using a single commercial laboratory.

BACKGROUND: Few data are available on factors associated with the quality of Papanicolaou smears performed in primary care. OBJECTIVE: To identify the patterns and proficiency of cervical cancer screening among different primary care specialties. MATERIALS AND METHODS: Clinical and cytologic data from 21,833 Papanicolaou smears, submitted to a single large commercial laboratory by 176 clinicians during a 7-month period, were correlated with individual clinician and specialty characteristics according to indexes of specimen quality. RESULTS: Obstetrician-gynecologists, nurse practitioners, and physician assistants provided screening to a younger population of women compared with family physicians, internists, and general practitioners. Factors positively associated with a greater probability of a "satisfactory" smear or the presence of endocervical cells (as a marker of adequate sampling) were increasing patient age, use of the cytobrush, and the specialty of the obstetrician-gynecologist. Satisfactory smears were not associated with any increased identification of cytologic abnormalities compared with "limited" smears. In contrast, smears with endocervical cells showed a higher proportion of abnormalities compared with specimens without such cells. CONCLUSIONS: Differences in the performance of obtaining Papanicolaou smears exist between primary care specialties, but need further clarification. The use of the cytobrush and the presence of endocervical cells are criteria that reflect clinician proficiency more realistically than the laboratory criterion of satisfactory smear.

Age Factors↗