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E A McKeen

Publications and source records attributed to E A McKeen.

16 recordsLinked to original sources
PubMed1987

Pregnancy outcome in cancer patients. Experience in a large cooperative group.

To evaluate the potential teratogenicity and mutagenicity of modern cancer treatment, the authors enumerated from a cooperative clinical trial group 133 pregnancies in 66 women with malignant neoplasms (53% with Hodgkin's disease, 26% with other lymphomas and leukemia, and 21% with solid tumors). The gestations were divided into the following groups: Group 1, 43 pregnancies ending before therapy; Group 2, therapy given at conception or during 32 pregnancies; and Group 3, 58 pregnancies after therapy. Although the total frequencies of abnormalities were similar in Groups 1 and 2 (23% of 35 pregnancies not electively aborted and 28% of 25, respectively), there were slightly more elective abortions and birth defects related to radiation exposure at a susceptible time of gestation in Group 2. Still, there were eight normal infants among the ten fetuses who were liveborn and had first trimester exposure to chemotherapy alone; so, drug therapy early in pregnancy is not inevitably teratogenic. The apparent and surprising excess of abnormal outcomes in Group 3, 40% of 50 pregnancies, was due to low birth weight and premature terminations of pregnancy, rather than an excess of congenital anomalies. The type of unfavorable outcomes in Group 3 and their concentration in the first year posttherapy suggested they could represent defects in factors (e.g., uterine or hormonal) that normally maintain gestations, and not genetic damage to oocytes. Limitations of the data, collected by mail from physicians and their patients, included biases of self-reporting and low statistical power. Prospective study, probably through interinstitutional collaboration, seems necessary, if accurate estimates are to be made of the frequency of certain outcomes, such as spontaneous abortion and minor anomalies.

Adolescent↗
PubMed1984

The concurrence of Saethre-Chotzen syndrome and malignancy in a family with in vitro immune dysfunction.

The occurrence among 13 siblings of a malformation-mental retardation syndrome and diverse malignancies was investigated for etiologic relationship by clinical, genetic, immunologic, and virologic techniques. Three sisters and their father had Saethre-Chotzen syndrome, an autosomal dominant trait with craniosynostosis and asymmetric facies. One affected sister also had nasopharyngeal carcinoma; tow nondysmorphic brothers had Hodgkin's disease, and another had seminoma with teratocarcinoma of the testis. Decreased in vitro lymphocytic proliferation to various mitogens was observed in both available siblings with tumor, one sibling with Saethre-Chotzen syndrome, and two clinically normal siblings and their father. Both parents and all siblings had normal karyotypes and no increase of antibodies to Epstein-Barr virus. The malformation syndrome and the various neoplasias segregated independently of each other and of 47 genetic markers, including histocompatibility antigens (HLA). This study illustrates an approach to defining etiology when rare disorders cluster in a family and suggests that the occurrence of malignancies in this family may be related to subclinical immune dysfunction. Whether the Saethre-Chotzen syndrome predisposed to malignancy, perhaps through impaired immunity, awaits additional observations.

Acrocephalosyndactylia↗
PubMed1983

Esophageal carcinoma following irradiation for breast cancer.

A patient previously irradiated for inner-quadrant breast cancer developed a midesophageal stricture that on repeated biopsies showed pathologic changes consistent with acute and chronic radiation injury. Eventually a focus of well-differentiated esophageal carcinoma was found in the stricture. The patient was the second in a series of 20 patients treated at Georgetown University Hospital, Medical Oncology Division, 1973-1978, for esophageal cancer, who gave a history of previous irradiation for breast carcinoma. This finding led to the review of related case reports, follow-up studies on irradiated spondylitic patients, and data from the Connecticut Tumor Registry on esophageal cancer following breast carcinoma. These data suggest that the modest increase in risk for esophageal cancer reported in studies of atomic bomb survivors is of clinical significance to patients receiving therapeutic radiation, and, that specifically, women irradiated for inner-quadrant breast cancer, in which the dose of radiation to the esophagus can be large, may be at risk for subsequent esophageal carcinoma.

Adult↗
PubMed1982

Abnormal sensitivity to UV-radiation in cultured skin fibroblasts from patients with hereditary cutaneous malignant melanoma and dysplastic nevus syndrome.

The dysplastic nevus syndrome (DNS) is a preneoplastic melanocyte abnormality which occurs in families affected by hereditary cutaneous malignant melanoma (HCMM). Although environmental exposures, especially solar UV-irradiation, have been implicated as risk factors in sporadic melanoma, the role of such exposures in the pathogenesis of HCMM is unknown. We have studied the in vitro radiation responses of six non-tumor skin fibroblast strains from HCMM/DNS patients representing five families. All six HCMM/DNS strains were found to show some degree of enhanced cell killing sensitivity, compared with normal controls, following 254 nm UV-irradiation. The abnormal survival responses appeared to relate to specific characteristics of HCMM/DNS cells since the six strains had essentially normal sensitivity to gamma-radiation. The enhanced photosensitivity was not associated with abnormal patterns in either DNA repair synthesis or UV-induced inhibition and recovery of de novo DNA synthesis. The survival results are consistent with the hypothesis that the genetically determined predisposition to malignant melanoma may directly or indirectly be the consequence of increased susceptibility to UV-induced cellular damage.

Adolescent↗
PubMed1981

Transmission of in-vitro radioresistance in a cancer-prone family.

Neoplasms of possible radiogenic origin developed in two members of a family prone to a diversity of cancers, including bone and soft-tissue sarcoma, brain and breast cancers, and leukaemia. Gamma-irradiation survival studies in these two patients and three other relatives, but not their spouses, over three generations demonstrated resistance to cell killing. The D10 value (radiation dose required to reduce survival to 10%) was significantly higher for the five radioresistant strains (491 +/- 30 rad) than for control cultures (405 +/- 18 rad). There was a significant correlation between individual D10 values and D0 survival-curve parameters, indicating that changes in the exponential slope of the survival curves accounted for much of the increase in D10 values. This novel radiation phenotype could be a manifestation of a basic cellular defect, predisposing to a variety of tumours in family members. Thus in-vitro radioresistance, like radiosensitivity, may be a phenotype of a mechanism that increases cancer risk in man.

Adolescent↗
PubMed1981

Polymastia and renal adenocarcinoma.

After two patients with renal adenocarcinoma were found to have polymastia, we did a survey in which six of 32 patients with renal cancer had this anomaly. This finding is substantially higher than the expected frequency of 0.3 based on surveys of the general population, and accessory nipples were not found in a comparison group of 32 patients with head and neck cancer. An excess of renal anomalies was found among the patients with renal cancer, including duplicate arteries among those with accessory nipples. Family members also seemed prone to renal anomalies and certain neoplasms, notably of the kidney and brain.

Adenocarcinoma↗
PubMed1980

Waldenström's macroglobulinemia and autoimmune disease in a family.

We diagnosed Waldenström's macroglobulinemia in a father and three offspring. Clinical and subclinical autoimmune disorders occurred excessively in the family. The HLA haplotype A2, B8, DRw3 was detected in all patients with Waldenström's macroglobulinemia and all but one family member with autoimmune manifestations. A lod score [log odds] of 4.86 favors linkage to the HLA complex of a gene predisposing to lymphoproliferative and autoimmune disorders. Associated with this HLA haplotype were the B-cell alloantigens Ia-172 and 350, previously reported in patients with the lymphoma-prone sicca syndrome.

Adult↗
PubMed1979

HLA antigens in familial Hodgkin's disease.

In a study of 13 families prone to Hodgkin's disease, the probands showed significant excesses of the HLA antigens Bw35 (7 cases) and Bw37 (3 cases). Although based on a small number of patients, the results suggest that immunogenetic mechanisms account at least partly for the familial predisposition to Hodgkin's disease.

Adolescent↗
PubMed1979

Immunologic abnormalities in melanoma-prone families.

Sixty members of 4 families prone to cutaneous malignant melanoma (CMM) and a genetically determined precursor nevus syndrome underwent extensive immunologic evaluation. The most consistent finding was a diminished in vitro response to pooled alloantigens in the one-way mixed leukocyte culture (MLC) and a tendency to low T-lymphocyte and B-lymphocyte levels. When compared to controls, low B-lymphocyte levels and reduced MLC responses were found not only in family members with CMM and/or precursor nevi but also in unaffected blood relatives and spouses. The genesis of the immune dysfunction and its possible relationship to melanoma pathogenesis remain to be clarified.

B-Lymphocytes↗
PubMed1977

Discussion: genetics of multiple primary tumors: a clinical etiologic approach illustrated by three patients.

Clinicians can shed new light on the genetic and environmental origins of cancer, particularly multiple primary malignancies, by asking additional questions at the bedside. Areas to explore include occupational history, personal habits, residence, and medical and family histories with emphasis on subtle clues of disorders predisposing to cancer, such as birth defects and benign neoplasms. When this bedside approach to cancer etiology was applied to three patients with a total of 19 primary malignancies, the most striking finding was a variety of benign neoplasms in the patients and a similar array of benign and malignant tumors among first-degree relatives, some of whom also had multiple primary tumors. A single gene trait, Cowden (multiple hamartoma) disease, was recognized in one patient. It is suggested that, in future studies of multiple tumors, epidemiologists consider not just malignancies, but all forms of neoplasia, both in the patient and in the family.

Adult↗