Biomedical subjects
Publications and source records attributed to D Walsh.
Thirty-four children of 11 mothers with untreated hyperphenylalaninemia had a pattern of malformation consisting of prenatal and postnatal growth retardation, microcephaly and central nervous system dysfunction, increased incidence of malformations, and a peculiar facial appearance. Maternal hyperphenylalaninemia appears to be teratogenic, with a variability related to the blood phenylalanine concentration.
Pregnant mice were exposed to a single dose of alcohol (0.03 ml of 25% alcohol X g-1 mouse) or two doses (2 X 0.015 ml of 25% alcohol X g-1 mouse) 4 h apart, by intraperitoneal injection or by gavage, on days 7, 8, 9 or 10 of gestation. The mice were killed on the day before term and the fetuses examined for heart defects. Alcohol exposure on day 8, 9 or 10 of gestation caused a high incidence of ventricular septal defects (60%, 75% and 15% respectively). Defects of both the membranous and muscular parts of the septum were seen as well as more complex ventricular septal defects involving the great vessels. Day 7 was resistant to the induction of heart defects. This study has demonstrated that a relatively short exposure to high doses of alcohol during pregnancy in mice can cause congenital heart defects. This has important implications both as a possible cause of congenital heart anomalies in humans and for the counselling of mothers of affected children.
Because it has been suggested that both the frequency of deliberate self-poisoning and the characteristics of those who self-poison differ between Ireland, and England and Wales on the one hand and Denmark on the other we have examined self-poisoning rates and suicide rates in these three countries. Higher self-poisoning rates were found for England and Wales than for the other two countries below age 35. After this age self-poisoning rates decline in both England and Ireland but female rates continue to rise in Denmark up to age 45. Danish suicide rates are conspicuously higher than those of both England and Wales, and Ireland. Because combined death rates for suicide, undetermined and accidental deaths diminish but do not remove the differences between countries it is suggested that the Danish suicide death rate reflects a genuinely higher rate of suicide in that country.
For over 200 years parts of Ireland have been thought to have a high prevalence of psychosis, and recent hospital and community studies have confirmed this impression. In an intensive study of a rural area, the authors found that 4% of the population over age 40 was actively psychotic, with diagnoses of schizophrenia, schizoaffective disorder, and bipolar disorder. Psychosis seems to be endemic in some rural, lower socioeconomic areas in Ireland. Possible etiological explanations are discussed.
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Radiation-associated thyroid carcinoma is of clinical importance in modern radiation therapy of both Hodgkin's disease (HD) and non-Hodgkin's lymphoma (NHL), because anatomically the thyroid is often in the radiation field. We have reviewed the records of HD and NHL patients seen at Roswell Park Memorial Institute (RPMI) between 1910 and 1960 to determine associated occurrence of thyroid cancer. Radiation therapy was the major therapeutic modality with the occasional use of single agent chemotherapy with nitrogen mustard, triethylene melamine (TEM), chlorambucil and prednisone. There were 519 patients with HD and 863 with NHL. The thyroid glands of 439 (84%) HD and 544 (63%) NHL patients were included in the field of radiation. The mean age of patients with HD was 39 yr while for those with NHL, it was 53 yr. The mean survival in HD was 4.2 yr and in NHL 3.8 yr. There were three cases of thyroid cancer among the HD patients occurring 31, 44 and 48 yr, respectively, after radiation therapy. When compared with the number of thyroid cancers expected to develop, the incidence was significantly greater (p less than 0.005). In contrast, three NHL patients were found to have thyroid cancer at the time of surgery or postmortem examination. This number is again greater than expected in such a population (p less than 0.005); however, in only two cases could the cancer be considered as a sequela to NHL treatment. In all three cases the cancer turned out to be subclinical thyroid carcinoma, incidentally found at surgery or autopsy. One of the patients is still alive without evidence of either disease. The reason for this difference between patients with HD and NHL treated with a similar principle is unclear. Some of the factors contributing to this difference may include: the younger age of HD patients at diagnosis; the longer survival of patients with HD as compared with those with NHL; differences in the sites of radiation and type of treatment given; and possible differences in immunological status between the two groups.
This research examined the relationship of symptom duration prior to treatment and tumor growth rate (as indicated by changes in symptoms before treatment) upon stage of disease, tumor size, and length of survival in a group of 160 females with an initial diagnosis of breast cancer. Cases were obtained from a 15% random sample of female breast cancer cases admitted to Roswell Park Memorial Institute between 1957 and 1964. Results showed that the association between duration of symptoms and survival varied depending upon the rate of tumor growth. Among patients characterized as having slower-growing tumors, duration of symptoms was inversely associated with length of survival. Among patients characterized as having faster-growing tumors, symptom duration had little influence on survival. These findings suggest that breast cancer control activities which decrease the interval from recognition of symptoms to diagnosis and treatment can favorably influence survival for patients with slower-growing tumors. For patients with faster-growing tumors, early diagnosis and treatment during the symptomatic period is not likely to substantially alter their chances for prolonged survival. For these patients, detection of asymptomatic cancer may be the best hope for improving their prognosis.
An analytical method for phenols has been adapted for the analysis of chlorophenylmercapturic acids in rat urine. Chlorothiophenols were produced from the mercapturic acids by hydrolytic cleavage with sodium hydroxide. Acetate esters of the chlorothiophenols were formed by addition of acetic anhydride to the aqueous alkaline solution. After acylation, the acetate derivatives were extracted into hexane. Forming the acetate esters of the chlorothiophenols prevented their oxidation to disulfides and significantly improved their chromatographic properties. Electron-capture gas chromatographic analysis of the stable acetate esters was performed on a mixed phase column, 4% SE-30 + 6% OV-210. Recoveries of four chlorothiophenols ranged from 82 to 93%. This method required no sample transfer steps; therefore, sample loss and analysis time were minimized.
A group of 227 cases of non-Hodgkin's lymphoma included seven favorable and four unfavorable histologic classes with collective median survival times of 83 and 16 months, respectively. The favorable group included three follicular subgroups (cleaved, mixed, and large noncleaved) and four diffuse classes (small lymphocytic, cleaved, Burkitt's noncleaved, and convoluted lymphocytic). The unfavorable group consisted of four diffuse subgroups (plasmacytoid lymphocytic, mixed, and small and large noncleaved). There were significant differences in collective median survivals between patients in Stage I--II and those in Stage III--IV in both the favorable group (not reached, NR versus 62 months, P less than 0.001) and the unfavorable group (57 months versus 12 months, P less than 0.01). The incidence of complete response to primary treatment was higher in the favorable than in the unfavorable group (75% versus 56%, P = 0.002) and in those with limited as compared with advanced disease. Complete responders in both prognostic groups had longer survival times than did partial or minimal responders. A significant difference in median complete remission duration was found between responders in Stage I--II versus Stages III-IV in the favorable group (not reached versus 40 months, P = 0.001) but not in the unfavorable one (56 months versus 22 months, P greater than 0.05). The absence of relapses after 41 months among complete responders in the favorable but not in the unfavorable group suggests a potential for cure in a proportion of cases from the former group. The incidence of complete response was lower and median remission duration was shorter after secondary as compared with primary treatment. The results of this study confirm the prognostic value of the Lukes and Collins classification system and the importance of initial staging and of achieving a complete response to primary treatment in both the favorable and unfavorable lymphomas.
Female Sprague-Dawley CD rats were fed 0, 60, 80, 100, 120 and 140 ppm hexachlorobenzene (HCB) continuously in the diet and 2 successive litters raised. These doses were selected to range from approximately the no observable effect level to lethality in suckling offspring of treated dams. In the F1a generation, the 21-day mortality was 9.2, 19.8, 30.0, 45.4, 93.1 and 92.6% in offspring of dms fed 0, 60, 80, 100, 120 and 140 ppm HCB, respectively. In the F1b generation, a similar mortality of 18.5, 21.5, 19.5, 45, 100, and 94.1% was observed at these 5 dose levels, respectively. The neonatal lethality observed was related to both maternal dose of HCB and the cumulative lactational exposure. Clinical signs of maternal toxicity were not observed and fertility and fecundity were unaffected. In the lungs of HCB treated dams, increased numbers f intraalveolar foamy histiocytes and hypertrophy and proliferation of the lining endothelial cells of pulmonary venules were observed. These microscopic findings of pulmonary effects of HCB confirmed findings of this laboratory.
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Clinical and laboratory findings at the time of diagnosis were correlated with the survival of 242 patients with chronic myelocytic leukemia. Twelve patients with the blastic stage of the disease (blasts greater than or equal to 29%) had a median survival of eight months. Of the nonblastic patients, 28 without the Philadelphia chromosome had a relatively constant mortality averaging 43% per year and a median survival of 13 months, markedly worse than the Ph1-positive group (mortality, 6% in the first year, 17% in the second year, and the 25% per year, with a median survival of 43 months; P less than 0.001). In the latter group of 202 patients, features reflecting the "quantity" of leukemia (leukocyte count, marrow cellularity, and M:E serum B12, different degrees of splenomegaly, presence or absence of symptoms) had weaker or short-term correlations with mortality, while "qualitative" abnormalities (e.g., increased percentage of circulating blast, extramedullary leukemic tumors, major abnormalities of erythropoiesis or platelet production, marked basophilia or eosinophilia) had strong and persistent correlations with mortality. Chromosome abnormalities in addition to the Ph appeared to have a delayed though significant effect on survival. Serum alkaline phosphatase and SGOT levels did not correlate significantly with survival, but major elevations of serum LDH were associated with increased mortality throughout the course of the disease.
In the past, birthplace has frequently been omitted in completing the Sheet, but in 1976, over 91 per cent of all first admissions to psychiatric hospitals in South-East England were analysed by birthplace, sex, age-groups and marital status. First admissions for schizophrenia were five times the expected number for immigrants from new Commonwealth America (the West Indies), four times the expected number for immigrants from New Commonwealth Africa (mostly ethnic Asians) and three times the expected number from India. Immigrants from Pakistan and the remaining New Commonwealth Asian countries did not show a significantly higher than expected number of admissions for schizophrenia, and their first admissions for alcoholic psychosis and alcoholism, psychoneuroses and personality and behaviour disorders were significantly fewer than expected. First admissions for schizophrenia were also significantly more than expected among immigrants from Ireland, Germany and Poland, but not from italy.
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A total of 813 patients admitted to Roswell Park Memorial Institute from 1963--1972 with non Hodgkin's lymphoma (NHL) were reviewed for gastrointestinal (GI) involvement. Primary involvement was found in 71 and secondary involvement in 31 patients. Occult GI involvement was detected in 46% of the autopsy cases. The median survival time after the diagnosis of secondary GI involvement was nine months. The occurrence of primary GI-NHL was: 33 in the stomach, 18 in the small intestine, 14 in the ileocecal area including appendix, and 6 in the large intestine. Retrospective staging according to the Ann Arbor staging classification showed 24 to have presented as Stage I, 30 as Stage II, 4 as Stage III, and 13 as Stage IV. The primary diagnostic and therapeutic approach was operative, except in 2 patients with rectal lymphoma. Resection of the principally involved site was carried out in 42 patients. The remainder had palliative procedures or biopsy examinations only. Postoperative radiation therapy was given to 38 patients. Prognostically important features for primary GI-NHL were: stage; histologic type; site of the primary disease; and whether or not radiotherapy was administered. The age of the patient, size or degree of local extension, and type of operative procedure were prognostically of no importance. The results of this study would indicate that in Stage I and II primary GI-NHL, elective resection is not necessary prior to radiation therapy and that resection alone cannot be considered adequate treatment. A modified staging classification is proposed.
In-patient data show high rates for mental illness in the Republic of Ireland, particularly for schizophrenia. 'One-day prevalence' figures from the Three County psychiatric case register have been compared with similar data from the Camberwell register. The results confirm much higher contact rates in Ireland.
The seasonality of births was examined for 4,855 schizophrenic patients born in Ireland between 1921 and 1955. All general births for the same years were used as controls. Schizophrenic births were found to be significantly elevated in the second quarter of the year (P less than .001). The excess was 11 per cent higher than for any European country examined to date.