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Biomedical subjects

G Marsh

Publications and source records attributed to G Marsh.

At least 19 recordsLinked to original sources

A third instance of the high oxygen affinity variant, Hb Heathrow [beta 103(G5)Phe- greater than Leu]: identification of the mutation by mass spectrometry and by DNA analysis.

Hb. Heathrow [beta 103(G5)Phe- greater than Leu] was identified in an Englishman with a life-long history of polycythemia, his father had been similarly affected. A hemoglobin variant was suspected from the high oxygen affinity of the patient's blood. The Hb Heathrow abnormal beta chain was resolved from the normal beta chain by high performance liquid chromatography, and the abnormal peptide and the amino acid replacement were identified by mass spectrometry. The corresponding base change (C- greater than G at codon 103) was demonstrated by sequence analysis of the polymerase chain reaction amplified exon 2 of the genomic beta-globin gene. This is only the third known instance of Hb Heathrow.

Aged

Two decades of increasing mortality from Parkinson's disease among the US elderly.

To examine the possible role of environmental factors in the cause of Parkinson's disease (PD), we reviewed mortality trends for PD in the United States from 1962 through 1984. We found that age-specific mortality for PD in all demographic groups had changed notably during this 23-year interval. Among whites of both sexes, substantial declines were observed among the middle-aged, while notable increases were seen in the geriatric age groups. Similar changes were found in nonwhites; among nonwhites in the geriatric age range, increases of 22% to 553% were observed among women. Men generally had a 100% higher risk of death due to PD than did women. Whites were at three times the risk of nonwhites. The observed temporal changes appear to reflect improved treatment, better case ascertainment, and a true rise in the incidence of PD, particularly among the elderly. This rise may be due to preventable environmental causes and will require further investigation.

Aged

Mortality of workers potentially exposed to epichlorohydrin.

An epidemiological study was undertaken to determine whether the animal carcinogen, epichlorohydrin (ECH), produces cancer in man. A total of 863 workers with probable exposure to ECH at two chemical plants during 1948-65 were followed up for deaths up to 1983. Twenty years or more after first exposure the all cancer SMR was 112.2 (22 deaths) and the SMR for leukaemia was 500.0 (three deaths), which is statistically significant. All cancer, leukaemia, and most other causes of death were related to estimated levels of exposure to ECH, except violence. The most consistent (both plants) relation was between exposure level and heart disease. Overall, the heart disease SMR 20 years or more after first exposure was 39.2 (five deaths) for low exposure and 105.4 (17 deaths) for high exposure. Limited evidence of a cardiovascular disease relation to ECH production in one other epidemiological study is supported by this study. Allyl chloride used in the production of ECH may play a part. The relation of heart disease and exposure does not appear to be an artifact, although the fact that many other causes of death were also related to exposure argues against a causal relation.

Cardiovascular Diseases

Parkinsonism death rates by race, sex and geography: a 1980s update.

To evaluate temporal changes in the geographic distribution of Parkinson's disease (PD) mortality in the United States, we reviewed death rates for PD in the nine regions of the United States for 1980-1984. Age-adjusted mortality for all ages and for the elderly (65 years of age and older) was analyzed. Variation in PD mortality was observed among the regions for all demographic groups. The patterns were different from those reported during 1959-1961. Changing geographic patterns in mortality provide evidence for an environmental etiology for PD.

Cause of Death

Mortality from pulmonary embolism in the United States: 1962 to 1984.

To examine the effect of advances in the prevention of and therapy for PE, we reviewed mortality for PE in the United States from 1962 to 1984. Age-adjusted PE mortality increased by 67 to 100 percent between 1962 and 1974 for white and non-white men and women. From 1975 to 1984, these rates declined by 20 to 28 percent. Non-white PE mortality was greater than white PE mortality; men had a greater risk of PE death than women. Age-specific patterns (more than 40 years of age) of PE mortality followed those of the age-adjusted death rates, with increases noted in all groups between 1962 and 1974 and declines during the 1975-1984 period. These patterns might reflect improved ascertainment of cases and better prevention of disease. The magnitude of the rates suggests that the list of indications for prophylactic anticoagulation should be re-examined for possible expansion.

Adult

Plasma concentrations of flurazepam and midazolam in chronic insomniacs during 14-day use and their relationship to therapeutic effects and next-day performance and mood.

Blood samples were drawn from each of 99 chronic insomniacs twice during washout (days -20 and -6) and six times during the study (mornings after study nights -1, 1, 2, 7, 13, and 14) to examine the relationship between morning-after drug plasma levels, sleep efficiency, next-day mood, and performance. Patients in the four treatment groups received either flurazepam 30 mg, flurazepam 15 mg, midazolam 15 mg, or placebo. Plasma drug concentrations of N-desalkylflurazepam and midazolam were measured by electron-capture gas chromatography. Values of midazolam during the 14-day study were at or near the sensitivity limit of the assay and were not used in the calculations. Levels of N-desalkylflurazepam increased as expected during the 14 days. Mean level for the high-dose flurazepam group was approximately twice that of the low-dose group. The main consistency in the correlations, which were found on days 13 and 14, was that the high-dose desalkylflurazepam concentrations had a negative correlation with two independent measures of sleep latency. However, otherwise there was little or no relationship between N-desalkylflurazepam levels and sleep efficiency or next-day behavior. Issues of tolerance, individual variability in baseline and response, and their contribution to the findings are discussed.

Adult

Rising mortality from motoneuron disease in the USA, 1962-84.

From 1962 to 1984, age-specific mortality for motoneuron disease (MND) in the United States rose in all demographic groups over the age of 40. The increase was seen in both men and women, and both whites and non-whites, and was most pronounced in the elderly (eg, 378% in white women aged 80-84 years). Men were at 50% higher risk than women, and whites had twice the risk of non-whites. These increases may reflect an improvement in case ascertainment, but they also seem to show a true rise in the incidence of MND, particularly among the elderly. Such an increase suggests an environmental aetiology.

Adult

Clinical staging and immunological findings in chronic lymphocytic leukemia.

Several immunological markers were tested in 52 untreated cases of chronic lymphocyte leukemia (CLL) to see whether their frequency differed according to the clinical stage in Rai's system. The leukemic cells in all cases had B-cell features as shown by monoclonal immunoglobulins on the cell surface (SmIg) and/or a high percentage of mouse RBC (M)-rosettes. Of the two B-cell markers, the M-rosette test was the more consistently positive. The frequency of these markers did not correlate with clinical staging. The percentage of T-lymphocytes, low in all cases, was found to correlate inversely with the lymphocyte counts, which were higher in advanced stages. The absolute number of T-lymphocytes was above normal in most cases, but did not relat to staging. At least one of the serum Ig, most commonly IgA, was decreased in 87% of cases. Low Ig were slightly less common in Stages 0-I than in advanced stages (II-IV). The above features were also examined in two groups of CLL patients: with stable (9) or progressive (16) disease. The only difference observed between the two groups was that surface IgM only was present in 1 of the 9 stable cases as compared to 9 of the 16 progressive ones. Our findings do not support the suggestions that surface IgM is a feature of a benign form of CLL or that the absolute number of T-lymphocytes correlates with prognosis.

Adult