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Biomedical subjects

G W Marsh

Publications and source records attributed to G W Marsh.

31 records · Page 2Linked to original sources

Determination of alpha thalassaemia phenotypes by messenger RNA analysis.

The possibility of using alpha/beta globin messenger RNA (mRNA) ratios to distinguish between the carrier states for different forms of alpha thalassaemia has been explored. Alpha/beta globin mRNA ratios were determined in the red cells of a series of normal individuals and in members of four Cypriot families, one Thai and one Chinese family in which at least one person has haemoglobin H disease. It was found that there was a clear distinction in the ratios between normals, alpha thalassaemia 1 carriers, alpha thalassaemia 2 carriers, and those with haemoglobin H disease. This method should be a valuable addition to haematological analysis, haemoglobin synthesis and restriction mapping of DNA for the further elucidation of the genetics of alpha thalassaemia.

DNA↗

The histopathology of prolymphocytic leukaemia with particular reference to the spleen: a comparison with chronic lymphocytic leukaemia.

The histological features of prolymphocytic leukaemia are described in spleen, lymph nodes, liver and bone marrow from nine cases. Eight patients had B-PLL one had T-PLL. These features were compared with those of six cases of B chronic lymphocytic leukaemia (B-CLL) with massive splenomegaly. Both PLL and B-CLL showed enlargement of the white pulp with nodule formation and diffuse infiltration of the red pulp. In both PLL and CLL larger cells were found in the white pulp nodules often concentrated on the periphery producing a bizonal appearance. The extent of involvement of the white pulp was greater in PLL than in uncomplicated CLL. However, this was not so in two cases of B-CLL in prolymphocytoid transformation in which the heavy replacement of the white pulp by large cells without a bizonal arrangement had effaced the red pulp. The cytological differences between PLL and CLL were best appreciated in splenic red pulp. The cells of CLL were small lymphocytes with clumped chromatin, those of PLL were larger with bigger nuclei, often indented in some cases, and distinct nucleoli. The pattern of infiltration in the bone marrow, liver and lymph nodes was similar in PLL and CLL. In conclusion, PLL can be distinguished from CLL by morphological and immunological features. The distinction is important clinically, because the survival of PLL is shorter than that of CLL.

Aged↗

Diagnosis of alpha-thalassemia trait from Coulter Counter 'S' indices.

A number of patients of Mediterranean and Asian origins were found to have unexplained microcytic hypochromic red blood cells. Iron deficiency and beta-thalassaemia trait were both satisfactorily excluded in all of them. The haematological indices of these patients, obtained on a Coulter Model 'S' Counter, were found to be very similar to those seen in obligatory heterozygotes for alpha-thalassaemia. It is postulated that these patients were also carriers for alpha-thalassaemia. Subsequent investigation of some of these patients showed the characteristically reduced rates of alpha-chain synthesis seen in this condition. The discriminant function of England and Fraser (1973) may be of help in diagnosing this state. alpha-Thalassaemia trait should be considered in all patients of 'high-risk' ethnic origins with a blood picture suggestive of beta-thalassaemia trait but in whom the levels of Hb A2 and Hb F are within normal limits.

Asia↗

Linkage relationships between beta- and delta-structural loci and African forms of beta thalassaemia.

Five families are described in which there have been matings between individuals doubly heterozygous for beta thalassaemia and the delta-chain variant haemoglobin A2' to normal persons. In all there were 24 informative offspring. There were no crossovers between the beta-thalassaemia and delta-chain loci; in three of the families the genes were linked in cis and in two families the genes were found in trans. Together with previously reported families there have now been 58 opportunities for crossing over between the beta-thalassaemia and delta-chain loci and there have been two possible and one highly probable crossovers. Of the total of 9 families reported to date 4 have had the genes for beta thalassaemia and Hb A2' in cis and 5 in trans. These findings are contrasted with the findings in families where a beta-chain structural variant and Hb A2' have been observed together and these genes have always been found in trans and never in cis. The reasons for linkage disequilibrium of this type are discussed. It is concluded tentatively that the distance between the delta-structural and beta-thalassaemia loci is greater than that between the delta-structural and beta-structural loci. To date this conclusion can only be applied to the beta+ -thalassaemia and beta-thalassaemia genes as found in the African population, since this is the only population with a high incidence of delta-chain mutants which allow linkage analysis of this type to be carried out.

Africa↗

Acute lymphoblastic leukaemia: cyclical chemotherapy with three combinations of four drugs (COAP-POMP-CART regimen).

Forty-two adults and children with previously untreated acute lymphoblastic leukaemia (ALL) were entered into a programme of chemotherapy in which three combinations, each of four drugs were administered in a predetermined cyclical rotation together with cranial irradiation and intrathecal injections of methotrexate. Forty-one patients (98%) entered remission and no patient developed neuroleukaemia. Relapse of ALL occurred in 10 patients, and three patients died during remission, while eight patients stopped treatment after two and a half years and have remained in remission for two to 26 months. Comparison of remission and survival experience in this mixed group of children and adults with the experience of children treated at Memphis and in the Medical Research Council's UKALL-I trial showed no significant differences. On the other hand, analysis by prognostic factors showed that neither age nor blast cell count at presentation had any adverse effect in patients treated in this study. No relapses occurred in nine patients with blast cell counts greater than 20 x 109/1 at presentation. This regimen is effective treatment for ALL and may be of special value in patients with poor prognoses. The regiment has not as yet proved superior for the treatment of children with ALL who do not have adverse prognostic features.

Adolescent↗

Different therapeutic approaches and outcome in the treatment of pterygium.

PURPOSE: This study was initiated to investigate the role of different therapeutic modalities in the outcome of the surgical treatment of pterygium. METHODS: The results of treatment of pterygia with a variety of surgical techniques were studied in 56 eyes (49 patients) operated on at Bristol Eye Hospital during a period of five years. The surgical techniques included simple excision; bare sclera; conjunctival autograft; sliding conjunctival flap; lamellar keratoplasty and penetrating keratoplasty. Twelve eyes received additional beta irradiation in a fractionated total dose of 40 Gys. RESULTS: The incidence of recurrence was 23.2% for the 43 treated primary pterygia, and 23% for the 13 recurrent pterygia. All recurrences occurred between 2.5 and 11 months postoperatively. None of the 11 cases where additional beta irradiation was used showed any recurrence or other complication within the study period. In the recurrent pterygia group, the cases treated with a combination of surgical excision and beta irradiation, showed significantly lower recurrence rate (p < 0.001) compared to those cases treated with surgical excision alone. CONCLUSIONS: Beta irradiation as a complement to surgical treatment of pterygium, is successful in treating high risk cases such as reoperations, whereas for the majority of primary pterygia surgical excision alone is adequate. Additionally, follow up of one year will reveal any recurrences.

Adolescent↗