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Biomedical subjects

A Kennedy

Publications and source records attributed to A Kennedy.

At least 199 records · Page 11Linked to original sources

Down syndrome and acute leukemia in children: a 10-year retrospective survey from Childrens Cancer Study Group.

Review of 5406 children with acute lymphoblastic (ALL) or nonlymphoblastic leukemia (ANLL) registered with Childrens Cancer Study Group (CCSG) since 1972 identified 115 patients (2.1%) with Down syndrome. The proportion of patients with Down syndrome was the same for ALL (2.1%) and ANLL (2.1%). Patients with ALL with and without Down syndrome did not differ significantly with respect to age at diagnosis, sex, race, morphology (FAB classification), cell surface markers, initial white blood cell count, pretreatment hemoglobin value, hepatomegaly, lymphadenopathy, presence of mediastinal mass, CNS disease at diagnosis, or prognostic group as defined by age and initial white blood cell count. Patients with ALL-Down syndrome less frequently had splenomegaly, had lower pretreatment platelet counts, and more often had normal or elevated IgG or IgA levels. In addition, they had a significantly lower rate of remission (81% versus 94%), a higher mortality during induction therapy (14% versus 3%), and a poorer overall survival with 5-year life table rates of 50% versus 65% (P less than 0.001). If an initial remission was achieved, there were no significant differences with respect to remission duration, survival, or disease-free survival. Patients with ANLL-Down syndrome were younger at diagnosis than those without Down syndrome. There was no significant difference in the remission rates between these patients. Analysis of findings in patients with ANLL provided results similar to those obtained for patients with ALL with regard to clinical outcome after achievement of an initial remission.

Adolescent↗

Galactitol accumulation by glucose-6-phosphate deficient fibroblasts: a cellular model for resistance to the complications of diabetes mellitus.

When incubated in high galactose media, fibroblasts from individuals with the severe (Mediterranean) variety of glucose-6-phosphate dehydrogenase (G6PD) deficiency accumulate significantly less galactitol than do fibroblasts from matched control subjects. The effect is not observed in fibroblasts from black subjects with the more common, and milder, A- variant of G6PD deficiency. Since aldose reductase and sorbitol dehydrogenase activities in experimental and control fibroblasts are identical, the effect is most likely due to the substantial reduction in NADPH levels in severely G6PD-deficient cells. Sorbitol does not accumulate either in control or in G6PD deficient fibroblasts incubated in high glucose medium, most likely because of the action of sorbitol dehydrogenase, and the presence of a carrier-mediated glucose transport system in the cell membrane which limits the concentration of glucose that can accumulate in these cells.

Adolescent↗

Aldose reductase activity in retinal and cerebral microvessels and cultured vascular cells.

Isolated microvessels (primarily capillaries) from bovine retina and cerebral cortex, as well as cultured bovine retinal capillary pericytes and porcine and canine retinal capillary endothelial cells contain apparent aldose reductase activity. This conclusion is based on the ability of these cultured cells and vessel fragments to reduce DL-glyceraldehyde in preference to D-glucuronate at low (0.1 mM) substrate concentrations, in the presence of NADPH, and in the accumulation of high levels of sorbitol or galactitol when retinal pericytes and endothelial cells are cultured in media enriched in glucose or galactose. The quantitative similarities of these activities in bovine retinal and cerebral microvessels, as well as the quantitatively similar ability of these two sets of microvessels to oxidize 14C-labeled glucose with the label either in the C-1 or the C-6 position, suggests that aldose reductase may not be a major causal factor in diabetic retinopathy. This conclusion is suggested because, while these metabolic activities are similar in bovine retinal and cerebral microvessels, only the retinal microvasculature suffers major anatomic and functional damage in diabetes. This conclusion must be viewed with caution, however, because other metabolic pathways that we have not investigated may be altered by an excess of sugar alcohols, and be present in differing activities in retinal and cerebral microvessels; species differences may exist; and similar experiments have not been conducted using human microvessels.

Aldehyde Reductase↗

Galactose-induced retinal capillary basement membrane thickening: prevention by Sorbinil.

Normotensive and spontaneously hypertensive rats fed a 30% galactose diet until 15-21 months of age developed significant (P less than 0.05) retinal capillary basement membrane thickening, compared with animals fed a standard test diet. Animals on the high galactose diet containing 250 mg/kg of the aldose reductase inhibitor, Sorbinil, did not develop basement membrane thickening. No cytologic abnormalities of pericytes or endothelial cells were noted, and pericyte:endothelial cell nuclear ratios did not differ in the various experimental groups. This model reproduces a characteristic lesion of diabetes mellitus in non-diabetic animals, and should facilitate study of the biochemical mechanisms of basement membrane thickening.

Animals↗

Fatal myocardial disease associated with industrial exposure to cobalt.

A man of 48 went into cardiac shock under anaesthesia during an operation for a duodenal ulcer. At necropsy he was found to have changes resembling those seen in cobalt cardiomyopathy and his myocardial cobalt level was grossly abnormal. Subsequent investigations established that he had been exposed to cobalt in his work which involved handling the powdered metal. The dangers of cobalt as an industrial hazard are pointed out and it is suggested that cobalt cardiomyopathy should be considered in the differential diagnosis of cardiac disease in those employed in the hard metal industry.

Cardiomyopathies↗

Characteristics of children with acute nonlymphocytic leukemia in long-term continuous remission: a report for Childrens Cancer Study Group.

Children and young adults less than 18 years of age with acute nonlymphocytic leukemia who remained in long term bone marrow and extramedullary remission for two years or longer since starting maintenance were compared to the remaining responders for the following characteristics: cell type, sex, age at diagnosis, race, pretreatment, white blood count, length of time from start to induction therapy to achievement of an M1 marrow, marrow rating at day 56 of therapy, marrow rating at the start of maintenance therapy, and specific study. Forty-eight patients of a group of 333 qualified as having long term remission (14.4%). Multivariant analysis indicated that patients between the ages of 3 and 10 years (p = 0.003) as well as the length of time to achieve an M1 marrow from the start of treatment (p = 0.03) were the only characteristics associated with achievement of a long term remission. Maintenance therapy was discontinued in 15 patients from 2.5 to 4.8 years after start of maintenance and all patients remained in bone marrow remission of periods from 0+ to 3.0+ years after stopping treatment. Of the 33 who have remained on a continuous maintenance therapy 12 have had bone marrow relapses. These data confirm the prognostic value of age and length of time to achieve remission during induction in acute nonlymphocytic leukemia and suggest that there may be no significant benefit from maintenance therapy continued beyond 2 years for patients in their initial remission.

Acute Disease↗

The diagnosis of pulmonary carcinoid tumours.

Carcinoid tumours of the lung are commonly misdiagnosed as carcinoma and even if they are recognized their behaviour may be unexpected. In a series of ten cases which had caused diagnostic difficulty there had been an incorrect interpretation of broncial biopsy material in four, of the resected tumours in another four, of a needle biopsy core in one and of autopsy material in another. In some cases these errors led to needless radiotherapy and to an unnecessarily poor prognosis being given. In all cases the diagnosis of carcinoid tumour was made retrospectively by the demonstration of argyrophil granules in the tumour cells or by electron microscopy. Electron-dense bodies could be found in material that had been fixed in formol saline or even embedded in paraffin so that this method may be used retrospectively. Two of these ten tumours behaved in a malignant fashion but progressed much more slowly than most samples of bronchial carcinoma. The possibility of carcinoid tumour should be considered in any patient with a tumour of the lung who is unusually young, or who is a non-smoker or where bone or calcification are present in the tumour. It is also suggested that unrecognized cases of carcinoid tumour may be found amongst long-term survivors with lung tumours which havebeen treated by radiotherapy or chemotherapy without surgery.

Adult↗

Adriamycin in combination for the treatment of breast cancer: a Southwest Oncology Group study.

Patients with advanced breast cancer who had not previously received chemotherapy were treated on a three-arm prospective study: adriamycin day 1 plus 5-FU on day 1 and 8 (AF), adriamycin day 1, plus 5-FU day 1 and 8, and cyclophosphamide day 1 (AFC), and adriamycin day 1 plus 5-FU day 1 and 8, cyclophosphamide day 1 and methotrexate day 1 (AFCM). These courses were repeated every 21 days. The response rate was 44/105 (42%) AF, 44/103 (43%) AFC and 52/105 (49%) AFCM. The length of response was 22, 33 and 35 weeks, respectively, for AF, AFC and AFCM (P = 0.21). The median survival, 64 weeks, was equal in all three limbs. The major toxicity was leukopenia. Twenty-eight percent developed a WBC of less than 2,000/microliter, which resulted in seven deaths (2.2%).

Adult↗

Acute abdominal complications of systemic lupus erythematosus.

Four patients with acute abdominal complications of systemic lupus erythematosus requiring laparotomy are presented. The complications consisted of intestinal ischaemia, without perforation, in 3 patients and omental infarction in the fourth. In 2 patients the abdominal emergency was the first manifestation of the collagen disease. Tissue removed from 3 patients showed a marked vasculitis on histological examination. The pathogenesis and management of acute abdominal complications of systemic lupus erythematosus are discussed and the literature reviewed.

Abdomen, Acute↗