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Biomedical subjects

A Stewart

Publications and source records attributed to A Stewart.

At least 199 records · Page 11Linked to original sources
PubMed1993

The use of nicotinamide in the prevention of type 1 diabetes.

Nicotinamide can protect the NOD mouse from diabetes if given early enough and in sufficient dose. The effect partly wanes with time. There is reduced islet inflammation. Similar protective effects can be demonstrated in quasi-experimental interventions in humans--both diabetes related and unrelated deemed at risk of developing diabetes by reason of having islet cell antibodies. Nicotinamide protects isolated islets in vitro from the toxicity of a number of agents, but only in doses that produce significant PARP inhibition, and increased intracellular levels of NAD. It is unlikely that the protective effect demonstrated in humans is due to significant PARP inhibition, as the levels of nicotinamide achieved with the doses used are too low. Other effects of the vitamin are more likely, e.g., increase in NAD pool size by de novo synthesis, or inhibition of free radical generation. The drug appears to be safe in the doses employed in humans.

Animals↗
PubMed1993

Cancer rates.

Explore the source record for details and available documents.

Humans↗
PubMed1993

The HIV quality audit marker (HIV-QAM): an outcome measure for hospitalized AIDS patients.

The development and validation of the HIV-Quality Audit Marker (HIV-QAM), an instrument designed to measure changes in the status of hospitalized AIDS patients due to nursing care, is reported. The HIV-QAM is designed to capture the nurse data-collector's judgment of the status of the patient based upon observations, interviews, record reviews, and listening to inter-shift report. The final version of the 10 item HIV-QAM includes three scales, Self-care (six items; Cronbach's alpha = 0.89), Ambulation (two items, alpha = 0.88), and Psychological Distress (two items, alpha = 0.84). Content validity was supported by selection of items from pre-existing scales, generation of items based on care plans for HIV/AIDS patients, and review and critique of items by a panel of nurse experts. Construct validity was supported by principal components factor analysis and multi-trait scaling analysis. Convergent and divergent concurrent validity with patient symptoms and intensity of nursing care required was demonstrated. The predictive validity of the HIV-QAM for mortality at 3 and 6 months after hospital treatment for Pneumocystis carinii pneumonia was also shown.

Activities of Daily Living↗
PubMed1993

Retroviral gene transduction of circulating progenitor cells in patients with metastatic breast cancer.

The use of somatic gene therapy for the treatment of breast cancer has many potential applications. Because chemotherapeutic protocols for breast cancer are commonly limited by bone marrow toxicity, transduction of genes into pleuripotent stem cells may allow the generation and maintenance of immune responses in the presence of lymphocytotoxic agents. The practical utility of stem cell isolation and transduction would be enhanced if stem cells circulating in the peripheral blood could be isolated in patients, however this approach has been limited by the small numbers of such cells in the circulation. In these studies, recombinant granulocyte colony stimulating factor (G-CSF) was administered to patients with metastatic breast cancer to increase the number of circulating stem cells. Stem cells in the peripheral blood were then isolated and a retroviral vector (LXSN) was used to transduce the neomycin phosphotransferase gene into these cells. Gene transduction was demonstrated by resistance to the toxic effects of a neomycin analog (G418) and the detection of retroviral DNA from transduced cells. A practical method of transfer of exogenous genes into the circulating pleuripotent stem cells of patients with metastatic breast cancer is documented by these experiments. Application of these findings may allow the generation of cells resistant to anti-neoplastic agents or unique lymphoid effector cells with potent immune functions for the treatment of patients with metastatic breast cancer.

Base Sequence↗
PubMed1993

Peripheral blood stem cell mobilization using high-dose cyclophosphamide and G-CSF in pretreated patients with lymphoma.

Peripheral blood stem cell (PBSC) mobilization for autologous transplantation is more difficult in treated patients and those with bone marrow involvement. In 17 pretreated lymphoma patients, cyclophosphamide (4 g/m2) and G-CSF mobilized a median circulating peak of 1959 CFU-GM/ml on day 12.5. PBSC harvesting commenced when WBC was 1 x 10(9)/l at day 10.5 collected a median of 21.2 x 10(4)/CFU-GM/kg. 13/17 (76%) patients exceeded the 10 x 10(4) CFU-GM/kg threshold for engraftment. The CFU-GM yield was significantly higher in patients whose WBC recovered from 1-5 x 10(9)/l in less than 3 days and correlated with the maximum WBC pre and post the cyclophosphamide induced nadir. This regime safely mobilized adequate PBSC in the majority of pretreated lymphoma patients.

Adult↗
PubMed1993

Is pure red cell aplasia (PRCA) a clonal disorder?

Pure red cell aplasia (PRCA) is an uncommon disorder, many cases lacking a well defined aetiology. This report describes three cases of PRCA (two idiopathic and one associated with B-CLL) who were investigated to assess the possibility of their PRCA being associated with a clonal proliferation of T-lymphocytes. The results show that one patient had evidence of T-cell receptor (TCR) gamma chain rearrangement, and the other had a TCR delta chain rearrangement. These two cases raise the possibility of PRCA being associated with a clonal proliferation of T-cells and further studies are warranted.

Aged↗
PubMed1993

Endothelial control of the pulmonary circulation in normal and chronically hypoxic rats.

1. The effect of blockade of nitric oxide synthesis in pulmonary endothelium by two L-arginine analogues was tested in isolated blood-perfused lungs of normal rats and rats exposed chronically to 10% O2. 2. In both groups of rats the analogues (N-monomethyl-L-arginine (L-NMMA) and N-nitro-L-arginine methyl ester (L-NAME)) enhanced hypoxic vasoconstriction. In normal rats, with rare exceptions, these analogues had little or no effect on pulmonary artery pressure (Ppa) at constant blood flow during normoxia. However, chronically hypoxic rats have pulmonary hypertension and in these rats the analogues always raised Ppa; the rise in Ppa after L-NMMA but not L-NAME could be partially reversed by L-arginine. L-NAME was more potent than L-NMMA. 3. To see whether the difference between rat groups was due to the high Ppa in chronically hypoxic rats, in control rats we raised Ppa passively by lung inflation to values higher than found in chronically hypoxic rats. L-NAME did not alter the effects of lung inflation on Ppa. 4. Ppa was also raised passively by plotting pressure-flow lines up to high flow rates; the lines were changed minimally by both analogues in control rats but in chronically hypoxic rats the lines were raised to higher pressures and steepened substantially. 5. In control rats, during vasoconstriction caused by hypoxia, endothelin 1 and almitrine, L-NAME caused further rises in pressure. We conclude that a stimulus for nitric oxide release in control rats is the narrowing of vessels caused by vasoconstriction rather than passive increases in intravascular pressure. 6. In chronically hypoxic rats arterioles are narrowed by growth of new muscle and there is some muscle tone even in normoxia. Thus narrowing of the vascular lumen is the stimulus common to both groups of rats which leads to nitric oxide synthesis and attenuation of Ppa by a negative feedback process. Narrowing is associated with a large increase in shear stress due to two factors; the pressure drop along a vessel segment is increased and the surface area of the lining of the affected segment is decreased. 7. Atrial natriuretic peptide caused dose-dependent pulmonary vasodilation in both rat groups but had a greater effect in chronically hypoxic rats. The action persisted and was enhanced after blockade of NO synthesis.

Almitrine↗
PubMed1993

Altered metabolism in the ex vivo remnant kidney. I. Effects of time, substrate and perfusion pressure.

Oxygen consumption is increased in the rat remnant kidney (RK), but the basis of this enhanced metabolic activity has not been defined fully. To characterize the hypermetabolism further, isolated RK and normal kidneys (NK) were perfused using a range of perfusion pressures and substrates, and at varying times after 5/6 nephrectomy. Altered and increased RK metabolism was found as early as 1 week after 5/6 nephrectomy. The rate of net glucose consumption was higher in RK than NK (e.g., 0-30 min, 2.42 +/- 0.28 vs. 1.21 +/- 0.33 mumol.min-1 x g-1), a difference not explained by changes in oxygen delivery or glycosuria. Ammonia production was significantly greater early in perfusion in RK than NK. Calculated nephron oxygen consumption (QO2) was greater in RK than NK for all substrates tested (e.g., pyruvate 5 mM: 552.3 +/- 43.1 vs. 173.3 +/- 25.6 pmol.min-1, p < 0.001). When considered together, site I mitochondrial substrates supported QO2 and net sodium reabsorption (TNa+) better than site II substrates. In RK, QO2 did not change with increasing perfusion pressure, and TNa+ rose only slightly for pressures > or = 120 mm Hg. In summary, RK hypermetabolism is characterized by increased oxygen consumption, glycolysis and ammoniagenesis, is not substrate-specific and does not appear to be an artefact of the altered physiology of remnant perfusion.

Ammonia↗
PubMed1993

Coronary heart disease case fatality in four countries. A community study. The Acute Myocardial Infarction Register Teams of Auckland, Augsburg, Bremen, FINMONICA, Newcastle, and Perth.

BACKGROUND: Community-based registers participating in the MONICA Project of the World Health Organization show markedly different attack and death rates of coronary heart disease. This variation is a function of both the incidence and case fatality occurring within countries. The contribution of case fatality to the international variation in coronary heart disease mortality rates is not well understood. METHODS AND RESULTS: The register data from eight study populations--Augsburg and Bremen in Germany, Auckland in New Zealand, Perth and Newcastle in Australia, and North Karelia, Kuopio, and Turku/Loimaa in Finland--were compared. All patients with definite myocardial infarction or coronary death aged 35 to 64 years occurring in the study populations in 1985 through 1989 are the basis for the case fatality calculations by different definitions: 28-day case fatality for all cases, for hospitalized cases, and for hospitalized 24-hour survivors; out-of-hospital case fatality; and 24-hour case fatality for hospitalized cases. Differences in case fatality were much smaller than differences in attack and mortality rates in these populations. About two thirds of deaths occurred before the patients reached a hospital. The 28-day case fatality ranged from 37% for men in Perth to 58% for women in Augsburg. Among those who reached the hospital alive, 28-day case fatality was 13% to 27% for men and 20% to 35% for women. In those who survived 24 hours from the onset of symptoms, 28-day case fatality was 8% to 17% for men and 12% to 26% for women. CONCLUSIONS: Differences in case fatality were not associated with differences in coronary mortality rates between these populations. As most deaths occurred before reaching a hospital, opportunities for reducing case fatality through improved hospital care are limited. This emphasizes the primary role of prevention in reducing coronary death rates.

Adult↗
PubMed1993

Cot death. Bereavement care for families.

Our society does not easily acknowledge or cope with death; nor do we allow people to grieve. The death of a baby is particularly distressing and has both short and long-term implications for the families concerned. Community health professionals have a key role in supporting bereaved families. In the first of a two-part series on care of families experiencing a sudden infant death, Alison Stewart and Peter Fleming review the effects of cot death on the family and suggest how health professionals can help families come to terms with their bereavement.

Aftercare↗