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Biomedical subjects

P Gatenby

Publications and source records attributed to P Gatenby.

At least 19 recordsLinked to original sources

Antiphospholipid antibodies and stroke in Down syndrome.

Two patients with Down syndrome and the primary antiphospholipid antibody are described. One patient had a vasculopathy similar to that previously described as Moyamoya. Down syndrome is characterized by immune defects including a tendency to autoimmune phenomena. This report extends the scope of these observations and particularly draws out the potential role of antiphospholipid antibodies. Indeed antiphospholipid antibodies may well explain the well-known association of Down syndrome and stroke.

Adult↗

The association between synthetic bedding and adverse respiratory outcomes among skin-prick test positive and skin-prick test negative children.

BACKGROUND: Synthetic bedding has been associated with increased child wheeze and also higher allergen levels in several studies. We aimed to examine whether the association between synthetic bedding and adverse respiratory outcomes was more evident among skin-prick test (SPT) positive children. METHODS: A cross-sectional survey involving a population sample of 758 (81% of eligible) school children aged 8-10 years from randomly selected schools in the Australian Capital Territory in 1999. Parental questionnaires for ISAAC respiratory symptoms and child bedding were obtained. SPT results of 10 common allergens were available on 722 of the subjects (77% of those eligible). Synthetic pillow or quilt use was termed synthetic upper bedding. RESULTS: Synthetic quilt use was associated with asthma (Adjusted Odds Ratio 1.67 (1.05, 2.65)), recent wheeze (AOR 1.63 (1.03, 2.59)) and allergic rhinoconjunctivitis (AOR 2.11 (1.33, 3.34)) among SPT-positive children. However, these associations were not apparent for SPT-negative children. Similarly, increasing synthetic upper bedding use was associated with more than 12 episodes of wheeze among SPT-positive children (AOR 1.69 (1.08, 2.64), P=0.02, per category) but not SPT-negative children (AOR 0.77 (0.26, 2.21), P=0.6, per category). CONCLUSION: The apparent association between synthetic upper bedding and adverse respiratory outcomes was evident among SPT-positive but not SPT-negative children. Prospective intervention studies that aim to examine the effect of upper bedding composition on child asthma among SPT-positive children are required.

Asthma↗

The relationship between low level nitrogen dioxide exposure and child lung function after cold air challenge.

BACKGROUND: Nitrogen dioxide (NO(2)) or home gas appliance use has been inconsistently associated with adverse respiratory outcomes in childhood. OBJECTIVES: (i) To examine the contribution of home gas appliance type and personal NO(2) exposure. (ii) To examine the relationship between NO(2) exposure and child lung function and respiratory history. (iii) To assess whether these relationships vary by house dust mite sensitization status. METHODS: A cross-sectional survey of 344 children (71% of the eligible group) with a mean age of 9.1 years from four randomly selected schools in the Australian Capital Territory from July to September 1999. Study measurements included a parental questionnaire, NO(2) exposure by passive gas samplers, skin prick testing for 10 aeroallergens and lung function at rest and after cold air challenge. RESULTS: Total NO(2) exposure was low with a mean concentration of 10.1 ppb. No associations were found between NO(2) exposure or gas appliance use and asthma, wheeze or baseline lung function. Personal NO(2) exposure was associated with a reduction in forced expiratory volume in one second (FEV1)/forced vital capacity (FVC) after cold air challenge (adjusted difference - 0.12% (- 0.23% to - 0.01%) per 1 ppb increase). After exclusion of children who had home heating changed because of asthma, gas heater use was also significantly associated with a reduction in this measure (adjusted difference - 2.0% (- 3.7% to - 0.2%)). There was some evidence that these reductions were greater among the non-mite-sensitized children. CONCLUSIONS: The effect of low-level NO(2) exposure on these respiratory outcomes was not marked. The possible effect of low-level NO(2) exposure on non-specific bronchial reactivity requires confirmation. Future studies on NO(2) and respiratory health should include measures of house dust mite sensitization and bronchial hyper-responsiveness.

Air↗

Family and twin studies in systemic lupus erythematosus.

We have estimated how much of the total genetic predisposition to SLE may be attributable to genes outside the HLA region by comparing figures for concordance of SLE in monozygotic twins with those for concordance in HLA identical siblings in Australia. None of six dizygotic co-twins of white Australian SLE probands was concordant for SLE. One of four (25%) monozygotic co-twins of white Australian SLE probands was concordant for SLE which when added to previously published figures for Caucasoid populations gives an overall concordance rate for SLE in monozygotic twins of 25%. None of 18 HLA identical, same sex siblings of SLE probands, had definite SLE by the study criteria (i.e. less than 6%). The comparison of these figures shows that most of the genetic predisposition to SLE is attributable to genes outside the HLA region.

Adolescent↗

Predictive factors in recurrent spontaneous aborters--a multicenter study.

PROBLEM: Compare data from several centers relating to success rates in recurrent spontaneous miscarriage and assess the significance of indicators of subsequent pregnancy loss. METHOD: Data from 777 couples with unexplained recurrent spontaneous abortion from independent studies at seven centers were analyzed using logistic regression analysis. The following covariates were considered: age of patient, number of previous spontaneous abortions, length of previous abortions history, sub-fertility index (defined as the product of the number of spontaneous abortions and the abortion history), whether a patient was a primary or secondary aborter, and whether a patient had received leukocyte immunotherapy. RESULTS: There was a highly significant difference between the seven centers in success rates in the subsequent pregnancy and a highly significant association between success rate and each of the following covariates: the number of previous abortions, the length of the previous abortion history and the sub-fertility index. In particular, for each increase of 10 units in the value of the sub-fertility index, up to a value of 30, the odds in favor of a successful pregnancy decreased by a factor of 0.6, i.e., 40%. There was, however, little evidence of an association between the success rate in the subsequent pregnancy and age, parity, or immunization with cells from the husband. CONCLUSIONS: The sub-fertility index may be a useful measure of likelihood of success in a subsequent pregnancy.

Abortion, Habitual↗

Randomized double-blind, placebo-controlled trial of twice-daily zidovudine in asymptomatic haemophiliacs infected with the human immunodeficiency virus type 1. European-Australian Haemophilia Collaborative Study Group.

In this double-blind, placebo-controlled trial of HIV-infected asymptomatic haemophiliacs, the efficacy of 2-year zidovudine therapy (1000 mg daily in two divided doses) in preventing progress of HIV infection was prospectively evaluated. Drug tolerance was also studied. 143 haemophiliacs from five European countries and Australia with p24 antigenaemia and/or CD4 cell counts of 0.1-0.4 x 10(9)/l were enrolled. The main measures of outcome were progression to AIDS, CDC group IV disease, symptomatic HIV-related disease, and a decrease in CD4+ T-lymphocyte count to fewer than 0.2 x 10(9)/l. There were no significant treatment differences in the proportion of patients progressing to AIDS, CDC group IV or symptomatic disease. Analysis of time to CD4+ counts less than 0.2 x 10(9)/l showed a non-significant trend in favour of zidovudine. Haemoglobin concentrations were less than 8 g/dl in 4% of zidovudine recipients; neutropenia was less than 0.75 x 10(9) cells/l in 5% of zidovudine recipients; alanine aminotransferase levels were greater than 10 times the upper normal limit in 3% of zidovudine recipients, but also in 4% of placebo recipients. Hence there was a very low prevalence of side-effects in haemophiliacs, despite the use of a higher zidovudine dosage than is currently widely used.

Acquired Immunodeficiency Syndrome↗

Focal cerebral ischemia and antiphospholipid antibodies: a case for cardiac embolism.

We report clinical, neuroimaging and immunological findings in seven women with antiphospholipid antibodies (APLA) and cerebral ischemia. Two patients had systemic lupus erythematosus (SLE) and five had the antiphospholipid syndrome (APS). Autopsies were done in 3 women who died acutely with focal neurological deficits. Evidence for cerebral embolism was found in all patients: a) pathology demonstrated multiple cerebral infarctions and cerebral emboli from underlying non-bacterial thrombotic endocarditis (NBTE) in the patients who died. b) Three patients had thickened mitral valves and embolic cerebral occlusions were identified with cerebral angiography. c) In one patient, echocardiography detected a thrombus on the posterior leaflet of a prolapsing mitral valve at the time of ictus. Our data provide further evidence to implicate valvular endothelium in the genesis of cerebral ischemia in some patients with APLA.

Adult↗

Antibodies to 65 kDa and 70 kDa heat shock proteins in rheumatoid arthritis and systemic lupus erythematosus.

To test the potential role of autoimmunity to the highly conserved heat shock proteins (HSP) in immune arthritides, the sera from 99 patients with rheumatoid arthritis (RA), 48 patients with systemic lupus erythematosus (SLE) and 65 normal controls were examined by ELISA for IgG and IgM antibodies to the 65 kDa and 70 kDa heat shock proteins from Mycobacterium bovis (Bacille Calmette-Guerin; BCG). In RA sera there are significant numbers of individuals with increased IgM anti-65 kDa and anti-BCG reactivity as well as IgG anti-70 kDa when compared with controls. In SLE both IgM and IgG anti-BCG, together with IgM anti-65 kDa, differed significantly from controls. The results were compared with previous reports in similar groups of patients, and it is clear that no consistent pattern of reactivity emerges. While further work may be justified looking carefully at the disease duration and other subsets of both RA and SLE, it is difficult at this stage to conclude that antibodies to autologous HSP that cross-react with mycobacterial HSP play a major role in disease pathogenesis.

Adolescent↗

Rat and human Schwann cells in vitro can synthesize and express MHC molecules.

The expression of MHC class I and II molecules on cultured rat and human Schwann cells (SCs) was studied to determine whether these molecules could be synthesized by SCs in the absence of T cells. Normal rat and human SCs in vitro expressed low levels of class I MHC, but this was markedly increased by incubation with interferon gamma (IFN-gamma). Untreated SCs of rat or human origin did not express detectable class II MHC molecules, but after 48 hours incubation with IFN-gamma 100 U/ml, 20% of rat SCs and 90% of human SCs were class II positive. Immunoelectron microscopy confirmed the surface expression of MHC molecules on SCs and demonstrated class II MHC within endocytotic vesicles. These findings provide further evidence for an immunological role for SCs as antigen presenting cells or as targets for cytotoxic T cells.

Animals↗

Clinical response of hairy-cell leukaemia to interferon-alpha: results of an Australian study.

Twelve patients with documented, progressive hairy-cell leukaemia were treated with human lymphoblastoid interferon-alpha. All patients initially received a three-month course of interferon-alpha (3 x 10(6) U each day) which resulted in two complete remissions and 10 partial remissions. All eight patients who were dependent upon packed red-cell transfusions became independent of them and the three patients with the most severe, pretreatment pancytopenia also became independent of platelet transfusions. The histological appearance of the bone marrow improved in all patients; in three patients, a complete resolution of the leukaemic infiltrate was recorded. Adverse reactions occurred in 10 patients, but these were mild and did not interrupt treatment in seven patients. Moderate reactions that required a temporary reduction in the dose of interferon-alpha were seen in three patients. Ten patients subsequently received maintenance therapy with interferon-alpha (3 x 10(6) U, three times a week). A haematological improvement continued to be seen in all patients, and the results, with a minimum of one year of follow-up, are presented.

Adult↗

Prediction of response to plasma exchange in chronic relapsing polyneuropathy. A clinico-pathological correlation.

The clinical features, results of nerve conduction studies and sural nerve biopsy findings have been compared in 5 patients with chronic relapsing polyneuropathy in whom plasma exchange was used in treatment. In 2 patients who consistently responded to plasma exchange, the dominant pathological findings was segmental demyelination without prominent onion bulb formation, whereas axonal degeneration was more prominent in the cases which did not respond. It is concluded that in cases of chronic relapsing polyneuritis where the clinical, electrophysiological and histological features suggest primary demyelination, plasma exchange may provide a useful adjunct to therapy.

Adult↗

Serum-induced demyelination: an electrophysiological and histological study.

Serum from rabbits with EAN in the acute phase of the disease has been injected into rat sciatic nerve, and compared to control rabbit serum and serum from patients with demyelinating neuropathy and to normal human control serum. Electrophysiological studies were performed on all rat sciatic nerves so injected, and the nerve was then removed and examined histologically. Control rabbit and human serum and neuropathic human serum, when injected in a 20 microL quantity through a 30 gauge needle, did not produce significant electrophysiological abnormalities. EAN serum, however, produced significant dispersion of the muscle action potential and conduction block. All serum produced some histological evidence of demyelination but that seen with EAN serum was quite profound compared to all other sera. It is concluded that humoral factors are present within animals with EAN which has potent demyelinating potential. We were not able to demonstrate the same effect from patients with demyelinating neuropathy in this test system.

Animals↗