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Biomedical subjects

S P Hanley

Publications and source records attributed to S P Hanley.

At least 19 recordsLinked to original sources
PubMed1992

Bronchial responsiveness in AIDS patients with Pneumocystis carinii pneumonia.

OBJECTIVE: To study bronchial responsiveness to inhaled histamine among HIV-infected patients. DESIGN: A prospective study in a regional infectious diseases unit. METHODS: Three groups of patients were studied. Group A consisted of AIDS patients (n = 7) who had had Pneumocystis carinii pneumonia (PCP), group B of AIDS patients (n = 7) not known to have had PCP, and group C of asymptomatic HIV-positive patients (n = 7). Inhalational histamine challenge in cumulative doses (0.03-3.91 mumol) was administered by a nebulizer. It was stopped when the forced expiratory volume in 1 sec (FEV1) had fallen by more than 20% of the baseline value or when the cumulative dose administered exceeded 3.91 mumol. Response was measured as percentage change in FEV1 from the baseline value, and plotted on a linear scale against log dose histamine to enable the dose of histamine causing a 20% fall in FEV1 (PD20-FEV1) to be determined. Statistical analysis was performed by analysis of variance. RESULTS: AIDS patients previously infected with PCP (group A) had a significantly lower PD20-FEV1 [(mean, 0.31 mumol; range, 0.07-0.95; s.d., 0.31; s.e., 0.12; 95% confidence interval (CI), 0.03-0.60)] than AIDS patients without PCP (group B; mean, 1.01 mumol; range, 0.20-2.00; s.d., 0.67; s.e., 0.25; 95% CI, 0.39-1.64) or asymptomatic HIV-positive patients (group C; mean, 1.28 mumol; range, 0.49-1.80; s.d., 0.51; s.e., 0.19; 95% CI, 0.81-1.76) (P < 0.05). There was no significant difference between groups B and C. All patients recorded PD20-FEV1 within the asthmatic range of bronchial hyper-responsiveness. CONCLUSIONS: These results suggest that development of PCP in a small group of HIV-infected patients induces a significantly greater degree of bronchial hyper-responsiveness.

AIDS-Related Opportunistic Infections↗
PubMed1990

Hypoxic neuropathy: relevance to human diabetic neuropathy.

Clinical and neurophysiological studies were conducted in 47 patients with chronic obstructive airways disease and compared with 46 age-matched control subjects. Symptomatic neuropathy was reported in 13% and ankle jerks were absent in 45% of hypoxic patients. Peroneal and median nerve conduction velocities and median and sural sensory nerve amplitudes were significantly reduced in hypoxic patients (p less than 0.01). Six hypoxic patients underwent biopsy of the sural nerve, soleus muscle and overlying skin. Nerve glucose, sorbitol, fructose and myo-inositol concentrations were normal. Detailed light and electronmicroscopy revealed both nerve fibre and microvascular pathology. Segmental demyelination (32%) and unmyelinated fibre degeneration were found to be prominent lesions. The sural nerve perineurium was thickened due to an increase in the number of perineurial lamellae and an increase in intraperineurial space. Basement membrane thickening was observed in capillaries of nerve, muscle and skin. Endothelial cell hyperplasia and hypertrophy were observed in nerve and muscle capillaries but not in skin capillaries. In conclusion, this study has provided neurological, neurophysiological and neuropathological evidence of a neuropathy in hypoxic patients with chronic obstructive airways disease. These findings may be of relevance to some aspects of the aetiology of human diabetic neuropathy.

Action Potentials↗
PubMed1989

Pulmonary vasculitis associated with cholangiocarcinoma of liver.

A 62 year old woman presented with an acute pulmonary vasculitis which responded to treatment with oral steroids. Investigations over one year revealed a cholangiocarcinoma of the liver. The association of vasculitis with neoplastic diseases remains a diagnostic challenge.

Acute Disease↗
PubMed1988

Is resistance to ischaemic conduction failure induced by hypoxia?

Resistance to ischaemic conduction failure is a recognised but unexplained property of diabetic peripheral nerve. We have studied matched groups of control, diabetic, and non-diabetic hypoxic subjects (hypoxia: arterial oxygen tension less than or equal to 60 mm Hg (8 kPa) on at least one occasion and secondary to chronic lung disease). Similar resistance to ischaemia was seen in the hypoxic and diabetic groups compared with control subjects (p less than 0.001). The degree of resistance correlated with arterial oxygen tension at the time of testing (r = 0.72, p less than 0.01). In all individuals with acute exacerbations of hypoxia, the resistance to ischaemia was normalised with improvement of respiratory function (p less than 0.02). These results are compatible with the hypothesis that endoneurial hypoxia may be a factor in the pathogenesis of diabetic neuropathy.

Aged↗
PubMed1988

Dose related effects of salbutamol and ipratropium bromide on airway calibre and reactivity in subjects with asthma.

The relationship between change in airway calibre and change in airway reactivity after administration of bronchodilator drugs has been investigated by comparing the effect of increasing doses of inhaled salbutamol and ipratropium bromide on the forced expiratory volume in one second (FEV1), specific airways conductance (sGaw), and the dose of histamine causing a 20% fall in FEV1 (PD20) in six subjects with mild asthma. On each of 10 occasions measurements were made of baseline FEV1, sGaw, and PD20 after 15 minutes' rest, and followed one hour later, when the FEV1 had returned to baseline, by a single nebulised dose of salbutamol (placebo, 5, 30, 200 and 1000 micrograms) or ipratropium (placebo, 5, 30, 200 and 1000 micrograms) given in random order. Measurements of FEV1, sGaw, and PD20 were repeated 15 minutes after salbutamol and 40 minutes after ipratropium. Salbutamol and ipratropium caused a similar dose related increase in FEV1 and sGaw, with a mean increase after the highest doses of 0.76 and 0.69 litres for FEV1 and 1.15 and 0.96 s-1 kPa-1 for sGaw. Salbutamol also caused a dose related increase in PD20 to a maximum of 2.87 (95% confidence interval 2.18-3.55) doubling doses of histamine after the 1000 micrograms dose, but ipratropium bromide caused no significant change in PD20 (maximum increase 0.24 doubling doses, 95% confidence interval -0.73 to 1.22). Thus bronchodilatation after salbutamol was associated with a significantly greater change in airway reactivity than a similar amount of bronchodilatation after ipratropium bromide. This study shows that the relation between change in airway reactivity and bronchodilatation is different for two drugs with different mechanisms of action, suggesting that change in airway calibre is not a major determinant of change in airway reactivity with bronchodilator drugs.

Administration, Inhalation↗
PubMed1987

The effect of an oral leukotriene D4 antagonist L-649,923 on the response to inhaled antigen in asthma.

We have compared the effects of the leukotriene (LT) D4 antagonist L-649,923 and placebo on the airway response to antigen challenge in eight men with mild asthma known to have both an early and late response to inhaled antigen. Subjects ingested 1000 mg of L-649,923 or placebo in a randomized, double-blind protocol and, two hours later, inhaled the dose of antigen known to induce a 20% fall in FEV1. Pulmonary function (specific conductance, FEV1, peak expiratory flow rate, and maximal flow at 25% of vital capacity) was measured at intervals before and up to 9 hours after antigen. FEV1 fell in one subject after L-649,923 ingestion. L-649,923 in the other seven subjects caused no change in baseline pulmonary function, a small reduction in the early response to antigen for FEV1, peak expiratory flow rate, and maximal flow at 25% of vital capacity but not for specific airway conductance (six subjects only) and no effect on the late response. The mean maximum fall in FEV1 in the early response was 1.35 L after L-649,923 ingestion and 1.78 after placebo ingestion. This relatively small degree of protection by L-649,923 suggests either that L-649,923 is not a sufficiently potent antagonist to diminish the effect of endogenous LTD4 in vivo or that LTD4 does not play a major role in the airway response to antigen challenge.

Administration, Inhalation↗
PubMed1985

The effect of platelet number and haematocrit on whole blood thromboxane synthesis.

Whole blood, allowed to clot at 37 degrees C in glass tubes, synthesized thromboxane A2 (TxA2) as determined by radioimmunoassay for thromboxane B2 (TxB2). The time course for TxB2 synthesis showed no further increase after 60 min and the concentration of TxB2 in serum obtained from 60 normal subjects positively correlated with the whole blood platelet count in EDTA anticoagulated blood from the same donor. Patients with chronic renal failure produced less serum TxB2 than age- and sex-matched controls; they also had lower haematocrits. After re-calculating TxB2 production as a function of platelet count and haematocrit all but one of the patients fell in the range of values obtained for controls. These results suggest that chronic renal failure may not be associated with a cyclooxygenase defect and that clotted whole blood TxB2 production should be expressed as a function of platelet count and haematocrit.

Adult↗
PubMed1985

Inhibition by aspirin of human arterial and venous prostacyclin synthesis.

Prostacyclin (PGI2) synthesis by human mesenteric arteries and veins was measured ex vivo in 62 patients who received either no medication or a single oral dose of aspirin 40 mg, 75 mg or 300 mg approximately 24 hrs pre-operatively. Each dose of aspirin caused a significant reduction in both arterial and venous PGI2 synthesis compared with the untreated group. Arterial PGI2 synthesis did not differ significantly from venous PGI2 synthesis whether assessed by sample weight or sample area.

Administration, Oral↗
PubMed1985

The effects of dazoxiben, an inhibitor of thromboxane synthetase, on cold-induced forearm vasoconstriction and platelet behaviour in different individuals.

The effect of dazoxiben, a thromboxane synthetase inhibitor, on cold-induced forearm vasoconstriction was determined in two groups of human volunteers, those in whom dazoxiben abolished the platelet aggregation and release reaction induced by sodium arachidonate (group I) and those in whom it did not (group II). Dazoxiben abolished cold-induced forearm vasoconstriction in group I volunteers but not in those of group II. These results imply a correlation between platelet behaviour and cold-induced changes in vascular tone. In the group I volunteers the effect of dazoxiben on cold-induced vasoconstriction was abolished by 1800 mg of aspirin, but not by 40 mg. Since the lower dose of aspirin inhibits platelet cyclo-oxygenase but has no effect on cyclo-oxygenase in blood vessel walls, it is possible that platelets play no part in the modulation of vascular tone by dazoxiben. It is more likely that the effects of dazoxiben are confined to the vessel wall.

Adult↗
PubMed1984

Within-breath modulation of the triggering of extrasystoles in man.

Sufficient isolated extrasystoles were recorded during a period of quiet breathing in nine patients to test the null hypothesis that there is no within-breath influence of respiration on the triggering of extrasystoles. In five patients a highly significant respiratory modulation of the firing of extrasystoles was seen. The frequency distribution of extrasystoles during the respiratory cycle appeared to be approximately sinusoidal. The phase relations varied with respiratory frequency, and the peak incidence occurred relatively later in the cycle when breaths were shorter: always at about 2 s after the start of inspiration. An autonomatic reflex mechanism, equivalent to that causing sinus arrhythmia, appears to be the most likely explanation.

Adult↗
PubMed1981

Differential inhibition by low-dose aspirin of human venous prostacyclin synthesis and platelet thromboxane synthesis.

The capacity of venous tissue for prostacyclin synthesis was determined in 68 patients undergoing surgery for removal of varicose veins. A single dose of aspirin (81 mg or 300 mg) taken 14 h preoperatively strongly inhibited its synthesis, and the effect of 300 mg was still evident 48 h after ingestion. A single dose of 40 mg aspirin taken 14 h preoperatively had no effect on prostacyclin synthesis. The capacity of blood platelets to synthesise thromboxane (measured as malondialdehyde) was determined in volunteers before and at various times after ingestion of 300 mg or 40 mg aspirin. Both doses had an inhibitory effect that lasted for at least 96 h. The length of time for which the amount of thromboxane synthesised was insufficient to support platelet aggregation and the platelet release reaction depended on both the donor and the dose of aspirin. If prostacyclin and thromboxane are important in the pathogenesis of thrombosis, then doses of aspirin much lower than those used previously should be tested. The long-lasting effect of 300 mg aspirin on both venous tissue and platelets indicates that this dose is unlikely to produce a favourable prostacyclin/thromboxane balance.

Aspirin↗