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M K Whyte

Publications and source records attributed to M K Whyte.

27 records · Page 2Linked to original sources
PubMed1993

Inhibition of apoptosis and prolongation of neutrophil functional longevity by inflammatory mediators.

Neutrophil apoptosis leads to macrophage ingestion of intact senescent neutrophils. This may represent a neutrophil removal mechanism that is important both in the control of inflammatory tissue injury and for the normal resolution processes of inflammation. Because apoptosis is likely to be a key control process in cell and tissue homeostasis, a number of inflammatory mediators were tested for their ability to modulate the rate of apoptosis in populations of neutrophils aging in culture. Endotoxic lipopolysaccharide, human recombinant complement factor 5a, and human recombinant granulocyte-macrophage colony-stimulating factor all markedly inhibited the rate of neutrophil apoptosis in a concentration-dependent fashion, without inducing necrosis (as assessed by trypan blue exclusion). This inhibitory effect on the rate of neutrophil apoptosis was shown by morphological criteria and confirmed by gel electrophoresis of extracted DNA. Inhibition of apoptosis of aging neutrophil populations was associated with prolongation of the functional life span of the population as assessed by the ability of neutrophils to spread on glass surfaces, to polarize in response to deliberate stimulation with N-formyl-Met-Leu-Phe (fMLP), and to release the granule enzyme marker myeloperoxidase on fMLP stimulation. These observations show that inflammatory mediators prolong the functional life span of neutrophils through modulation of apoptosis. Further elucidation of these mechanisms will lead to a better understanding of the processes controlling neutrophil residence and function in inflamed tissues and may provide further insights into the molecular mechanisms of apoptosis, which is of widespread importance in tissue biology.

Apoptosis↗
PubMed1992

Quantification of right to left shunt at rest and during exercise in patients with pulmonary arteriovenous malformations.

BACKGROUND: Current treatment of patients with pulmonary arteriovenous malformations requires serial embolisations by means of steel coils or balloons. Measurement of right to left shunt is the most specific index of response to treatment. A new method of measuring shunt has been developed that is less invasive than traditional methods. METHODS: Right to left pulmonary shunt (expressed as percentage of cardiac output) was measured at rest in 19 patients with pulmonary arteriovenous malformations and six normal subjects by using intravenously injected albumin microspheres labelled with technetium-99m. The technique was compared with a simultaneous shunt measurement in subjects breathing 100% oxygen while they rested. The microsphere technique was adapted to measure the right to left shunt during exercise in 12 patients and five normal subjects with a new method of quantification. RESULTS: The mean (SD) shunt at rest as measured by the microsphere method was 23.2% (15.6%) in the patients and 2.7% (1.2%) in the normal subjects. When these values were compared with those of the 100% oxygen method the difference in mean values was 1% and the limits of agreement between the two methods -32% to +45%. The microsphere method is less invasive (arterial blood gas sampling is not required), quicker, and more comfortable for patients than the 100% oxygen method. In five of the normal subjects the mean (SD) 99mTc microsphere shunt increased from 2.9% (1.3%) at rest to 5.1% (2.9%) during exercise. In the 12 patients studied during exercise the shunt increased from 33.7% (12.7%) at rest to 41.7% (13.3%) during exercise in eight but decreased from 22.6% (2.4%) at rest to 17.6% (2.2%) during exercise in four. Arterial desaturation during exercise correlated with change in the size of the right to left shunt during exercise (r = +0.80). CONCLUSIONS: The microsphere method allows measurement of right to left shunt at rest and during exercise. Serial measurements at rest provide a simple, safe assessment of the physiological response to embolisation in patients with pulmonary arteriovenous malformations.

Adolescent↗
PubMed1990

Effect of percutaneous transcatheter embolization on pulmonary function, right-to-left shunt, and arterial oxygenation in patients with pulmonary arteriovenous malformations.

The effects of percutaneous transcatheter embolization on pulmonary function and exercise capacity were assessed in 15 patients with pulmonary arteriovenous malformations (PAVM). Vital capacity (VC), FEV1, DLCO, SaO2, exercise performance, and right-to-left shunt (100% oxygen method) were measured before and 2 to 6 months after treatment. Surgical correction had been attempted in 9 patients prior to referral, and 11 had associated hereditary hemorrhagic telangiectasia (HHT). Lung function tests before intervention showed normal VC and FEV1/VC ratios, reduced DLCO (mean 71% predicted, range 36 to 123%), a resting supine SaO2 of 86% (range 67 to 95%) and mean shunt fraction of 33% (range 15 to 47%). Despite further marked falls in SaO2 on exertion, exercise capacity was well preserved. Following steel coil embolization of all PAVM with a feed vessel internal diameter greater than 3 mm (one to four sessions per patient), mean shunt fraction improved from 33 to 19% and resting SaO2 from 86 to 92% with no change in VC. A consistent improvement in diffusing capacity was seen only in patients with coexisting HHT. Exercise capacity increased in the majority (unchanged in 6), and SaO2 during maximal exercise improved in all except one patient. There were no long-term complications following embolization. These findings indicate that embolization of all macroscopic PAVM, undertaken primarily to reduce the risk of paradoxical embolization, is safe and results in substantial improvements in resting and exercise SaO2 without evidence of loss of normal lung. The right-to-left shunts remaining following embolization may reflect the presence of numerous microscopic PAVM in these patients.

Adolescent↗
PubMed1990

Coil embolization of pulmonary arteriovenous malformations.

Sixteen patients with pulmonary arteriovenous malformations (PAVM) have been treated by percutaneous transvenous coil embolization. In the ten patients who have had all their angiographically demonstrable PAVM's embolised there has been a reduction of right to left shunting from a mean of 28.1% to 13% and an improvement in mean arterial oxygen saturation from 87.4% to 92.4%. Eight of these ten patients now have oxygen saturations of more than 90%. All patients have shown symptomatic improvement. There have been three complications relating to the embolizations, none of which has been serious. Coil embolization of PAVM's is an effective, safe and well tolerated procedure. Embolization should be performed in all cases of PAVM's to prevent paradoxical embolization.

Adolescent↗
PubMed1989

Absence of circulating products of oxygen derived free radicals in acute severe asthma.

Oxygen derived free radicals (ODFRs), generated by eosinophils, neutrophils, alveolar macrophages and mast cells, have been proposed as important mediators of inflammatory damage in asthma. We attempted to assess the role of these free radicals in patients with acute asthma by determining serum concentrations of phospholipid-esterified 9, 11 and the parent 9, 12-linoleic acid isomers (9, 11-LA, 9, 12-LA), using HPLC and diode array detection. The diene conjugate, 9, 11-LA, has been shown to be a sensitive and specific marker of free radical activity in other inflammatory conditions. Eight patients (6 female, aged 19-42 years) with acute asthma (mean peak expiratory flow 92 +/- (26) m (SEM) l.min-1, mean PaO2 8.4 (1.0) kPa were studied at 0, 6, 12, 24 and 48 hours after admission to hospital and again 4-6 weeks later. Initial blood samples were taken prior to the administration of oxygen or drug therapy. On admission, mean concentrations of 9, 11-LA and 9, 12-LA were normal at 18.0 (2.8) and 1024 (118) mumol.l-1. All subsequent 9, 11-LA serum concentrations were likewise in the normal range. The serum 9, 11-LA/9, 12-LA ratio was 1.9 (0.4) on admission and 1.6 (0.2) in convalescence (Normal Range 1.0-3.8). These findings in peripheral blood do not support a major role or oxygen derived free radical production in acute asthma, but local airway production cannot be excluded.

Adult↗
PubMedDate not supplied

CT-guided extrapleural drainage of bronchogenic cyst.

A patient with a subcarinal bronchogenic cyst is described. The cyst was aspirated using an extrapleural percutaneous approach under CT guidance, employing repeated injections of 4-5 ml of saline to split the parietal pleura from the chest wall. Thus we describe a technique that allows the insertion of a catheter into a cyst and complete evacuation of its contents.

Adult↗