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Biomedical subjects

P S Ward

Publications and source records attributed to P S Ward.

At least 19 recordsLinked to original sources
PubMed1993

Long term trigger ventilation in neonatal respiratory distress syndrome.

Experience of using an SLE 2000 neonatal trigger ventilator as the sole means of ventilation in 68 infants with respiratory distress syndrome was reviewed. No death or complication was seen in 22 infants with a birth weight above 1500 g. Forty five infants under 1500 g birth weight including 18 infants between 23 and 28 weeks' gestation were trigger ventilated throughout. Six infants died, four of whom were under 28 weeks' gestation. Two infants under 1500 g birth weight sustained a pneumothorax while being ventilated. Nine of 61 infants (15%) had radiological evidence of pulmonary interstitial emphysema, which was mild in seven infants. Intraventricular haemorrhage occurred in 10 babies under 1500 g, four of these being grade III or IV. Twenty two (48%) of the babies under 1500 g required added oxygen at 28 days. The preliminary clinical experience of this trigger ventilator suggests that it is capable of providing respiratory support from birth to extubation in even the most immature infants with respiratory distress syndrome. A controlled clinical trial is now required to compare the safety and efficacy of patient triggered ventilation with conventional neonatal ventilation.

Humans↗
PubMed1991

Systemic and renal production of thromboxane A2 and prostacyclin in decompensated liver disease and hepatorenal syndrome.

To assess the role of altered renal and systemic production of thromboxane A2 and prostacyclin in the hepatorenal syndrome, urinary excretion of their major renal and extrarenal metabolites was measured in patients with compensated and decompensated liver disease, chronic renal failure, and hepatorenal syndrome. Urinary excretion rates of all prostanoids (renal and extrarenal) were increased in subjects with liver disease compared with normal controls. Moreover, they were considerably higher in subjects with severe hepatic decompensation but good renal function compared with those with hepatorenal syndrome. In contrast, the excretion rate of all metabolites was reduced in patients with chronic renal failure. The excretion rate of all metabolites was markedly elevated during the early stages of hepatorenal syndrome and decreased in parallel with creatinine clearance. When corrected for creatinine clearance, there was a strong correlation between prostanoid excretion and serum bilirubin in subjects with liver disease; there was no difference, however, in the excretion of renal and extrarenal prostanoids between hepatorenal syndrome and severe hepatic decompensation. It is concluded that hepatic decompensation is associated with a progressive increase in prostanoid excretion but that changes in production of prostacyclin or thromboxane A2 are unlikely to be major factors in the pathogenesis of the hepatorenal syndrome.

Adult↗
PubMed1991

Excretion of metabolites of prostacyclin and thromboxane by rats with nephrotoxic nephritis: effects of interleukin-1.

1. To obtain direct evidence of abnormal eicosanoid biosynthesis in rats injected with anti-glomerular-basement-membrane antibodies (a-GBM), products derived from thromboxane A2 (TXA2) and prostacyclin (PGI2) were measured in 24 h urine collections before and after a-GBM. 2. Administration of a-GBM (9.5 mg) caused albuminuria, decreased creatinine clearance, increased numbers of intra-glomerular neutrophils and increased excretion of TXB2, 2,3-dinor-TXB2 (products of TXA2) and 6-oxo-PGF 1 alpha and 2,3-dinor-6-oxo-PGF 1 alpha (products of PGI2) at 24 h. 3. Interleukin-1 (IL-1 beta; 5 micrograms) alone caused an increase in PGI2 metabolite excretion but had no effect on TXA2 metabolites. It had no effect on creatinine clearance but increased numbers of glomerular neutrophils by approximately 4-5 fold compared to a-GBM. 4. Pretreatment of rats with IL-1 beta before a-GBM synergistically increased albumin excretion but only additively increased eicosanoid excretion. Numbers of intra-glomerular neutrophils and creatinine clearance were unchanged compared to IL-1 beta alone. 5. The cyclo-oxygenase inhibitor, ibuprofen (10 mgkg-1 i.p., twice daily for 4 days) inhibited both serum TXB2 production and urinary prostaglandin excretion. It also caused an almost complete attenuation of albumin excretion. Creatinine clearance and glomerular neutrophils remained unchanged after a-GBM/IL-1 beta. 6. We conclude that the 50% inhibition of thromboxane production induced by ibuprofen does not modify the fall in creatinine clearance of accumulation of neutrophils in the glomerulus caused by the a-GBM. This degree of inhibition of eicosanoid production was associated with a striking decrease in proteinuria, but this may reflect a haemodynamic rather than a disease modifying action.

6-Ketoprostaglandin F1 alpha↗
PubMed1991

Inhaled PAF stimulates leukotriene and thromboxane A2 production in humans.

Platelet-activating factor (PAF) is a potent bronchoconstrictor in humans and has been implicated as an inflammatory mediator in asthma. This study was performed to evaluate whether PAF-induced bronchoconstriction in vivo could be mediated through the release of the bronchoconstrictor eicosanoids, thromboxane (Tx) A2 and the cysteinyl leukotrienes. Ten asthmatic subjects were studied on three occasions after bronchial challenges with aerosolized PAF, methacholine, or isotonic saline. PAF caused bronchoconstriction in all 10 subjects (mean maximal percent fall in specific airway conductance 48.2 +/- 4.6) and was matched by methacholine challenge. Saline caused no changes in specific airway conductance. Urinary leukotriene E4 was significantly elevated after inhaled PAF (366.0 +/- 66.9 ng/mmol creatinine, P less than 0.01) compared with methacholine (41.6 +/- 13.3) and saline (33.6 +/- 4.6). The major urinary TxA2 metabolite 2,3-dinor TxB2 was elevated after inhaled PAF (41.3 +/- 7.1 ng/mmol creatinine, P less than 0.01) compared with methacholine (14.0 +/- 2.7) and saline (17.1 +/- 3.9). Urinary 2,3-dinor 6-oxo-prostaglandin F1 alpha after PAF (22.2 +/- 1.4) was raised with respect to the methacholine challenge (13.9 +/- 1.8, P less than 0.02), although no significant increase was observed compared with the saline control (18.6 +/- 3.3). Inhaled PAF leads to the secondary generation of cysteinyl leukotrienes and TxA2, and it is possible that these mediate some of the acute effects of inhaled PAF in vivo.

Administration, Inhalation↗
PubMed1991

Thromboxane A2 biosynthesis in acute asthma and after antigen challenge.

Thromboxane A2 is a potent bronchial smooth muscle spasmogen in vitro, and it has been implicated in airway inflammation and in the genesis of bronchial hyperresponsiveness in asthma. We have examined the urinary excretion of a variety of products derived from thromboxane A2 (thromboxane B2, 2,3-dinor, and 11-dehydro-thromboxane B2) and prostacyclin (6-oxo-PGF1 alpha and 2,3-dinor-6-oxo-PGF1 alpha) using gas chromatography-mass spectrometry in patients admitted acutely to hospital with severe asthma and in atopic volunteers after bronchial antigen challenge. Urinary excretion of all thromboxane-derived products was markedly increased in a number of patients with severe acute asthma compared with that in a nonsmoking control population, in some cases approaching those previously described in myocardial infarction: TXB2, 31.6 +/- 12.0 versus 6.5 +/- 0.9; 2,3-dinor-TXB2, 79.0 +/- 19.2 versus 29.5 +/- 2.7; and 11-dehydro-TXB2, 234.3 +/- 65.3 versus 25.0 +/- 2.1 ng/mmol creatinine (p less than 0.001). Urinary prostacyclin-derived products were also significantly raised in acute asthma. In contrast, after inhaled allergen challenge in atopic volunteers, which caused significant bronchoconstriction, urinary excretion of thromboxane-derived products was not significantly elevated: TXB2, 5.6 +/- 1.1 versus 5.7 +/- 1.0; 2,3-dinor-TXB2, 41.2 +/- 12.5 versus 28.5 +/- 6.9; and 11-dehydro-TXB2, 69.8 +/- 17.6 versus 39.7 +/- 11.2 ng/mmol creatinine. In a separate experiment, less than 2% of exogenously administered TXB2 to the airway appeared as urinary thromboxane-derived products, suggesting that production of greater than or equal to 1 microgram of TXA2 in vivo would be required to increase urinary thromboxane excretion twofold.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease↗
PubMed1989

Cigarette smoking: profiles of thromboxane- and prostacyclin-derived products in human urine.

Thromboxane (TX) B2, 2,3-dinor-TXB2, 11-dehydro-TXB2, 6-oxoprostaglandin (PG)F1 alpha and 2,3-dinor-6-oxo-PGF1 alpha were measured in 24 h urine samples obtained from 30 apparently healthy chronic cigarette smokers and 37 closely matched non-smoking control subjects. Samples were analysed using a newly developed assay based on immunoaffinity chromatography and capillary column gas chromatography/electron capture negative ion chemical ionisation mass spectrometry. There were significant and comparable increases in the excretion rates of both 2,3-dinor-TXB2 and 11-dehydro-TXB2 in the smoking compared with the non-smoking group (2P less than 0.001). Excretion rates of 2,3-dinor-TXB2 were 418 +/- 35 and 265 +/- 26 pg/mg creatinine in the two groups, respectively. 11-Dehydro-TXB2 excretion rates were 440 +/- 54 and 221 +/- 18 pg/mg creatinine, respectively (mean +/- S.E.). There were significant (2P less than 0.05) positive correlations between average reported cigarette consumption and excretion of both thromboxane metabolites. There were small but significant (2P less than 0.02) increases in the excretion rates of both 6-oxo-PGF1 alpha and 2,3-dinor-6-oxo-PGF1 alpha in the smoking compared with the non-smoking group. There was no significant difference in the rates of excretion of TXB2 in the two groups. The effects of acute cigarette smoke exposure (five cigarettes in 2 h) was also studied in four normally non-smoking healthy volunteers. There was no significant change in the excretion rate of any of the eicosanoids measured during control and smoking periods (at least 2 weeks apart), indicating that increased TXA2 biosynthesis in chronic smokers is unlikely to be a consequence of acute platelet activation.

6-Ketoprostaglandin F1 alpha↗
PubMed1985

Screening Rastafarian children for nutritional rickets.

We examined 42 Rastafarian children under 5 years of age who were registered with a single inner city general practice to determine the prevalence of nutritional rickets. Twenty children were receiving a strict vegan(I-tal) diet and were considered to be at high risk of developing rickets and were referred for biochemical and radiological investigation. Seven of 20 children investigated had rickets, giving an overall prevalence of 7/42. Treatment with oral cholecalciferol was successful in all seven children. Fourteen out of 18 children had evidence of iron deficiency, with low haemoglobin concentrations and hypochromic-microcytic blood films. Before this study Rastafarian children rarely attended the well baby clinic, received no vitamin supplements, and few had been immunised. They now regularly attend the clinic, receive vitamin and iron supplements, and all have completed primary immunisation.

Alkaline Phosphatase↗
PubMed1985

Reversible inhibition of central precocious puberty with a long acting GnRH analogue.

A 7 year old girl with precocious puberty was treated with buserelin, a long acting analogue of gonadotrophin releasing hormone. Spontaneous and stimulated gonadotrophin secretion became prepubertal but returned to pubertal values when buserelin was withdrawn, suggesting that normal sexual maturation should follow cessation of treatment.

Buserelin↗
PubMed1985

Growth hormone responses to sleep, insulin hypoglycaemia and arginine infusion.

This study compares the peak serum growth hormone (GH) concentration during slow wave sleep with the serum GH responses to insulin-induced hypoglycaemia and intravenous arginine infusion in 23 children referred because of short stature (20) or precocious puberty (3). Peak serum GH concentration during sleep correlated significantly with peak GH response to insulin hypoglycaemia (r = 0.64, p less than 0.01) and arginine infusion (r = 0.57, p less than 0.01). 3 children had subnormal (less than 15 mU/l) peak serum GH concentrations during sleep but normal responses to either insulin-induced hypoglycaemia or intravenous arginine infusion. 1 child had a normal peak serum GH response to sleep but subnormal responses to insulin and arginine. Sleep studies of GH secretion may be indicated when the GH responses to pharmacological stimuli are inconsistent with the observed growth pattern.

Adolescent↗
PubMed1984

Changes in fiber type composition in growing muscle as a result of dynamic exercise and static overload.

The effects of dynamic exercise (jumping) and static overload (synergist tenotomy) on rat soleus muscle were investigated during a growing phase in juvenile animals. The relative proportions of slow twitch (type 1), fast twitch (type 2a) and intermediate (type 2c) fibers were determined histochemically. The control animals, as part developmental process, lost type 2a fibers apparently by conversion to type 1 fibers via the type 2c form. Synergist tenotomy enhanced the conversion of type 2a fibers to type 2c fibers as these muscles displayed fewer type 2a fibers than control animals at the same age. In contrast, the dynamic exercise delayed the loss of type 2a fibers from the soleus. When the two exercises were combined the effects on fiber type proportions cancelled each other; this group also had a large number of type 2c fibers. This present study indicates that the activity imposed on a muscle influences the maturational development of the constituent fiber types.

Animals↗
PubMed1984

Cushing's syndrome and bronchial carcinoid tumour.

Adrenal function test results in a girl with Cushing's syndrome and a bronchial carcinoid tumour suggested pituitary dependent hypercortisolism. Resolution after excision of the tumour indicated that her condition had been caused by ectopic adrenocorticotrophic hormone secretion. Conventional tests of adrenal function may be misleading in cases of adrenocorticotrophic hormone secreting bronchial carcinoid tumours.

Adolescent↗