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Biomedical subjects

I Blair

Publications and source records attributed to I Blair.

31 records · Page 2Linked to original sources
PubMed1993

A large Q fever outbreak in the West Midlands: clinical aspects.

In the spring of 1989 the largest outbreak of acute Q fever recorded in the United Kingdom occurred in Solihull and surrounding areas of the West Midlands. The diagnosis was confirmed in 147 people, mainly males of working age. Windborne spread from farmland to the south of the urban area was the most likely route of infection. Fever was the commonest symptom, seen in 101/102 (99%) cases, followed by weight loss reported by 83/101 (82%). Headache, often severe, was experienced by 69/101 (68%). The commonest respiratory symptom was breathlessness, 65/102 (64%), followed by cough, 52/102 (51%), and chest pain, 46/102 (45%). Neurological features, seen in 23% of cases, were more prominent in this outbreak than is commonly recognized. Persisting ill health 6 months following the acute episode not due to chronic Q fever was also a prominent feature of this largely urban outbreak.

Adolescent↗
PubMed1990

Cytochrome P-450-dependent oxidation of arachidonic acid to 16-, 17-, and 18-hydroxyeicosatetraenoic acids.

Incubation of rat liver microsomal fractions with arachidonic acid in the presence of NADPH results in the formation of three novel monohydroxylated fatty acid metabolites. Utilizing chromatographic and mass spectral techniques, these metabolites have been identified as 16-, 17-, and 18-hydroxyeicosatetraenoic acids. The NADPH-dependent microsomal metabolism of arachidonic acid to 16-, 17-, 18-, and 19-hydroxyeicosatetraenoic acids is induced after animal treatment with beta-naphthoflavone. Reconstitution of the arachidonic acid oxygenase utilizing individual purified cytochrome P-450 enzymes demonstrates regioselectivity, controlled by the protein catalyst, for the hydroxylation of the sp3 carbon atoms adjacent to the methyl end of the fatty acid.

Animals↗
PubMed1990

Predominant functional roles for thromboxane A2 and prostaglandin E2 during late nephrotoxic serum glomerulonephritis in the rat.

While much is known regarding acute nephrotoxic serum (NTS)-induced glomerular injury, the glomerular dynamics and pathophysiologic mediators of the more relevant chronic autologous phase remain poorly defined. Studies were performed in rats 14 d after injection of rabbit serum (n = 6), NTS in the absence (n = 6), or presence, of a cyclooxygenase inhibitor, ibuprofen (n = 6) or a thromboxane A2 (TxA2) receptor antagonist, L-670,596 (n = 5). A mesangial macrophage/monocyte infiltrate was noted with equal intensity in all NTS-treated rats. Glomerular generation rates of prostaglandin (PG) E2, PGF2a, and TxA2 in nephritic kidneys were dramatically increased as compared to controls. 2 wk after NTS, there was an increase in glomerular plasma flow rate (SNPF), attainment of filtration pressure disequilibrium, and augmentation of net transcapillary hydraulic pressure difference (delta P). Glomerular filtration rate (GFR), however, was reduced, due to a marked fall in the glomerular capillary ultrafiltration coefficient (Kf). Cyclooxygenase inhibition resulted in normalization of glomerular eicosanoid generation rates, amelioration of proteinuria, afferent vasoconstriction, and normalization of SNPF, delta P, Kf, and GFR. Selective antagonism of TxA2 also led to preservation of Kf, but was without effect on SNPF, thereby leading to elevated values for GFR. Thus, in contrast to the pathophysiologic role of arachidonate-lipoxygenase products in the early heterologous phase, PG-mediated vasodilatation and TxA2-induced reductions in Kf and GFR underlie glomerular functional changes during autologous mesangioproliferative glomerulonephritis.

Animals↗
PubMed1990

Epoxygenase products of arachidonic acid are endogenous constituents of the hypothalamus involved in D2 receptor-mediated, dopamine-induced release of somatostatin.

The epoxyeicosatrienoic acids (EETs) were discovered as products of a cyclooxygenase/lipoxygenase-independent, cytochrome P-450 catalyzed metabolism of arachidonic acid (AA) termed the "epoxygenase" pathway. The rat hypothalamus is able to synthesize EETs from exogenous AA, and 5,6-EET has been found to release the neuropeptide somatostatin (SRIF) from hypothalamic nerve terminals of the median eminence (ME). In the present study, hypothalami from male rats were examined for the presence of endogenous EETs, using chemical, chromatographic, and mass spectral analysis procedures. The samples were initially separated in a C18 Sepralyte column, fractionated on TLC plates, and purified by reverse phase HPLC. Thereafter, they were esterified (pentafluorobenzyl esters) and subjected to negative ion chemical ionization/gas chromatography (GC)/mass spectral (MS) analysis. The GC retention time and the MS fragmentation patterns revealed the presence of a mixture of 8,9-, 11,12- and 14,15-EETs; instability of 5,6-EET during the isolation protocol precluded its identification. Total hypothalamic EET concentration was estimated to be 120 ng/g wet tissue. The 8,9-regiosomer released SRIF from ME nerve terminals with an ED50 of 5 x 10(-12) M; Dopamine (DA) and the D2 receptor agonist PPHT, but not the D1 receptor agonist SKF-38393, induced SRIF release from the ME. This effect was blocked by clotrimazole and ketoconazole, two inhibitors of microsomal cytochrome P-450 function and AA epoxygenase in particular. In contrast, the inhibitors failed to affect the increase in SRIF release induced by 8,9-EET. These results indicate that: 1) in addition to cyclooxygenase and lipoxygenase products, epoxygenase metabolites of AA are endogenous compounds of the hypothalamus, and 2) EETs may mediate the increase in SRIF release from hypothalamic neurons induced by the interaction of DA with D2 receptors.

Animals↗
PubMed1989

Endogenous epoxyeicosatrienoic acids. Cytochrome P-450 controlled stereoselectivity of the hepatic arachidonic acid epoxygenase.

Chiral analysis of the endogenous rat liver epoxyeicosatrienoic acids shows the biosynthesis of 8,9-, 11,12-, and 14,15-epoxyeicosatrienoic acids in a 4:1, 2:1, and 3:1 ratio of antipodes, respectively. Animal treatment with phenobarbital results in a 3.7-fold increase in microsomal cytochrome P-450 concentration and a concomitant, regioselective 6.8- and 3.4-fold increase in the liver concentration of 8,9- and 14,15-epoxyeicosatrienoic acids, respectively. Phenobarbital induces the in vivo synthesis of both regioisomers as nearly optically pure enantiomers. These results demonstrate the enzymatic origin of the epoxyeicosatrienoic acids present in rat liver and document a novel metabolic function for cytochrome P-450 in the regio- and enatioselective epoxygenation of endogenous pools of arachidonic acid.

8,11,14-Eicosatrienoic Acid↗
PubMed1988

The effect of pH adjustment of bupivacaine on onset and duration of epidural anaesthesia for caesarean section.

Previous studies have reported that elevation of the pH of local anaesthetics results in more rapid onset of action, with enhanced quality and duration of block. This study investigated the effect of pH adjustment of 0.5 per cent bupivacaine immediately prior to epidural anaesthesia for Caesarean section. Addition of 0.1 ml of 8.4 per cent sodium bicarbonate to 20 ml of 0.5 per cent bupivacaine consistently raised the pH of the local anaesthetic from 5.49 to 7.04 (mean values). One hundred patients, presenting for elective Caesarean section under epidural anaesthesia participated in the study. Forty patients received epidural anaesthesia, using pH-adjusted 0.5 per cent bupivacaine, in a dosage adequate to produce block to the T4 level. A control group of 40 patients received the standard commercial preparation of 0.5 per cent bupivacaine. A further ten patients in each group received epidural anaesthesia using 0.5 per cent bupivacaine with the addition of 1:400,000 epinephrine, to study the effect of epinephrine on pH adjustment of the local anaesthetic. Elevation of the pH of the local anaesthetic significantly increased the speed of onset of action from 6.4 minutes to 3.2 minutes and the time to peak effect from 24.8 minutes to 18.1 minutes, while the duration of anaesthesia was increased from 124.8 minutes to 147.3 minutes. The time to S2 segment blockade was also shortened from 13.5 to 8.6 minutes. Addition of 1:400,000 epinephrine to the local anaesthetic did not influence the effect of pH adjustment. Maternal and umbilical cord plasma levels of bupivacaine were not affected by pH adjustment of the local anaesthetic, while MV/UV and UA/UV ratios were unaltered.

Adult↗
PubMed1988

Prostaglandin E2 attenuation of sheep lung responses to endotoxin.

Prostaglandin (PG) E2 can inhibit inflammatory responses of neutrophils and lymphocytes, including eicosanoid release. Diffuse lung injury after endotoxemia in sheep is accompanied by sequestration of neutrophils and lymphocytes in the lungs, and eicosanoids mediate some of the pathophysiology of the response. To determine whether exogenous PGE2 could prevent the endotoxin response, we measured pulmonary hemodynamics, gas exchange, and lung lymph responses to infusion of Escherichia coli endotoxin (0.5 micrograms/kg iv over 30 min) in unanesthetized sheep in the presence and absence of PGE2 (0.5 micrograms.kg-1.min-1) infused intravenously for 4 h beginning 0.5 h before endotoxin infusion. We also measured lung lymph concentrations of thromboxane B2 (TxB2) and prostacyclin metabolite, 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha), by radioimmunoassay and leukotriene B4 (LTB4) by gas chromatography-mass spectrometry. PGE2 decreased endotoxin-induced pulmonary hypertension and hypoxemia and markedly attenuated the lymph flow and lymph protein clearance responses. PGE2 also attenuated endotoxin-induced increases in lung lymph TxB2 and 6-keto-PGF1 alpha and decreased lymph LTB4 flow after endotoxin without decreasing lymph LTB4 concentrations. We conclude that PGE2 infusion attenuates lung dysfunction caused by endotoxemia, possibly by preventing endogenous release of other eicosanoids.

6-Ketoprostaglandin F1 alpha↗
PubMed1987

Oxygen saturation during transfer from operating room to recovery after anaesthesia.

Transcutaneous oxygen saturation of haemoglobin was measured in 101 patients en route from the operating room to the recovery room. Twenty-nine became significantly hypoxaemic during the journey. The incidence of hypoxaemia was not found to relate to age, weight, duration or type of surgery, type of anaesthesia or pre-existing disease. Duration of the interval between cessation of oxygen in the operating room and arrival in recovery room was the only significant finding in patients who became hypoxaemic.

Adolescent↗