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Biomedical subjects

L McLoughlin

Publications and source records attributed to L McLoughlin.

At least 19 recordsLinked to original sources
PubMed2004

Anaesthesia for caesarean section in spinal muscular atrophy type III.

We describe the conduct of general anaesthesia for a patient with spinal muscular atrophy Type III (Kugelberg-Welander disease) undergoing elective caesarean section. Apart from a delayed return of skeletal muscle power following non-depolarising neuromuscular blockade the procedure was uneventful. We found no previously published reports of general anaesthesia for caesarean section in this condition in the English language literature. We review the available literature and discuss the potential anaesthetic problems in the management of obstetric patients with this degenerative neuromuscular disorder.

Adult↗
PubMed2003

Pregnancy and lymphangioleiomyomatosis: anaesthetic management.

Lymphangioleiomyomatosis is a rare, progressive cystic pulmonary disease related to tuberous sclerosis complex, affecting almost exclusively females of childbearing age. Progression of the disease is variable but may lead to terminal respiratory failure. As the disease may be oestrogen-dependent, it can arise de novo in pregnancy or established disease may undergo exacerbation. We report on the successful labour and delivery of such a patient and present the results of an internet survey of 30 pregnancies in 15 patients worldwide with lymphangioleiomyomatosis conducted by our patient before delivery.

Journal Article↗
PubMed2002

Lack of toxicity and persistence in the mouse associated with administration of candidate DNA- and modified vaccinia virus Ankara (MVA)-based HIV vaccines for Kenya.

Toxicity, biodistribution and persistence of candidate HIV vaccines pTHr.HIVA, a recombinant DNA, and MVA.HIVA, a recombinant modified vaccinia virus Ankara, were determined in the Balb/c mouse. The mice were injected with either two doses of intramuscular pTHr.HIVA DNA (50 microg each, separated by an interval of 14 days), two doses of intradermal MVA.HIVA (10(6) plaque-forming units each, separated by an interval of 14 days), or a combination of the two vaccines, each given in two doses, in a prime-boost regimen. The study showed no significant toxic effects, either local or systemic, under any of these employed dosing regimens. With the exception of the sites of delivery, the vaccine-derived HIVA DNA sequences were undetectable 5 weeks after the last dosing. Thus, both the vaccines alone and in a combination were considered safe and suitable for the use in phase I trials in humans.

AIDS Vaccines↗
PubMed2002

Medical training.

Explore the source record for details and available documents.

Anesthesiology↗
PubMed2001

Ultraviolet-B-induced erythema is mediated by nitric oxide and prostaglandin E2 in combination.

Ultraviolet-B-induced erythema (one, two, or four times the minimal erythema dose) was reduced but not abolished by application of 1% indomethacin gel immediately after irradiation of human skin. Continuous synthesis of prostaglandins is reflected by similar levels of indomethacin-mediated inhibition of erythema at any time within 48 h after irradiation. Repeated applications of indomethacin did not increase the inhibition. Twenty-four hours after irradiation with four minimal erythema doses, mean prostaglandin E2 levels in suction blisters were 27.2 ng per ml (SEM 11) compared with 8.6 ng per ml in unirradiated skin (n = 25; p < 0.01). Prosta glandin E2 levels in dermal tissues, sampled by microdialysis (depth 0.6 +/- 0.1 mm), were 310 pg per ml (SEM 123) and 237 pg per ml (SEM 88) in irradiated and unirradiated skin, respectively (n = 7, n.s.). Nitric oxide also made a significant contribution to ultraviolet-B-induced erythema. Ultraviolet erythema was inhibited by L-NAME in a dose-related fashion with 2 mM L-NAME causing total abolition of the response. L-NAME was effective at all time points up to 48 h suggesting that NO was produced continuously. NO was undetectable in suction blister fluid but in dermal microdialysate NO was present at 44.3 ng per ml (SEM 6.2) following ultraviolet B compared with 26.0 ng per ml (SEM 8.0) in unirradiated skin (p < 0.05), approximately 1000 times the molar concentration of prostaglandin E2. These findings confirm prostaglandin E2 and NO to be mediators of ultraviolet-induced erythema. They also show that there is prolonged synthesis of both mediators within the erythemal response and that synthesis of NO is induced by lower doses of ultraviolet B compared with that of prostaglandin E2.

Blister↗
PubMed2000

The stentless xenograft aortic valve: the wheel turns around.

BACKGROUND: A brief overview of the historical pathways of both stented and stentless porcine xenografts is presented in order to understand the return to and continuing clinical use of stentless devices. In addition, 7-11 years of durability with various models of stentless porcine valves has now accumulated and is beginning to be of relevance in determining the future place of this xenograft. Stentlessness and anticalcium agents, coupled with the poor results of stented xenografts in certain patient groups, have led to a resurgence of the clinical use of stentless xenograft valves for aortic valve replacement. An overview of the present state and future of stentless valves is given. METHODS: At both The Prince Charles Hospital and St Andrew's War Memorial Hospital, Queensland, Australia, 307 patients have received the Model 300 CryoLife-O'Brien stentless composite aortic xenograft from December 1992 to February 2000. Associated procedures were required in 56% of patients (mostly coronary artery bypass, mean 2.4 grafts, in 144 patients (47%) and left ventricular myomectomy in 34 patients (11%)). RESULTS: The hospital mortality (four early deaths) has been 1.3 +/- 1% (CL 95%) and the follow-up 100% for this analysis. The mean patient age was 73 years (range 57-89 years with 16% being 80 years and over). Morbid events have included six perivalvar leaks: four trivial and identified only on echo Doppler (no clinical murmurs) and two patients requiring reoperation at 10 days and 12 weeks with simple successful repair verified on subsequent echocardiograms. Of the 307 patients over the 7 year period, three valves only have been explanted, two for endocarditis at 1.5 and 3.5 years and one for possible technically induced structural failure at 15 months (probable needle damage). With this exception, there has been as yet no other intrinsic leaflet failure. Four early thromboembolic events (4 days-5 weeks) in patients with atrial fibrillation (no anticoagulants used postoperatively with the first 80 patients) constituted the important early morbid events. Late mortality of this elderly patient cohort has occurred in 27 patients over 7 years of maximum follow-up. One death (endocarditis) has been valve related at 5 years. Serial echocardiography (some 700 echoes in the study of this valve) has demonstrated a mean gradient of 7-9 mmHg with a very low incidence of trivial incompetence (96%) on Doppler examination with implant valve sizes ranging from 21 to 29 mm. One patient had significant regurgitation requiring reoperation. There has been no progression of either incompetence or stenosis of the remaining patients in this follow-up, now into the eighth postoperative year. CONCLUSION: The early and intermediate results appear excellent in this elderly patient cohort. Nevertheless, important surveillance is obviously required to determine the durability at 10-12 years, a crucial time when stented porcine xenografts began to show an obvious failure rate from structural deterioration, in the middle and elderly aged patient cohort. An attempt is made to outline the future of this type of stentless xenograft and to justify that its cautious use should probably be extended down to the over 50 year age patient cohort.

Journal Article↗
PubMed1997

Genetic and morphological findings in progressive familial intrahepatic cholestasis (Byler disease [PFIC-1] and Byler syndrome): evidence for heterogeneity.

Byler disease (ByD) is an autosomal recessive disorder in which cholestasis of onset in infancy leads to hepatic fibrosis and death. Children who have a clinically similar disorder, but are not members of the Amish kindred in which ByD was described, are said to have Byler syndrome (ByS). Controversy exists as to whether ByD and ByS (subtypes of progressive familial intrahepatic cholestasis [PFIC]) represent one clinicopathological entity. The gene for ByD has been mapped to a 19-cM region of 18q21-q22. PFIC caused by a lesion in this region, including ByD, can be designated PFIC-1. Examination of haplotypes in siblings with ByS in two unrelated non-Amish families showed that the gene(s) responsible for their disorder(s) did not lie in the PFIC-1 candidate region. On light microscopy and transmission electron microscopy (TEM), liver tissue differed between Amish children with PFIC-1, who had coarsely granular bile and at presentation had bland intracanalicular cholestasis, and the children with ByS in the two non-Amish families, who had amorphous or finely filamentous bile and at presentation had neonatal hepatitis. Bile acid composition of bile also differed: In the Amish children with PFIC-1 and in one ByS family, the proportional concentration of chenodeoxycholic acid (CDCA) in bile was low compared with normal bile; in the other ByS family, it was only slightly reduced. Genetic analysis and light microscopy and TEM of liver may help distinguish PFIC-1 from other forms of ByS.

Bile↗
PubMed1995

Cholecystokinin is a satiety hormone in humans at physiological post-prandial plasma concentrations.

1. Intravenous infusions of the brain/gut hormone, cholecystokinin, have been shown to reduce food intake in a subsequent test meal. However, in previous studies the doses administered were large and likely to have produced plasma concentrations far in excess of the normal post-prandial range. 2. In this study cholecystokinin-8 was infused intravenously to six healthy subjects in doses that reproduced physiological post-prandial concentrations. Plasma concentrations of cholecystokinin were measured using a novel sensitive and specific radioimmunoassay. The effect of cholecystokinin-8 infusion on subsequent food intake in a standard test meal was compared with the effect of saline infusion in the same subjects. 3. Food intake (mean +/- SEM) was significantly less during cholecystokinin (5092 +/- 665 kJ) than during saline infusion (6418 +/- 723 kJ, P = 0.03). During cholecystokinin infusion, plasma concentrations increased from 0.45 +/- 0.06 pmol/l to 7.28 +/- 2.43 pmol/l immediately before the meal. With saline infusion there was no premeal increase in plasma cholecystokinin concentration. 4. This paper describes a novel radioimmunoassay for measurement of plasma concentrations of cholecystokinin. Using this assay we have demonstrated that cholecystokinin is important in control of satiety in humans.

Adult↗
PubMed1995

Continuous administration of human corticotropin-releasing hormone in the absence of glucocorticoid feedback in man.

Continuous 24-hour infusions of a maximally stimulating dose (1 microgram/kg/h) of corticotropin-releasing hormone (CRH) have been shown to cause elevations of plasma cortisol and ACTH, but the pattern of results were confounded by serum cortisol causing feedback changes. We have looked at ACTH responses to saline or CRH infusions over 24 h in 6 normal subjects who, in addition, received either placebo or metyrapone, an 11 beta-hydroxylase inhibitor which blocks the formation of cortisol and thus abolishes glucocorticoid feedback. Cortisol and ACTH levels were measured by radioimmunoassay. Before metyrapone, CRH infusion resulted in exaggerated ACTH peaks throughout the day, as compared with normal saline: there was no influence on the noctural rise in ACTH. Following metyrapone alone, absolute cortisol levels were lower but circadian rhythmicity was preserved. Circadian rhythm of ACTH was maintained, with a fall in the evening to 14.5 +/- 4 pg/ml (mean +/- SE) at midnight and an exaggerated rise overnight, reaching a peak level of 90 +/- 33 pg/ml at 07:00 h. Subjects receiving CRH with metyrapone showed a similar pattern of responses, but with further enhanced ACTH levels. The evening fall reached a nadir of 30 +/- 6 pg/ml at 01:00 h. With diminished glucocorticoid feedback the nocturnal rise in ACTH was augmented by CRH infusion, with a morning peak of 193 +/- 21 pg/ml at 07:00 h. Thus, continuous infusion of CRH in the absence of steroid feedback leads to a retention of the circadian rhythmicity in ACTH secretion, reset at a higher absolute level.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenal Cortex Hormones↗
PubMed1993

Familial glucocorticoid deficiency associated with point mutation in the adrenocorticotropin receptor.

Familial glucocorticoid deficiency is an uncommon disorder that appears to be due to congenital insensitivity or resistance to adrenocorticotropin (ACTH), and is usually inherited in an autosomal recessive pattern. We investigated the DNA base sequence in a family with this condition by polymerase chain reaction amplification of DNA with pairs of primers that span the ACTH-receptor domain. The affected male proband showed a single base mutation, ser74-->ile, in the sequence coding for the second transmembrane domain of the ACTH receptor. A similar defect was found in an affected sister, a normal sequence in an unaffected brother, and both alleles in each parent. This is only the second clinical disorder associated with a GTP-binding-protein-linked hormone-receptor mutation.

Adolescent↗
PubMed1993

Parvovirus B19 infection in pediatric transplant patients.

Evidence of recent parvovirus virus infection (as determined by the presence of a positive IgM antibody titer) without other identified causes of anemia was found in 5 of 26 pediatric solid-organ transplant recipients evaluated for moderate-to-severe anemia between June 1990 and July 1991. Anemia tended to be chronic (median duration of anemia at the time of diagnosis was 12 weeks) and was associated with normal red blood cell indices in the absence of reticulocytes. The median age of the children at the time of presentation with anemia due to parvovirus was 1.8 years at a median time of 8 months after transplantation. Four of the 5 children were treated with i.v. immunoglobulin because of persistence of anemia requiring blood transfusions. A response characterized by an increase in reticulocyte count and normalization of hemoglobin was seen in each of these patients 2-4 weeks after treatment. The remaining patient experienced a spontaneous recovery from her anemia. Parvovirus infection should be included in the differential diagnosis of solid-organ transplant recipients presenting with severe anemia associated with low or absent reticulocytes.

Anemia↗
PubMed1993

Hyperactivity of the hypothalamo-pituitary-adrenal axis in obesity: a study of ACTH, AVP, beta-lipotrophin and cortisol responses to insulin-induced hypoglycaemia.

OBJECTIVE: The purpose of this study was to determine whether alterations in the hypothalamo-pituitary-adrenal axis and arginine vasopressin secretion, which have been associated with animal obesity, also occur in man. DESIGN: Cross-sectional analysis of extremely obese women and normal weight controls. PATIENTS: Thirty-three obese premenopausal, non-diabetic women (mean age 31 years, mean body mass index (BMI) 41), and 15 normal weight controls (mean age 24 years, mean BMI 22). MEASUREMENTS AND RESULTS: Arginine vasopressin (AVP), ACTH, beta-lipotrophin and cortisol responses to insulin-induced hypoglycaemia (0.2 units Actrapid/kg body weight for obese; 0.15 unit/kg for controls) were measured. The obese women were further characterized by anthropometric measurements (weight, body mass index, fat distribution) and indices of insulin secretion/resistance: fasting insulin, insulin secretion during 75-g oral glucose tolerance test area under curve, insulin-stimulated glucose disposal and an index of insulin resistance. No significant differences were found in the basal levels of ACTH, AVP, beta-lipotrophin or cortisol. An augmented peak beta-LPH (n = 16, P < 0.02, the difference of the mean 3.65, 95% confidence interval 1.33-10) and ACTH (n = 16, P = 0.05, the difference of the mean 2.12, 95% CI 1.0-4.5) response were found in obese as compared with normal weight controls. Both ACTH and AVP areas under the curve were similar in both groups studied. There was additionally a direct positive association between the integrated ACTH response (area under the curve) and the weight of the obese subjects (P < 0.05, r2 = 0.265). The cortisol response was negatively correlated with insulin-stimulated glucose disposal (P < 0.01, r2 = 0.23), but not with other indices of insulin secretion/resistance (fasting insulin, oral glucose tolerance test area under the curve, index of insulin resistance) or fat distribution. Comparable responses to hypoglycaemia were seen for AVP and cortisol. There was no correlation between the ACTH, AVP or cortisol responses. CONCLUSION: Obesity is associated with increased activity of the hypothalamo-pituitary-adrenal axis as supported by augmented ACTH and beta-lipotrophin secretion in response to insulin-induced hypoglycaemia and the positive association between the ACTH response and the body weight of obese women studied.

Adrenocorticotropic Hormone↗
PubMed1992

Explanation at the opioid receptor level for differing toxicity of morphine and morphine 6-glucuronide.

The radiolabelled opioid receptor binding affinities of morphine and its active metabolite morphine 6-glucuronide at the total mu, mu 1, mu 2 and delta receptors were determined. Morphine 6-glucuronide was found to have a 4-fold lower affinity for the mu 2 receptor (IC50 17 nM and 82 nM for morphine and morphine 6-glucuronide respectively, P = 0.01), the receptor postulated to be responsible for mediating the respiratory depression and gastrointestinal effects after morphine. This provides a possible explanation for the reduced respiratory depression and vomiting seen following morphine 6-glucuronide in man. A similar reduction in affinity of morphine 6-glucuronide was seen at the total mu receptor whilst there was no significant difference seen at the mu 1 or delta receptor. Hence the increased analgesic potency of morphine 6-glucuronide over morphine remains unexplained.

Animals↗