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Biomedical subjects

M Kavanagh

Publications and source records attributed to M Kavanagh.

16 recordsLinked to original sources
PubMed2001

Effect of ABT-627 (A-147627), a potent selective ET(A) receptor antagonist, on the cardiopulmonary profile of newborn lambs with surgically-induced diaphragmatic hernia.

1. Postnatal mortality in isolated congenital diaphragmatic hernia (CDH) is mainly related to the associated pulmonary hypertension (PH) and to right-to-left shunting. 2. Endothelins (ETs) are potent vasoconstrictors and pro-mitogenic peptides. Strong evidences support their participation in CDH and in the etiology of PH via the activation of ET(A) receptors (ET(A)-Rs). 3. Evaluation of the effect of ABT-627, a selective non-peptidic ET(A)-R antagonist, given from -15 to 210 min post-delivery (1 mg kg(-1) bolus +0.01 mg kg(-1) h(-1) infusion, i.v.), was conducted in the lamb model of CDH. 4. Severity of CDH was assessed in comparison to untreated controls (n=5). Untreated CDH lambs (n=7) had a higher mean pulmonary arterial pressure (MPAP; P<0.0001), lower mean blood pressure (MBP; P=0.0004), higher MPAP / MBP ratio (P<0.0001), lower arterial pH (P<0.0001), higher paCO(2) (P<0.0001), lower paO(2) (P<0.0001) and lower post-ductal pulsatile SaO(2) (P<0.0001) than untreated controls. 5. Treated controls (n=7) showed a higher MPAP, lower MBP, higher MPAP/MBP ratio, lower arterial pH, higher paCO(2), lower paO(2), lower post-ductal pulsatile SaO(2) and lower plasmatic ir-ET ratios compared to untreated controls (P<0.0001). 6. Treated CDH lambs (n=8) showed a higher MBP (P<0.0001), lower MPAP / MBP ratio (P<0.0001), higher arterial pH (P<0.0001), lower paCO(2) (P<0.0001), higher paO(2) (P=0.0228), higher post-ductal pulsatile SaO(2) (P=0.0016) and lower plasmatic ir-ET ratios (P=0.0247) when compared to untreated CDH lambs. 7. These observations revealed that, although acute perinatal treatment with a selective non-peptidic ET(A)-R antagonist had some adverse effects in controls, it attenuated the progressive cardiopulmonary deterioration that occurred after birth in CDH lambs.

Animals↗
PubMed2000

Effect of CGS 26303, an endothelin-converting enzyme-neutral endopeptidase inhibitor, on nitrofen-induced congenital diaphragmatic hernia in the rat.

BACKGROUND/PURPOSE: The pathophysiology of congenital diaphragmatic hernia (CDH) associated with lung hypoplasia and pulmonary hypertension is not understood fully. Endothelins (ETs) are the most potent vasoconstrictors that also act as promitogenic agents. They may play a role during pregnancy in leading to the condition found at birth and ongoing mortality in CDH. Therefore, the authors studied the effect of CGS 26303, a nonselective endothelin-converting enzyme and neutral endopeptidase inhibitor, in the rat model of CDH. METHODS: Pregnant Sprague-Dawley rats were divided into 3 groups: group 1 (n = 4) received CGS 26303 (50 mg/kg, subcutaneously, twice a day), from gestational day 12 until term (21 to 23 days); group 2 (n = 8) received nitrofen (100 mg/kg, orally) at gestational day 11.5; group 3 (n = 8) received both nitrofen and CGS 26303. The survival of the newborn rats was monitored up to 240 minutes. After natural death or euthanasia, they were weighed and microdissected. The degree of hernia was quantified as small, moderate, or severe, and lungs and liver were harvested and weighed. RESULTS: Newborn rats from mothers of group 3 (n = 81) survived 196 +/- 8 minutes compared with 173 +/- 9 minutes of those of group 2 (n = 97). Severe CDH from group 3 (n = 20) had a mean survival time of 66 +/- 13 minutes compared with 26 +/- 4 minutes for those of group 2 (n = 27). Lung index in severe CDH pups of group 3 was increased by 13% compared with those from group 2 (P < .0001), whereas their liver index went down by 8% (P < .05). CONCLUSIONS: These results suggest that CGS 26303 might have a beneficial effect when given during pregnancy in increasing survival at birth and reducing the severity of the pulmonary hypoplasia in newborn rats with nitrofen-induced CDH.

Animals↗
PubMed1992

New developments in sustained-release antihypertensive therapy: formulation and pharmacokinetic considerations.

In order to achieve a consistently absorbed form of nifedipine over 24 hours, a novel formulation approach, INDAS, was used to develop a once-daily, sustained-release (SR) form of nifedipine that could provide effective control of blood pressure at a low total daily dose. The pharmacokinetic characteristics of this new formulation of nifedipine-SR were compared with those of divided doses of conventional nifedipine. The SR formulation was shown to achieve a lower peak plasma nifedipine level but with a prolonged plasma profile characterized by an extended time to peak plasma levels (Tmax), a higher trough plasma level, a longer apparent half-life, and a markedly lower peak-to-trough fluctuation in plasma nifedipine concentrations. In a separate study, the gastrointestinal transit parameters and physical characteristics of the SR tablet were evaluated. This study established that the large intestine is the major site of residence and absorption for this dosage form. The physical erosion and disintegration characteristics of the SR formulation are such that a well-maintained absorption of nifedipine is consistently achieved over the 24 hour dosing interval.

Adult↗
PubMed1991

The effects of lipid lowering on diabetic retinopathy.

The effect of lipid lowering on hard exudates was determined in six consecutive patients with insulin-dependent diabetes mellitus. Diet and hypolipidemic drug therapy including the use of pravastatin, a new inhibitor of 3-hydroxy-3-methylglutaryl coenzyme-A reductase, were used to treat patients for one year. The total cholesterol concentration decreased from a mean baseline value of 231 mg/dl to a treatment mean value of 165 mg/dl. The mean low-density lipoprotein cholesterol concentration decreased from 157 mg/dl to 93 mg/dl. Masked grading of fundus photographs indicated an improvement in hard exudates in all six patients and a decrease in microaneurysms in four patients. Visual acuity improved in one patient and did not change (one line or less change) in five patients. No remarkable side effects resulting from treatment were observed. Our pilot study suggests that aggressive therapy of diabetic patients with hyperlipidemia may have a beneficial effect on background retinopathy.

Adult↗
PubMed1990

Prevalence of dental caries and dental fluorosis in students, 11-17 years of age, in fluoridated and non-fluoridated cities in Quebec.

The purpose of this study was to evaluate the difference in dental caries and fluorosis prevalence in 936 randomly selected life-long residents selected from public and private schools in Trois-Rivières (1.0 ppm F in 1987) and Sherbrooke (less than 0.1 ppm F), Que., Canada. Students, 11-17 years of age, were examined for dental caries using the National Institute for Dental Research criteria and for dental fluorosis using the Tooth Surface Index of Fluorosis. Because of an inconsistent fluoridation history in Trois-Rivières, comparisons were carried out between two age strata: students 11-14 years of age who consumed for a longer duration suboptimally fluoridated water than those in the second stratum: students 15-17 years of age. Only public school students, 15-17 years of age, from Trois-Rivières had significantly lower mean filled surface and decayed, missing, and filled tooth surface (DMFS) scores (28 and 24%, respectively) than similar students in Sherbrooke. Among private school students, differences were not found, except in the youngest age group in Sherbrooke who had significantly lower mean DMFS than similar students from Trois-Rivières. The prevalence of fluorosis was 45.6% and 58.0% in Trois-Rivières public and private schools, respectively, and 31.1% and 30.1% in Sherbrooke public and private schools, respectively. The use of fluoride tablets was significantly associated with fluorosis. This study showed that water fluoridation benefitted students from public schools and that the risk factors for dental fluorosis were the use of fluoridated water and fluoride tablets.

Adolescent↗
PubMed1989

Transdermal delivery of nicotine in normal human volunteers: a single dose and multiple dose study.

The absorption of nicotine delivered by a transdermal delivery system (TDS) was investigated in two separate studies, (A) a dose proportionality study and (B) a multiple dose study. In the dose range of 15-60 mg nicotine, the AUC and Cmax values were proportional to the dose. The levels achieved were in the same range as reported in smokers, following absorption from nicotine chewing gum. The TDS used in the present study produced sustained levels of nicotine for 24 h. No significant accumulation of nicotine was evident as a result of multiple dose administration using a 30-mg nicotine patch. Absorption of nicotine from the TDS was 80-90% and the rate of delivery was similar during both studies.

Administration, Cutaneous↗
PubMed1987

Are indices of free radical damage related to exercise intensity.

The possibility that plasma levels of malonaldehyde (MDA) are altered by exercise has been examined. The presence of MDA has been recognized to reflect peroxidation of lipids resulting from reactions with free radicals. Maximal exercise, eliciting 100% of maximal oxygen consumption (VO2max) resulted in a 26% increase in plasma MDA (P less than 0.005). Short periods of intermittent exercise, the intensity of which was varied, indicated a correlation between lactate and MDA (r2 = 0.51) (p less than 0.001). Blood lactate concentrations increased throughout this exercise regimen. A significant decrease (10.3%) in plasma MDA occurred at 40% VO2max. At 70% VO2max plasma MDA was still below resting values, however the trend to an increase in MDA with exercise intensity was evident. At exhaustion, plasma MDA and lactate were significantly greater than at rest. These results suggest, that exhaustive maximal exercise induces free radical generation while short periods of submaximal exercise (i.e. less than 70% VO2max) may inhibit it and lipid peroxidation.

Adult↗
PubMed1979

Flowering forests.

Explore the source record for details and available documents.

Journal Article↗
PubMed1978

The diet and feeding behaviour of Cercopithecus aethiops tantalus.

The feeding behaviour of representative groups of tantalus monkeys (Cercopithecus aethiops tantalus) was observed during 1974-1975 in three habitats in Cameroon. Observations took place during the wet and dry seasons in sahelian savannah, guinea savannah and farmed forest. The tantalus monkeys were similar to other races of C.aethiops that have been studied in that they were omnivorous and lacked any narrow specialisations of either diet or feeding techniques. The dietary range was similar in all three habitats, although considerable seasonal variation occurred. About one third of all feeding took place on the ground.

Animals↗
PubMedDate not supplied

Surgery for locally aggressive bone tumours.

Treatment of 16 patients with aggressive benign bone tumours and one patient with a low grade malignancy with a combined regimen of cryosurgery, phenolization and acrylic cementation is reported. Patients were aged between 9 and 51 years and were treated by this method between the years 1986 and 1993. Minimal follow up was 13 months. The commonest histological diagnosis was giant cell tumour (7), followed by aneurysmal bone cyst (6), chondromyxoidfibroma (3) and low grade chondrosarcoma (1). Patients were assessed for functional outcome and local recurrence. On average 86 per cent of premorbid function was restored at follow up and there was one local recurrence (6.29 per cent). We conclude that this is a satisfactory method of gaining local control of these tumours.

Adolescent↗