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Biomedical subjects

G Howarth

Publications and source records attributed to G Howarth.

12 recordsLinked to original sources
PubMed2000

Oral misoprostol for induction of labour with a viable fetus.

BACKGROUND: Misoprostol is a synthetic prostaglandin which has been used to induce labour. Oral use of the drug misoprostol may be convenient, but an overdose could cause uterine hyperstimulation and precipitate labour which may be life-threatening for both mother and fetus. OBJECTIVES: The objective of this review was to assess the effects of oral misoprostol used for labour induction in women with a viable fetus. SEARCH STRATEGY: We searched the Cochrane Pregnancy and Childbirth Group trials register and the Cochrane Controlled Trials Register. SELECTION CRITERIA: Randomised trials of oral misoprostol versus any other method, placebo or no treatment given to women with a viable fetus for induction of labour. DATA COLLECTION AND ANALYSIS: The selection of trials and data extraction were undertaken by one reviewer and independently checked by two other reviewers. MAIN RESULTS: Five trials were included. In one placebo trial, oral misoprostol reduced the need for oxytocin infusion and shortened delivery time in women with prelabour rupture of membranes at term. In another trial, compared to vaginal prostaglandins, oral misoprostol reduced the need for oxytocin (relative risk 0.62, 95% confidence interval 0.47 to 0.82). Based on two trials, the caesarean section rate with oral misoprostol was 20. 2% (55/272) compared with 15.5% (42/270) for vaginal prostaglandins (relative risk 1.29, 95% confidence interval 0.90 to 1.86). Different doses (100 micrograms three hourly and 200 micrograms six hourly) were used in the two trials that compared oral with vaginal misoprostol. The caesarean section rate was 21.8% in the oral misoprostol group compared with 13.5% for vaginal misoprostol (relative risk 1.62, 95% confidence interval 0.85 to 3.09). The uterine hyperstimulation rate with oral misoprostol was 37.5% (36/96) compared with 28% (25/89) for vaginal misoprostol (relative risk 1.32, 95% confidence interval 0.86 to 2.04). There was significant heterogeneity between these two trials. REVIEWER'S CONCLUSIONS: Oral misoprostol may be an effective method for labour induction. However clinically effective oral regimens may have an unacceptably high incidence of uterine hyperstimulation and possibly uterine rupture.

Female↗
PubMed2000

Divergence of mucosal and motor effects of insulin-like growth factor (IGF)-I and LR3IGF-I on rat isolated ileum following abdominal irradiation.

BACKGROUND AND AIMS: In addition to its beneficial effects on small intestinal mucosal development and repair, insulin-like growth factor (IGF)-I has also been reported to improve neural function in toxic neuropathies. It has recently been recognized that enteric neural abnormalities contribute to the small intestinal dysmotility observed during and after abdominal radiotherapy for gynecological and pelvic malignancy. The aim of the present study was to evaluate the effects of IGF-I (5 mg/kg per day) and the more potent analog LR3IGF-I (5 mg/kg per day) on neurally mediated ileal dysmotility following irradiation. METHODS: Intestinal motor activity was recorded from 6-8 cm segments of explanted rat ileum using a miniaturized manometric technique during arterial perfusion with oxygenated fluorocarbon solution. Studies were performed 4 days after treatment with 10 Gy abdominal irradiation. At the time of irradiation, all rats underwent implantation of an osmotic mini-pump that contained 100 mmol/L acetic acid vehicle (n = 8), IGF-I (n = 8) or LR3IGF-I (n = 7). For each experiment, the total number of pressure waves, high-amplitude long-duration (defined as > 20 mmHg, > 6 s; HALD) pressure waves and long bursts (> 20) of pressure waves were determined. Ileal segments from 12 non-irradiated rats were used as controls for manometric studies. In radiotherapy treated animals, the degree of mucosal damage was determined using a standardized histologic scoring system. RESULTS: The HALD pressure waves were infrequent in non-irradiated rats but occurred in all irradiated animals. Insulin-like growth factor-I and LR3IGF-I had no effect on the frequency, amplitude or migration characteristics of HALD pressure waves compared with vehicle. Histologic damage was reduced in animals that received IGF-I and LR3IGF-I compared with vehicle-treated animals. CONCLUSIONS: In radiation enteritis, IGF-I has no effect on neurally mediated small intestinal dysmotility while improving mucosal histology. The disparity between these results suggests that parallel but separate pathologic processes underlie mucosal and motor abnormalities in radiation enteritis.

Animals↗
PubMed1999

Design and synthesis of thrombin inhibitors: analogues of MD-805 with reduced stereogenicity and improved potency.

Mitsubishi's MD-805, a potent and selective inhibitor of thrombin which contains four stereogenic centers, has been the starting point for an optimization program. A systematic synthetic study resulted in thrombin inhibitors achiral at P2 and P3 but with a 10-fold increase in potency over the original lead. A number of 4-substituted piperidines were synthesized and examined as replacements for 2-carboxy-4-methylpiperidine at P2; 4-fluoroethylpiperidine (FEP) among others provided inhibitors (e.g. 45g) of increased potency. An enantioselective route was developed to 3(R)-methyl-1,2,3,4-tetrahydroquinolinesulfonyl chloride. Inhibitors containing this enantiomerically pure P3 (42d) had similar potency to the racemic material and provided support, with modeling studies, for the preparation of the gem 3,3-disubstituted compounds. A series of inhibitors containing the novel 3, 3-dimethyl-1,2,3,4-tetrahydroquinolinesulfonyl (DMTHQS) P3 (Table 5) were synthesized and showed a similar activity profile as the monomethyl series. The combination of P3-DMTHQS, P2-FEP, and P1-arginine (45g) had a K(i) of 6 nM (MD-805 K(i) = 85 nM). In animal models of both venous and arterial thrombosis, one inhibitor (42e) was shown to produce a dose-dependent inhibition of thrombus formation that in some situations was superior to that of MD-805.

Animals↗
PubMed1998

Small intestinal dysmotility following abdominal irradiation in the rat small intestine.

Abdominal symptoms such as diarrhoea, abdominal cramps and vomiting are common during and after abdominal radiotherapy for gynaecological and pelvic malignancy. It has recently been recognized that small intestinal dysmotility may contribute to these symptoms but the underlying mechanisms are unclear in part because of the technical difficulties inherent in performing studies in irradiated small intestine. The aim of the current study was to evaluate small intestinal motor activity using perfused micromanometric techniques in 6-8-cm segments of ileum during arterial perfusion with isotonic oxygenated fluorocarbon solution. Intestinal segments from six rats were studied 4 days after treatment with 10 Gy abdominal irradiation. Ileal segments from nine nonirradiated animals acted as controls. For each experiment the total number of pressure waves, high-amplitude (> 20 mmHg, long-duration > 6 sec) pressure waves, and long (> 20 associated) bursts of pressure waves were determined. Irradiation had no effect on the overall number of pressure waves, but increased high-amplitude long-duration (HALD) pressure waves (248 vs 7, P < 0.01). In control animals HALD waves were localized to a single recording site but after radiotherapy 74% of HALD waves were temporally associated with similar pressure waves in other manometric channels. Forty-seven per cent of associated HALD waves migrated aborally. Retrograde migration of HALD waves was seen in five segments following irradiation. Irradiation abolished bursts of > 20 pressure waves.

Abdomen↗
PubMed1996

Euthanasia: sociological perspectives.

The potential of medicine to intervene to prolong or shorten the life of those considered to be dying or of those whose life is rated as of little or even negative value has only recently surfaced. It is an issue likely to affect society and the normative social relationships which that society believes it is duty to promote. It is probable that, covertly, members of the medical profession have long played a role in speeding up the process of dying, with or without the consent of affected individuals. The openness, however, with which the moral issues involved in hastening or prolonging life by medical means are now discussed is a late 20th century phenomenon. Sociologists are beginning to study the circumstances surrounding the issues and the wider societal implications of possible changes in the law, professional practices and normative values. Their work may well begin to influence public policy as well as private practice.

Aged↗
PubMed1995

Ketanserin and hydralazine in hypertension in pregnancy--a randomised double-blind trial.

OBJECTIVES: To compare ketanserin with hydralazine in the treatment of hypertension in late pregnancy. STUDY DESIGN: Randomised control trial. Ten milligrams ketanserin were compared with 5 mg hydralazine, both given intravenously to 10 patients in each group. Blood pressure, maternal and fetal heart rate and umbilical and arcuate artery Doppler flow velocimetry waveforms were recorded before and every 10 minutes after administration of the drug. RESULTS: No significant differences were found between the two drugs in respect of initial blood pressures and readings taken 10 minutes after each 30-minute administration. One patient in the hydralazine group developed severe hypotension and fetal distress for which a caesarean section was performed. No change in the flow velocity waveforms of umbilical and arcuate arteries was noticed. CONCLUSION: No unforeseen complications followed the administration of ketanserin. No major differences in the effects of the two drugs could be detected. Ketanserin appears to be safer as no hypotension occurred, and it reduced blood pressure more gradually. As ketanserin could become an alternative to hydralazine, more studies with larger numbers of patients are needed to compare it with hydralazine.

Adolescent↗