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Biomedical subjects

D Edwards

Publications and source records attributed to D Edwards.

At least 55 records · Page 3Linked to original sources

Ergometrine--a partial agonist at 5-HT receptors in the uterus isolated from the oestrogen-primed rat.

The mechanism of action of ergometrine has been studied in isolated uterus from the oestrogen-primed non-pregnant rat. Ergometrine (30 nM-1 microM) induced spasm and was antagonised selectively by methysergide and ICI 169,369, a proposed competitive antagonist at 5-hydroxytryptamine (5-HT2) receptors. The pA2 values of ICI 169,369 against 5-HT and ergometrine were not significantly different. Ergometrine (0.1-10 microM) was also a selective antagonist of 5-HT with no effect against acetylcholine or potassium chloride. It is suggested that ergometrine is a partial agonist involving 5-HT receptors in rat uterus.

Animals

Chlamydia screening.

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Chlamydia Infections

Ethinyl oestradiol and D-norgestrel is an effective emergency postcoital contraceptive: a report of its use in 1,200 patients in a family planning clinic.

We describe a prospective study of 1,200 patients using the Yuzpe regimen of hormonal postcoital contraception. There was an 85% follow-up rate, and of the 1,015 patients followed there were 13 pregnancies, giving a pregnancy rate of 1.3%. The number of expected pregnancies at mid-cycle was reduced by 83%; 12 of the 13 pregnancies went on to abortion. The patients were young: 86% were under 25, and 10% were under 15. The most frequent reason for presentation was that no contraception had been used (57%). All patients received an antiemetic; 57% experienced no side-effects, 28% had some nausea and 9.6% some vomiting. It is concluded that this is a safe form of emergency contraception, which is an effective way of reducing the number of unwanted pregnancies, especially in the very young.

Adolescent

Computed tomography of the brain, chest, and abdomen in the preoperative assessment of non-small cell lung cancer.

The benefit to be gained from carrying out computed tomography of brain and abdomen in addition to the chest has been evaluated retrospectively in 114 consecutive patients with non-small cell lung cancer who, on the basis of history, clinical examination, chest radiography, and bronchoscopy had been considered potentially operable. Computed tomography of the chest showed potentially inoperable tumour in 37 patients, of whom 25 had tumour confined to the chest. Three patients were shown to have malignant disease within the mediastinum and abdomen; five within the mediastinum and brain; and four within the mediastinum, abdomen, and brain. Computed tomography of the abdomen disclosed deposits in nine patients, but in only two were the abnormalities restricted to the abdomen. Computed tomography of the brain showed metastases in 10 patients, of whom only one had metastatic disease confined to the brain. Thus three patients had isolated deposits in the abdomen and brain. In 12 patients the identification of metastases in the abdomen and brain removed the need for mediastinoscopy. Preoperative computed tomography of the abdomen and brain detected occult metastases in 15 patients (13%) in this study. In three patients the extrathoracic abnormality proved the only contraindication to surgery, but in the other 12 it provided valuable corroborative evidence of incurability and facilitated the assessment of the mediastinal abnormality.

Abdominal Neoplasms

Metabolic predictors of carbon monoxide poisoning.

In a retrospective study of 54 carbon monoxide (CO) levels greater than 10%, we looked for correlations with glucose, electrolytes and anion gap. Electrolytes and anion gap were not found to be significant. We did find, however, that 8 out of the 12 CO levels greater than 25 had glucose values greater than 110. We, therefore, conclude that if a patient presents with the appropriate history or signs of vague CNS symptoms and an increased blood glucose, a measurement of CO should be considered.

Blood Glucose

Increased incidence of cervical intraepithelial neoplasia grade 3 and human papillomavirus infection at a family planning clinic.

A five-fold increase in the incidence of histologically-proven cervical intraepithelial neoplasia grade 3 (CIN3) was observed for patients attending the Christchurch family planning clinic in 1985 compared with the preceding three years. There were 51 new cases in 1985 and a yearly average of 9.3 between 1982 and 1984. There was an increase also in cervical smears showing evidence of human papillomavirus (HPV) infection. The time interval between the last normal smear and the diagnosis of CIN3 was short, averaging 2.3 years. CIN3 patients were young (average 28.9 years); they had a high average number of sexual partners (10.1). These findings support the theory of a sexually transmitted precursor to the development of CIN3. The 1985 surge in CIN3 may reflect an increased prevalence of this oncogenic agent. The aim of screening is to prevent invasive cervical carcinoma. Annual smears should therefore be considered for young sexually-active women in view of the short time interval between normal smears and the development of CIN3.

Adolescent

Risk factors for Chlamydia trachomatis infection of the cervix: a prospective study of 2000 patients at a family planning clinic.

Two thousand and thirty-four patients attending a family planning clinic were tested for the presence of Chlamydia trachomatis infection of the cervix. The incidence of infection was 17.5%. Pregnant patients had a higher incidence of infection (23%), than nonpregnant patients (16.8%; p less than 0.05), and in the former this was not related to age. In nonpregnant women age was found to be an important determinant of infection rate, 22% in the 20 and under age group, and 9% in those over 25 years (p less than 0.01). There was a higher rate of infection in those with abnormal cervical smears, and in those with a coincident sexually transmitted infection; this was not statistically significant. Risk factors for acquiring this infection were identified as patients with more than five life time partners, those 20 years old or less, and pregnant patients, regardless of age or number of partners.

Adult

Cell cycle changes in water properties in sea urchin eggs.

This study concerned changes in the motional properties of cellular water during the first cell cycle of fertilized sea urchin eggs (Lytechinus variegatus). There was a significant decrease in proton NMR T1 relaxation time and in cytoplasmic ice crystal growth during mitosis and a significant increase in T1 time and cytoplasmic ice crystal size during cleavage. This was not caused by egg water content changes as reflected by egg volume measurements. Removal of both the fertilization membrane and the hyaline layer shortly after fertilization did not alter the pattern of T1 time changes at mitosis and cleavage as compared to whole eggs; thus, the pattern of T1 time changes was attributed to intracellular events. Treatment of fertilized eggs with cytochalasin B, an inhibitor of actin polymerization, did not block the fall in T1 time at mitosis, but did block cytokinesis and the increase in T1 time, which normally occurred at cleavage. A significant pattern of actin disassembly and reassembly at mitosis and cytokinesis was found by studies on the total amount of monomeric actin (G actin) using the DNase I assay. This led to the hypothesis that the observed changes in T1 time and ice crystal size during the first cell cycle were due to the depolymerization and polymerization of cytoplasmic actin. To test this, the effect of the in vitro polymerization of purified actin on the T1 time and on ice crystal growth was examined. It was concluded that changes in the T1 time and ice crystal growth upon polymerization of actin in vitro resembled the changes seen in vivo. These results suggest that changes in the motional properties of cytoplasmic water during the first cell cycle are due, at least in part, to the state of polymerization of cytoplasmic actin.

Actins

The effect of cimetidine on the single dose pharmacokinetics of oral clobazam and N-desmethylclobazam.

The effect of cimetidine on the single dose pharmacokinetics of orally administered clobazam and N-desmethylclobazam (NDMC) was studied in volunteers. Cimetidine inhibited the elimination of both clobazam and NDMC and inhibited the rate of formation of NDMC from clobazam. The increase in the AUC for NDMC generated from clobazam was relatively greater than that for clobazam itself. This suggests that NDMC elimination is inhibited to a relatively greater extent than clobazam elimination. The increase in AUC for NDMC generated from clobazam was also relatively greater than that for NDMC administered orally. This would suggest that cimetidine either increases the bioavailability of clobazam or reduces that of NDMC. The increases in the AUC for NDMC and for clobazam in some individuals was of a magnitude which is likely to be clinically significant.

Adult

Diltiazem pharmacokinetics in the rat and relationship between its serum concentration and uterine and cardiovascular effects.

1 The kinetics of diltiazem were investigated in ovariectomized (ovx) non-pregnant and intact late pregnant anaesthetized rats following a bolus i.v. injection (2 mg kg-1) and during a 180 min i.v. infusion (50 micrograms kg-1 min-1 and 100 micrograms kg-1 min-1). Uterine contractions, mean blood pressure and heart rate were measured in the non-pregnant rats. 2 Measurement of serum diltiazem concentrations after bolus i.v. injection in ovx non-pregnant rats showed a biexponential decay with time from which the following parameters were calculated: volume of distribution area (V(area)) - 256 +/- 46 ml; rate constants k12 - 0.46 +/- 0.10 min-1; k21 - 0.09 +/- 0.01 min-1; kel - 0.13 +/- 0.03 min-1; elimination clearance - 3.2 +/- 0.3 ml min-1; distribution t1/2 (t1/2) - 1.4 +/- 0.3 min; elimination t1/2 (t1/2 beta) - 61.2 +/- 13.0 min. In pregnant rats, a biexponential decay was also observed with similar parameters to those in non-pregnant animals except for markedly increased V(area) - 1004 +/- 184 ml; kel - 0.54 +/- 0.16 min-1 and elimination clearance - 14.8 +/- 2.3 ml min-1. 3 Measurement of serum diltiazem concentrations during infusion yielded the following parameters in non-pregnant ovx rats: V(ss)--79 +/- 10 ml; rate constants k12 - 1.02 +/- 0.21 min-1; k21 - 0.03 +/- 0.01 min-1; kel - 0.39 +/- 0.06 min-1; elimination clearance - 7.8 +/- 1.2 ml min-1. In pregnant rats a marked increase was observed in kel - 1.25 +/- 0.38 min-1 and elimination clearance - 36.4 +/- 13.8 ml min-1. 4 An immediate reduction in uterine contractions, mean blood pressure and heart rate was observed after bolus i.v. injection of diltiazem with a return towards control values as serum diltiazem concentrations declined. There were significant correlations between the inhibition of the 3 parameters and the log serum concentrations of diltiazem. Serum concentration-response curves indicated IC50 values of 0.5 microgram ml-1 for inhibition of uterine contractions, 0.7 microgram ml-1 for reduction in blood pressure and 1.2 micrograms ml-1 for reduction in heart rate. There were maintained reductions in the integral of uterine contractions, mean blood pressure and heart rate during infusion. 5 The metabolite desacetyldiltiazem was rarely detected after i.v. bolus injection and was not found in 5/13 rats infused with diltiazem, yet significant inhibition of uterine contractions was observed in all rats. Diltiazem was 3.2 fold more potent than desacetyldiltiazem as an inhibitor of contractions of the rat isolated uterus. 6 These findings indicate that the inhibition of uterine contractions is due to a direct action of diltiazem, and not the metabolite desacetyldiltiazem, and suggest only a slight selectivity for uterine inhibition compared to cardiovascular effects.

Animals