Search PubMed⌕ Search

Biomedical subjects

M J Turner

Publications and source records attributed to M J Turner.

At least 55 records · Page 3Linked to original sources
PubMed1999

Emergency obstetric hysterectomy - an increasing incidence.

Ten women underwent obstetric hysterectomy at St George's Hospital, London between 1992 and 1998, with an apparent seven-fold increase in incidence in recent years. All hysterectomies were performed as emergency procedures, with massive postpartum haemorrhage being the major indication for operation in nine cases. Abnormal placentation was the single commonest cause, seven cases being associated with previous caesarean section. There were no maternal or fetal mortalities, but major surgical complications, including urinary tract and vascular injury occurred in one case. In view of the increasing risk of obstetric hysterectomy following previous caesarean section, high risk cases associated with abnormal placentation may be identified using ultrasound, allowing appropriate pre-operative counselling regarding the risk of peripartum hysterectomy.

Journal Article↗
PubMed1999

Effects of age and gender on cardiovascular responses to phenylephrine.

BACKGROUND: The age-associated impairment in left ventricular (LV) systolic function appears to be mostly detectable during exercise or sympathetic stimulation. We hypothesized that the decline in cardiac function could be unmasked by an acute increase in afterload induced by phenylephrine. We further sought to examine whether the deterioration in cardiac function is influenced by gender. METHODS: We studied 17 young (20-31 years old) and 21 older healthy subjects (60-75 years old) who were given infusions of incremental doses of phenylephrine following cardiac muscarinic receptor blockade with atropine. Left ventricular systolic function was assessed with 2-D echocardiography. RESULTS: The young subjects exhibited a paradoxical increase in heart rate in response to alpha-adrenergic stimulation, but the older subjects did not (p < .01). The increase in systolic blood pressure in response to phenylephrine was influenced by age and gender (i.e., greater in the younger men and older women), whereas the increase in diastolic blood pressure was greater in the younger than the older subjects of both sexes. The changes in LV end-diastolic diameter with phenylephrine were unaffected by age or gender. The slope of the systolic shortening-end systolic wall stress relationship was significantly steeper in the older subjects, suggesting a decline in the contractile response to an acute increase in afterload with aging. CONCLUSIONS: This study's findings suggest that age can significantly influence the cardiovascular responses to alpha-adrenergic stimulation and that phenylephrine, by acutely increasing afterload, is effective in unmasking the age-associated deterioration in left ventricular systolic function. Further, it appears that the increase in systolic blood pressure in response to an alpha-adrenergic challenge is significantly influenced not only by age but also by gender.

Adrenergic alpha-Agonists↗
PubMed1999

Effects of age and gender on the cardiovascular responses to isoproterenol.

We studied the effects of age and gender on cardiovascular responses to beta-adrenergic stimulation with the use of two-dimensional echocardiography in 16 young (aged 20-31) and 20 older (aged 60-75) healthy individuals. Following administration of atropine, each subject was given an infusion of isoproterenol at incremental doses from 0.010 to 0.030 microgram kg-1 min-1. The slopes of the fractional shortening-end-systolic wall stress (FS-sigma es) relationships were steeper in the young men (-0.87 +/- 0.28, n = 8) compared to the older men (-0.41 +/- 0.13, n = 10), and in the young women (-0.55 +/- 0.14, n = 8) compared to the older women (-0.38 +/- 0.13, n = 10). Furthermore, the magnitude of the age-associated differences in these slopes was larger in the men (old vs young) than in the women (old vs young) which, in the absence of changes in preload, suggests a greater decline in the contractile response to isoproterenol with advancing age in men compared to women. Furthermore, the men exhibited a greater attenuation of chronotropic response to isoproterenol than did the women. These observations suggest that gender plays a significant role in the age-associated decline in inotropic and chronotropic responses to beta-adrenergic stimulation, with men exhibiting a greater decline with aging than women.

Adrenergic beta-Agonists↗
PubMed1999

Induction of labour after 1 previous Caesarean section.

The aim of this study was, after induction of labour in women with a previous Caesarean section, to compare the outcome in women with a history of a previous vaginal delivery with women who had never delivered vaginally. A retrospective analysis was performed over a 2-year period, in a Dublin teaching hospital. One hundred and three women who had had 1 previous lower segment Caesarean section had labour induced. Particular attention was given to delivery outcome, history of a vaginal delivery, cervical effacement at induction, influence of epidural analgesia, indication for induction and incidence of uterine rupture. The repeat Caesarean section rate after induction was 20.4%. Of the 51 women who had never previously delivered vaginally, the repeat section rate was 37.3% compared with only 3.9% of the 52 women who had previously delivered vaginally (p < 0.01). Fourteen women who had never delivered vaginally had an uneffaced cervix at induction and the repeat Caesarean section rate in this group was 64.3%. The commonest indication for induction was a postdates pregnancy. The use of epidural analgesia was greater in women who had never delivered vaginally. There were 2 cases of uterine scar rupture. Induction of labour following Caesarean section is associated with a significantly higher incidence of repeat Caesarean section in women who have not had a previous vaginal delivery. If the cervix is not effaced at induction, the repeat Caesarean section rate is higher than if the cervix has started to efface.

Adult↗
PubMed1999

Evaluation of modified BACTEC 12B radiometric medium and solid media for culture of Mycobacterium avium subsp. paratuberculosis from sheep.

Definitive diagnosis of Johne's disease in ruminants depends on confirming the presence of the causative bacterium, Mycobacterium avium subsp. paratuberculosis, in tissues of the host. This is readily achieved in most ruminant species by culture. However, culture of clinical specimens from sheep in many countries has been unrewarding. Such a culture from sheep was achieved recently in Australia by using a radiometric culture medium. The aims of the present study were to evaluate the culture of M. avium subsp. paratuberculosis from sheep by using modified BACTEC 12B radiometric medium, to determine the sensitivity of culture in relation to histopathology, and to evaluate a range of solid media. Culture of M. avium subsp. paratuberculosis from sheep with Johne's disease is a sensitive method of diagnosis: intestinal tissues from all 43 animals with multibacillary disease and all 22 animals with paucibacillary disease were culture positive, while 98% of feces from 53 animals with multibacillary disease and 48% of feces from 31 animals with paucibacillary disease were culture positive. Of sheep without histological evidence of Johne's disease from infected flocks, intestinal tissue from 32% of 41 were culture positive, while feces from 17% of 41 were culture positive. Consequently, culture is recommended as the "gold standard" test for detection of ovine Johne's disease. Of the wide range of solid media that were evaluated, only modified Middlebrook 7H10 and 7H11 agars, which were very similar in composition to modified BACTEC 12B medium, yielded growth of ovine strains of M. avium subsp. paratuberculosis. The sensitivity of detection of M. avium subsp. paratuberculosis on solid media was slightly lower than that in modified BACTEC 12B radiometric medium. Both egg yolk and mycobactin J were essential additives for growth of ovine strains of M. avium subsp. paratuberculosis in both liquid and solid media.

Animals↗
PubMed1998

Ethylene oxide dosimetry in the mouse.

Ethylene oxide (EO) is a direct-acting mutagen and animal carcinogen used as an industrial intermediate and sterilant with a high potential for human exposure. Understanding the exposure-dose relationship for EO in rodents is critical for developing human EO exposure-dose models. The study reported here examined the dosimetry of EO in male B6C3F1 mice by direct determination of blood EO concentrations. Steady-state blood EO concentrations were measured during a single 4-h nose-only inhalation exposure (0, 50, 100, 200, 300, or 400 ppm EO). In addition, glutathione (GSH) concentrations were measured in liver, lung, kidney, and testis to assess the role of the GSH depletion in the saturable metabolism previously observed in mice (Brown et al., Toxicol. Appl. Pharmacol. 136, 8-19, 1996). Blood EO concentrations were found to increase linearly with exposure concentration up to 200 ppm. Markedly sublinear blood dosimetry was observed at exposure concentrations exceeding 200 ppm. An EO exposure concentration-dependent reduction in tissue GSH levels was observed, with both liver and lung GSH levels significantly depressed at EO exposure concentrations of 100 ppm or greater. Our results also indicate that depletion of GSH is likely responsible for nonlinear dosimetry of EO in mice and that GSH depletion corresponds with reports of dose-rate effects in mice exposed to EO.

Administration, Inhalation↗
PubMed1998

Does increased resistance on umbilical artery Doppler preclude a trial of labour?

OBJECTIVE: To determine whether patients with increased resistance on umbilical artery Doppler velocimetry could be safely allowed a trial of labour. DESIGN: The Coombe Womens' Hospital is a university teaching hospital which takes tertiary referrals. All singleton pregnancies found to have increased resistance (>2 SD above the mean for gestational age) on umbilical artery Doppler ultrasound between 1993 and 1995 inclusively were identified from the ultrasound database and reviewed, retrospectively. Cases where the umbilical artery waveform reverted to normal or deteriorated to absent end diastolic flow on a subsequent scan were excluded. The 118 cases identified were divided into two groups, those that were delivered by elective caesarean section and those that laboured. RESULTS: Forty-five patients were delivered by elective caesarean section and 73 were allowed to labour. In the group that laboured over 90% delivered vaginally and 9.8% were delivered by emergency caesarean section. Three babies had a cord pH less than 7.20 in the group that laboured. Two babies had an Apgar score of less than 7 at 5 min in the group that were delivered electively. There were no neonatal seizures or perinatal deaths in either of the two groups. CONCLUSIONS: This study shows that patients with increased resistance on umbilical artery Doppler can be allowed a trial of labour without compromising the fetal outcome. We would suggest that consideration be given to induction of labour in selected patients as an alternative to elective section.

Adult↗
PubMed1998

What are the maternal implications of a classical caesarean section?

Sixty-two caesarean sections involving a vertical upper uterine segment incision were performed at the Coombe Women's Hospital between January 1983 and December 1995. A detailed chart review was performed. There were no maternal deaths. The maternal outcome was complicated by infection in 49% of cases, and haemorrhage in 19% requiring hysterectomy in two cases. In 15 subsequent pregnancies scar rupture occurred in one case and scar separation in two cases. The perinatal mortality was 200/ 1000; no perinatal death was directly related to the surgery. The operation is associated with a high incidence of maternal morbidity. It also has implications for subsequent deliveries. We recommend that every effort should be made to evaluate critically the need for a caesarean section in the first place and where possible to use a lower uterine segment transverse incision. The patient should be informed of the additional morbidity and long-term risks associated with a vertical incision.

Journal Article↗
PubMed1998

Rapid detection of Mycobacterium paratuberculosis in clinical samples from ruminants and in spiked environmental samples by modified BACTEC 12B radiometric culture and direct confirmation by IS900 PCR.

The suitability of a radiometric culture medium consisting of BACTEC 12B with PANTA PLUS, mycobactin J, and egg yolk was evaluated for detection of Mycobacterium paratuberculosis in feces, mesenteric lymph nodes, and intestinal walls from cattle, sheep, and goats. In addition, a simple method that would enable the rapid identification of Mycobacterium paratuberculosis by IS900 PCR in the primary cultures was sought so that subculture to secondary egg-free radiometric medium could be avoided. An ethanol extraction followed by differential centrifugation was used to separate M. paratuberculosis from PCR inhibitors in the primary culture. PCR was then undertaken with the pellet, after boiling to lyse the mycobacteria; if this test was negative, the DNA in the lysate was purified with guanidine thiocyanate and silica. Cultures of feces, ilea, and mesenteric lymph nodes from cattle, sheep, and goats known to have or suspected of having Johne's disease yielded positive PCR results 1 to 7 weeks after inoculation. Similar results were obtained with soil and pasture samples that had been spiked with M. paratuberculosis. The results suggested that radiometric culture was more sensitive than histopathology in detecting M. paratuberculosis infection in sheep and goats and more sensitive than culture on Herrold's egg yolk medium for the detection of the infection in cattle. Of 259 individual PCR tests with samples from cultures with growth indices of > or = 10,237 (91.5%) were positive, with only 28 (11.8%) requiring both ethanol and silica preparation to yield a positive result. Of the 22 negative PCR results for samples from cultures with growth indices of > or = 10, 18 were for samples from cultures that had only just developed evidence of growth. PCR-positive cultures tended to remain PCR positive over successive weeks. Flexibility in the timing of the sampling for PCR is thus possible, facilitating batch processing of samples in large-scale disease control programs for ruminants.

Animals↗
PubMed1998

Beta-adrenergic-mediated improvement in left ventricular function by exercise training in older men.

To test the hypothesis that the training-induced improvement in the age-related decline in left ventricular (LV) function is mediated by enhanced inotropic responses to beta-adrenergic stimulation, 10 sedentary healthy men, 65 +/- 1 yr (mean +/- SE) of age, exercised for 9 mo, which resulted in a 28% increase in aerobic exercise capacity. Training induced a greater increase in LV systolic shortening, assessed with two-dimensional echocardiography, in response to isoproterenol with a steeper slope of the fractional shortening-end-systolic wall stress (sigma es) relationship and an upward shift of the sigma es-systolic diameter relationship without an acute increase in heart rate or preload. The increase in the early-to-late diastolic flow velocity ratio, normalized for heart rate and preload, in response to isoproterenol was larger after training. LV systolic reserve and cardiac output during peak exercise were higher after training. beta-Adrenergic blockade with esmolol HCl abolished the adaptive increases in LV systolic reserve capacity and cardiac output during peak exercise in the trained state. The results suggest that one of the underlying mechanisms responsible for the adaptive increase in LV systolic function in response to exercise training is an enhanced inotropic sensitivity to catecholamines. Furthermore, the enhanced inotropic responses are associated with increased diastolic filling.

Adaptation, Physiological↗
PubMed1998

A transgenic strategy for analyzing the regulatory regions of the human prostate-specific antigen gene: potential applications for the treatment of prostate cancer (Review).

Prostate-specific antigen (PSA) has been used clinically as a marker for the diagnosis and staging of prostate cancer due to its specific expression in prostate epithelial cells. In addition to its medical importance, its complex hormonal and tissue-specific regulation makes it an attractive model to study gene regulation. Two approaches have been applied to the identification of regulatory regions which confer this specific expression pattern. In vitro analysis of the regulatory regions of the human PSA gene using promoter reporter constructs and tumor cell lines has revealed a number of the DNA sequences involved in the hormone-dependent expression of PSA. We have pursued an alternative in vivo approach using transgenic animal technology, which is the focus of this review. Using this second approach, a transgenic mouse was generated using a 14 kilobase (kb) region of the human PSA gene encompassing the coding region and intervening sequences as well as 6 kb of upstream sequence and 2 kb of downstream sequence. This genomic DNA clone confers a PSA expression pattern in mice which appears to be very similar if not identical to that of humans, allowing us to investigate tissue-specificity and developmental regulation of PSA expression. In addition, these mice, for which PSA is a self-antigen, provide a model to test the feasibility and efficacy of PSA-directed immunotherapy for prostate cancer. The further identification of the PSA regulatory regions important for tissue-specificity may ultimately allow the design of new therapeutics for the treatment of prostate cancer.

Animals↗
PubMed1998

Regulation of human prostate-specific antigen gene expression in transgenic mice: evidence for an enhancer between the PSA and human glandular kallikrein-1 genes.

The human prostate-specific antigen (PSA) and glandular kallikrein-1 (hGK-1, also known as hK2) genes are tandemly located on chromosome 19, separated by a 12-kb intergenic region. The coordinate regulation of these two genes suggests the presence of common regulatory elements responsible for tissue specificity and/or levels of expression within this region. To identify such regulatory elements, we generated two sets of transgenic mice, which had incorporated either the PSA gene alone or together with the intergenic region. Both sets of transgenics exhibit remarkably prostate-specific expression of the transgene. However, the presence of the intergenic region abrogates the dependence on high PSA gene copy-number for high levels of PSA expression. This suggests the existence of a positive regulatory element in the intergenic region. By using a previously identified distal enhancer element of PSA (termed DEE 1) as a probe, we identified a cross-hybridizing fragment, which we termed DEE 2, in the intergenic region. Sequence analysis shows that DEE 2 is 76% identical to DEE 1, and it includes a putative androgen-responsive element. Here, we propose a model to illustrate how the two enhancers may work to regulate the transcription of PSA and hK2.

Animals↗
PubMed1997

Disposition of butadiene epoxides in Sprague-Dawley rats.

1,2-Epoxybutene (BMO) and diepoxybutane (BDE) are metabolic products of 1,3-butadiene in rodents. Both BMO and BDE are suspect in the development of tumors in rats and mice. To understand the distribution and elimination of these compounds in the absence of the rate-limiting production from butadiene, the pharmacokinetics of BMO and BDE in blood were determined in adult male Sprague-Dawley rats following intravenous administration. All animals were dually cannulated in these studies. For the BMO studies, rats were dosed with 71, 143, or 286 mumol/kg BMO (n = 3 for each dose group). For the BDE studies, rats were dosed with 523 mumol/kg BDE (n = 3). All animals tolerated the BMO and BDE doses without grossly observable adverse effects. Blood was drawn at predetermined time points and extracted in methylene chloride. BDE and BMO concentrations were quantitated by gas chromatography or gas chromatography/mass spectrometry. The BMO distribution half-lives were short and ranged from 1.4 min at the lowest dose to 1.8 min at the highest dose. Volume of distribution at steady state ranged from 0.53 +/- 0.17 to 0.59 +/- 0.31 l/kg. Systemic clearances ranged from 67 +/- 17 to 114 +/- 20 ml/min per kg. The terminal elimination half-lives were also short and ranged from 5.7 to 8.5 min among the doses. The pharmacokinetic parameters after an i.v. dose of 523 mumol/kg BDE were a distribution half-life of 2.7 min, terminal elimination T1/2 of 14 min, volume of distribution at steady state of 0.73 +/- 0.06 l/kg, and systemic clearance of 76 +/- 8 ml/min per kg. These pharmacokinetic parameters demonstrate the similarity between disposition of the two epoxides in rats, that include a rapid distribution after i.v. administration into a small extravascular body compartment as well as a rapid elimination from blood. These pharmacokinetic data provide useful blood clearance information for assessing the critical physiological and biochemical determinants underlying the disposition of butadiene epoxides.

Animals↗
PubMed1997

Correctly selecting a liquid-filled nasogastric infant feeding catheter to measure intraesophageal pressure.

Polyvinyl chloride (PVC) nasogastric feeding catheters are used clinically to measure intraesophageal pressure as an estimate of pleural pressure for calculating lung compliance in infants. The accuracy of pressure measurement of 4 French gauge (FG) catheter sizes and three brands of liquid-filled catheter manometer systems (CMS) was evaluated by determining their resonance-frequency amplitude and phase properties. All CMS were underdamped and resonated. No CMS exhibited a uniform mean frequency response above 11 Hz. The maximum respiratory rate (Frr) within which CMS could potentially measure dynamic intraesophageal pressure within a 5% error limit was determined (Frr): the highest mean Frr recorded reliably in large-diameter catheters was 82 breaths/min. Significant CMS differences in accuracy existed between catheter FG sizes and between catheters of similar diameters but differing brands. Correlation (r2) between catheter inner diameter and CMS Frr was 0.66 across brands. In conclusion, intraesophageal PVC liquid-filled feeding catheters are suitable for estimating pleural pressures in subjects mechanically ventilated without sharp inspiratory waveforms or high respiratory rates. Quantitative frequency response characterization of different nasogastric catheter brands and different diameters is mandatory prior to their utilization.

Age Factors↗