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Biomedical subjects

M Roche

Publications and source records attributed to M Roche.

At least 37 records · Page 2Linked to original sources
PubMed2000

Noninvasive assessment of cerebral oxygenation during acclimation to hypobaric hypoxia.

Factors regulating cerebral tissue PO2 (PtO2) are complex. With the increased use of clinical PtO2 monitors, it has become important to elucidate these mechanisms. The authors are investigating a new methodology (electron paramagnetic resonance oximetry) for use in monitoring cerebral PtO2 in awake animals over time courses of weeks. The authors used this to study cerebral PtO2 in rats during chronic acclimation to hypoxia predicting that such acclimation would cause an increase in PtO2 because of increases that occur in capillary density and oxygen carrying capacity. The average PtO2 between 7 and 21 days was increased by 228% over controls.

Acclimatization↗
PubMed2000

Communicating genetic risk: pros, cons, and counsel.

Shortly before his death in 1995, Kenneth B. Schwartz, a cancer patient at Massachusetts General Hospital (MGH), founded The Kenneth B. Schwartz Center at MGH. The Schwartz Center is a non-profit organization dedicated to supporting and advancing compassionate health care delivery, which provides hope to the patient, support to caregivers, and encourages the healing process. The center sponsors the Schwartz Center Rounds, a monthly multidisciplinary forum where caregivers reflect on important psychosocial issues faced by patients, their families, and their caregivers, and gain insight and support from fellow staff members. This case is of a woman with a personal, and a strong family history of breast cancer, who considered genetic testing for mutations in the BRCA1 and BRCA2 genes. The details of the case have been altered to protect the patient's anonymity. The patient was very anxious and there was disagreement between her healthcare providers about the potential benefits of genetic testing. The discussion of the case focused on several controversial issues, particularly the ownership of genetic information, and who is responsible for disseminating information to the family members at risk. The difficulties in communicating risk, providing emotional support and coping with the continuing uncertainties about screening and intervention are reviewed with an overview of the molecular biology, inheritance, and epidemiology of the BRCA1 and BRCA2 genes.

Adaptation, Psychological↗
PubMed1999

Measurement of arterial, venous, and interstitial pO2 during acute hypoxia in rat brain using a time-resolved luminescence-based oxygen sensor.

This is the first publication using a fiber optic "optode" and a luminescence based pO2 detection method for assessing neural tissue oxygenation. The system was used to simultaneously monitor pO2 in tissue (PtO2) and venous blood (PvO2) during normoxia, hyperoxia and hypoxia. PaO2 was varied by changing inspired oxygen (FiO2) from 0.3 to 0.13. Tissue and arterial pO2 were measured in 5 rats while the simultaneous venous measurements were undertaken in 3 animals. The PtO2 was 29 +/- 10 at an arterial pO2 of 116 +/- 10 (mean +/- SE, n = 5). The PvO2 was consistently higher than PtO2 although PvO2 approached PtO2 as PaO2 declined to 50 mmHg and was lower than tissue pO2 during the complete hypoxic period in one animal. These data indicate that brain venous pO2 is not representative of brain tissue pO2 and support published models predicting that in brain PvO2 is higher than PtO2.

Animals↗
PubMed1996

Hormone replacement therapy in a risk-benefit perspective.

The relative cost-effectiveness of different treatment strategies for hormone replacement therapy (HRT) was assessed within the framework of a computer model. Where data were lacking, it was necessary to make assumptions about the effects of HRT, particularly in relation to combined oestrogen-progestogen therapy and cardiovascular disease; however, sensitivity analyses were performed to assess the impact of changing these assumptions on the cost-effectiveness equation. It appears that net expenditure by the NHS will depend critically on the direct costs of treatment, rather than on any indirect costs incurred or saved as a result of side-effects. In terms of mortality, a reduction in cardiovascular disease risk would have greatest impact and would overshadow any small increase in breast cancer risk which may be associated with long-term use. If the cardioprotective effect of oestrogen is real, our results suggest that long-term prophylactic treatment of hysterectomised women would be relatively cost-effective. Treatment of symptomatic menopausal women for any period of time appears to offer very good value for money. The lack of data relating to combined oestrogen-progestogen therapy and cardioprotection, and the major importance of the latter in the equation of benefits and risks, make it more difficult to draw conclusions about the cost-effectiveness of treating non-hysterectomised asymptomatic women for prophylactic reasons.

Aged↗
PubMed1996

Peripheral neurotensin participates in the modulation of pre- and postprandial intestinal motility in rats.

The present study was undertaken to determine whether neurotensin is involved in the regulation of the intestinal postprandial motor response and, if so, whether the regulatory pathway depends upon peripheral or central neurotensin secretion. Neurotensin, injected by the i.v. route (5 micrograms/kg) during the fasting state, induced firstly an increased irregular spiking activity during 30-40 min. This effect was followed by an increase of frequency of the myoelectrical complexes during 60 min. When injected by the i.c.v. route, neurotensin (0.5 microgram/kg) reinforced the fasting motility pattern of the small intestine after a latency of 70 min. Neurotensin was ineffective on the colon. The neurotensin receptor antagonist SR 48692 (200 micrograms/kg i.v.) reduced the duration of the postprandial motor response of the small intestine and blocked the late postprandial phase on the proximal colon while it suppressed the early postprandial phase on the distal colon. When administered i.c.v. (20 micrograms/kg), SR 48692 had no effect. It is concluded that neurotensin modulates intestinal postprandial motility essentially by a peripheral regulatory pathway. Endogenous neurotensin is involved in the maintenance of the postprandial motility pattern on the small intestine and the proximal colon while it is involved in the initiation of this response on the distal colon. This suggests that endogenous neurotensin acts via both endocrine and nervous mechanisms.

Animals↗
PubMed1995

A microtiter plate assay for measurement of serum alanine aminotransferase in blood donors.

BACKGROUND: Alanine aminotransferase (ALT) testing in blood donors is required in many countries as a surrogate test for viral hepatitis. Current automated ALT assays do not fulfill some operational requirements of blood banks. STUDY DESIGN AND METHODS: The standard ALT measurement method of the International Federation of Clinical Chemistry was adapted to the 96-well microtiter plate to obtain optimal conditions. The method was compared with a reference biochemical method using an analyzer on 251 serum samples. RESULTS: The analytical variability was minimal (2.3% for an ALT level of 59 IU/L and 3.6% for an ALT level of 33 IU/L) after a total analysis time of 8 minutes and a time of 7 minutes before the first reading. With these measures, a linear standard curve was obtained in the range of 10 to 130 IU per L.A computerized validation procedure allowed rejection of samples with high ALT levels. Comparison with the analyzer gave a correlation coefficient, r = 0.935. The method proved to be efficient and time-saving in routine use over an 8-month period. CONCLUSION: The microtiter plate ALT assay is helpful in allowing the simultaneous distribution of ALT and immunoenzymatic assays. It provides accurate results and a minimal risk of false-negative results.

Alanine Transaminase↗
PubMed1995

Age and experimental obstructive emphysema. A morphometrical study on the rat.

Age, as a risk factor in the development of experimental obstructive emphysema, is proposed as the hypothesis of this study. Ninety-two Wistar rats were organized into two age groups: adult (16 weeks) and middle-aged (56 weeks). Each age group was subdivided into three groups: a control group, consisting of unmanipulated animals; a "cannula" group consisting of animals into whose trachea a cannula was implanted; and a "valve" group, consisting of animals into whose trachea a valve had been implanted. The survival was one month. A histomorphometric study was performed on the lungs and the results were compared statistically. Throughout the experiment the amount of food consumed by each animal and the variations in weight were monitored. After sacrifice, the lungs were processed for light microscopy. Thirteen histomorphometric variables were quantified and subsequently systematized into three groups: those which quantified the size of the distal airspace ("area of the alveolar section", "alveolar chord" and "mean linear intercept"): those which quantified the tissue ("wall thickness", "tissue density", "internal perimeter of each alveolar section", "internal alveolar perimeter per field" and "alveolar section/section perimeter"); and those which quantified the elastic fibre ("elastic fibre area", "elastic fibre perimeter", "elastic fibre area/elastic fibre perimeter", "elastic fibre density" and "elastic fibre density per tissue density"). The results were compared statistically and the sensitivity, specificity and misclassification indices were calculated, as well as the attributable and relative risk. From the results, it was observed that, in general, the animals of the valve and cannula groups in both age groups displayed a decrease in food intake and a body weight loss. The middle-aged animals were the only group which displayed significant differences in all the morphometric variables except wall thickness, when the cannula and valve groups were compared with the control group. In both the cannula and valve groups, the values of the variables which quantified the distal airspace increased, while the values of the variables which quantified the lung tissue and the elastic fibre decreased. In the manipulated middle-aged group, the attributable risk of developing emphysema was 56.66% and the relative risk 5.55; in the group of manipulated adult animals, the attributable risk was 23.55% and the relative risk 1.66. The results of this study lead us to propose that the middle-aged rats with experimental airflow obstruction displayed a greater risk of developing emphysema than the adult rats which were subjected to the same procedure.

Aging↗
PubMed1994

Hypothyroidism increases TRH and TRH precursor levels in rat anterior pituitary.

Thyroliberin (TRH) has been reported to be synthesized in anterior pituitary. Modulations of anterior pituitary concentrations of TRH and its precursor (proTRH) were investigated in rats rendered hypothyroid for 21 and 48 days. In hypothyroid rats, as expected, plasma TSH levels were increased and plasma free T4 concentrations were reduced, whereas anterior pituitary concentrations of TRH were markedly increased (mean +/- SEM fmol/mg protein, 106.9 +/- 21.1 at 21 days and 181.8 +/- 59.0 at 48 days vs 42.2 +/- 13.4 in controls). Significant increases of proTRH concentrations were found in hypothyroid rats (mean +/- SEM fmol/mg protein, 266.5 +/- 16.7 at 21 days and 320.4 +/- 51.1 at 48 days vs 214.1 +/- 18.3 in controls). Daily administration of L-T4 for the last week of PTU treatment (days 41 to 48) reversed hypothyroidism by lowering plasma TSH levels and by increasing plasma free T4 concentrations. Concomitantly, T4 administration significantly decreased anterior pituitary TRH contents (114.4 +/- 35.9) as well as proTRH contents (250.4 +/- 11.7). The fact that hypothyroidism regulates anterior pituitary TRH and proTRH contents strengthens the view that TRH might play a role in local regulatory mechanisms within the anterior pituitary on the thyrotropic function.

Animals↗
PubMed1994

Effect of the slow-release formulation of somatuline (BIM 23014) on estrogen-induced hyperprolactinemia and lactotroph hyperplasia in the female rat.

Somatuline, in common with other SRIH analogues, exerts antiproliferative and antisecretory activities on various tumors. Our purpose was to test the effectiveness of a slow-release formulation of somatuline on lactotroph hyperplasia and PRL hypersecretion induced by estrogens (17 beta E2) in rats. Female rats were primed with 17 beta E2 for 6 weeks before receiving somatuline (2 mg/kg) intramuscular injections every 10 days for one month. The mean anterior pituitary weight was 11.22 +/- 0.32 mg (mean +/- SEM) in non-estrogenized rats, 29.62 +/- 1.63 mg in 17 beta E2-primed rats and 23.58 +/- 1.26 mg in 17 beta E2-primed somatuline-treated rats. Mean plasma PRL level was 5.63 +/- 0.97 ng/ml, 182.37 +/- 27.55 ng/ml and 113.89 +/- 15.07 ng/ml in the same groups respectively. Thus, the 17 beta E2-induced pituitary enlargement and hyperprolactinemia were 20% and 38% lower respectively when animals were treated with somatuline during the last month of estrogenization. The 17 beta E2-induced increase in PRL cell density was also reduced by somatuline treatment. We conclude that the slow-release formulation of somatuline impedes 17 beta E2-induced hyperprolactinemia and pituitary enlargement concomittantly, at least in part by acting on lactotroph proliferation.

Animals↗
PubMed1994

A possible interaction between serotonin and cholecystokinin-8 in the ileo-colonic motor responses to feeding in rats.

The effects of cholecystokinin (CCK)-A, CCK-B, and 5-hydroxytryptamine-2 (5-HT2) receptor antagonists on the postprandial myoelectric activity of the ileum and the proximal and distal colon in rats were studied. After L364,718, a CCK-A receptor antagonist, or ritanserin, 5-HT2 receptor antagonist, the duration of the ileal postprandial motor pattern was reduced by 60%. In contrast, L365,260, a CCK-B receptor antagonist, had no effect. In the distal colon, the postprandial response was inhibited by CCK-A, CCK-B, and 5-HT2 receptor antagonists, whereas they were inactive in the proximal colon. CCK-8 administered at the end of the meal suppressed the inhibitory effect of ritanserin on the ileum and the distal colon. These results suggest that, in rats, CCK-8 is involved in the control of the ileal motor response to feeding through CCK-A receptors and in that of the distal colon through both CCK-A and CCK-B receptors. Serotonin seems to play a role in CCK-8 control through 5-HT2 receptors.

Animals↗
PubMed1993

Measuring the impact of menopausal symptoms on quality of life.

OBJECTIVE: To examine the impact of menopausal symptoms on the overall quality of life of women. DESIGN: Data collection with a questionnaire administered by an interviewer, incorporating two different quality of life measurement techniques (time trade off and rating scale). SETTING: Specialist menopause clinic and two general practices in Oxford. SUBJECTS: 63 women aged 45-60 years recruited opportunistically during a clinic or appointment with a general practitioner; no exclusion criteria. RESULTS: Subjects gave very low quality of life ratings for health states with menopausal symptoms. The time trade off method of measuring preferences for these health states (on a scale from 0 to 1, where preference for full health is given as 1) yielded utility values of 0.64 for severe menopausal symptoms and 0.85 for mild symptoms. The rating scale measurement technique yielded even lower values: utilities of 0.30 and 0.65 were obtained for severe and mild symptoms respectively. Kappa scores indicated that the two methods produced results that were poorly related but not contradictory. Comparison of quality of life ratings before and after treatment with hormone replacement therapy showed significant improvements: with the rating scale measurement technique mean increases in utility values after the relief of severe and mild menopausal symptoms were 0.56 and 0.18 respectively. CONCLUSIONS: Quality of life may be severely compromised in women with menopausal symptoms, and perceived improvements in quality of life in users of hormone replacement therapy seem to be substantial. This emphasises the need to include quality of life measurements when assessing outcomes of hormone replacement therapy. Several limitations may exist with widely applied measurement techniques, calling for the development of appropriate and well validated instruments for measuring quality of life associated with reduced health states.

Data Collection↗
PubMed1993

Action of enkephalinase (EC 3.4.24.11) inhibition on the pre- and post-prandial electromyographic patterns of colon in rats.

Endogenous opioids are an important regulatory factor for the digestive tract and specially for its motility pattern. Enkephalin degradation includes an enkephalinase (EC 3.4.24. 11) and the effects on the colic electromyographic profile of its inhibition by acetorphan has been investigated in the unrestrained rat. Electromyogram consisted of Long Spike Bursts (LSB). In fasted state, they propagated indifferently in both aboral or oral directions from any point of the colon. Feeding privileges LSB which start near the cecal junction and propagated aborally to the distal colon. The acetorphan treatment (A) increases the percentage of LSB propagating aborally on the entire colon in fasted state and (B) reinforces the increased percentage of LSB which propagated down on the entire colon induced by feeding. All the actions of acetorphan on colic motility pattern disappear after inhibition of opioid receptors by naloxone. That may account for involvement of enkephalins in acetorphan properties on the pattern of the colic electrical activity.

Animals↗
PubMed1993

Effect of some gastrointestinal hormones on motor and electrical activity of the digestive tract in the conscious cat.

Three peptides structurally related to gastrin and known to be full agonists of antral motility in the conscious cat, pentagastrin (PG), cholecystokinin (CCK) and synthetic octapeptide of cholecystokinin (OP-CCK), were compared in relation to antral and duodenal electrical activity. They induced the same antral effect in eliciting an increase in the basal electrical rhythm (BER) and a short-lasting decrease in the frequency of the bursts of spikes. The electrical changes were correlated with lumen pressure changes measured in parallel, consisting of a decrease in the frequency of high-amplitude peaks and an increase in low-amplitude peaks. The additive effect of PG and CCK shows that the peptides are full agonists for antral electrical activity, as they are for antral motility and acid secretion. In contrast to the antrum, the three peptides increased the frequency of the duodenal spike bursts, CCK and OP-CCK decreased the BER frequency, while PG increased BER slightly. The increase in antral and duodenal BER obtained after a beef-liver meal, which produced a large endogenous gastrin release, suggests a major role for gastrin in antral motility induced by feeding, at least in the cat.

Animals↗
PubMed1993

An economic appraisal of alternative pre-natal screening programmes for Down's syndrome.

The objective of this study was to evaluate economically a screening programme within the Oxford Regional Health Authority for Down's syndrome, based on maternal serum alpha fetoprotein, unconjugated oestriol and human chorionic gonadotrophin as well as maternal age (the triple test) against maternal age alone. The design of the study involved cost-effectiveness analysis of the triple test relative to the maternal age screening programme, and the main outcome measure was the cost per Down's birth avoided. It was found that the triple test is more cost-effective over a wide range of assumptions concerning detection rates and procedure costs. Indirect costs are important in considering the cost-effectiveness of the screening programmes. The most efficient detection rate is around 58 per cent for which the cost per Down's birth avoided is approximately 29,600 pounds if only direct costs are evaluated, 20,100 pounds if all NHS costs are considered and -49,800 pounds if all resource consequences are analysed. It may be concluded that screening for Down's syndrome using the triple test is cost-effective over a wide range of assumptions concerning detection rate and procedure costs. If all resource costs are considered, the programme is highly cost-effective in comparison with other health care interventions.

Abortion, Therapeutic↗
PubMed1993

[Implication of melatonin in the control of the interdigestive ileocecal-colic electromyographic profile in rats].

In the interdigestive period, intestinal motility displays myoelectrical complexes occurring cyclically at a constant rhythm. Since it is established that the pineal gland plays an important role in the control of circadian rhythms via its melatonin secretion, we decided to study the effects of pinealectomy and melatonin on the organization of the ileo-ceco-colic electromyogram of the rat. Pinealectomy resulted in the disappearance of ileal myoelectrical complexes and, concurrently, an excitomotor effect on the cecocolic tract. In pinealectomized rats a single intravenous injection of melatonin during lighting period induced an immediate recovery of the ileal myoelectrical complexes and a progressive return to the control electromyographic pattern of the ceco-colic tract. The melatonin action was definitive.

Animals↗