Biomedical subjects
M Morgan
Publications and source records attributed to M Morgan.
Hydrogen peroxide enhances signal-responsive arachidonic acid release from neurons: role of mitogen-activated protein kinase.
Hydrogen peroxide (H2O2) is a potent stimulator of signal-responsive phospholipase A2 (PLA2) in vascular smooth muscle and cultured endothelial cells. We investigated whether H2O2 plays a similar regulatory role in neurons. H2O2 did not stimulate a release of arachidonic acid from cultured neurons when applied alone but strongly enhanced the liberation of arachidonic acid evoked by maximally effective concentrations of either glutamate, the glutamate receptor agonist N-methyl-D-aspartate (NMDA), the muscarinic receptor agonist carbachol, the Na+-channel opener veratridine, or the Ca2+-ionophore ionomycin. The potentiating effects of H2O2 were strongly inhibited in the presence of the PLA2 inhibitor mepacrine, suggesting that the site of action was within the signal responsive arachidonic acid cascade. The enhancing effect of H2O2 was not reversed by protein kinase C inhibitors (chelerythrine chloride or GF 109203X) nor was it mimicked by phorbol ester treatment. H2O2 alone strongly enhanced the levels of immunodetectable activated mitogen-activated protein kinase (activated MAP kinases ERK1 and ERK2) in a Ca2+-dependent manner and this effect was additive with increases in the levels of activated MAP kinase evoked by glutamate. The enhanced release of arachidonic acid, however, was not clearly reversed by the MAP kinase kinase (MEK) inhibitor PD 98059, although this treatment effectively abolished H2O2 activation of MAP kinase. Thus, MAP kinase activation and Ca2+-dependent arachidonic acid release are regulated by oxidative stress in cultured striatal neurons.
Intravenous anaesthesia: a step forward.
Explore the source record for details and available documents.
The changing role of dental auxiliaries: a literature review.
A review of the literature on dental auxiliaries and their utilization in the dental workforce is presented, and their future role is examined in the light of broader issues relating to changing disease patterns and service delivery. Legislative factors, productivity, quality assurance and the potential scope for dental auxiliaries in both the public sector and private practice setting are discussed. A strategy for adopting a team approach in the delivery of dental services is suggested, which would necessitate the dentist taking on the role of team leader and maintaining responsibility for overall treatment planning and quality assurance. Dental auxiliaries could provide basic preventive and restorative dental services, allowing dentists to concentrate on providing more complex high-technology treatment. Implications for the future training of dental auxiliaries are presented.
Quality of midwifery led care: assessing the effects of different models of continuity for women's satisfaction.
BACKGROUND: Changing Childbirth (1993), a report on the future of maternity services in the United Kingdom, endorsed the development of a primarily community based midwifery led service for normal pregnancy, with priority given to the provision of "woman centred care". This has led to the development of local schemes emphasising continuity of midwifery care and increased choice and control for women. AIMS: To compare two models of midwifery group practices (shared caseload and personal caseload) in terms of: (a) the extent to which women see the same midwife antenatally and know the delivery midwife, and (b) women's preference for continuity and satisfaction with their care. METHODS: A review of maternity case notes and survey of a cohort of women at 36 weeks of gestation and 2 weeks postpartum who attended the two midwifery group practices. Questionnaires were completed by 247 women antenatally (72% response) and 222 (68%) postnatally. Outcome measures were the level of continuity experienced during antenatal, intrapartum, and postnatal care, women's preferences for continuity of carer, and ratings of satisfaction with care. RESULTS: The higher level of antenatal continuity of carer with personal caseload midwifery was associated with a lower percentage having previously met their main delivery midwife (60% v 74%). Women's preferences for antenatal continuity were significantly associated with their experiences. Postnatal rating of knowing the delivery midwife as "very important indeed" was associated with both previous antenatal ratings of its importance, and women's actual experiences. Personal continuity of carer was not a clear predictor of women's satisfaction with care. Of greater importance were women's expectations, their relations with midwives, communication, and involvement in decision making. CONCLUSIONS: Midwifery led schemes based on both shared and personal caseloads are acceptable to women. More important determinants of quality and women's satisfaction are the ethos of care consistency of care, good communication, and participation in decisions.
Morbidity of intracranial hemorrhage in patients with cerebral arteriovenous malformation.
Explore the source record for details and available documents.
Developmental stages and spiritual coping responses among economically impoverished women living with HIV disease.
Identifies environmental markers, situational appraisals, perceived ability to mediate situations and outcomes, primary coping strategies, and purposes served by religion and spirituality in 10 HIV-positive women recruited from a regional health care clinic. Findings indicated that the women experienced a disintegration of family during their early developmental years, yielding feelings of hopelessness and isolation; that their sexual development was marked by rape and incest, and their early adulthood was characterized by failed relationships, pregnancies, drugs, and alcohol. Reports that the women's religious influences were predominantly maternal and provided a model for intercessory prayer. Notes that prior to their diagnosis of HIV, participants described their coping as escapist, while after diagnosis they believed there was a divine intercession renewing their spiritual growth and connectedness with others. Reports that the women's personal spirituality was greatly influenced by prayer, television ministries, and reading the Bible. Suggests the interventions that actively recruit women into social support services, health care systems, and faith congregations are needed and that television ministries may serve as access points for connecting women with necessary services.
Letrozole, a new oral aromatase inhibitor for advanced breast cancer: double-blind randomized trial showing a dose effect and improved efficacy and tolerability compared with megestrol acetate.
PURPOSE: To compare two doses of letrozole and megestrol acetate (MA) as second-line therapy in postmenopausal women with advanced breast cancer previously treated with antiestrogens. PATIENTS AND METHODS: Five hundred fifty-one patients with locally advanced, locoregionally recurrent or metastatic breast cancer were randomly assigned to receive letrozole 2.5 mg (n = 174), letrozole 0.5 mg (n = 188), or MA 160 mg (n = 189) once daily in a double-blind, multicenter trial. Data were analyzed for tumor response and safety variables up to 33 months of follow-up evaluation and for survival up to 45 months. RESULTS: Letrozole 2.5 mg produced a significantly higher overall objective response rate (24%) compared with MA (16%; logistic regression, P = .04) or letrozole 0.5 mg (13%; P = .004). Duration of objective response was significantly longer for letrozole 2.5 mg compared with MA (Cox regression, P = .02). Letrozole 2.5 mg was significantly superior to MA and letrozole 0.5 mg in time to treatment failure (P = .04 and P = .002, respectively). For time to progression, letrozole 2.5 mg was superior to letrozole 0.5 mg (P = .02), but not to MA (P = .07). There was a significant dose effect in overall survival in favor of letrozole 2.5 mg (P = .03) compared with letrozole 0.5 mg. Letrozole was significantly better tolerated than MA with respect to serious adverse experiences, discontinuation due to poor tolerability, cardiovascular side effects, and weight gain. CONCLUSION: The data show letrozole 2.5 mg once daily to be more effective and better tolerated than MA in the treatment of postmenopausal women with advanced breast cancer previously treated with antiestrogens.
General practitioners' attitudes to the development of midwifery group practices.
BACKGROUND: The report Changing childbirth (1993) has led to the development of midwifery-led schemes that aim to increase the continuity of maternity care. AIM: To determine the impact of midwifery group practices on the work of general practitioners (GPs) and their perceptions of midwifery group practice care. METHOD: Postal questionnaires were sent to 58 GPs referring women to the care of midwifery group practices (group-practice GPs), and a shorter questionnaire was sent to the remaining 67 GPs (non-group-practice GPs) within the same postcode area as a comparison group. In-depth interviews were conducted with 12 GPs. RESULTS: Questionnaires were returned by 71% of group-practice GPs and 81% of non-group practice GPs. One third of the group practice GPs felt that they were seeing group practice women too few times, and 50% thought midwives discouraged women from visiting their GP for antenatal checks. Over 80% of group practice GPs believed that midwives had the skills to detect deviation from the normal, and 66% would confidently refer women to their care. However, only 14% of group practice GPs believed that their own role was clear, while 64% agreed that communication with group practice midwives was poor, and concerns were expressed about the level of consultation before establishing schemes. Of the non-group practice GPs, 87% said they would consider referring women to the care of a midwifery group practice in the future. CONCLUSIONS: General practitioners were generally positive about the quality of care provided by midwifery group practices but identified issues that require addressing in developing this model of care.
A COSTAR interface using WWW technology.
The concentration of industry on modern relational databases has left many nonrelational and proprietary databases without support for integration with new technologies. Emerging interface tools and data-access methodologies can be applied with difficulty to medical record systems which have proprietary data representation. Users of such medical record systems usually must access the clinical content of such record systems with keyboard-intensive and time-consuming interfaces. COSTAR is a legacy ambulatory medical record system developed over 25 years ago that is still popular and extensively used at the Massachusetts General Hospital. We define a model for using middle layer services to extract and cache data from non-relational databases, and present an intuitive World-Wide Web interface to COSTAR. This model has been implemented and successfully piloted in the Internal Medicine Associates at Massachusetts General Hospital.
Ethanol modulates N-methyl-D-aspartate-evoked arachidonic acid release from neurones.
Glutamate-evokes a Ca2+-dependent release of arachidonic acid from cultured neurones via the activation of NMDA and AMPA receptors. In this study we investigated whether exposing cultured striatal neurones either acutely or chronically to ethanol would modify these responses. Acute ethanol (100 mM, 15 min) inhibited the liberation of arachidonic acid evoked by a maximally effective concentration of glutamate, an affect which appeared to be mediated primarily by a reduction in NMDA receptor responsiveness. In contrast, chronic ethanol exposure caused a dose-dependent increase in the glutamate, N-methyl-D-aspartate (NMDA) and alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA) evoked release of arachidonic acid, although ethanol was less potent at the AMPA response. Basal responses were not altered by acute or chronic ethanol and the concentrations of ethanol employed were not toxic. Chronic ethanol (100 mM, 48 h) increased NMDA-mediated neuronal damage at sub-maximal concentrations of the agonist, suggesting that an enhanced mobilisation of arachidonic acid may underly the potentiated excitotoxic neuronal loss observed following exposure to ethanol.
Foot morbidity and exposure to chiropody: population based study.
Explore the source record for details and available documents.
Portal venous transfusion up-regulates Kupffer cell cyclooxygenase activity: a mechanism of immunosuppression in organ transplantation.
Portal venous transfusions (PVTs) of blood have been shown to induce significant immunosuppression in animal models of organ transplantation. A proposed mechanism of PVT-induced immunosuppression is via alteration of Kupffer cell arachidonic acid metabolism with increased secretion of the suppressive metabolite prostaglandin E2 (PGE2). This study assessed the hypothesis that PVT increases Kupffer cell PGE2 production via up-regulation of Kupffer cell phospholipase A2 (PLA2) as well as constitutive (COX1) and inducible (COX2) cyclooxygenase. Kupffer cells from Lewis rats were harvested 1 hr after PVT with either 1 ml of Wistar-Furth blood, systemic transfusion (SVT), or saline via portal vein (PVSal). After lipopolysaccharide stimulation, 24-hr Kupffer cell supernatant fractions were assayed for PGE2. PGE2 was increased after SVT (1465+/-234 pg/ml) compared with PVSal (597+/-99; P<0.01). PVT increased Kupffer cell PGE2 (5370+/-533; P<0.001 vs. SVT and vs. PVSal) even more substantially. Kupffer cells from PVT-treated rats were then cultured in the presence of inhibitors of PLA2, COX1, or COX2. When Kupffer cells were treated with mepacrine to inhibit PLA2 (5575+/-453 pg/ml), PGE2 production was not different from that by PVSal-treated controls (6467+/-614 pg/ml), but when Kupffer cells were incubated in the presence of the COX1 inhibitor flurbiprofen (3512+/-407 pg/ml) or the COX2 inhibitor nimesulide (2800+/-830 pg/ml), production was decreased 46.7% and 56.7%, respectively, over control activity without added inhibitor. PVT also increased Kupffer cells COX1 and COX2 mRNA as measured by Northern blot. Heart transplants were then performed from Wistar-Furth donors into Lewis recipients at the time of PVT, SVT, PVSal, or PVT + indomethacin (COX1/2 inhibitor). PVT prolonged allograft survival (12.0+/-0.9 days) compared with PVSal (6.3+/-0.3; P<0.01) or SVT (6.3+/-0.3; P<0.04). Indomethacin shortened graft survival when given with PVT (6.5+/-0.3 days). In summary, PVT increased Kupffer cell PGE2 production, up-regulated transcription of Kupffer cells COX1 and COX2 mRNA, and prolonged cardiac allograft survival. COX1/2 inhibition abrogated the effect of PVT. The results indicated that the immunosuppressive effect of PVT may be mediated by up-regulation of Kupffer cell COX1 and COX2. Manipulation of Kupffer cell arachidonic acid metabolism may be useful in augmentation of PVT-induced immunosuppression.
Progesterone metabolite allopregnanolone in women with premenstrual syndrome.
OBJECTIVE: To evaluate the anxiolytic 3alpha-5alpha-reduced progesterone metabolite allopregnanolone in the luteal phase of the menstrual cycle in women with premenstrual syndrome (PMS) and controls. METHODS: Thirty-five women with prospectively documented PMS and 36 controls were evaluated. Serum progesterone and allopregnanolone levels were measured on days 19 and 26 of the cycle as determined by urinary LH detection kits. Analysis of variance and Student t tests were used to analyze the data. RESULTS: Allopregnanolone levels were significantly lower on day 26 in the PMS group than in controls (3.6 +/- 0.8 versus 7.5 +/- 1.3 ng/mL; P < .04). Significant differences in the ratio of the metabolite to progesterone also were noted, with a smaller ratio in the PMS subjects (0.9 +/- 0.3 versus 3.2 +/- 1.3 ng/mL; P < .05). There were no significant differences between the PMS and control groups with respect to serum progesterone levels. CONCLUSION: Subjects with PMS manifested lower levels of the anxiolytic metabolite allopregnanolone in the luteal phase when compared with controls. Diminished concentrations of allopregnanolone in women with PMS may lead to an inability to enhance gamma aminobutyric acid-mediated inhibition during states of altered central nervous system excitability, such as ovulation or physiologic or psychological stress. The lowered metabolite levels could contribute to the genesis of various mood symptoms of the disorder, such as anxiety, tension, and depression.
Cavernous lymphangioma in the adult parotid.
Cavernous lymphangioma is a benign congenital lesion that usually appears in childhood. It rarely presents in the adult but may be diagnosed at this late stage due to the slow growing nature of the tumour. It is rarely found in the salivary glands and when it does occur, the gland is usually incorporated by lymphangioma of surrounding tissue. We present and discuss the case of a cavernous lymphangioma in the parotid gland of an adult male.
In vitro assessment of the influence of nutrition, temperature and larval density on trapping of the infective larvae of Heligmosomoides polygyrus by Arthrobotrys oligospora, Duddingtonia flagrans and Monacrosporium megalosporum.
The influence of nutrient level, temperature and larval density on the trapping of Heligmosomoides polygyrus L3 by the nematophagous fungi Arthrobotrys oligospora, Duddingtonia flagrans and Monacrosporium megalosporum were investigated by quantification of trapped nematodes. All 3 factors were found to have a significant effect on the number of larvae trapped by A. oligospora and M. megalosporum. Decreased nutrient concentrations resulted in increased trapping for these 2 fungi, but nutrient availability was not found to have a significant effect on trapping by D. flagrans. The 3 fungi were found to have similar responses to temperature, with peak trapping occurring at or near the optimum growth temperatures. Nematode trapping was found to be density dependent for all 3 fungi, with increased percentage trapping at increased larval densities. Comparison in a single experiment of the relative importance of these factors to each fungus showed that nutrient level was the main factor influencing trapping by A. oligospora, whereas D. flagrans and M. megalosporum were more dependent on larval density.
Patients' perceptions of changes in their blood pressure.
OBJECTIVES: (1) To investigate patients' experience of changes in their blood pressure (BP) in an every day setting and the accuracy of patients' predictions; and (2) to examine what influences patients' belief that they can tell when their BP is up. SUBJECTS: A total of 102 hypertensive patients were recruited sequentially as they presented for routine BP checks. The setting was an inner city general practice. DESIGN: Patients attended for BP checks on a weekly basis. Before each check they were asked whether they thought their BP was higher, lower or the same as usual. Subjects were classified as predictors if they thought they could tell when their BP was up. On completing their series of BP checks each subject completed symptom and Hospital Anxiety and Depression questionnaires. MAIN OUTCOME MEASURES: Accuracy of BP predictions, BP levels and variability, number of symptoms reported and anxiety level. RESULTS: One hundred and two hypertensive patients entered the study of whom 51 patients were predictors. The majority (86%) of predictors could not accurately predict their BP. There were no significant differences in either BP or variability between predictors and non-predictors. Predictors were significantly more anxious and reported more symptoms than non-predictors. CONCLUSIONS: For the majority of predictors there is no significant relationship between predictions of BP and clinical measurements. Predictor status is associated with the reporting of more symptoms and higher levels of anxiety. Doctors should counsel patients against using subjective BP assessments to guide their use of antihypertensive medication.
A group programme for postnatally distressed women and their partners.
A group programme for postnatally distressed women and their partners is described. The programme consists of eight sessions, including one session for the couple. The concerns of the women centre around their anxieties and feelings towards their partners, their own mothers and their infants. Psychotherapeutic and cognitive-behavioural strategies are employed to assist them in dealing with these concerns. The concerns of the men centre around their attempts to provide emotional and practical support to their partner. Invariably such support results in an increase in tension between the partners, and the programme helps the men to understand why this happens. Formal measures show a decrease in maternal distress over time and an increase in their level of self-esteem. About half of the men show elevated levels of distress.