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Biomedical subjects

P Morgan

Publications and source records attributed to P Morgan.

At least 73 records · Page 4Linked to original sources
PubMed1995

Regional distribution of iodomelatonin binding sites within the suprachiasmatic nucleus of the Syrian hamster and the Siberian hamster.

The pineal hormone melatonin is a potent regulator of seasonal and circadian rhythms in vertebrates. In order to characterize potential target tissues of melatonin, the distribution of iodomelatonin (IMEL)-binding sites was examined within neurochemically and anatomically defined subdivisions of the suprachiasmatic nucleus (SCN), a structure necessary for seasonal and circadian rhythms in mammals. Studies were carried out in both the adult Syrian (Mesocricetus auratus) and Siberian (Phodopus sungorus) hamster. The retinoreceptive zone of the SCN was identified anatomically by immunocytochemical (ICC) visualization of cholera toxin B subunit tracer (ChTB-ir) following its intra-ocular injection. Photically-responsive SCN cells were identified by immunostaining for the protein product of the immediate-early gene c-fos (Fos-ir) following exposure of the animal to light. The non-photoresponsive zone of the SCN was identified using in situ hybridization (ISH) for arginine vasopressin (AVP) mRNA, whilst sites of IMEL-binding in the SCN were identified by in vitro film autoradiography using the specific ligand 2-[125I]-iodomelatonin. To compare directly the distribution of IMEL-binding sites and one of the functional zones of the nucleus, alternate serial coronal sections through the SCN were processed for autoradiography for IMEL and one of the following: ICC for ChTB-ir or Fos-ir, or ISH for AVP mRNA. Overall, the regional distribution of the various markers within the SCN was comparable in the two species. The retinorecipient (ChTB-ir) and photically-responsive (Fos-ir) zones of the SCN mapped together to the middle and caudal thirds of the nucleus, predominantly in its ventro-lateral division.(ABSTRACT TRUNCATED AT 250 WORDS)

Afferent Pathways↗
PubMed1994

Synthesis and structure-activity relationships of novel naphthalenic and bioisosteric related amidic derivatives as melatonin receptor ligands.

A series of N-naphthylethyl amide derivatives were synthesized and evaluated as melatonin receptor ligands. The affinity of each compound for the melatonin receptor was determined by binding studies using [2-125I]iodomelatonin on ovine pars tuberalis membrane homogenates. Structure-activity relationships led to the conclusion that naphthalene is a bioisostere of the indole moiety of melatonin. Moreover it appears that the affinity is strongly affected by the size of the substituent of the nitrogen of the amidic function. Many of these ligands give biphasic dose-response curves which suggests that there may be two melatonin receptor subtypes within the ovine pars tuberalis cells. The replacement of naphthalene by benzofuran or benzothiophene did not strongly alter the affinity for the melatonin receptor. In contrast, the benzimidazole analogue was a poor ligand. Compound 7, the naphthalenic analogue of melatonin, a selective ligand of the melatonin receptor and an agonist derivative, has been selected for clinical development.

Acetamides↗
PubMed1994

Product-induced stabilization of tertiary and quaternary structure in Escherichia coli dehydroquinase.

The effects of irreversibly attaching product at the active site of type I dehydroquinase from Escherichia coli have been investigated at the level of the secondary, tertiary, and quaternary structure of the protein by spectroscopic and hydrodynamic techniques. The results agree with the previously identified stabilization of the enzyme but show for the first time that the protein dimer is also stabilized and suggest that the E. coli dehydroquinase subunit may be bilobal.

Circular Dichroism↗
PubMed1994

The role of vasopressors in the management of hypotension induced by spinal and epidural anaesthesia.

Although spinal and epidural blocks provide excellent anaesthesia for many operations, they are frequently accompanied by hypotension. This is largely the result of sympathetic nerve blockade. Excessive hypotension may potentially produce myocardial and cerebral ischaemia, and is associated with neonatal acidaemia in obstetric practice. How to prevent and treat this hypotension has been the subject of much investigation and controversy. One of the mainstays of management is the use of vasopressor agents and those currently available are not perfect. In this review, the role of vasopressor agents is discussed and possible future management strategies are commented upon. Ephedrine was the first agent used for this purpose and it has withstood the test of time: it is the agent against which all others are compared. It remains the first-line agent in obstetric anaesthesia as it does not affect the fetus adversely, but it cannot be relied upon to be 100% successful and other agents must be considered when it is inadequate. It is best given by infusion. In non-obstetric practice, ephedrine has a good track record but again its success rate is less than 100%. As there is no fetus to consider, it may be more appropriate to consider using a pure vasoconstrictor agent such as methoxamine or phenylephrine as a first-line therapy in such cases. This judgment can only be made on an individual patient basis as ephedrine produces a tachycardia while phenylephrine and methoxamine both produce bradycardia.

Anesthesia, Epidural↗
PubMed1994

The natural history of euploid pregnancies with first-trimester cystic hygromas.

OBJECTIVES: Little information is available with regard to prognosis of euploid fetuses with first-trimester nuchal hygromas. To evaluate this population, the natural history, pregnancy outcome, and pediatric implication of this lesion were determined. STUDY DESIGN: Fetuses with cystic hygromas detected in the first trimester were retrospectively identified, and karyotype results were documented. Pregnancy outcome of those fetuses having a euploid karyotype was obtained, and physical examination of the live-born neonates and infants was performed by a clinical geneticist. RESULTS: A normal karyotype was identified in 22 (51%) of these pregnancies. Eighty-two percent of the euploid pregnancies were continued, with 89% of the fetuses surviving to the third trimester. Dysmorphic sequelae were documented in three children, including Noonan syndrome in one. CONCLUSION: In the presence of a normal karyotype fetuses with a first-trimester nuchal hygroma have an excellent prognosis. Normal outcome was seen in 80% of pregnancies carried to the third trimester.

Aneuploidy↗
PubMed1994

Continuous quality improvement in an acute hospital: a report of an action research project in three hospital departments.

Describes an action research project to improve quality in three hospital departments including operating theatres, X-ray, and medical records. The approach combined quality assurance (QA) or audit methods with those of continuous quality improvement (CQI) or TQM. The intention was to bring about improved organizational performance through an emphasis on bottom-up rather than top-down methodology, and to assess the relative effectiveness of different quality strategies being used within the hospital. Baseline studies of organizational climate and of patient perceptions enabled evaluation of effectiveness. Provides a description of the background to various health-care quality strategies, and argues that several perspectives are required if all stakeholders (e.g. policy makers, professionals, patients, and managers) are to be satisfied. Describes the responses of staff, superiors and professionals and recommendations offered for more effective quality strategy implementation.

Attitude of Health Personnel↗
PubMed1994

Cloning and expression of a new member of the melanocyte-stimulating hormone receptor family.

A new member of the G protein-coupled receptor superfamily has been isolated from an ovine genomic library with a probe generated by the application of the PCR technique, using cDNA synthesized on a mRNA template isolated from the ovine pars tuberalis. This genomic clone encodes a novel receptor of 325 amino acids with seven transmembrane domains. These domains share homology with other members of this family, but the best homology is with the recently cloned human MC-1 (50% in the transmembrane domains) and MC-3 (69% in the transmembrane domains) MSH receptors and the human ACTH (42% in the transmembrane domains) receptor. When this receptor was expressed in Cos7 cells, it was able to bind a potent analogue of alpha-MSH, [Nle4,D-Phe7]-alpha-MSH (NDP-MSH), with high affinity. This binding could be displaced by pro-opiomelanocortin-derived and related peptides, with the order of potency NDP-MSH > alpha-MSH = ACTH > beta-MSH and with no effect of gamma-MSH, delta-MSH or beta-endorphin. The expressed receptor was demonstrated to be functionally coupled to the adenylate cyclase second messenger pathway, with alpha-MSH, beta-MSH and ACTH stimulating cyclic AMP production. The amount of the mRNA for this receptor was found to be very low. The tissue distribution of this receptor could only be observed using the reverse transcription-PCR technique and the receptor was found to be present in a number of somatic tissues. These data indicate that this is a new and distinct member of the melanocortin receptor family.

Amino Acid Sequence↗
PubMed1993

Development of a structured interview scale for measuring quality of life of the severely mentally ill.

An objective, semi-structured interview questionnaire (QOLIS) was designed and tested with 201 severely mentally ill people who were living in a state hospital and in community residential facilities. Factor analysis resulted in eight factors with face validity and acceptable coefficient alphas. The factors were found to be related meaningfully to overall level of functioning, total symptom scores, self-reported life satisfaction, and an established objective measure of quality of life. Criterion validity was established and the QOLIS factors significantly differentiated people who were living in the community vs. living in a state hospital. These results suggest that the QOLIS has potential as a valid outcome measure and program evaluation tool.

Activities of Daily Living↗
PubMed1993

Recurrent squamous cell carcinoma of the vulva: a study of 73 cases.

In a study of 73 patients, diagnosed with recurrent squamous cell carcinoma of the vulva between 1975 and 1990, the effect of clinical variables on the outcome was evaluated. The overall 5-year survival rate was 35.2%. Of the 73 patients, 33 (45.2%) originally had Stage I or II disease and 40 (54.8%) Stage III or IVA; 49 (67.1%) recurred less than 2 years and 24 (32.9%) more than 2 years after initial surgery; and 39 (53.4%) recurred on the vulva only, while 34 (46.6%) recurred beyond the vulva. Of 59 patients who had groin lymph node dissection at initial surgery, 26 (44%) had negative and 33 (56%) had positive nodes. By means of univariate analyses, a significant worsening in outcome was demonstrated with advancing original stage of disease (P < 0.001), positivity of groin lymph nodes (P < 0.01), shortening of recurrence-free interval (P < 0.001), and extension of recurrence beyond the vulva (P < 0.001). In a multivariate analysis (Cox proportional hazards model) recurrence site was the strongest and the only significant predictor of survival. The death risk showed a 3.7-fold increase (95% confidence intervals: 1.6 to 8.7, P = 0.002) for recurrence beyond the vulva over recurrence on the vulva only. For patients who recurred in the vulva only, wide radical local excision provided acceptable survival results, while for all other patients, regardless of type of treatment, the outcome was poor.

Adult↗
PubMed1993

The case for conservative management of "incomplete excision" of CIN after laser conization.

Three hundred thirteen laser cone biopsies were performed for cervical intraepithelial neoplasia (CIN) over a 4-year period. The mean age of the patients was 39.9 years and average cytology follow-up was just under 3 years. Six patients defaulted colposcopic review and were excluded from analysis. Of the 75 cases with CIN extending to the endocervical resection margin, 9 (12%) were found to have residual disease. Only 2 (3.6%) of 56 cases with CIN extending to the ectocervical margin had residual CIN detected. In the 176 cases in which the CIN lesion was excised completely there have been no cases of residual CIN. The overall detection of residual disease was 3.6%. Further surgery in those cases with CIN extending to the resection margin is excessive. These patients should be managed conservatively with regular cytological follow-up.

Adult↗
PubMed1993

Biodegradation of benzene, toluene, ethylbenzene and xylenes in gas-condensate-contaminated ground-water.

The rate and extent of biodegradation of benzene, toluene, ethylbenzene and xylenes (BTEX) in ground-water was studied in samples from a contaminated site which contained total BTEX concentrations of up to 20 000 microg litre(-1). All compounds were rapidly degraded under natural aerobic conditions. Elevation of incubation temperature, supply of organic nutrients or addition of inorganic fertiliser did not increase the rate or extent of biodegradation and it appeared that oxygen supply was the factor limiting BTEX degradation at this site. Attempts to increase the dissolved oxygen concentration in the ground-water by the addition of hydrogen peroxide to give a final concentration of 200 mg litre(-1) resulted in the complete inhibition of biodegradation. No biodegradation occurred under anaerobic conditions except when nitrate was provided as a terminal electron acceptor for microbial respiration. Under denitrifying conditions there was apparent biodegradation of benzene, toluene, ethyl-benzene, m-xylene and p-xylene but o-xylene was not degraded. Degradation under denitrifying conditions occurred at a much slower rate than under oxygenated conditions.

Journal Article↗
PubMed1993

Assessment of elderly people in general practice. 4. Depression, functional ability and contact with services.

The aim of this study was to look at the interrelationship between depression, physical disability and contact with services. In a random sample of 239 people aged 75 years and over from nine general practices in north London, depression (as measured by a shortened version of the comprehensive assessment and referral evaluation schedule) was found to be significantly associated with being a woman, and inability to perform a number of activities of daily living. Consumption of three or more prescribed medicines, a home visit by the general practitioner in the previous three months and contact with health visitors and home helps were all significantly more likely among depressed patients. There were also significant associations between loss of functional abilities, measured using items from an activities of daily living scale, and use of certain services: general practitioner home visits and reduced mobility indoors and both home help and district nurse visits to those with difficulty in bathing. Multiple logistic regression analysis suggested that contact with services was principally associated with loss of mobility, although contact with home helps was independently associated with depression, when adjustment was made for functional impairment.

Aged↗
PubMed1993

Prenatal diagnosis in twin gestations: a comparison between second-trimester amniocentesis and first-trimester chorionic villus sampling.

OBJECTIVE: To evaluate prospectively the relative risks and accuracy of first-trimester chorionic villus sampling (CVS) and second-trimester amniocentesis in the genetic evaluation of twin gestations. METHODS: Between March 1984 and August 1990, patients presenting for prenatal diagnosis of a twin gestation of less than 12 weeks were offered sampling by either first-trimester CVS or amniocentesis at 16-18 weeks' gestation. Selection was based solely on patient preference and was obtained before ultrasound identification of placental position. Women presenting beyond 12 weeks' gestation were sampled by amniocentesis. Clinical and laboratory outcomes were evaluated. RESULTS: Eighty-one women had amniocentesis (nine of whom also had CVS), and 161 women had CVS. All fetuses in both groups were successfully sampled and karyotyped; 85.3% of the amniocentesis patients and 75.8% of the CVS patients were sampled in two or fewer passes (P = not significant). There were three cases of twin-twin villus contamination following CVS; one of these led to incorrect gender assignment because of erroneous laboratory interpretation. Loss of the entire pregnancy from the time of sampling until the 28th week of gestation followed amniocentesis in 2.9% of the cass and CVS in 3.2%. The total fetal loss rates were 9.3% for amniocentesis and 4.9% for CVS (P = not significant). When pregnancies having mosaic or abnormal karyotype results are excluded, the total amniocentesis loss rate remained 9.3% and the CVS loss rate became 3.9% (P < .05). CONCLUSION: In the hands of experienced operators, CVS is at least as safe and effective as amniocentesis for the prenatal diagnosis of twin gestations.

Abortion, Eugenic↗
PubMed1992

Oxidative dehalogenation of 2-fluoro-17 alpha-ethynyloestradiol in vivo. A distal structure-metabolism relationship of 17 alpha-ethynylation.

Metabolic activation to catechols and their oxidation products is variously considered to contribute to the genotoxic, cytotoxic, transforming and tumour-promoting activities of exogenous steroidal oestrogens. 2-Fluoro-17 alpha-ethynyloestradiol (2-FEE2) was synthesized as a prototype of pharmacologically active derivatives of 17 beta-oestradiol which are resistant to metabolic activation in vivo. It possessed high affinity for the rat uterine oestrogen receptor and was oestrogenic in rats. Biliary metabolites of [6,7-3H]2-FEE2 (0.73 mumol/kg, 157 micrograms/kg, i.v.) in female rats were characterized: 87% of the radiolabel was excreted, principally as 2-FEE2 glucuronide, over 6 hr. Although 2-fluoro-17 beta-oestradiol is not metabolized to C-2 oxygenated products in vivo, 2-FEE2 underwent rapid and appreciable oxidative defluorination. 2-Hydroxy-17 alpha-ethynyloestradiol and 2-methoxy-17 alpha-ethynyloestradiol represented, respectively, 8% and 13% of the dose. Fluorination nevertheless restricted C-2 oxygenation to ca. 28% of that which 17 alpha-ethynyloestradiol undergoes in female rats. C-4 oxygenation of 2-FEE2, resulting in catechol formation, occurred but to a lesser extent (ca. 12% of dose). None of the major and identified minor biliary metabolites was a product of metabolic activation at the ethynyl function. A mechanistic rationalization of the long range enhancement by 17 alpha-ethynylation of oxidative defluorination at C-2 is presented.

Animals↗