Biomedical subjects

L Newton

Publications and source records attributed to L Newton.

At least 19 recordsLinked to original sources

PubMed2006

Effects of dose and duration of continuous GnRH-agonist treatment on induction of estrus in beagle dogs: competing and concurrent up-regulation and down-regulation of LH release.

Dose-response estrus-induction trials were conducted during anestrus in 93 treated and 6 control bitches, a continuous administration of the GnRH-agonist lutrelin with a potency 150 x GnRH, and at six different doses from 0.2 to 4.8 microg/kg/d for 7-14 days in 15 groups of six to eight dogs each in defined stages of natural or pharmacologically determined anestrus. Agonist treatment induced clinically and cytologically normal proestrus (in 89% of cases) within 4.8 +/- 0.2 x days, and resulted in behavioral estrus (71%), spontaneous late-proestrus LH (and FSH) surges, ovulation (59%) and pregnancy (44%) in a dose dependent manner. Outcomes of ovulation and pregnancy in most cases required that the dose be sufficiently large enough to routinely stimulate a large initial increase in LH and FSH (i.e., > or = 0.6 microg/kg/d), and of sufficient duration (i.e., > 7 days) to ensure that supra-basal gonadotropin levels persistedntil no longer needed for spontaneous continuation of an induced proestrus. Success additionally required that the GnRH dose be modest enough (i.e., < 1.8 microg/kg/d) to not excessively down-regulate spontaneous pre-ovulatory surge release of gonadotropin or be removed shortly before or at the time when the LH surges typically occurred (10-13 days after initiation of treatment). The 1.8 microg dose was compared to saline to assess the time course of its down-regulation action on serum LH in six ovariohysterectomized bitches compared to four saline-related controls. Results in intact bitches receiving the 1.8-microg doses demonstrated an LH-releasing effect for 10-11 days that overlapped a period of obvious down-regulation seen with the same dose after 3 days in the ovariohysterectomized bitches. In the latter, however, complete down-regulation to anestrus-like values did not occur until after 18-21 days of treatment. A dose of 0.6 microg/kg/d for 12 days yielded the best estrus-induction results, including pregnancy rates of 100% in six bitches treated in natural-anestrus bitches, six bitches in which anestrus had been advanced by a luteolytic prostaglandin treatment and in six bitches in which anestrus had been extended by progesterone implants administered for 3 months. Although lutrelin is not commercially available, these results provide guidelines for the development of estrus-inducing protocols with other GnRH-agonists of known biopotencies.

Anestrus↗

PubMed2002

Spontaneous frequency of exon skipping in the human HPRT gene.

In order to elucidate the mechanisms of mRNA splicing fidelity and the mutagenic potential of aberrant mis-spliced transcripts we have investigated the frequency of spontaneous exon skipping in the human hypoxanthine-guanine phosphoribosyl transferase (HPRT) gene in well characterized human primary fibroblasts isolated from two different individuals. In these cells, coexisting with the WT species, we also detected three aberrant HPRT transcripts missing exon IV, VII, or VIII. We were unable to detect transcripts missing exon II, III, V, or VI. Significantly, all the exons affected by skipping do not generate new stop codons more than 50 nucleotides upstream from the 3' most exon-exon junction. Exon VIII was the most prone to skipping with a relative frequency to WT of 0.019+/-0.004 (approximately one aberrant transcript per 50 WT transcripts). Exon IV exhibited a relative frequency of skipping of 0.006+/-0.002 ((approximately one aberrant transcript per 150 WT transcripts) and exon VII exhibited a relative frequency of skipping of 0.003+/-0.002 ((approximately one aberrant transcript per 300 WT transcripts). These data demonstrate that aberrant transcripts with exon skipped are generated spontaneously in humans and some appear to persist in the cell.

Exons↗

PubMed2001

Moving out and moving on: some ethnographic observations of deinstitutionalization in an Australian community.

Since the 1950s deinstitutionalization has taken place for people with mental illnesses in the Western world. The growth of community care and residential facilities, as well as planning and implementation of policies, has varied in timing and orientation. An appreciation of the process of change affecting people discharged to the community highlights their strength, resilience, and vulnerabilities. This paper outlines a two and a half year ethnographic qualitative study undertaken in Australia, where 47 long-stay psychiatric inpatients were discharged to the community. The process accompanied the amalgamation of two major psychiatric hospitals, resulting in the closure of one. Findings demonstrated slow but positive change for residents as they reintegrated into the community. A separate quantitative and economic study was undertaken alongside the qualitative study (for results see Hobbs, et al., 2000; Newton, et al, 2000; Lapsley, et al., 2000).

Adult↗

PubMed2000

Deinstitutionalisation for long-term mental illness: cost differences in hospital and community care.

OBJECTIVE: This project studied the cost analysis of psychiatric hospital and then community care for long-stay patients with chronic mental illness discharged during the closure of a psychiatric hospital in Sydney. METHOD: Expenditure and income data in both settings were collected. Costs were analysed on an occupied bed-day basis. RESULTS: The hospital setting cost more per patient per day compared with the various community costs which were one-third to one-half of the comparable hospital costs. CONCLUSIONS: The analysis demonstrated overall that hospital care was nearly twice as expensive as care in the community setting. The factors which may have influenced, although not necessarily altered, the substance of the findings largely related to 'organisational efficiency'. The mental hospital as an older, more rigid system was likely to be less efficient than the newer community service provision which was under intensive scrutiny both clinically and financially by all interested parties.

Australia↗

PubMed2000

Deinstitutionalisation for long-term mental illness: an ethnographic study.

OBJECTIVE: Deinstitutionalisation of seriously mentally ill people in the developed world, including Australia, has occurred since the middle of this century. Evaluation of the effects of this change on the lives of individuals is of paramount importance to ensure that policies are acceptable and effective. Increasingly, multifaceted studies are considered essential for comprehensive health research. The qualitative aspect of this study complements the clinical and economic components. METHOD: An ethnographic approach enabled contextual, qualitative data to be gathered from within the social world of 47 hospital residents as they moved to the community. A social anthropologist acting explicitly as a participant observer undertook fieldwork over two and a half years both pre- and post-discharge. Qualitative data were collected, stored and analysed separately from quantitative and economic data. RESULTS: Ethnographic findings generally supported and, in many cases, mirrored clinical results. Of the total cohort of 47 patients transferred to the community, the 40 who continue to live outside of hospital all reported a preference for community living. The importance of freedom and simple liberties cannot be underestimated as factors that enabled this resilient group of people to work creatively through difficult periods. CONCLUSION: Properly planned and resourced deinstitutionalisation not only maintains people with a prolonged mental illness outside of hospital, it also enhances their quality of life. Subjective descriptive material focusing on personal experiences adds meaning to quantitative research data allowing health professionals to more fully understand the implications of health policy on the lives of individuals.

Anthropology↗

PubMed2000

Deinstitutionalisation for long-term mental illness: a 2-year clinical evaluation.

OBJECTIVE: The closure of a long-stay psychiatric hospital in Sydney caused the transfer of an initial 40 very long-term patients to four community residences, each with 10 beds, for a continuing process of deinstitutionalisation. Community psychiatric service support and 24-h supervision were provided. This paper describes the residents' clinical progress which was assessed over a 2-year period. METHOD: This study employed a quasi-experimental longitudinal design. Evaluation commenced prior to discharge and continued for 2 years following community relocation using the Brief Psychiatric Rating Scale, Life Skills Profile, Social Behaviour Scale, Montgomery Asberg Depression Rating Scale and Quality Of Life measures. Readmission, demographic, case history and medication data were also collected. RESULTS: Of the 40 patients initially transferred to the community, seven required long-term readmission to hospital (either prior to or after amalgamation) and one patient died of medical causes. Additional patients transferred from the hospital to the community following the readmissions. Three of these additional patients had achieved a 2-year community tenure during the study period and were included in the clinical evaluation. The 35 residents in total who remained in the community for 2 years, demonstrated a significant improvement in psychotic symptoms, without significant change in the level of neuroleptic medication. Importantly, the 2 years of community living resulted in a significant increase in the residents' life satisfaction. There were no statistically significant changes in residents' living skills, depressive symptoms or social behaviour problems over the 2 years, indicative of the need for supervision and community service support following deinstitutionalisation. Over the 2-year period, some 37% of the residents required temporary readmission. CONCLUSION: This study demonstrates the clinical effectiveness of deinstitutionalisation, when planned within a mental health system with adequate community resources.

Adolescent↗

PubMed1998

Potential impact of antiarrhythmic drugs versus implantable defibrillators on the management of ventricular arrhythmias: the Midlands trial of empirical amiodarone versus electrophysiologically guided intervention and cardioverter implant registry data.

BACKGROUND: Survival was prolonged in selected patients with sustained ventricular arrhythmias who received implantable cardioverter defibrillators (ICDs) in the antiarrhythmics versus implantable defibrillators (AVID) study. The Midlands trial of empirical amiodarone versus electrophysiologically guided intervention and cardioverter implant in ventricular arrhythmias (MAVERIC) registry is a population based trial. OBJECTIVE: To determine the number of patients who satisfy the AVID criteria because of the high cost of ICDs. DESIGN: Observational study, based on a continuing trial. SETTING: All coronary care units in the Midlands region in the United Kingdom (population 9.1 million). PATIENTS: Patients presenting to a coronary care unit with sustained ventricular arrhythmias not related to an acute myocardial infarction are entered onto the registry. Those who consent to the MAVERIC study are randomised to receive either empirical amiodarone or electrophysiologically guided treatment. Demographic data, details of clinical presentation, and echocardiographic findings are collected. These data have been used to calculate the number of patients who satisfy the AVID criteria and would benefit from ICD implantation. The financial implications have been calculated for the region and nationally. RESULTS: 132 patients were entered onto the registry during the first five months of the MAVERIC study; 69 patients fulfilled the AVID criteria. Extrapolation of these data over a 12 month period suggests implantation of at least 166 new ICDs (compared with 23 implants in 1996). This would increase the UK ICD implant rate from five to at least 18 per million of the population, costing the National Health Service 24.1 Pounds million per annum. CONCLUSION: Application of the AVID criteria in the UK will cause a great increase in the ICD implant rate, with serious financial implications.

Aged↗

PubMed1997

Incidence of spontaneous ovulation in young, group-housed cats based on serum and faecal concentrations of progesterone.

Cats are considered to be reflex ovulators that exhibit a luteal phase (pregnancy or pseudopregnancy) only after copulatory stimulation. In a group-housed colony of 15 1-year-old domestic queens, 23 noncopulatory, spontaneous ovulations were observed in 87% of the queens over 4.5 months based upon the detection of increased concentrations of progesterone in faeces, serum, or both. Luteal phases were detectable for periods of 3 to 5 weeks with peak progesterone concentrations averaging 21 +/- 1 ng ml-1 in serum and 1874 +/- 281 ng g-1 in faeces. Individual cats exhibited from 0 to 3 spontaneous ovulations and subsequent pseudopregnancies each. A male was added to a separate cage within the room during the last 1.5 months of the study. The incidence of ovulation per 10 day period ranged from 0% to 22% before introduction of the male and from 33% to 57% immediately after introduction of the male, suggesting a potential noncopulatory influence of the male on the incidence of spontaneous ovulation in young, group-housed cats.

Animals↗

PubMed1996

Postimplantation increase in plasma fibrinogen concentration with increase in relaxin concentration in pregnant dogs.

OBJECTIVE: To determine time courses of pregnancy-related changes in plasma fibrinogen, serum relaxin, and serum C-reactive protein-like immunoreactivity (CRP-LI) concentrations in pregnant and nonpregnant dogs. ANIMALS: 16 pregnant and 13 nonpregnant Beagles, 6 pregnant Beagles, and 3 pregnant and 3 nonpregnant dogs of other breeds. PROCEDURE: Fibrinogen was measured by nephelometric centrifugal analysis of light scatter in plasma samples of all dogs, and CRP-LI was measured by fluorescence immunoassay in selected sera from 10 pregnant and 10 nonpregnant dogs. Relaxin was measured in selected sera from 7 pregnant and 7 nonpregnant dogs. RESULTS: During pregnancy, fibrinogen concentration increased between days 21 and 30 after the luteinizing hormone surge, and was > 280 mg/dl between days 29 and 50 in 84 of 86 samples, with peak values 539 +/- 29 mg/ dl higher (P < 0.01) than those in nonpregnant dogs (188 +/- 8 mg/dl), higher values from days 21 to 50 (P < 0.01) than those in nonpregnant dogs, and values similar to those in nonpregnant dogs after day 50. Relaxin concentration was increased from days 26 to 30 and 0 to 4 days after fibrinogen concentration increased in pregnant dogs, and was not detectable in nonpregnant dogs. The CRP-LI concentration was higher in pregnant dogs at days 26 to 50, but values were inconsistent within and among dogs, and near the limit of sensitivity of the assay. CONCLUSIONS: Concentration of the acute-phase reactant protein fibrinogen increases after day 20 following implantation in dogs, at or just before the pregnancy-specific increase in relaxin concentration from days 26 to 30, and persists until day 50. CLINICAL RELEVANCE: Fibrinogen assay may be useful for pregnancy diagnosis in dogs.

Acute-Phase Proteins↗

PubMed1995

Effect of hydrocortisone and disodium cromoglycate on mast cell-mediator release induced by substance P.

Release of inflammatory mediators from mast cells following immunoglobulin bridging by specific allergens triggers episodes of asthma and bronchial hyperreactivity. Recent evidence has shown that neuropeptides, such as substance P (SP), may modulate the pulmonary inflammatory response in these airway diseases. This suggests that SP may affect secretory events of mast cells. To investigate these effects, resident peritoneal mast cells were collected from Sprague-Dawley male rats and stimulated with Con A (utilizes surface-bound immunoglobulin), compound 48/80 (acts in a peptide-like manner) and SP. Secretion was assessed as the release of preloaded [14C]serotonin. All secretagogues induced dose-dependent release. Pharmacologic modulation of release was then studied with two drugs employed for treatment of airway disease, hydrocortisone, a classical anti-inflammatory steroid, and disodium cromoglycate (DSCG). Following pretreatment with 5 mumol/l hydrocortisone, serotonin release induced by Con A was inhibited by 59%. No inhibition was noted with compound 48/80 or SP release. Similarly, following DSCG (300 mumol/l) pretreatment, 40% inhibition of release was noted with Con A, but no inhibition occurred following compound 48/80- or SP-stimulated release. Collectively, these results suggest that mast cells possess multiple activation-secretion coupling pathways which respond differently to clinically used pharmacologic agents. Diseases involving SP modulation of mast cell mediator release may not be successfully treated with anti-inflammatory steroids or DSCG.

Alkaloids↗

PubMed1994

Determination of blood flow to the transplanted kidney. A novel application of phase-contrast, cine magnetic resonance imaging.

There is at present no noninvasive method that reliably measures blood flow in the poorly functioning renal allograft. The present study was designed to evaluate phase-contrast cine magnetic resonance imaging (PC-cine-MRI) for this purpose. We recruited for study 18 patients who had received kidney transplants 13-66 months earlier from closely related living donors. As judged by the glomerular filtration rate, which was elevated for a single kidney (76 +/- 4 ml/min 1.73 m2), allograft function was excellent, permitting the assumption of unimpaired renal extraction of paminohippuric acid (PAH). Allograft blood flow was determined consecutively on the same day, first by the standard PAH clearance technique and they by the product of the velocity of protons and renal vein cross-sectional area using PC-cine-MRI. MRI determinations could not be completed because of claustrophobia in two patients and failure to image the terminus of the allograft vein another two. Comparison of blood flow in the remaining 14 subjects revealed the two techniques to be strongly related (r = 0.91, P < 0.001). On the average, the renal blood flow rate was similar by each method; 732 +/- 62 by PAH clearance and 703 +/- 69 ml/min by PC-cine-MRI, but the agreement among individuals between the two methods was only modest, with a 95% confidence interval of agreement from -214 to +254 ml/min. We conclude that PC-cine-MRI provides a fairly accurate and noninvasive method for determining the rate of blood flow in the transplanted kidney. With further refinement it should permit the role of depressed blood flow in a variety of acute and chronic forms of human allograft dysfunction to be elucidated in humans for the first time.

Glomerular Filtration Rate↗

PubMed1993

Listeriosis surveillance: 1992.

The annual reported totals of cases of listeriosis in England, Wales and Northern Ireland have remained low over the last three years and a total of 108 cases was reported in 1992. The clinical and epidemiological features reported in 1992 were similar to those in previous years and in other countries, except for a shift in the seasonal peak to the summer (a pattern consistently seen before the upsurge in 1987) and a reduction in the case fatality rate of non pregnancy-associated cases.

Adult↗

PubMed1993

Reye's syndrome in the British Isles: report for 1990/91 and the first decade of surveillance.

The Reye's syndrome (RS) surveillance scheme for the British Isles, jointly organised by the British Paediatric Association and the PHLS Communicable Disease Surveillance Centre, was established in 1981. In the ten years that have followed, there has been a gradual decline in the number, and the age, of cases reported. However, the proportion of cases whose diagnosis was subsequently revised to that of an inherited metabolic disorder, has increased. These trends have been influenced by the change from 'passive' to 'active' case ascertainment in 1986; the aspirin warning issued by the Committee on Safety of Medicines in June 1986; the 1989 influenza epidemic; and the increasing awareness of conditions that mimic RS, particularly inherited metabolic disorders involving defects of fatty acid oxidation. The cases reported in 1990/91 showed the lowest annual incidence recorded so far and a median age of less than ten months (compared with 15 months in the first six years of surveillance). There was a reduction in the case fatality rate in 1990/91 (although still high at 38%) but it is of concern that two children had had pre-admission exposure to aspirin. Parents should be kept aware of the dangers of giving aspirin preparations to children with feverish illnesses.

Adolescent↗

PubMed1993

Management of Kawasaki disease in the British Isles.

Kawasaki disease in the British Isles was surveyed by an active reporting scheme, based on all cases reported to the British Paediatric Surveillance Unit that were diagnosed between 1 January and 31 December 1990. The study was prompted by the need to investigate the high case fatality rate of Kawasaki disease of 2% observed in 1988. One hundred and sixty three patients were identified of whom six (3.7%) died. Forty five children (28%) suffered cardiac complications of which 39 (24%) were coronary artery abnormalities; five children were diagnosed at postmortem examination, and coronary artery abnormalities were detected by echocardiography in 34. One hundred and forty nine children (93%) had echocardiography. High thrombocytosis, leucocytosis, duration of fever, and younger age were associated with the presence of coronary artery abnormalities. Erythrocyte sedimentation rate, sex, and the number of diagnostic criteria were not. One hundred and thirty three children (87%) received aspirin. Ninety three children (61%) received intravenous gammaglobulin (IVGG). Children were more likely to receive IVGG if they had thrombocytosis or typical Kawasaki disease. The incidence of coronary artery abnormalities was found to be similar in those treated with IVGG (29%) and those untreated (20%), including those treated within 10 days of onset. This may have reflected selection of the more serious cases to receive IVGG or that Kawasaki disease in the British Isles is a different illness to that experienced elsewhere. It amy be, however, that IVGG is less effective in the treatment of British patients with Kawasaki disease than has been the experience in the United States and Japan. These observations emphasise the need for a therapeutic trial of treatment modalities for Kawasaki disease in the UK and the Republic of Ireland.

Adolescent↗

PubMed1992

Listeriosis surveillance: 1991.

A total of 130 cases of listeriosis was reported in England, Wales and Northern Ireland in 1991. This represents a slight increase on the 1990 total of 118 reports but a marked decline compared with the peak incidence of reporting of 291 in 1988, which was part of an upsurge of cases between 1987 and mid 1989. Two epidemiological features of note in 1991 were the reappearance of a late summer-autumn peak in cases (commonly seen prior to 1987) and an increase in the number of reports among younger patients and children. The decline in listeriosis observed during the second half of 1989, which followed government health warnings about the consumption of pâté, and the continued low level of reporting since 1989 may be due to the disappearance of a common food source. However, in the light of the recent outbreak of listeriosis in France it is important that diagnostic vigilance and warnings about high risk foods are maintained.

Adolescent↗

PubMed1992

Short-term responsiveness of membranous glomerulopathy to cyclosporine.

We administered a 12-week course of cyclosporine (CsA) (4 to 6 mg/kg/24 h) to nephrotic patients with membranous glomerulopathy (MG). Nephrotic patients with minimal change nephropathy (MCN) served as a comparison group. We evaluated the effects of CsA on proteinuria, glomerular function, and the release of cytokines by peripheral blood mononuclear cells in culture. Proteinuria was restored to normal levels within 2 to 4 weeks in MCN. Proteinuria declined from nephrotic to subnephrotic levels (< 3,500 mg/24 h) in 10 of 14 patients with MG, also within 2 to 4 weeks of onset of therapy. The four nonresponders exhibited a rapidly progressive and presumably irreversible form of MG culminating in renal failure. On average, fractional clearances of albumin and IgG declined by 59% and 73% in MG (P < 0.005); corresponding declines in MCN were by 99% (P < .0001). Corresponding rates of glomerular filtration in each glomerular injury remained unchanged. A strong trend for proteinuria to relapse after CsA was withdrawn was evident in both disorders. The release of tumor necrosis factor (TNF)-alpha by mononuclear cells in culture was enhanced in each glomerular injury, both before and after the course of CsA. We conclude that the proteinuria in most cases of MG exhibits a responsiveness to CsA that is qualitatively similar to, but less complete than, that in MCN. The rapidity with which barrier function improves suggests a possible role for cell-mediated immune injury in MG.

Adult↗

PubMed1992

Normal renal blood flow measurement using phase-contrast cine magnetic resonance imaging.

RATIONALE AND OBJECTIVES: This study assesses the ability of a cardiac-gated phase-contrast magnetic resonance imaging (MRI) technique to measure renal blood flow (RBF) noninvasively in humans. METHODS: In nine normal volunteers, total RBF in the renal arteries and in the left renal vein was estimated by MRI and correlated with RBF determined by the clearance of para-aminohippuric acid (CPAH) and the hematocrit level. RESULTS: Correlation of RBF estimated from left renal vein flow, with RBF by CPAH-hematocrit, yielded r = .86 (P less than .003). Repeated measurement of RBF by MRI demonstrated a high degree of reproducibility, with coefficients of variation ranging from 4.8% to 8.9%. However, the MRI measurements of arterial flow did not significantly correlate with the standard measurements. CONCLUSIONS: Reproducible noninvasive measurement of normal RBF is possible with the phase-contrast MRI technique used to measure renal venous blood flow.

Adult↗

PubMed1991

Listeriosis surveillance: 1990.

The annual numbers of reports of listeriosis in England, Wales and Northern Ireland received by the PHLS Communicable Disease Surveillance Centre (CDSC) and the Division of Microbiological Reagents (DMR) have shown remarkable changes in recent years. There was a near doubling in 1987 compared to 1986; a further increase in 1988; a sharp decline in 1989 (which occurred in the second half of that year) and, finally, the total in 1990 was the lowest since 1984. The rise and fall particularly (but not exclusively) involved pregnancy-associated cases and illness caused by serotype 4. The epidemiological and clinical features reported in 1990 were otherwise similar to those reported in previous years and in other countries. Patients with the non pregnancy-associated (also called 'adult/juvenile') type were in the majority, most of whom had an underlying disorder associated with impaired immunity. The reason for the changes in reported incidence is not completely understood but is probably due to the emergence and disappearance of a common food source of the organism. There is, however, no cause for complacency. Diagnostic vigilance must be maintained and vulnerable groups should adhere to existing dietary advice.

Adolescent↗