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Biomedical subjects

C Flood

Publications and source records attributed to C Flood.

At least 19 recordsLinked to original sources

Preliminary outcomes of a trial to reduce conflict and containment on acute psychiatric wards: City Nurses.

Acute psychiatric wards experience high levels of conflict behaviours (violence, absconding, self-harm, rule breaking and medication refusal) by patients. These events cause stress and injury to staff and patients. Their management through containment methods (e.g. sedation, restraint, seclusion) is contentious, and nurses are ambivalent about their use. The aim of this study was to reduce conflict and containment on two acute psychiatric wards through changes in nurses' beliefs, attitudes and practices. Two 'City Nurses' were employed to work with two acute wards for 1 year, assisting with the implementation of changes according to a working model of conflict and containment generation, itself based on previous research. Evaluation was via before-and-after measures. Statistically and clinically significant decreases in conflict occurred, with falls in aggression, absconding and self-harm. Ward atmosphere improved and nurse-patient interaction rates increased. There was no significant change in containment method use. Significant reductions in aggression, absconding and self-harm can be achieved on acute psychiatric wards. However, it does not appear that containment can be reduced, even through large reductions in conflict.

Attitude of Health Personnel↗

Reflections on the process of change on acute psychiatric wards during the City Nurse Project.

The intention of this paper is to discuss the process of therapeutic change on two acute psychiatric wards during a research project that aimed to reduce conflict and containment. Analysis of fieldwork notes, reflection, team discussion and supervision. The City Nurse Project successfully reduced patient aggression, self-harm and absconding. This paper reports on the reflections made over the course of the year as changes and developments to acute wards took place. Specifically discussed are the beneficial effects of an action research approach, the role of the City Nurse, support for ward managers, education and training, clinical supervision as well as difficulties and barriers to the overall process of change. At an interim stage of the project, the staff have shown a willingness to engage in efforts to change and improve two acute wards. This paper shows the potential to improve acute wards and produce positive outcomes using a working model.

Behavior Control↗

Constraints and blocks to change and improvement on acute psychiatric wards--lessons from the City Nurses project.

Recent years have seen sustained criticism and inspection of acute inpatient psychiatric wards, with the publication of reports and research leading to policy developments and a variety of efforts to improve perceived deficits. The City Nurses project seeks to reduce levels of conflict and containment on acute wards through the placement of expert nurses on wards to assist with the implementation of changes according to a working model of conflict and containment generation, based on previous research. Evaluation has shown significant decreases in aggression, absconding and self-harm by patients. However, in the course of working with the wards, various constraints and blocks to change have been identified and we describe these in detail in this paper. Analysis of the fieldwork diaries of the two City Nurses identified that change was hindered by limited staffing resources, problems with the physical environment and other resources, insufficient beds and the process of bed management, hierarchical ambiguity and multidisciplinary issues, the overdemanding role of the ward manager, and pervasive anxiety about the potential for serious untoward incidents and their implications for staff. We argue that sustained positive change in acute inpatient psychiatry requires these underlying structural issues to be both acknowledged and, if possible, resolved.

Acute Disease↗

Short-term cost effectiveness and long-term cost analysis comparing laparoscopic Nissen fundoplication with proton-pump inhibitor maintenance for gastro-oesophageal reflux disease.

BACKGROUND: This study examined the short-term cost-effectiveness and long-term cost of laparoscopic Nissen fundoplication (LNF) versus maintenance proton-pump inhibitor (PPI) medication for severe gastro-oesophageal reflux disease (GORD) based on a randomized clinical trial. METHODS: Costs and outcomes for 12 months were obtained from the first 100 patients in the trial. Detailed costing was performed using resource use data from hospital records and general practitioners' notes. Short-term incremental cost-effectiveness ratios, calculated as the cost difference divided by the effectiveness difference between LNF and PPI therapy, were analysed using net benefit and bootstrap approaches. Long-term cost was examined using sensitivity analyses incorporating published data from other large series. RESULTS: The incremental cost of LNF compared with PPI therapy per additional patient returned to a physiologically normal acid score (less than 13.9) at 3 months was pound5515 (95 per cent confidence interval (c.i.) pound3655 to pound13 400) and the incremental cost per point improvement in combined Gastro-Intestinal and Psychological Well-being score at 12 months was pound293 (90 per cent c.i. pound149 to pound5250). On average, LNF cost pound2247 (95 per cent c.i. pound2020 to pound2473) more than PPI therapy in year 1 and broke even in year 8. Break-even was highly sensitive to hospital unit costs but less sensitive to PPI ingestion rate after LNF, LNF reoperation rate, PPI relapse rate, future PPI price, PPI dose escalation and discount rate. CONCLUSION: From a National Health Service perspective, LNF may be cost-saving after 8 years compared with maintenance PPI therapy for the treatment of GORD.

Cost-Benefit Analysis↗

Retention of atherogenic lipoproteins in atherogenesis.

Atherosclerosis is a multifactorial disease whose pathogenesis is still unclear. Mounting evidence, however, supports the concept that subendothelial retention of apoB100-containing lipoproteins is the initiating event in atherogenesis. Subsequently, a series of biological responses to this retained material leads to specific molecular and cellular processes that promote lesion formation.

Apolipoproteins B↗

A randomized controlled trial of the NEAT expandable tip continence device.

Urethral devices are one conservative management option for stress and mixed urinary incontinence, but there is little published data about their use. The aims of this study were to assess the safety and efficacy of a new urethral device (NEAT) and compare it with the Reliance Insert. The ease of use of both devices was then evaluated. Twenty-four women with mixed or stress urinary incontinence, patients at our tertiary care urogynecology unit and who met the inclusion and exclusion criteria, were enrolled in the study. Study subjects were blinded and randomly assigned to a device group. Device efficacy was assessed by pad weighing at 0 and 4 months. Success was defined as a 50% or greater reduction in urine loss using the formula 100[(pad weight without device -pad weight with device)/pad weight with device]. Safety was evaluated using urinalysis and urine cultures. Ease of use assessment scales were also completed. Eleven patients were randomized to the Reliance Insert and 13 to the NEAT device. There were no significant differences between the two groups in age, height, weight, duration of incontinence, pad weight, leakage score, parity or quality of life score. Based on the pad weight success formula, there was no significant difference in device success between the two groups at 4 months. Women who were postmenopausal had a trend towards a higher level of success in reduction of their pad weight. Previous treatment, diagnosis and hormone replacement therapy all had no relationship to device success. Leakage score data showed that subjects had a significant decrease in urine leakage when using either device. There was no statistically significant difference in ease of use between the two devices. Adverse symptoms most commonly noted were awareness of the device (62.5%), urgency (29.2%), and urethral discomfort or pain (20.8%). One urinary tract infection (UTI) was observed. The most common finding on urinalysis was trace hematuria (15.8%). Our conclusions are that the NEAT device appears to be at least as effective and safe as the Reliance Insert. Both devices are effective at decreasing urine leakage in patients with stress or mixed urinary incontinence. The risk of UTI is low, but these devices may cause trace hematuria.

Equipment Design↗

Transforming growth factor-beta1 in the cerebrospinal fluid of patients with subarachnoid hemorrhage: titers derived from exogenous and endogenous sources.

Transforming growth factor-beta1 (TGF-beta1) is a fibrogenic cytokine that is involved in postinjury repair and is implicated in the etiology of postsubarachnoid hemorrhage (SAH) chronic communicating hydrocephalus. TGF-beta1 was measured by enzyme-linked immunosorbant assay (ELISA) in sequential samples of cerebrospinal fluid (CSF) in 11 patients with hydrocephalus after SAH; levels were seen to be biphasically elevated and sources were investigated. TGF-beta1 levels were compared with albumin levels that estimated CSF blood content. Control samples from nonhemorrhagic hydrocephalics were tested similarly. Mean total TGF-beta1 levels were elevated to 4400+/-3435 (+/-SD) pg/mL greater than control levels of 97+/-42 at 1 to 2 days posthemorrhage. Thereafter, levels fell to 714+/-401 by 5 to 6 days posthemorrhage, then rose to a second peak of 1667+/-774 at 9 to 10 days posthemorrhage, remaining significantly increased until 19 days posthemorrhage (P = 0.007). The first peak probably derived from extravasated platelets and correlated with increased albumin levels in the CSF. The second TGF-beta1 peak rose greater than CSF albumin levels that had stabilized at this time, and thus was attributed to a tissue-specific response rather than a re-bleed. TGF-beta1 was detected in the choroid secretory epithelium from controls, but levels were greater in SAH patients at 10 to 12 days posthemorrhage. The authors conclude that the elevated levels of TGF-beta1 in CSF after SAH are derived initially from blood and later from endogenous sources such as the choroid plexus.

Adult↗

Role of extracellular retention of low density lipoproteins in atherosclerosis.

The pathogenesis for atherosclerosis is still unclear, and several hypotheses have been articulated to explain the initiating events in atherogenesis. Although these hypotheses are by no means mutually exclusive, there is a growing body of recent evidence that has led to the concept that subendothelial retention of apolipoprotein B100-containing lipoproteins is the initiating event in atherogenesis. Subsequently, a series of biological responses to this retained material leads to specific molecular and cellular processes that promote lesion formation. The present review assesses some of the studies that support this concept.

Animals↗

The metabolism of estrone sulfate in the female rhesus monkey.

In order to study the metabolism of estrone sulfate in the adult female rhesus monkey, we gave four monkeys a pulse injection of [3H]estrone sulfate and obtained blood samples at 15, 30, 60, 120, 300, and 1,440 minutes after the pulse. All blood samples were analyzed for [3H]estrone sulfate. The mean +/- SE for the initial volume of distribution was 4.6 +/- 0.9 L. The mean metabolic clearance rate (MCR) was 42.0 +/- 2.9 L/day. In addition, 2 monkeys were infused for 240 minutes with [3H]estrone sulfate and 5 monkeys were infused for 240 minutes with [3H]estrone sulfate/[14C]estrone. Three blood samples were obtained during the last hour of the infusions and analyzed for radioactivity as estrone sulfate, estrone, and estradiol, and MCRs, conversion ratios, and [rho]BB values were calculated. The mean +/- SE for the MCR was 67.5 +/- 8.3 L/day, and for the conversion ratio, estradiol to estrone sulfate was 0.054 +/- 0.016. The mean [rho]BB value for estrone sulfate conversion to estrone was 43.6 +/- 3.4% and for estrone conversion to estrone sulfate was 33.5 +/- 6.6%. Thus estrone sulfate is cleared slowly and is converted to both estrone and estradiol. The hydrolysis of estrone sulfate to estrone is not significantly different than the conversion of estrone to estrone sulfate.

Animals↗

The effects of ovariectomy and progesterone on peripheral aromatization in the female rhesus monkey.

We investigated the acute effects of surgery, i.e. ovariectomy, the long-term effects of ovariectomy, and the effects of progesterone on the peripheral aromatization of androstenedione in rhesus monkeys (Macaca mulatta). For the acute effects of surgery, 7 rhesus monkeys were given a pulse of [3H]androstenedione/[14C]estrone 2 weeks before and immediately after ovariectomy. In each case all urine was collected for 4 days and analyzed for radioactivity as estrone glucuronide and the peripheral aromatization calculated from the isotope ratios. Similarly, 5 monkeys were studied before and 18 months after ovariectomy. The acute effects of surgery resulted in a significant decrease in the peripheral aromatization of androstenedione to estrone from a mean +/- SE of 0.94 +/- 0.26 to 0.61 +/- 0.19%, P = 0.0452. Conversely, the long-term effects of ovariectomy resulted in a significant increase in peripheral aromatization from 0.38 +/- 0.06 to 0.67 +/- 0.12%, P = 0.0207. In 7 monkeys the peripheral aromatization was measured before and 10 days after the administration of progesterone, 100 mg in oil. There was no difference in peripheral aromatization before, 0.62 +/- 0.04% and after progesterone, 0.58 +/- 0.05%, P = 0.10. We conclude that the acute stress of ovariectomy, or possibly the loss of ovarian aromatizing tissue, results in a decline in peripheral aromatization, but ovariectomy will have the long-term effect of an increase in aromatization, and that the presence or absence of progesterone does not play a role.

Androstenedione↗

Hyperventilation in head injury does it do more harm than good?

During the past decade the management of clients with severe head injuries has been influenced by the use of hyperventilation. Increased intracranial pressure (I.C.P.) is the major cause of death following head injury and outcome has been linked to the ability of the practitioner to control intracranial hypertension. Hyperventilation is one method that is frequently employed to control increases in I.C.P. There is no doubt that hyperventilation effectively reduces intracranial pressure, but controversy surrounds the influence that this procedure may inflict upon the cerebral hemodynamic reserve (C.H.R.). The literature indicates that in spite of normal cerebral perfusion pressure, associated with raised I.C.P., that C.H.R. may be compromised. This paper will examine the controversy that surrounds the use of hyperventilation in the client with severe head injury.

Cerebrovascular Circulation↗

Toronto-Rochester Depression study of 116 HLA-typed kindreds.

The Toronto-Rochester Depression study consisted of 116 pedigrees ascertained for multiple cases of major affective disorders. Among the 857 psychiatrically evaluated family members, of whom more than 85% were given a structured interview, 363 had major affective disorder by Research Diagnostic Criteria and 385 had no history of psychological aberration. HLA region genes were typed in 804 of these persons.

Canada↗

Confirmation of the relationship of HLA (chromosome 6) genes to depression and manic depression. II. The Ontario follow-up and analysis of 117 kindreds.

HLA typing was conducted on 577 family members of 86 families having at least two first-degree family members with a lifetime history of major depression or bipolar disorder. The results were combined with a follow-up study of 10 Newfoundland kindreds and with the data obtained from our previous studies, giving a total cohort of 117 families of diverse ethnic and geographic origin. There was increased sharing of HLA haplotypes, as compared with random expectation, over all possible pairwise comparisons both in the follow-up studies (P less than 0.025) and in the total data (P less than 0.01). The increase in HLA haplotype sharing over random expectation was greater if comparisons within heavily loaded sibships (by prior convention, sibships with three or more affected siblings) were omitted from the analysis (P less than 0.002). There was also non-random transmission of HLA haplotypes in 50 families selected for a low-load, unaffected parent (P less than 0.005). Thus, we conclude that genes in the HLA region of chromosome 6 constitute one of the elements in the multifactorial etiology of affective disorder. This conclusion does not depend on any assumption concerning genetic heterogeneity or epistasis or on specific modes of transmission, penetrance values or linkage distances. In addition, the data suggest that chromosome 6 region genes may have a different effect in unipolar and bipolar illness.

Bipolar Disorder↗

The relationship of HLA to depression and manic depression. I. The Newfoundland follow-up.

This report constitutes the Newfoundland component of a large scale replication study to assess the relationship of HLA to affective disorders; the Ontario component will be published subsequently. In a collaborative study between the University of Toronto, Memorial University and the University of Rochester, first degree family members of Probands with major affective disorder in Newfoundland were assessed for the lifetime presence of psychiatric disorder; their blood was also typed for Human Leucocyte Antigens (HLA). Because of the high rate of refusal to participate, only 10 Newfoundland families could be assessed completely. While this number of families is too small to evaluate the role of HLA as a marker of susceptibility to affective disorder, the results will be added to those of the larger Ontario component. Some problems of conducting research in communities similar to those found in Newfoundland are briefly discussed in the context of characteristics of the Probands in the study group as compared with those of subjects who refused entry into the study.

Adult↗

5 alpha-reductase activity in rat adipose tissue.

We measured the 5 alpha-reductase activity in isolated cell preparations of rat adipose tissue using the formation of [3H]dihydrotestosterone from [3H]testosterone as an endpoint. Stromal cells were prepared from the epididymal fat pad, perinephric fat, and subcutaneous fat of male rats and from perinephric fat of female rats. Adipocytes were prepared from the epididymal fat pad and perinephric fat of male rats. Stromal cells from the epididymal fat pad and perinephric fat contained greater 5 alpha-reductase activity than did the adipocytes from these depots. Stromal cells from the epididymal fat pad contained greater activity than those from perinephric and subcutaneous depots. Perinephric stromal cells from female rats were slightly more active than those from male rats. Estradiol (10(-8) M), when added to the medium, caused a 90% decrease in 5 alpha-reductase activity. Aromatase activity was minimal, several orders of magnitude less than 5 alpha-reductase activity in each tissue studied.

3-Oxo-5-alpha-Steroid 4-Dehydrogenase↗

Steroid dynamics in the rabbit.

Male rabbits were infused at a constant rate with 3H-androstenedione/14C-estrone (n = 5) or 3H-testosterone/14C-estradiol-17 beta (n = 3) for 3 1/2 hr and blood samples were obtained over the last hour and analyzed for radioactivity as androstenedione (A), testosterone (T), estrone (E1), estradiol-17 beta (E2 beta) and estradiol-17 alpha (E2 alpha). The mean value for the metabolic clearance rate of androstenedione (MCRA) was 85 +/- 10 l/day/kg, which was significantly greater than the mean MCRE1 59 +/- 10 l/day/kg. MCRT, 42 +/- 8 l/day/kg, and MCRE2 beta, 45 +/- 9 l/day/kg were not different. The conversion ratio of androstenedione to testosterone (CRA,T) was greater than CRT,A but for the estrogens, CRE2 beta, E1 was greater than CRE1,E2 beta. CRE2 beta, E2 alpha was greater than CRE1,E2 alpha. The overall aromatization of androstenedione to estrone, the fraction of 3H-androstenedione infused into the blood and measured as 3H-estrone in blood [( rho]A,E1BB) was 0.0005 +/- 0.0001 and for [rho]T,E2 beta BB was 0.0012 +/- 0.0006. In the rabbit both sex hormone binding globulin (SHBG) and albumin binding may effect the MCRs, and peripheral aromatization of androgens occurs to a far lesser degree than in humans and primates.

Androstenedione↗

The occurrence of secondary affective disorder in an in-patient population with severe and recurrent affective disorder.

One hundred and eighty nine consecutive in-patients with treatment-resistant affective disorder were administered the Renard Diagnostic Interview to determine whether the 45 with secondary affective disorder (SAD) differed from the 144 with primary affective disorder (PAD). The SAD group, including 15 subjects with bipolar disorder, had an earlier mean age of onset of depression and contained more unmarried individuals. The total secondary group could not usefully be differentiated by assessment of clinical symptoms or discriminating analysis of social and clinical variables. While the present study of a severely depressed population does not lend itself to generalisability, this combined sample does have characteristics of patients used in biological investigations. No significant inter-group discrimination was found to support a previous assumption that identification of a prior psychiatric disorder provides the most suitable mechanism for selecting a population for research in affective disorders.

Adult↗

Metabolism of 2-methoxyestrone in normal men.

We studied, in four normal men, the metabolism of 2-methoxyestrone (2-MeOE1) using pulse injections of either [3H]2MeOE1 (two men) or [14C]methoxy-2-MeOE1 plus [3H]2-MeOE1 (two men) by analysis of blood samples drawn at increasing time intervals after the pulse and of urine collected for 5 days. The disappearance from the blood of radioactivity as 2-MeOE1 could be characterized as a function that was the sum of three exponentials. The mean +/- SE value for the initial volume of distribution was 32 +/- 9 liters, and the mean MCR was 2470 +/- 770 liters/day. The disappearance of total 3H radioactivity from the blood was considerably slower, with a mean MCR of 290 +/- 30 liters/day, indicating the presence of a slowly turning over pool of 2-MeOE1 metabolites, probably including the 2-MeOE1 3-sulfate conjugate. The disappearance of total 14C radioactivity was slower than that of total 3H, indicating considerable demethylation of 2-MeOE1 with a very slow excretion of 14C from the released methyl group. In none of the subjects could we find in the blood radioactivity as unconjugated [3H]2-hydroxyestrone ( [3H]2-OHE1). However, examination of the urine indicated that considerable demethylation of [3H]2-MeOE1 had occurred. At least 64% of the urinary 3H-containing metabolites from the mixed dose had lost the 14C-bearing methoxylcarbon atom. The fractionated metabolites were qualitatively and quantitatively similar to those found earlier for [3H]2-OHE1. We conclude that 2-MeOE1, which of itself has little biological activity, can act as a pool of potentially active 2-OHE1 in the tissues.

Adult↗