Search PubMed⌕ Search

Biomedical subjects

J Rose

Publications and source records attributed to J Rose.

At least 37 records · Page 2Linked to original sources

Development of a novel, nonimmunogenic, soluble human TNF receptor type I (sTNFR-I) construct in the baboon.

Pharmacokinetics and immunogenicity of six different recombinant human soluble p55 tumor necrosis factor (TNF) receptor I (sTNFR-I) constructs were evaluated in juvenile baboons. The constructs included either an sTNFR-I IgG1 immunoadhesin (p55 sTNFR-I Fc) or five different sTNFR-I constructs covalently linked to polyethylene glycol. The constructs were administered intravenously three times, and pharmacokinetics and immunogenicity were examined over 63 days. All of the constructs were immunogenic, with the exception of a 2.6-domain monomeric sTNFR-I. To evaluate whether the nonimmunogenic 2.6-domain monomeric construct could protect baboons against TNF-alpha-induced mortality, baboons were pretreated with 1, 5, or 10 mg/kg body wt and were compared with baboons receiving either placebo or 1 mg/kg body wt of the dimeric 4.0-domain sTNFR-I construct (n = 3 each) before lethal Escherichia coli bacteremia. The monomeric construct protected baboons and neutralized TNF bioactivity, although greater quantities were required compared with the dimeric 4.0-domain sTNFR-I construct. We conclude that E. coli-recombinant-derived human sTNFR-I constructs can be generated with minimal immunogenicity on repeated administration and still protect against the consequences of exaggerated TNF-alpha production.

Amino Acid Sequence↗

Bereavement education for childcare professionals.

Bereavement is a stressor that affects not only the child but also the whole family. Children need time and support to come to terms with their grief. Current evidence suggests that professionals feel ill equipped to deal with these issues. Inter-professional, multi-agency collaboration and support can provide effective, integrated and supportive services. A 12-day modular course was developed within the Exeter Community Trust and accredited by the University of Plymouth.

Bereavement↗

Ruptured abdominal aortic aneurysms: clinical presentation in Auckland 1993-1997.

BACKGROUND: Rupture of an abdominal aortic aneurysm (RAAA) carries a reported mortality rate in the range of 32-95%. Survival requires prompt diagnosis and surgical management. The presenting features, however, are varied, often insidious and potentially misleading with Osler noting nearly 100 years ago that a correct premortem diagnosis was achieved in only 33% of cases. The present study aims to review our present accuracy in diagnosing this condition and outline demographic and presenting features of patients with RAAA. METHODS: A review was undertaken of hospital and Coroner's files of all patients residing in the Auckland Coronial region who had RAAA between 1 January 1993 and 31 December 1997. RESULTS: Three hundred and twenty-nine cases of RAAA were identified, and they occurred most commonly in the 8th decade. The male:female ratio was 3:1 and at least 73% of patients were Caucasian. The overall mortality was 71%. Nearly half underwent surgery and the hospital averaged mortality rate was 46%. No patient survived without surgery. Classic presenting features of RAAA were absent in many cases. Abdominal pain, back pain and a palpable mass occurred in only 49%, 36% and 18% of patients, respectively. Other common presenting symptoms included vomiting, general malaise and pelvic or hip pain. Forty-three patients (16%) were initially misdiagnosed. CONCLUSIONS: Although our ability to correctly diagnose a RAAA has improved since Osler's time, the initial misdiagnosis rate of 16% leaves no room for complacency. Ruptured abdominal aortic aneurysms must be included in the differential diagnosis of any patient over the age of 55 years who presents with shock, even if the pain is non-specific or atypical.

Aged↗

No confirmation for a causal role of volume-regulated chloride channels in ischemic preconditioning in rabbits.

Volume-regulated chloride channels have recently been proposed to be end-effectors in ischemic preconditioning. The present study attempted to confirm this hypothesis by looking both at cardioprotection and channel activity. In isolated rabbit cardiomyocytes, hypo-osmotic stress (167 mosm/l) induced a current with a magnitude of 2-5 pA/pF at 60 mV. That current could be blocked by the selective chloride channel blockers 5-nitro-2-(3-phenylpropylamino) benzoic acid (NPPB) or indanyloxyacetic acid 94 (IAA-94), but only at 100 microM and 1 m M respectively. Lower concentrations were not effective. Because the channel-blocking concentrations were toxic in isolated perfused rabbit hearts, as evidenced by cessation of cardiac contraction and massive infarction, neither agent could be tested against preconditioning's anti-infarct effect. NPPB and IAA-94 at 1 microM and 10 microM, respectively (the doses used in a previous report), did not affect coronary flow, heart rate and developed pressure, and also did not prevent the infarct size reduction of ischemic preconditioning with 5 min global ischemia/10 min reperfusion preceding 30 min of regional ischemia and 120 min of reperfusion [11. 4(+/-3.6) and (11.1(+/-3.7)% infarction of risk area, respectively]. The volume-regulated chloride and organic osmolyte channel blocker 4, 4;-diisothiocyanostilbene-2,2;-disulfonic acid (DIDS) at 100 microM blocked the hypo-osmotically induced current in myocytes, but again could not be used, since it induced total cessation of cardiac contraction and reduced infarct size in non-preconditioned hearts. Our data do not confirm a prior study on a causal role for volume-regulated chloride channels in the protection of ischemic preconditioning. This hypothesis remains to be adequately tested.

Animals↗

Extending the indications for curative liver resection by portal vein embolization

AIMS: The aim of ipsilateral portal vein embolization is to induce hypertrophy of normal tissue when resection of a cancerous portion of the liver is contraindicated only by the volume of liver that would remain following surgery. This study reports its use in primary and metastatic liver tumours. METHODS: Eight patients with inoperable liver tumours (three women and five men of median age 68. 5 years; three colorectal hepatic metastases, two cholangiocarcinomas and three hepatocellular cancers) were selected for portal vein embolization. Selected portal branches were occluded distally with microbeads and proximally with coils. Liver volumes were determined by magnetic resonance imaging before embolization and again before surgery, 6-8 weeks later. RESULTS: Embolization was performed successfully in seven patients by the percutaneous-transhepatic route; one further patient required an open cannulation of the inferior mesenteric vein. Management was altered in six patients, who proceeded to 'curative' surgery. The projected remaining (predominantly left lobe) liver volumes increased significantly from a median of 350 to 550 ml (P < 0.05, Wilcoxon matched pairs test). Two patients had disease progression such that surgery was no longer indicated. One patient, whose disease progressed, had the left portal branch occluded unintentionally by a misplaced coil that was successfully retrieved, although the left portal branch remained occluded. CONCLUSIONS: Portal vein embolization produced significant hypertrophy of the normal liver and extended the option of 'curative' surgery to six of the eight patients in whom it was attempted. It appears to be equally effective for primary and metastatic liver tumours in selected patients.

Journal Article↗

Pulmonary edema in patients after liver transplantation.

The aim of this study is to determine the incidence of radiological pulmonary edema in elective liver transplant recipients and its relationship to perioperative factors and postoperative course. We reviewed 102 chest radiographs from 34 patients who had undergone orthotopic liver transplantation (OLT). Films were assessed by 2 trained radiologists for evidence of pulmonary edema using a standardized system. Clinical and outcome data from the 34 patients were also recorded. There was a high incidence (47%) of postoperative radiological pulmonary edema that was associated with deterioration in gaseous exchange, elevated pulmonary artery pressure, and increased duration of ventilator dependence and intensive care stay. Eighteen percent of the patients developed edema immediately after surgery, which was associated with greater pulmonary artery pressure and transfusion requirements during surgery. An additional 29% developed edema during the next 16 to 20 hours, but there was no association with fluid replacement. We conclude that pulmonary edema is common after OLT and will influence postoperative recovery in a substantial proportion of transplant recipients. Excess perioperative fluid replacement is unlikely to be the sole mechanism of edema in these patients.

Female↗

Molecular aspects of arrhythmias associated with cardiomyopathies.

The increased risk of sudden cardiac death in patients with myocardial hypertrophy and heart failure is the result of remodeling that occurs in both the myocyte and interstitial compartments of the heart. Action potential prolongation is a hallmark of hypertrophied and failing myocardium and is a consequence of differential expression and function of membrane currents and transporters. Functional downregulation of K currents in the ventricle is a recurring theme in hypertrophy and failure; the reduction in the density of the transient outward current (I(to)) is the most consistent observation, whereas data on the density of the inward (I(K1)) and the delayed rectifier (I(K)) currents are more contradictory. The altered intracellular Ca handling of the myopathic hearts prolongs the decay of the L-type Ca current and favors extrusion of cytosolic Ca2+ via the Na+-Ca2+ exchanger. The interaction between such altered membrane currents and a changed neurohumoral milieu creates a substrate that is highly susceptible to potentially lethal ventricular arrhythmias.

Action Potentials↗

Less afterload sensitivity in short-term hibernating than in acutely ischemic and stunned myocardium.

Short-term hibernating myocardium is characterized by reduced contractile function during persistent moderate ischemia, the recovery of metabolic parameters, and the absence of necrosis. To study the afterload dependence of regional wall excursion in short-term hibernating myocardium, in 11 enflurane-anesthetized swine the left anterior descending coronary artery was cannulated and hypoperfused for 90 min to reduce anterior systolic wall thickening (WT, sonomicrometry) by 60%. Under control conditions, at 5 and 90 min ischemia the descending thoracic aorta was acutely constricted to increase left ventricular (LV) pressure by 30 mmHg. Under control conditions, increased LV pressure resulted in decreased WT [i.e., a negative slope of the relationship between WT and LV end-systolic pressure: -11.2 +/- 4.2 (SD) microm/mmHg]. This slope was further significantly decreased at 5 min ischemia (-26.5 +/- 8.8 microm/mmHg) but returned toward control values in short-term hibernating myocardium at 90 min ischemia (-17.2 +/- 6.6 microm/mmHg). At 30 min reperfusion, the slope was once more significantly decreased (-27.8 +/- 8.1 microm/mmHg). In conclusion, WT in short-term hibernating myocardium is less afterload dependent than in acutely ischemic and reperfused myocardium.

Acute Disease↗

Symbols and their function in managing the anxiety of change: an intersubjective approach.

The author suggests that change inevitably creates anxiety because of loss and confrontation with the unknown. It is proposed that one function of symbols is to manage the anxiety of change. They do this by creating a means by which anxieties can be presented to the subject and then communicated to another mind. These creations are called symbolic because, it is proposed, their purpose is the communication as well as the incorporation of internal anxieties and desires with external exigencies, which might be termed symptoms. Viewing them in this way enables the analyst to put symbolic phenomena as they emerge in an analysis into an intersubjective perspective. The author suggests that thinking of symbols as purely intrasubjective phenomena limits our perspective. It is more technically useful to look at the communicative aspects of symbols as they present themselves to the symbolising subject; and, subsequently, to the analyst in the dialogue within the psychoanalytic setting because the objective and temporal dimension of the setting can thereby be included. Two clinical examples of symbols are discussed, one that was brought for analysis and a second that developed in the course of an analysis. One is given as an example of resistance to change, whereas the other revealed an unconscious drive for change.

Anxiety↗

Nebulised steroid in the treatment of croup: a systematic review of randomised controlled trials.

BACKGROUND: Croup is one of the commonest respiratory complaints among children. There is growing evidence that steroids may be an effective treatment. AIM: To assess the effectiveness of treatment with nebulised steroid for children with croup. METHOD: Systematic review of randomised controlled trials comparing administration of nebulised steroid with placebo. Trials were identified from searches of three bibliographic databases, the Cochrane Controlled Trials Register, correspondence with the manufacturers of nebulised steroid, and one round of manual citation searching. RESULTS: Eight randomised controlled trials were identified including 574 children with mild to severe croup. Overall, the mean age was 25.2 months and 72% of children were male. All trials were hospital-based and of good methodological quality, with adequate concealment of treatment allocation and blind outcome assessment. Children treated with nebulised steroid were significantly more likely to show an improvement in croup score by five hours (combined relative risk = 1.48, 95% confidence interval [CI] = 1.27 to 1.74) and significantly less likely to need hospital admission after attending the emergency department (combined relative risk = 0.56, 95% CI = 0.42 to 0.75) than the placebo group. The funnel plot indicated the presence of publication bias, with smaller studies showing the larger effects, but this could also be owing to less pronounced effects in studies of older children with milder croup. CONCLUSIONS: Nebulised steroids are effective in the treatment of children attending hospital departments with croup. A meta-analysis based on individual patient data could clarify to what extent the effect depends on age and severity of disease. New trials are needed to define the indications for, and effectiveness of, steroid treatment of croup in the community.

Anti-Inflammatory Agents↗

Do out-of-hours co-operatives improve general practitioners' health?

General practitioners (GPs) have been found to have a higher level of anxiety and depression then hospital managers and consultants. In 1995 and 1998, we surveyed GPs in Buckinghamshire. We found that the development of out-of-hours co-operatives was an important factor in the improvement in GPs' health status.

Female↗

Health management in the new millennium. Technology brings value.

Informatics tools and agreements, evidence-based guidelines and principles, narrowed practice variation and better knowledge of appropriate and cost-effective techniques for managing health could allow us to control much of the rising cost of health care arising each year from increases in the volume and intensity of medical services, determined by clinical decisions.

Cost Control↗

Simultaneous X-Ray and TeV Observations of a Rapid Flare from Markarian 421.

Mrk 421 was observed for about 2 days with BeppoSAX in 1998 April as part of a worldwide multiwavelength campaign. A large, well-defined flare was observed in X-rays. The same flare was observed simultaneously at TeV energies by the Whipple Observatory gamma-ray telescope. These data provide (1) the first evidence that the X-ray and TeV intensities are well correlated on timescales of hours and (2) the first exactly simultaneous X-ray and TeV spectra. The results imply that the X-ray and TeV photons derive from the same region and from the same population of relativistic electrons. The physical parameters deduced from a homogeneous synchrotron self-Compton model for the spectral energy distribution yield electron cooling times close to the observed variability timescales.

Journal Article↗

Role of prolactin in regulating the onset of winter fur growth in mink (Mustela vison): A reconsideration.

The objectives of this study were to determine: (1) if the onset of winter hair growth (anagen) in mink could be delayed or inhibited by elevating endogenous PRL concentrations; (2) if bilaterally adrenalectomy (ADX)-induced winter anagen occurs concomitantly with a reduction in serum PRL concentrations, and (3) if exogenous dehydroepiandrosterone (DHEA), an adrenal steroid or Delta(5)-DIOL (a peripherally produced metabolite of DHEA), would delay or inhibit the onset of winter anagen. During early July, while in the resting (telogen) stage of the hair growth cycle, mink were treated with slow release implants containing haloperidol (HAL, a dopaminergic antagonist), melatonin (MEL), deoxycorticosterone (DOC), DHEA and Delta(5)-DIOL. In addition, mink were ADX'd and supplemented with DOC and DHEA. MEL reduced PRL levels to basal levels and induced winter anagen 7 weeks earlier than controls. Surprisingly, HAL initiated winter anagen 7 weeks earlier than controls (P < 0.05), although serum PRL levels were not different between the two groups. Mink that were ADX'd or ADX + DHEA-treated exhibited winter anagen 6 weeks earlier than controls (P < 0.05), but serum PRL concentrations were not different between the three groups. The administration of DHEA or Delta(5)-DIOL to mink with intact adrenals had no effect on the time of onset of winter anagen or serum PRL levels. Our findings suggest that a reduction in circulating PRL levels is not essential for onset of winter anagen in the mink and that the apparent inhibitory effects of the adrenal glands on initiation of winter anagen is not mediated through DHEA or its metabolite Delta(5)-DIOL. J. Exp. Zool. 284:437-444, 1999.

Adrenalectomy↗

Suicide in Auckland 1989 to 1997.

AIM: The aim of this study was to describe the population of people who had committed suicide in Auckland in the nine years, 1989 to 1997. METHODS: We extracted data from the police records to the coroner and the autopsy reports on people who had killed themselves in the Auckland coronial region. RESULTS: Suicide is common and disproportionately affects young men, the unemployed and sickness beneficiaries. Few people who kill themselves appear to be in contact with the mental health services. CONCLUSIONS: For effective prevention, up to date local information on suicide and deliberate self-harm is needed.

Adolescent↗