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Biomedical subjects

A Farley

Publications and source records attributed to A Farley.

At least 19 recordsLinked to original sources
PubMed2003

Efficacy and safety of single-triple capsules of bismuth biskalcitrate, metronidazole and tetracycline, given with omeprazole, for the eradication of Helicobacter pylori: an international multicentre study.

BACKGROUND: The high prevalence of Helicobacter pylori resistance to metronidazole demands treatments more effective than standard bismuth-based triple therapy against these strains. AIM: To evaluate the H. pylori eradication rate in both metronidazole-sensitive and -resistant strains following quadruple therapy using single-triple capsules of bismuth biskalcitrate, metronidazole and tetracycline, given with omeprazole. METHODS: One hundred and seventy valid patients with duodenal ulcer, gastric ulcer or non-ulcer dyspepsia were treated in eight centres located in five countries. H. pylori was confirmed at baseline using 13C-urea breath test, histology and/or culture. Patients received three single-triple capsules q.i.d. and omeprazole, 20 mg b.d., for 10 days. Each capsule contained bismuth biskalcitrate, 140 mg (as 40 mg Bi2O3 equivalent), metronidazole, 125 mg, and tetracycline, 125 mg. 13C-Urea breath test was repeated at least 4 and 8 weeks post-treatment. RESULTS: Overall eradication rates were 93% (158/170) by modified intention-to-treat analysis and 97% (142/146) by per protocol analysis. Eradication rates were 93% (40/43) and 95% (38/40) for strains resistant to metronidazole and 95% (82/86) and 99% (75/76) for strains sensitive to metronidazole by modified intention-to-treat and per protocol analysis, respectively. CONCLUSION: This omeprazole-bismuth biskalcitrate-metronidazole-tetracycline 10-day regimen is a very effective and well-tolerated treatment, which overcomes metronidazole resistance.

Adolescent↗
PubMed2001

Nasogastric feeding in children and adolescents with eating disorders: toward good practice.

OBJECTIVE: This study aimed to provide an insight into the subjective experiences of nasogastric feeding from the perspective of patients with eating disorders and their parents. METHOD: A semistructured self-report questionnaire was completed by patients from two specialist eating disorders units who had received nasogastric feeding. Parents' views were also assessed via a similar self-report questionnaire. RESULTS: Diverse views were expressed by both patients and parents. Some regarded the experience of nasogastric feeding as wholly negative, but acknowledged the lack of suitable alternatives. Others had a more positive view and identified several helpful aspects. CONCLUSION: Reactions were generally more positive than had been anticipated. A number of useful suggestions were made regarding how to improve the procedure. These have informed the development of guidelines for good practice.

Adolescent↗
PubMed2001

The effect of 2,3,7,8-tetrachlorodibenzo-p-dioxin on corticotrophin-releasing hormone, arginine vasopressin, and pro-opiomelanocortin mRNA levels in the hypothalamus of the cynomolgus monkey.

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is a widespread environmental contaminant that has profound deleterious effects on development and reproduction. TCDD may act at one or more levels to alter the hypothalamic-pituitary-adrenal (HPA) and hypothalamic-pituitary-gonadal (HPG) axes. The objective of this study was to investigate whether TCDD modulates neuroendocrine systems by altering gene expression of arginine vasopressin (AVP), corticotrophin-releasing hormone (CRH), or pro-opiomelanocortin (POMC), which are important neuroregulators of the HPA and HPG axes. Four groups of female cynomolgus monkeys (Macaca fascicularis) were administered daily oral doses of gelatin capsule containing TCDD (0, 1, 5, or 25 ng/kg body weight) mixed with glucose 5 days a week for 1 year. At the end of the dosing period, animals were euthanized and brains were harvested. CRH, AVP, and POMC mRNA levels were semiquantified by in situ hybridization histochemistry on 30-microm coronal sections of the brain. Blood collected on the day of euthanasia was assayed for cortisol and progesterone. CRH mRNA levels in the paraventricular nucleus (PVN) were significantly increased by the 2 higher TCDD doses (5 and 25 ng/kg/day) compared to controls (p < 0.05). There was a trend towards increased AVP mRNA levels in both the supraoptic nucleus (SON) and PVN. No effect of TCDD on POMC was observed. Cortisol levels were significantly increased in TCDD-exposed animals. Progesterone concentrations and menstruation data indicated that TCDD did not interfere with ovulation. We conclude that TCDD stimulated the HPA axis by a central effect involving CRH, but had no effect on the HPG axis at the doses tested.

Administration, Oral↗
PubMed2001

The role of gown and glove isolation and strict handwashing in the reduction of nosocomial infection in children with solid organ transplantation.

OBJECTIVE: Nosocomial infection is an important contributor to morbidity and mortality in pediatric solid organ transplantation. The relative effect of protective gown and glove isolation was compared with strict handwashing in pediatric intensive care unit (PICU) patients with solid organ transplantation. DESIGN/SETTING: A prospective, randomized design was used; children in a 23-bed PICU with solid organ transplantation were enrolled into a gown and glove protective isolation protocol or a strict handwashing protocol. PATIENTS: All children admitted to the PICU immediately after solid organ transplantation, excluding renal transplantation, and at subsequent readmissions to the PICU were eligible for the study. Children with current infection or known exposure to varicella were excluded from the study initially or at readmission. INTERVENTIONS: By using a block randomization design based on organ transplanted, age, and initial admission vs. readmission, each patient was randomized to either strict handwashing or protective gown and glove isolation intervention groups. MEASUREMENTS: We analyzed demographics, infection outcomes (defined according to Centers for Disease Control criteria), and monitoring of patient contacts in compliance with protocols. RESULTS: The infection rate in the overall PICU population did not change significantly from the year before the study compared with during the study (2.1 per 100 vs. 1.95 per 100 patient days; p =.4) The infection rate in the gown and glove group (2.3 per 100 patient days) was reduced significantly compared with the prestudy infection rate in the transplant population (4.9 per 100 patient days; p =.0008). Strict handwashing also significantly reduced the infection rate in the transplant population (3.0 per 100 patient days; p =.008). Compliance with gowning and gloving was 82% and compliance with handwashing was 76% (compared with 22% before study [p <.0001] and 52% after the study [p <.0001]). Despite an increased mean length of stay in the PICU in the gown and glove group (p =.014), there was a trend toward reduction in the incidence of infection (Fisher's exact test, p =.07; odds ratio,.76) in the gown and glove group. CONCLUSIONS: Increased compliance with handwashing was associated with a reduction in nosocomial infections, and gown and glove isolation appeared to have an additional protective effect. Some nosocomial infections may be preventable in the pediatric solid organ transplantation population.

Child↗
PubMed2001

Bismuth-based quadruple therapy with bismuth subcitrate, metronidazole, tetracycline and omeprazole in the eradication of Helicobacter pylori.

BACKGROUND: A previous study showed that 14 days of qid bismuth-based triple therapy with tetracycline 500 mg, metronidazole 250 mg and colloidal bismuth subcitrate 120 mg resulted in excellent Helicobacter pylori eradication rates (89.5%). The present study looked at a shorter treatment period by adding omeprazole and by reducing the dose of tetracycline. METHODS: One hundred sixty-one patients with H pylori confirmed by histology and (13)carbon urea breath test were included in the study. They were treated for seven days with bismuth subcitrate 120 mg plus metronidazole 250 mg plus tetracycline 250 mg qid plus omeprazole 20 mg bid (OBMT). Patients were 18 to 75 years of age and had dyspepsia with or without a history of peptic ulcer. Patients with irritable bowel syndrome, active ulcer or previous attempt at eradication, or those who had used antibiotics or antiulcer drugs in the previous 30 days were excluded. Eradication was determined by two (13)carbon urea breath tests done one and three months, respectively, after treatment. Strains with minimal inhibitory concentrations of 8 microg/mL or higher were considered to be resistant to metronidazole. RESULTS: The overall per protocol eradication rate was 84%-89.5% in metronidazole-sensitive and 70.8% in metronidazole-resistant strains. Modified intent-to-treat analysis resulted in a 80% eradication rate--82.5% in metronidazole-sensitive and 66.7% in metronidazole-resistant strains. Only one patient discontinued treatment because of adverse events. CONCLUSIONS: The OBMT regimen used in this study is safe and effective against metronidazole-sensitive H pylori strains.

Adolescent↗
PubMed2000

Suppressor of cytokine signaling-3 preferentially binds to the SHP-2-binding site on the shared cytokine receptor subunit gp130.

Suppressor of cytokine signaling-3 (SOCS-3) is one member of a family of intracellular inhibitors of signaling pathways initiated by cytokines that use, among others, the common receptor subunit gp130. The SH2 domain of SOCS-3 has been shown to be essential for this inhibitory activity, and we have used a quantitative binding analysis of SOCS-3 to synthetic phosphopeptides to map the potential sites of interaction of SOCS-3 with different components of the gp130 signaling pathway. The only high-affinity ligand found corresponded to the region of gp130 centered around phosphotyrosine-757 (pY757), previously shown to be a docking site for the tyrosine phosphatase SHP-2. By contrast, phosphopeptides corresponding to other regions within gp130, Janus kinase, or signal transducer and activator of transcription proteins bound to SOCS-3 with weak or undetectable affinity. The significance of pY757 in gp130 as a biologically relevant SOCS-3 docking site was investigated by using transfected 293T fibroblasts. Although SOCS-3 inhibited signaling in cells transfected with a chimeric receptor containing the wild-type gp130 intracellular domain, inhibition was considerably impaired for a receptor carrying a Y-->F point mutation at residue 757. Taken together, these data suggest that the mechanism by which SOCS-3 inhibits the gp130 signaling pathway depends on recruitment to the phosphorylated gp130 receptor, and that some of the negative regulatory roles previously attributed to the phosphatase SHP-2 might in fact be caused by the action of SOCS-3.

Amino Acid Sequence↗
PubMed2000

Rabeprazole versus ranitidine for the treatment of erosive gastroesophageal reflux disease: a double-blind, randomized clinical trial. Raberprazole Study Group.

OBJECTIVE: The objective of this study was to compare the efficacy and safety of the proton pump inhibitor rabeprazole to that of the histamine-2 (H2)-receptor antagonist ranitidine in the treatment of erosive gastroesophageal reflux disease. The primary indicator of efficacy was the absence of esophageal erosions or ulcerations as determined by posttreatment endoscopy. Secondary indicators of efficacy included improvement in frequency and severity of daytime and nighttime heartburn. METHODS: A total of 338 patients were enrolled and randomly assigned to therapy with rabeprazole 20 mg once daily in the morning or to ranitidine 150 mg four times daily. At baseline and at 4 wk, patients underwent endoscopy for evaluation of esophageal lesions. Patients whose lesions healed by wk 4 had therapy discontinued; others remained on therapy and had repeat endoscopy at 8 wk. Also recorded at study visits were patients' ratings of heartburn symptoms and overall sense of well being, patients' reports of time lost from daily activities, antacid use, and adverse events. Serum gastrin levels were measured and argyrophil enterochromaffin-like cell histology evaluated at baseline and when the patient ended therapy. RESULTS: At wk 4, healing was observed in 59% (98/167) of patients assigned to rabeprazole therapy, compared with 36% (60/169) of those receiving ranitidine (p < 0.001). By 8 wk, healing was seen in 87% (146/167) and 66% (112/169) of patients in the rabeprazole and ranitidine groups, respectively (p < 0.001). There were also significant differences between the two groups favoring rabeprazole with respect to resolution or improvement of heartburn symptoms and improvement in sense of well-being. No drug-related serious adverse events were seen with either therapy; fewer patients assigned to rabeprazole had treatment-emergent signs and symptoms. Serum gastrin levels increased over baseline in the rabeprazole group, but the mean value remained within normal limits. CONCLUSIONS: Rabeprazole was superior to ranitidine in esophageal healing and symptom relief in patients with erosive gastroesophageal reflux disease, and was equally well tolerated.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed1999

Suckling defect in mice lacking the soluble haemopoietin receptor NR6.

Cytokines control a variety of cellular responses including proliferation, differentiation, survival and functional activation, via binding to specific receptors expressed on the surface of target cells [1]. The cytokine receptors of the haemopoietin family are defined by the presence of a conserved 200 amino acid extracellular domain known as the haemopoietin domain [2]. We report here the isolation of NR6, a haemopoietin receptor that, like the p40 subunit of interleukin-12 (IL-12) [3] and the EBI3 gene induced by Epstein-Barr virus infection in lymphocytes [4], contains a typical haemopoietin domain but lacks transmembrane and cytoplasmic domains. Although in situ hybridisation revealed NR6 expression at multiple sites in the developing embryo, mice lacking NR6 did not display obvious abnormalities and were born in the expected numbers. Neonatal NR6(-/-) mice failed to suckle, however, and died within 24 hours of birth, suggesting that NR6 is necessary for the recognition or processing of pheromonal signals or for the mechanics of suckling itself. In addition, NR6(-/-) mice had reduced numbers of haemopoietic progenitor cells, suggesting a potential role in the regulation of primitive haemopoiesis.

Amino Acid Sequence↗
PubMed1999

The conserved SOCS box motif in suppressors of cytokine signaling binds to elongins B and C and may couple bound proteins to proteasomal degradation.

The suppressors of cytokine signaling (SOCS) family of proteins act as intracellular inhibitors of several cytokine signal transduction pathways. Their expression is induced by cytokine activation of the Janus kinase/signal transducer and activator of transcription (JAK/STAT) pathway and they act as a negative feedback loop by subsequently inhibiting the JAK/STAT pathway either by direct interaction with activated JAKs or with the receptors. These interactions are mediated at least in part by the SH2 domain of SOCS proteins but these proteins also contain a highly conserved C-terminal homology domain termed the SOCS box. Here we show that the SOCS box mediates interactions with elongins B and C, which in turn may couple SOCS proteins and their substrates to the proteasomal protein degradation pathway. Analogous to the family of F-box-containing proteins, it appears that the SOCS proteins may act as adaptor molecules that target activated cell signaling proteins to the protein degradation pathway.

Amino Acid Sequence↗
PubMed1999

Mutational analyses of the SOCS proteins suggest a dual domain requirement but distinct mechanisms for inhibition of LIF and IL-6 signal transduction.

SOCS-1 (suppressor of cytokine signaling-1) is a representative of a family of negative regulators of cytokine signaling (SOCS-1 to SOCS-7 and CIS) characterized by a highly conserved C-terminal SOCS box preceded by an SH2 domain. This study comprehensively examined the ability of several SOCS family members to negatively regulate the gp130 signaling pathway. SOCS-1 and SOCS-3 inhibited both interleukin-6 (IL-6)- and leukemia inhibitory factor (LIF)-induced macrophage differentiation of murine monocytic leukemic M1 cells and LIF induction of a Stat3-responsive reporter construct in 293T fibroblasts. Deletion of amino acids 51-78 in the N-terminal region of SOCS-1 prevented inhibition of LIF signaling. The SOCS-1 and SOCS-3 N-terminal regions were functionally interchangeable, but this did not extend to other SOCS family members. Mutation of SH2 domains abrogated the ability of both SOCS-1 and SOCS-3 to inhibit LIF signal transduction. Unlike SOCS-1, SOCS-3 was unable to inhibit JAK kinase activity in vitro, suggesting that SOCS-1 and SOCS-3 act on the JAK-STAT pathway in different ways. Thus, although inhibition of signaling by SOCS-1 and SOCS-3 requires both the SH2 and N-terminal domains, their mechanisms of action appear to be biochemically different.

Animals↗
PubMed1999

Suppressors of cytokine signaling (SOCS): negative regulators of signal transduction.

SOCS-1 was originally identified as an inhibitor of interleukin-6 signal transduction and is a member of a family of proteins (SOCS-1 to SOCS-7 and CIS) that contain an SH2 domain and a conserved carboxyl-terminal SOCS box motif. Mutation studies have established that critical contributions from both the amino-terminal and SH2 domains are essential for SOCS-1 and SOCS-3 to inhibit cytokine signaling. Inhibition of cytokine-dependent activation of STAT3 occurred in cells expressing either SOCS-1 or SOCS-3, but unlike SOCS-1, SOCS-3 did not directly interact with or inhibit the activity of JAK kinases. Although the conserved SOCS box motif appeared to be dispensable for SOCS-1 and SOCS-3 action when overexpressed, this domain interacts with elongin proteins and may be important in regulating protein turnover. In gene knockout studies, SOCS-1(-/-) mice were born but failed to thrive and died within 3 weeks of age with fatty degeneration of the liver and hemopoietic infiltration of several organs. The thymus in SOCS-1(-/-) mice was small, the animals were lymphopenic, and deficiencies in B lymphocytes were evident within hemopoietic organs. We propose that the absence of SOCS-1 in these mice prevents lymphocytes and liver cells from appropriately controlling signals from cytokines with cytotoxic side effects.

Animals↗
PubMed1999

The DU-MACH study: eradication of Helicobacter pylori and ulcer healing in patients with acute duodenal ulcer using omeprazole based triple therapy.

AIM: To investigate the efficacy of two omeprazole triple therapies for the eradication of Helicobacter pylori, ulcer healing and ulcer relapse during a 6-month treatment-free period in patients with active duodenal ulcer. METHODS: This was a double-blind, randomized study in 15 centres across Canada. Patients (n = 149) were randomized to omeprazole 20 mg once daily (O) or one of two 1-week b. d. eradication regimens: omeprazole 20 mg, metronidazole 400 mg and clarithromycin 250 mg (OMC) or omeprazole 20 mg, amoxycillin 1000 mg and clarithromycin 500 mg (OAC). All patients were treated for three additional weeks with omeprazole 20 mg once daily. Ulcer healing was assessed by endoscopy after 4 weeks of study therapy. H. pylori eradication was determined by a 13C-urea breath test and histology, performed at pre-entry, at 4 weeks after the end of all therapy and at 6 months. RESULTS: The intention-to-treat (intention-to-treat) analysis contained 146 patients and the per protocol (per protocol) analysis, 114 patients. The eradication rates were (intention-to-treat/per protocol): OMC-85% and 92%, OAC-78% and 87% and O-0% (O). Ulcer healing (intention-to-treat) was greater than 90% in all groups. The differences in the eradication and relapse rates between O vs. OMC and O vs. OAC were statistically significant (all, P < 0.001). Treatment was well tolerated and compliance was high. CONCLUSION: The OMC and OAC 1-week treatment regimens are safe and effective for eradication, healing and the prevention of relapse in duodenal ulcer patients.

Acute Disease↗
PubMed1999

Comparison of ranitidine bismuth citrate plus clarithromycin with omeprazole plus clarithromycin for the eradication of Helicobacter pylori.

BACKGROUND: Many dual and triple therapy treatment regimens have been proposed for the eradication of Helicobacter pylori. However, assessing the relative efficacy of these regimens is complicated by differences in study design, and few well-controlled comparative studies have been reported. METHODS: This multicentre, randomized, double-blind study involved 530 duodenal ulcer patients, of whom 520 had confirmed H. pylori infection. Patients received 14 days b.d. dual therapy of either ranitidine bismuth citrate (RBC) 400 mg or omeprazole 20 mg, both with clarithromycin 500 mg to eradicate H. pylori, followed by a further 14 days of treatment with RBC 400 mg b. d. or omeprazole 20 mg o.d. to facilitate ulcer healing. H. pylori eradication and ulcer healing were assessed at least 26 days after the end of treatment. Adverse events were recorded throughout the study. RESULTS: H. pylori was eradicated in 90% of patients who received RBC with clarithromycin and in 66% of patients who received omeprazole with clarithromycin (per protocol; P<0.001). intention-to-treat eradication rates were 77% and 60%, respectively (P<0.001). Ulcer healing rates were 97% in the RBC treatment group and 95% in the omeprazole treatment group. Only 3% and 1% of patients in the RBC and omeprazole treatment groups, respectively, were withdrawn due to adverse events. CONCLUSIONS: RBC with clarithromycin is a simple and highly effective dual therapy regimen for the eradication of H. pylori, and is significantly more effective than omeprazole with clarithromycin. Both treatment regimens are well tolerated and effectively heal duodenal ulcers.

Adolescent↗
PubMed1998

Influence of sex, age and smoking status on patient comfort during gastroscopy with pharyngeal anesthesia by a new benzocaine-tetracaine preparation.

Thirty-seven patients underwent gastroscopy under pharyngeal anaesthesia with benzocaine-tetracaine (Endospray; Axcan Pharma). Patients recorded their perception of intubation, of the rest of the procedure, of taste and of throat well-being on visual analogue scales. Throat well-being and taste scores were better for men than for women. There was a strong trend for smokers to be more intolerant to intubation than nonsmokers. There was a weak but significant correlation for younger patients to be more intolerant to intubation. This study points to age and smoking status as possible factors influencing the perception of gastroscopy under pharyngeal anesthesia.

Adult↗
PubMed1998

[Integrated occupational work capacity evaluation in medical rehabilitation--experiences and prospects exemplified by psychosomatic rehabilitation].

Psychosomatic rehabilitation is often initiated when lasting work disability, loss of job, and pension application have occurred. After a review of the relevance of vocational strains and of predictors for reintegration, we present a model of an integrated work hardening programme in Psychosomatic Rehabilitation. Results for 64 patients are illustrated by case vignettes. Especially when lasting work disability and unemployment have undermined the patients' sense of competence and endurance, work hardening promotes return to work, realistic self-appraisal and vocational reorientation. The social and medical assessment and the coordination of vocational rehabilitation measures are improved. The implementation of a work hardening programme requires the provision of a variety of (unpaid) work opportunities, independent assessment of work performance by supervisors and social worker, psychological support and close cooperation with rehabilitation services.

Adolescent↗
PubMed1997

Teaching practical skills: a guide for preceptors.

Concern has been expressed that recently qualified nurses may be deficient in clinical skills. In this article the authors explore psychomotor skills learning and suggest strategies to support preceptors who have responsibility for developing such skills in students. The advice should prove helpful to clinical staff who are involved in teaching clinical skills to nursing students.

Clinical Competence↗
PubMed1997

Efficacy of thermal treatment and copper-silver ionization for controlling Legionella pneumophila in high-volume hot water plumbing systems in hospitals.

BACKGROUND: Thermal treatment and copper-silver ionization are often used for controlling Legionella pneumophila in high-volume hospital plumbing systems, although the comparative efficacies of these measures in high-volume systems are unknown. METHODS: Thermal treatment of a hot water circuit was accomplished by flushing hot water (> 60 degrees C) through distal fixtures for 10 minutes. Copper-silver ionization was conducted in three circuits by installing units into return lines immediately upstream from hot water tanks. Recovery rates of L. pneumophila were monitored by culturing swab samples from faucets. Concentrations of copper and silver in water samples were determined by atomic absorption spectrophotometry. RESULTS: Four heat-flush treatments failed to provide long-term control of L. pneumophila. In contrast, ionization treatment reduced the rate of recovery of L. pneumophila from 108 faucets from 72% to 2% within 1 month and maintained effective control for at least 22 months. Only three samples (1.9%) of hot water from faucets exceeded Environmental Protection Agency standards for silver, and none exceeded the standards for copper. Of 24 samples obtained from hot water tanks, 42% and 50% exceeded the silver and copper standards, respectively. CONCLUSIONS: Copper-silver ionization effectively controls L. pneumophila in high-volume plumbing systems and is superior to thermal treatment; however, high concentrations of copper and silver can accumulate at the bottom of hot water tanks.

Copper↗