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Biomedical subjects

J Rhodes

Publications and source records attributed to J Rhodes.

At least 55 records · Page 3Linked to original sources
PubMed1999

Intra-luminal nicotine reduces smooth muscle tone and contractile activity in the distal large bowel.

BACKGROUND: Nicotine may be of therapeutic value in ulcerative colitis (UC), although its mechanism of action has not been established. OBJECTIVE: To examine the effect of a solution of nicotine on sustained resting pressure (tone) and contractile activity in the human colon. METHODS: Ten healthy volunteers, and seven with UC in symptomatic remission took part; all were non-smokers. All 17 subjects were given nicotine or placebo solution on two separate occasions in a randomized sequence. A water-perfused manometry catheter, with openings at 5, 10 and 15 cm from the tip, was placed by rigid sigmoidoscopy in the recto-sigmoid region. Baseline tone and activity were measured for 15 min prior to instillation of 20 ml of saline alone or with nicotine, 1.2 mg, at pH 4.5. Observations were made over the subsequent 15-20 min. RESULTS: Baseline spontaneous activity in all subjects showed both high- and low-frequency components; in three patients with UC, the low-frequency activity was of high amplitude. The nicotine reduced both tone and activity in all subjects, with reduction or abolition of the large contractions in UC. Tone in all 17 subjects was reduced significantly at 3 min after nicotine (P = 0.000015, sign test); the rate of recovery varied in individuals. Results from normals and UC did not differ significantly from each other. No significant change in tone or activity was observed with the saline solution. CONCLUSION: Intra-luminal nicotine significantly reduces both smooth muscle tone and contractile activity in the recto-sigmoid colon in both normal subjects and patients with UC.

Adult↗
PubMed1999

Effectiveness of cognitive therapy for delusions in routine clinical practice.

BACKGROUND: Previous studies have suggested that cognitive therapy is effective in modifying delusions. AIMS: To assess the effectiveness of cognitive therapy on patients seen in routine clinical work. METHOD: Eighteen patients with chronic delusions were treated using cognitive therapy, after the method of Chadwick and Lowe. A single-case multiple-baseline experimental design was used, including a control treatment. Each subject was used as their own control. RESULTS: Six patients reduced conviction in their delusions during cognitive therapy and not during the control treatment. Seven patients' conviction ratings did not change. Five patients showed a variable response. Degree of conviction did not fall to zero in any patient. All patients reported that the therapy had been helpful; six spontaneously mentioned changes in psychotic thinking. CONCLUSIONS: One-third of patients with chronic delusions whom we treated responded to delusion modification with a reduction in degree of belief. Change within therapy sessions predicted outcome, as did variation in the conviction during baseline. Cognitive therapy with delusions should aim at reducing distress as well as conviction.

Case-Control Studies↗
PubMed1998

Thrombopoietin induces association of Crkl with STAT5 but not STAT3 in human platelets.

Crkl, a 39-kD SH2, SH3 domain-containing adapter protein, is constitutively tyrosine phosphorylated in hematopoietic cells from chronic myelogenous leukemia (CML) patients. We recently reported that thrombopoietin induces tyrosine phosphorylation of Crkl in normal platelets. In this study, we demonstrate that thrombopoietin induces association of Crkl with a tyrosine phosphorylated 95- to 100-kD protein in platelets and in UT7/TPO cells, a thrombopoietin-dependent megakaryocytic cell line. With specific antibodies against STAT5, we demonstrate that the 95- to 100-kD protein in Crkl immunoprecipitates is STAT5. This coimmunoprecipitation was specific in that Crkl immunoprecipitates do not contain STAT3, although STAT3 becomes tyrosine phosphorylated in thrombopoietin-stimulated platelets. The coimmunoprecipitaion of Crkl with STAT5 was inhibited by the immunizing peptide for Crkl antisera or phenyl phosphate (20 mmol/L). After denaturing of Crkl immunoprecipitates, Crkl was still immunoprecipitated by Crkl antisera. However, coimmunoprecipitation of STAT5 was not observed. Coincident with STAT5 tyrosine phosphorylation, thrombopoietin induces activation of STAT5 DNA-binding activity as demonstrated by electrophoretic mobility shift assays (EMSA). Using a beta-casein promoter STAT5 binding site as a probe, we have also demonstrated that Crkl antisera supershift the STAT5-DNA complex, suggesting that Crkl is a component of the complex in the nucleus. Furthermore, interleukin-3 (IL-3), granulocyte-macrophage colony-stimulating factor (GM-CSF), and erythropoietin also induce Crkl-STAT5 complex formation in responding cells in a stimulation-dependent manner. In vitro, glutathione S-transferase (GST)-Crkl bound to STAT5 inducibly through its SH2 domain. These results indicate that thrombopoietin, IL-3, GM-CSF, and erythropoietin commonly induce association of STAT5 and Crkl and that the complex translocates to the nucleus and binds to DNA. Interestingly, such association between STAT5 and Crkl was not observed in cytokine-stimulated murine cells, suggesting an intriguing possibility that components of the human STAT5-DNA complex may be different from those of the murine counterpart.

Acute-Phase Proteins↗
PubMed1998

Localization of a novel septin protein, hCDCrel-1, in neurons of human brain.

Synaptic function is critical for cell-cell communication and the characterization of proteins that function during vesicle formation, transport and fusion events will yield further insight into the mechanisms of synaptic transmission. We have cloned and characterized a gene product expressed in human brain called hCDCrel-1. This protein is a new member of the septin family of gene products that functions during cytokinesis in lower eukaryotes. In this study we characterize the expression of the hCDCrel-1 gene and localize the hCDCrel-1 protein to neurons in adult human brain. hCDCrel-1 co-purifies with SNAP-25 and synaptophysin marked synaptosomes, suggesting a novel function for this gene family in the brain. Our data indicate that members of the septin family of proteins may function in synaptic vesicle transport, fusion or recycling events in the human brain.

Adult↗
PubMed1998

Effect of pulmonary artery stenoses on the cardiopulmonary response to exercise following repair of tetralogy of Fallot.

Data from exercise tests, echocardiograms, and lung perfusion scans were analyzed to determine whether the excessive minute ventilation (VE) often encountered among patients with tetralogy of Fallot is due to ventilation-perfusion mismatch secondary to branch pulmonary artery stenoses. Patients with branch PA stenoses had lower peak oxygen consumptions and higher VE during exercise than did patients without stenoses, and a strong correlation existed between the degree of pulmonary blood flow maldistribution on lung perfusion scan and the amount of excessive VE during exercise.

Adolescent↗
PubMed1998

Transoesophageal echocardiography during scoliosis repair: comparison with CVP monitoring.

PURPOSE: Accurate haemodynamic assessment during surgical repair of scoliosis is crucial to the care of the patient. The purpose of this study was to compare transoesophageal echocardiography (TEE) with central venous pressure monitoring in patients with spinal deformities requiring surgery in the prone position. METHODS: Twelve paediatric patients undergoing corrective spinal surgery for scoliosis/kyphosis in the prone position were studied. Monitoring included TEE, intra-arterial and central venous pressure monitoring (CVP). Haemodynamic assessment was performed prior to and immediately after positioning the patient prone on the Relton-Hall table. Data consisted of mean arterial blood pressure (mBP), heart rate (HR), CVP, left ventricular end-systolic and end-diastolic diameters (LVESD and LVEDD respectively) and fractional shortening (FS). Right ventricular (RV) function and tricuspid regurgitation (TR) were assessed qualitatively. Analysis was performed using descriptive statistics, Student's t test, sign rank, and correlation analysis. RESULTS: There was an increase in CVP (8.7 mmHg to 17.7 mmHg; P < .01), and decreases in LVEDD (37.1 mm to 33.2 mm; P < .05), and mean blood pressure (75.0 mmHg to 65.7 mmHg; P < .05) when patients were placed in the prone position. Fractional shortening, LVESD, and HR did not change from the supine to the prone position. Right ventricular systolic function and tricuspid regurgitation were unchanged. CONCLUSION: These data indicate that the CVP is a misleading monitor of cardiac volume in patients with kyphosis/scoliosis in the prone position. This is consistent with previous studies. In this clinical situation, TEE may be a more useful monitoring tool to assess on-line ventricular size and function.

Adolescent↗
PubMed1998

Inflammatory bowel disease and smoking--a review.

The relationship between smoking and inflammatory bowel disease is a curious but well-established one. It is negatively associated with ulcerative colitis but positively associated with Crohn's disease. It also has opposite influences on the clinical course of the two conditions with possible beneficial effect in ulcerative colitis and detrimental effect in Crohn's disease. The diametrically "opposite" relationship of smoking status with the two conditions has been the subject of much interest in the hope that it may reveal pathogenic mechanisms responsible for the two conditions and possibly offer the key to alternative therapeutic options. Nicotine may be the principal agent in smoking responsible for the association; trials have shown it to be of some benefit in ulcerative colitis, but further research is required to establish its therapeutic role and possible mechanisms of action. In this article, we review the historical, clinical, and therapeutic aspects of the association between smoking and inflammatory bowel disease.

Colitis, Ulcerative↗
PubMed1998

Clinical status of ulcerative colitis in patients who smoke.

OBJECTIVES: Ulcerative colitis (UC) is largely a disease of nonsmokers. There are few patients who are current smokers, but we have identified a group and reviewed their clinical status, disease activity, and nicotine exposure to examine whether they remain well controlled while smoking. METHODS: Fifty-one patients from three centers with verified UC were reviewed. RESULTS: Thirty of the group were men; mean age 50 yr, with a mean age of onset of 37 yr. Twenty-two patients had proctosigmoid disease, 12 involvement of left colon, and 17 total colitis. All were current smokers; 41 were cigarette smokers averaging 17 daily. At the onset of colitis 30 were nonsmokers, 25 of them were ex-smokers and 19 developed colitis within 2 yr of stopping smoking. Twenty-eight believed smoking improved disease activity and none felt smoking had a detrimental effect on their UC. Eleven were receiving no medication for UC, 40 were receiving 5-ASA (5-aminosalicylic acid) preparations, and only two took oral steroids. All were in clinical remission, with the exception of one patient; mean St. Marks score was 1.5, out of a possible total of 22. Sigmoidoscopic grades were inactive in all patients except three. Histological assessment showed significant activity in only five. Median serum nicotine was 8 ng/ml (range, 0.4-24.4), median serum cotinine 180 ng/ml (range, 20-453), with corresponding salivary cotinine of 255 ng/ml (range, 34-683). Median rise in nicotine 2 min after a cigarette in 35 patients was 12.1 ng/ml (range, 0.4-44). CONCLUSIONS: Because most current smokers with UC have inactive disease, smoking may contribute to the clinical remission in these patients.

Adult↗
PubMed1998

Expression of beta-defensin genes in bovine alveolar macrophages.

Bovine alveolar macrophages (BAM) were examined for the expression of beta-defensins and to determine whether their expression could be upregulated by bacterial lipopolysaccharide (LPS), as observed with beta-defensins expressed in bovine tracheal epithelial cells. Four beta-defensins were expressed constitutively in BAM, with bovine neutrophil beta-defensin (BNBD)-4 and BNBD-5 being the most predominant. This is the first evidence of beta-defensin gene expression in a mature myeloid cell. LPS had no effect on beta-defensin expression in BAM, even though tumor necrosis factor alpha (TNF-alpha) production was induced. Nonbacterial inflammatory particles had little effect on beta-defensin gene expression or TNF-alpha production in BAM. We hypothesize that constitutively expressed beta-defensins of alveolar macrophages may have a role in lung host defense.

Amino Acid Sequence↗
PubMed1998

Controlled trial of antituberculous chemotherapy in Crohn's disease: a five year follow up study.

BACKGROUND: It has been suggested that Mycobacterium paratuberculosis is the cause of Crohn's disease. In a previous report the immediate effect of two years treatment with antituberculous chemotherapy showed no clinical benefit. AIMS: To assess both the immediate and longer term effect of treatment on the disease. METHODS: Patients were followed for five years from their date of entry to the study. One hundred and thirty patients entered the initial study, and of these 111 (81%) were followed regularly. RESULTS: Overall, there was no evidence of consistent benefit or disadvantage from antituberculous chemotherapy in any of the assessments made, including the number of acute relapses, surgical episodes, hospital admissions, disease activity, blood tests, or medication required for Crohn's disease during the follow up period. CONCLUSION: The absence of any benefit at the end of the initial two year trial period, and during the three year subsequent follow up, fails to support the hypothesis that mycobacteria play an important part in the pathogenesis of Crohn's disease, or that antituberculous chemotherapy may be of benefit.

Antitubercular Agents↗
PubMed1998

Nicotine carbomer enemas--pharmacokinetics of a revised formulation.

AIMS: Ulcerative colitis is predominantly a disease of non-smokers, and transdermal nicotine has therapeutic benefit but causes frequent side-effects. We have previously developed a topical enema combining nicotine with a polyacrylic carbomer; pharmacokinetic parameters were similar in healthy volunteers and patients with active ulcerative colitis. This enema was reformulated to reduce and delay nicotine absorption, thereby improving tolerance. METHOD: Pharmacokinetic observations and side-effects with both formulations are compared in the same 8 healthy volunteers--all non-smokers, 3 male, mean age 33 years. Six milligrams of nicotine were complexed with 400 mg of carbomer in a 100 ml liquid enema. The original formulation was buffered with potassium/phosphate to pH 5.5, kinematic viscosity was 3 mNm; the revised preparation incorporated trometamol 1% solution to buffer to pH 4.2, viscosity 5 mNm. All subjects had the two formulations on separate occasions at least a month apart, with serial blood measurements and side-effect profile recorded for 8 hours. RESULTS: The revised enema formulation significantly reduced Cmax for nicotine from 8.3 +/- 2.7 to 6.6 +/- 2.1, p = 0.03 with some reduction in nicotine absorption and improved tolerance. Although there was considerable intersubject variation in profiles for nicotine and cotinine, they were similar for each subject on both occasions. CONCLUSIONS: The lower pH and greater viscosity reduced the amount of free nicotine in its unionised form available for absorption, but made it possible to expose colonic mucosa to the same nicotine dose. In other drug formulations where side-effects are a limiting factor these modifications may also be relevant.

Acrylic Resins↗
PubMed1997

Fate of mitral regurgitation following repair of atrioventricular septal defect.

The purpose of this study was to evaluate the fate of mitral regurgitation (MR) following repair of atrioventricular septal defects (AVSDs). Echocardiograms of all survivors of isolated AVSD surgery between 1986 and 1996, who had had > or =2 postoperative color Doppler studies (39 patients), were reviewed. On each study, MR severity was graded on a 1+ to 4+ scale, based upon the size of the MR jet. Median age at surgery was 9 months (range 3 to 169); median age at postoperative follow-up was 45 months (range 3 to 107). Mild deterioration of mitral valve function was fairly common. MR severity increased by > or =1 grade in 16 patients (41%) during the course of the study. However, the deterioration in mitral valve function occurred primarily during the early postoperative time intervals. After the initial 32 postoperative months, MR worsened on only 4 occasions and in each instance worsened by only 1 grade. Deterioration to 4+ MR occurred in only 3 patients, and was not observed after the initial 30 postoperative months. Survival curve analysis predicted a 90% probability of not having severe (4+) MR after 30 months (lower 95% confidence bound: 80%). Postoperative MR remains fairly stable following AVSD repair. Serious deterioration is rare, especially after the initial 30 postoperative months.

Child, Preschool↗
PubMed1997

Convergence of Schiff base costimulatory signaling and TCR signaling at the level of mitogen-activated protein kinase ERK2.

Schiff base formation on specialized T cell surface amines provides a costimulatory signal to T cells through a mechanism that activates Na+ and K+ transport, substantially enhancing TCR-dependent IL-2 production. Schiff base-forming molecules that mimic the natural carbonyl donor potently enhance immune responses and provide the first mechanism-based, orally active immunopotentiatory agents. In the present study, costimulation by the Schiff base-forming molecule tucaresol was investigated at the level of mitogen-activated protein kinase (MAPK) in T cell lines. Both TCR-directed stimulation by anti-CD3 and Schiff base stimulation by tucaresol produced a distinct mobility shift in MAPK, characterized by direct immunoblotting of cell lysate proteins subjected to SDS-PAGE, that corresponded with increased phosphorylation. Combined TCR-CD3 and tucaresol stimulation substantially enhanced and prolonged the MAPK response, providing a biochemical basis for the costimulatory nature of the pathway utilized by Schiff base signaling. The MAPK affected was identified by immunoprecipitation as ERK2. Both the direct effects and the TCR signal-enhancing effects of tucaresol on MAPK activation were also demonstrated in a functional MAPK assay measuring substrate phosphorylation. Borohydride reduction of tucaresol's Schiff base-forming carbonyl group abolished both enhancement of MAPK phosphorylation and IL-2 production, as did a selective inhibitor of the MAPKK, MEK1. Tucaresol had no effect on TCR-mediated rises in intracellular free Ca2+ or inositol 1,4,5-triphosphate generation, while tucaresol signaling occurred normally in the lck-deficient J.CaM1.6 T cell line, consistent with convergence of tucaresol- and TCR-induced signals downstream of early TCR-mediated events.

Benzaldehydes↗
PubMed1997

Pharmacokinetics of nicotine carbomer enemas: a new treatment modality for ulcerative colitis.

BACKGROUND: Ulcerative colitis is largely a disease of nonsmokers, and transdermal nicotine is of therapeutic value in the active disease. Because side effects are common, we developed a topical enema formulation of nicotine. OBJECTIVE: To study the pharmacokinetics of nicotine complexed with a polyacrylic carbomer and administered by enema to eight healthy volunteers and to eight patients with active ulcerative colitis, verified sigmoidoscopically. PATIENTS AND METHODS: All 16 subjects were nonsmokers. The mean age for normal subjects was 33 years; the mean for patients with ulcerative colitis was 60 years. Median stool frequency for patients with ulcerative colitis was four daily. Patients were taking 5-amino salicylic acid compounds and five were taking oral prednisolone (median dose, 12 mg daily). Nicotine, 6 mg, complexed with carbomer 974P, 400 mg, was administered in a 100 ml enema after an overnight fast, with serial blood measurements taken over 8 hours. Serum nicotine and cotinine were measured by gas liquid chromatography. Area under the concentration-time curves were calculated by the trapezoidal method, and the terminal elimination half-life was derived by extrapolation of the log-linear terminal phase. RESULTS: With the exception of nicotine time to reach peak concentration, which was longer in patients (median of 60 minutes compared with 45 minutes; p < 0.005), other comparisons between normal subjects and patients showed no statistically significant difference, although there was considerable inter-subject variation. Maximum concentration of nicotine, 8.1 +/- 3.5 ng/ml, in the 16 subjects occurred after a median of 60 minutes (range, 30 to 180 minutes); maximum cotinine concentrations of 60.4 +/- 11.5 ng/ml occurred after 4 hours. Side effects in five subjects were mild (four subjects) or moderate (one subject) and included lightheadedness, nausea, and headache; these five subjects were female lifelong nonsmokers of low body weight. CONCLUSION: Because most of the active ingredient of nicotine is converted to continine on the first pass through the liver, substantial concentrations can be achieved at the site of disease with only modest rises in serum nicotine, which are responsible for side effects; cotinine has low pharmacologic activity. Topical administration of nicotine may be useful treatment for distal ulcerative colitis.

Acrylic Resins↗