... Richard GT Gipps Richard Gipps gained his PhD on the philosophical understanding of schizophr... more ... Richard GT Gipps Richard Gipps gained his PhD on the philosophical understanding of schizophrenia from Warwick University in 2002, and his doctorate in Clinical Psychology from Christ Church University, Canterbury in 2009. ...
Right ventricular outflow tract (RVOT) conduit dysfunction is a limitation of the Ross procedure.... more Right ventricular outflow tract (RVOT) conduit dysfunction is a limitation of the Ross procedure. Transcatheter pulmonary valve replacement (TPVR) could alter the impact of conduit dysfunction and the risk-benefit balance for the Ross procedure. Retrospective review of databases from 3 prospective Melody TPV (Medtronic Inc, Minneapolis, MN) trials. Among 358 patients who were catheterized with the intent to implant a Melody TPV for RVOT conduit stenosis or regurgitation (PR) as part of 3 prospective multicenter studies, 67 (19%) had a prior Ross procedure. Of these, 56 (84%) received a Melody valve; in 5 of the 11 patients who did not, the implant was aborted due to concern for coronary artery compression, and 1 implanted patient required emergent surgery for left coronary compression. The RVOT gradient decreased from a median 38 mm Hg to 13.5 mm Hg (p < 0.001). There was no or trivial PR in all but 4 patients, in whom it was mild. At a median follow-up of 4.0 years, 1 patient died from sepsis. Twelve patients underwent 14 transcatheter (n = 8) or surgical (n = 6) TPV reinterventions for obstruction with stent fracture (n = 9), endocarditis with conduit obstruction (n = 3), or reoperation (n = 2). Freedom from TPV explant was 89% ± 5% at 4 years. Among patients who did not undergo reintervention for obstruction, there was no change in RVOT gradient over time, and all but 1 patient had mild or less PR at last follow-up. The TPVR with the Melody valve provides acceptable early outcomes and durable valve function in the majority of Ross patients. Recurrent RVOT obstruction associated with stent fracture was the main reason for reintervention. Coronary compression is not uncommon in Ross patients and should be assessed prior to TPVR.
Journal of the American Society of Echocardiography : official publication of the American Society of Echocardiography, Jan 24, 2015
Speckle-tracking echocardiographic (STE) measures of right ventricular (RV) function appear to im... more Speckle-tracking echocardiographic (STE) measures of right ventricular (RV) function appear to improve after transcatheter pulmonary valve implantation (TPVI). Measures of exercise function, such as ventilatory efficiency (the minute ventilation [VE]/carbon dioxide production [Vco2] slope), have been shown to be prognostic of mortality in patients who may require TPVI. The aim of this study was to evaluate the correlation between STE measures of RV function and changes in VE/Vco2 after TPVI. Speckle-tracking echocardiography and cardiopulmonary exercise testing were performed at baseline and 6 months after TPVI in 24 patients from four centers. Conventional echocardiographic measures of RV function were also assessed. Echocardiographic and exercise stress test results were interpreted by single blinded observers at separate core laboratories. All patients demonstrated relief of pulmonary regurgitation and stenosis after TPVI. Improvements in RV longitudinal strain (-16.9 ± 3.5% vs -...
The relationship between smoking and inflammatory bowel disease is a curious but well-established... more 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 t...
The state of activation of human peripheral blood monocytes was examined by using a rosette assay... more The state of activation of human peripheral blood monocytes was examined by using a rosette assay that detects changes in Fc receptor expression. Monocytes from patients with uncomplicated Plasmodium falciparum malaria showed a significant increase in the number of rosettes relative to healthy controls. In addition, the monocytes from these patients were tested for their ability to phagocytose Candida albicans, but this ability did not differ from that of normal individuals. Finally, the monocytes from patients with cerebral malaria were also tested for Fc receptor expression. In contrast to the results from uncomplicated cases, the activity of the monocytes from these patients was no different from that of controls. We concluded that uncomplicated P. falciparum malaria caused an increase in monocyte Fc receptor expression which did not occur in cerebral malaria and that this difference in activation may be important in the pathogenesis of cerebral malaria.
Ulcerative colitis is largely a disease of nonsmokers, and transdermal nicotine is of therapeutic... more 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. 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. 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. 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. 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.
... Richard GT Gipps Richard Gipps gained his PhD on the philosophical understanding of schizophr... more ... Richard GT Gipps Richard Gipps gained his PhD on the philosophical understanding of schizophrenia from Warwick University in 2002, and his doctorate in Clinical Psychology from Christ Church University, Canterbury in 2009. ...
Right ventricular outflow tract (RVOT) conduit dysfunction is a limitation of the Ross procedure.... more Right ventricular outflow tract (RVOT) conduit dysfunction is a limitation of the Ross procedure. Transcatheter pulmonary valve replacement (TPVR) could alter the impact of conduit dysfunction and the risk-benefit balance for the Ross procedure. Retrospective review of databases from 3 prospective Melody TPV (Medtronic Inc, Minneapolis, MN) trials. Among 358 patients who were catheterized with the intent to implant a Melody TPV for RVOT conduit stenosis or regurgitation (PR) as part of 3 prospective multicenter studies, 67 (19%) had a prior Ross procedure. Of these, 56 (84%) received a Melody valve; in 5 of the 11 patients who did not, the implant was aborted due to concern for coronary artery compression, and 1 implanted patient required emergent surgery for left coronary compression. The RVOT gradient decreased from a median 38 mm Hg to 13.5 mm Hg (p < 0.001). There was no or trivial PR in all but 4 patients, in whom it was mild. At a median follow-up of 4.0 years, 1 patient died from sepsis. Twelve patients underwent 14 transcatheter (n = 8) or surgical (n = 6) TPV reinterventions for obstruction with stent fracture (n = 9), endocarditis with conduit obstruction (n = 3), or reoperation (n = 2). Freedom from TPV explant was 89% ± 5% at 4 years. Among patients who did not undergo reintervention for obstruction, there was no change in RVOT gradient over time, and all but 1 patient had mild or less PR at last follow-up. The TPVR with the Melody valve provides acceptable early outcomes and durable valve function in the majority of Ross patients. Recurrent RVOT obstruction associated with stent fracture was the main reason for reintervention. Coronary compression is not uncommon in Ross patients and should be assessed prior to TPVR.
Journal of the American Society of Echocardiography : official publication of the American Society of Echocardiography, Jan 24, 2015
Speckle-tracking echocardiographic (STE) measures of right ventricular (RV) function appear to im... more Speckle-tracking echocardiographic (STE) measures of right ventricular (RV) function appear to improve after transcatheter pulmonary valve implantation (TPVI). Measures of exercise function, such as ventilatory efficiency (the minute ventilation [VE]/carbon dioxide production [Vco2] slope), have been shown to be prognostic of mortality in patients who may require TPVI. The aim of this study was to evaluate the correlation between STE measures of RV function and changes in VE/Vco2 after TPVI. Speckle-tracking echocardiography and cardiopulmonary exercise testing were performed at baseline and 6 months after TPVI in 24 patients from four centers. Conventional echocardiographic measures of RV function were also assessed. Echocardiographic and exercise stress test results were interpreted by single blinded observers at separate core laboratories. All patients demonstrated relief of pulmonary regurgitation and stenosis after TPVI. Improvements in RV longitudinal strain (-16.9 ± 3.5% vs -...
The relationship between smoking and inflammatory bowel disease is a curious but well-established... more 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 t...
The state of activation of human peripheral blood monocytes was examined by using a rosette assay... more The state of activation of human peripheral blood monocytes was examined by using a rosette assay that detects changes in Fc receptor expression. Monocytes from patients with uncomplicated Plasmodium falciparum malaria showed a significant increase in the number of rosettes relative to healthy controls. In addition, the monocytes from these patients were tested for their ability to phagocytose Candida albicans, but this ability did not differ from that of normal individuals. Finally, the monocytes from patients with cerebral malaria were also tested for Fc receptor expression. In contrast to the results from uncomplicated cases, the activity of the monocytes from these patients was no different from that of controls. We concluded that uncomplicated P. falciparum malaria caused an increase in monocyte Fc receptor expression which did not occur in cerebral malaria and that this difference in activation may be important in the pathogenesis of cerebral malaria.
Ulcerative colitis is largely a disease of nonsmokers, and transdermal nicotine is of therapeutic... more 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. 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. 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. 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. 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.
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