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Biomedical subjects

Paul Neary

Publications and source records attributed to Paul Neary.

9 recordsLinked to original sources
PubMed2006

A case of probable ibuprofen-induced acute pancreatitis.

CONTEXT: The incidence of drug-induced pancreatitis is rare. There have been no prior definite cases reported of ibuprofen-induced pancreatitis. CASE REPORT: We present a case of a young man with acute pancreatitis probably secondary to an ibuprofen overdose. Immediately preceding the onset of the attack he took a 51 mg/kg dose of ibuprofen. He had other causes of acute pancreatitis excluded by clinical history, serum toxicology and abdominal imaging. DISCUSSION: In the absence of re-challenge we believe it is probable that ibuprofen has a causative link with acute pancreatitis.

Acute Disease↗
PubMed2005

Adjuvant radiotherapy is associated with increased sexual dysfunction in male patients undergoing resection for rectal cancer: a predictive model.

OBJECTIVES: The objectives of this study were to evaluate the effect of radiotherapy (RT) on sexual function in patients undergoing oncologic resection for rectal cancer, and to develop a mathematical model for quantifying the risk of sexual dysfunction through time for this group of patients. METHODS: Data were prospectively collected on patients undergoing proctosigmoidectomy (group 1: n = 101) or adjuvant radiotherapy (40-50 Gy) and resection (group 2: n = 100) for rectal cancer at a tertiary referral center between December 1998 and July 2004. Study end points were recorded at 7 time intervals (preoperatively, 4 months, 8 months, 1 year, 2 years, 3 years, and 4 years after surgery) and included: 1) ability to have an erection, 2) maintain an erection, 3) attain orgasm, 4) dry orgasm, and 5) whether they were sexually active. Multilevel logistic regression analysis for repeated measures was used to identify factors associated with the sexual dysfunction. A predictive model was developed and internally validated by comparing observed and model-predicted outcomes. RESULTS: Radiotherapy had an adverse effect on the ability to get an erection, maintain an erection, attain orgasm, and being sexually active in comparison with patients undergoing surgery alone (7.4%, 12.6%, 16.2%, and 13.7% reduction 8 months after surgery respectively; P < 0.05). The effect of sexual dysfunction deteriorated with age (odds ratio for erectile function, 0.40 per 10-year increase in age; 95% confidence interval, 0.29-0.49; P < 0.001). A significant variability in sexual function was present among the 7 time points with a maximal deterioration occurring at 8 months after surgery with subsequent slow but not complete recovery (P < 0.001). The predictive model showed adequate discrimination on 4 of the 5 domains of sexual dysfunction (area under the receiver operating characteristic curve >0.70). CONCLUSIONS: Radiotherapy has an adverse effect on sexual function, the effect being maximal at 8 months after surgery. The risk of sexual dysfunction can be quantified preoperatively using the proposed index and can assist patients in making better informed choices on the type of treatment they receive.

Aged↗
PubMed2005

Alvimopan.

Alvimopan is a synthetic peripherally restricted mu-receptor opioid antagonist. Alvimopan has a greater affinity for the mu-receptor than the kappa- or sigma-opioid receptors (Ki = 0.77 nM). The polarity of the molecule limits gastrointestinal absorption and central nervous system penetration. It has limited systemic bioavailability and higher affinity for the mu-opioid receptor than naloxone (Ki = 3.7 nM). Completed Phase III trials suggest efficacy in accelerating the recovery of gastrointestinal function after abdominal surgery. Adverse events with all doses have been similar to placebo groups. Further efficacy in alleviating opioid-induced bowel dysfunction in patients with chronic opioid usage has also been demonstrated. This evidence-based review assesses this new drug and discusses its potential role in clinical practice.

Abdomen↗
PubMed2004

Dynamic magnetic resonance imaging of the pelvic floor in patients with idiopathic combined fecal and urinary incontinence.

The etiologies of combined fecal and urinary incontinence may be interrelated but remain poorly understood. A potential variable in this process is global pelvic floor dysfunction. The aim of this study was to prospectively assess the use of phased-array, body coil dynamic MRI in identifying pelvic floor abnormalities in patients with combined incontinence symptoms. Symptomatic patients were compared to asymptomatic control subjects and were selected from those referred to the pelvic physiology laboratory with complaints of combined urinary and fecal incontinence. All patients underwent standard urodynamic studies and anorectal physiologic assessment. Colonoscopy and endoanal ultrasonography were also performed. A standardized protocol was used for dynamic MRI, and the parameters were measured using workstation software (callipers, compass, and densitometer). In the incontinent group there was a significant difference, when compared to control subjects, in the angle of the levator ani muscle arch of the levator plate complex (3.0+/-5 degrees vs. 14+/-10 degrees; P=0.004), the width of the levator hiatus (58.3+/-8 mm vs. 46.5+/-8 mm; P=0.001), the area and tissue density of the levator ani muscle (19.5+/-1 mm(2) vs. 26.9+/-1 mm(2); P=0.001, and 157.3+/-47 pixels vs. 126.1+/-23 pixels; P=0.025, respectively), and in the length of the external anal sphincter (20.0+/-5 mm vs. 26.6+/-13 mm; P=0.03). Body coil dynamic MRI is a noninvasive and well-tolerated imaging modality. Our data show that it can identify changes in pelvic muscle morphology in patients with disorders of incontinence, and this may help in planning better management strategies.

Adult↗
PubMed2004

Electromyographic biofeedback can improve subjective and objective measures of fecal incontinence in the short term.

Electromyographic biofeedback therapy has demonstrated subjective improvement in patients with fecal incontinence that is comparable to surgery. We assessed the efficacy of biofeedback therapy in a consecutive heterogeneous group of patients using both subjective and objective assessment criteria. These 28 patients with fecal incontinence were studied retrospectively. Patients were assessed using a quality-of-life questionnaire (QOL), the Vaizey and Wexner incontinence scoring systems, and anorectal manometry for efficacy of treatment, before and after biofeedback therapy. Eighty-six percent of patients completed the study. Median follow-up was 18 months. Eighty percent of patients demonstrated significant improvements in their Vaizey and Wexner scores (P<0.001 and P<0.001, respectively). The mean QOL score improved from 62 to 77 (P<0.01). Significant improvements were also demonstrated in the mean resting pressure (P<0.01), peak amplitude of squeeze (P<0.01), and the duration of squeeze pressure (P<0.05). The deferred 15-minute evacuation time also significantly increased (P<0.001). This study reported significant short-term improvement in fecal incontinence with electromyographic biofeedback therapy using validated subjective and objective scoring systems. Similarly, this treatment also significantly improved anorectal manometric findings. Our data confirm the role of biofeedback therapy in the multimodality approach to patients with fecal incontinence.

Adult↗
PubMed2004

A comparison of wide local excision with abdominoperineal resection in anorectal melanoma.

Anorectal melanoma is a rare condition and its surgical management is controversial. Seventeen large case series from over the past 10 years were reviewed. The survival of patients treated by either abdominoperineal resection (APR) or wide local excision (WLE) was analysed according to the stage of the disease. Comparison of the survival of patients who underwent APR with those who underwent WLE showed no statistically significant advantage for either procedure in patients at all disease stages. APR should therefore only be performed when local excision is not possible or for palliative purposes.

Anus Neoplasms↗
PubMed2003

Taurine attenuates calcium-dependent, Fas-mediated neutrophil apoptosis.

The pathway involved in Fas-mediated neutrophil apoptosis remains to be fully elucidated. We examined whether this pathway involved either oxygen-dependent or calcium-dependent mechanisms. We also investigated whether taurine, a powerful antioxidant and regulator of intracellular calcium fluxes, could inhibit Fas-mediated neutrophil apoptosis. Neutrophils were stimulated with Fas monoclonal antibody in the presence or absence of taurine. Fas receptor ligation resulted in significant neutrophil apoptosis at 18 h. Engagement of the Fas receptor rapidly resulted in a significant decrease in intracellular calcium. Apoptosis was inhibited and intracellular calcium levels were maintained in the presence of calcium ionophore A23187 or taurine. Fas ligation did not result in an increase in intracellular reactive oxygen species. We have demonstrated that Fas-mediated neutrophil apoptosis occurs after a decrease in intracellular calcium and is reactive oxygen intermediate independent. Furthermore, the amino acid taurine attenuates this pathway of neutrophil apoptosis by calcium regulation. This newly identified role of taurine in the inhibition of Fas-mediated neutrophil apoptosis may have significant implications for future manipulation of host pro-inflammatory cell function.

Apoptosis↗
PubMed2002

Assessment of sarcoplasmic reticulum Ca(2+) flux pathways in cardiomyocytes from rabbits with infarct-induced left-ventricular dysfunction.

The aim of the study was to correlate intracellular Ca(2+) transients with Ca(2+) uptake and efflux characteristics of the sarcoplasmic reticulum (SR) in ventricular myocytes isolated from rabbits with left-ventricular dysfunction (LVD). Chronic (8 weeks) ligation of a coronary artery caused marked LVD in rabbits. Measurements of intracellular [Ca(2+)] were made using Fura-2 on intact, single, left-ventricular myocytes. SR Ca(2+) flux rates associated with sarco-endoplasmic reticulum Ca(2+) ATPase type 2 (SERCA2)-mediated uptake, ryanodine receptor type 2 (RyR2)-mediated Ca(2+) efflux and background SR Ca(2+) leak were measured in suspensions of permeabilised myocytes. Measurements on single, permeabilised myocytes were used to assess the steady-state Ca(2+) content of the SR and the characteristics of spontaneous SR Ca(2+) release. Peak systolic [Ca(2+)] was significantly lower; time-to-peak and Ca(2+) transient duration were significantly longer in LVD myocytes. SERCA2-mediated Ca(2+) uptake was reduced to approximately 50% in myocytes from the LVD group. Ruthenium red (RuR)-sensitive Ca(2+) efflux (mediated by the RyR2) was also reduced in the LVD group by approximately 50%, as was the remaining (RuR-insensitive) background Ca(2+) leak. Measurements from single, permeabilised myocytes showed a lower steady-state SR Ca(2+) content. The frequency and amplitude of spontaneous SR Ca(2+) release from LVD hearts was also reduced. Partial inhibition of SERCA2 by thapsigargin depressed both the amplitude and the frequency of spontaneous release. Partial inhibition of RyR2-mediated-Ca(2+) efflux with tetracaine enhanced spontaneous Ca(2+) release amplitude and decreased frequency. Increased background Ca(2+) leak with ionomycin decreased the frequency of spontaneous release. It is concluded that partial inhibition of SERCA2 mimics some aspects of altered SR function in LVD, but reduced RyR2 function cannot explain the other functional alterations observed. Reduced background Ca(2+) leak from the SR may compensate partly for the reduced Ca(2+) uptake capacity of the SR in the LVD group.

Animals↗