Curcumin modulation of high fat diet-induced atherosclerosis and steatohepatosis in LDL receptor deficient mice.

OBJECTIVE: Consuming curcumin may benefit health by modulating lipid metabolism and suppressing atherogenesis. Fatty acid binding proteins (FABP-4/aP2) and CD36 expression are key factors in lipid accumulation in macrophages and foam cell formation in atherogenesis. Our earlier observations suggest that curcumin's suppression of atherogenesis might be mediated through changes in aP2 and CD36 expression in macrophages. Thus, this study aimed to further elucidate the impact of increasing doses of curcumin on modulation of these molecular mediators on high fat diet-induced atherogenesis, inflammation, and steatohepatosis in Ldlr(-/-) mice. METHODS: Ldlr(-/-) mice were fed low fat (LF) or high fat (HF) diet supplemented with curcumin (500 HF + LC; 1000 HF + MC; 1500 HF + HC mg/kg diet) for 16 wks. Fecal samples were analyzed for total lipid content. Lipids accumulation in THP-1 cells and expression of aP2, CD36 and lipid accumulation in peritoneal macrophages were measured. Fatty streak lesions and expression of IL-6 and MCP-1 in descending aortas were quantified. Aortic root was stained for fatty and fibrotic deposits and for the expression of aP2 and VCAM-1. Total free fatty acids, insulin, glucose, triglycerides, and cholesterol as well as several inflammatory cytokines were measured in plasma. The liver's total lipids, cholesterol, triglycerides, and HDL content were measured, and the presence of fat droplets, peri-portal fibrosis and glycogen was examined histologically. RESULTS: Curcumin dose-dependently reduced uptake of oxLDL in THP-1 cells. Curcumin also reduced body weight gain and body fat without affecting fat distribution. During early intervention, curcumin decreased fecal fat, but at later stages, it increased fat excretion. Curcumin at medium doses of 500-1000 mg/kg diet was effective at reducing fatty streak formation and suppressing aortic expression of IL-6 in the descending aorta and blood levels of several inflammatory cytokines, but at a higher dose (HF + HC, 1500 mg/kg diet), it had adverse effects on some of these parameters. This U-shape like trend was also present when aortic root sections were examined histologically. However, at a high dose, curcumin suppressed development of steatohepatosis, reduced fibrotic tissue, and preserved glycogen levels in liver. CONCLUSION: Curcumin through a series of complex mechanisms, alleviated the adverse effects of high fat diet on weight gain, fatty liver development, dyslipidemia, expression of inflammatory cytokines and atherosclerosis in Ldlr(-/-) mouse model of human atherosclerosis. One of the mechanisms by which low dose curcumin modulates atherogenesis is through suppression of aP2 and CD36 expression in macrophages, which are the key players in atherogenesis. Overall, these effects of curcumin are dose-dependent; specifically, a medium dose of curcumin in HF diet appears to be more effective than a higher dose of curcumin.

Safety and efficacy of percutaneous nephrolithotomy for the treatment of paediatric urolithiasis.

INTRODUCTION: Paediatric percutaneous nephrolithotomy (PCNL) has revolutionised the treatment of paediatric nephrolithiasis. Paediatric PCNL has been performed using both adult and paediatric instruments. Stone clearance rates and complications vary according to the technique used and surgeon experience. We present our experience with PCNL using adult instruments and a 28Fr access tract for large renal calculi in children under 18 years. METHODS: All patients undergoing PCNL at our institution between 2000 and 2009 were reviewed. Demographics, surgical details and post-operative follow-up information were obtained to identify stone clearance rates and complications. RESULTS: PCNL was performed in 32 renal units in 31 patients (mean age: 10.8 years). The mean stone diameter was 19mm (range: 5-40mm). Twenty-six cases required single puncture and six required multiple tracts. Overall, 11 staghorn stones, 10 multiple calyceal stones and 11 single stones were treated. Twenty-seven patients (84%) were completely stone free following initial PCNL. Two cases had extracorporeal shock wave lithotripsy for residual fragments, giving an overall stone free rate of 91% following treatment. There was no significant bleeding or sepsis encountered either during the operation or in the post-operative setting. No patient required or received a blood transfusion. CONCLUSIONS: Paediatric PCNL can be performed safely with minimal morbidity using adult instruments for large stone burden, enabling rapid and complete stone clearance.

Electron-phonon relaxation in disordered two-dimensional electron gas with dynamically screened deformation potential.

We study the effect of a dynamically screened deformation potential on the electron longitudinal phonon relaxation in a disordered two-dimensional electron gas. On consideration of the dynamic dielectric function and polarization operator, and the frequency ω dependence, we find a significant change in the temperature exponent as well as the pre-factor α from the earlier reported approximate temperature power law dependence αT(4) obtained under static strong screening and impurity limit. More strikingly, a reversal in the character of the dependence of scattering rate on the mean free path takes place on the incorporation of dynamic screening, where the behaviour changes from the static 1/l to the dynamic l(2) at T = 1.0 K and l = 10 nm.

The 22-mm vs the 32-mm femoral head in cemented primary hip arthroplasty long-term clinical and radiological follow-up study.

A retrospective clinical and radiological analysis was performed on 117 patients (138 hips) with a mean age of 75 years and a mean follow-up of 11 years. The prostheses used were 2 similar monoblock femoral components with 22- and 32-mm head sizes; their effects on the wear of the high-density polyethylene cup were studied. Wear of component was determined by evaluating the standardized initial and follow-up radiographs. The mean rate of linear wear was higher in the 22-mm femoral head, whereas the volumetric wear was higher in the 32-mm femoral head. In both groups, volumetric wear was significantly correlated with cup lysis. Increasing body weight in both groups was associated with more volumetric wear. The radiological evidence of prosthetic loosening did not correlate well with clinical evaluation of the hip.

Neuromodulation in bladder dysfunction.

Neuromodulation is one option for the management of a wide variety of lower urinary tract disorders, including non-neuropathic and neuropathic bladder dysfunctions. The mechanisms of action of the reported techniques remain unclear; urodynamic changes are minimal, but symptomatic improvements are common. Although the treatment is relatively free from side-effects compared with more aggressive surgical options, the placebo effect is likely to be significant. Its exact cost effectiveness is unclear, but the technology is a welcome addition to the range of treatment options for lower urinary tract dysfunctions, such as urgency and urge incontinence.

Transcutaneous electrical nerve stimulation and temporary S3 neuromodulation in idiopathic detrusor instability.

PURPOSE: We studied the effects of electrical stimulation on idiopathic detrusor instability. MATERIALS AND METHODS: Between January 1993 and December 1994, 30 men and 41 women (mean age plus or minus standard deviation 48 +/- 16 years) underwent transcutaneous electrical nerve stimulation (TENS) of the S2-S3 dermatomes, and 13 men and 22 women (mean age 48 +/- 12 years) underwent S3 neuromodulation. Subjective assessment was performed using a diary and symptom score of 0 to 14. Objective outcome was analyzed with urodynamic studies. RESULTS: Mean duration of TENS was 3 +/- 1 weeks (range 2 to 4). Although there were no major complications 31% of the patients reported local skin irritation. The overall urinary symptom scores improved from 10 +/- 2 (range 5 to 14) before the study to 7 +/- 3 (range 1 to 14) during stimulation. Urodynamic analysis revealed significant (p < 0.05) improvements in total bladder capacity and voided volume, and decreases in the number and frequency of unstable contractions. Mean duration of S3 neuromodulation was 6 +/- 1 days (range 4 to 8 days). Four procedures failed due to electrode displacement in 3 cases and procedure intolerance in 1. Hemorrhage from the puncture site occurred in 1 patient. Overall urinary symptom scores were 10 +/- 3 (range 5 to 14) before the study and 5 +/- 2 (range 2 to 10) during stimulation. Although symptomatic relief was more pronounced with S3 neuromodulation, no statistically significant differences were found regarding urinary symptoms compared to TENS. CONCLUSIONS: In patients with severe detrusor instability refractory to conservative treatments the use of TENS and S3 neuromodulation produced significant changes in urodynamic parameters and presenting symptoms. Our results appear to justify evaluation with neuromodulatory techniques before definitive surgical intervention in these patients.

Surface localization of sacral foramina for neuromodulation of bladder function. An anatomical study.

A method is described for percutaneous localization of the sacral foramina, for neuromodulation of bladder function. We carried out an anatomical study of 5 male and 5 female human cadaver pelves. Using the described surface markings, needles were placed percutaneously into all sacral foramina from nine different angles. Paths of needle entry were studied by subsequent dissection. We observed that although it was possible to enter any sacral foramen at a wide range of insertion angles, the incidence of nerve root/vascular penetration increased with increasing angle of needle entry. Also, the incidence of nerve root penetration was higher with the medial approach compared with lateral entry. The insertion of a needle into the S1 foramen was associated with a higher incidence of nerve root penetration and presents a potential for arterial haemorrhage. On the other hand the smaller S3 and S4 nerve roots were surrounded by venous plexuses, presenting a potential source of venous haemorrhage during procedures. Our study suggests a new method for identifying the surface markings of sacral foramina and it describes the paths of inserted needles into the respective foramina. In addition, it has highlighted some potential risk factors secondary to needle insertion.

TENS: a treatment option for bladder dysfunction.

To ascertain the mode of action and benefits of transcutaneous electrical nerve stimulation (TENS) in detrusor overactivity, stress incontinence and interstitial cystitis, an English-language literature search using Medline (1984-1995) was undertaken with detrusor instability, incontinence, interstitial cystitis, neuromodulation, transcutaneous electrical nerve stimulation and urodynamics as keywords and the material so identified was reviewed. The mode of action of TENS and optimal stimulation parameters in bladder dysfunction remain unclear. Lack of strict selection criteria and deficient reporting of subjective and objective outcomes precluded full assessment of therapeutic efficacy. A beneficial effect was evident in some studies of detrusor overactivity and interstitial cystitis. A trial of TENS in detrusor overactivity and interstitial cystitis refractory to conventional therapy would seem justified. Continued experimental research and further clinical studies will lead to refinement of the treatment modality.

Clinical outcome and quality of life following enterocystoplasty for idiopathic detrusor instability and neurogenic bladder dysfunction.

OBJECTIVE: To study the long-term outcome of patients undergoing enterocystoplasty. PATIENTS AND METHODS: The study comprised 48 patients (17 men and 31 women; mean age 46 years) who underwent enterocystoplasty for idiopathic detrusor instability (DI, 35 patients) or neurogenic bladder dysfunction (13 patients). Symptoms were scored from 0 to 14 and the overall outcome and generic quality of life were assessed using a Visick grading system (groups A to E) and the Nottingham Health Profile (NHP). These assessments were carried out before, 3 months after operation and at the final follow-up (38 +/- 18 months, range 13-78). Urodynamic studies were performed before and after operation. RESULTS: No patient died after operation and there was minimal early morbidity. Late complications (> 30 days) included incisional hernia (3), anastomotic perforation (1), calculus formation (1) and urethral stricture (1). Clean intermittent self-catheterization (CISC) was performed by 36 (75%) patients. Early symptomatic outcome was good in 40 (83%) patients, moderate in seven (15%) and unsatisfactory in one (2%) patient. The mean symptom scores before and 3 months after surgery were 10 (range 2-14) and 3 (range 2-14), respectively (P < 0.001). There was a significant increase in total bladder capacity (307 +/- 140 to 588 +/- 217 mL; P < 0.001) and bladder compliance (37 +/- 50 to 169 +/- 162 mL/cm H2O; P < 0.001). DI persisted in 15 (31%) patients. NHP scores revealed significant improvements in all domains. Final assessment showed a less satisfactory situation, with recurrent urinary tract infection (UTI) in 17 (37%) patients, a need for long-term antibiotic therapy in seven (15%) and a change in bowel habit in 15 (33%) (13 DI, two with neurogenic bladder dysfunction). CISC was performed by 39 (85%) patients. The long-term outcome was good or moderate in 12 patients (92%) with neurogenic bladder dysfunction and good or moderate in only 19 patients (58%) with DI. CONCLUSION: Clam enterocystoplasty remains an effective management option in some patients with DI, but most patients with neurogenic bladder dysfunction do well. The procedure is, however, associated with long-term complications such as disturbance of bowel habit and recurrent UTIs, which impair the outcome in the long-term in patients with DI despite general improvements in irritative bladder symptoms.

Outcome of endoscopic bladder transection.

OBJECTIVE: To determine the clinical, symptomatic and objective urodynamic outcome of patients undergoing endoscopic bladder transection. PATIENTS AND METHODS: The study included 20 men and 30 women (mean age of 50 +/- 15 years, range 20-86) who underwent endoscopic bladder transection. Their underlying diagnoses were idiopathic detrusor instability (41), enuresis with instability (6), multiple sclerosis (2) and Parkinson's disease (1). A full-thickness endoscopic transection of the bladder was performed under general anaesthesia. Subjective assessment was performed using symptom scores (0-14 points) and a Visick grading system (group A-E). Objective assessment was carried out using urodynamic studies. The mean follow-up period was 6 years (57 +/- 22 months, range 6-85). RESULTS: The mean hospital stay was 8 +/- 3 days (range 3-22). No patients died after the operation. Postoperative complications included extra-peritoneal extravasation (2), recurrent urinary tract infection (5) and urethral stricture (1). Symptom scores before and after the operation were 9 +/- 2 (range 4-14) and 8 +/- 3 (range 1-14) points respectively. The overall outcome of the procedure was satisfactory in only eight (16%) patients. The mean duration of symptomatic relief was 17 weeks (range 3-53). There was no significant difference between urodynamic results before and after the operation. Bladder instability observed in all patients before operating was demonstrated in 93% of patients after the operation. CONCLUSION: The results of our study suggests that endoscopic bladder transection produces only a transient symptomatic relief in a few of those patients who have failed to respond to pharmacological manipulations. We do not feel that its continued role is justified.

Transrectal ultrasound guided needle electromyography of the urethral sphincter in males.

Needle electromyography (EMG) of the urethral sphincter in males is commonly performed using a transperineal approach. The technique involves transcutaneous insertion of an EMG needle into the sphincter guided by the investigator's finger placed in the rectum. We describe a new method of needle placement into the urethral sphincter in males using transrectal ultrasound (TRUS). With the patient in the left lateral position, the apex of the prostate gland is identified in the longitudinal plane. Using the TRUS biopsy channel, a specially designed long EMG needle is inserted into the sphincter commencing approximately 1.5-2 cm distal to the prostatic apex in an oblique fashion. This method allows precise identification of the site for needle insertion, reducing blind attempts at localization. The transrectal route is much less uncomfortable to patients, potentially improving patient compliance and overall effectiveness of the technique.

Continent urinary diversion using the Mitrofanoff principle.

OBJECTIVE: To review the clinical and symptomatic outcome of patients undergoing cystectomy and continent urinary diversion using the Mitrofanoff principle. PATIENTS AND METHODS: There were seven men and five women (median age 62 +/- 21 years: range 21-79). The underlying diagnoses were: bladder carcinoma (8), neuropathic bladder disease (1), bladder exstrophy (1), tuberculosis (1) and interstitial cystitis (1). An ileo-caecal segment was used for construction of the reservoir. The appendix was used as a catheterizable conduit in 11 patients and a narrowed ileal tube in one patient. Symptomatic outcome was assessed by using a modified Visick grading. The median follow-up period was 15 +/- 10 months (range 6-39). RESULTS: The median hospital stay was 22 days. There were no post-operative deaths, but major post-operative complications developed in three patients and included intra-abdominal lymphocele (1), intra-abdominal abscess formation (1) and prolonged ileus (1). In the late post-operative period (> 30 days), four patients developed stenosis of the mucocutaneous junction and required dilatation. The overall symptomatic outcome was satisfactory in 11 patients. There were no deaths in the peri-operative period and none of the patients has since required revision. Urinary continence was achieved in all 12 patients during the day. One patient reported minimal, occasional leakage at nights. The median catheterization interval was 4 +/- 1 hours during the day (range 3-5) and 7 +/- 1 hours at night (range 6-9). CONCLUSION: Our experience with the Mitrofanoff procedure has been limited to a small number of patients. Despite this, the clinical outcome of the procedure was satisfactory. The procedure potentially offers an effective continence mechanism with acceptable post-operative morbidity.

Same day diagnostic service for new cases of haematuria--a district general hospital experience.

OBJECTIVE: To describe the running of a special haematuria diagnostic service which catered for a flexible cystoscopy on the same day as the first clinical visit. The impact of this service especially with regard to the timing of the intravenous urogram (IVU) is discussed. The service was designed to facilitate early diagnosis, particularly of bladder tumours, in new cases of haematuria. Potentially this would allow a more effective planning of operating lists and implementation of early definitive treatment. PATIENTS AND METHODS: Within the setting of a District General Hospital, new cases of haematuria were studied (42 male, 29 female, mean age 60 +/- 13 years). Fifty-one had a pre-clinic IVU whereas 20 had this deferred until after their first visit. All patients underwent a flexible cystoscopy under local anaesthesia on their first visit. New cases of bladder cancer were placed on the next available list for definitive treatment whilst patients with normal cystoscopy were referred back to the clinic for further investigations. RESULTS: Altering the timing of the IVU helped in reducing hospital delay from 33 +/- 19 days (range 9-92 days) to 22 +/- 9 days (range 8-52 days; P < 0.04); the number of diagnostic cystoscopies performed within 4 weeks increased from 65% to 95%. CONCLUSION: The same day diagnostic service has not been difficult to administer. Patient acceptability was excellent and design objectives were achieved.

Cystodiathermy under local anaesthesia using the flexible cystoscope.

The use of the flexible cytoscope in the follow-up of patients with bladder carcinoma is becoming more widespread. In a series of 17 patients, cystodiathermy of small recurrent tumours using the flexible cytoscope and topical urethral anaesthesia proved to be a safe, effective and well tolerated procedure.