The pharmacokinetics of equoral versus neoral in stable renal transplant patients: a multinational multicenter study

We studied the pharmacokinetics (PKs) of the new generic cyclosporine formulation, Equoral capsules, after the switch from original formulation Neoral capsules in stable renal transplant patients. The study was carried out in accordance with the basic principles defined in the US 21 CFR Part 312.20 and the principles of the Declaration of Helsinki. The study included clinically stable first renal transplant patients maintained on cyclosporine with no rejection episode during the past 6 months. Hematology, biochemistry, and urine chemistry were determined on day 7, and day 21. The patients were all switched to Neoral (lot number 416MFD0601) on day 0 when the first sparse sampling PK was performed. On day 14 a 12-hour PK profile included predose, 30 minutes; 1 hour; 1 hour 30 minutes; 2 hours; 3 hours; 4 hours; 5 hours; 6 hours; 8 hours; 10-hours and 12-hour samples. Cyclosporine levels were determined using a CYA kit (Abbott TDx). On day 15 the patients were switched from Neoral capsules to Equoral capsules (lot 5T111014) at an equivalent dosage (mg/mg). The second sparse sampling PK was performed on day 21 and a 12-hour PK was performed on day 28. On the morning of day 29 patients were switched from Equoral capsules to Neoral capsules at an equivalent dosage (mg/mg). Additional concentrations were measured on days -7, 18, and 35. Safety parameters were monitored at each visit. The pharmacokinetics of both formulations were equivalent. The mean AUC for Neoral and Equoral was 2856 and 2892, respectively. The ratios of LSM and the 90% confidence intervals for the in-transformed parameters (AUC o-t, AUC inf, and Cmax) of Equoral and Neoral SGC were 98% and 95%, respectively, suggesting that Equoral and Neoral SGC are bioequivalent.     

Observer Variability of Iliac Artery Measurements in Endovascular Repair of Abdominal Aortic Aneurysms

Accurate measurement of iliac arteries is essential for successful delivery of aortic endografts without iliac limb endoleak. Although intravascular ultrasound measurements may be reliable, they require an invasive procedure. Therefore, helical computed tomography (hCT) has become the most commonly used modality for obtaining preprocedure arterial diameter measurements. The accuracy of hCT remains ill-defined, however, because an anatomic gold standard with which to compare the measurements is not available. We therefore assessed inter- and intraobserver variability of hCT measurements. We also applied accepted cutoff measurements to determine the clinical impact of observer variability in predicting the need for adjunctive iliac access and iliac limb seal procedures. hCT scans were analyzed in 30 patients who had undergone successful placement of a bifurcated endograft (26 Ancure, 4 Aneurex). Mean age of patients was 75 years, the male/female ratio was 27:3. Three blinded observers measured transverse diameters (maximal aortic aneurysm [Amax], narrowest infrarenal aortic neck [Amin], maximal common iliac [Imax], and narrowest iliac artery [Imin]). Inter- and intraobserver variability was calculated as standard deviation of mean pair differences according to the method of Bland and Altman. The true incidence of adjunctive procedures to facilitate delivery of the device into the aorta and ensure iliac limb seal was compared with that predicted by the observers to obtain sensitivity, specificity, and positive (PPV) and negative predictive value (NPV) for the measurements. Interobserver variability of iliac measurements was higher than intraobserver variability (p < 0.05). Interobserver variability of Amax ranged from 4.37 to 10.73% of the mean Amax. Conversely, variability of Amin was 8.91-18.89%, that of Imax was 12.11-22.23%, and that of Imin was 10.51-18.73% (p < 0.05 vs. Amax). Therefore, interobserver variability influenced aortic neck and iliac diameter twice as much as it did aneurysm measurements. To successfully place 30 endografts we performed 8 adjunctive access procedures (4 angioplasties, 4 common iliac artery conduits) and 17 adjunctive procedures in 60 limbs to ensure limb seal (9 unilateral IIA coil embolizations, 8 stents). We used 8.5 (Ancure) and 8.0 (Aneurex) mm as lower limits of acceptability for uncomplicated access, and 13.4 (Ancure) and 16 (Aneurex) mm as the upper limits of acceptability for uncomplicated iliac limb seal. These limits were applied to measurements from the three observers to predict need for adjunctive access or iliac seal procedures in this cohort. Sensitivity, specificity, PPV, and NPV of these observer measurements for a need to perform additional access procedures were 0.67, 0.80, 0.55, and 0.87; the same values for a need to perform additional seal procedures were 0.71, 0.74, 0.52, and 0.86, respectively. Interobserver variability was approximately 20% of measured iliac diameter. This explains why helical CT measurements were noted to have low PPV in predicting the need for an adjunctive access or limb seal procedure. These data establish PPV and NPV for hCT and provide objective evidence for the need to improve iliac artery imaging. Until more accurate imaging becomes available, we recommend oversizing of iliac limbs by 10-20% in patients with wide landing zones and that surgeons be prepared to resolve unexpected iliac artery access or seal problems intraoperatively.Presented at the 13th Annual Winter Meeting of the Peripheral Vascular Surgery Society, Steamboat Springs, CO, January 31-February 2, 2004.     

Minimally Invasive Gastric Bypass in a Morbidly Obese Patient with Myasthenia Gravis

Associated or rare diseases, such as myasthenia gravis, introduce a challenge to the perioperative management of severely obese patients undergoing bariatric surgery. We report the surgical management and unique anesthetic approach to a 55-year-old morbidly obese woman with a complex past medical history that included myasthenia gravis, who underwent laparoscopic gastric bypass. Her myasthenia was controlled on pyridostigmine and her greatest concern was the potential need for postoperative mechanical ventilation. While the laparoscopic surgical approach was ideal to reduce pain and the adverse effects on ventilatory mechanics associated with open upper abdominal surgery, a combined inhalational and intravenous anesthetic without muscle relaxants resulted in satisfactory surgical conditions, and allowed for immediate postoperative extubation followed by an uneventful postoperative course. Continued perioperative anticholinesterase administration may have facilitated this successful outcome. We conclude that a diagnosis of myasthenia gravis does not mandate postoperative mechanical ventilation following laparoscopic gastric bypass.     

Peer review audit of trauma deaths in a developing country

OBJECTIVES: Peer review of trauma deaths can be used to evaluate the efficacy of trauma systems. The objective of this study was to estimate teh proportion of preventable trauma deaths and the factors contributing to poor outcome using peer review in a tertiary care hospital in a developing country. METHODS: All trauma deaths during a 2-year period (1 January 1998 to 30 December 1998) were identified and registered in a computerized trauma registry, and the probability of survival was calculated for all patients. Summary data, including registry information and details of prehospital, emergency room, and definitive care, were provided to all members of the peer review committee 1 week before the committee meeting. The committee then reviewed all cases and classified each death as preventable, potentially preventable, or non-preventable. RESULTS AND CONCLUSION: A total fo 279 patients were registered in the trauma registry during the study period, including 18 trauma deaths. Peer review judged that six were preventable, seven were potentially preventable, and four were non-preventable. One patient was excluded because the record was not available for review. The proportion of preventable and potentially preventable deaths was significantly higher in our study than from developed countries. Of the multiple contributing factors identified, the most important were inadequate prehospital transfer, limited hospital resources, and an absence of integrated and organized trauma care. This study summarizes the challenges faced in trauma care in a developing country.     

Malignant hyperthermia

Malignant hyperthermia refers to covert myopathies, which do not affect the individual during daily life activities, but may lead to life-threatening tachycardia, rigor, labile blood pressure and most importantly high-grade temperature when exposed to general anaesthesia. This conditions is mimicked by thyroid storm, neuroleptic malignant syndrome, phaeochromocytoma and sepsis. We present a presumptive case of malignant hyperthermia.     

Two displaced intrauterine contraceptive devices (copper-T)

An unusual case of two displaced intrauterine contraceptive devices (copper-T) is described in a 34 years old lady. One copper-T was found in the urinary bladder with stone formation around it and the other embedded in the posterior wall of the urinary bladder. This was managed operatively and the patient made a smooth recovery.     

Percutaneous nephrolithotomy in children before school age: experience of a Pakistani centre

OBJECTIVE: To review our experience of percutaneous nephrolithotomy (PCNL) in children before school age, and determine its efficacy and safety in this age group. PATIENTS AND METHODS: The records of children aged < or = 5 years undergoing PCNL were reviewed. Variables assessed included stone number, size, location and type. The PCNL puncture site and number were also recorded. We reviewed stone clearance with PCNL, ancillary procedures used, complication rates and follow-up status of the children. RESULTS: There were 30 renal units in 29 children (median age 3.8 years, range 1.4-5). Because of poor growth the mean (SD) body weight of the children was only 12.2 (2.8) kg, which is near the 50th percentile for children of mean age 3.5 years. The median (range) stone burden was 2.35 (1.3-6) cm; 60% of the patients had single stones while 28% had more than five. There were five staghorn stones. All PCNL was primary and with one puncture, using a 17 F angled nephroscope; stones were fragmented using a pneumatic lithoclast. After PCNL stones were completely cleared in 60% of the renal units, which increased to 100% after combining it with extracorporeal shockwave lithotripsy. The median (range) follow-up was 24.9 (4-51) months; the overall complication rate was 6%. In the long follow-up hypertension was not detected in any child and isotopic renograms in 17 kidneys detected no new scarring or loss of renal function. CONCLUSION: PCNL is a safe and effective for treating renal stones in very young children.     

Effect of pupillary dilation on retinal nerve fiber layer thickness measurements using optical coherence tomography

PURPOSE: To evaluate the effect of pupillary dilation on retinal nerve fiber layer thickness (RNFL) measurements using optical coherence tomography (OCT-3). METHODS: Randomly chosen eyes of healthy individuals were scanned before and after pupillary dilation by two trained operators (R.G.O., R.V.) using OCT-3 (Carl Zeiss Meditec, Inc., Dublin, CA). Fast and regular RNFL (256 A-scans) OCT-3 protocols (software version A1.1) were used in each scanning session. RNFL thickness measurements before and after dilation were compared. RESULTS: Ten eyes of 10 subjects (6 females, 4 males) were enrolled. Mean age was 32.0 +/- 11.2 years (range, 21 to 52 years). Mean pupillary diameter before and after dilation was 2.9 +/- 0.6 mm and 7.6 +/- 0.8 mm, respectively (P < 0.0001, paired t-test). There was no significant difference in RNFL thickness measurements before and after dilation using both fast and regular RNFL protocols (P > or = 0.05 for all comparisons, paired t-test). Mean coefficients of variation for mean RNFL thickness measurements were 15.3% before and 13.7% after dilation for operator 1; and 10.8% before and 12.7% after dilation for operator 2 for the fast RNFL protocol and 11.3% versus 10.4% and 12.9 versus 11.1%, respectively, for the regular RNFL protocol. CONCLUSION: Pupillary dilation is not necessary in all subjects to obtain reproducible RNFL thickness measurements using OCT-3.     

Peyronie's disease: an update of the medical management

Peyronie's disease (PD) is characterised by penile plaque formation, pain, penile deformity and erectile dysfunction. It is a fibrotic disorder of the tunica albuginea with a poorly understood aetiology and epidemiology. PD may be classified into inflammatory (acute) and chronic stages. Medical treatment is usually instigated during the inflammatory phase of the disease. A review of the literature reveals a wide range of oral, intralesional and alternative therapies that are discussed in relation to established pathophysiological mechanisms of the disease. The advantages and disadvantages of each treatment are summarised. This review also discusses the ongoing therapeutic dilemmas of PD and suggests a treatment strategy based on an analysis of the urological literature.