Six-month clinical outcome of cyclosporine microemulsion formulation (Sigmasporin Microral) in stable renal transplant patients previously maintained on sandimmun neoral

The trial objective was to investigate the feasibility and safety of conversion to a generic microemulsion cyclosporine in stable renal transplant patients premaintained on Neoral. We enrolled 75 patients from seven centers in five Middle Eastern countries monitored them for 6 months after conversion to Sigmasporin Microral. Readings at 0, 0.5, 1, 2, 3, 4.5, and 6 months included cyclosporine blood level, serum creatinine, liver enzymes, lipid profile, blood sugar, blood pressure and adverse events. Patients included 54 men and 21 women of mean age 38.9 +/- 10.7 years at 30.3 +/- 29.3 months post-transplantation maintained on Sigmasporin Microral dose of 2.8 +/- 1.0 mg/kg per day; they were observed to be stable throughout the study period as reflected by the therapeutic blood C(0) level of 181.6 +/- 102.1 and C(2) of 759.2 +/- 384.4. Their absorption profile as represented by C(2)/C(0) was 4.9 +/- 2.8, and C(2)/cyclosporine dose of 282.3 +/- 128.8. An average serum creatinine level of 116.1 +/- 29.5 mumol/L denoted stable graft function and their liver enzymes did not change during the study. No new-onset cases of hypertension, diabetes mellitus, or hyperlipidemia were reported among the patients. Graft function was stable for all patients, except for two incidences of mild acute rejection and two of mild cyclosporine nephrotoxicity; graft and patient survival rates were both 100%. Results of this 6-month study showed that Sigmasporin Microral was effective to maintain stable renal function in kidney transplant patients converted from Neoral with similar safety and tolerability profiles as those reported in the literature.     

Long-term administration of nicorandil abolishes ischemic and pharmacologic preconditioning of the human myocardium: role of mitochondrial adenosine triphosphate-dependent potassium channels

BACKGROUND: Acute administration of mitochondrial adenosine triphosphate-dependent potassium channel openers preconditions the heart, but whether their long-term administration induces a permanent state of protection is unknown. These studies investigate the effect of long-term treatment with the mitochondrial adenosine triphosphate-dependent potassium channel opener nicorandil on the response of the human myocardium to ischemia and preconditioning. METHODS: Right atrial tissue obtained from patients regularly treated with or without nicorandil (mean of 20 mg/d for 18.6 +/- 2.5 months) and undergoing cardiac surgery was sliced and equilibrated for 30 minutes and then subjected to 90 minutes of simulated ischemia, followed by 120 minutes of reoxygenation. In study 1 the following groups were studied to investigate the effect of nicorandil on the susceptibility of the myocardium to ischemia and on the protective effect of ischemic and pharmacologic preconditioning: (1) aerobic control; (2) simulated ischemia and reoxygenation alone; (3) ischemic preconditioning with 5 minutes of simulated ischemia and 5 minutes of reoxygenation; and (4) phenylephrine (0.1 micromol/L) for 5 minutes and 5 minutes' washout before simulated ischemia and reoxygenation. In study 2 the following groups were studied to investigate the effect of nicorandil on the responsiveness of mitochondrial adenosine triphosphate-dependent potassium channels: (1) aerobic control; (2) simulated ischemia and reoxygenation; (3) ischemic preconditioning; (4) diazoxide (100 micromol/L) for 10 minutes before simulated ischemia and reoxygenation, and (5) 5-hydroxydecanoate (1 mmol/L) for 10 minutes before simulated ischemia and reoxygenation. In study 3 the following groups were included to investigate the effect of the long-term administration of nicorandil on the kinase pathway involved in preconditioning: (1) aerobic control; (2) simulated ischemia and reoxygenation alone; (3) ischemic preconditioning; (4) phorbol 12-myristate 13-acetate (1 micromol/L), a protein kinase C activator, for 10 minutes before simulated ischemia and reoxygenation; and (5) anisomycin (1 nmol/L), a p38 mitogen-activated protein kinase activator, for 10 minutes before simulated ischemia and reoxygenation. At the end of each protocol, the leakage of creatine kinase (in units per gram wet weight) and the reduction of 3-[4,5 dimethylthiazol-2-yl]-2,5 diphenyltetrazolium bromide into insoluble formazan dye (in millimoles per gram wet weight) were measured. RESULTS: In study 1 the leakage of creatine kinase and the reduction of 3-[4,5 dimethylthiazol-2-yl]-2,5 diphenyltetrazolium bromide induced by simulated ischemia and reoxygenation were similar in the groups with or without nicorandil (creatine kinase, 3.4 +/- 0.1 and 3.5 +/- 0.2, respectively; 3-[4,5 dimethylthiazol-2-yl]-2,5 diphenyltetrazolium bromide, 74.6 +/- 3.9 and 67.9 +/- 7.3, respectively; P >.2 in each instance). Ischemic preconditioning and pharmacologic preconditioning protected the myocardium from patients without nicorandil (creatine kinase, 2.3 +/- 0.1 and 2.4 +/- 0.1, respectively; 3-[4,5 dimethylthiazol-2-yl]-2,5 diphenyltetrazolium bromide, 131.4 +/- 4.9 and 128.4 +/- 5.6, respectively; P < 0.001 vs simulated ischemia and reoxygenation alone in each instance) but not the myocardium from patients receiving nicorandil (creatine kinase, 3.3 +/- 0.1 and 3.3 +/- 0.2, respectively; 3-[4,5 dimethylthiazol-2-yl]-2,5 diphenyltetrazolium bromide, 89.7 +/- 6.5 and 86.4 +/- 5.2, respectively; P >.2 vs simulated ischemia and reoxygenation alone in each instance). In study 2 the administration of diazoxide had identical protection to that of ischemic preconditioning in the myocardium of patients not receiving nicorandil (creatine kinase, 2.1 +/- 0.2 and 2.3 +/- 0.1, respectively; 3-[4,5 dimethylthiazol-2-yl]-2,5 diphenyltetrazolium bromide, 141.4 +/- 7.4 and 131.4 +/- 4.9, respectively; P < 0.001 vs simulated ischemia and reoxygenation alone in each instance) but failed to precondition the myocardium from patients treated with nicorandil (creatine kinase, 3.3 +/- 0.2 and 3.4 +/- 0.1, respectively; 3-[4,5 dimethylthiazol-2-yl]-2,5 diphenyltetrazolium bromide, 90.1 +/- 7.2 and 86.4 +/- 5.2, respectively; P > 0.2 vs simulated ischemia and reoxygenation alone in each instance). In study 3 phorbol 12-myristate 13-acetate or anisomycin given for 10 minutes before simulated ischemia and reoxygenation afforded similar protection to that of ischemic preconditioning in the myocardium from patients with (creatine kinase, 1.5 +/- 0.3 and 1.4 +/- 0.1, respectively; 3-[4,5 dimethylthiazol-2-yl]-2,5 diphenyltetrazolium bromide, 147.0 +/- 4.9 and 160.0 +/- 16.1, respectively; P < 0.001 vs simulated ischemia and reoxygenation alone in each instance) and without nicorandil (creatine kinase, 1.7 +/- 0.4 and 1.4 +/- 0.2, respectively; 3-[4,5 dimethylthiazol-2-yl]-2,5 diphenyltetrazolium bromide, 160.3 +/- 13.6 and 158.3 +/- 11.8, respectively; P <.001 vs simulated ischemia and reoxygenation alone in each instance). CONCLUSION: The myocardium of patients chronically treated with nicorandil cannot be preconditioned either by ischemia or pharmacologically, and this is because of unresponsive mitochondrial adenosine triphosphate-dependent potassium channels. However, protection can be obtained by protein kinase C and p38 mitogen-activated protein kinase activation, which are downstream of mitochondrial adenosine triphosphate-dependent potassium channels in the signaling transduction pathway of preconditioning.     

Sexual function in women after rectocele repair with acellular porcine dermis graft vs site-specific rectovaginal fascia repair

The objective of the study was to compare preoperative and postoperative sexual function between women undergoing rectocele repair with porcine dermis graft and women undergoing site-specific repair of rectovaginal fascia. A standardized, validated questionnaire (Pelvic Organ Prolapse/Urinary Incontinence Sexual Function Questionnaire [PISQ]) was used to collect preoperative sexual function data from 100 patients with rectocele pelvic organ prolapse quantification stage 2 or greater. Fifty women underwent rectocele repair utilizing porcine dermis graft (group 1) and 50 women underwent a site-specific repair of the rectovaginal fascia (group 2). The same questionnaire was administered to all subjects 6 months after surgery. The two groups were similar in age, race, parity, prior hysterectomy, and postmenopausal hormone use. Preoperative sexual function scores were similar in the two groups (group 1 81.4 ± 7.3 and group 2: 83.6 ± 8.2, p = 1.0). Six months after surgery, PISQ scores in group 1 significantly increased (score increase 19.9 ± 2.2, p = 0.01). The mean increase in PISQ scores for group 2 was 6.9 ± 3.1 (p = 0.08). When compared with group 2, subjects undergoing rectocele repair with porcine dermis graft scored significantly higher on the PISQ 6 months after surgery (group 1 101.3 ± 6.4 and group 2 89.7 ± 7.1, p = 0.01). We conclude that rectocele repair using porcine dermis graft is associated with improved sexual functioning when compared with site-specific rectovaginal fascia repair.     

Dexamethasone 8 mg in combination with ondansetron 4 mg appears to be the optimal dose for the prevention of nausea and vomiting after laparoscopic cholecystectomy

PURPOSE: The combination of antiemetic drugs could be a solution to prevent severe postoperative nausea and vomiting (PONV). The aim of this randomized double blind, dose-ranging study was to determine the minimum single effective dose of dexamethasone combined with ondansetron for the prevention of PONV in patients undergoing laparoscopic cholecystectomy. METHODS: One hundred eighty patients were allocated randomly to one of six groups to receive saline (P group), ondansetron 4 mg (O group), or ondansetron 4 mg and dexamethasone at doses of 2 mg (OD2 group), 4 mg (OD4 group), 8 mg (OD8 group), and 16 mg (OD16 group). A standardized general anesthetic was used. All episodes of PONV during the intervals of zero to six hours, 6-12 hr and 12-24 hr after surgery were evaluated using a numeric scoring system. Mean visual analogue scale pain scores at rest and on movement, the time to first demand of analgesia, total analgesic consumption in 12 hr epochs, duration of hospital stay, and side effects were recorded. RESULTS: The incidence of PONV in the OD8 (16%) and OD16 (16%) groups was lower than in the 83% (P < 0.001) and O groups (50%) at the 12-24 hr epoch (P < 0.05). There were no differences in antiemetic effect between the O, OD2 and OD4 groups and between the OD8 and OD16 groups. Pain scores, total analgesic consumption, duration of hospital stay and side effects were similar among groups. CONCLUSION: Our results suggest that 8 mg is the minimum dose of dexamethasone that, combined with ondansetron 4 mg will effectively prevent PONV in patients undergoing laparoscopic cholecystectomy.     

Open complete anterior dislocation of the sacro-iliac joint in a 4-year-old boy: a case report of a rare injury with 5-year follow-up

Pelvic fractures are uncommon in children and account for between 0.3 and 7.5% of all pediatric injuries. Open pelvic fractures only account for up to 12.9% of all pediatric pelvic fractures. An unusual case of open complete anterior sacro-iliac joint dislocation in a 4-year-old boy is presented with a long-term follow-up. The multidisciplinary approach is reported with review of the current literature. A 4-year-old male presented to our institution in January 2012 after having been run over by a tractor. He presented with gross hemodynamical instability, MISS of 25, and an unstable lateral compression type III pelvic fracture with complete anterior dislocation of the left hemipelvis and a groin wound extending into the left thigh. The patient was managed in accordance with the ATLS and open fracture guidelines. Reduction in the dislocated SI joint was achieved via a posterior approach to the SI joint, followed by fixation with 2K wires in S1 and S2 sacral segments, with an anterior external fixator. Pelvic asymmetry post-reduction was 0.9 cm, compared to 16 cm post-injury, and asymmetry persisted till final follow-up at 5 years. At 5 years, patient regained full function, including recreational sport activities. Patients scored a 96/96 on the Majeed score (after excluding 4 points for sexual function). We believe that posterior reduction in an anteriorly dislocated SI joint in the pediatric population is a viable option. A coordinated, multidisciplinary approach and restoration of pelvic ring stability can lead to optimal outcome.     

Extracorporeal life support in pediatric cardiac dysfunction

Background  

Low cardiac output (LCO) after corrective surgery remains a serious complication in pediatric congenital heart diseases (CHD). In the case of refractory LCO, extra corporeal life support (ECLS) extra corporeal membrane oxygenation (ECMO) or ventricle assist devices (VAD) is the final therapeutic option. In the present study we have reviewed the outcomes of pediatric patients after corrective surgery necessitating ECLS and compared outcomes with pediatric patients necessitating ECLS because of dilatated cardiomyopathy (DCM).     

The new “dual osteotomy”: combined open wedge and tibial tuberosity anteriorisation osteotomies

The high frequency with which medial compartment osteoarthritis is associated with patellofemoral osteoarthritis makes the addition of tibial tuberosity anteriorisation to high tibial osteotomy an appealing solution, despite the discouraging previously reported long-term results when tubercle anteriorisation was combined with a Coventry closed wedge technique. We conducted a prospective study of a new osteotomy combination: “the dual osteotomy”. An open wedge high tibial osteotomy was combined with 1- to 1.5-cm Maquet-like tibial tuberosity anteriorisation. Thirty-four knees in 30 patients underwent surgery, including ten knees in nine male patients and 24 knees in 21 female patients with a mean age of 45 years (age range 34−58 years). All patients had varus medial compartment osteoarthritis and patellofemoral osteoarthritis with preoperative anatomical tibiofemoral angle exceeding 5°. Twenty-four months after surgery, final evaluation detected improvement in the Knee Society clinical rating system function score from a mean of 61.3 (range 30−80) preoperatively to a mean of 87.3 (range 50−100) postoperatively and in the knee pain score from 27.3 (range 10−30) to 47 (range 30−50) postoperatively. Based on the rating system, at final follow-up, 70% of patients experienced no pain, 13% had mild or occasional pain, 10% had pain on stairs only, and 7% had pain during walking and on stairs. Anatomical tibiofemoral angles from 0 to 10° valgus were achieved in 91% of operated knees, and union was achieved in all cases within six to twelve weeks after surgery. The dual osteotomy was effective in the short term in cases of medial compartment osteoarthritis associated with patellofemoral osteoarthritis.     

Combination therapy with intra‐articular injection of mesenchymal stem cells and articulated joint distraction for repair of a chronic osteochondral defect in the rabbit

The present study investigated intra‐articular injection of bone‐marrow‐derived mesenchymal stem cells (MSCs) combined with articulated joint distraction as treatment for osteochondral defects. Large osteochondral defects were created in the weight‐bearing area of the medial femoral condyle in rabbit knees. Four weeks after defect creation, rabbits were divided into six groups: control group, MSC group, distraction group, distraction + MSC group, temporary distraction group, and temporary distraction + MSC group. Groups with MSC received intra‐articular injection of MSCs. Groups with distraction underwent articulated distraction arthroplasty. Groups with temporary distraction discontinued the distraction after 4 weeks. The rabbits were euthanized at 4, 8, and 12 weeks after treatment except temporary distraction groups which were euthanized at only 12 weeks. Histological scores in the distraction + MSC group were significantly better than in the control, MSC group or distraction group at 4 and 8 weeks, but showed no further improvement. At 12 weeks, the temporary distraction + MSC group showed the best results, demonstrating hyaline cartilage repair with regeneration of the osteochondral junction. In conclusion, joint distraction with intra‐articular injection of MSCs promotes early cartilage repair, and compressive loading of the repair tissue after temporary distraction stimulates articular cartilage regeneration. © 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 33:1466–1473, 2015.