The role of CC chemokine receptor 5 (CCR5) in islet allograft rejection

Chemokines are important regulators in the development, differentiation, and anatomic location of leukocytes. CC chemokine receptor 5 (CCR5) is expressed preferentially by CD4(+) T helper 1 (Th1) cells. We sought to determine the role of CCR5 in islet allograft rejection in a streptozotocin-induced diabetic mouse model. BALB/c islet allografts transplanted into CCR5(-/-) (C57BL/6) recipients survived significantly longer (mean survival time, 38 +/- 8 days) compared with those transplanted into wild-type control mice (10 +/- 2 days; P < 0.0001). Twenty percent of islet allografts in CCR5(-/-) animals without other treatment survived >90 days. In CCR5(-/-) mice, intragraft mRNA expression of interleukin-4 and -5 was increased, whereas that of interferon-gamma was decreased, corresponding to a Th2 pattern of T-cell activation in the target tissues compared with a Th1 pattern observed in controls. A similar Th2 response pattern was also observed in the periphery (splenocytes responding to donor cells) by enzyme-linked immunosorbent spot assay. We conclude that CCR5 plays an important role in orchestrating the Th1 immune response leading to islet allograft rejection. Targeting this chemokine receptor, therefore, may provide a clinically useful strategy to prevent islet allograft rejection.     

Primary localized amyloidosis of the bladder: experience with dimethyl sulfoxide therapy

PURPOSE: We present our long-term experience with intravesical dimethyl sulfoxide (DMSO) for primary localized amyloidosis of the bladder. MATERIALS AND METHODS: The study included 4 males and 2 females 28 to 68 years old (mean age 54) at diagnosis of biopsy proven primary localized amyloidosis involving the bladder diffusely or extensively in 1 locale. All patients had normal upper urinary tracts. They continued to be symptomatic (hematuria in 3, irritative voiding symptoms in 1, and hematuria and irritative voiding symptoms in 2) despite conventional transurethral destructive therapy. Every 2 weeks they received 30-minute instillations of 50 ml. 50% DMSO intravesically for 3 months (patient 1), 6 months (1) and 1 year (4). RESULTS: Therapy failed at 3 and 6 months in 2 patients of whom 1 with a contracted bladder underwent cystectomy and another was stabilized for 1 year with laser therapy. In the remaining 4 patients who were followed for 6 years disease stabilized for 2 to 6 years (mean 3.5) but 3 later required additional therapy including repeat DMSO in 1 and laser therapy in 2. CONCLUSIONS: Diffuse or locally extensive bladder involvement by primary localized amyloidosis usually fails to respond to conventional transurethral destructive surgical procedures. Collectively, our experience and the literature suggest that intravesical DMSO can be a bladder saving measure and help resolve ureterovesical obstruction in some patients. High recurrence rate mandates lifelong cystoscopic surveillance.     

Symphysiotomy: a viable approach for delayed management of posterior urethral injuries in children

PURPOSE: The outcome of symphysiotomy for accessing pelvic fracture related, obliterative urethral strictures is described. MATERIALS AND METHOD: In 7 boys and 3 girls 4 to 13 years old (mean age 6) surgical correction of a pelvic fracture related, obliterative urethral stricture was achieved through symphysiotomy. The stricture involved a prostatomembranous location in boys and complete vesicourethral distraction in girls. Patients were followed an average of 2.5 years (range 6 months to 4 years) by physical examination, urethrography and endoscopy. RESULTS: The stricture was successfully corrected in all patients and all void with a normal flow. All boys are continent but 2 of the 3 girls had early incontinence, which resolved with time in 1. In 2 of the 10 cases a previous attempt at perineal repair had already failed. No patient required urethrotomy or dilation and none had significant hemorrhage, fistulization, bladder hernia, chronic pain or secondary gait disturbance. CONCLUSIONS: Symphysiotomy is hereby revisited as a simple and effective approach for repairing traumatic posterior urethral injuries in the pediatric population. It can be performed instead of transpubic urethroplasty to manage long or otherwise complicated strictures.     

Greater trochanteric preserving hip arthroplasty in the treatment of infantile septic arthritis: long-term results

Background  

Balanced forces around the hip joint are critical for normal development of the hip joint, so it should be considered in every hip reconstructive procedure.     

Indicators of a Reduced Intercarotid Artery Distance in Patients Undergoing Endoscopic Transsphenoidal Surgery

Objective To identify clinicopathologic factors associated with a reduced intercarotid distance (ICD) and subgroups at risk for internal carotid artery injury during transsphenoidal surgery. Design A retrospective case-control study. Setting This study was conducted at the McGill University Health Centre, a university-affiliated tertiary care center. Participants Patients with a sellar or parasellar tumor and nontumor controls were included in the study. Main Outcome Measures The smallest distance between the internal carotid arteries at the clival, cavernous, and paraclinoid segments on coronal magnetic resonance imaging was measured. Demographic profiles, cephalometric measurements, tumor dimensions, and sphenoid configuration were assessed as potential determinants of the ICD. Results A total of 212 cases and 34 controls were analyzed. Widening of the ICD at the three segments of the internal carotid arteries was found in patients with pituitary macroadenomas (p < 0.01). Patients with a growth hormone–secreting adenoma had a markedly reduced ICD at the clivus compared with controls (1.59 cm versus 1.77 cm; p = 0.02; 95% confidence interval [CI], 0.03–0.32). The paraclinoid ICD was reduced in patients with an anterior fossa meningioma (1.24 cm versus 1.33 cm; p = 0.04; 95% CI, 0.01–0.45). Conclusion Identifying clinicopathologic factors affecting the ICD can help surgeons recognize constraints to endoscopic access of the skull base and avoid inadvertent arterial injury.     

Solution of a specific class of nonlinear fractional optimal control problems including multiple delays

This research provides a new framework based on a hybrid of block‐pulse functions and Legendre polynomials for the numerical examination of a special class of scalar nonlinear fractional optimal control problems involving delay. The concepts of the fractional derivative and the fractional integral are employed in the Caputo sense and the Riemann‐Liouville sense, respectively. In accordance with the notion of the Riemann‐Liouville integral, we derive a new integral operator related to the proposed basis called the operational matrix of fractional integration. By employing two significant operators, namely, the delay operator and the integral operator connected to the hybrid basis, the system dynamics of the primal optimal control problem converts to another system involving algebraic equations. Consequently, the optimal control problem under study is reduced to a static optimization one that is solved by existing well‐established optimization procedures. Some new theoretical results regarding the new basis are obtained. Various kinds of fractional optimal control problems containing delay are examined to measure the accuracy of the new method. The simulation results justify the merits and superiority of the devised procedure over the existing optimization methods in the literature.     

Serum zinc and copper levels in children with chronic renal failure

We evaluated changes in serum zinc (Zn) and copper (Cu) levels in two groups of children with chronic renal failure (CRF) – children with CRF who were on regular hemodialysis (Group 1, n=40) and children with CRF who were on conservative management (Group 2, n=31) – and in one group of healthy children (Group 3, n=30). All of the participants in the study were between 5–18 years old, and the composition of the three groups was almost identical with respect to age and sex. The length of time the children in Group 1 had been on hemodialysis varied between 3 and 52 months (mean: 20.97±14.8 months). To evaluate the impact of the duration of dialysis on serum levels of Zn, we further sub-divided Group 1 patients into two subgroups: Subgroup A patients (n=20) had been on hemodialysis therapy for less than 18 months (mean: 8.85±4.83 months); Subgroup B patients (n=20) had been on hemodialysis therapy for longer than 18 months (mean: 33.1±10.86 months). The PIXE (proton-induced X-ray emission) was used for measuring the trace elements. Results: The mean serum level of Zn was lower in the Group 1 (hemodialysis group) children than in the children of Group 2 (on conservative management) and group 3 (healthy children) (p<0.001), but the difference was not significant between Groups 2 and 3. No significant differences in serum levels of Cu were found among the three groups. The serum level of Zn was lower in Subgroup B than in Subgroup A (p<0.001). The correlation test showed that there was an inverse linear relation between the length of time the child was on the hemodialysis regimen and serum Zn levels. Conclusion: Chronic hemodialysis may lead to abnormalities in the serum levels of some trace elements in children with CRF that increase in severity with increasing duration of hemodialysis. Deficiencies of these trace elements – zinc in particular – may contribute to various conditions and symptoms in children undergoing chronic hemodialysis.     

Right pulmonary artery occlusion by an acute dissecting aneurysm of the ascending aorta

We describe the case of a 76-year old female who presented with a Type A aortic dissection requiring repair with an interposition graft and aortic valve replacement. Post-operatively she had clinical features and computerised tomographic images suggestive of a pulmonary embolus and died 24 hours later. The extremely rare finding of intramural thrombus occluding the right pulmonary artery was seen at post mortem.