Arrhythmogenic gene remodelling in elderly patients with type 2 diabetes with aortic stenosis and normal left ventricular ejection fraction.

NEW FINDINGS: What is the central question of this study? Type 2 diabetes is associated with a higher rate of ventricular arrhythmias compared with the non-diabetic population, but the associated myocardial gene expression changes are unknown; furthermore, it is also unknown whether any changes are attributable to chronic hyperglycaemia or are a consequence of structural changes. What is the main finding and its importance? We found downregulation of left ventricular ERG gene expression and increased NCX1 gene expression in humans with type 2 diabetes compared with control patients with comparable left ventricular hypertrophy and possible myocardial fibrosis. This was associated with QT interval prolongation. Diabetes and associated chronic hyperglycaemia may therefore promote ventricular arrhythmogenesis independently of structural changes. Type 2 diabetes is associated with a higher rate of ventricular arrhythmias, and this is hypothesized to be independent of coronary artery disease or hypertension. To investigate further, we compared changes in left ventricular myocardial gene expression in type 2 diabetes patients with patients in a control group with left ventricular hypertrophy. Nine control patients and seven patients with type 2 diabetes with aortic stenosis undergoing aortic valve replacement had standard ECGs, signal-averaged ECGs and echocardiograms before surgery. During surgery, a left ventricular biopsy was taken, and mRNA expressions for genes relevant to the cardiac action potential were estimated by RT-PCR. Mathematical modelling of the action potential and calcium transient was undertaken using the O'Hara-Rudy model using scaled changes in gene expression. Echocardiography revealed similar values for left ventricular size, filling pressures and ejection fraction between groups. No difference was seen in positive signal-averaged ECGs between groups, but the standard ECG demonstrated a prolonged QT interval in the diabetes group. Gene expression of KCNH2 and KCNJ3 were lower in the diabetes group, whereas KCNJ2, KCNJ5 and SLC8A1 expression were higher. Modelling suggested that these changes would lead to prolongation of the action potential duration with generation of early after-depolarizations secondary to a reduction in density of the rapid delayed rectifier K+ current and increased Na+ -Ca2+ exchange current. These data suggest that diabetes leads to pro-arrythmogenic changes in myocardial gene expression independently of left ventricular hypertrophy or fibrosis in an elderly population.

Pharmacokinetics of liposomal encapsulated buprenorphine suspension following subcutaneous administration to cats.

We investigated the effects of liposome encapsulation at prolonging the systemic exposure of buprenorphine following subcutaneous administration in cats. Seven healthy male cats were dosed intravenously with 0.02 mg/kg buprenorphine solution (STD-BUP), followed 14 days later by a subcutaneous injection of 0.2 mg/kg buprenorphine as a liposomal suspension (SUS-BUP) containing drug molecules both in liposomes and the suspending vehicle. Buprenorphine time plasma concentration data for both dosing routes were analyzed simultaneously with four compartmental models. Goodness of fit was assessed both graphically and with the Akaike information criterion. The time-course of intravenous STD-BUP was biphasic, with a 4.39 h average terminal half-life. The subcutaneous SUS-BUP produced plasma buprenorphine concentrations above 0.5 µg/L for more than 96 h, with three distinct peaks in the first 15 h. The model with best fit comprised a central and a peripheral compartment, plus three subcutaneous absorption compartments: one of dissolved drug molecules that were absorbed through a first-order process, and two of liposome-encapsulated drug molecules that were transferred to the solution compartment through separate zero-order processes. Liposomes effectively prolonged the systemic exposure of buprenorphine in cats.

Laparoscopic Transplantation Following Transvaginal Insertion of the Kidney: Description of Technique and Outcome.

Laparoscopic kidney transplantation (LKT) is well accepted modality of treatment for ESRD patients at our center. Usually, the kidney is inserted through small Pfannenstiel incision. With the permission of the Internal Review Board, we carried out LKT in eight female recipients following insertion of the kidney through the vagina. The kidney was procured by the retroperitoneoscopic approach. Antibiotic prophylaxis was given. All cases were carried out successfully with immediate graft function and 100% graft and patient survival at 1 year of follow-up. Estimated glomerular filtration rate at 1 month and 1 year was similar to eight randomly selected female recipients who underwent open kidney transplantation (OKT). No analgesia was required in seven out of eight patients after the 3rd postoperative day. In summary, vaginal insertion of kidney and LKT is safe and feasible in a selected group of patients. It is associated with better analgesia and has similar allograft function as compare to OKT.

The analgesic efficacy of continuous transversus abdominis plane block in renal transplant recipients.

BACKGROUND AND AIMS: Transversus abdominis plane (TAP) block is suitable for operations where parietal pain is a major cause of pain. Renal transplant recipients are ideally suited to gain maximum benefit from TAP block as the incision classically involves the lower abdomen. This study was conducted to evaluate the analgesic efficacy of continuous TAP block in transplant recipients. MATERIAL AND METHODS: In a prospective double-blind study, 40 chronic renal failure patients undergoing open renal transplant were randomly divided into two groups. At the end of surgery during closure, a multiorifice epidural catheter was placed in TAP plane. Study group (Group S) received Inj bupivacaine bolus 1 mg/kg (0.25%) followed by infusion 0.25 mg/kg (0.125%) through the catheter, whereas control group (Group C) received normal saline through the catheter. Inj pentazocine (0.3 mg/kg) was given as rescue analgesic at visual analogue score (VAS) > 3 in any group at rest or on movement. The analgesic efficacy was judged by VAS, time of first rescue analgesic, and total analgesic consumption in 24 h. RESULTS: Patients in Group S had significant lower VAS scores, longer time to first rescue analgesic (270 ± 347.96 vs. 42.85 ± 32.27 min) and lower pentazocine consumption (9.75 ± 13.95 vs. 56.42 ± 12.46 mg) in 24 h. There was significant sedation in Group C. CONCLUSION: The TAP catheter technique for postoperative pain control after renal transplant has proved to be effective in relieving the postoperative pain after renal transplant with less pentazocine requirement and less sedation.

First Report of Diplodia seriata Causing Pear Branch Canker Dieback in California.

California produces 26% of the United States pear crop on approximately 5,600 ha. A survey of seven northern California pear orchards (Pyrus communis cv. Bartlett) in summer 2010 revealed the presence of wedge-shaped cankers on 2- to 5-cm diameter branches, equating to 1- to 3-year-old wood. Many of the observed cankers occurred near pruning wounds, and there was decreased foliation on infected branches. Infected wood was surface disinfected with 95% ethanol and briefly flamed. After removing bark, small sections of diseased tissue were plated onto 4% potato dextrose agar (PDA) amended with 0.01% tetracycline and placed on the lab bench at 22°C until fungal growth emerged. Fungal colonies that were consistently isolated were transferred to fresh PDA using hyphal tip isolation. Fungal colonies were dark brown to gray with aerial mycelium and formed pycnidia after 15 days of incubation at 22°C. Conidia were brown, oval to oblong, and measured (16.5-) 20 to 24 (-26) × (7.5) 8.75 to 11 (-12.5) µm (n = 50). DNA from 14- to 21-day-old colonies was extracted and sequences of the rDNA internal transcribed spacer region and part of the ß-tubulin gene were amplified using primers ITS4/ITS5 and Bt2a/Bt2b, respectively (2). The DNA sequences of fungal isolates from California showed 99 to 100% homology with the ex-type Diplodia seriata De Not. (1) CBS112555 deposited in GenBank. DNA sequences from three California isolates were submitted to GenBank with accession numbers KC937062, KC937065, KF481957, KF481598, KF481959, and KF481960. Pathogenicity tests were performed in March 2011 on 3-year-old Bartlett pear trees planted at an experimental farm in Davis, CA. A single, circular, 2-cm pruning wound at the top of the trunk was inoculated on each of three single-tree replications using 2-cm mycelial plugs from 14-day-old colonies growing on PDA. After inoculation, mycelial plugs were covered and sealed with Parafilm and aluminum foil for the duration of the trial. Three control trees were inoculated using sterile PDA plugs. Twelve months after inoculation, UCD103 and UCD105 were consistently re-isolated from the margin between necrotic and healthy tissue using the same methods described for the original isolation, and UCD102 was re-isolated in two out of three plants. The average lesion lengths of UCD102, UCD103, UCD105, and control plants were 12.5, 17.3, 23, and 1 mm, respectively. Control lesions were short and sterile, and seemed to be a physiological reaction from the plant. A second pathogenicity test was completed in 5 months beginning in June 2012. UCD105 was consistently re-isolated, and UCD102 and UCD103 were re-isolated in two out of three plants. The average lesion lengths for UCD102, UCD103, UCD105, and control plants were 2, 3, 5, and 1 mm, respectively. Compared to grapevine (Vitis vinifera), the pathogen grows more slowly in pear tissue under natural conditions. To our knowledge, this is the first report describing D. seriata as a causal agent of pear branch canker in California. Canker diseases can reduce the lifespan of perennial plants, ultimately leading to long term economic losses for growers (3). References: (1) A. J. L. Phillips et al. Fungal Diversity 25:141, 2007. (2) J. R. Urbez-Torres et al. Plant Dis. 90:1490, 2006. (3) J. R. Urbez-Torres and W. D. Gubler. Plant Dis. 93:584, 2009.

Laparoscopic kidney transplantation: an initial experience.

Laparoscopic donor nephrectomy has the advantages of less pain, early ambulation and shorter hospitalization compared to open donor nephrectomy. Kidney recipient surgery is, however, traditionally performed by open surgery. Our aim was to study feasibility and safety of laparoscopic kidney transplantation (LKT). After permission from Internal Review Board, LKT was performed in four patients. All kidneys were procured from deceased donors. Left kidney was used for LKT and transplanted in left iliac fossa while right kidney was used for standard open kidney transplantation (OKT). All transplantation procedures were performed successfully. Cold ischemia time varied between 4 h and 14 h. For LKT, mean time for anastomosis was 65 (range 62-72) min, mean operative time was 3.97 (range 3.5-5) h, mean blood loss was 131.25 mL (range 45-350) mL. Mean wound length was 7 cm in LKT group and 18.4 cm in OKT group. Delayed graft function was observed in one patient in each group. One patient was lost in OKT group due to posttransplant bacterial meningitis. At 6 months, both groups have comparable value of serum creatinine. In conclusion, LKT is technically feasible and safe. Long term outcome needs to be evaluated in a larger study.

Use of an automated knot fastener shortens operative times in minimally invasive mitral valve repair.

INTRODUCTION: Longer durations of cardiopulmonary bypass and aortic cross clamp are associated with increased morbidity and mortality. Little is known about the effect of automated knot fasteners (Cor-Knot®) in minimally invasive mitral valve repair on operative times and outcomes. The aim of this study was to evaluate whether these devices shortened cardiopulmonary bypass and aortic cross clamp times and whether this impacted on postoperative outcomes. MATERIALS AND METHODS: All patients undergoing isolated minimally invasive mitral valve repair by a single surgeon between March 2011 and March 2016 were included (n = 108). Two cohorts were created based on the use (n = 52) or non-use (n = 56) of an automated knot fastener. Data concerning intraoperative variables and postoperative outcomes were collected and compared. RESULTS: Preoperative demographics were well matched between groups with no significant difference in logistic Euroscore (manual vs automated: median 3.1, interquartile range, IQR, 2.1-5.5, vs 5.4, IQR 2.2-8.3; P = 0.07, respectively). Comparing manually tied knots to an automated fastener, cardiopulmonary bypass and aortic cross clamp times were significantly shorter in the automated group (cardiopulmonary bypass: median 200 minutes, IQR 180-227, vs 165 minutes (IQR 145-189 minutes), P < 0.001; aortic cross clamp 134 minutes (IQR 121-150 minutes) vs 111 minutes (IQR 91-137 minutes), P < 0.001, respectively). There was no mortality and no strokes, nor were there any differences in postoperative outcomes including reoperation for bleeding, renal failure, intensive care or hospital stay. CONCLUSIONS: The use of an automated knot fastener significantly reduces cardiopulmonary bypass and aortic cross clamp times in minimally invasive mitral valve repair but this does not translate into an improved clinical outcome.

Significance of pretransplant urinary tract infection in short-term renal allograft function and survival.

UNLABELLED: Renal transplant recipients are susceptible to postoperative infections, among which those in the urinary tract (UTI) are the most common. We examined the effect of pretransplant bacterial UTI on the incidence of posttransplant UTI as well as complications and short-term outcomes. PATIENTS AND METHODS: We examined the case records of 100 patients who underwent living-related donor renal transplantation at our institute from November 2006 to June 2007. RESULTS: Nineteen patients had positive pretransplant bacterial urine cultures and four required native nephrectomy for control of persistent bacterial UTI. All patients were transplanted under a tolerance induction protocol using low-dose immunosuppression after negative suprapubic culture reports. There was no urinary leak/obstruction or vascular complication. The incidence of postoperative bacterial UTI was 31.6% (6 of 19) compared with 6.2% (6 of 81) among patients without pretransplant UTI. E. coli was the most common isolated organism. All patients were doing well with 100% graft survival at 3 months and a mean serum creatinine of 1.27 mg%. CONCLUSION: Preoperative UTI predicted an increased likelihood of postoperative UTI without a significant effect on graft/patient survival and graft function.

Novel topical BoNTA (CosmeTox, toxin type A) cream used to treat hyperfunctional wrinkles of the face, mouth, and neck.

BACKGROUND: This study aimed to compare the effect of the stabilized novel topical botulinum neurotoxin type A (BoNTA) cream (CosmeTox) and a placebo cream on subjects, to compare clinician-reported outcomes, and to assess the safety and utility of the novel topical BoNTA cream for treating the entire upper face, chin, and neck areas. METHODS: This study randomized 40 female subjects to receive either topical BoNTA (CosmeTox) cream (2 U/ml) or an identical placebo cream (without BoNTA) on the face, chin, and neck areas. The subjects were followed for 12 weeks. The main outcome measures were the Facial Line Outcomes questionnaire scores and results from the Self-Perception of Age instrument, which assesses age of appearance relative to actual age. RESULTS: The BoNTA topical cream (CosmeTox) treatment produced significant improvements in the Facial Lines Outcome scores, which were maintained throughout the study period and lasted more than 3 months. The BoNTA topical cream treatment also reduced the age of appearance for a majority of subjects. The placebo had no effect on any measure. No serious adverse events occurred during the entire study period. CONCLUSION: Topical treatment with the stabilized BoNTA cream (CosmeTox) to the entire upper facial lines resulted in significantly improved facial features and age appearance, as measured by the subjects and clinicians. The BoNTA cream (CosmeTox) resulted in a significantly younger, more satisfying, relaxed appearance.

Impact of retroperitoneoscopic donor nephrectomy on renal allograft in Indian and African recipients.

AIM: To evaluate the impact of laparoscopic donor nephrectomy on renal allografts in Indian and African recipients. MATERIAL AND METHODS: Between September 2004 and August 2006, 125 retroperitoneoscopic donor nephrectomies were performed. Ninety-four donors were Indian (group A) and 32, African (group B). Three ports were used for left-sided and four for right-sided surgery, respectively. Hem-o-lok clips were used to control arteries and veins on left side and arteries on right side while an Endo-TA stapler was used on the right side to obtain an inferior vena caval cuff. RESULTS: The mean operative times in groups A and B were 130 and 134 minutes; mean blood loss, 100.4 mL and 85.3 mL; and mean warm ischemia time, 242.1 seconds and 234.5 seconds, respectively. Recipient mean serum creatinine value on day 7 was 1.9 and 1.6 mg%, and on day 28, 1.44 mg% and 1.4 mg%, respectively. CONCLUSION: Early adequate allograft function following retroperitoneoscopic donor nephrectomy was comparable in African and Indian patients, suggesting that no racial advantage was observed in this procedure.

Management of calculi in a donor kidney.

INTRODUCTION: We evaluated the safety and efficacy of ex vivo ureteroscopy (ExURS) and extracorporeal shock wave lithotripsy (ESWL) as means of rendering a donated kidney stone-free in living related and deceased donor renal transplantation. MATERIAL AND METHODS: Three cases with calculi in donor kidneys were managed; 1 was from a living related donor and 2 were from deceased donors. Immediately after cold perfusion, ExURS was performed with iced saline solution in 2 cases. Access to the collecting system was via the ureteral stump. Calculi were fragmented with pneumatic intracorporeal lithotripsy and fragments were removed with forceps. Posttransplantation ESWL was given to 1 patient for migration of a small lower caliceal calculus in the upper ureter in 1 allograft of a dual-kidney transplantation. RESULTS: Access to the renal collecting system and stone fragmentation was technically successful in both cases. Indwelling ureteral stents were kept during transplantation in all cases. There were no intraoperative or postoperative ureteral complications. Following ESWL, stone was fragmented and cleared on its own within a week. At mean follow up of 2.2 years no new stone formed in any recipient or donor. CONCLUSIONS: ExURS was technically feasible to render a stone-bearing kidney stone- free without compromising ureteral integrity or renal allograft function. ESWL could be performed at a later date.

In pursuit of the ultimate: the initial Ahmedabad journey toward transplantation tolerance.

We designed a prospective clinical trial of 357 patients divided in two groups--treated (n = 201) and controls (n = 156)--to evaluate effects of donor hematopoietic stem cell transplantation (HSCT) with minimal nonmyeloablative conditioning for tolerance induction in living related donor renal allograft recipients. Conditioning included donor leukocyte infusions, target-specific irradiation, anti-T-cell antibody, cyclophosphamide, cyclosporine (CsA), followed by bone marrow (BM)-derived and peripheral blood stem cell (PBSC) infusion into thymus, liver, BM, and periphery, with mean total dose of 20 x 10(8) nucleated cells/kg body weight (BW) (mean CD34(+) count: 0.9%) pretransplantation. CsA (3 mg/kg BW/d) and prednisolone (10 mg/d) were used for immunosuppression. Azathioprine/mycophenolate mofetil were added in the event of an acute rejection episode. The controls underwent transplantation with three drug immunosuppression. With a mean follow-up of 21.5 months, the treated cohort showed better allograft function with mean serum creatinine (SCr), 1.42 +/- 0.31 mg% in contrast with the controls mean SCr, 1.61 +/- 0.52 mg% (P < .0001) at 23.9 months follow-up. One-year allograft/patient survival was 95%/96.7% versus 89%/93.4%, respectively. Peripheral blood chimerism by fluorescent in situ hybridization was 0.8% +/- 0.2% in the subset of treated patients with gender-mismatched donors. No graft-versus-host disease was noted. Nine patients with donor-specific cytotoxic alloantibodies pretransplantation showed a decrease in positivity to <15% post-HSCT and were transplanted safely. A transient rise in donor-specific cytotoxic alloantibodies was noted in 19 treated patients post-HSCT, 14 of whom returned to the transplantable range within 2 weeks and five required a desensitization protocol. "Prope" tolerance may be induced in living related donor renal transplantation across major histocompatability complex barriers using HSCT with minimal nonmyeloablative conditioning.

Hematopoietic stem cell transplantation in autoimmune diseases: the Ahmedabad experience.

INTRODUCTION: Autoimmune disease represents a (AD) breakdown of natural tolerance against autoreactive antigens leading to a high mortality and morbidity. The reaction is usually polyclonal; T- and B-cell components of the hematopoietic system are responsible for disease progression. Allogeneic/autologous hematopoietic stem cell transplantation (HSCT) are the current modalities for treating drug-resistant AD. PATIENTS AND METHODS: We present a single-center retrospective evaluation of allogeneic HSCT with nonmyeloablative, low-intensity conditioning in nine patients (five males, four females) with pemphigus vulgaris (PV) and 27 patients with systemic lupus erythematosus (SLE; 3 males, 24 females). The mean follow-up period was 4.24 years for PV and 4.9 years for SLE. Cytokine-mobilized HSC from unmatched related donors, with mean dose of 21.3 x 10(8) nucleated cells/kg body weight (BW; mean CD34(+) count, 6 x 10(6)/kg BW) was administered in to the thymus as well as the portal and peripheral circulations of recipients. Cyclosporine (4 +/- 1 mg/kg BW per day) and prednisolone (10 mg/kg BW per day) were administered for 6 months to protect mixed chimerism. A subset of patients with cross-gender donors were analyzed for peripheral blood chimerism at 1 month post-HSCT and every 3 months thereafter. RESULTS: Sustained clinical remission with peripheral lymphohematopoietic chimerism of 0.7 +/- 0.3% was observed in PV, whereas SLE relapsed after mean of 7.35 months of disease-free interval associated with fall in chimerism from 5 +/- 3% to < or =0.08 +/- 0.03%. CONCLUSION: HSCT was effective to achieve early clinical remission of PV; and in SLE relapsed after a 7.35-month disease-free interval accompanied by a fall in mixed lymphohematopoietic chimerism.

Cadaveric renal transplantation: our experience at the Institute of Kidney Diseases & Research Centre, Institute of Transplantation Sciences, Ahmedabad.

In a developing country such as India, cadaveric renal transplantation accounts for only less than 1% of total renal transplantations. The reasons for such a low rate of cadaveric transplantation are many, ranging from lack of awareness to socioeconomic reasons. Our institute conducted a statewide public awareness program and initiated an intercity organ harvesting program. This doubled the cadaveric renal transplantations in the last 2 years. We performed 38 cadaveric transplantations among 190 renal transplantations in the last year (August 2005 to July 2006). We retrieved kidneys from 21 donors, of whom 9 were outside our city. From 21 donors we transplanted 38 recipients; out of whom 3 received dual kidneys and one kidney was discarded. The Mean age of the donors was 41.4 +/- 18.2 years with a mean cold ischemia time of 6.9 +/- 3.8 hours. Sixty-eight percent had delayed graft function. At the last follow-up, which was 190 +/- 98 days, patient survival rate was 90%: 4 patients died, including 2 due to bacterial sepsis and 2 due to cytomegalovirus (CMV) disease. The Graft survival rate was 85%, and the death-censored graft survival rate was 90%. Mean serum creatinine value at the last follow-up was 1.2 +/- 0.3 mg%. There were 5 episodes of acute rejection in 31 patients during first 3 months (16% acute rejection rate). The increase in cadaveric transplantations was associated with satisfactory patient and graft survival despite the high incidence of delayed graft function.

The Learning Curve of Pure Retroperitoneoscopic Donor Nephrectomy.

BACKGROUND: Retroperitoneoscopic donor nephrectomy (RDN) is a well-established modality for the procurement of kidneys for renal transplantation. However the learning curve of pure RDN is not yet defined. Defining the learning curve will help in proper mentorship of the new donor surgeons besides providing safety to the donors. OBJECTIVE: To define the learning curve of pure RDN. METHODS: We analyzed the prospectively collected data of 102 voluntary kidney donors who underwent RDN by a single surgeon between August 2012 and April 2015 at our center. The donors were classified into group A (1-34), group B (35-68), and group C (69-102) according to the chronological order of their surgery. Left RDN was performed in 28 (82%), 25 (74%), and 28 (82%) donors of group A, B, and C, respectively. Right RDN was performed in 6 (18%), 9 (26%), and 6 (18%) donors of group A, B, and C, respectively. The clinical data were analyzed for each group. RESULTS: Statistically significant difference was observed for the mean operative time (p<0.01) and warm ischemia time (p<0.04). The operative time remained around 200 minutes after the initial 35 cases. CONCLUSION: The learning curve of pure RDN was 35 cases, although the mastery requires more number of cases to be performed.

Embryonic stem cell derived and adult hematopoietic stem cell transplantation for tolerance induction in a renal allograft recipient:--a case report.

UNLABELLED: We generated an human embryonic stem cell (hESC) line to augment chimerism-associated tolerance. A 40-year-old African with chronic glomerulonephritis-chronic renal failure with 100% G6PD enzyme deficiency presented for renal transplantation with a 27-year-old, 6/6 HLA-matched sister as a willing donor. METHOD: We generated an hESC line from the donor's oocytes using long ovarian stimulation protocol simultaneously with tolerance induction protocol. A nuclear transfer (NT)-hESC line was derived by transferring a donor cumulus cell into an enucleated oocyte, subjected to electrical fusion, and cultured for 5 days. ESCs hatched from the blastocyst on day 6 were cocultured with her unmodified bone marrow for 2 days and suspended in Ringer's lactate. Five milliliters of suspension were collected for cell counting, viability, pluripotency, flow cytometry, and karyotyping. The remaining suspension was infused into the periphery of the recipient. Transplantation was performed 1 week later following a negative lymphocytotoxicity cross-match test using no immunosuppression. Peripheral blood chimerism (PBC) was studied using fluorescent in situ hybridization technique. Allograft biopsy was performed on day 7. RESULTS: NT-hESC CD34+ count was 7.6%, viability 100%, karyotyping normal, pluripotency markers: SSEA-1, SSEA-4, OCT-3/4, TRA-1/60:positive; 12% PBC was noted at 1 week after transplantation. Serum creatinine was 1.2 mg%, graft biopsy was unremarkable, and G6PD enzyme deficiency was corrected to 0% at 100 days posttransplant. Liver function tests and hematology profile were unremarkable for graft-versus-host disease. CONCLUSION: This is the first report of tolerance induction using NT-hESC-induced hematopoietic chimerism with synergistic use of adult bone marrow. It was safe and effective.

Primary ethmoid sinus squamous cell carcinoma in a young adult man.

In this case report we describe an aggressive primary ethmoid squamous cell carcinoma in an unusually young patient.

Buccal Mucosal Graft Urethroplasty in Patients Awaiting Renal Transplantation.

OBJECTIVE: To assess the perioperative morbidity and early outcome of buccal mucosal graft (BMG) urethroplasty in patients with urethral stricture awaiting renal transplantation. METHODS: Thirteen patients awaiting renal transplantation underwent BMG urethroplasty for long anterior urethral stricture between June 2011 and March 2013. The management issues, complications, and outcome of the BMG urethroplasty in this cohort of patients were studied. RESULTS: Mean age of the patient was 38.7 ± 12.7 years. History of urethral manipulation was present in 8 patients. Mean stricture length was 6.92 ± 2.90 cm. Mean serum creatinine of the patient was 8.1 ± 3.6 mg%. Three patients required oral exploration for bleeding. Two patients had urinary extravasation, 3 patients had infected hematoma, and 1 patient developed dry gangrene of the glans. One patient had sepsis due to pyonephrosis in the postoperative period and succumbed to it. Mean follow-up of the patients was 34.54 ± 6.46 months. Three patients underwent VIU for recurrence of the stricture in the follow-up. At 3-month follow-up mean Qmax was 23.8 mL/sec, whereas at 6-month and 1-year follow-up, Qmax was 23.6 and 23.4 mL/sec, respectively. CONCLUSION: This study shows a relatively higher complication rate of urethroplasty in prerenal transplant patients. Although the number of cases is too small to arrive at any definite conclusion, this study does gives an insight into the management issues, complications, and success of urethroplasty in this group of patients.

Allogeneic hematopoietic stem-cell transplantation, mixed chimerism, and tolerance in living related donor renal allograft recipients.

OBJECTIVE: We designed a prospective, randomized, and controlled clinical trial to evaluate the efficacy and safety of achieving a mixed chimerism-associated tolerance protocol for recipients of living related donor (LRD) renal allografts. PATIENTS AND METHODS: Sixty-six consecutive patients were divided into two equal groups of 33 patients with end-stage renal disease. They were enrolled for transplantation after negative lymphocytotoxicity cross-matching (LCM). Both groups (treated [Tn] and control [Cn]) showed similar clinical and laboratory parameters and donor HLA match profiles. The Tn group underwent thymic transplantation of donor renal tissue, two donor-specific transfusions, low-intensity conditioning, and high-dose hematopoietic stem-cell transplantation (HSCT) before renal transplantation. The conditioning regimen included low-dose, target-specific irradiation (to abdominal and inguinal lymph nodes, bone marrow [BM] from thoracolumbar vertebrae and part of the pelvis on alternate days, 100 rad x 4), anti-T-cell antibodies (1.5 mg/kg body weight [BW]), cyclophosphamide (10 mg/kg BW x 2 consecutive days), and cyclosporine (CyA; >3 mg/kg BW/d). Unfractionated HSCT procured from the donor marrow was administered into the BM, portal and peripheral circulations, within 24 hours of achieving CD 4+/CD 8+ T-cell count less than 10% of normal. This infusion was supplemented with a dose of peripherally mobilized stem cells (mean total dose of 20 x 10(8) cells/kg recipient BW) administered peripherally. Renal transplantation was performed after negative LCM. Donor-specific cytotoxic antibodies were eliminated with intravenous immunoglobulins and plasmapheresis before renal transplantation. Mixed chimerism was evaluated before and after transplantation at monthly intervals in patients with donors of opposite gender by the FISH technique. Both groups received CyA and prednisolone for immunosuppression; Cn subjects also received mycophenolate mofetil/azathioprine. Rejection was treated with standard treatment. Immunosuppression was withdrawn 6 months after renal transplantation for patients with consistently positive chimerism. Clinical tolerance was defined as stable allograft function for more than 100 days without immunosuppression and confirmed by allograft biopsy. RESULTS: Over a mean follow-up of 210 days, all Tn patients showed stable allograft function with mean serum creatinines (SCr) of 1.20 mg/dL, no rejection/CMV infections/graft or patient loss. A low-level donor-specific cytotoxic antibody was observed in all Tn patients. The CyA toxicity was noted in 10 (30.3%) patients. Persistent mixed hematopoietic chimerism was seen in all 21 patients irrespective of donor-recipient HLA matching (mean 0.5% before and 1 +/- 0.3% after transplantation). All four patients on drug withdrawal have shown donor-specific tolerance at a mean follow-up of 129.8 days. Other Tn patients are in the process of being weaned off immunosuppression. Mean SCr of controls was 1.45 mg/dL over a mean follow-up of 216 days. Acute rejection was observed in 17 (51.5%) patients; no CMV infection/patient loss was noted and one (3.03%) graft was lost in controls. No patient was lost in controls. No graft-versus-host disease was observed in Tn patients. CONCLUSION: We have achieved mixed hematopoietic chimerism-associated tolerance with high-dose HSCT, intrathymic donor renal tissue transplantation, and minimal conditioning without any adverse effects.