Seeking graduation in medical colleges outside India: Is it a 'win-win' or 'lose-lose' situation for the stakeholders and the nation?

The future of Indian students who return as 'foreign medical graduates' (FMG) after training in certain countries is often uncertain. We collected data from newspapers, government resources and agencies involved in handling this issue. We analysed the current status of medical education in India, the Commonwealth of Independent States (CIS) and some neighbouring countries. Of approximately 1.4 million (14 lakh) students taking the National Eligibility cum Entrance Test (NEET), about 5.8% get admission in medical colleges. There are about 554 medical colleges in India with 82 550 MBBS seats, 51.9% seats belong to the government quota. Parents who send their children to a foreign country to do medicine spend ₹1.5 million (15 lakh) tò4 million (40 lakh) against an estimated annual income of ₹1.2 million (12 lakh) and the child spends 4-6 years in a foreign country. Of 38 150 FMGs who took the examinations conducted by the National Board of Examinations from 2015 to 2018, 18.9% passed the FMG examination mandatory for registration to practise medicine in India. The National Medical Commission is trying to solve this issue by removing the age bar for entry to MBBS and recommending lowering of fees for MBBS in government quota. Seeking graduation in medical colleges outside India may not be advisable for those from the middle/ low-income group of India.

Lupus nephritis associated with CD20+ B-cell NHL.

The combination of NHL and documented malignancy-associated glomerulonephritis is uncommon. Also, no single renal pathological entity is consistently found in patients with NHL. Epstein-Barr virus (EBV) infection may manifest as systemic lupus erythematosus (SLE) and/or diffuse large cell lymphoma (DLBCL) in a genetically/ immunologically susceptible individual with defective cytotoxic T-cell response against EBV. We describe lupus nephritis in a 45 years old male suffering from untreated NHL. CD20+ DLBCL was demonstrated by immunohistochemistry of the neck lymph node (LN) biopsy performed for generalized lymphadenopathy. Renal biopsy revealed class V + IV lupus nephritis. Serology demonstrated EBV infection. Complete clinical remission of both SLE and DLBCL was achieved post-therapy with six-cycle rituximab, cyclophosphamide, vincristin, adriablastin, methylprednisolone (R-CHOP) regime. This case report demonstrated the complex relationships between NHL, SLE, EBV and membranous glomerulonephritis. The presented case is remarkable not only because of the rare association of SLE and DLBCL, but also because of its successful treatment with R-CHOP.

Post-exposure prophylaxis for H1N1 with oseltamivir in renal allograft recipient--safe and effective without any immunosuppresive drug interaction.

Kidney transplant recipients are at a high risk for H1N1 infection associated complications during the current pandemic. Prevention of infection by immunization, together with early recognition and prompt antiviral treatment are critical. Post-exposure prophylaxis of H1N1 with oseltamivir was safe, effective and well tolerated to prevent H1N1 influenza A virus infection in newly transplanted renal allograft recipient receiving triple immunosuppression without any interaction with tacrolimus level. Oseltamivir was effective for post-exposure prophylaxis of H1N1 in close contact.

Study of acute antibody-mediated rejection in renal allograft biopsies.

INTRODUCTION: Acute B-cell-mediated rejection (AMR) was ill-defined until the 6(th) Banff meeting establishing the criteria. We performed a retrospective analysis of renal allograft biopsies to evaluate immune injury with reference to the Ahmedabad Tolerance Induction Protocols (ATIP). METHODS: We evaluated renal allograft biopsies belonging to 3 groups: group A patients (n = 120) underwent a modified ATIP with addition of mesenchymal stem cells, anti-B-cell antibodies, and higher target-specific irradiation; group B patients (n = 351) belong to the old ATIP; and group C (n = 142) were controls who opted out of ATIP. The majority were biopsied 2 or 3 times. Biopsies were subdivided:

Renal transplantation in primary focal segmental glomerulosclerosis using a tolerance induction protocol.

UNLABELLED: We report our experience of transplantation using Ahmedabad Tolerance Induction Protocol (ATIP) in primary focal segmental glomerulosclerosis (FSGS) known to recur leading to graft loss. METHODS: Twenty-four primary FSGS patients were transplanted at our centre from 1997 to 2007. The 15 ATIP patients using hematopoietic stem cell transplantation (HSCT) under minimum nonmyeloablative conditioning was performed using living donors. Recipient mean age was 28 years and mean follow-up is 4.4 years. In contrast, nine control subjects of mean age 36 years had 4.8-year follow-up and received standard immunosuppression. Our Institutional Ethics Committee approved ATIP. Donor-recipient HLA match was similar. RESULTS: Mean serum creatinine (SCr) values of the 12 ATIP patients who were doing well at 1, 3, 5 years and at present were: 1.62, 1.48, 1.6, and 1.92 mg%, respectively, on cyclosporine (1.5 +/- 1 mg/kg per day) and prednisone (7.5 mg/day). No recurrence was observed. One patient died at 19 months posttransplant following relentless acute rejection; two patients with unrelated grafts were lost due to acute rejection at 11 weeks and 2 years posttransplant. Two graft biopsies performed at 1 and 2 years posttransplant revealed unremarkable histology, seven showed acute CsA toxicity at 1 year posttransplant. No chronic changes were noted. Among control group B, with 5 of 9 functioning grafts, two were obtained from deceased and three from unrelated donors with mean SCr values at 1, 3, and 4 years as well as present, were 1.77, 1.65, 1.6, and 1.53 mg%, respectively. Four patients displayed recurrences at 8 days, 1 month, and 1 and 2 years posttransplant. One patient died at 1 year posttransplant; one patient received a subsequent cadaver donor graft and two are on maintenance dialysis. CONCLUSION: Transplantation under ATIP seemed to mitigate recurrence of primary FSGS.

Posttransplant diabetes mellitus: a single-center study.

BACKGROUND: Posttransplant diabetes mellitus (PTDM) is a common complication of renal transplantation. We evaluated risk factors for PTDM. PATIENTS AND METHODS: This retrospective evaluation of 1112 patients transplanted from January 2001 to July 2007 was performed based on PTDM diagnosis using The American Diabetes Association criteria. After informed consent, The Ahmedabad Tolerance induction protocol (ATIP) was carried out in 846 of 988 living-related donor (LRD) cases versus 266 who underwent grafting under conventional immunosuppression (controls). RESULTS: PTDM was observed in 6.6% ATIP and 19.1% controls. Mean body mass index increased by 5.2% posttransplant among PTDM versus 1.2% in non-PTDM patients. There were 14.2% hepatitis C virus (HCV)-positive patients treated with ATIP, 27.5% among the controls; 8.3% of ATIP patients developed PTDM versus 15.4% of controls. Mean PTDM age was 43.6 years versus 41.4 years in the non-PTDM group. In ATIP, 20% HCV-positive patients were on tacrolimus versus 33.3% of controls. Antirejection therapy was necessary in 5.3% ATIP, 31.6% controls with 20% of both cohorts developing PTDM. For PTDM control, none of the ATIP subjects required insulin but 39.3%, oral hypoglycemic agents (OHA) and 60.7% diet versus 22.2% of controls on insulin, 37% OHA, and 40.7% diet control. ATIP showed higher chances of PTDM in the early posttransplant period versus delayed-onset in the controls. Calcineurin inhibitors increased PTDM risk. Mean serum creatinine in PTDM was comparable in all groups. HCV positivity increased PTDM risk with 20% to 33% cumulative effect of bolus steroid and tacrolimus therapy. CONCLUSION: Risk factors for PTDM were higher HCV positivity, BMI, and use of tacrolimus, cyclosporine or pulse steroids. ATIP seemed to be safer than the controls.

Human adipose tissue-derived mesenchymal stem cells combined with hematopoietic stem cell transplantation synthesize insulin.

BACKGROUND: Type 1 diabetes mellitus (DM) is an autoimmune disorder with disturbed glucose/insulin metabolism, which has no medical treatment other than life-long insulin therapy, despite which 30% of subjects develop organ failure. Herein we have reported the use of human adipose-tissue-derived, insulin-making mesenchymal stem cells (h-AD-MSC) transfused with unfractionated cultured bone marrow (CBM) in 5 insulinopenic DM patients. PATIENTS AND METHODS: Five (M:F, 2:3) insulinopenic DM patients of 0.6 to 10 years' duration, ages 14 to 28 years under treatment insulin (Human with 14-70 U/d) showed postprandial blood sugars between 156 to 470 mg%, glycosylated hemoglobin 6.8% to 9.9% and c-peptide levels of 0.02 to 0.2 ng/mL. They underwent intraportal administration of xenogeneic-free h-AD-MSC (mean dose = 1.5 mL; cell counts, 2.1 x 10(3)/muL). The CD45-/90+/73(+) cells (29.8/16.8%) showed c-peptide levels of 3.08 ng/mL, insulin level of 1578 micro IU/mL. The aliquot was supplemented with CBM (mean dose 94 mL with cell counts: 18.7 x 10(3)/microL) containing CD45-/34+ elements of 0.93%. The Institutional Review Board approved the study protocol and consent forms. RESULTS: All patients were successfully infused CBM plus h-AD-MSC without any untoward effects and showed 30% to 50% decreased insulin requirements with 4- to 26-fold increased serum c-peptide levels, with a mean follow-up of 2.9 months. CONCLUSION: This report describes safe and effective treatment of insulinopenic diabetics using insulin-producing h-AD-MSC plus CBM without xenogeneic materials.

Postrenal transplant hemolytic uremic syndrome/thrombotic microangiopathy: Ahmedabad experience.

BACKGROUND: Hemolytic uremic syndrome (HUS)/thrombotic microangiopathy (TMA) (tissue-limited HUS) is a well-recognized serious complication of renal transplantation, affecting 3% to 14% patients who are administered calcineurin inhibitor-based immunosuppression. We performed a retrospective study to examine the incidence, etiology, course, and outcome of HUS/TMA in our experience. PATIENTS AND METHODS: This retrospective study of 1540 renal allograft biopsies performed between January 2000 and October 2007 was performed to assess the incidence of HUS/TMA. Institute Transplant Registry records were reviewed for clinical history, laboratory findings, medications, and outcome. The offending drug was substituted in all subjects and plasmapheresis was added as an adjuvant until recovery of allograft function. RESULTS: TMA was observed in 17 (1.1%) biopsies. Two of 17 patients experienced recurrent HUS; 15 were drug-induced (12 with cyclosporine, three with Sirolimus); 10 were TMA; and five HUS. Nine patients developed HUS/TMA within 3 months of transplantation with eight developing it within 1 year posttransplantation. Graft function recovered in 12, while five did not recover. The HUS group showed 60% recovery compared with 80% among the TMA group. Two patients were lost; both displayed HCV seropositivity and one also showed anti-cardiolipin antibody. CONCLUSION: Early allograft biopsy with prompt diagnosis and management by drug substitution +/- plasmapheresis in posttransplant HUS/TMA plays an important role in allograft outcome. TMA showed better recovery than HUS.

Chronic rejection: an enduring enigma of transplantation biology.

Renal transplantation has achieved reasonably good success over the years in controlling acute rejection episodes; however, the immunology of chronic rejection is still not well understood. The problem haunts transplanters across the globe. We describe the presentation, brief immunopathological events, and recent advances suggested by pathologists to define chronic rejection and differentiate it from chronic allograft nephropathy. Our experience using tolerance induction is briefly mentioned including a reduced incidence of acute rejection episodes, chronic rejection events, or calcineurin inhibitor toxicity using lower drug levels.

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.

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.

Successful generation of donor specific hematopoietic stem cell lines from co-cultured bone marrow with human embryonic stem cell line: a new methodology.

We report the generation of 30 healthy human embryonic stem cell (h-ESC) lines from 33 voluntary oocyte donors using a donor somatic cell nuclear transfer (SCNT) technique on 190 oocytes. Our aim was to coculture them with their own bone marrow (BM) to generate hematopoietic progenitor cells for therapeutic purposes. Pluripotency and undifferentiated stage were confirmed using molecular cell surface markers. Normal karyotype of these cell lines was confirmed. Here we demonstrate that SCNT-h-ESCs differentiate to hematopoietic precursors when cocultured with unmodified, nonirradiated donor BM. We did not use any xenogeneic material for this hematopoietic differentiation. Hematopoietic precursors derived from them expressed cell surface antigens CD45/34. When further cultured with hematopoietic growth factors these hematopoietic precursors formed characteristic myeloid, erythroid, and megakaryocyte lineages. Phenotypic CD34+ cells derived from NT-h-ESCs were functionally similar to their counterparts in primary hematopoietic tissues like BM, umbilical cord, and blood. More terminally differentiated hematopoietic cells derived from h-ESCs under these culture conditions also expressed normal surface antigens like glycophorin A on erythroid cells, CD15 on myeloid cells, and CD41 on megakaryocytes. We report generation of hematopoietic progenitor cells from h-ESC lines by a SCNT technique, with differentiation into further lineages with structural and functional similarities to their adult counterparts in vivo. This novel alternative source of CD34+ stem cells from h-ESC lines generated without any xenogeneic material might be used to create transplantation tolerance, to implement regenerative medicine, and to treat autoimmune disorders.

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.

Collapsing Glomerulopathy- A Troublemaker for the Renal Allograft: Lessons Learnt.

Collapsing glomerulopathy (CG) is a well-recognized distinct morphological pattern of proliferative parenchymal injury leading to rapid graft failure. We conducted a single-center retrospective study to evaluate the prevalence, clinicopathological features, and prognosis of CG in renal transplant recepient. We analyzed 2518 renal allograft biopsies performed from 2007 to 2015 and correlated their clinicopathological features. The prevalence of CG was 0.83% (21 out of 2518) of allograft biopsies with a higher prevalence of 1.4% during the period from 2012 to 2015. Out of 21 patients, 18 (85.71%) patients had undergone live donor and 3 (14.28%) patients had undergone deceased donor renal transplant. Hypertension was observed in 3 (14.28%) patients. The mean duration of diagnosis for CG was 1.85 ± 1.91 years. Urinalysis revealed microhematuria in 5 (23.8%) patients. The mean 24 h urinary protein excretion was 4.77 ± 5.3 g and serum creatinine was 2.12 ± 1.5 mg/dl. The predominant native kidney diseases in recipients were chronic glomerulonephritis of unknown etiology in 12 (57.14%) patients and hypertensive nephropathy in 3 (14.28%) patients. CG was associated with rejection in 9 (42.85%), calcineurin-inhibitor toxicity in 2 (9.5%), and BK virus nephropathy in 1 patient. All patients received standard triple immunosuppression. Eleven (52.38%) patients developed graft failure over a mean period of 2.2 ± 1.7 years and 6 (28.57%) patients recovered with stable graft function. CG can coexist with viral infection, drug toxicity, rejection, microvascular injury, etc. CG usually presents with moderate to severe proteinuria and may lead to rapid graft dysfunction and subsequent graft failure in most of the patients.

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.

Crescentic Glomerulonephritis Associated with Pulmonary Tuberculosis.

Tuberculosis of kidney and urinary tract is caused by members of the Mycobacterium tuberculosis complex. Kidney is usually infected by haematogenous spread of bacilli from focus of infection in the lungs. Glomerular involvement in tuberculosis presenting as a rapidly progressive glomerulonephritis is a rare entity. We report a rare case of crescentic glomerulonephritis associated with pulmonary tuberculosis in a 26-year-old man. Patient was treated with corticosteroids, haemodialysis, intravenous immunoglobulin and four cycles of plasmapheresis. He did not respond to 4-drug anti-tuberculosis treatment for renal pathology and was switched over to maintenance haemodialysis. However, he responded to pulmonary TB.

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.

Rare Co-existence of Squamous Cell Carcinoma with Infiltration of Renal Vein and Xanthogranulomatous Pyelonephritis.

Primary renal squamous cell carcinoma is a very rare malignancy of the upper urinary tract. Most patients have history of chronic urolithiasis, analgesics abuse, radiotherapy or infection. Co-existence of SCC with xanthogranulomatous pyelonephritis is exceedingly rare with only few reports in the literature. We report a case of a 60-year-old male presented with right flank pain and mild tenderness of abdomen. Computed tomography of the abdomen revealed gross hydronephrosis with parenchymal thinning and irregular thick enhancing wall of pelvicalyceal system with multiple calculi in right kidney. Right renal vein appeared distended, filled with hypo dense material. Right nephrectomy was performed and sent for pathological examination. Histological evaluation revealed keratinizing squamous cell carcinoma with infiltration of renal vein and xanthogranulomatous pyelonephritis.

Histological and Clinicopathological Evaluation of Liver Allograft Biopsy: An Initial Experience of Fifty Six Biopsies.

INTRODUCTION: Liver biopsy is gold standard for diagnosis of allograft dysfunction. AIM: The aim of study was to evaluate liver allograft biopsies performed for graft dysfunction, study the pattern of injury and intensity, and timeline of occurrence of graft dysfunction. MATERIALS AND METHODS: Retrospective study was carried out of 56 liver allograft biopsies and their histological findings with clinical presentation were correlated. Totally 56 needle liver allograft biopsies from January 1210 to July 2014, obtained from 35 patients were studied for histological and clinicopathological evaluation. RESULTS: The mean age was 53.2±5.48 years. The most common original disease was alcoholic cirrhosis. The most common histological lesion was acute cellular rejection (ACR) in 31 (55.36%) biopsies followed by preservation-reperfusion injury (PRI) in 10 (17.86%) biopsies and drug toxicity in 8 (14.29%) biopsies. Chronic rejection was reported in 2 (3.57%) and recurrence of HCV in 3 (5.36%). Ischemic coagulative necrosis and acute cholangitis were seen in 1 (1.79 %) case each. CONCLUSION: Alcoholic cirrhosis was the most common etiology for end stage liver disease. ACR and PRI were the major complications in liver allograft biopsies at our centre.

Novel therapy for insulin-dependent diabetes mellitus: infusion of in vitro-generated insulin-secreting cells.

Insulin-dependent diabetes mellitus (IDDM) is a metabolic disease usually resulting from autoimmune-mediated ß-cell destruction requiring lifetime exogenous insulin replacement. Mesenchymal stem cells (MSC) hold promising therapy. We present our experience of treating IDDM with co-infusion of in vitro autologous adipose tissue-derived MSC-differentiated insulin-secreting cells (ISC) with hematopoietic stem cells (HSC). This was an Institutional Review Board approved prospective non-randomized open-labeled clinical trial after informed consent from ten patients. ISC were differentiated from autologous adipose tissue-derived MSC and were infused with bone marrow-derived HSC in portal, thymic circulation by mini-laparotomy and in subcutaneous circulation. Patients were monitored for blood sugar levels, serum C-peptide levels, glycosylated hemoglobin (Hb1Ac) and glutamic acid decarboxylase (GAD) antibodies. Insulin administration was made on sliding scale with an objective of maintaining FBS < 150 mg/dL and PPBS around 200 mg/dL. Mean 3.34 mL cell inoculums with 5.25 × 10(4) cells/µL were infused. No untoward effects were observed. Over a mean follow-up of 31.71 months, mean serum C-peptide of 0.22 ng/mL before infusion had sustained rise of 0.92 ng/mL with decreased exogenous insulin requirement from 63.9 international units (IU)/day to 38.6 IU/day. Improvement in mean Hb1Ac was observed from 10.99 to 6.72%. Mean GAD antibodies were positive in all patients with mean of 331.10 IU/mL, which decreased to mean of 123 IU/mL. Co-infusion of autologous ISC with HSC represents a viable novel therapeutic option for IDDM.