Immunomodulation in stable renal transplant recipients with concomitant tacrolimus and sirolimus therapy

BACKGROUND: Long term treatment with immunosuppressive agents results in nephrotoxicity in renal transplant recipients. We explored the effect of combination of Tacrolimus (TAC) and Sirolimus (SRL) on the immune system in renal transplant recipients. METHODS: 10 stable renal transplant recipients were selected to participate in a pharmacokinetic study with a combination of TAC and SRL. Blood was drawn on day zero and 14 days post treatment. Lymphocyte proliferation was quantified by (3)H-thymidine uptake assay (results expressed as counts per minute). The mRNA expression was studied by RT-PCR and serum levels of cytokines were quantified by ELISA and a cytokine bead array system. RESULTS: Lymphocyte proliferative response to PHA (p < 0.05), Con A (p < 0.006) and Anti-CD3 (p <0.005) were significantly decreased in patients who received both TAC and SRL compared to TAC alone. The mRNA expression of proinflammatory cytokines TNF-α (p < 0.05), cyclins G (p < 0.01) and E (p < 05) were decreased, and of TGF-β (p < 0.03) and p21 (p < 0.05) were increased in patients treated with this combination. Circulating levels of IFN-γ (p < 0.04), IL-4 (p < 0.02), and Il-2 (p < 0.03) were significantly inhibited and elevation of TGF-β (p < 0.04) was observed in patients treated with TAC and SRL combination. CONCLUSION: These novel findings demonstrate that addition of SRL to TAC therapy enhances immuno modulation and causes increased immunosuppression providing a rationale for this concomitant therapy

AUTONOMIC NEUROPATHY AND DIABETIC FOOT SYNDROME

Introduction Autonomic Neuropathy in diabetics, contrary to the general belief that it is a late complication, can occur not only early in the natural course of the disease but even precede the diagnosis of diabetes, the best example being impotence. The assessment of autonomic neural involvement is usually done by evaluating cardiac autonomic reflex functions. The current evidence suggests that these tests reflect autonomic nervous damage not only in the heart but also elsewhere in the body. In the present study ninety six diabetic patients were screened for cardiovascular autonomic dysfunction using the four standard tests of cardiac autonomic functions namely (1) The heart rate response to Valsalva manoeuvre, (2) Heart rate variation during deep breathing (3) Blood pressure response to sustained hand grip and (4) immediate blood pressure response to standing from lying. The results of the study were correlated with the clinical symptoms of autonomic neuropathy and peripheral neuropathy in the patients tested. Materials and Methods Ninety six diabetic patients attending the Diabetic Clinic of the Govt. General Hospital, Madras formed the subjects of this study. Out of these ninety six subjects ten were insulin dependent diabetics and the rest were non-insulin dependent diabetics. The age group of the study subjects ranged from 20-60 years and the duration of diabetes from one year to 23 years. All were subjected to a careful clinical assessment, particular attention being given to the presence of clinical evidence of peripheral and autonomic neuropathy. A routine resting twelve lead ECG was done and detailed fundus examination was carried out. Patients with ECG evidence of IHD and those who had proliferative diabetic retinopathy were excluded from this study. Twenty age matched healthy controls were also assessed for the presence of cardiac autonomic neural dysfunction. Department of Diabetology, Madras Medical College &amp; Govt. General Hospital, Madras-3. January, 1988 90 Study Protocol: All the ninety six subjects were subjected to the tests in the morning hours between 10 AM and 12 Noon. No smoking was allowed on the morning of the study and subjects were instructed not to take medications like aspirin, vitamins or anti-histamines for atleast 48 hours before the test. The results of the four tests were categorised and depending on it the subjects were put into one of the following four groups

Percussion hemoglobinuria - a novel term for hand trauma-induced mechanical hemolysis: a case report

<p>Abstract</p> <p>Introduction</p> <p>Extracorpuscular hemolysis caused by mechanical trauma has been well described in relation to lower extremity use, such as in soldiers and runners. Terms such as "march hemoglobinuria", "foot strike hemolysis" and "runners hemoglobinuria" have previously been coined and are easily recalled. Newer cases, however, are being identified in individuals vigorously using their upper extremities, such as drum players who use their hands to strike the instrument. Given the increased recognition of upper extremity-related mechanical hemolysis and hemoglobinuria in drummers, and the use of hand drumming worldwide, we would like introduce a novel term for this condition and call it "percussion hemoglobinuria".</p> <p>Case presentation</p> <p>A 24-year-old Caucasian man presented with reddish brown discoloration of his urine after playing the djembe drum. Urine examination after a rigorous practice session revealed blood on the dipstick, and 0 to 2 red blood cells per high power field microscopically. The urine sample was negative for myoglobulin. Other causes of hemolysis and hematuria were excluded and cessation of drum playing resulted in resolution of his symptoms.</p> <p>Conclusions</p> <p>The association of mechanical trauma-induced hemoglobinuria and playing hand percussion instruments is increasingly being recognized. We, however, feel that the true prevalence is higher than what has been previously recorded in the literature. By coining the term "percussion hemoglobinuria" we hope to raise the awareness of screening for upper extremity trauma-induced mechanical hemolysis in the evaluation of a patient with hemoglobinuria.</p

Preparation of titanium boride in an arc furnace

Titanium diboride is being evaluated as a substitute cathode material in aluminum cells for energy savings. A reduction of approximately 1 volt in the cell voltage and 20% power savings have been reported. Various methods of preparation of titanium boride include arc melting of TiOz, B2O3 and carbon mixture. Conditions for the preparation of TiB2 in a 60 KVA arc furnace have been worked out and the results presented. 95% TiBp was obtained

Refractory coatings on graphite electrodes using flame and plasma spray techniques

Studies have been undertaken to protect graphite electrodes thereby minimising their consumption in the a,c furnaces. In this paper, results of the experiments conducted to provide hard and adherent coatings employing 4-5 micron size spherical alumina - titania powder are presented. Flame and plasma spray methods were employed for evaluating the coatings performance. The merit of the coatings is discussed from a comparison of the SEM photographs of the coated specimen as such and of the high temperature tested specime

A scanning electron microscopic study of refractory coatings on graphite

The surrface characteristics of refractory coatings incorporated on graphite by dipping. Electroplating and plasma techniques have been evaluated using scanning electron Microscope. Fused alumina-sodium silicate, silicon carbide-nickel,fused alumina-nickel, fused alumina and calcined alumina coatings were examined. The coatings obtained by electroplating and plasma were found to be encouraging for further studies

BK Virus Nephritis after Renal Transplantation

BK virus nephritis is an increasing problem and is posing a threat to improving renal transplant graft survival. The pathogenesis of this condition remains to be investigated. Higher prevalence of BK virus infection in recent years has been correlated with declining acute rejection rates and the use of potent immunosuppressive agents. Patients with this infection usually have asymptomatic viremia and/or nephritis with or without worsening of renal function. The diagnosis of this disease is based on detecting the virus or its effects in urine, blood, and renal tissue. In the past, approximately 30 to 60% of patients with BK virus nephritis developed graft failure. In recent years, the combination of early detection, prompt diagnosis, and therapies including preventive measures have resulted in better outcomes

Similar risk profiles for post-transplant renal dysfunction and long-term graft failure: UNOS/OPTN database analysis

Similar risk profiles for post-transplant renal dysfunction and long-term graft failure: UNOS/OPTN database analysis.BackgroundRenal dysfunction measured by serum creatinine (>1.5mg/dL) at 1year post-transplant correlates with long-term kidney graft survival. The purpose of this study was to compare the risk factors for elevated serum creatinine (SCr) >1.5mg/dL at 1year post-transplantation, and for long-term graft failure.MethodsBetween 1988 and 1999, 117,501 adult kidney transplants were reported to Organ Procurement and Transplantation Network/United Network for Organ Sharing (OPTN/UNOS). Of these, 96,091 were functioning at 1year and SCr was available on 85,135 transplants. Donor and recipient demographics (age, sex, and race), transplant [living vs. cadaveric, previous transplantation, panel reactive antibody (PRA), human leukoocyte antigen (HLA) mismatch, cold ischemic time (CIT) and post-transplant delayed graft function (DGF), use of azathioprone vs. mycophenolate mofetil (MMF), cyclosporine A (CsA) vs. tacrolimus (Tac)], induction antibody, acute rejection within 1year variables were used in the logistic regression model to estimate odds ratio (OR) for elevated 1year serum creatinine (SCr). A Cox proportional hazard model was used to estimate the relative risk (RR) for long-term kidney graft failure with and without censoring for death with a functioning graft.ResultsFive-year actuarial graft survival for living donor transplant with SCr >1.5 and ≤1.5mg/dL at 1year post-transplant was 83% and 88.6% (P < 0.001). The corresponding values for cadaveric transplant grafts were 66.5% and 77.9% (P < 0.001). The overall prevalence of renal dysfunction at 1year post-transplant (SCr >1.5mg/dL) declined from 54.5% in 1988 to 42.3% in 1999. There was a strong concordance between the key variables, such as cadaveric transplant, increasing CIT, HLA mismatch, DGF, and acute rejection, recipient race (black), younger age, and nondiabetics status; and donor race (black) and older age for elevated SCr and long-term graft failure.ConclusionDonor (age), race (black), recipient race (black), immunologic variables (HLA mismatch, DGF, acute rejection) were identified as important risk factors for elevated SCr at 1year post-transplantation and long-term graft failure. Elevated SCr should be used as a short-term marker for predicting long-term transplant survival