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Biomedical subjects

R M Jindal

Publications and source records attributed to R M Jindal.

At least 19 recordsLinked to original sources

Noncompliance after kidney transplantation: a systematic review.

We performed a systematic review of the literature on medical noncompliance after kidney transplantation in the cyclosporine era. We wished to define commonalities that may help the clinician identify patients for early intervention. We found that patients who were at a higher risk of noncompliance after kidney transplants were younger, female, unmarried, and non-Caucasians. Patients who were recipients of living donor transplants and had been transplanted for a longer time with a history of a previous transplant were also at risk of noncompliance. We also found that patients displaying emotional problems, such as anxiety, hostility, depression, distress, lack of coping, and avoidant behaviors, were also at risk for noncompliance after kidney transplantation.

Female↗

Influence of dialysis on post-transplant events.

INTRODUCTION: We examined the effect of haemodialysis (HD) or peritoneal dialysis (PD) on acute rejection, delayed graft function (DGF), graft and patient survival after cadaveric renal transplantation. MATERIALS AND METHODS: We carried out a retrospective analysis of 325 patients (cyclosporin [CyA]-based therapy) who had their first cadaver renal transplant between January 1991 and December 1996 and followed up for a mean of 61 +/- 26 months. They were divided into three groups: HD, PD and CD (where both PD and HD was used for at least 3 months). Delayed graft function was diagnosed if the patient needed dialysis in the first week post-transplant while primary non-function (PNF) was diagnosed if the kidney never achieved function. Graft rejection was confirmed by biopsy; early acute rejection (EAR) was defined as acute rejection occurring before 90 days and late acute rejection (LAR) as one after 90 d. RESULTS: A total of 183 patients had PD, 117 HD and 25 CD. The mean time period in which the patients were on dialysis for PD was 24 months, HD 34.5 months and CD 50.6 months (p < 0.01). The recipients were matched for age and gender. The donor variables (age, gender and cold ischaemia time) did not differ between the groups. The mean time for the development of first acute rejection following renal transplant in each group was as follows: PD group: 68.8 d, HD group: 81.3 d and CD group: 105 d (p = 0.08). The number of patients who developed EAR was 90 (49.2%) in PD group, 51 (43.6%) in HD group and 11 (56%) in CD group (p = 0.6); the number who developed LAR was nine in PD group (4.9%), six in HD group (5.1%) and one in CD group (4%) (p = 0.9). Fifty-six patients with PD had DGF compared with 58 with HD (p = 0.01). There was no difference in the number and severity of rejection episodes or DGF based on the duration of dialysis. The 5-yr survival of patients was 79% for PD, 81% HD and 78% CD groups (p = n.s), while the graft survival for PD group was 61%, HD group 63% and CD group 74% (p = n.s). SUMMARY: We could find no difference in the patient or graft survival between patients who had pre-transplant HD, PD or CD. There was no difference in the incidence of acute rejection episodes between the three groups of patients as well. However, we found a significantly higher rate of DGF in the HD versus PD patients.

Adolescent↗

Use of rapamycin in a transplant patient who developed cyclosporin neurotoxicity.

We describe the case of a paediatric kidney transplant patient who developed cyclosporin neurotoxicity on day 7 post-transplant. Consequently, her cyclosporin was stopped and she was commenced on rapamycin. Over the next 3 weeks her creatinine remained elevated and she had several episodes of biopsy proven rejection, despite increasing the initial dose of rapamycin by tenfold. Her whole blood rapamycin levels also remained well below the target range of 10-20 ng/ml. On day 38 post-transplant, the decision was made to add tacrolimus to her immunosuppression. At the same time, phenytoin, which had been commenced during her episode of cyclosporin neurotoxicity, was withdrawn. After this point her rapamycin blood levels rapidly increased to within the therapeutic range and she improved clinically. We propose that phenytoin, as a p450 cytochrome enzyme inducer, increased the metabolism of rapamycin in this patient and hence decreased the initial therapeutic effectiveness of this drug.

Anticonvulsants↗

Influence of diabetes mellitus on patient and graft survival in recipients of kidney transplantation.

AIMS: To investigate the outcomes in patients who have pre-existing diabetes and those who develop post-transplant diabetes mellitus (PTDM). METHODS: We retrospectively reviewed the charts of 939 patients who received a first functioning renal transplant in the cyclosporine (CyA) era between 1984 and 1999. RESULTS: Sixty-six (7%) patients had renal failure due to insulin-dependent diabetes mellitus (IDDM) and 7 (0.8%) patients due to non-insulin-dependent diabetes mellitus (NIDDM). Ten (1.1%) patients had coexistent diabetes and 48 (5.1%) recipients developed PTDM. The mean graft survival for the patients with PTDM was 9.7 yr versus 11.3 yr for the non-diabetic patients, while mean graft survival was 10.1 yr for patients with IDDM and 2.9 yr with NIDDM and 8.3 yr for those with coexistent diabetes (p=ns). However, there was a statistically significant difference in patient survival between patients who developed PTDM and in those who did not develop this complication. The mean survivals of patients with IDDM, NIDDM, coexistent diabetics and PTDM were 8.4, 3.7, 8.6 and 10.3 yr, respectively. The mean survival of the patients without pre-existing diabetes or PTDM was 12.8 yr (p<0.001). The survival of patients older than 55 yr with PTDM was no different to the control group. However, in those younger than 55 yr, PTDM was associated with a higher risk of death (relative risk of 2.54, p<0.001). Fifty percent of patients with IDDM developed acute rejection episodes, whereas rejection rate was 57.1% in NIDDM group, 50.0% in the PTDM group, 20.0% in the coexistent diabetes group and 44.3% in the control group (p=ns). CONCLUSION: Patient survival, but not graft survival, was adversely affected by both pre-existing diabetes and by PTDM, particularly in those with an age less than 55 yr.

Acute Disease↗

The impact of late acute rejection after cadaveric kidney transplantation.

BACKGROUND: Acute graft rejection (AR) following renal transplantation results in reduced graft survival. However, there is uncertainty regarding the definition, aetiology and long-term graft and patient outcome of AR occurring late in the post-transplant period. AIM: To determine if rejection episodes can be classified by time from transplantation by their impact on graft survival into early acute rejection (EAR) and late acute rejection (LAR). MATERIALS AND METHODS: 687 consecutive adult renal transplant recipients who received their first cadaveric renal transplant at a single centre. All received cyclosporine (CyA)-based immunosuppression, from 1984 to 1996, with a median follow-up of 6.9 yr. Details were abstracted from clinical records, with emphasis on age, sex, co-morbid conditions, HLA matching, rejection episodes, patient and graft survival. ANALYSIS: Patients were classified by the presence and time to AR from the date of transplantation. Using those patients who had no AR (NAR) as a baseline, we determined the relative risk of graft failure by time to rejection. The characteristics of patients who had no rejection, EAR and LAR were compared. RESULTS: Compared with NAR, the risk of graft failure was higher for those patients who suffered a rejection episode. A much higher risk of graft failure was seen when the first rejection episode occurred after 90 d. Thus, a period of 90 d was taken to separate EAR and LAR (relative risk of 3.06 and 5.27 compared with NAR as baseline, p<0.001). Seventy-eight patients (11.4%) had LAR, 271 (39.4%) had EAR and 338 (49.2%) had NAR. The mean age for each of these groups differed (LAR 39.6 yr, EAR 40.8 yr compared with NAR 44 yr, p<0.003). The 5-yr graft survival for those who had LAR was 45% and 10-yr survival was 28%. HLA mismatches were more frequent in those with EAR vs. NAR (zero mismatches in HLA-A: 36 vs. 24%, HLA-B: 35 vs. 23% and HLA-DR: 63 vs. 41%, p<0.003). There was no difference in mismatching frequency between NAR and LAR. CONCLUSIONS: AR had a deleterious impact on graft survival, particularly if occurring after 90 d. AR episodes should therefore be divided into early and late phases. In view of the very poor graft survival associated with LAR, it is important to gain further insight into the main aetiological factors. Those such as suboptimal CyA blood levels and non-compliance with medication should be further investigated with the aim of developing more effective immunosuppressive regimens in order to reduce the incidence of LAR.

Acute Disease↗

A retroperitoneal bronchogenic cyst: a rare cause of a mass in the adrenal region.

This report documents a bronchogenic cyst presenting as an adrenal tumour in a 51 year old man with persistent epigastric pain. The cyst is regarded as a developmental abnormality of the primitive foregut, which typically occurs in the chest. Subdiaphragmatic, and retroperitoneal locations in particular, are unusual. The differential diagnosis of a bronchogenic cyst in the retroperitoneum includes cystic teratoma, bronchopulmonary sequestration, cysts of urothelial and mullerian origin, and other foregut cysts.

Adrenal Gland Neoplasms↗

Renal arterial stenosis in renal allografts: retrospective study of predisposing factors and outcome after percutaneous transluminal angioplasty.

PURPOSE: To determine the predisposing factors to transplant renal arterial stenosis (TRAS) and assess the outcome of percutaneous transluminal angioplasty (PTA) as the primary treatment. MATERIALS AND METHODS: Of 831 renal allograft recipients (584 cadaveric, 247 living related) between January 1991 and December 1998, 72 had hypertension and/or renal dysfunction. All 72 underwent arteriography, and their medical charts were retrospectively reviewed. RESULTS: Prevalence of TRAS was 3.1% (26 of 831). Technical success rate of PTA was 94% (16 of 17), and clinical success rate was 82% (14 of 17). Those with renal dysfunction had a mean pre-PTA creatinine value of 2.6 mg/dL (230 micromol/L) +/- 0.5 (SD) versus a 1-week post-PTA value of 1.7 mg/dL (150 micromol/L) +/- 0.3 (P <.001). Of those with hypertension, all but one had substantial improvement in mean diastolic blood pressure. At 26.9 months mean follow-up in 16 patients with successful PTA, two stenoses reoccurred, and two grafts were lost to chronic rejection. TRAS was present in 14 of 45 end-to-side anastomoses and 12 of 27 end-to-end anastomoses (P =.31), and TRAS was more prevalent in cadaveric grafts (24 of 584) than in living related grafts (two of 247). In cadaveric grafts, the mean cold ischemia time was 29.0 hours +/- 6.9 in those with TRAS (n = 24), as compared with 25.5 hours +/- 8.1 in those with no TRAS (n = 39; P = .35). Seven of 17 patients with acute rejection and six of 35 with chronic rejection had TRAS. CONCLUSION: Primary treatment of TRAS with PTA has good intermediate-term results. TRAS is more prevalent in cadaveric allografts with long cold ischemia time.

Adult↗

Prevention of diabetes in the NOD mouse by intra-muscular injection of recombinant adeno-associated virus containing the preproinsulin II gene.

Using the Adeno-associated virus (AAV) as a gene delivery vehicle, we have constructed a recombinant vector containing the full length rat preproinsulin gene (vLP-1). Utilizing the well described non-obese diabetic (NOD) mouse model, an experimental group (n = 10) of animals were intramuscularly (i.m.) injected with 10(7) rAAV virions containing the insulin gene and compared to a mock-injected control group (n = 10). Blood glucose (glc) was then measured weekly for 16 weeks. Data showed that the experimental group contained 70% euglycemic animals (defined as glc<200 mg/dL) versus 10% of the control animals (P < .05) at 14 weeks. Mean weight in the treated group was greater than the untreated group. Insulin mRNA was detected at the injection site of all of the treated animals, but not controls. Complete destruction of islets was confirmed by histology ruling out the possibility of spontaneous reversal of insulinitis. We conclude that i.m. delivery of the insulin gene in the NOD mouse was able to prevent clinical DM up to 14 weeks in a majority of treated animals. Our experimental data suggests that gene therapy may be an alternative treatment for IDDM in the future.

Animals↗

Outcome for arterio-venous fistula at the elbow for haemodialysis.

BACKGROUND: Few studies have examined the outcome of arterio-venous fistulas (AVF) at the elbow for haemodialysis. METHODS: All AVFs at the elbow created between 1994 and 1998 were identified retrospectively from case notes and the computerised database. Patients were followed until fistula failure, death, or for a minimum of 6 months until June 1999. Life table analysis and Kaplan-Meier actuarial curves with the log rank test were used to assess the influence of age, sex, diabetes, hypertension, heart disease, cerebrovascular disease, use of erythropoietin, aspirin or warfarin, previous insertion of subclavian vein catheter and the levels of haemoglobin and serum albumin on long-term AVF survival. RESULTS: A total of 137 AVFs (primary procedure in 84 and as a secondary procedure in 53 cases) at the elbow were performed in 130 patients; 7 patients had AVFs attempted at both elbows. The mean age was 56.57 yr with a mean follow-up of 48.54 months. Twenty-two patients died with a functioning AVF, while 7 patients also with a functioning AVF received a renal transplant. Overall 74% of AVF were patent at the end of 1 yr, while 22.5% failed or did not mature immediately after the procedure. Two patients had their AVFs tied off due to steal syndrome. Of the various factors known to affect long-term survival of AVF in patients receiving haemodialysis, only plasma albumin > 35 g/L was associated with poorer long-term patency in our study. CONCLUSION: Our report supports the view that AVF at the elbow may obviate the disadvantages of AVF at the wrist in elderly patients, females and in diabetics. In this group of patients it may be preferable to create a primary AVF at the elbow rather than the wrist. Patients who have a failed attempt at creating an AVF at the wrist should undergo AVF at the elbow before the placement of a synthetic graft. This strategy will result in saving time and avoid multiple operations. There may also be a reduction in the use of synthetic grafts resulting in cost savings and avoiding the complications associated with synthetic grafts.

Aged↗

Microchimerism and rejection: a meta-analysis.

AIMS: To study the relationship between graft rejection and microchimerism with and without donor bone marrow infusion in recipients of kidney, liver, heart and lung transplants. Selection of manuscripts. Thirty-seven manuscripts presenting clinical data on microchimerism and rejection, published between 1991 and 1997, were identified. Of these, 16 were excluded due to duplication or insufficient data. Inclusion criteria were data on microchimerism, bone marrow infusion and rejection episodes. STATISTICAL TESTS: A mixed effect logistic model was used to test for homogeneity of transplant centers. The centers were found to be homogeneous for rejection rates controlling for microchimerism and bone marrow infusion. Using rejection episodes at 3, 6, and 12 months post-transplant as the outcome, we evaluated logistic regression models to derive odds ratios for rejection with microchimerism and with bone marrow infusion for each organ. RESULTS: Microchimerism was generally associated with a higher incidence of acute rejection for heart, lung, and kidney transplants and a lower incidence for liver transplants, especially at 12 months and above. Bone marrow infusion decreased the risk of acute rejection for heart transplants and increased the risk for lung and, to a lesser extent, for liver transplants. No consistent effect was seen in kidney transplants. At 12 months and longer, microchimerism was associated with a decreased incidence of chronic rejection in recipients of lung transplants, but there were insufficient data to determine this outcome for other organs. CONCLUSIONS: (i) Microchimerism was detected in the majority of patients. (ii) The effect of microchimerism and bone marrow infusion on rejection episodes varied with the organ and, for a given organ, it was time-dependent. (iii) These findings demonstrate the need for more extensive studies on microchimerism and donor-specific hyporesponsiveness.

Graft Rejection↗

Stable transfection of rat preporinsulin II gene into rat hematopoietic stem cells via recombinant adeno-associated virus.

We investigated the ability of recombinant adeno-associated virus (rAAV), to mediate the transfer of rat preproinsulin II (rI2) gene into rat hematopoietic stem cells in vitro and expression of rI2 following intra-venous (i.v.) injection of infected stem cells into syngeneic rats. The pLP-1 recombinant plasmid containing rI2 was engineered as follows: rI2 with RSV-promoter was released from pBC 12BI (ATCC), purified, and inserted into BamH1 site of rAAV vector plasmid pWP-19. Plasmid pLP-1, together with pAAV¿AD (Somatix Corp.), was used to co-transfect cell line 293 (ATCC). The rAAV genome was rescued using helper adenovirus and packaged into mature rAAV virions (vLP-1). Bone-marrow from female Wistar-Furth rats was enriched for stem cells by using plastic adherence and negative selection with monoclonal anti-rat CD3 and CD45RA to deplete T and B cells. The remaining cells were exposed to vLP-1 (moi=50:1) for 2 hours. Transfection was confirmed by PCR of neomycin resistance gene (neoR) after 8 days in culture. For in vivo studies, ten million exposed stem cells were injected i.v. into syngeneic rats (n=3). The results represent 3 identical experiments. Expression of neoR and rI2 was analyzed by RT-PCR. At week 1, neoR and rI2 were expressed in liver, spleen, thymus, peripheral blood lymphocytes and bone marrow. At week 2, neoR was expressed in spleen and brain, while at week 6, thymus, lymph nodes, bone-marrow, liver, spleen, and brain expressed neoR. rI2 was not detected after week 1. In summary, we showed that rAAV was efficient for transferring neoR and rI2 into rat hematopoietic stem cells.

Animals↗