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R M Jindal

Publications and source records attributed to R M Jindal.

At least 37 records · Page 2Linked to original sources
PubMed1999

Prospective study of microchimerism in transplant recipients.

BACKGROUND: We evaluated peripheral blood microchimerism in 48 consecutive organ transplant recipients (35 kidneys, ten livers, one kidney-liver, one kidney-pancreatic islet, one kidney pancreas) up to 12 months post-transplantation. Patients were categorized according to the presence or absence of rejection episodes, and the patterns of microchimerism in the two groups were then compared. METHODS: DNA was extracted from donor, pre-transplant, and post-transplant peripheral blood samples. Several polymerase chain reaction (PCR)-based assays were developed for the detection of microchimerism. Assay sensitivities ranged from 0.0001 to 3%. RESULTS: Microchimerism was detected only in sex-mismatched cases (male donors and female recipients) using nested PCR for a Y-chromosome marker. There were ten such cases (six kidneys, two livers, and two combined organ transplants). In patients without rejection (n = 7), there was a peak of donor-DNA at 1-3 wk post-transplantation followed by a second peak between 3 wk and 4 months. In patients with biopsy-proven rejection (n = 3), the peaks were absent and the levels of microchimerism were extremely low (< 0.001%). Microchimerism levels declined in all 10 patients and were barely detectable 1 yr post-transplantation. Microchimerism was not detected in the remaining 38 patients despite using a battery of sensitive PCR-based assays. CONCLUSIONS: In our study, microchimerism was detected using the Y-chromosome PCR assay only and the level of donor-DNA in a given patient varied over time. This study highlights the difficulties in establishing a correlation between microchimerism and transplant tolerance.

Adolescent↗
PubMed1999

Lymphocyte subset analysis for the diagnosis of rejection and infection in recipients of liver transplants.

We retrospectively investigated the predictive value of lymphocyte subset changes in the peripheral blood of 37 consecutive liver transplant recipients for rejection and infection, both bacterial and cytomegalovirus, during a period of 2 years. Total lymphocyte count correlated with biopsy-proven rejection. There was moderate elevation of CD16+ count during the course of bacterial infection.

Bacterial Infections↗
PubMed1998

Evaluation of seven PCR-based assays for the analysis of microchimerism.

OBJECTIVE: The presence of small numbers of cells of donor origin in the circulation of recipients of organ transplants (microchimerism) may correlate with immunologic tolerance. As part of our ongoing studies on microchimerism, we evaluated the utility of seven PCR-based assays for the detection of the less abundant DNA in paired mixtures (100 ng total DNA). DESIGN AND METHODS: DNA samples were screened to identify pairs informative for one or more PCR assays. DNA mixtures from the informative pairs were then analyzed using at least one assay. The assays were based on the X-Y homologous region; a Y chromosome microsatellite locus; three autosomal microsatellite loci; the D1S80 minisatellite locus; and sequence specific oligonucleotide probe (SSOP) analysis of the HLA DRB1 locus. RESULTS: About 0.1% of male DNA against a background of female DNA was detectable using primers for the X-Y homologous region, but the sensitivity was increased to 0.0001% using nested primers for the Y chromosome microsatellite marker. Analysis of the minor DNA component was difficult with the three autosomal microsatellite assays because of the presence of shadow bands. Similar problems with the D1S80 assay were resolved using more stringent PCR conditions, and the sensitivity was 0.1%. Using the DRB1 locus, we were able to detect 1% DNA in the mixed samples. CONCLUSIONS: These studies show that: (a) nested PCR for the Y chromosome is the most sensitive assay for the detection of microchimerism; (b) D1S80 is a useful marker for microchimerism; (c) additional optimization of analytical conditions is required if autosomal microsatellite markers and the SSOP assay are to be used for microchimerism analysis.

Female↗
PubMed1998

Prostate-specific antigen values and their clinical significance in renal transplant recipients.

BACKGROUND: In the diagnosis of prostate cancer, prostate-specific antigen (PSA) is the most clinically useful tumor marker. Its utility in renal transplant patients is unclear. We hypothesized that PSA values might be affected by the renal function, immunosuppression, or proteinuria. METHODS: Three hundred four PSA values were measured in 166 patients >40 years (53.5 +/- 7.2 years, mean +/- SD, range 44.4 to 76.2). Charts were reviewed for 24-hour creatinine clearance, 24-hour urinary protein, cyclosporine use, age at the time of each PSA test, and evaluation done in response to the PSA result. Analyses used the Mann-Whitney U test and simple regression model. RESULTS: Twenty-five values in 13 patients were >4.0 ng/mL. Of these, 6 patients (6 values) had normal repeat PSA values; 3 patients (11 values) had negative evaluations for prostate cancer; and 4 patients (8 values) were diagnosed with prostate cancer. The latter 4 patients were excluded from the denoted normal group leaving 294 PSA values in 162 patients. The mean normal PSA was 1.3 +/- 1.8 ng/mL, range 0.1 to 20.2. The pretreatment mean PSA for recipients with prostate cancer was 302 +/- 800, range 8.0 to 2,281. An elevated PSA value was associated with a 31% incidence of prostate cancer. There was no association of PSA levels with cyclosporine use, 24-hour creatinine clearance, or 24-hour urinary protein, but there was with age. CONCLUSIONS: Prostate-specific antigen values in renal transplant recipients are similar to those in the general population and are not influenced by cyclosporine or by renal function. We recommend routine measurement of PSA in male transplant recipients.

Adult↗
PubMed1998

Current status of transjugular intrahepatic portosystemic shunts.

The use of the transjugular intrahepatic portosystemic shunt (TIPS) has emerged as an important nonoperative modality for variceal bleeding, intractable ascites, and for selected cases of hepatic venous obstruction. We believe that TIPS should be viewed as a 'bridge' to liver transplantation and should be carried out only in experienced centres. The adverse haemodynamic changes on the cardiopulmonary system after TIPS should be borne in mind. Prospective trials to evaluate the role of TIPS versus sclerotherapy in variceal bleeding will be watched with interest. There is, however, an urgent need to improve long-term results of TIPS as stent thrombosis and stenosis occur frequently. We advocate routine surveillance to detect these problems at an early stage.

Hemodynamics↗
PubMed1997

Predictive value of enzyme-linked immunosorbent assay-detected IgG anti-HLA antibodies for pediatric renal allograft rejection.

BACKGROUND: Measurement of panel-reactive antibody (PRA) with an enzyme-linked immunosorbent assay using soluble HLA class I molecules (PRA-STAT) in adult renal transplant recipients predicted graft loss and rejection. We sought to confirm this finding in pediatric recipients, an immunologically distinct group. METHODS: The population consisted of 158 renal transplants in 146 patients (age range, 1-21 years). PRA was determined with PRA-STAT and microlymphocytotoxicity (CDC), using final cross-match sera. An elevated test was defined as > or =5% reactivity. Statistical analysis for rejection used the chi-square test and for graft survival used the log-rank test. RESULTS: Thirty-five patients (22%) had %PRA-STAT > or =5%, compared with 26 (16%) with %PRA-CDC > or =5%. The percentage with elevated %PRA-STAT was found to correlate with subsequent transplantations (first, 15%; second, 67%; third, 75%). Subsequent analyses utilized only the 136 primary recipients, of whom 20 (15%) had %PRA-STAT > or =5% and 16 (12%) had %PRA-CDC > or =5%. Elevated %PRA-STAT correlated with rejection at 3 months (65% vs. 36%), 12 months (84% vs. 50%), and 24 months (84% vs. 54%) (P<0.05). No association was found between elevated %PRA-CDC and rejection. Patients with %PRA-STAT > or =5% vs. %PRA-STAT <5% had graft survival at 1 year of 89% vs. 84%, at 2 years of 88% vs. 77%, and at 3 years of 61% vs. 72% (not significant). CONCLUSIONS: Use of %PRA-STAT > or =5% identifies pediatric recipients who are at increased risk for rejection and may benefit from more potent immunosuppression and/or closer monitoring of graft function.

Adolescent↗
PubMed1997

Intraoperative placement of a Wallstent for portal vein stenosis and thrombosis after liver transplantation.

We report a case of orthotopic liver transplantation, in which portal vein thrombosis developed in the immediate postoperative period. Surgical thrombectomy and intraoperative placement of a large caliber Wallstent resulted in long-term patency. The unique feature of this case is the intraoperative placement of the stent via the inferior mesenteric vein under fluoroscopic guidance. The use of a large caliber (16 mm) stent obviated the need for postoperative anticoagulation.

Adult↗
PubMed1997

Construction of recombinant adeno-associated virus vector containing the rat preproinsulin II gene.

We have investigated a possible delivery system for the rat preproinsulin II gene (rI2) utilising a recombinant adeno-associated virus (rAAV) vector system, with the long-term goal of engineering stably infected insulin-producing cell lines. The rAAV vector was chosen because it is a safe and nonpathogenic method for gene transfer. The plasmid pBC12BI (ATCC) was purified and digested with restriction enzymes SepI and StuI to release a fragment containing the Rous sarcoma virus long terminal repeat (RSV-LTR) promoter-driven rat preproinsulin II gene (rI2). Subsequently, the RSV-rI2 gene fragment was cloned into the BamHI site of rAAV vector plasmid pWP-19 to produce the rI2 recombinant plasmid designated pLP-1. The pWP-19 also encodes the AAV inverted terminal repeats for integration and replication and the herpes virus thymidine kinase promoter-driven gene for neomycin resistance (neoR). The cell line 293 (ATCC) was then cotransfected with pLP-1 and helper plasmid pAAV/AD, which is required for viral replication. The rAAV genome, now containing rI2, was rescued using adenovirus and packaged into mature AAV virions termed vLP-1. Finally, human pancreatic adenocarcinoma cells (HPAC; ATCC) were exposed to vLP-1, selected for G418 resistance, and screened for insulin production. Successful rescue was confirmed by Southern blot analysis using the rI2 gene probe derived from the original plasmid. The final titer of 1.25 x 10(9) particles/ ml was determined by DNA slot blots using pLP-1 as the standard, HPAC cells were infected with vLP-1 (termed HPAC/rI2). Integration of the rI2 genome in G418-resistant clones was confirmed by Southern blot analysis and again after 6 months in culture by amplification of the rI2 gene by PCR. Insulin gene transcription was confirmed by RT-PCR. We have developed a rAAV-mediated gene transfer system for the rat preproinsulin II gene. Successful transduction and stable integration of rI2 into HPAC was achieved. Production of insulin by HPAC/rI2 was confirmed by RIA and RT-PCR, validating this system as an effective approach to experimental gene therapy.

Adenocarcinoma↗
PubMed1997

The role of cell migration and microchimerism in the induction of tolerance after solid organ transplantation.

A new hypothesis has been proposed which states that microchimerism is the basis for the clinical tolerance seen in long-term survivors of solid organ transplants. Efforts to enhance microchimerism include simultaneous infusion of bone marrow of donor origin and transplantation of a solid organ. Studies are in progress to verify the phenomenon of microchimerism and its role in clinical tolerance.

Bone Marrow Transplantation↗
PubMed1997

Post-transplant hyperlipidaemia.

The correction of post-transplant hyperlipidaemia warrants the judicious and timely use of pharmacological agents with dietary modification and exercise. Reduction in hyperlipidaemia may have some role in decreasing the incidence of chronic rejection of allografts. The awareness that the morbidity and mortality of atherosclerotic disease may be lowered by active intervention will result in a better quality of life for transplant recipients.

Cyclosporine↗
PubMed1997

Post-transplant diabetes mellitus. The role of immunosuppression.

Immunosuppressive agents increase the risk of death due to coronary disease or stroke by their ability to cause 3 different adverse effects: dyslipidaemia, hypertension and hyperglycaemia. Post-transplant diabetes mellitus has emerged as a major adverse effect of immunosuppressants. As recipients of organ transplants survive longer, the secondary complications of diabetes mellitus have assumed greater importance. There is a need for a precise definition of post-transplant diabetes mellitus to facilitate inter-centre comparison and to study the natural history of post-transplant diabetes mellitus. We recommend broad criteria to define hyperglycaemia, as a fasting blood glucose level of > 400 mg/dl at any point or > 200 mg/dl for 2 weeks, or a need for insulin treatment for at least 2 weeks. We also recommend serial measurements of HbA1c. Cyclosporin and tacrolimus cause post-transplant diabetes mellitus by a number of mechanisms, including decreased insulin secretion, increased insulin resistance or a direct toxic effect on the beta cell. For corticosteroids, the induction of insulin resistance seems to be the predominant factor. However, few studies have examined the mechanism of diabetogenicity at the molecular level. This may hold the key for pharmacological manipulation of current immunosuppressive regimens which may result in decreased metabolic complications. Corticosteroid sparing regimens have been shown to reduce the metabolic complications of immunosuppressants including post-transplant diabetes mellitus. However, their use should be balanced against the increased incidence of transplant rejections. Post-transplant diabetes mellitus may be organ-specific irrespective of the immunosuppressant used. Tacrolimus causes a high incidence of post-transplant diabetes mellitus in recipients of kidney transplants (upto 20% in some reports); the diabetogenicity of cyclosporin-based regimens is comparable with that of tacrolimus-based regimens in recipients of liver transplants. A few clinical studies in which attempts were made to discontinue cyclosporin resulted in an unacceptable loss of the transplant. In the case of tacrolimus, complete withdrawal of immunosuppression may be possible in selected patients with liver transplants. However, post-transplant recipients who may benefit from this approach are difficult to identify. In some early series, patients received doses of tacrolimus that were approximately 2 to 3 times higher than those currently used, which may have resulted in a higher incidence of post-transplant diabetes mellitus. More recently, it has been shown that tacrolimus was successful in salvaging whole pancreatic grafts which were maintained on cyclosporin. Tacrolimus-based immunosuppression as primary therapy was also used with remarkable success in solitary whole pancreas transplants. Strategies to reduce the metabolic complications of immunosuppressants should be pursued aggressively as this will directly lead to a decrease in long term cardiovascular adverse effects.

Adrenal Cortex Hormones↗