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Biomedical subjects

A Tejani

Publications and source records attributed to A Tejani.

At least 19 recordsLinked to original sources
PubMed2006

Recombinant activated factor VII for bleeding in patients without inherited bleeding disorders.

(1) Recombinant activated factor VII (rFVIIa) is licensed in Canada for the prevention and treatment of bleeding in hemophiliacs, but it is increasingly used to control bleeding in non-hemophilic patients during surgery, or during treatment for severe trauma or intracerebral hemorrhage (ICH). (2) In one clinical trial, there was a significant reduction in mortality among patients with ICH treated with rFVIIa. In another trial, administration of rFVIIa significantly reduced the number of trauma patients needing massive blood transfusions although there was no significant difference in mortality. (3) Adequately powered randomized controlled trials are needed to clarify the efficacy and safety of rFVIIa for non-bleeding disorder indications. Phase III trials in ICH and trauma are underway. (4) There is potential for non-hemophilic use, particularly if clinical efficacy and cost effectiveness are established.

Canada↗
PubMed2001

The contribution of renal transplantation to final adult height: a report of the North American Pediatric Renal Transplant Cooperative Study (NAPRTCS).

Final adult height following renal transplantation was assessed in 237 recipients enrolled in NAPRTCS before the ages of 11 (girls) and 12 (boys) years and followed for at least 6 months with a functioning graft at or after 18 years of age. The overall change in standardized height (SDS) from baseline to final adult height (FH) was 0.0; however, delta SDS was significantly better for the youngest recipients (6-8 years) than for the older age group. Retarded FH was associated with higher average prednisone dosage and better FH was associated with good graft function. Low baseline SDS was also predictive of retarded FH. Final adult height continues to be suboptimal in the cyclosporine A era.

Aging↗
PubMed2001

Rejection profile of recent pediatric renal transplant recipients compared with historical controls: a report of the North American Pediatric Renal Transplant Cooperative Study (NAPRTCS).

Historically, higher acute rejection rates, earlier first rejection, and an inability to reverse the rejection characterize pediatric renal transplantation. In recent years, short-term (1-year) graft survival of pediatric renal transplants has steadily improved. To test the hypothesis that these improvements were mediated by changes in acute rejection, we considered the rejection profile of patients who received a renal allograft between 1987 and 1989 (cohort A) and compared it with recipients transplanted between 1997 and 1999 (Cohort B). Cohort A comprised 1469 transplants and cohort B comprised 1189 transplants. Restricting the data to the first year of follow-up, rejection ratios were 1.6 and 0.7, respectively (p < 0.001). Sixty per cent of the later cohort (B) were rejection free at 1 year, compared with 29% for the earlier cohort (A) (p < 0.001). Controlling for donor source, the rejection reversal rate for the later cohort was significantly better than that of the early cohort (p < 0.001). Cumulative distribution of times to first rejection was significantly better for cohort B (p < 0.001). One-year graft survival for cohort B at 94% was significantly better than 80% for cohort A (p < 0.001). We conclude that the improved short-term graft survival is mediated by improvements in the rejection profile in more recently transplanted patients and that this may translate into a better half-life for pediatric renal transplant recipients who received an allograft in the years 1997-99.

Adolescent↗
PubMed2001

Loss of living donor renal allograft survival advantage in children with focal segmental glomerulosclerosis.

BACKGROUND: Because of concerns of increased risk of graft loss with recurrent disease, living donor (LD) transplantation in children with focal segmental glomerulosclerosis (FSGS) has been controversial. METHODS: The North American Pediatric Renal Transplant Cooperative Study (NAPRTCS) database from January 1987 to January 2000 was examined to determine differences in demographics, treatment, and outcomes in children with FSGS compared with other renal diseases. RESULTS: Data on 6484 children, 752 (11.6%) with FSGS, demonstrated that FSGS patients were more likely to be older and black, and were less likely to receive either pre-emptive or LD transplant (P < 0.001). No differences existed in human lymphocyte antigen (HLA) matching or immunosuppression regimens. Acute tubular necrosis occurred in more FSGS patients following LD (11.8 vs. 4.6%) or cadaveric (CD; 27.9 vs. 16.3%) transplants (P < 0.001). Graft survival was worse for LD FSGS patients (5 years 69%) compared with no FSGS (82%, P < 0.001) and was not significantly different than CD graft survival in the FSGS (60%) and No FSGS groups (67%). The LD to CD ratios of relative risk of graft failure were higher in FSGS patients (test for interaction, P = 0.01). Recurrence of original disease was the only cause of graft failure that differed between groups (P < 0.001). A greater percentage of LD FSGS graft failures was attributed to recurrence (P = 0.06). CONCLUSIONS: The impact of FSGS on graft survival in children is greatest in LD transplants, resulting in loss of expected LD graft survival advantage. The rationale for LD grafts in children with FSGS should be based on factors other than better outcomes typically associated with LD transplantation.

Child↗
PubMed2001

Acute and chronic rejection.

The major histocompatibility complex molecules are the primary antigens responsible for causing graft rejection, and T-cell recognition of alloantigens is the cardinal event initiating cellular rejection. Current concepts suggest that direct allorecognition mediates acute rejection, whereas indirect allorecognition mediates chronic rejection. In biopsy tissue of rejecting human renal allografts, several cytotoxic T-lymphocyte molecules are upregulated. The net result of cytokine release and the acquisition of cell surface receptors is the emergence of antigen-specific and graft-destructive T cells. Acute rejection is more frequent in children than in adults. By the end of the first year posttransplantation, 45% of living donor recipients and 60% of cadaver donor recipients will have an episode of rejection. In recent years, with improved immunosuppressive therapy, the incidence of acute rejection is decreasing at a rate of about 8% each year, however, chronic rejection graft loss has increased to 41% of all graft losses in the last 2 years. The mechanisms leading to chronic rejection and attempts to reduce acute rejections should provide a better half-life to children postrenal transplantation.

Acute Disease↗
PubMed2001

The 12th Annual Report of the North American Pediatric Renal Transplant Cooperative Study: renal transplantation from 1987 through 1998.

The North American Pediatric Renal Transplant Cooperative Study (NAPRTCS) presents an annual report for all transplants registered from January 1987 onwards. In this report we reviewed 6,534 renal transplants recorded for 5,958 patients who had entered the study by January 1999, and attempted to identify changes in practice patterns that had led to improved graft survival. There has been a steady decline in cadaver source transplants nationally and our accrual for 1996 and 1997 reflected this trend. There has also been a decrease in the number of infants and young children receiving a transplant in recent years. From a peak of 23.3% in the 1987-91 cohort, the current report shows that children under 6 yr of age now account for only 20.4% of all transplants. Changing disease patterns and rates of progression of disease have decreased the percentage of Caucasian children in the transplant registry, from 68.5% in the first 5 yr to 62.9% in the most recent cohort. Changing practice patterns have markedly reduced the use of cadaver donor (CD) kidneys (recovered from donors younger than 10 yr of age) from 35% in 1991 to 22% in the current report. Acute rejection patterns are identical for CD and living donor (LD) grafts for the first 2 weeks post-transplant. The comparative percentages on days 30 and 45 are 36% and 44% for CD, and 26% and 32% for LD recipients respectively. By the end of the first year post-transplant, 45% of LD and 60% CD recipients have had an acute rejection. There has been a marked improvement in our ability to reverse the initial episode of rejection; in 1987, 52% were completely reversed in LD recipients, and in 1997 61% were reversed. Rejection percentages continued to be lower in patients maintained on cyclosporin A (CsA) doses of > 6.4 mg/kg. One-, 3-, and 5-yr graft survival probabilities were 91%, 85%, and 80%, respectively, for LD recipients, and 83%, 73%, and 65% for CD recipients. Comparative 1- and 3-yr figures from 1987 to 1991 were 88% and 81% for LD and 74% and 63% for CD recipients. When short-term graft survival (1 yr) results were compared, a significant improvement was demonstrated from 71.7% in 1987/88 to 92.6% in 1998/1999 for CD transplants. Hence, changing practice patterns have gradually brought the short-term graft survival of CD transplants very close to that of LD transplants. The continuing decrease in the incidence of acute rejections in more recent years should translate into a further delay in the onset of chronic rejection, thus improving graft longevity.

Adolescent↗
PubMed2000

Increased nuclear factor-kappaB and angiotensinogen gene expression in posttransplant recurrent focal segmental glomerulosclerosis.

In an attempt to identify potential markers of steroid-resistance in focal segmental glomerulosclerosis (FSGS) we evaluated intra-graft gene expression of IkappaBalpha, nuclear factor-kappaB (NF-kappaB), and angiotensinogen in 60 biopsies from 27 pediatric renal transplant recipients. Intra-graft NF-kappaB expression was significantly elevated in recurrent FSGS (R-FSGS) (218.3 + 55.6 ag/fg versus NON-FSGS 121.1 + 19.9, P=0.04) but not in acute rejection. NF-kappaB:IkappaBalpha ratios were higher in cadaveric donor versus living related donor recipients (15.7 + 2.8 vs. 8.8 + 1.3, respectively, P=0.015), and in African-American versus Caucasian recipients (15.6 + 2.9 vs. 9.1 + 1.3, respectively, P=0.03). Intra-graft angiotensinogen gene expression was significantly elevated in R-FSGS (30.5 + 8.8 ag/fg R-FSGS vs. 16.0 + 4.7 NON-FSGS, P=0.009). We conclude that increased NF-kappaB and angiotensinogen gene expression are associated with R-FSGS. Increased NF-kappaB:IkappaBalpha ratios are associated with cadaveric donor recipients and African-American race.

Adolescent↗
PubMed2000

The impact of recombinant human growth hormone treatment on final adult height.

There are limited data addressing the issue of final adult height following treatment with recombinant human growth hormone (rhGH). Utilizing the chronological age of 18 years as the arbitrary age of final adult height for children with chronic renal insufficiency, all patients enrolled in the North American Pediatric Renal Transplant Cooperative Study prior to January 1999, and who had at least one follow-up visit at age 18 years or older, were evaluated. When comparing the final adult height in those patients receiving prior rhGH with a group not receiving rhGH, the delta height standard deviation score was greater in the rhGH treatment group.

Adult↗
PubMed2000

The impact of acute rejection on chronic rejection: a report of the North American Pediatric Renal Transplant Cooperative Study.

The North American Pediatric Renal Transplant Cooperative Study (NAPRTCS) group has analyzed its database from January 1987 to October 1998. During this time we enrolled 6,395 transplants: of these, 5,323 were primary and 1,072 were repeat transplants. Overall, 30.8% (483/1,566) of the grafts failed as a result of chronic rejection. For living donor (LD) grafts, the failure rate as a result of chronic rejection was 32% (175/553), and it was 30% (308/1,013) for cadaveric donor (CD) transplants. A proportional hazards model identified first acute rejection, multiple rejections, and a late acute rejection as risk factors for the development of chronic rejection. Additional risk factors for the development of chronic rejection were African-American race, a repeat transplant, and a cyclosporin A (CsA) dose of < 5 mg/kg/day. Our analysis found that one acute rejection episode increases the risk of chronic rejection graft failure three-fold. Patients with two or more acute rejections have a 12-fold increased relative risk (RR) of chronic rejection graft loss (CRGL). A late acute rejection (> 365 days post-transplant) increases the RR by six-fold. Two or more acute rejections, when the first is a late initial rejection, increases the RR 26-fold. Based on this information we have initiated a multicenter trial of intervention in patients with one or more acute rejections.

Acute Disease↗
PubMed2000

Do six-antigen-matched cadaver donor kidneys provide better graft survival to children compared with one-haploidentical living-related donor transplants? A report of the North American Pediatric Renal Transplant Cooperative Study.

Since 1991, more than 50% of pediatric transplant recipients have received a living donor (LD) kidney, and approximately equals 85% of these allografts were one-haploidentical parental kidneys. Short-term (1 yr) and long-term (5 yr) graft survival of LD kidneys are 10% and 15% better, respectively, than that of cadaver donor (CD) kidneys. Because of these results, children are frequently not placed on a cadaver waiting list until the possibility of a LD is excluded--a process that may take up to 1 yr. The hypothesis for this study was that the graft outcome of a six-antigen-matched CD kidney is superior to that of a one-haploidentical LD kidney, and that children are at a disadvantage by not being placed on a CD list whilst waiting for a LD. The database of the North American Pediatric Renal Transplant Cooperative Study (NAPRTCS) for 11 yrs (1987-98), was reviewed to identify children who were recipients of a six-antigen-matched CD kidney (primary and repeat transplants), and those who were recipients of a one-haploidentical LD kidney (primary and repeat transplants). Using standard statistical methods, the morbidity, rejection episodes, post-transplant hospitalizations, renal function, long- and short-term graft survival, and half-life of primary recipients were compared in the two groups. Unlike adult patients, only 2.7% (87/3313) of CD recipients in the pediatric age range received a six-antigen-matched kidney, and the annual accrual rate over 11 yrs was never higher than 4%. Comparison of 57 primary six-antigen-CD kidneys (PCD) with 2,472 primary LD (PLD) kidneys revealed that morbidity, rejection rates, and ratios were identical in the two groups. Renal function and subsequent hospitalizations were also identical in the two groups. Five-year graft survival of the PCD group was 90% compared with 80% for the PLD group, and the half-life of the PCD group was 25 +/- 12.9 yrs compared with 19.6 +/- 1.3 yrs. Our data suggest that the six-antigen-matched CD kidney may have less graft loss as a result of chronic rejection and would therefore confer a better long-term outcome. Based on these findings we recommend that all children, whilst waiting for a LD work-up, be listed with the United Network for Organ Sharing (UNOS) registry for a CD kidney.

Cadaver↗
PubMed2000

Continuing improvement in cadaver donor graft survival in North American children: the 1998 annual report of the North American Pediatric Renal Transplant Cooperative Study (NAPRTCS).

This report of the North American Pediatric Renal Transplant Cooperative Study (NAPRTCS) covers the years 1987-1997, and analyses data on 3,133 cadaver donor (CD) transplants performed in 2,736 patients. There has been a steady decline in the number of CD transplants in children since 1996. Kidneys recovered from donors under 10 years of age accounted for 35% of all transplants in 1987, whereas by 1996 they comprised less than 20%. Caucasian children received 54% of CD transplants, whereas African-American children received 21%. Children under 6 years of age received 17% of CD transplants. Approximately half (46%) of the patients were induced with a T-cell antibody, and at 7 years post-transplant triple therapy is used in 70% of those with a functioning graft. Cyclosporin A is the primary immunosuppressant, with 92% of the patients being maintained on it at 5 years post-transplant. Among patients receiving a transplant in 1997, 11% were initiated with another calcineurin inhibitor, tacrolimus. At 15 days post-transplant 20% of the patients have had a rejection episode and by day 45, 46% have had an acute rejection. The probability of developing a rejection within the first year was reduced from 71% in 1987-1988 to 47% in 1995-1996.

Adolescent↗
PubMed2000

A decade of living donor transplantation in North American children: the 1998 annual report of the North American Pediatric Renal Transplant Cooperative Study (NAPRTCS).

This report of the North American Pediatric Renal Transplant Cooperative Study (NAPRTCS) covers the years 1987-1997, and analyzes data on 2,904 living donor (LD) transplants performed in 2,779 patients. Since 1991, approximately 300 LD transplants have been performed each year at the participating centers of the NAPRTCS. Caucasian children account for 72% of all LD recipients while African-American children constitute only 11%. There has been a gradual decline in the number of transplants performed in children under the age of 6 years from a peak of 30% in 1987, to 21% in 1997. Preoperative calcineurin inhibitor therapy has dropped from 71% in 1987 to 38% in 1997. Through 1996, at six months post-transplant 97% of recipients were receiving prednisone, 88% were maintained on cyclosporin A, and 79% were receiving azathioprine. Of patients transplanted in 1997, 47% are maintained on mycophenolate and 10% are maintained on tacrolimus. By day 15, 20% of index transplant patients have had an acute rejection and by the end of the first year 47% have had a rejection episode. Among patients transplanted in 1995-1996, 40% had a rejection in the first year. Nine per cent of rejection episodes are irreversible in children under 2 years of age and 5% of the episodes are irreversible in 25-year-old children. Estimated graft survival probability at 1 year is 91%, at 3 years it is 84% and at 5 years it is 78.5%. Rejection accounts for 33% of graft loss and recurrence constitutes another 10%. Influential prognostic variables for graft survival are race (African-American vs. others, relative risk (RR) = 2.0, p < 0.001), > 5 random transfusions (RR = 1.6, p < 0.001, T cell induction therapy (RR = 0.78, p = 0.01), and later year of entry (1989-1990 vs. 1994-1995, RR = 0.95, p = 0.04). Patient survival at 1 and 3 years was 97% and 96.5%, respectively, however, the 3-year patient survival of children under 2 years was 89%. The mean height deficit baseline (n=2,677) was -1.86, at 1 year post-transplant (n=1,459) it was -1.80, and at 5 years post-transplant (n=592) it was -2,06. This report, devoted specifically to LD pediatric transplants, raises the issues regarding the use of immunosuppression such as preoperative calcineurin inhibitors and T-cell antibodies. Studies to address the high incidence of chronic rejection and recurrence of original disease are necessary. Additional areas of concern are the high infant mortality and continued growth retardation post-transplantation.

Adolescent↗
PubMed2000

Cognitive functioning in children on dialysis and post-transplantation.

We studied 124 children, 62 patient-subjects who had end-stage renal disease (ESRD) and 62 sibling-controls who closely matched the patient-subjects in terms of their ethnicity and their socioeconomic status, to discern whether children with ESRD would perform less well than their siblings on standardized achievement and intelligence quotient (IQ) tests, and to determine whether ethnicity would influence such results. The subjects were recruited from nine pediatric transplant and dialysis centers across the United States. Thirty-one subjects were white (Euro-American), 17 were African-American, and 14 were categorized as 'other'. The average age of the patient-subjects was 13.7 +/- 0.44 yr; and of the sibling-controls 13.7 +/- 0.38 yr. Most patients (61%) and siblings (84%) were in regular school classes, and most (87% and 92%, respectively) attended school full-time. The average IQ percentile rank for the patients was significantly lower than their siblings (31 +/- 4 vs. 44 +/- 5, respectively, with normal = 50). Patients tended to score lower on achievement tests compared with their siblings (spelling: 88.7 +/- 4 vs. 94.6 +/- 2; arithmetic: 88.5 +/- 2 vs. 94.0 +/- 2; reading: 91.9 +/- 2 vs. 100 +/- 3, respectively). Patients scores on achievement tests were influenced by age at diagnosis and by the mother/caregiver's lower achievement. Also, increased time on dialysis predicted lower scores on achievement tests. Neither dialysis/transplant status nor ethnicity significantly affected outcome. Our data suggest that ESRD, but not ethnicity or dialysis/transplant status, is a risk factor for lower IQ and academic achievement, especially in younger children, in children who spend more time living with ESRD, and in children whose mother's/caregiver's have lower educational levels.

Adolescent↗
PubMed2000

Predictive value of repeat renal biopsies in children with nephrotic syndrome.

In children who exhibit a frequently relapsing course of minimal change disease (MCD), treatment is often difficult and frustrating to the physician and the family since the goal of a sustained remission remains elusive. The progression of the disease is often unpredictable from its clinical presentation since the lesion of MCD may evolve into a more severe form, such as mesangial IgM nephropathy or focal segmental glomerulosclerosis (FSGS), without alteration in signs and symptoms. Alkylating agents such as cyclophosphamide, or immunosuppressives such as cyclosporine can induce a more sustained remission, but are fraught with inherent toxicity, which makes difficult the decision to use these drugs in patients with MCD. Over a 10-year period we studied 49 patients who had more than one renal biopsy. Repeat biopsies were performed either to delineate the morphological lesion prior to change in therapy, or to confirm suspected drug toxicity, which would necessitate discontinuation of therapy. A total of 83 repeat biopsies were performed in these 49 patients. Of the 49 patients, 25 had MCD, and in 21 of these the lesion evolved into either IgM nephropathy (n = 7) or FSGS (n = 14). Of patients with IgM nephropathy (n = 12), 50% evolved into FSGS. The clinical diagnosis made prior to the repeat biopsy did not confirm with the histological diagnosis in 43% of cases, and a change in therapy or cessation of therapy was carried out in 43 of 83 repeat biopsy instances. Since the complications were mild and the ability of clinical findings to accurately predict the histological lesion limited, we conclude that repeat renal biopsies are a useful tool to fashion optimal therapy in children with frequently relapsing nephrotic syndrome.

Adolescent↗
PubMed1999

Safety of kidney biopsy in pediatric transplantation: a report of the Controlled Clinical Trials in Pediatric Transplantation Trial of Induction Therapy Study Group.

BACKGROUND: Historically, young children undergoing renal transplantation have lower allograft survival than adults, and potential causes of this are being addressed by the North American Pediatric Renal Transplant Cooperative Study through the National Institutes of Health-sponsored study Cooperative Clinical Trials in Pediatric Transplantation. Included in this study is evaluation of surveillance renal biopsies (SB) and clinically indicated biopsies (CB). Few data exist in children to identify the risk involved with renal transplant biopsies. METHODS: Questionnaires were mailed to 21 participating centers asking for descriptions of adverse events associated with kidney biopsies, with choices limited to none, gross hematuria, perinephric hematoma, and other. Further clinical details were obtained from review of medical records of all patients with reported adverse events. Data were collected from 19 centers on 126 patients. RESULTS: Eighty-six patients had undergone 212 biopsies (75 SB and 137 CB). Nine biopsy-related adverse events were reported (4.2%): three SB (4.0%) and six CB (4.4%). Gross hematuria was reported in six patients (2.8%): two SB (2.7%) and four CB (2.9%). A perinephric hematoma was reported in one patient. Two patients with intraperitoneal kidneys developed significant bleeding after biopsy and required transfusions and surgical exploration. No patient lost kidney function or required nephrectomy after biopsy. No difference was noted in adverse events between SB at day 5 or 12 versus CB. CONCLUSION: Evaluation of transplanted kidney tissue may provide important information for the care of the transplantation patient. This analysis suggests that transplanted kidney biopsies can be performed with minimal risks in pediatric patients.

Adolescent↗
PubMed1999

One-center experience with cyclosporine in refractory nephrotic syndrome in children.

Uncontrolled or refractory nephrotic syndrome (NS), seen in a variety of glomerular disorders, leads to end-stage renal disease (ESRD). This study describes the use and efficacy of cyclosporine (CSA) for the treatment of refractory NS in 83 children seen over a 10-year period. The histological diagnosis leading to the NS was focal segmental glomerulosclerosis (FSGS) in 51% (n = 42), IgM nephropathy in 20% (n = 17), membranoproliferative glomerulonephritis in 10% (n = 8), lupus nephritis in 6% (n = 5), human immunodeficiency virus (HIV) nephropathy in 5% (n = 4), minimal change disease in 7% (n = 6), and membranous nephropathy in 1% (n = 1) of patients. During CSA therapy the mean proteinuria of the study population decreased from 5.14 g/24 h (4.80 g/m2 per 24 h) to 1.23 g/24 h (0.92 g/m2 per 24 h) (P < 0.001), the mean serum albumin increased from 2.13 g/dl to 3.53 g/dl (P < 0.001), the mean serum cholesterol decreased from 364 mg/dl to 223 mg/dl (P < 0.001), and the mean serum creatinine increased from 0.77 mg/dl to 1.2 mg/dl (P < 0.01). When analyzed by histological diagnosis, similar significant trends of reduction in proteinuria were seen in all but the lupus group. There was a rise in serum creatinine following the use of CSA in patients with FSGS, lupus nephritis, and HIV nephropathy; however the elevated serum creatinine was only significant in patients with FSGS. At the end of the study period, 20 patients had reached ESRD, of which 11 had FSGS, 5 had lupus nephritis, and 4 were patients with HIV nephropathy. Fifty-four patients were in remission at the end of the study period (48 with proteinuria < 100 mg/24 h and 6 with proteinuria < 500 mg/24 h). In conclusion, among children with refractory NS, CSA induced a remission in a large proportion. However toxicity, as noted by the rise in serum creatinine, was observed in several patients. Since this toxicity may be drug induced or a natural progression of the disease, careful monitoring and close follow-up are essential.

Child↗