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Biomedical subjects

R Alloway

Publications and source records attributed to R Alloway.

At least 19 recordsLinked to original sources
PubMed2005

Conversion of stable liver transplant recipients from a twice-daily Prograf-based regimen to a once-daily modified release tacrolimus-based regimen.

INTRODUCTION: Modified release (MR) tacrolimus is an extended release formulation administered once daily. The purpose of this pharmacokinetic (PK) study was to evaluate tacrolimus exposure in stable liver transplant recipients converted from Prograf twice a day to MR tacrolimus once daily. METHODS: This was an open-label, multicenter study with a single sequence, four-period crossover design. Eligible patients were 18 to 65 years of age, >6 months posttransplant with stable renal and hepatic function and receiving stable doses of Prograf twice a day for >2 weeks prior to enrollment. Patients received Prograf twice a day on days 1 to 14 and 29 to 42. Patients were converted to the same milligram-for-milligram daily dose of MR once daily on days 15 to 28 and 43 to 56. Twenty-four-hour PK profiles were obtained on days 14, 28, 42, and 56. Laboratory and safety parameters were also evaluated. RESULTS: Of 70 patients, 62 completed all four PK profiles. The AUC0-24 of tacrolimus was comparable for Prograf twice a day (days 14 and 42) and MR tacrolimus once daily (days 28 and 56). The 90% confidence intervals for MR tacrolimus versus Prograf at steady state (days 28 and 56 vs days 14 and 42) was 0.85 to 0.92 for AUC0-24. MR tacrolimus was well tolerated with a safety profile comparable to that of Prograf. AUC0-24 was highly correlated to Cmin for Prograf (day 14, r = .93; Day 42, r = .89) and for MR tacrolimus (day 28, r = .93; day 56, r = .92). Renal and liver function remained stable. One patient experienced acute rejection. CONCLUSION: The steady-state tacrolimus exposure of MR tacrolimus once daily is equivalent to Prograf twice a day after a milligram-for-milligram conversion in stable liver transplant recipients.

Area Under Curve↗
PubMed2005

Early steroid withdrawal does not increase risk for recurrent focal segmental glomerulosclerosis.

UNLABELLED: Experience with early corticosteroid withdrawal (CSWD) in renal transplant recipients with focal segmental glomerulosclerosis (FSGS) has not been previously reported. Since corticosteroids are used to treat primary FSGS, concern exists as to whether early CSWD regimens will be associated with an increased risk of FSGS recurrence posttransplant. The purpose of the present study was to evaluate the results of early CSWD in FSGS recipients and compare these results to a historic control group of FSGS patients who underwent renal transplantation under corticosteroid-based immunosuppression. METHODS: Forty-three patients with FSGS underwent renal transplantation with early CSWD. Results in these patients were compared to FSGS patients that underwent renal transplantation with chronic corticosteroid therapy. All rejection episodes were biopsy proven with grading by Banff criteria. Statistical analyses included Student's t test and chi square tests. RESULTS: Results in 43 patients with a median follow-up of 569 days were analyzed and compared to control patients. There was no significant difference in recurrent FSGS, time to recurrence, or graft loss. CONCLUSION: CSWD does not increase risk for recurrence of FSGS. These observations indicate that ECSW can be achieved in FSGS patients, thereby affording them the benefits of steroid elimination.

Adrenal Cortex Hormones↗
PubMed2005

Conversion of stable kidney transplant recipients from a twice daily Prograf-based regimen to a once daily modified release tacrolimus-based regimen.

UNLABELLED: Modified release (MR) tacrolimus is an extended release formulation administered once daily (qD). The purpose of this pharmacokinetic (PK) study was to evaluate tacrolimus exposure in stable kidney transplant recipients converted from Prograf twice a day to MR tacrolimus qD. METHODS: This was an open-label, multicenter study with a crossover design. Eligible patients were 18 to 65 years of age, more than 6 months posttransplant with stable renal function, and received stable Prograf doses more than 2 weeks prior to enrollment. Patients received Prograf twice a day through day 7; 24-hour PK profiles were obtained on days 1 and 7. Patients were converted to the same milligram-for-milligram daily dose of MR tacrolimus qD in the morning on day 8; 24-hour PK profiles were obtained for MR tacrolimus on days 8, 14, and 21. Laboratory and safety parameters were also evaluated. RESULTS: Most patients (67 of 70) completed all 5 PK profiles. The 90% confidence intervals (CI) for the MR tacrolimus vs Prograf comparison at steady state (days 14 and 21 vs days 1 and 7) were 90.7 and 99.4 for AUC0-24 and 82.7 and 91.9 for Cmin. MR tacrolimus was well tolerated with a safety profile comparable to that of Prograf. AUC0-24 was highly correlated to Cmin for Prograf (day 1, r = 0.80; day 7, r = 0.84) and MR tacrolimus (day 14, r = 0.92; day 21, r = 0.86). Renal function remained stable after conversion to MR tacrolimus. CONCLUSION: The steady state PK of MR tacrolimus are equivalent to Prograf after a milligram-for-milligram conversion in stable kidney transplant recipients. The results provide evidence to support a safe 1:1 conversion from Prograf twice a day to MR tacrolimus.

Adult↗
PubMed2001

Immunosuppressant side effect profile does not differ between organ transplant types.

Transplantation has enhanced the quality of life of all transplant recipients, but concern remains regarding the side effects of immunosuppressant drugs. In order to respond to these concerns, a survey to ascertain the side effect profile of transplant recipients was undertaken to identify the impact of chronic immunosuppression on quality of life. A nationwide survey of solid organ transplant recipients was carried out using a newly developed immunosuppressant side effect survey. Kidney, kidney-pancreas, liver and heart recipients responded to the survey (n = 505) and reflect the national distribution based on the UNOS data for organ type, recipient race and gender. The survey had four subscales: emotional burden, life/role responsibilities, mobility and GI distress. A fifth subscale included miscellaneous side effects that are more prevalent during the first 2 years post-transplant. Frequency and severity of each side effect were coded on a scale of 0-4 from 'no problem' to 'always' a problem. The entire range of possible scores (0-160) was reported, reflecting adequate variability in the responses. The sample consisted of 51% males, 77% Caucasians, 15% African Americans, with the remaining 8% other races. There were 225 (44.5%) kidney, 147 (29.1%) liver, 101 (20%) heart and 32 (6.4%) pancreas included. Age ranged from 18-71 years with time since transplant 1-21 years. Overall frequency (12.1 +/- 6.08), severity (10.5 +/- 6.96) and weighted scores (25.4 +/- 19.9) were low suggesting that, as a whole, immunosuppressant side effects, while present, were not severe or troublesome for most patients. Side effect profiles appeared similar among organ types. Differences were detected in the GI distress subscale with the heart recipients reporting significantly less GI distress than liver recipients (13.8 vs. 19.2; P<0.05). Side effect impact on mobility tended to increase between time eras; however, no statistical significance was detected. Side effects are a concern among health-care professionals; however, based on the results of this study, immunosuppressant-related side effects are not detrimental to quality of life and show no differences between types of organ transplanted.

Adult↗
PubMed2001

Transmission of donor cancer into cardiothoracic transplant recipients.

BACKGROUND: The demand for transplantable organs exceeds donor supply. Patients with central nervous system (CNS) or other tumors are controversial donors, and the donor cancer transmission rates in cardiothoracic transplant recipients have not been determined. The Israel Penn International Transplant Tumor Registry (IPITTR) was queried to define the risk of donor cancer transmission in cardiothoracic transplant recipients. METHODS: All heart, lung, or heart-lung recipients of organs from donors with a history of malignancy were reviewed. Donor and recipient demographics, histologic findings, and recurrence were reviewed. RESULTS: Twenty-two patients received 17 hearts, 3 lungs, and 2 heart-lung transplants from donors with known CNS or other malignancies. No malignancy transmissions were noted with astrocytomas (n = 3) or glioblastomas (n = 1), except a medulloblastoma that recurred at 6 months. The transmission rate for CNS tumors was 17% (1 of 6), and 1- and 3-year survivals were 67% and 50%, respectively. The most common non-CNS donor cancer was renal cell carcinoma (n = 5). Two renal cell cancer transmissions occurred, both when vascular extension was present. The most aggressive tumor transmission was choriocarcinoma (n = 2) and melanoma (n = 2). Two of 3 choriocarcinomas metastasized with 67% mortality, and both melanomas were transmitted and resulted in death. Other donor cancers included angiosarcoma (n = 2), cervical (n = 1), lung (n = 1), prostate (n = 1), and a liver adenocarcinoma. The transmission rate for all non-CNS groups was 56% (9 of 16) with a 2-year survival of 40%. CONCLUSIONS: The IPITTR experience indicates that tumor transmission is high (10 of 22, 45%) in cardiothoracic transplant recipients. Similar to intra-abdominal organ recipients in the IPITTR, (1) renal cell carcinomas without capsular invasion appear safe with no transmission, (2) vascular invasion in renal cell carcinoma appears to result in early tumor transmission, and (3) melanoma and choriocarcinoma have high rates of transmission with early and almost universal death.

Brain Neoplasms↗
PubMed2000

Simultaneous kidney-pancreas transplantation without antilymphocyte induction.

BACKGROUND: The introduction of potent new immunosuppressive agents may allow simultaneous kidney-pancreas transplantation to be performed without antilymphocyte induction. METHODS: We analyzed 30 simultaneous kidney-pancreas transplantations receiving tacrolimus, mycophenolate mofetil, and steroids without without antilymphocyte induction. Eighteen patients underwent pancreas transplantation with portal-enteric (P-E) drainage and the remaining 12 had systemic bladder (S-B) drainage. Target 12 hr trough tacrolimus levels for the first 3 months after simultaneous kidney-pancreas transplantation were 15-20 ng/ml. The oral mycophenolate mofetil dose was 2-3 g/day begun immediately posttransplant in two to four divided doses. Steroids were tapered according to protocol. RESULTS: All patients experienced immediate function of both kidney and pancreas grafts. One-year actuarial patient, kidney, and pancreas graft survival rates are 93, 93, and 90%, respectively. Nine patients (30%) had a total of 13 rejection episodes (12 biopsy proven) including 4 within 2 weeks, 6 between 2 weeks and 3 months, and 3 beyond 3 months after simultaneous kidney-pancreas transplantation. Three rejection episodes were treated with steroids alone and 10 were treated with antilymphocyte therapy (5 OKT3 and 5 ATGAM). A total of seven patients (23%) received antilymphocyte therapy. Three patients (10%) had more than one rejection episode. Two pancreas grafts (7%) and one kidney graft (3%) were lost from rejection. Four patients (13%) developed cytomegalovirus infection, but none had tissue-invasive cytomegalovirus. At present, 22 surviving patients (81%) remain on triple immunosuppression with tacrolimus, mycophenolate mofetil, and prednisone with excellent dual graft function. CONCLUSION: Tacrolimus, mycophenolate mofetil, and prednisone immunosuppression without without antilymphocyte induction is safe and effective after simultaneous kidney-pancreas transplantation.

Adult↗
PubMed1999

Surgical complications after pancreas transplantation with portal-enteric drainage.

BACKGROUND: Despite recent advances, surgical complications remain an important source of morbidity after pancreas transplantation (PTX). Several previous studies have delineated the surgical complications after PTX with systemic-bladder (S-B) drainage, but data are limited regarding the incidence and outcomes of surgical complications after PTX with portal-enteric (P-E) drainage. STUDY DESIGN: We retrospectively studied surgical complications after 83 vascularized PTXs with P-E drainage in 79 patients (65 simultaneous kidney-PTXs [SKPT] and 18 solitary PTXs [SPT], 8 pancreas alone and 10 pancreas after kidney transplantation). Twelve (15%) were retransplants. A surgical complication was defined as the need for repeat laparotomy within the first 3 months after PTX. RESULTS: A total of 53 surgical complications requiring repeat laparotomy occurred in 31 patients (37%). The incidence of surgical complications in SKPT and SPT was 38% and 33%, respectively. The most common indications for repeat laparotomy were: vascular thrombosis in 13% (SKPT 14% and SPT 11%), intraabdominal infection in 10% (SKPT 12% and SPT 0%), intraabdominal bleeding in 8% (SKPT 8% and SPT 11%), and duodenal allograft leak in 4% (SKPT 3% and SPT 6%). Patient survival rates at 1 and 3 years with versus without surgical complications were 84% and 80% versus 94% and 86%, respectively (p = NS). Pancreas graft survival rates at 1 and 3 years with versus without surgical complications were 48% and 44% versus 89% and 76%, respectively (p < 0.0001). The incidence of surgical complications was 45% in the first 42 P-E transplantations performed between 1990 and 1995, compared with 29% in the next 41 transplantations performed during 1996 and 1997 (p = NS). The mean number of repeat laparotomies per patient decreased from 1.2 in the former group to 0.5 in the latter group (p = NS). The incidence rates of vascular thrombosis, intraabdominal infection, and duodenal leak in the former and latter groups were 17% versus 10%, 12% versus 7%, and 2% versus 5%, respectively. CONCLUSIONS: Surgical complications after PTX are common, and their incidence and outcomes with P-E drainage are similar to those with S-B drainage. The complication rate does not vary according to the type of transplant (SKPT versus SPT). Increasing experience with P-E drainage results in a decreased incidence of surgical complications.

Adult↗
PubMed1999

A limited sampling strategy for the estimation of 12-hour SangCya and neoral AUCs in renal transplant recipients.

Neoral and SangCya are new cyclosporine formulations with more consistent pharmacokinetic profiles than the older formulation of cyclosporine, Sandimmune. Limited sampling strategies have been derived to estimate the full area under the curve (AUC) for both Neoral and Sandimmune. In addition, no limited sampling strategy has been derived for SangCya, and no rigorous prospective testing has been done on any of these formulas. The authors studied 32 renal transplant patients who received Neoral and then SangCya during a formulation conversion study. Full AUCs were drawn on all patients (twice while on Neoral, once while on SangCya). Abbreviated formulas were derived using linear regression models and then tested for the prediction error. The authors found that several abbreviated formulas offer excellent estimations of the full AUC for both SangCya and Neoral. The generated formulas worked equally well with either formulation. In addition, the authors found that limited sampling strategies using a 1.5-hour sample may predict a full AUC more accurately than those that use a 2-hour sample. The use of these abbreviated formulas allows for a convenient and accurate estimate of CsA exposure.

Area Under Curve↗
PubMed1998

Development of Sang-35: a cyclosporine formulation bioequivalent to Neoral.

During a research program, SangStat Medical Corporation developed more than 270 oral cyclosporine formulations. On the basis of animal and clinical trials, Sang-35 was chosen for clinical development, and bioequivalence with the cyclosporine microemulsion Neoral was established. In a cross-over study involving 36 healthy male volunteers, single 500 mg cyclosporine doses of Sang-35 (AUC0-infinity: 13,900 +/- 2470 micrograms.h.L-1, mean +/- standard deviation (SD)) and of Neoral (AUC0-infinity: 14,000 +/- 2900 micrograms.h.L-1) resulted in equal areas-under-the-time-concentration curve (AUC0-infinity). Sang-35 and Neoral were also bioequivalent in healthy male subjects after high-fat meals as well as in female and African-American subjects. In stable kidney transplant patients (n = 12) receiving a mean (+/- SD) cyclosporine dose of mg/d (3.6 +/- 1.6 mg/kg/d), AUC0-12 h after Sang-35 was, as expected, significantly higher than that after Sandimmune (4550 +/- 1858 vs 3468 +/- 1402 micrograms.h.L-1, p < 0.01). Sang-35 and Neoral resulted in equivalent cyclosporine AUC0-12 h values (4120 +/- 1508 and 4377 +/- 1579 micrograms.h.L-1, respectively) in stable kidney transplant patients (dose: 293 +/- 114 mg/d or 3.7 +/- 1.5 mg/kg/d, n = 32). In an additional study, 42 stable kidney graft patients were switched from Sandimmune to Sang-35. Based on a conversion strategy targeting AUC equivalence, only one dose adjustment was required in 55% of the patients, and 95% of patients (40 of 42) needed three or fewer dose adjustments. The mean Sang-35 dose was 7% lower than the mean Sandimmune dose. During the studies, Sang-35 and Neoral exhibited similar safety and tolerability profiles. It is concluded that Sang-35 and Neoral are bioequivalent and that patients can safely and easily be switched from Neoral or, in combination with dose adjustment, from Sandimmune to Sang-35.

Administration, Oral↗
PubMed1997

Lessons to be learned: a case study approach. Hyperactivity and confusion in the presentation of hyoscine overdose.

The case report is presented of a ten-and-a-half year old boy with acute onset of confusion and visual hallucinations, subsequently confirmed to be due to hyoscine toxicity following ingestion of over-the-counter (OTC) travel sickness tablets. It is suggested that packs of such pills should carry a prominent cautionary label. A clear clinical history is very important--not only in aiding the differentiation of acute viral infections involving the central nervous system (such as acute encephalitis) from drug toxicity, but also in rationalizing any further diagnostic investigations. The possible underlying reasons for drug ingestion in this case are discussed.

Antiemetics↗
PubMed1996

Use of FK506 immunosuppressive therapy in pancreas transplantation.

The purpose of this study was to evaluate the safety, efficacy, and transplant outcomes associated with FK506 rescue and maintenance therapy in pancreas transplant recipients. A chart review was conducted on 10 patients receiving FK506 after pancreas transplantation. Transplant outcomes were compared with an equivalent group of patients receiving cyclosporine. Medication dose, side effects, infections, rejection episodes, glycemic control, and graft survival were recorded from 2 to 28 weeks after transplant. Rescue therapy was successful in the patients who were converted to FK506 prior to a significant decline in glycemic control, whereas those patients who were converted after a decline in glycemic control were required to return to exogenous insulin administration. Neurological complications, nephrotoxicity, incidence of infection, hypertension, rejection, and graft survival were similar for both groups. Use of FK506 is comparable to cyclosporine in pancreas allograft recipients and successful conversion from cyclosporine to FK506 can be undertaken for rescue therapy.

Adult↗
PubMed1993

Randomized double-blind study of standard versus low-dose OKT3 induction therapy in renal allograft recipients.

A double-blind, randomized, prospective study was undertaken to determine if the dose of OKT3 used for induction immunosuppression following kidney and kidney-pancreas transplantation affected clinical outcomes. Twenty-five patients were randomized in each group. Five patients in each group received a combined kidney/pancreas transplant. All patients received sequential quadruple immune suppression (azathioprine and methylprednisolone, followed by oral prednisone and cyclosporine A), regardless of randomization to the standard (5 mg) or low-dose (2 mg) OKT3 group. OKT3 was administered for 7 to 14 days. The dose of OKT3 was adjusted to ascertain the clearance of peripheral positive CD3 lymphocytes. The mean cumulative OKT3 dose for the standard dose group was 52.0 mg versus 23.4 mg for the low-dose group (P < 0.00001). Dosage increases were necessary for 29% of the standard dose and 32% of the low-dose patients. The side effect score for the standard versus low-dose group was not statistically different (0.79 +/- 0.58 v 0.84 +/- 0.68), except for chills, which occurred more frequently in the low-dose-treated patients (P = 0.003). Anti-OKT3 antibodies developed with similar frequency in both dosage groups, with 8% exhibiting titers of 1:500 or greater at the end of treatment. Kidney graft survival was 96% for the standard dose and 92% for the low-dose group. The overall incidence of rejection was similar in both groups; however the low-dose group did experience an increase in early rejection episodes. The incidence of major and minor viral and bacterial infections was also similar for both dosage groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1988

Physical complications in anorexia nervosa. Haematological and neuromuscular changes in 12 patients.

Of twelve patients consecutively admitted to the Maudsley Hospital Eating Disorders Unit, four had neuromuscular abnormality, eight haematological abnormality, and four no abnormality. All those having neuromuscular signs had concomitant haematological dysfunction. Vomiting, and food restriction with vegetarianism, appeared more likely to lead to complications than either food restriction alone or laxative abuse. The physical status of severely underweight patients admitted for refeeding needs to be carefully monitored.

Adolescent↗
PubMed1987

The buffer theory of social support--a review of the literature.

The buffer theory postulates that social support moderates the power of psychosocial adversity to precipitate episodes of illness. In this paper, we review the theory as applied to minor affective disturbances. Research in this area suffers because of the many disparate conceptualizations of social support and the resulting difficulty of deciding on the content of measures. Moreover, the meaning of the term buffering is itself unclear. These problems have not, however, inhibited research, and many cross-sectional and longitudinal studies have now been carried out. Our review leads to the conclusion that evidence for a buffering role of social support is inconsistent, reflecting methodological differences between studies but probably also indicating that buffering effects are not of dramatic proportions. Moreover, it is possible that the observed relationships are the result of spurious association or contamination of measures.

Adaptation, Psychological↗