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Biomedical subjects

M R First

Publications and source records attributed to M R First.

At least 91 records · Page 5Linked to original sources
PubMed1995

Living-related donor transplants should be performed with caution in patients with focal segmental glomerulosclerosis.

The success rates of living-related donor (LRD) transplants are clearly superior to those obtained with cadaver donors. However, caution should be exercised when considering LRD transplantation for a condition which has an increased chance of recurring after transplantation and causing ultimate graft failure. The recurrence rate of focal segmental glomerulosclerosis (FSGS) in the allograft is 20%-40%, with graft failure resulting in 40%-50% of these cases. However, these figures may be an underestimation of the true rate of recurrence of FSGS. Once a first transplant fails due to recurrent disease, the risk of recurrence in the second transplant approaches 80%. Subgroups of patients at high risk for recurrence have been identified. In patients not at high risk for recurrent FSGS, the use of a LRD should be considered, provided that the donor and recipient and their families have been informed that the disease may recur and lead to graft failure. In patients at high risk for recurrence, a LRD transplant should be avoided. Hopefully, future development of a simple and reliable test to predict the likelihood of recurrence will enable us to counsel and advise our patients with FSGS about the wisdom or dangers of proceeding with a LRD transplant.

Child↗
PubMed1995

Optimizing the use of cyclosporine in renal transplantation.

OBJECTIVE: To review the existing data on the use of cyclosporine (CsA) in kidney transplantation, particularly with respect to therapeutic drug monitoring. DATA SOURCES: A literature search was conducted of applicable articles related to therapeutic drug monitoring of cyclosporine in renal transplantation. Previous consensus guidelines were examined. Discussions on issues related to this topic convened in Toronto, ON, on June 15-16, 1994. DATA SYNTHESIS: The literature was analyzed to examine patient factors and drug interactions affecting CsA concentrations, the effect of CsA concentrations on patient outcome, current methods of analysis, pharmacodynamic monitoring, and new immunosuppressants. CONCLUSIONS: CsA has improved the success of kidney transplantation, reducing the incidence and severity of acute rejection and improving short-term patient and graft survival. The rate of graft loss after the first year (primarily due to chronic rejection) has remained largely unchanged. Sandimmune Neoral offers promise due to its better bioavailability and limited dependence on bile flow for absorption. Long-term studies are underway to determine its effectiveness and safety. Indications for therapeutic drug monitoring for CsA are provided.

Cyclosporine↗
PubMed1995

Pregnancy in a combined liver and kidney transplant recipient with type 1 primary hyperoxaluria.

BACKGROUND: Little is known about pregnancy outcomes in multiple organ transplant recipients. We present a case of pregnancy in a patient after liver and kidney transplantation for the genetic disorder of type 1 primary hyperoxaluria. CASE: A 14-year-old Hispanic teenager presented with end-stage renal disease and had a kidney biopsy that revealed hyperoxaluria. A liver biopsy revealed type 1 primary hyperoxaluria. After a year of dialysis and worsening renal status, she underwent a combined orthotopic liver and kidney transplant. The patient subsequently became pregnant, but she required no antihypertensive therapy throughout the prenatal or postpartum period and showed no signs of renal or liver graft rejection. She delivered by cesarean at 38 weeks. CONCLUSION: Combined liver and kidney transplant recipients who become pregnant can have a successful outcome.

Adolescent↗
PubMed1994

Variations in serum OKT3 concentration based upon age, sex, transplanted organ, treatment regimen, and anti-OKT3 antibody status.

An essential parameter of the efficacy of OKT3 therapy is serial determinations of serum OKT3 levels. We hypothesized that precise monitoring of these levels would optimize treatment protocols. Therefore, enzyme-linked immunosorbent assay (ELISA) technology was utilized to measure OKT3 serum concentrations daily during 263 OKT3 treatment courses in recipients of solid organ grafts. Patient characteristics were: mean age 33 years (0.1-71), 147 male/116 female, 134 kidney/82 liver/47 heart, 122 prophylaxis/141 rejection, and 213 conventional dosing/50 increased dosing. Mean OKT3 levels were higher in women than in men at all time points from day 1 to day 14, reaching the greatest difference between groups on day 7 (849 versus 598 ng/ml, p = 0.004). Patients receiving OKT3 as a component of a prophylactic protocol had higher levels than those receiving the drug for treatment of rejection from day 1 to day 6, with the greatest difference between groups occurring on day 1 (678 versus 333 ng/ml, p < 0.00001). However, from day 7 to day 14 patients receiving OKT3 prophylactically had lower mean OKT3 levels than did those receiving OKT3 for rejection, with the greatest difference between groups occurring on day 11 (555 versus 784 ng/ml, p < 0.05). Liver transplant recipients had significantly higher OKT3 levels than did kidney or heart transplants at all time points. However, more liver patients required increased OKT3 doses to modulate peripheral blood CD3+ cells to < 25/mm3. Kidney recipients had higher levels than did heart recipients. Children < 10 years of age had higher OKT3 levels than did older patients at all time points.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1994

Steroid-free immunosuppression after renal transplantation.

Concerns about the side effects of chronic steroid therapy have prompted increasing interest in steroid-free immunosuppression for renal transplant recipients who are maintained on cyclosporine-based regimens. Studies to date suggest that at least 50% of cyclosporine-treated patients can be managed without steroid therapy. Reported benefits of avoiding or withdrawing steroid therapy have included improvements in hyperlipidemia, hypertension, and glucose intolerance and accelerated growth in children. Whether these effects will increase patient or allograft survival remains to be proved. Furthermore, the benefits of steroid-free immunosuppression must be weighed against the risk of precipitating allograft rejection. Although the elimination of steroids clearly increases the short-term risk of acute rejection, further studies are needed to determine the effects of steroid-free immunosuppression on long-term allograft function and to identify clinical or immunologic factors that can predict a successful outcome after the elimination of steroids.

Adrenal Cortex Hormones↗
PubMed1994

Hypertension after renal transplantation.

Hypertension is a frequent complication after organ transplantation in both children and adults and is a significant risk factor for the development of cardiovascular disease and graft dysfunction. There are multiple mechanisms responsible for the development of posttransplant hypertension. In the precyclosporine era, chronic rejection was the most common cause. The introduction of cyclosporine A has increased the prevalence of hypertension in solid organ transplant recipients. Cyclosporine increases renal vascular resistance by causing vasoconstriction of the afferent arteriole. From a pathophysiologic point of view, a calcium channel blocker should be used as the initial therapy in patients with cyclosporine-associated hypertension. Hypertension needs to be treated aggressively in all transplant recipients in an attempt to minimize allograft and cardiovascular damage.

Adult↗
PubMed1994

Safety and efficacy of recombinant human erythropoietin in correcting the anemia of patients with chronic renal allograft dysfunction.

Recombinant human erythropoietin (rHuEPO) is effective in correcting anemia in hemodialysis, peritoneal dialysis, and predialysis patients. Limited studies in patients with failing renal allografts suggest a similar efficacy but provide little information concerning benefits, dose requirements, or adverse events. This study examined these considerations in a group of 40 patients (18 men; 22 women) aged 40.3 +/- 13.8 yr with stable, chronic renal allograft failure. All patients had a hemoglobin < 95 g/L and a serum creatinine > 250 mumol/L at baseline. Patients received rHuEPO (50 U/kg sc) three times weekly for 24 wk along with iron po if serum ferritin was < 100 micrograms/L. Mean hemoglobin rose from 78.9 +/- 10.4 to 102.6 +/- 18.4 g/L after 24 wk. Mean rHuEPO dose at 24 wk was 129.8 +/- 81.9 U/kg per week. With oral iron supplementation only, serum ferritin fell throughout the 24 wk, whereas serum iron, transferrin saturation, and total iron-binding capacity remained stable. Quality of life was assessed by use of the general Sickness Impact Profile and the disease-specific Transplant Disease Questionnaire measures at baseline and every 8 wk during rHuEPO therapy. Significant improvement was noted in global Sickness Impact Profile scores and in four of five dimensions of the Transplant Disease Questionnaire. Serious adverse events were infrequent. No change in mean systolic or diastolic blood pressure was noted, although there was a significantly increased need for antihypertensive drugs in 18 patients (P = 0.0002). A significant inverse correlation was noted between baseline renal function and maintenance rHuEPO dose (r = -0.45; P < 0.05). Twelve patients returned to dialysis during the study.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1993

Clinical course of malignancies in renal transplant recipients.

BACKGROUND: The incidence of cancers after renal transplantation is significantly higher than in populations that have not undergone transplantation. The authors report a group of renal transplant patients from the University of Cincinnati who had cancer develop; the focus is on the patients' clinical course. METHODS: Since 1968, 876 renal transplantations have been performed for a variety of causes of end stage renal disease. Charts of transplant patients who had neoplasms were reviewed. RESULTS: Forty-four patients had epithelial skin cancers, and 36 had nonskin cancers or melanoma. No correlations could be established between disease course and type of immunosuppressive agent, type of disease for which transplantation was required, or type of renal allograft donor. The skin cancers demonstrated a propensity for multifocality: 22 of the 44 patients had multiple separate lesions develop. Of the patients with cancer not of the skin, six were treated surgically for carcinoma in situ, and none have experienced disease recurrence. Of 11 patients treated for early invasive disease, 6 are disease-free, 3 died of intercurrent disease, and 2 died of progressive disease 11 and 13 months, respectively, after disease diagnosis. Nineteen patients had advanced disease, and only 1 is alive and disease-free. Sixteen died of progressive disease at a median of 1 month from the time of diagnosis, and 2 died of intercurrent disease within 1 week of diagnosis. CONCLUSIONS: The natural history of cancers developing in renal transplant patients often is more aggressive than would be expected in patients who have not undergone transplants. The immunosuppression induced to allow viability of the renal allograft may allow tumor cells to thrive.

Adult↗
PubMed1993

Utility of bronchoalveolar lavage in assessing pneumonia in immunosuppressed renal transplant recipients.

PURPOSE: To determine if initial results obtained from diagnostic bronchoalveolar lavage (BAL) in immunosuppressed renal transplant patients with pulmonary infiltrates, fever, or hypoxemia can affect therapeutic decisions, morbidity, and mortality. DESIGN: A retrospective study of all BAL specimens obtained from renal transplant patients from January 1985 through June 1991. Initial results of Gram stain, cytology, cell differential count, and semi-quantitative bacterial cultures, all available within 24 hours of bronchoscopy, were compared with clinical outcomes and final diagnoses. SETTING: University hospital nephrology-transplant/pulmonary service. PATIENTS: Seventy renal transplant patients with a suspected pneumonia were stratified into 3 groups. A total of 48 patients underwent 58 bronchoscopies. Group 1 was comprised of 32 BALs that yielded 1 or more infectious organisms and was considered diagnostic. Group 2 (n = 26) were those BALs in which no organism was isolated and were thus nondiagnostic. Twenty-two additional immunosuppressed renal transplant recipients with pneumonia were considered by the admitting transplant nephrologist to have an uncomplicated community-acquired lung infection and thus were empirically treated and did not undergo BAL (Group 3). METHODS: BAL fluid analysis included cell differential count, cytopathologic examination, and culture for mycobacteria, legionella, fungi, viruses, and bacteria using a semi-quantitative technique. Etiologic diagnosis and the time of onset of the infectious processes were recorded. Therapeutic outcome and mortality were determined for each group. RESULTS: Thirty-nine etiologic organisms were found in 32 patients, with 6 patients having more than 1 infection. Twenty-two patients had 26 negative BALs, and 8 of these patients were clinically believed to have a volume overload state. Eight of 13 (61%) patients with bacterial pneumonia had BAL neutrophil counts greater than 20%, whereas 11 of 13 (84%) patients without bacterial pneumonia had neutrophil counts less than 20% (p < 0.05). Those patients with an infectious etiology remained in the hospital longer than patients without a specific etiologic organism identified (p < 0.02). Therapeutic decisions leading to the institution of specific antibiotics were more frequently made in patients with a diagnostic BAL (p < 0.0001). An overall 3-month mortality (16%) was low compared with the historical rate (30%). CONCLUSION: BAL is a useful procedure in the diagnosis of an infectious process in immunosuppressed renal transplant patients where initial results can alter therapy in more than 70% of cases.

Analysis of Variance↗