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Biomedical subjects

J M Morales

Publications and source records attributed to J M Morales.

At least 19 recordsLinked to original sources

Pancreas preservation with the University of Wisconsin versus Celsior solutions.

INTRODUCTION: The use of Celsior solution for organ preservation has not been thoroughly studied in pancreas transplantation. The aim of this study was to compare University of Wisconsin and Celsior solutions for preservation of pancreas grafts. PATIENTS AND METHODS: From March 1995 to December 2005, 72 patients with type 1 diabetes underwent pancreas transplantation. There were 42 men and 30 women, with a mean age at transplantation of 38.1 +/- 7.5 years (range: 27 to 55 years), and a mean duration of diabetes of 22.5 +/- 6.6 years. Recipients were classified into two groups according to the preservation solution: (A) Celsior (n = 28, 38.9%) and (B) Wisconsin (n = 44, 61.1%). RESULTS: The donor and recipient characteristics were similar in both groups. There were five cases of venous thrombosis in the Wisconsin group and two in the Celsior group (P = NS). The venous drainage technique in the former group was portocaval in 19 patients and portoiliac in 25; in the Celsior group, portocaval in 23 patients and portoiliac in five (P = .001). Enteric drainage was used in 19 patients from the Celsior group and 17 patients from the Wisconsin group (P = .01). Actuarial 2-year graft survival was 74.6% in the Wisconsin group and 77.4% in the Celsior group (P = NS). CONCLUSIONS: No differences were observed in venous thrombosis between the two groups. The lower rate of venous thrombosis with the portocaval technique was related to the type of venous drainage rather than the type of preservation solution. Celsior solution may be considered as good as Wisconsin solution for pancreas transplantation.

Adenosine↗

Efficacy and safety of valsartan, an angiotensin II receptor antagonist, in hypertension after renal transplantation: a randomized multicenter study.

BACKGROUND: The prevalence of posttransplant hypertension is high, and it appears to be a major risk factor for graft and patient survival. The aim of this study was to assess the efficacy and safety of valsartan, an angiotensin-receptor blocker (ARB), in the treatment of posttransplant hypertension. METHODS: A multinational, multicenter, prospective, randomized, double-blind, placebo-controlled study was performed on the treatment of hypertension (systolic blood pressure [BP] >/= 140 and/or diastolic BP >/= 90 mm Hg) in adult cyclosporin-treated renal transplant recipients randomized to receive either valsartan (80 mg once daily) or a matching placebo for 8 weeks. After the first 4 weeks, furosemide 20 mg twice daily was added on a open basis if systolic BP remained >/= 130 mm Hg and/or diastolic BP remained >/= 85 mm Hg. RESULTS: One hundred fifteen (valsartan = 57, placebo = 58) uncontrolled hypertensive patients despite monotherapy for hypertension, other than angiotensin-converting enzyme inhibitor or ARB, were randomized. In the valsartan group, significant decreases were seen in systolic BP (from 153 +/- 11 to 140.9 +/- 18.35 mm Hg at 4 weeks, and 136.5 +/- 15 mm Hg at 8 weeks) and diastolic BP (from 93 +/- 9 to 85.2 +/- 11.28 mm Hg at 4 weeks, and 83.8 +/- 9.2 mm Hg at 8 weeks). There was no significant change in the placebo group. In the valsartan group, a statistically but not clinically significant reduction was observed in the mean hemoglobin concentration (12.9 +/- 1.6 g/dL versus 13.8 +/- 1.6 g/dL at 4 weeks, P < .01; and 12.3 +/- 1.6 versus 13.8 +/- 1.7 at 8 weeks; P < .001) as well as a significant increase in serum potassium (4.4 +/- 0.5 mmol/L versus 4.1 +/- 0.4 mmol/L at 4 weeks, P < .01) vs placebo. CONCLUSIONS: Valsartan is effective in the treatment of posttransplant hypertension and is well tolerated.

Adult↗

Posttransplant diabetes mellitus in renal allograft recipients: A prospective multicenter study at 2 years.

The purpose of this study was to investigate the incidence and risk factors for the development of diabetes mellitus after kidney transplantation (PTDM). A total of 1783 nondiabetic renal allograft recipients transplanted from January 2000 to December 2002 were included. Diabetes was diagnosed following American Diabetes Association criteria. While 1276 patients were treated with tacrolimus (Tac), mycophenolate mofetil (MMF), and steroids, 507 patients received cyclosporine-ME (CsA), MMF, and steroids. PTDM incidence at 6, 12, and 24 months was 14.2%, 12.8%, and 13.3%, respectively. Cumulative incidence during the follow-up was 21.6%. Only 121 of the diabetic patients (47.6%) at 6 months remained diabetic at 24 months. Furthermore, 60 patients of 116 patients on insulin at 6 months (51.7%) remained on treatment at 24 months. The cumulative incidence of PTDM was similar in the two immunosuppressive treatments (19.7% on CsA-MMF vs 22.3% on Tac-MMF; P = NS). However, at 24 months, 14 of 50 diabetic patients on CsA-MMF (28%) and 74 of 161 patients on Tac-MMF (45.9%) were on insulin treatment (P < .05). By Cox regression analysis, age older than 60 years (RR 1.61; 95%CI 1.28-2.04; P < .001), body mass index (BMI) > 30 kg/m2 at transplantation (RR 1.66; 95%CI 1.27-2.16; P < .001), and immunosuppression with Tac (RR 1.30; 95%CI 1.02-1-66; P = .033) were associated with PTDM. In conclusions, the incidence of PTDM at 24 months in immunosuppressive protocols including MMF is about 22%, and it is associated with older age, increased BMI, and immnunosuppression with Tac.

Adrenal Cortex Hormones↗

Sirolimus-based therapy with or without cyclosporine: long-term follow-up in renal transplant patients.

This open-label, phase 3b, extension trial in renal transplant recipients (Sirolimus Study 311) assessed the long-term safety of sirolimus (SRL) administered with cyclosporine (CsA) (SRL + CsA group, n = 98) or without CsA (SRL group, n = 69). Renal transplant recipients who had either completed one of seven previous SRL studies sponsored by Wyeth Research or had participated for > or =3 months and reached a protocol-designated endpoint were eligible for enrollment. Data were available for 167 patients, all of whom initially received steroids. Mean total SRL exposure was 1526 days, including previous study participation. After enrollment in the extension study, there were significantly more acute rejections in the SRL + CsA group (6.1% vs 0%, P < .05). Differences in rates of graft loss (3.1% vs 1.4%) and death (6.1% vs 1.4%) were not significantly different between SRL + CsA and SRL groups, respectively. At 48 months after transplantation, calculated GFR (53.4 vs 70.9 mL/min) and hemoglobin (124.9 vs 136.6 g/L) were significantly better in the SRL group. Lipid values were not significantly different between groups at 48 months. The incidence of treatment-emergent increased creatinine, anemia, hypertension, headache, epistaxis, abnormal kidney function, and upper respiratory infection were significantly higher in the SRL + CsA group, whereas no adverse events were significantly higher in the SRL group. Malignancies were reported more frequently (11.2% vs 0%) with SRL + CsA. Results from this extension study indicate that SRL-based therapy without CsA is a safe alternative to combination therapy with CsA, offering long-term improvement in renal function with no increased risk of late acute rejection.

Adult↗

Tacrolimus as basic immunosuppression in pregnancy after renal transplantation. A single-center experience.

Renal transplantation restores fertility within an average of 6 months, so women of childbearing age are able to consider pregnancy. Successful pregnancies have been reported in recent years under different immunosuppressive regimens, but the optimal treatment to achieve the maximum safety for both the mother and fetus remains unclear. Tacrolimus has been demonstrated to provide long-term immunosuppression and prevent rejection in most renal transplants. It seems safe, but experience is limited compared with cyclosporine. We report our experience highlighting the high rate of successful pregnancies attained in women treated with tacrolimus as the basic immunosuppressant and advised of recommendations to achieve a healthy newborn. Renal function was preserved during the pregnancy. The puerperal period and the rate of gestation-related difficulties appeared similar to that of the general population.

Female↗

Rapamycin at six years can exhibit normal renal function without proteinuria or neoplasia after renal transplantation. A single-center experience.

Currently, long-term experience with Rapamune (RAPA) after renal transplantation is scarce. We present our experience with RAPA in patients who were included in clinical trials. Between 1996 and 1999, 27 renal transplant patients received RAPA alone or in combination with cyclosporine (CyA). We study 15 of them (9 males, 6 females; mean age 36 years) who are currently functioning with a mean follow-up of 6 years (range, 5.2-8 years). The presence of delayed graft function was 40% and acute rejection 26.6%, all of them controlled with steroids. Notably, no patients experienced an acute rejection episode after the first year. Among 15 patients, 12 received steroids, RAPA and CyA; and 3 received steroids, RAPA, azathioprine (AZA) or mycophenolate mofetil (MMF) for immunosuppression. At the end of follow-up, the situation was the opposite: 12 patients received steroids (2.5-5 mg/d) and RAPA associated with or without AZA/MMF, and 3 were maintained with steroids, RAPA and CyA. Renal function was excellent in the entire group: mean SCr 1.1 mg/dL (range, 0.7-1.8) with mean RAPA blood levels (HPLC) of 11 ng/dL (range 8-16). Hyperlipidemia was universal with all patients (100%) receiving statins maintaining acceptable levels of cholesterol (mean 209 +/- 28 mg/dL) and tryglycerides (mean 154 +/- 76 mg/dL). Arterial hypertension present in 12 of 15 (80%) patients was controlled with a mean of 1.5 drugs. Notably, no patient presented with proteinuria, neoplasia, posttransplant diabetes, or cardiovascular events. In conclusion, these single-center results suggest that Rapamune may be useful in the long-run after renal transplantation. The presence of normal renal function and the absence of proteinuria and neoplasia in these renal transplant patients may have important clinical implications.

Adrenal Cortex Hormones↗

Pregnancy in renal transplant recipients.

Fertility is restored after renal transplantation when good function is achieved. Our aim was to describe the gestations of our transplanted patients, analyzing outcomes and complications as well as long-term evolution of renal function. From 1976 to 2004, 43 gestations occurred in 35 renal transplanted women: their mean age was 31.7 +/- 4.06 years, with a mean time from the transplant to pregnancy of 4.32 years (0.4-13). At conception, all showed normal renal function (SCr 1.05 +/- 0.2 mg/dL). There were 19 abortions (43.8%), 9 of them spontaneous (21%) and 10 therapeutic (six cases for noncompliance with described criteria of European Best Practice Guidelines for Renal Transplantation, especially pregnancy less than 6 months after transplantation). Excluding these six cases of therapeutic abortions, 24 successful pregnancies occurred in 37 women (65.7%), although eight (29.1%) had premature delivery with live fetuses. Arterial hypertension was the most frequently complication (64%). Preeclampsia occurred in nine (37.5%) pregnancies, with proteinuria in five and only two with mild renal function deterioration. The majority of patients received cyclosporine (n = 20) or tacrolimus (n = 19). Since 1996, mycophenolate mofetil and sirolimus were stopped before conception. Birth weight was lower than 2500 g in 33.3% of pregnancies. Every newborn baby was healthy. Afterward, of the 24 patients with successfully pregnancy, 21 (87.5%) have functioning renal transplants at 53.2 months. After delivery, all currently show good renal function (SCr 1.16 +/- 0.35 mg/dL, CrCl 91 +/- 28.45 mL/m). In conclusion, pregnancy in our renal transplant women shows a success rate of 65.6%. However, complications related to arterial hypertension such as preeclampsia are frequent. The incidence of spontaneous abortions was similar to other series (21%). Long-term graft survival does not seem to be negatively affected by pregnancy.

Adult↗

Anti-CD25 monoclonal antibody sequential immunosuppressive induction therapy in renal transplants with high risk of delayed graft function.

There is little experience on the use of monoclonal antibodies that block the high-affinity interleukin-2 receptor (basiliximab and daclizumab) in sequential therapy in renal transplants with risk of delayed graft function. This study sougth to test the efficacy and safety of the substitution of anticalcineurins with two doses of basiliximab or daclizumab in the immediate posttransplant period for recipients at risk of delayed renal graft function. Immunosuppression consisted of steroids, mycophenolate mofetil, and two doses of basiliximab (20 mg/day) on days 0 and 4 posttransplant or daclizumab (1 mg/kg per day) on days 0 and 15 posttransplant. Anticalcineurins were not administered until the beginning of graft function. Among 49 recipients (mean age 63.5 +/- 10.5 years), 40 received a kidney from a donor over 60 years of age, three from a non-heart-beating donor, and six from donors with an acute elevation of serum creatinine to 2.4 +/- 0.86 (1.7-3.7). At a mean follow-up of 14.2 +/- 8.4 months, five patients experienced acute rejection episodes. Only 15 patients needed posttransplant dialysis (2.7 +/- 1.6). In 11 patients, cyclosporine (CsA) was introduced at 6 +/- 2.9 days posttransplant and in 37, tacrolimus on 8.6 +/- 3.6 days posttransplant. The incidence of kidney graft loss was 16.3%. Patient survival was 96%. Thirty-nine recipients are alive with functioning grafts, with mean serum creatinine of 1.4 mg/dL. In conclusion, substitution for anticalcineurins with interleukin-2-receptor blockade in the immediate posttransplant period for patients at risk of delayed graft function minimizes nephrotoxicity and reduces tubular necrosis, without increasing the risk of an acute rejection episode.

Adolescent↗

Ten years of treatment with tacrolimus is related to an excellent renal function, allowing monotherapy in a large proportion of cases: unicentric results of the tacrolimus versus cyclosporine A European Multicentric Study in kidney transplant patients.

Tacrolimus (Tac) is the most frequently used base inmunosuppressant for transplantation in Spain and the United States. However, long-term data on its use in renal transplant patients are lacking. The aim of this study was to analyze the 10-year outcome of patients from our institution treated with Tac or cyclosporine (CsA) who were included in the European Multicenter Study of kidney transplantation (1993 to 1994). This trial compared the efficacy and safety of steroids + Tac + azathioprine versus steroids + CsA + azathioprine at 1 year, showing a significantly lower acute rejection rate in Tac patients, with no differences in graft or patient survival. In our long-term analysis, we included patients with a functioning graft after the first year: 15 patients on Tac and 11 on CsA. In the "intent-to-treat" (ITT) analysis, patient survival was 14/15 (93%) versus 9/11 (82%) and death noncensored graft survival was 10/15 (67%) versus 8/11 (73%) in Tac and CsA, respectively. Analyzing patients "into treatment" (TT), death/noncensored graft survival was 11/16 (69%) versus 6/9 (67%), respectively. Serum creatinine tended to be lower in Tac group (ITT 1.26 +/- 0.42 vs 1.63 +/- 1.16 mg/dL, P = NS; TT 1.23 +/- 0.4 vs 1.86 +/- 1.28 mg/dL, P = NS). However, in the TT analysis, Tac patients exhibited a significantly better creatinine clearance (89.3 +/- 40 vs 46.8 +/- 21 mL/min, P = .037) and lower systolic blood pressure (125 +/- 5 vs 140 +/- 12 mm Hg, P = .007) at 10 years. No other significant differences were observed in blood pressure, lipid profile, or glucose metabolism. Outstandingly, Tac monotherapy was the most frequently used regimen after 10 years: ITT 6/9 (67%) versus 1/8 (12.5%), P = .05, TT 7/10 (70%) versus 0/6 (0%), P = .011. Patients under Tac monotherapy exhibited an excellent graft function (serum creatinine 1.08 +/- 0.14 mg/dL) and negative proteinuria, with Tac trough levels of 7.9 +/- 1.3 ng/mL. In summary, our results suggest that Tac-based immunosuppression provides an excellent kidney function 10 years after transplantation and allows monotherapy in a high percentage of kidney transplant patients.

Adult↗

Is double renal transplantation a risk factor for cytomegalovirus disease?

We performed a retrospective study to identify the risk factors for cytomegalovirus (CMV) disease among 570 renal transplant recipients. By means of a multivariate analysis we identified antilymphocyte antibody therapy (odds ratio [OR]: 4.6; 95% confidence interval [CI]: 2.0 to 10.6), high doses of corticosteroids (OR: 3.4; 95% CI: 1.2 to 10.1), and double renal transplant (OR: 4.1; 95% CI: 1.5 to 11.5). To the best of our knowledge, this is the first study to suggest that in addition to other well-known risk factors for CMV disease (ie, therapy with anti-lymphocyte antibodies or high doses of corticosteroids), the use of double renal transplantation appears to increase the risk of CMV disease in this population.

Adrenal Cortex Hormones↗

Detection and treatment of post kidney transplant hyperglycemia: a Spanish multicenter cross-sectional study.

INTRODUCTION: The prevalence of diabetes mellitus (DM) is greater among patients with solid organ transplants than in the general population, although the factors associated with posttransplant DM (PTDM) are unknown. OBJECTIVES: The objective of this study was to estimate the prevalence of and assess the risk factors for PTDM. PATIENTS AND METHODS: We included outpatients with functioning isolated solid organ allografts (kidney, liver, heart, and lung). We collected demographic and posttransplant clinical data that included DM diagnostic ADA criteria, DM treatment, DM family history, presence of hepatitis C virus (HCV), immunosuppression treatment, hypertension, and dyslipidemia. RESULTS: A total of 2178 patients included, 1410 kidney recipients, 489 liver transplants, 207 heart transplants, and 72 lung recipients. Seventeen and four-tenths percent of the patients who did not have DM prior to transplantation, developed PTDM (median time: 79 days). A greater prevalence was observed among patients with a family history, HCV, and tacrolimus treatment (with or without steroids P < .05). By logistic regression analyses, OR for these factors were 1.51, 1.65, and 1.38, respectively. Of those patients who did not suffer PTDM, 55.2% showed basal blood glucose values under 100 mg/dL; only 68% presented with a hemoglobin Alc under 6. CONCLUSIONS: The prevalence of PTDM among kidney recipients was higher than that in the general population. DM family history, HCV positive, and tacrolimus were risk factors associated with this entity.

Adult↗

Efficacy and safety of valgancyclovir as preemptive therapy for the prevention of cytomegalovirus disease in solid organ transplant recipients.

We prospectively followed 70 CMV-seropositive solid organ transplant recipients to evaluate the efficacy and safety of valganciclovir (VGCV) as preemptive therapy based on antigenemia test to prevent cytomegalovirus (CMV) disease. From December 2003 to May 2004, 12 of 70 (17%) asymptomatic patients who showed an antigenemia value > or =25 positive cells per 2 x 10(5) polymorphonuclear (PMN) were treated with VGCV (900 mg twice a day adjusted to renal function) until resolution of CMV antigenemia, a minimum of 14 days. No patient developed CMV disease during follow-up. Only one who showed an asymptomatic relapse of the antigenemia test > or =25 positive cells was successfully treated with a repeated course of VGCV. Mean duration of VGCV therapy was 18 days (range, 14 to 28). Antigenemia was negative in 7 of 12 (58%) patients after 14 days and negative in all patients 4 weeks after the administration of VGCV. No significant side effects were associated with the use of VGCV therapy. Preemptive VGCV therapy is safe and effective in the prevention of CMV disease in seropositive solid organ transplant recipients.

Antigens, Viral↗

Incidence of pancreas graft thrombosis in portoiliac and portocaval venous anastomosis.

BACKGROUND: Pancreas graft thromboses represent more than 70% of all technical failures; multiple risk factors have been implicated. We analyzed the thrombosis rates using portoiliac versus portocaval vein anastomoses. PATIENTS AND METHODS: The series includes 53 patients who underwent pancreas transplantation: 49 simultaneous pancreas-kidney and 4 pancreas after kidney. There were 27 men and 26 women, of mean age of 37.2 +/- 7.0 years. We compared two groups of recipients that were classified according to venous anastomosis: (A) portoiliac (n = 30), and (B) portocaval (n = 23). RESULTS: The recipients did not show significant differences in age, gender, or duration of diabetes mellitus, but body mass index was significantly higher among the portocaval group. A bladder-drained pancreas technique was more frequently performed in the portoiliac group (93% of patients) versus an enteric-drained pancreas in the portocaval group (81%; P < .001). Heparinization was performed in 12 recipients: 11 (36.6%) in the portoiliac group and 1 (4.3%) in the portocaval group (P < .01). Vascular graft thrombosis (venous in six and arterial in one) developed in seven patients (13.2%) all in the portoiliac group (23%) (P < .02). Two-year patient survival was 93% in the portoiliac group and 94% in portocaval group (P = NS). Two-year graft survival was 66.6% in the portoiliac group and 85.9% in portocaval group (P = .07). CONCLUSION: There was no graft thrombosis among patients with a portocaval vein anastomosis.

Adult↗

[Regional correlations between MR imaging perfusion and SPECT in Alzheimer's disease].

INTRODUCTION: Dynamic susceptibility contrast (DSC) is a magnetic resonance (MR) technique that provides an estimation of cerebral blood flow (CBF) through the obtention of a cerebral blood volume map. As observed with nuclear medicine methods, DSC MR studies have demonstrated a temporoparietal hypoperfusion in Alzheimer's disease (AD). However, the concurrent validity of DSC and nuclear medicine techniques has not been sufficiently investigated. PATIENTS AND METHODS: A single-photon emission computed tomography (SPECT) and a DSC MR perfusion study were performed consecutively in 14 AD patients. Expert based qualitative assessments of CBF were carried out in eight regions of interest (ROI). RESULTS: Level of agreement in the studied ROI was highly variable. Presence of large blood vessels and patient head movement were possibly the main causes of this variability. Nevertheless, when interrater variability was eliminated, intraclass correlation coefficients became more uniform, ranging from 0.32 to 0.71. CONCLUSIONS: DSC MR imaging was concordant with SPECT at the different cerebral lobes of AD patients. The positive findings should be confirmed under better technical and methodological conditions.

Aged↗

Methods and demographic findings of the baseline survey of the NEDICES cohort: a door-to-door survey of neurological disorders in three communities from Central Spain.

OBJECTIVE: To describe the methods and general results of the baseline longitudinal survey in a defined cohort of elderly people from three areas of Central Spain (urban and rural). The survey was designed to study dementia, essential tremor, Parkinson's disease and stroke. STUDY DESIGN: A population-based longitudinal study with door-to-door interviews. METHODS: This study was carried out in two phases: Phase 1 (health status questionnaire and screening performed by lay interviewers) and Phase 2 (diagnosis of neurological illnesses by neurologists). RESULTS: The study flow chart, screening instruments for neurological disorders, main demographic data (age, sex, educational attainment, occupation) and general health status of the 5,278 screened participants (2,238 men and 3,040 women) are given for the two phases. The response rate was 85.3%, and participation was higher in men and in the urban area. CONCLUSIONS: Participation rates were good in both phases of the NEDICES baseline study, and this was influenced by age, sex and setting of the participants. Educational attainment, occupation and health status data are analogous to other Spanish studies performed in the elderly. As the study population was large and good participation rates were achieved, precise analysis of morbidity of the neurological disorders investigated will be possible.

Age Factors↗

Hepatitis C virus infection and renal disease after renal transplantation.

Hepatitis C virus (HCV) infection is the main cause of chronic liver disease after renal transplantation (RT). It is considered in some series to be a risk factor for graft loss and patient death. Also, HCV has been implicated in the pathogenesis of glomerular diseases in native and transplanted kidneys. The presence of membranoproliferative (MP) or membranous (M) glomerulonephritis (GN) in HCV-positive patients has been well documented after RT, but there is no clear data concerning the real prevalence of HCV-induced glomerulonephritis. MPGN with or without cryoglobulinemia and MGN have been described in HCV RNA-positive patients in general without severe liver disease. Also, there is a possible association between HCV infection and acute/chronic transplant glomerulopathy. Renal thrombotic microangiopathy has been described in HCV-positive patients with positive anti-cardolipin antibodies. The pathogenesis of MPGN and MGN in HCV patients after RT seems to be similar to that which occurs in native kidneys: the deposition of immune complexes containing HCV proteins in the glomeruli. Renal biopsy, using light microscopy, immunofluorescence techniques, and electron microscopy, is useful to achieve a correct diagnosis. Unfortunately, interferon is not recommended due to the significant risk of rejection. The possibility of pegylated interferon needs to be tested. Ribavirin can improve proteinuria but HCV RNA remains positive. Finally, recent data suggest that the use of interferon in HCV patients on dialysis can negate HCV RNA and prevent associated glomerulonephritis after RT.

Glomerulonephritis↗