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J Pascual

Publications and source records attributed to J Pascual.

At least 55 records · Page 3Linked to original sources
PubMed2004

Spanish experience with cyclosporine.

Our experience with cyclosporine (CsA) in de novo renal transplantation (RT) may be systematized in four consecutive periods. From February 1986 to December 1989, patient survival was higher among 128 consecutive CsA-prednisone-treated cadaver allograft recipients than in previous patients on azathioprine. One-year graft survival was significantly higher in CsA patients, a difference that was thereafter progressively reduced: at 10 years graft survivals were 50% versus 45%, and at 15 years 37% versus 35%, respectively. The most frequent cause of graft loss was death with a functioning graft. Acute rejection caused more graft losses among Aza-treated patients than CsA-treated ones. However, chronic allograft nephropathy produced more graft losses in CsA patients. After this initial experience with CsA-based immunosuppression we developed a second phase in which better results were obtained in 209 first cadaveric RT recipients. The use of lower initial CsA doses, more rapid steroid tapering, and a better approach to CsA nephrotoxicity or chronic nephropathy by substantial reductions in CsA exposure and delayed azathioprine addition, lead to these improvements. From March 1995 through 2000, we used the new microemulsion CsA formulation (Neoral) with steroids or azathioprine in 110 first de novo RT recipients. Mean donor and recipient ages were significantly higher in this phase than in previous ones; consequently, survival and function results were slightly worse. Blood CsA concentrations measured 2 hours after administration represent a more precise predictor of exposure than trough concentrations. The last step in optimizing Neoral use in RT on our service was application of reduced-dosage with C2 monitoring instead of classical C0 testing. Acute rejection and treatment failure rates were low and renal allograft function improved with respect to previous full-dose C0 experiences. CsA use has evolved in these two decades in four consecutive phases. Short-term results have improved or been maintained from phase to phase, even with expanded-criteria donors until excellent features during last years with C2 monitoring and combination with potent drugs such as MMF or everolimus. During the coming years, new drugs and protocols will allow even more optimized use.

Cyclosporins↗
PubMed2004

[Metastasis in renal graft of primary renal adenocarcinoma].

Acquired cystic renal disease (A.C.R.D.) is a risk factor for the development of renal carcinoma in the patient's own kidney after renal transplant (R.T.), development of a primitive tumor in the renal graft is infrequent, but the presence of metastasis of an epithelial tumor is very rare. This is the second case reported in the literature of metastasis of an epithelial tumor in the renal graft and the first case described of renal cell carcinoma metastasis (R.C.C.) in the renal graft. This paper describes the case of a patient with a normally functioning renal transplant and A.C.R.D. who develops RCC in his own kidney, with metastasis in the renal graft.

Adenocarcinoma↗
PubMed2004

Alternating hemiplegia of childhood: no mutations in the second familial hemiplegic migraine gene ATP1A2.

Alternating hemiplegia of childhood (AHC) is a rare disorder mainly characterised by attacks of hemiplegia and mental retardation. AHC has often been associated with migraine. Previously, we have excluded the involvement of the familial hemiplegic migraine (FHM) CACNA1A gene in four patients with AHC. A second gene for FHM was discovered recently: the ATP1A2 gene on chromosome 1q23, coding for the alpha 2 subunit of Na+,K+-ATPase. We performed a mutation analysis of the ATP1A2 gene in six patients, using direct sequencing, but found no mutations in any of the 23 exons. Other cerebral ion channel genes remain candidate genes for AHC.

Adolescent↗
PubMed2004

MTHFR T677 homozygosis influences the presence of aura in migraineurs.

It has been suggested that folate metabolism could be involved in migraine pathogenesis. We analysed the 5',10'-methylenetetrahydrofolate reductase (MTHFR) genotypic distribution in a large migraine sample. We genotyped 230 migraine patients (152 migraine without aura (MO) and 78 migraine with aura (MA)) and 204 nonheadache controls. The incidence of TT homozygosis for migraine in general (12%), MO (9%) and MA (18%) did not significantly differ from that found in healthy controls (13%). Differences were significant when the frequency of TT homozygosis between MA and MO (P = 0.03, OR = 2.34, 95% CI = 1.04-5.26) was compared. There was a tendency for a higher frequency of the MTHFR T allele in the MA group (42%) as compared to MO (29%) and controls (36%). These differences were significant only in the case of MA vs. MO (P = 0.006, OR = 1.75, 95% CI = 1.15-2.65). These results could indicate that the MTHFR C677T polymorphism, causing mild hyperhomocystinaemia, might be a genetic risk factor for experiencing aura among migraineurs. Overall, however, there was no association between migraine and the C677T MTHFR polymorphism.

Adult↗
PubMed2004

[Influence of botulinum toxin treatment on previous primary headaches in patients with cranio-cervical dystonia].

INTRODUCTION: Preliminary data suggest some beneficial effects of botulinum toxin type A (BT-A) on primary headaches. OBJECTIVE: To analyze the subjective influence of BT-A on previous primary headaches of those patients receiving this treatment due to a variety of cranio-cervical dystonia (CD). PATIENTS AND METHODS: All patients receiving BT-A due to CD were interviewed with an ad hoc questionnaire on the presence or not of headaches prior to BT treatment. Diagnosis and subjective effects of BT-A on these previous headaches were recorded. RESULTS: Thirty-eight patients (28 women) were interviewed; 21 (19 women) reported a history of previous primary headache (12 migraine, 10 tension-type headache). Nine (41 %) reported sustained response ( > 50 % reduction in headache frequency) since the beginning of BT-A treatment. Patients with cervical dystonia or those receiving high doses ( > 50 U) showed the best responses. Age, gender, pain location, duration of BT-A treatment and headache diagnosis did not seem to correlate with response. CONCLUSIONS: BT-A seems to have sustained beneficial effect on primary headaches of some patients with CD, especially at doses higher than 50 U and in patients with the diagnosis of spasmodic torticollis.

Adult↗
PubMed2004

[Spanish contribution to the clinical development of eletriptan: an analysis of controlled studies].

INTRODUCTION: Eletriptan is a recently marketed second-generation triptan with a potent agonist activity on 5-HT1B/ 1D receptors. Our aim has been to analyze the specific results from the Spanish participation in phase IIIa and IIIb clinical trials vs placebo and compare them with the results obtained in the global clinical development of eletriptan. PATIENTS AND METHODS: Analysis of the results obtained in 40 centers in Spain (358 patients) vs global sample 4,677 patients) for the first migraine attack in 6 controlled clinical trials with eletriptan 40 mg, eletriptan 80 mg and placebo. This ad hoc analysis was carried out for those treatment groups with more than 50 patients, which reduced the final number of patients from Spain to 250. RESULTS: The proportion of patients with relief at 2 hours (main endpoint) in the Spanish sample was 22 %, 59 % and 67 % for placebo, eletriptan 40 mg and eletriptan 80 mg, respectively. These values were significantly higher (p < 0.05) than those of placebo and similar to those from the total sample. The proportion of pain free patients at 2 hours in the Spanish sample was 10 %, 36 % and 41 % for placebo, eletriptan 40 mg and eletriptan 80 mg, respectively. These values were significantly better than those for placebo (p < 0.05) and about 15 %-20 % higher than those from the total sample. Recurrence rate in the Spanish sample was 50 %, 16 % and 25 % for placebo, eletriptan 40 and eletriptan 80 mg, respectively, and did not differ from that of the total sample. Sustained relief for the two eletriptan doses was 46 % for both eletriptan 40 and eletriptan 80, this being significant (p < 0.05) over placebo (11 %) for the Spanish sample and similar to that of the global sample. The results for other efficacy parameters, such as need of rescue medication, functional response at 2 hours, complete response for pain-freeness and acceptability followed a similar pattern. Eletriptan was, in general, well-tolerated. Adverse events were slight-moderate in intensity, transient and were not different, either in profile or proportion, from those from the global sample. CONCLUSIONS: These results confirm eletriptan 40 mg and 80 mg as an excellent option for the symptomatic treatment of migraine in our setting.

Clinical Trials, Phase III as Topic↗
PubMed2004

[Treatment of pain in the oncology patient].

Pain is a symptom with a high prevalence in patients with cancer and causes an important deterioration in their quality of life. With the measures laid out by the WHO in 1986, which divides the different therapeutic options available in three ascending steps, pain can be controlled in a high percentage of cases. Those patients who are difficult to control with these measures can benefit from the application of neuromodulation techniques by experts in the treatment of chronic pain. The correct employment of the different medicines (non-steroidal anti-inflammatory medicines, opiates and coadjuvants), knowledge of the secondary effects, loss of fear in the face of opiates and knowledge of the different algic syndromes associated with the oncology patient, must be accompanied by a suitable evaluation of the pain according to the different scales, both in the phase of the treatment's initiation and in the follow-up of the patient.

Analgesics↗
PubMed2003

Comparison of C0 and C2 cyclosporine monitoring in long-term renal transplant recipients.

Recent data show that monitoring cyclosporine A (CsA) concentrations with 2-hour postdose levels (C2) correlates with the incidence of rejection and graft outcome in de novo renal transplant patients. The purpose of the present work was to evaluate the advantage of C2 monitoring after the first year of kidney transplantation. We studied 161 patients, 96 on CsA-prednisone and 65 on triple therapy (Aza or MMF) who had been transplanted for a mean of 103+/-44 months. Mean serum creatinine (SCr) was 1.65+/-0.69 mg/dL, mean C0 was 174+/-44, and C2 was 667+/-194 ng/mL. Patients were classified according to C2 values: >850 (n=29), between 850 and 450 (n=109), and <450 (n=23) ng/mL. Patients with C2 <450 ng/mL displayed higher SCr values (1.97+/-0.99; 1.59+/-0.51; 1.52+/-0.4 mg/dL; P<.001), received lower CsA doses (172+/-54; 207+/-54; 227+/-56 mg/d, P<.01), showed lower C0 levels (155+/-48; 172+/-41; 199+/-45 ng/mL; P< .001), and included more patients on triple therapy (54.5%; 44%; 17.2%; P<.05). We found weak correlations between C0 and C2 (r=0.37), between C2 and CsA dose (r=0.36), and between C0 and SCr (r=-0.37). Among 117 patients followed up for 1 year with several C0 and C2 measurements, the coefficient of variation of C0 was 17% and of C2 was 21%. Graft functional deterioration occurred in 16 patients independent of the differences among the C2 groups, but 7 recipients (43.7%) had C0 <150 ng/mL and C2/C0 >5. We conclude that C2 in monitoring stable patients needs further evaluation.

Azathioprine↗
PubMed2003

A low incidence of new-onset insulin-dependent diabetes mellitus using tacrolimus in kidney recipients in Europe.

Employing tacrolimus (Tac) for routine immunosuppression in renal transplantation (RT), produced an incidence of new-onset, insulin-treated, diabetes mellitus (newDM) as high as 20%. More recently, several large multicenter kidney studies using Tac as the primary immunosuppressant have been reported in Europe. Between 1997 and 2001, we performed 155 RTs using Tac (0.2 mg/k/per day, targeting whole blood trough levels <15 ng/mL) with a rapid steroid taper. The acute rejection rate was 13%, and 89% of grafts are still functioning. Only 5 Tac-treated patients not previously requiring insulin needed insulin therapy for > or =30 days (3.2%). Eight separate studies employing Tac in at least one arm (N=2728) have been reported between 1997 and 2002. Tac was combined with azathioprine or MMF, and/or steroids. The incidence of new DM at study end ranged from 2.3% to 8.3%. The only trial with >6% incidence was the first one, using an initial dose of 0.3 mg/kg per day. The most recent studies utilized an initial dose of 0.2 mg/kg per day, targeting whole blood trough levels of <15 ng/mL and a steroid taper, with newDM at <6%. On the basis of these data, we confirm in that the use of Tac as a first-line immunosuppressant in renal transplant patients affords protection against acute rejection with a low level of newDM. The tendency to employ lower oral doses of Tac, lower blood target levels, and a reduced steroid dose appear to minimize glucose disturbances in RT.

Diabetes Mellitus, Type 1↗
PubMed2003

Comparison between a two-drug regimen with tacrolimus and steroids and a triple one with azathioprine in kidney transplantation: results of a European trial with 3-year follow up.

This study was designed to assess the efficacy and safety of two immunosuppressant regimens in kidney transplantation based on the administration of tacrolimus-one of them with tacrolimus, azathioprine, and corticosteroids (n=239) and the other with tacrolimus, and corticosteroids (n=236). After completing the initial 3-month study, the patients remaining in the study (197 and 195, respectively) were assessed for 3 years. The incidence of acute rejection (AR) episodes treated during this period was 28.8% with dual-drug therapy and 29.7% with triple-drug therapy. Late AR: episodes between 4 and 36 months were scarce (3.3% in dual and 4.2% in triple therapy). Chronic rejection incidence was 7.7% and 8.9%, respectively. The patients who experienced AR episodes during the first 3 months developed chronic rejection more frequently than those who did not suffer AR. Patient survival at 3 years was 95% vs 95.6%, and graft survival was 86.6% vs 86.5% (NS). Doses and blood levels of tacrolimus were similar in the two groups. Adverse effects were similar among both treatment groups. Median SCr was 123.8 micromol/L vs 114.9 micromol/L in patients who did experience AR: 145.9 micromol/L vs 132.6 micromol/L in those with early AR; and 194.5 micromol/L vs 152 micromol/L in those who presented with late AR. Need for de novo posttransplant insulin was 4.2% in the dual-drug group and 3.8% in the triple-drug cohort. These results demonstrate that, after 3 years of follow up, there were similar efficacy data among the dual- and triple-drug regimens. Thus, addition of azathioprine does not contribute any advantage in the middle term.

Acute Disease↗
PubMed2003

Renal transplant recipient outcome after losing the first graft.

Renal transplantation is the optimal therapy for end-stage renal failure and considerable attention has been given to graft and patient survival and the effectiveness of immunosuppressive regimens. However, little attention has been given to outcome for patients who lose their grafts. We retrospectively reviewed the outcomes of the 793 first renal transplants performed at our institution between November 1979 and December 2001. A total of 348 patients lost their grafts, 116 by death with a functioning graft (33.3%) and 232 patients for other causes (66.7%). Eighty-six patients (37.1%) received a second transplant 3.5+/-2.4 years after returning to dialysis and the remainder continued on dialysis. Retransplanted patients were younger at the time of the first transplant (P=.000), and both time on dialysis (P=.012) and duration of graft function (P=.057) were shorter than for those remaining on dialysis. Therefore, retransplant patient survival at 1, 5, and 10 years was better than among those patients on dialysis not included on the waiting list (P<.001), but when compared with the relisted patients the survival rate was almost identical (96%, 85%, and 67% vs 97%, 82%, and 67%; P=NS). Almost 40% of patients who lost their first grafts were retransplanted. We did not observe differences in patient survival between retransplant and relisted patients. Because the number of cases is limited, our results need to be confirmed by larger series.

Adult↗
PubMed2003

Influence of laparoscopic live donor nephrectomy in ischemia-reperfusion syndrome and renal function after kidney transplantation: an experimental study.

The increase of intra-abdominal pressure during laparoscopic techniques provokes oliguria and reduction of the renal blood flow (RBF). The aim of this study is to evaluate this effect during living donor nephrectomy and its influence in the ischemia-reperfusion syndrome and renal function after kidney transplantation. Autotransplantation was performed using 22 pigs (15 after conventional open nephrectomy and 7 after laparoscopic nephrectomy). During donor nephrectomy a significant reduction in RBF was observed in the laparoscopic group (70 mL/min) vs the open group (260 mL/min) (P<.05). After a cold ischemia period of 24 hours an autotransplantation was performed. During the first hour after revascularization RBF was lower for the laparoscopic than for the open group: 60 vs 180 mL/s at 1 minute and 160 vs 400 mL/s at 60 minutes (P<.05). The decrease of creatinine was slower for the laparoscopic than for the open group during the first posttransplant week (2 vs 1.3 mg/dL on the first day and 1.4 vs 0.8 mg/dL on the seventh day posttransplant, respectively) (P<.05).

Animals↗
PubMed2003

Influence of immunosuppression on the prevalence of cancer after kidney transplantation.

The prevalence of cancer in renal transplant patients is greater than in the general population. It is influenced by demographic and ethnic characteristics. We performed a retrospective study of 793 patients who received 872 kidney transplants at our center during 23 years. The age at transplantation was 41.4+/-14.0 years, the follow up 75.4+/-69.4 months. The cohorts include 203 patients treated with azathioprine-prednisone; 510, cyclosporine-based therapy; and 159, tacrolimus-based therapy. There were 95 patients (10.9%) who developed at least one neoplasm with 9 having more than one type of tumor. The incidence was of 17.3 cases per 1000 patients-years. Forty-four (46.3%) had skin cancer, 8 (8.4%) Kaposi sarcoma and 43 (45.3%) a non-skin cancer. Seven of eight patients with Kaposi sarcoma were on CsA therapy. The risk of developing a neoplasm at 5, 10, and 15 years was 8%, 17%, and 30% respectively. In a multivariate analysis, the risk factors associated with neoplastic diseases were older age (OR=1.061; 95% CI 1.039-1.084; P=.000), male sex (OR=2.658; 95% CI 1.536-4.599; P=.000), length of follow-up (OR=1.121; 95% CI 1.073-1.172; P =.000), and immunosuppression with CsA (OR=4.448; 95% CI 1.334-14.764; P=.015). Cancer was the cause of death in 26 patients, the fourth most common cause after cardiovascular disease, infection, and liver failure. We conclude that malignancies are an important cause of morbidity and mortality among transplant patients. Special attention must be devoted to older male patients with a long-term follow up to develop preventive and surveillance strategies.

Adult↗
PubMed2003

Cytomegalovirus infection after renal transplantation: selective prophylaxis and treatment.

We have reviewed our experience in selective cytomegalovirus (CMV) infection prophylaxis and treatment in our renal transplant population. Between 1996 and 2001, 263 cadaveric renal transplant recipients had at least 6 months follow up. Immunosuppression was based on cyclosporine Neoral (n=108) or tacrolimus (n=155). CMV infection prophylaxis (oral acyclovir or gancyclovir at half usual doses) was only prescribed in recipients receiving a CMV positive ve kidney and in recipients treated with OKT3. CMV infection was diagnosed by a positive pp65 antigenemia upon appearance of CMV-related symptoms, leading to specific treatment (IV ganciclovir) only if symptoms were intense or there was visceral involvement. Thus, no preemptive treatment or programmed or periodic antigenemia was performed in any case. Nineteen episodes of symptomatic CMV infection were diagnosed (prevalence 7.2%). The frequency was similar for all immunosuppressive regimens. Only 9 of 19 (47%) of patients were given IV ganciclovir; the others were not treated. All patients survived without apparent complications, relapses, or recurrences. No oral gancyclovir was delivered after IV treatment. Our CMV prophylaxis protocol was limited to high-risk patients, using lower gancyclovir dosages than those usually advocated. It does not include programmed or scheduled search for CMV antigenemia in asymptomatic renal transplant patients. Despite these factors, our CMV infection rate and severity were similar to those reported with more aggressive protocols, with extended prophylaxis, preemptive therapy, or intense surveillance.

Acyclovir↗
PubMed2003

Tilt table testing in patients referred from an epilepsy clinic.

OBJECTIVE: To assess the role of head up tilt testing (HUT) in diagnosing probable or possible vasovagal syncope (VVS) in patients referred from an epilepsy clinic. METHODS: One hundred thirty two patients underwent HUT over 36 months. Complete data were available on 128 patients (52 male) aged 14-80 (mean 36.7) years. The main indication for HUT (head up tilt at 70 degrees for 45 minutes) was recurrent undiagnosed blackouts, likely to be VVS. Patients were divided, prior to knowledge of the HUT results, into probable VVS, possible VVS, or probable/possible VVS associated with definite epilepsy. RESULTS: HUT was positive in 72 patients (56%), and led to an alternative definite diagnosis in 31 (24%). Diagnostic change was more likely in those provisionally labelled either as possible VVS (15 of 34; 44%) or as a combination of epilepsy with possible or probable VVS (12 of 19; 63%) compared to those with probable VVS (4 of 75; 5%; P<0.01).Of the 45 patients previously treated with antiepileptic medications 27 did not have epilepsy. CONCLUSION: HUT has an important role in confirming or refuting the diagnosis of VVS in patients presenting with undiagnosed blackouts to an epilepsy clinic, and particularly so in patients with possible rather than probable VVS, and in those thought to have a combination of epilepsy and possible or probable VVS.

Adolescent↗