Search PubMed⌕ Search

Biomedical subjects

J Pascual

Publications and source records attributed to J Pascual.

At least 19 recordsLinked to original sources
PubMed2007

How many migraine patients need prolonged (>1 year) preventive treatment? Experience with topiramate.

The usual recommended duration of preventive treatment for migraine is 3-6 months. Our aim was to explore how many patients attending a specialised clinic need prolonged preventive treatment for longer than one year. Eighty consecutive migraine patients who received preventive treatment with topiramate for 3 months with good response and tolerability were included in this observational study. All patients continued on topiramate until they had completed 6 months, when this drug was stopped. Topiramate was reintroduced if there was a worsening. Topiramate was kept for 6 more months and then discontinued again. Those patients whose headaches became worse after this second withdrawal received topiramate again and were followed-up for at least half a year. Headaches did not worsen after the first withdrawal at 6 months in 40 patients (50%), while they clearly worsened in the remaining 40 patients. At the end of the first year only two patients out of these 40 (5%) discontinued topiramate and did not notice an increase in headache frequency after two months. In conclusion, around half of the patients attending a specialised clinic due to frequent headache need preventive treatment for more than one year. Our data suggest that the current practice recommending periods of preventive treatment of 3-6 months should be reconsidered for many patients.

Adult↗
PubMed2007

Almotriptan and zolmitriptan in the acute treatment of migraine.

OBJECTIVE: To compare almotriptan and zolmitriptan in the treatment of acute migraine. METHODS: This multicentre, double-blind trial randomized adult migraineurs to almotriptan 12.5 mg (n = 532) or zolmitriptan 2.5 mg (n = 530) for the treatment of a single migraine attack. The primary end point was sustained pain free plus no adverse events (SNAE); other end points included pain relief and pain free at several time points, sustained pain free, headache recurrence, use of rescue medication, functional impairment, time lost because of migraine, treatment acceptability, and overall treatment satisfaction. RESULTS: No significant difference was seen in SNAE (almotriptan 29.2% vs zolmitriptan 31.8%) or the other efficacy end points measured. The incidence of triptan-associated AEs and triptan-associated central nervous system AEs was significantly lower for patients receiving almotriptan compared to zolmitriptan. CONCLUSIONS: Almotriptan and zolmitriptan were associated with similar efficacy and overall tolerability in the treatment of acute migraine. Almotriptan was associated with a significantly lower rate of triptan-associated AEs.

Acute Disease↗
PubMed2007

Testing the combination beta-blocker plus topiramate in refractory migraine.

OBJECTIVE: To test treatment combining a beta-blocker plus topiramate in migraine patients previously resistant to the two medications in monotherapy. PATIENTS AND METHODS: Those patients who had not responded to a beta-blocker and topiramate received combined treatment. RESULTS: Fifty-eight patients (47 women, age 25-76 years) received the combined treatment. Thirty-three (57%) met criteria for chronic migraine/medication overuse headache, 18 (31%) for migraine without aura and seven (12%) with aura. Ten (17%) discontinued due to adverse events. Among the 48 patients who tolerated the combination, 36 (75%, 62% of the total series) showed response (>50% reduction in frequency), while 12 (25%) did not. The number of days with headache/month decreased from 15.1 to 6.5 (-57%). Sixteen (44% of responders) showed an excellent (>75%) response. Eighteen patients (38%) experienced a total of 26 adverse events (mild-moderate). CONCLUSIONS: The combination of beta-blocker plus topiramate showed a benefit in around 60% of patients who had not previously responded to monotherapy. Adverse events led to discontinuation in one out of six patients. From these open results, it seems reasonable to recommend this combination, complementary in terms of mechanism of action, as a potential strategy in patients with refractory migraine.

Adrenergic beta-Antagonists↗
PubMed2006

Interactions between bacteria and Cryptosporidium molnari in gilthead sea bream (Sparus aurata) under farm and laboratory conditions.

The possible interaction of Cryptosporidium molnari and bacteria in gilthead sea bream (Sparus aurata) was studied. Epidemiological data from a pathological survey under farm conditions were analyzed. In addition, parasite and bacteria burdens were studied in experimental models in which naturally and experimentally parasitized fish were challenged with a particular strain of Vibrio harveyi (H57). All the bacteria species present were studied. Under farm conditions, the parasite was more prevalent when mortality or morbidity cases (study C) occurred than in randomly sampled fish (study B). In study C, parasite abundance was significantly higher in bacteria-negative fish, and total bacteria abundance was significantly higher within non-parasitized fish. V. harveyi and V. splendidus were the most prevalent among bacteria carriers in studies B and C, respectively. In study C, among bacteria carriers, most isolates were slightly more prevalent in parasitized than in non-parasitized fish. Two groups (G1, G2) of naturally parasitized fish were inoculated with H57 by intracoelomic injection (ICI) and by oral intubation (OI). H57 was recovered only in G1 inoculated fish, which had a significantly higher basal abundance of total bacteria, and where the only ones with mortalities. In G1, the mortality rate and the prevalence of other V. harveyi strains different from the H57 molecular type were higher in ICI than in OI fish, and the total bacteria abundance was also significantly higher in ICI fish. C. molnari abundance was significantly higher in G1 than in G2, and also in OI than in ICI fish within G1. When H57 was IC inoculated to fish (G3, from the same farm as G2) experimentally infected with C. molnari, H57 was not recovered from any fish. A low mortality was recorded, and only in those fish inoculated with both pathogens. Also in these fish, the prevalence of infection of C. molnari was higher and histopathological damage to the stomach was greater than in fish inoculated only with the parasite. Therefore, the impact of the parasite would be reduced notably when the bacterial burden or the intensity of parasite infection are low (G2, G3).

Animals↗
PubMed2006

Conversion from calcineurin inhibitors to everolimus in kidney transplant recipients with malignant neoplasia.

Cancer has been reported to be more common among kidney transplant recipients than waiting-list patients or the general population. Use of anticalcineurin agents and azathioprine are relevant risk factors. Nine renal allograft recipients (seven men and two women) of mean age 67.6 (55-77) years and mean time after transplantation of 30.7 (58-216) months were switched to everolimus-based immunosuppression because of the presence of biopsy-proven malignancies (eight patients) or neurological tacrolimus toxicity (one patient). One patient with posttransplant lymphoproliferative disease also received chemotherapy with a good evolution at 6 months. He showed an initial increase in the protein to creatinine ratio (peak 3.3 mg/mg at 3 months) that was controlled by increasing the enalapril dose. One patient with skin cancer and severe atheromatosis (baseline SCr 2.5 mg/dL, creatinine clearance 17 mL/min, and protein to creatinine ratio 3.2 mg/mg), had cyclosporine and everolimus overlapped for 25 days, showing a continued poor evolution requiring dialysis initiation at 3 months after switch. The other six patients with recurrent skin cancers had good cancer evolution, with no new skin tumors and regression of skin lesions in three, including not biopsied actinic keratosis. Sudden switching from calcineurin inhibitors to everolimus is safe and may be used in long-term transplant recipients with malignancies. In patients with advanced chronic nephropathy this approach appeared to be less beneficial.

Aged↗
PubMed2006

Mycophenolate mofetil tolerability and dose changes in tacrolimus-treated renal allograft recipients.

Mycophenolate mofetil (MMF) reduces acute rejection episodes (AREs) and may be associated with better renal graft survival than azathioprine. However, MMF-related adverse events are frequent; dose reduction or even withdrawal are quite common. Between 1999 and 2003, 115 renal transplantation patients were treated with tacrolimus, MMF, and steroids. An observational study was undertaken until graft loss (n = 7), death with a functioning graft (n = 2), or October 31, 2005 (mean follow-up-50 months). We assessed MMF dose reductions due to adverse events with the possible consequences on AREs and graft function. Treated acute ARE occurred in 11.3% of recipients, all of which were steroid-responsive. The median MMF initial daily dose was 1000 mg. In 44 patients (38.3%), the MMF dose was not changed; in 48 (41.7%) it was reduced; and in 23 (20%), withdrawn. The causes for dose modification were diarrhea (n = 33, 28.7% of all patients), leukopenia (n = 22, 19.1%), both of these (n = 7, 6.1%), or other events (n = 9, 7.8%). No AREs were attributed to MMF dose changes. Tacrolimus blood levels were higher at 3 years and serum creatinine values at 4 years among patients with dose changes (8.43 +/- 2.42 vs 7.37 +/- 2.23 ng/mL; P = .051 and 1.75 +/- 0.71 vs 1.48 +/- 0.38 mg/dL; P = .038, respectively). The need for MMF dose reduction or withdrawal was frequent in our patients with diarrhea or leukopenia during treatment with tacrolimus, MMF, and steroids. These adverse event-related changes were not associated with AREs, but produced deleterious effects on long-term graft function.

Creatinine↗
PubMed2006

Pancreas islet transplantation in the genitourinary tract associated with renal transplantation: an experimental study.

Conceptually, pancreas islet transplantation (PIT) associated with renal transplantation (RT) should resolve not only chronic renal failure but also diabetes. Although the most frequently used site for PIT is the portal vein, genitourinary locations could be technically feasible during RT. Seventeen pigs (age 3 to 4 months; mean weight 34.5 kg) underwent the following experimental steps: On day 1 a left nephrectomy was performed and the kidney was perfused with cold Wisconsin solution. This was followed by a caudal pancreatectomy and islet isolation by means of digestion with intraductal collagenase. Islets were stained with Dithizone and cultured overnight al 37 degrees C and 5% CO(2). On day 2 a right nephrectomy and orthotopic RT of the preserved left kidney were performed. The islets were transplanted into four different sites: subcapsular in the kidney graft, in the bladder submucosa, in the testis by puncture, and in the testis by infusion through the vas deferens. On day 7 the animals were sacrificed. Islet viability was determined by histological examination with insulin immunostaining and determination of insulin in the blood of the veins draining the implantation sites. The mean weight of the pancreatic specimens was 27.8 g (13 to 46). The mean number of islets was 536,000 (16,600 to 1,5000,000). Islets were shown in the bladder submucosa and the testes after vas deferens infusion. The number of viable islets in the other implantation sites was very scarce. The insulin levels of the venous effluents were: 15.1 microU/mL for bladder submucosa, 10.2 microU/mL for intradeferential injection in the testis, 7.3 microU/mL for intratesticular injection by puncture, and 2.6 microU/mL for subcapsular implantation in the graft. In conclusion, the bladder submucosa and testis via the vas deferens might represent alternative sites for PIT. The latter route may benefit from the immunoprivileged and special trophic conditions of the testis. For the first time, the feasibility of the bladder submucosa as an implantation site for pancreas islets was demonstrated.

Animals↗
PubMed2006

Post-kidney transplant surgical complications under new immunosuppressive regimens.

New immunosuppressive regimens have decreased acute rejection rates after kidney transplant. However, the use of these new agents has modified the profile of surgical complications. We compared the incidence of surgical complications in relation with the use of three types of drugs: calcineurin inhibitors, antiproliferative agents, and mammalian target of rapamycin (mTOR) inhibitors. This retrospective study included 359 cadaveric recipients who received an allograft between 1997 and 2004. The mean age was 54 years. The prevalence of diabetes was 8.5% and that of obesity (body mass index > 30 kg/m(2)) was 15.4%. The mean follow-up time was 44 +/- 5.6 months. The regimen most frequently used was tacrolimus (TACRO), mycophenolate mofetil (MMF), and prednisone (PRED) (n = 172), followed by TACRO-PRED (n = 49), cyclosporine (CSA) and MMF and PRED (n = 41), and CSA-azathioprine (AZA) and PRED (n = 24). A surgical complication was considered to be any type of event during the first year, although minimal, directly related to surgery. The rate of surgical complications was 34.8% (122/350). Collections and bleeding were higher in CSA than in TACRO regimens, 12% versus 3.8% (P < .05) and 11.5% versus 3% (P = .002), respectively. The incidence of lymphoceles was higher in regimens with than without mTOR inhibitors: 16% versus 3.7% (P = .012). The incidence of surgical complications was not influenced by the use of MMF or diabetes. In conclusion, the use of mTOR inhibitor-based immunosuppressive regimens leads to a higher incidence of lymphoceles, while the use of MMF does not increase the incidence of surgical complications.

Drug Therapy, Combination↗
PubMed2006

Epidemiology of headache in Europe.

The present review of epidemiologic studies on migraine and headache in Europe is part of a larger initiative by the European Brain Council to estimate the costs incurred because of brain disorders. Summarizing the data on 1-year prevalence, the proportion of adults in Europe reporting headache was 51%, migraine 14%, and 'chronic headache' (i.e. > or =15 days/month or 'daily') 4%. Generally, migraine, and to a lesser degree headache, are most prevalent during the most productive years of adulthood, from age 20 to 50 years. Several European studies document the negative influence of headache disorders on the quality of life, and health-economic studies indicate that 15% of adults were absent from work during the last year because of headache. Very few studies have been performed in Eastern Europe, and there are also surprisingly little data on tension-type headache from any country. Although the methodology and the quality of the published studies vary considerably, making direct comparisons between different countries difficult, the present review clearly demonstrates that headache disorders are extremely prevalent and have a vast impact on public health. The data collected should be used as arguments to increase resources to headache research and care for headache patients all over the continent.

Adolescent↗
PubMed2006

Efficacy, speed of action and tolerability of almotriptan in the acute treatment of migraine: pooled individual patient data from four randomized, double-blind, placebo-controlled clinical trials.

A meta-analysis of pooled individual patient data from four randomized, placebo-controlled, double-blind trials comparing several doses of almotriptan (n = 1,908) with placebo (n = 386) was used to investigate the efficacy, speed of onset and tolerability of almotriptan in the acute treatment of migraine. As early as 30 min after dosing, almotriptan 12.5 mg was significantly more effective than placebo for pain relief (14.9% vs. 8.2%; P < 0.05) and pain free (2.5% vs. 0.7%; P < 0.05). At 2 h, pain-relief rates were 56.0%, 63.7% and 66.0% for almotriptan 6.25, 12.5 and 25 mg, respectively, compared with 35% for placebo; 2-h pain-free rates were 26.7%, 36.4% and 43.4% compared with 13.9% for placebo. All almotriptan dosages were significantly more effective than placebo in eliminating migraine-associated symptoms (P < 0.05) and in achieving sustained pain relief up to 24 h (P < 0.05). The incidence of adverse events after almotriptan 6.25 mg and 12.5 mg was not significantly different from that of placebo. This meta-analysis confirms the findings of individual clinical trials, while demonstrating for the first time, significant pain-free efficacy at 30 min compared with placebo.

Acute Disease↗
PubMed2006

Premonitory and resolution symptoms in migraine: a prospective study in 100 unselected patients.

The nosology of migraine premonitory (PS) and resolution (RS) symptoms was studied in 100 migraineurs consulting their general physician. They were asked to fill in, for three attacks, a PS and RS questionnaire. 'True' PS/RS were those experienced the day before (or the day after) the headache had started only if they were not present in a questionnaire completed in a pain-free period. True PS and RS were experienced by 84% and 80%, respectively, of subjects for the first attack. The mean and range (per patient) of PS were 6.8 and 0-21 and of RS 4.7 and 0-15. Anxiety, phonophobia, irritability, unhappiness and yawning were the commonest PS, whereas asthenia, tiredness, somnolence and concentration difficulties were the most common RS. Gender, age and Migraine Disability Assessment scores did not influence PS and RS. Both PS and RS were more frequent in migraine with aura subjects. Patients on preventatives showed a decreased frequency of PS and, to a lesser degree, of RS. Severity of headache was associated with a higher frequency of RS. Individual RS and especially PS were quite consistent after three attacks. Almost two-thirds of the symptoms were noticed in at least two out of three attacks, while more than a half of PS and more than a quarter of RS repeated in three out of three attacks. In conclusion, around 80% of unselected migraineurs experience RS and PS. Migraine with aura and severe pain are risk factors for experiencing PS and RS, while preventatives were protective, especially for PS.

Adolescent↗
PubMed2006

Review of clinical trials using early acute intervention with oral triptans for migraine management.

Most of the data on triptan use are from clinical trials in which patients were instructed to wait until migraine headache pain was moderate/severe in intensity. In the real world, patients may hesitate to use a triptan until headache pain is moderate/severe because of the cost of these agents or limited supply allowed by their health service organisation. However, accumulating data indicate that early intervention with an oral triptan when headache pain is still mild may be the most effective acute treatment strategy. Economic analyses also support early triptan intervention in migraine attacks. Tolerability is expected to be particularly important in early intervention, as patients treating mild migraine pain may be more reluctant to risk adverse events. Thus, an agent selected for use as early intervention should have both a demonstrated efficacy in treating mild migraine headache and placebo-like tolerability. This article reviews retrospective and prospective clinical trials which investigated the use of triptans for early acute migraine therapy.

Administration, Oral↗
PubMed2006

[Experience with intranasal zolmitriptan in cluster headache].

INTRODUCTION: The objective is to analyse our experience with the new intranasal formulation of zolmitriptan 5 mg in the symptomatic treatment of cluster headache in daily clinical practice. PATIENTS AND METHODS: We collected a total of 18 patients with cluster headache and experience with intranasal zolmitriptan; 17 had used subcutaneous sumatriptan and 8 oral triptans. The main reasons for trying intranasal zolmitriptan were: poor tolerability in 12 patients and insufficient efficacy in 6. RESULTS: Among the 17 patients experienced in subcutaneous sumatriptan, 12 (71 %) preferred nasal zolmitriptan, 2 (18 %) subcutaneous sumatriptan and 2 (12 %) did not express any preference. The reasons for preferring intranasal zolmitriptan were: higher convenience (n = 6), better tolerability (n = 5), lower price (n = 2) and higher efficacy (n = 1). Seven out of the 8 patients who had taken oral triptans preferred nasal zolmitriptan, in all cases due to higher subjective efficacy. A total of 11 patients showed efficacy within 30 minutes. Only 3 patients referred to adverse events, always mild. CONCLUSIONS: The 5 mg nasal formulation of zolmitriptan is a potential new option for the symptomatic treatment of cluster headache. This formulation should be considered in patients with poor tolerability to subcutaneous sumatriptan and in those attacks where quick access to inhaled oxygen is not possible. These results suggest that a controlled trial with nasal zolmitriptan in this indication would be worthwhile.

Administration, Intranasal↗
PubMed2006

[Renal transplantation in HIV-infected patients in Spain].

HIV infection has experienced dramatic improvement in morbidity and mortality with the highly active antiretroviral therapy (HAART). This prompted a reevaluation of organ-solid transplantation as a treatment option for HIV-infected patients. Some trials in the United States have shown that one- and 2-year graft and patient survival is comparable to HIV-negative transplant population. In Europe the experience is still scarce. The aim of this study is to analyse the outcome and the clinical characteristics of HIV-infected patients who received kidney transplantation in Spain in the HAART era. Ten patients were transplanted in our country since 2001. Only one patient was black. The main cause of end-stage renal disease reported was glomerulonephritis. Six of the recipients were coinfected by hepatitis C virus. Inclusion criteria included undetectable HIV viral load and CD4 counts greater than 200/pL. Immunosuppression consisted of steroids, tacrolimus and mycophenolate mofetil, with antibody induction in 4 cases. The median and mean follow-up was 11 and 16.3+/-15.6 (3-46) months, respectively. One recipient lost his graft because of early renal venous thrombosis. The remaining patients are functioning graft with mean serum creatinina level of 1.5 +/- 0.5 mg/dl. Biopsy-proven acute rejection was diagnosed in 4 recipients and was reversed in all cases with antirejection treatment. The plasma HIV RNA levels have remained controlled and CD4 counts have been stable in excess of 200 cell/microL. None of patients have developed AIDS complications. Recipients receiving protease inhibitor-based HAART regimens required significant dosing modification to maintain appropriate tacrolimus levels. Our results show that renal transplantation can be a safe and effective treatment in select HIV-infected patients. Like other series, the acute rejection rate was higher than in non-HIV recipients. The reasons of this rejection incidence remain unknown.

Adult↗
PubMed2006

[Symptomatic treatment of migraine with zolmitriptan: experience with 82 patients].

OBJECTIVES: To analyze our experience with the new, 5 mg intranasal formulation of zolmitriptan in the symptomatic treatment of migraine attacks. PATIENTS AND METHODS: This series includes 82 patients who had treated an average of 7 migraine attacks. Eighty patients had taken oral triptans and 20 subcutaneous sumatriptan. The main reasons for using nasal zolmitriptan were: poor efficacy of oral triptans (41.5 % of the patients), use of subcutaneous sumatriptan (24.4%) or medical criteria (34.5%). RESULTS: Among the 80 patients who had been treated with oral triptans, 50 (62.5 %) preferred nasal zolmitriptan, 14 (17.5 %) oral triptans and the remaining 16 (20 %) did not express any preference. The main reasons for this preference were shorter speed of action and better efficacy. Within those 20 patients who were using subcutaneous sumatriptan, 8 (40 %) preferred subcutaneous sumatriptan, 5 (25%) nasal zolmitriptan and 7 (35%) did not express any preference. The reasons for preference of intranasal zolmitriptan over subcutaneous sumatriptan were greater convenience, better tolerability and lower price. A total of 55 patients noticed efficacy within 60 min. Half experienced at least one adverse event, always mild. The most frequent were local: bad taste (n=23) or nasal irritation/itching (n=8). CONCLUSIONS: The new intranasal formulation of 5 mg zolmitriptan is a good option for the symptomatic treatment of migraine, which could be considered as an intermediate between oral triptans and the subcutaneous formulation of sumatriptan.

Administration, Intranasal↗