PubMed Health⌕ Search

Biomedical subjects

Julio Pascual

Publications and source records attributed to Julio Pascual.

At least 19 recordsLinked to original sources
PubMed2007

Is Chiari type I malformation a reason for chronic daily headache.

This article briefly reviews the spectrum of headaches associated with Chiari type I malformation and specifically analyzes current data on the possibility of this malformation as an etiology for some cases of chronic daily headache (CDH). Chiari type I malformation is definitely associated with cough headache and not with primary episodic headaches, with the rare exception of basilar migraine-like cases. With regard to CDH, there is no clear evidence supporting an association with this malformation. An MRI study would be justified only in patients showing either a Valsalva-aggravating component or cervicogenic features. Hydrocephalus and low intracranial pressure syndrome should be ruled out in patients showing tonsillar herniation in an MRI study and consulting due to daily headache.

Arnold-Chiari Malformation↗
PubMed2007

12-month safety and efficacy of everolimus with reduced exposure cyclosporine in de novo renal transplant recipients.

The proliferation signal inhibitor everolimus (Certican), has demonstrated efficacy with full-dose cyclosporine (CsA) (Neoral). Two multicenter randomized controlled studies were performed to compare 12-month efficacy and safety of everolimus 1.5 and 3.0 mg/day with reduced-dose CsA. Study 1 enrolled 237 de novo renal allograft recipients, randomizing 222 nonblack patients to either everolimus 1.5 or 3.0 mg/day, with the Neoral) dose guided by C(2) (monitoring of CsA concentration 2 h after dosing). Study 2 had a similar protocol, with basiliximab included, enrolling 256 recipients and randomizing 243 nonblack patients. In Study 1, there was a lower incidence of acute rejection in nonblack patients on 3 mg/day (16.4%) compared with 1.5 mg/day (25.9%), P = 0.08. In Study 2, the inclusion of basiliximab lowered the overall incidence of acute rejection; 14.3% of nonblack patients (3 mg/day) and 13.6% of nonblack patients (1.5 mg/day) had acute rejection by 12 months (P =0.891). Renal function was preserved throughout the study, with no differences observed between groups within studies. Everolimus was well tolerated with no significant differences between doses. Everolimus, in combination with reduced-dose Neoral), demonstrated efficacy and was well tolerated. Basiliximab allows for utilization of lower doses of everolimus with reduced dosing of Neoral).

Adult↗
PubMed2006

Three-year observational follow-up of a multicenter, randomized trial on tacrolimus-based therapy with withdrawal of steroids or mycophenolate mofetil after renal transplant.

BACKGROUND: The challenge in renal transplantation is to improve long-term patient and graft survival without increasing early acute rejection by minimizing immunosuppression. METHODS: This multicenter, observational study investigated the effects of withdrawal of steroids or mycophenolate mofetil (MMF) from a tacrolimus-based triple regimen (tac/MMF/steroids) 3 months posttransplant at 3 years; no additional interventions or assessments were undertaken. Adult patients, included in the intent-to-treat population of the THOMAS study, participated. Patient and graft survival, adverse events, rejection episodes, and immunosuppressive and concomitant medications were assessed. RESULTS: Data at Year 3 was available for 718 patients (triple therapy, n=237; steroid stop, n=235; MMF stop, n=246). The original randomized regimen was maintained in 45.6% of patients in the triple, 62.6% in the steroid stop, and 53.9% in the MMF stop groups. Graft survival rates were 88.1% (triple), 86.4% (steroid stop), and 85.8% (MMF stop); patient survival was 96.1%, 95.9%, and 95.7%, respectively. The incidence of biopsy-proven acute rejection was similar in all groups between Month 7 and Year 3: 1.2% (triple), 2.0% (steroid stop) and 2.0% (MMF stop). Patients in the steroid stop group had less hypertension and significantly lower mean total cholesterol and LDL-cholesterol at Year 3 compared with Month 3 (P=0.02). Median serum creatinine levels remained stable throughout the follow-up and were comparable between groups. CONCLUSION: Immunosuppression minimization initiated at Month 3 was maintained at Year 3 in over half of the patients. Steroid withdrawal was advantageous in reducing the cardiovascular risk factors hyperlipidemia, hypertension and diabetes mellitus. Renal function was stable in all groups.

Cardiovascular Diseases↗
PubMed2006

Lumbar bone mineral density in renal transplant patients on neoral and tacrolimus: a four-year prospective study.

BACKGROUND: This prospective study was designed to investigate the long-term evolution of bone mineral density (BMD) in kidney transplant recipients. METHODS: In 86 patients with functioning grafts, 65 on tacrolimus-based immunosuppression and 21 on cyclosporine-based immunosuppression, laboratory parameters and BMD measurements in lumbar spine (L2-L4) and femoral neck (FN) were performed by DEXA in the first month after transplantation (baseline) and yearly thereafter up to the fourth year. RESULTS: BMD did not change at 12 months in lumbar spine nor in the FN. Detailed analysis identified three patterns of BMD in lumbar spine at 12 months: BMD remained stable in 27 patients (31.4%), decreased >2% in 31 (36.0%) and increased >2% in 28 (32.6%). Patients with no change or gain presented a parallel increase of BMD in FN (P<0.001 in both groups). On multivariate analysis, the variables associated with no change or lumbar BMD loss were total prednisone dose in grams at 12 months (OR 1.402; 95% CI 1.038-1.893; P=0.028), calcitriol levels at 12 months (OR 0.936; 95% CI 0.892-0.982; P=0.007) and lumbar BMD at baseline (OR 1.006; 95% CI 1.002-1.010; P=0.002). Late treatment with calcium supplements and calcitriol did not improve osteopenia. CONCLUSIONS: One third of patients had bone loss mainly during the first year of follow-up. Bone loss was associated to higher baseline BMD, high steroid dose, and lower calcitriol levels at 1 year. Late administration of calcitriol and calcium supplements did not improve posttransplant osteopenia. More than 50% of patients were osteopenic 4 years after transplantation.

Adult↗
PubMed2006

Permanent dysphasia after status epilepticus: long-term follow-up in an elderly patient.

We report the long-term follow-up of an elderly patient who developed a permanent sensorimotor dysphasia after status epilepticus. Magnetic resonance imaging of the brain and magnetic resonance angiography failed to demonstrate structural cerebral damage; however, a fluorodeoxyglucose positron emission tomography scan revealed marked hypometabolism involving a large area in the left hemisphere and contralateral cerebellar cortex. Our case illustrates that permanent language dysfunction may occur after recurrent complex partial and secondarily generalized seizures.

Aged↗
PubMed2006

Value of postmarketing surveillance studies in achieving a complete picture of antimigraine agents: using almotriptan as an example.

Randomised controlled trials cannot collect all the data relevant for use in everyday clinical practice because drug exposure is limited, endpoints are restricted and some patient populations are excluded. Postmarketing surveillance (PS) studies can add important information for real-world clinical practice. Acute migraine therapy with almotriptan 12.5 mg was evaluated in 4 PS studies, 2 conducted in Spain, 1 in Germany and 1 in France. Almotriptan was associated with a high rate of treatment response and was well tolerated in all 4 studies. In the Spanish and German studies, 2-hour pain-relief, 2-hour pain-free, and sustained painfree rates were enhanced when patients treated mild pain. Patient satisfaction with almotriptan, assessed in the German and French studies, was high and the majority of patients preferred almotriptan to their previous acute migraine therapy. In conclusion, PS studies augment our knowledge of antimigraine therapy, giving a more complete picture of how such agents work in the general population.

Humans↗
PubMed2006

Association of migraine and ESR1 G325C polymorphism.

Migraine is a genetically complex disorder in which sexual hormones influence the phenotype. ESR1 G594A polymorphism has been associated with migraine in Australians. We performed a case-control study with G594A and G325C polymorphisms to determine whether ESR1 is associated with migraine in our population. An association between G594A and migraine could not be demonstrated here. By contrast, we observed that the C325 allele conferred a 1.6 (95% confidence interval=1.1-2.4) higher risk for suffering from migraine in women than the G allele. Women carrying the C352C genotype were over 3 times more likely to suffer from migraine than those carrying the G325G genotype. Therefore, we conclude that ESR1 G325C polymorphism is associated with migraine in our population.

Adult↗
PubMed2006

Conversion to everolimus in a patient with arterial hypertension and recurrent cutaneous neoplasia--a case report.

Calcineurin inhibitors (CNIs) are frequently associated with side effects such as nephrotoxicity and hypertension, so CNI withdrawal from immunosuppressive regimens is desirable in certain cases. The proliferation signal inhibitors/mammalian target of rapamycin inhibitors everolimus and sirolimus may play an important role in achieving CNI withdrawal. Studies on sirolimus have shown that conversion from CNIs is associated with improvements in renal function and hypertension. A case report is presented of a renal transplant recipient who experienced hypertension and recurrent cutaneous neoplasia while receiving a ciclosporin (CsA)-based immunosuppressive regimen. After transplantation, the patient received full-dose CsA and prednisolone. After 7 years, the patient's serum creatinine increased from 1.9 mg/dl to 2.5 mg/dl, and mycophenolate mofetil (MMF, 1000 mg/day) was introduced, enabling the CsA dose to be reduced to 100 mg b.i.d. The patient also required resection of five cutaneous neoplastic lesions; this led to the decision to stop CsA and start treatment with everolimus 1.5 mg/day, which was increased to 3.0 mg/day to achieve target trough blood levels of 3 ng/ml. To avoid over-immunosuppression, the MMF dose was reduced to 500 mg/day. After conversion, the patient experienced a substantial improvement in blood pressure, from 175/85 mmHg to 155/70 mmHg. Serum creatinine levels decreased to 1.6 mg/dl, and there has been no recurrence of cutaneous neoplasia in 9 months of follow-up. Therefore, conversion to everolimus from CsA in a renal transplant recipient led to improvements in blood pressure and resolution of recurrent cutaneous neoplasia, with no evidence of rejection or changes in renal function.

Blood Pressure↗
PubMed2006

Everolimus in clinical practice--renal transplantation.

Everolimus is a proliferation signal inhibitor (PSI)/mammalian target of rapamycin inhibitor that is structurally similar to sirolimus, but with a number of important pharmacokinetic differences, including a shorter half-life and time to steady state. In clinical trials, the efficacy of everolimus 1.5 mg/day and 3.0 mg/day combined with ciclosporin (CsA) and steroids in de novo renal transplant recipients is similar to that of mycophenolate mofetil, with one study showing a significantly lower risk of antibody-treated acute rejection with everolimus. When combined with reduced-dose CsA, everolimus is associated with improved renal function compared with full-dose CsA, with no decrease in efficacy. Thus, everolimus may play an important role in calcineurin inhibitor (CNI)-sparing regimens for renal transplant recipients. Studies with sirolimus have shown that CNI withdrawal is associated with a significant improvement in renal function, although there may be an increase in the risk of acute rejection. however, patient and graft survival are not adversely affected by CNI withdrawal. Notably, proteinuria <800 mg/day before conversion is a strong predictor of successful response to sirolimus treatment, and hypertensive therapy and serum lactate dehydrogenase levels may also predict response. Adverse events commonly associated with the PSIs include dyslipidaemia, proteinuria and anaemia, although these can usually be managed without difficulty. Data are also available to suggest that the PSIs are associated with a lower risk of malignancy than other immunosuppressive agents. In conclusion, everolimus may permit reduced exposure to CNIs in renal transplant recipients, with the potential to improve tolerability and renal function.

Acute Disease↗
PubMed2006

Efficacy of therapeutic intervention in headache units in patients with frequent headaches: the EFUNCE study.

Data confirming that therapeutic intervention in headache units is superior to care received by patients in other levels of the health system are scant. This is a pilot study that includes patients seen in 4 headache units for at least 1 year, who had a headache frequency of more than 15 days per month. The results of the first 30 patients showed a significant improvement in different headache parameters and a high degree of satisfaction with the treatment received.

Adult↗
PubMed2006

Ischemic heart disease after renal transplantation in patients on cyclosporine in Spain.

Ischemic heart disease (IHD), more common among transplant recipients than in the general population, accounts for approximately 50% of cardiovascular deaths. Despite its importance, only a few publications have addressed the prevalence of and risk factors for this complication. This was a retrospective cohort study in 2382 cadaver renal transplant recipients who were treated with cyclosporine as initial immunosuppression. Two groups were formed. The first group consisted of 163 patients with IHD, and the second group consisted of 326 patients without IHD. The prevalence of IHD was 6.8%, and the incidence was 15.7/1000 patient-years. Cardiac events presented during the first year in 62 (38%) patients. Multivariate analysis showed that the risk factors for IHD were age at transplant in years (relative risk [RR] 1.054; 95% confidence interval [CI] 1.033 to 1.075; P = 0.000), male gender (RR 1.940; 95% CI 1.221 to 3.081; P = 0.005), body weight at transplant in kg (RR 1.020; 95% CI 1.007 to 1.033; P = 0.002), pretransplantation cardiovascular disease (RR 2.150; 95% CI 1.733 to 3.359; P = 0.001), and a history of pretransplantation hypercholesterolemia (RR 2.032; 95% CI 1.378 to 2.998; P = 0.000). When only ischemic events that occurred 12 mo after transplantation were taken into consideration, the risk factors were age, male gender, body weight, smoking, and pretransplantation and posttransplantation hypercholesterolemia, whereas pretransplantation cardiovascular disease disappeared from the model. IHD affected nearly 7% of transplant recipients. Smoking, hypertension, and hypercholesterolemia constituted the treatable risk factors for IHD in this population. Emphasis should be placed on the need to stop smoking and to control hypertension and pre- and posttransplantation levels of serum cholesterol.

Adult↗
PubMed2005

LRRK2 G2019S is a common mutation in Spanish patients with late-onset Parkinson's disease.

Mutations in the leucine-rich repat kinase 2 (LRRK2) gene have been shown to cause both autosomal dominant and sporadic Parkinson's disease (PD). The common G2019S mutation shows wide geographical distribution while R1441G has been only reported in Northern Spain. The overall frequency of these mutations remains to be established. To determine the prevalence of G2019S and R1441G mutations in our population of Cantabria (Northern Spain), we recruited 105 consecutive PD patients and 310 controls and conducted genetic analysis of these mutations. G2019S was detected in eight late-onset patients (7.6%). Five of them had no relevant family history. R1441G was not detected in any of our study subjects. The prevalence of G2019S mutation in unselected late-onset PD patients might be higher than previously reported: 3/16 (18.7%) of familial PD and 5/82 (6.1%) of sporadic PD.

Age of Onset↗
PubMed2005

Thymidylate synthase promoter tandem repeat and MTHFD1 R653Q polymorphisms modulate the risk for migraine conferred by the MTHFR T677 allele.

There is growing evidence that folate metabolism is involved in migraine pathophysiology, mainly in migraine with aura. Even though folate metabolism is regulated by a number of enzymes, only two functional polymorphisms have been tested in association studies with migraine. Here, we have explored the possible role in migraine of other folate-metabolizing enzymes which are in close interdependency with 5',10'-methylenetetrahydrofolate reductase analyzing functional polymorphisms of these enzymes in a case-control study. Individually, thymidylate synthase (TS), methenyltetrahydrofolate cyclohydrolase formyltetrahydrofolate synthase (MTHFD1), or methionine synthase (MS) polymorphisms did not modify the general risk for suffering migraine. Nevertheless, we observed a strong interaction between TS and MTHFR mutated genotypes, which increased over 8-fold the risk for experiencing aura among migraineurs; MTHFD1 and MTHFR mutated genotypes also increased together the risk for migraine in general (OR = 3.08; 95% CI = 1.3-7.4). We conclude that the pathogenetic role of the MTHFR T677 allele in migraine is modulated by functional polymorphisms of TS and MTHFD1.

Adult↗
PubMed2005

Clinical experience with everolimus (Certican) in elderly recipients: the "old-for-old" concept.

BACKGROUND: With an increasing number of elderly patients now waiting for a kidney transplant, and the percentage of kidney donors over 55 years also rising, harvesting older kidneys specifically for use in older recipients is a way of extending the donor pool for renal transplantation. METHODS: Two case studies from an everolimus (Certican) Phase III trial (A2306) are presented. They illustrate clinical experience of achieving stable graft function in the "old-for-old" kidney transplant program at the Ramon y Cajal Hospital in Madrid, Spain. RESULTS: The first case study demonstrates that stable graft function can be achieved in an "old-for-old" kidney transplant patient, who receives everolimus in combination with reduced-exposure cyclosporine (CsA). To optimize graft function in the long-term, CsA C(2) blood levels should be <400 ng/ml. The second case study highlights how "old-for-old" renal transplant recipients can be at risk of calcineurin-inhibitor (CNI)-induced nephrotoxicity. Here, graft function did not improve following CsA dose reduction; thus, CsA was withdrawn 1 year posttransplant. Stable graft function that is acceptable for an "old-for-old" kidney transplant was then achieved with everolimus trough blood levels of 10-15 ng/ml and low-dose prednisone. CONCLUSIONS: In these cases, everolimus was used safely and effectively in the "old-for-old" kidney transplant setting. Its combination with reduced-exposure CsA, or its facilitation of CsA withdrawal, minimized the risk of nephrotoxicity in the older renal graft. These findings need to be confirmed in larger studies specific to this population.

Age Factors↗
PubMed2005

Clinical experience with everolimus (Certican): optimizing dose and tolerability.

BACKGROUND: Everolimus (Certican), a novel proliferation signal inhibitor, allows calcineurin inhibitor dose reduction in transplant patients, minimizing risk of nephrotoxicity without loss of immunosuppressive efficacy. As a result of its mode of action, this class of agent (i.e., everolimus and sirolimus) is associated with certain adverse events (e.g., lymphocele, arthralgia, edema and hyperlipidemia). METHODS: Three case studies from within an everolimus Phase III trial (A2306) are presented with the aim of illustrating how treatment-related adverse events can be managed. RESULTS: The combination of everolimus with reduced-exposure cyclosporine was efficacious in these patients. One experienced mild acute rejection that was managed with steroid boluses. All have acceptable graft function during follow-up to date. Moderate lymphocele either resolved spontaneously or was easily managed by povidine-iodine instillations. One patient developed serious early lymphocele that, unusually, required surgical intervention. Everolimus dose reduction or withdrawal was not necessary to effectively manage lymphocele of any severity. A case of bilateral multiple arthralgia was effectively managed with everolimus dose reduction, but still maintained everolimus trough blood levels at approximately 3 ng/ml. Eyelid and ankle edemas were also easily managed with low dose furosemide, preferably coupled with cyclosporine and everolimus dose reduction. Hyperlipidemia responded to statin therapy. CONCLUSIONS: Everolimus-related adverse events can be effectively managed either with other treatments or, where necessary, by everolimus dose reduction, without loss of efficacy. Discontinuing everolimus therapy is generally not necessary.

Adult↗
PubMed2005

Concentration-controlled everolimus (Certican): combination with reduced dose calcineurin inhibitors.

The calcineurin inhibitors (CNIs) have been the cornerstone of immunosuppressive therapy in recent years, though their association with dose-related nephrotoxicity is a major factor in the development of chronic allograft nephropathy in kidney transplant recipients. The novel proliferation signal inhibitor everolimus (Certican) has a mode of action distinct and complementary to the CNIs, which is thought to underlie the demonstrated synergy between everolimus and cyclosporine (CsA) in preclinical models. This finding suggests that everolimus may allow for CNI dose reduction, enabling nephrotoxicity to be minimized without compromising efficacy. Two prospective, multicenter, randomized studies have investigated the efficacy and safety of everolimus (1.5 or 3.0 mg/day) combined with reduced-exposure CsA (Neoral) in de novo renal transplant patients. In these studies, the everolimus trough level was maintained at > or =3 ng/ml with therapeutic drug monitoring and the CsA dose optimized with C(2) monitoring. The incidence of efficacy failure with this regimen was shown to be comparable with that provided by regimens employing full-dose CNIs, but with good renal function. Furthermore, everolimus (trough levels 3-8 ng/ml) plus reduced-exposure CsA was associated with a marked reduction in acute rejection compared with regimens using fixed-dose everolimus or mycophenolate mofetil plus full-dose CsA. At 12 months follow-up, CsA trough level was 57% lower in these trials than in previous trials in which patients received full-dose CsA. This suggests that concentration-controlled everolimus can be successfully combined with optimized administration of CsA and that this regimen may maximize immunosuppression, whilst preserving renal function.

Calcineurin Inhibitors↗
PubMed2005

Efficacy and tolerability of almotriptan in postmarketing surveillance studies.

While randomized, double-blind, placebo-controlled trials are considered the gold standard of clinical evidence, they are limited by patient numbers, duration of patient exposure, and restricted patient populations. Data from controlled trials may not be generalizable to all individuals likely to take the drug under investigation. Postmarketing surveillance studies are designed to measure efficacy and safety in larger and more diverse populations, allowing them to detect less common and delayed adverse events. However, postmarketing surveillance studies are limited by their lack of randomization, open-label design that can result in patient and physician bias, incomplete follow-up, less than rigorous outcome measurement, and lack of a contemporaneous control group. With regard to acute treatment of migraine, clinical trials using per protocol primary endpoints do not reflect the more favorable experience with triptans in general practice. Postmarketing surveillance studies have been performed to determine whether the high levels of efficacy and tolerability of almotriptan reported in controlled clinical trials can been reproduced in routine practice. An observational study conducted in Spain with 2,074 migraine sufferers (4,183 attacks) reported a 2-hour pain-relief rate of 86.9%, a 2-hour pain-free rate of 51.5%, and a sustained pain-free rate of 46.0%; 1.1% of patients reported adverse reactions. A German postmarketing study in 899 patients (2,131 attacks) with acute migraine treated with almotriptan 12.5 mg reported 2-hour pain relief in 84.5% of attacks and 2-hour pain free in 41.4%; 1.1% of patients reported adverse reactions. The consistency of response (at least two out of three attacks successfully treated) with almotriptan 12.5 mg was 87.3%. Regarding satisfaction, 88.5% of patients were satisfied or very satisfied and 80.3% of patients stated that almotriptan was better compared to their prior therapy; 92% of physicians indicated that they would continue treating their patients' migraines with almotriptan. The results of these studies demonstrate that the high levels of efficacy and tolerability seen with almotriptan in controlled clinical trials are achieved in real-world clinical settings. In conclusion, a combination of controlled clinical trials, postmarketing surveillance studies, and physician's experience in the general population can give us a better understanding of the efficacy and tolerability of acute migraine agents.

Germany↗