Pericranial nerve blockade as a preventive treatment for migraine: Experience in 60 patients. / Bloqueo anestésico de nervios pericraneales como tratamiento preventivo de migraña: experiencia en una serie de 60 pacientes.

INTRODUCTION: Anaesthetic blockade of pericranial nerves is frequently used to treat headache disorders. There is no evidence on indication of this treatment for migraine. We aim to evaluate its effectiveness as a preventive treatment for migraine using specific indication criteria. METHODS: Between January 2009 and May 2013 we offered pericranial nerve blockade to migraine patients with a history of preventive drug intolerance or failure. We selected patients with tenderness to palpation of at least one greater occipital nerve (GON) or supraorbital nerve (SON). Responses at 3 months were categorised as complete response (no pain), partial response (reduction of at least 50% in severity or frequency of headache episodes), or no response. RESULTS: Anaesthetic blockade was performed in 60 patients (52 females, 8 males; mean age 40.6 ± 12.4 years, range 19-76). The most common procedure was blockade of GON and SON on both sides. Complete response lasting at least 2 weeks was recorded in 23 patients (38.3%), with partial response in 24 patients (40%), and no response in 13 (21.7%). In the group presenting complete response, age and length of history of migraine were significantly lower. No severe side effects were detected. Response time ranged from 2 weeks to 3 months. CONCLUSIONS: Pericranial nerves blockade using tenderness to palpation as an inclusion criterion is safe and potentially effective as prophylactic treatment for migraine. The best responses in our series were observed in younger patients with shorter histories of migraine.

Headache in young patients: Clinical characteristics of a series of 651 cases. / Cefalea en jóvenes: características clínicas en una serie de 651 casos.

INTRODUCTION: Headache has a negative impact on health-related quality of life in young patients. We aim to analyse the characteristics of a series of young patients visiting a headache clinic and estimate the burden of different types of headaches listed by the International Classification of Headache Disorders (ICHD). METHODS: We prospectively recruited patients aged 14 to 25 years who were treated at our clinic during a period of 6.5 years. We recorded each patient's sex, complementary test results, and previous treatment. We subsequently compared the characteristics of our sample to those of patients older than 25. RESULTS: During the study period, we treated 651 patients aged 14 to 25 years; 95.6% had received symptomatic treatment, and 30.1% had received preventive treatment. A total of 755 headaches were recorded. Only 80 were secondary headaches, most of which were included in Group 8; 77.2% were included in Group 1, 3.1% in Group 2, 1.2% in Group 3, 5% in Group 4, 0.6% in Group 13, and 0.9% in Group 14. According to Headache Impact Test (HIT-6) scores, headache had at least a moderate impact on the quality of life of 449 patients. CONCLUSION: Most headaches in young patients can be classified according to ICHD criteria. Migraine was the most frequent diagnosis in our sample. Although headache was commonly associated with a negative impact on quality of life, most patients had received little preventive treatment before being referred to our clinic.

Association of ANRIL gene polymorphisms with major adverse cardiovascular events in hemodialysis patients.

BACKGROUND: Cardiovascular disease is the leading cause of death in patients with chronic kidney disease (CKD). Single nucleotide polymorphisms (SNPs) in ANRIL gene have been associated with higher cardiovascular morbidity and mortality in general population. The main objective was to ascertain whether ANRIL polymorphisms could identify risk of major adverse cardiovascular event (MACE) in patients starting on hemodialysis (HD). METHODS: This was a prospective observational cohort study. 284 CKD patients starting on HD were included in the study and followed until achievement of the primary end-point (MACE) or end of the study. All patients were genotyped for four ANRIL SNPs (rs10757278, rs4977574, rs10757274 and rs6475606). Kaplan-Meier curves and multivariate Cox survival analyses, together with multiple logistic regression were used to analyze the association between ANRIL SNPs and MACE. RESULTS: We found that ANRIL SNP rs10757278 was a representative SNP of a strong linkage disequilibrium block and showed significant genotypic associations with MACE in hemodialysis patients. Homozygous patients for the risk allele (GG) showed 2.17 (1.05-4.49) fold increased risk of MACE during hemodialysis than carriers of the protective allele (AA or AG). Diabetes mellitus was a strong enhancer of this effect. CONCLUSIONS: Our results indicate that ANRIL polymorphisms may confer risk to development of MACE in incident patients on hemodialysis.

Data on genotypic distribution and linkage disequilibrium of several ANRIL polymorphisms in hemodialysis patients.

A long non-coding RNA called ANRIL located on chromosome 9p21.3 has been identified as a novel genetic factor associated with cardiovascular disease. Investigation of several single nucleotide polymorphisms (SNPs) of Noncoding Antisense RNA in the INK4 Locus (ANRIL) gene are of particular interest. This article reports data related to the research article entitled: "Association of ANRIL gene polymorphisms with major adverse cardiovascular events in hemodialysis patients" (Arbiol-Roca et al. [1]). Data presented show the genotypic distribution of four selected ANRIL SNPs: rs10757278, rs4977574, rs10757274 and rs6475606 in a cohort constituted by 284 hemodialysis patients. This article analyzes the Hardy-Weinberg disequilibrium of each studied SNP, and the linkage disequilibrium between them.

Low-dose cyclosporine and mycophenolate mofetil in renal allograft recipients with suboptimal renal function.

BACKGROUND: Cyclosporine (CsA) nephrotoxicity can be identified by functional changes and chronic renal damage. CsA-associated renal fibrosis has been related to the overproduction of transforming growth factor (TGF)-beta1, a fibrogenic cytokine. Mycophenolate mofetil (MMF) may allow CsA dose reduction without increasing the risk of rejection. METHODS: We studied the impact of CsA dose reduction in association with MMF on renal function and TGF-beta1, production in 16 long-term renal allograft recipients with suspected CsA nephrotoxicity. Two grams/day of MMF were introduced, and CsA dose was reduced to reach whole-blood levels between 40 and 60 ng/ml within 1 month. CsA dose and levels, renal function parameters, and platelet-poor plasma TGF-beta1 levels were evaluated before and 6 months thereafter. RESULTS: MMF allowed a decrease in both the mean dose of CsA (3.8+/-1.35 vs. 2.2+/-0.73 mg/kg/day; P<0.01) and CsA levels (148+/-36 vs. 53+/-19 ng/ml; P<0.001). The reduction of CsA was associated with a decrement of serum creatinine levels (210+/-46 vs. 172+/-41 micromol/L; P<0.001) and an increase in both the glomerular filtration rate (32.9+/-12 vs. 39.1+/-14 ml/min/1.73 m2; P<0.02) and renal plasma flow (195+/-79 to 218.6+/-74.02 ml/min/1.73 m2; P<0.02). There was a reduction in plasma TGF-beta1 levels (4.6+/-4.2 vs. 2.0+/-1.4 ng/ml; P=0.003) and CsA levels correlated with TGF-beta1 (r=0.536, P=0.002). No rejection episodes occurred, and an improvement in both systolic (149+/-13 vs. 137+/-12 mmHg; P<0.01) and diastolic blood pressure (89+/-14 vs. 83+/-10 mmHg; P<0.04) were observed. CONCLUSIONS: These short-term results show that MMF introduction allows a CsA dose reduction, which improves renal function, reduces TGF-beta1 production, and improves the control of hypertension, without increasing the incidence of acute rejection.

Recipient body surface area as a predictor of posttransplant renal allograft evolution.

BACKGROUND: The aim of the present study was to analyze whether minor differences in recipient body surface area have any predictive value on renal allograft evolution. METHODS: For this study, we considered 236 pairs of recipients who received a kidney from the same donor at our center between March 1985 and December 1995. Pairs in whom at least one patient presented any of the following events were excluded: graft loss during the first year of follow-up, diabetes mellitus, noncompliance with treatment, chronic pyelonephritis, and recurrent or de novo glomerulonephritis. Recipients of each pair were classified as large or small according to their body surface area (BSA). The percentage difference of BSA in each pair was calculated, and two cohorts of pairs were defined: BSA difference < or = 10% (n=76 pairs) and BSA difference >10% (n=70 pairs). RESULTS: The large recipients of the cohort with a BSA difference >10% showed a higher incidence of posttransplant delayed graft function (22/70 vs. 12/70, P=0.075), hypertension at 1 year of follow-up (51/70 vs. 35/70, P=0.006), and a higher serum creatinine level at 1-year follow-up (173 vs. 142 micromol/L, P=0.003), whereas in the cohort with a BSA difference < or = 10%, posttransplant evolution in large and small recipients was not different. Multivariate analysis showed that recipient BSA was an independent predictor of delayed graft function, posttransplant hypertension, and serum creatinine at 1-year follow-up. CONCLUSIONS: Relatively small differences in recipient BSA influence renal allograft evolution. Consequently, our data support that recipient size should be taken into consideration for renal allograft allocation.

Protocol renal allograft biopsies and the design of clinical trials aimed to prevent or treat chronic allograft nephropathy.

BACKGROUND: The minimum sample size to perform a clinical trial aimed to modify the natural history of chronic allograft nephropathy (CAN) is very large. Since the presence of chronic tubulointerstitial damage in renal protocol biopsy specimens is an independent predictor of late outcome, we evaluated whether protocol biopsies could facilitate the design of trials aimed to prevent or treat CAN. METHODS: Two hundred eighty-two protocol biopsy specimens were obtained 3 months after transplantation in 280 patients with serum creatinine levels <300 micromol/L, proteinuria <1000 mg/day, and stable function. The specimens were evaluated according to the Banff criteria. RESULTS: Graft survival depended on the presence of CAN and renal transplant vasculopathy (RTV). Thus, biopsy specimens were classified as: (a) no CAN (n=174); (b) CAN without RTV (n=87); and (c) CAN with RTV (n=21). Graft survival at 10 years was 95%, 82%, and 41%, respectively (P=0.001). Total serum cholesterol before transplantation was 4.5+/-1.1, 4.6+/-1.1, and 5.3+/-1.6 mmol/L, respectively (P=0.009) and it was the only predictor of RTV. Power analysis (beta=20%, alpha=5%) was done to evaluate whether protocol biopsies can facilitate the design of clinical trials aimed either to prevent or treat CAN. We showed that the most feasible approach would be to use the presence of CAN as the primary efficacy end point in a prevention trial. To demonstrate a 50% reduction in the incidence of CAN at 3 months, 570 patients would be required. CONCLUSIONS: Protocol biopsies may allow a reduction of sample size and especially the time of follow-up in a trial aimed to prevent CAN.

Treatment of hypertension after renal transplantation: long-term efficacy of verapamil, enalapril, and doxazosin.

Normal blood pressure is a good marker of graft survival after renal transplantation, and effective antihypertensive treatment reduces the progression of graft damage. We conducted a long-term follow-up study of 88 hypertensive renal transplant recipients, all of whom were taking sustained cyclosporine A (CsA) immunosuppression. The patients were treated for at least three years, and initially received 240 mg/day of verapamil (N = 24, group I), 5 mg/day of enalapril (N = 24, group II) or 1 mg/day of doxazosin (N = 40, group III). Baseline creatinine did not differ in the three groups, but proteinuria was higher in the enalapril group (7 patients had proteinuria > 1.5 g/day). Treatment was withdrawn in 5 patients in the verapamil group, 5 in the enalapril group and 2 in the doxazosin group due to drug-related side effects. Blood pressure (BP) control at three years was equivalent in the three groups (systolic BP, group I 157 +/- 12; group II 149 +/- 19; group III 154 +/- 21; diastolic BP, group I 90 +/- 8.7, group II 84 +/- 9.8, group III 90.5 +/- 16; mean BP, group I 113 +/- 7, group II 106 +/- 10, group III 106 +/- 29). Two patients in group I, 3 in group II and 15 in group III required additional antihypertensive drugs. CsA levels increased in the verapamil-treated patients, allowing for an early decrease in CsA doses (1 year doses, 3.3 +/- 1 mg/kg body wt/day in group I, 4.3 +/- 1.6 in group II, 3.7 +/- 1.6 in group III). Six cardiovascular events occurred, 3 in group I, 1 in group II, and 2 in group III patients. One patient died in the enalapril group and another in the doxazosin group. Eight verapamil-treated patients, 8 enalapril-treated patients and 4 doxazosin-treated patients lost their grafts due to biopsy-proven chronic transplant nephropathy. In conclusion, the three antihypertensive agents are effective in reducing blood pressure, with no clear advantage of one above any other. Verapamil allows the CsA dose to be reduced, thus decreasing the cost of immunosupression. Enalapril can be a more effective antiproteinuric agent, but hyperkalemia or impaired allograft function may occur in patients with non-optimal allograft function. Doxazosin offers an excellent safety and efficacy profile, and when not efficient by itself in controlling blood pressure, is an ideal concomitant agent in hypertensive renal transplant patients.

Histologic findings in protocol biopsies performed in stable renal allografts under different immunosuppressive schedules.

Protocol biopsies performed in stable renal allografts show different degrees of acute and chronic lesions. Histologic findings in protocol biopsies have been related to graft outcome. We evaluated histologic lesions observed in protocol biopsies performed in patients under different immunosuppression therapies. From June 1988 a protocol biopsy was performed at approximately 4 months in patients who fulfilled the following criteria: serum creatinine <300 micromol/L; stable renal function; and proteinuria <1 g/d. Histologic lesions were graded according to 1997 Banff criteria. For the present study we considered the following groups according to immunosuppressive schedule: (i) induction therapy with polyclonal or monoclonal antilymphocytic antibodies associated with cyclosporine and prednisone (n=201); (ii) cyclosporine, mycophenolate mofetil, and prednisone (n=127); and (iii) tacrolimus, mycophenolate mofetil, and prednisone (n=51). On protocol biopsy patients treated with tacrolimus displayed a lower acute score (0.61+/-1.01 vs 1.24+/-1.23 in group I, 1.28+/-1.41 in group II; P<.0001) and a higher proportion of normal biopsies (57.1% vs 41.9% in group I, 45.1% in group II; P=.016). A similar proportion of chronic lesions (chronic score of group I: 1.30+/-1.56; group II: 1.34+/-1.80; group III: 1.51+/-0.95; P=NS) was observed in the three groups. Protocol biopsies displayed fewer acute lesions in patients treated with tacrolimus. This result suggests that the efficacy of new immunosuppression schedules can be evaluated using the protocol biopsy as a surrogate marker of graft outcome.

[Influence of glycemic blood glucose control and incipient diabetic nephropathy on the urinary excretion of N-acetyl-glucosaminidase (NAG) in diabetes mellitus]. / Influencia del control glucémico y la nefropatía diabética incipiente sobre la excreción urinaria de N-acetil-glucosaminidasa (NAG) en la diabetes mellitus.

Plasma glucose, glycated hemoglobin lc (HbAlc), urinary albumin excretion rate (AER) and urinary N-acetyl-glucosaminidase (NAG): creatinine ratio were studied in 100 normotensive diabetic patients with no evidence of overt renal disease and in 45 controls, to find out whether the glycaemic control and incipient nephropathy may influence the urinary excretion of NAG. Twenty-three of the diabetics had microalbuminuria (group II). Group I comprised the 77 diabetics without microalbuminuria. The groups I and II of diabetics were divided into two according to plasma glucose were greater o smaller to 140 mg/dl. The group I of diabetics had greater NAG: creatinine ratio than controls, too (0.41 +/- 0.24 and 0.16 +/- 0.08 mu/mmol creatinine, p < 0.0005); in this group urinary NAG was found to positively correlate with plasma glucose and creatinine (p < 0.0005, r = 0.45). Multiple regression analysis was performed in the whole of diabetics and significant association were identified between urinary NAG excretion and plasma glucose, AER and plasma creatinine (p < 0.0005, r = 0.42). The diabetics with plasma glucose lower to 140 mg/dl had more important correlation NAG: creatinine ratio-AER (p < 0.0001, r = 0.70). It is concluded that measurement of urinary NAG may be of value in the detection of diabetic nephropathy at a potentially reversible stage if the plasma glucose is take into account.