Fine-needle aspiration of peritumoral lymph nodes in esophageal cancer with endobronchial ultrasound.
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Biomedical subjects
Publications and source records attributed to J M Pascual.
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OBJECTIVE: To evaluate the efficacy of dichloroacetate (DCA) in the treatment of mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes (MELAS). BACKGROUND: High levels of ventricular lactate, the brain spectroscopic signature of MELAS, correlate with more severe neurologic impairment. The authors hypothesized that chronic cerebral lactic acidosis exacerbates neuronal injury in MELAS and therefore, investigated DCA, a potent lactate-lowering agent, as potential treatment for MELAS. METHODS: The authors conducted a double-blind, placebo-controlled, randomized, 3-year cross-over trial of DCA (25 mg/kg/day) in 30 patients (aged 10 to 60 years) with MELAS and the A3243G mutation. Primary outcome measure was a Global Assessment of Treatment Efficacy (GATE) score based on a health-related event inventory, and on neurologic, neuropsychological, and daily living functioning. Biologic outcome measures included venous, CSF, and 1H MRSI-estimated brain lactate. Blood tests and nerve conduction studies were performed to monitor safety. RESULTS: During the initial 24-month treatment period, 15 of 15 patients randomized to DCA were taken off study medication, compared to 4 of 15 patients randomized to placebo. Study medication was discontinued in 17 of 19 patients because of onset or worsening of peripheral neuropathy. The clinical trial was terminated early because of peripheral nerve toxicity. The mean GATE score was not significantly different between treatment arms. CONCLUSION: DCA at 25 mg/kg/day is associated with peripheral nerve toxicity resulting in a high rate of medication discontinuation and early study termination. Under these experimental conditions, the authors were unable to detect any beneficial effect. The findings show that DCA-associated neuropathy overshadows the assessment of any potential benefit in MELAS.
OBJECTIVE: C-reactive protein (CRP) is considered a marker of subclinical atherosclerosis. The aim of the study was to assess whether the metabolic syndrome (MS) and parameters involved in its diagnosis might influence serum CRP values. PATIENTS AND METHOD: Cross-sectional study in outpatients of a HTA and Vascular Risk clinic. MS was diagnosed according to National Cholesterol Educational Program ATP-III guidelines, and hs-CRP was analyzed by nephelometry. RESULTS: A total of 1,969 patients (47% male) were evaluated and distributed into four groups: 1) 1,220 non-diabetics without MS; 2) 384 non-diabetics with MS; 3) 153 diabetics without MS, and 4) 212 diabetics with MS. Patients with MS had higher CRP in both non-diabetic 3.0 (1.7-4.4) mg/l vs. 1.7 (0.9-3.4) mg/l; p=0.001 (MW), and diabetic patients: 2.8 (1.5-4.6) mg/l vs. 2.2 (0.9-4.3) mg/l; p=0.01 (MW). Diabetic patients without MS had CRP values not different to non-diabetic without MS. CRP values increased in relation to the number of parameters included in the MS from 1.7 (2.2) mg/l, in patients without any parameters, to 4.2 (2.8) mg/l in patients who fulfilled five parameters (p=0.001) (KW). In multiple regression analysis abdominal obesity (p=0.001), TG (p=0.001) and glucose (p=0.02) were associated with CRP levels after correcting for other factors. Abdominal obesity (OR: 1.9; 95% CI: 1.5-2.4; p=0.001) and TG (OR: 1.4; 95% CI: 1.1 -1.7; p=0.003), but not glucose were independent factors related to the presence of high levels of CRP (>3 mg/l) in a logistic regression analysis. CONCLUSIONS: Diabetic and non-diabetic patients with MS have high CRP levels. Of the five components of MS, the most closely related to CRP is abdominal obesity.
Its indications should only be considered in patients with morbid obesity (BMI>40 kg/m2) or severe obesity (BMI>35 kg/m2) with serious associated comorbidity. In general, significant weight loss with marked improvement of the cardiovascular comorbidity is obtained. There are still no studies that show long term survival. It must be stressed that the patients should follow a subsequent and continuous medical monitoring to prevent important secondary metabolic complications.
OBJECTIVE: The last modifications of the National Cholesterol Education Program (NCEP) indicate some lower therapeutic targets of low density protein cholesterol (LDL-c) in patients with very high vascular risk. Our study aims to establish the degree of compliance of the therapeutic targets defined by these modifications. PATIENTS AND METHOD: Descriptive and cross sectional study of patients from a cardiovascular clinic. Low-density lipoprotein cholesterol (LDL-c) was calculated and targets were established according the new update of NCEP-ATP III. RESULTS: 836 patients, 625 (75%) with HR and 211(25%) with VHR were studied 45% of HR and 67% of VHR were receiving treatment with statins (p < 0.001) but only 38% of HR and 15% of VHR achieved target LDL-c levels. The percentage of patients who could achieve LDL-goals using the maximum approved dose of the statins plus other lipid lowering drug was calculated: The 31% of HR and 51% of VHR were unable to achieve the LDL-c targets. CONCLUSIONS: Only 15% of very high risk patients achieve target levels of LDL-c according to the new NCEP-ATP III recommendations. Even using maximum dose of statins in combination with other lipid lowering drugs, less than half of the patients will be able to achieve LDL-c goal (< 70 mg/dl).
UNLABELLED: A glioblastoma presenting as a solitary third ventricle mass is exceptional. CASE DESCRIPTION: We report the case of a 29-year-old woman who lost consciousness, was taken to hospital and referred a previous history of depression and diabetes insipidus. Magnetic resonance imaging study revealed a heterogeneous anterior third ventricle mass with ring enhancement after contrast administration. It was approached and subtotally resected by a transcortical-transventricular route and histological diagnosis proved it to be a glioblastoma. There are only two other similar well-described cases and another nine have been previously reported in surgical series of high grade gliomas and glioblastomas. The possible origin of this lesion is discussed.
BACKGROUND: This retrospective study analyzes the clinical, neuroradiological, pathological and surgical characteristics of well-described intraventricular craniopharyngiomas with the aims of: (i) critically to review the criteria used to affirm the diagnosis of an intraventricular location (ii) defining more accurately this topographical diagnosis preoperatively, and (iii) to investigate factors influencing the surgical outcome. METHOD: Clinical, neuroradiological, pathological and surgical objective data of 104 well-described intraventricular craniopharyngiomas (IVC) reported in the literature, in addition to a new case, were analyzed. On the basis of the proofs provided for third ventricle intactness, a new topographical classification for IVC was developed, distinguishing between: (i) strict IVC, with a proved third ventricle floor integrity and (ii) non-strict IVC, without any reliable proof confirming the intactness of the third ventricle floor. Following this classification, clinical features, pathology and surgical outcome for strictly and non-strictly IVC were compared. FINDINGS: For 105 IVC compiled, 36 belonged to the strictly group and 69 to the non-strictly group. Two pathological features were associated with the non-strictly IVC group: a preferentially adamantinomatous pattern (p=0.106) and wider and tighter adherences to third ventricle margins (p=0.01). The non-strict topography was also associated with a worse postoperative outcome (p=0.046). There was a significant relationship between the surgical approach and the final outcome (p=0.05), being the translamina terminalis approach associated with the best outcome. CONCLUSIONS: Two different topographies might be considered among IVC: strict and non-strict intraventricular location. Non-strictly IVC have wider and tighter adhesions to third ventricle boundaries and this subtype is associated with a worse outcome.
BACKGROUND: The objective of this study was to analyse the relationship of polymorphisms of the angiotensinogen (AGT) gene with the changes in microalbuminuria during 3 years of antihypertensive treatment in a group of young adults with essential hypertension. METHODS: Essential hypertensives, less than 50 years old, never previously treated with antihypertensive drugs and in the absence of diabetes mellitus were included. After the initial evaluation, patients were treated using only nonpharmacological measures (n=23), only beta-blockers (n=26), only angiotensin-converting enzyme inhibitors (ACEi) (n=57) or a combination of treatments (n=25). The office blood pressure, biochemical profile and urinary albumin excretion (UAE) were measured at the beginning and then yearly. The polymorphism A-6G of the AGT gene located in the promoter region was analysed. RESULTS: In total, 131 patients, 35 (27%) microalbuminurics, were included. Although no significant differences in systolic blood pressure (SBP), diastolic blood pressure (DBP), fasting glucose and UAE were observed among genotypes at the initial examination, during the 3 years of antihypertensive treatment the slope values for the DBP, fasting glucose and UAE differed significantly despite no differences in the distribution of treatments being present. The subjects carrying the AA-6 genotype had the largest DBP decrease, but the lowest UAE reduction and the highest slope of glucose. Out of 35 initially microalbuminuric patients, 24 became normoalbuminuric and the lowest reduction rates were observed in subjects who carried the allele A-6. No interaction between the type of treatment and genotype was observed on the changes in UAE, BP or glucose values. In the subset of 57 patients treated with ACEi, the changes in UAE, BP and glucose had the same trend as was observed in the total population. CONCLUSIONS: Subjects carrying the AA genotype of the A-6G AGT gene polymorphism are resistant to a reduction of microalbuminuria. Whether this can be attributed to a predisposition to glucose metabolic disturbance or not needs to be confirmed in further studies.
Cerebral revascularization is an useful tool in the treatment of giant or complex cerebral aneurysms that can not be clipped directly by different causes. In turn, interventionist endovascular therapy, an emergent technique with very good results in the treatment of cerebral aneurysms during the last five years, is a new complementary tool to cerebral revascularization for the treatment of complex aneurysms. In the present manuscript we emphasize the beneficial effect of revascularization, followed in a short period of time by the endovascular technique in order to either occlude the parent vessel or to exclude the aneurysm from cerebral circulation. Advantages of this form of therapy, as well as the selection of patients and the present revascularization procedures, are commented.
Anterior communicating artery complex accounts for the most frequent site of cerebral aneurysms and it is characterized by its great anatomical variability. The development of aneurysms in this complex has been associated with the asymmetry of its afferent vessels. An anatomical and hemodynamic study of the anterior communicating artery was performed. Twenty brain samples obtained from adult necropsies were studied by means of microsurgical dissection. Additionally; 118 cerebral angiographies from patients with spontaneous subarachnoid hemorrhage were studied. A high number of perforanting vessels originated at the anterior communicating artery complex was a relevant finding. The number, distribution and size of these vessels is reported accurately. Analysis of the angiographies showed the association between the existence of an anterior communicating artery aneurysm and the presence of a blood flow predominance through one of the two proximal anterior cerebral arterias.
Primary central nervous system lymphomas (PCNSL) are infrequent tumors and their presentation as a solitary hypothalamic-third ventricle mass can be considered exceptional. We report the case of a 57-year-old woman with progressive visual deterioration, diabetes insipidus and mental confusion. She had a diffuse and homogeneous tumoral lesion involving the third ventricle and the adjacent hypothalamic area with marked enhancement after contrast administration on both, competed tomography scan and magnetic resonance images. It was approached and partially resected by the translamina terminalis route. Histological diagnosis proved to be a diffuse non-Hodgkin lymphoma and the patient subsequently was treated with adjuvant radiotherapy and chemotherapy. Followup examination showed visual acuity recover but persistent confessional state. Eight similar well described cases reported in the literature are reviewed with a description of the major diffenciating features of this neurological entity. Treatment of PCNSL remains a challenge, and the topographical location within the hypothalamic-third ventricle area is even more complex.
BACKGROUND: The goal of this study was to analyse the association between essential hypertension and the main genetic polymorphisms at the renin-angiotensin system in the Spanish population. PATIENTS AND METHOD: Case-control study including 185 essential hypertensive subjects(age [SD] 39.6 [7.5] years, 52% women, systolic blood pressure 151.2 [17.4] mmHg, diastolic blood pressure 96.0 [9.4] mmHg) and 350 sex- and age-matched normotensive individuals selected from a sample of the general population of the Comunidad Valenciana, Spain (age 39.4 [8.0] years, 51.7% women, systolic blood pressure 116.0 [12.0] mmHg, diastolic blood pressure 69.6 [8.5] mmHg). A PCR was performed to determine I/D angiotensin converting enzyme (ACE) gene polymorphism, A-6G and M235T angiotensinogen gene polymorphism and A1166C polymorphism of the angiotensin II type 1 receptor. RESULTS: There were no differences between cases and controls with regard to genotypic and allelic distributions. In hypertensive patients,there were no differences in genotypic or allelic distributions after considering the presence or absence of a familial history of hypertension or comparing tertiles of systolic and diastolic blood pressure values. Only in women, the combination of a C allele of A1166C polymorphism with an A-6G angiotensinogen polymorphism A allele (p = 0.007), or an M235T angiotensinogen polymorphism T allele (p = 0.007), was associated with a higher risk of hypertension. CONCLUSIONS: We found no association between essential hypertension risk and I/D ACE gene, M235T and A-6G angiotensinogen gene, or A1166C angiotensin II type 1 receptor gene polymorphisms. An epistatic effect was observed in young women between angiotensin II type 1 receptor polymorphisms and angiotensinogen polymorphisms.
The authors evaluated education attainment and neuropsychological deficits in children with sickle cell disease (SCD) and silent cerebral infarcts. Children with silent infarcts had twice the rate of school difficulties as children without infarcts. Eighty percent of silent infarct cases had clinically significant cognitive deficits, whereas 35% had deficits in academic skills. Children with silent cerebral infarcts show high rates of poor educational attainment, cognitive deficits, and frontal lobe injury. Poor school performance in SCD is one indicator of silent infarcts.
Glut-1 deficiency syndrome was first described in 1991 as a sporadic clinical condition, later shown to be the result of haploinsufficiency. We now report a family with Glut-1 deficiency syndrome affecting 5 members over 3 generations. The syndrome behaves as an autosomal dominant condition. Affected family members manifested mild to severe seizures, developmental delay, ataxia, hypoglycorrhachia, and decreased erythrocyte 3-O-methyl-D-glucose uptake. Seizure frequency and severity were aggravated by fasting, and responded to a carbohydrate load. Glut-1 immunoreactivity in erythrocyte membranes was normal. A heterozygous R126H missense mutation was identified in the 3 patients available for testing, 2 brothers (Generation 3) and their mother (Generation 2). The sister and her father were clinically and genotypically normal. In vitro mutagenesis studies in Xenopus laevis oocytes demonstrated significant decreases in the transport of 3-O-methyl-D-glucose and dehydroascorbic acid. Xenopus oocyte membranes expressed high amounts of the R126H mutant Glut-1. Kinetic analysis indicated that replacement of arginine-126 by histidine in the mutant Glut-1 resulted in a lower Vmax. These studies demonstrate the pathogenicity of the R126H missense mutation and transmission of Glut-1 deficiency syndrome as an autosomal dominant trait.
The objective of this study was to analyze the relationship of polymorphisms of the angiotensin II AT1 receptor gene with microalbuminuria in a group of young adults with essential hypertension. Essential hypertensives, less than 50 years old, never previously treated with antihypertensive drugs, and in absence of diabetes mellitus were included. Office blood pressure (BP), 24-h ambulatory BP monitoring, urinary albumin excretion (UAE) measurements, and DNA analysis were performed. Polymorphisms of the angiotensin II AT1-receptor gene (A1166C and C573T) were studied by polymerase chain reaction and single-strand conformation polymorphism techniques. One hundred eighty-three patients, 49 (27%) microalbuminurics, were included. Office and ambulatory BP values were significantly higher in the microalbuminuria group. No differences in the presence of microalbuminuria were observed among the genotypes of either A1166C or C573T polymorphisms of the angiotensin II receptor AT1 gene, or in the allele frequency of the A1166C or the C573T polymorphism. LogUAE was significantly different among genotypes of the C573T polymorphism [CC 1.30(1.15-1.45), CT 1.14(1.00-1.28), and TT 0.94(0.68-1.20), P < .05]. Both office and ambulatory blood pressure and the TT/C573T genotype were independently related to logUAE, and, at the same BP values, UAE was lower in subjects with this genotype. We have found that the C573T polymorphism is on linkage disequilibrium with A1166C, as the 573T allele is closely linked to the presence of the 1166A allele, but not vice versa. Haplotype analysis among subjects with the AA genotype for the A1166C polymorphism confirms the influence of the TT genotype of the C573T polymorphism on the UAE in hypertensives. The C573T polymorphism of the angiotensin II receptor AT1 gene seems to be a genetic protective factor for UAE in a population of essential hypertensives.
BACKGROUND: The objective of the present study was to characterize the spectrum of circadian blood pressure changes in type I diabetes at different stages of nephropathy by using two monitorings in each patient in order to avoid intra-individual variability. PATIENTS AND METHODS: A total of 80 type I diabetic subjects and the same number of age, sex and awake mean blood pressure (BP)-matched controls were included. According to urinary albumin excretion, there were 57 normoalbuminurics, 15 persistent microalbuminurics and eight proteinurics. Two 24 h ambulatory blood pressure monitorings were performed at the same urinary albumin excretion stage in absence of antihypertensive treatment for each diabetic subject and for their respective control. Blood pressure and heart rate averages during 24 h, awake, sleep, and day: night ratio were calculated. RESULTS: Seven of the eight proteinuric subjects were hypertensives, whereas hypertension was absent in the normoalbuminuric and microalbuminuric groups. The intraindividual reproducibility in diabetics showed repeatability coefficients for the 24 h systolic and diastolic pressure of 33 and 42%, respectively. This reproducibility for the day: night ratio was generally worse, 57% for systolic and 59% for diastolic. A progressive increment in the mean ambulatory BP was observed across the three groups of diabetics and the differences in BP observed were most evident during the night-time period. Though no differences in the 24 h circadian pattern were present between the normoalbuminurics and their controls, nocturnal differences were observed, not only in microalbuminurics for systolic BP (P < 0.05), but also in proteinurics for both systolic BP (P < 0.01) as well as diastolic BP (P < 0.05). No differences were observed in heart rate among the diabetic groups. The non-dipping pattern in the two monitorings was observed in 80, 58, 18 and 10% of the proteinurics, microalbuminurics, normoalbuminurics and control groups, respectively. CONCLUSIONS: Persistent abnormal circadian variability seems to be an early and frequent characteristic of type I diabetics with an increased urinary albumin excretion. Although present in some normalbuminuric subjects, the frequency of this abnormality increases as the incipient nephropathy progresses. By the time proteinuria is established, nearly all subjects present the abnormal pattern.
OBJECTIVE: The objective of the present study was to analyze the influence of the insertion/deletion (I/D) polymorphism of the angiotensin-converting enzyme on ambulatory blood pressure values and circadian variability in untreated patients with hypertension. MATERIAL AND METHODS: Ninety-nine essential hypertensive patients, less than 50 years old (mean age 39.5+/-7.0 years), previously untreated with antihypertensive drugs were included. Twenty-four hour ambulatory blood pressure monitoring (ABPM) was performed with a Spacelabs (90202 and 90207) monitor, during a regular working day in unrestricted ambulatory conditions. The I/D polymorphism of the ACE was determined by PCR. RESULTS: The distributions of genotypes were in Hardy-Weinberg equilibrium: I=17 (17%), ID=41 (41.5%), DD=41 (41.5%). No significant differences were present among the groups in terms of age, sex, and biochemical and lipid profiles. The average of 24-h ambulatory blood pressure was slightly higher in patients with the DD genotype as compared with patients with the II and ID genotypes. This was the result of higher nighttime blood pressure values, because no differences in blood pressure were observed during daytime. The systolic blood pressure (SBP) day:night ratio, as an estimate of circadian variability, was significantly lower in subjects homozygous for the D allele than it was in patients carrying the I allele (1.13+/-0.09 vs. 1.17+/-0.08, P=0.014). The subjects in the lowest tertile of the SBP day:night ratio, exhibited a higher frequency of the D allele when compared with those in the middle tertile (0.74 vs. 0.59, P<0.05) or with those in the highest tertile (0.74 vs. 0.54, P<0.01). By using two-way ANOVA with repeated measures, significant differences in SBP variation over time were observed when comparing homozygous for the D allele with subjects carrying the I allele (F=2.11, P=0.002). CONCLUSIONS: Among the genotypes of the I/D polymorphism, subjects carrying DD genotype showed a blunted decline of the physiological nocturnal fall of blood pressure that was significant for SBP.
BACKGROUND: The objective of the present study was to analyze the factors related with changes of microalbuminuria during antihypertensive treatment in patients with essential hypertension. METHODS: One hundred and six patients (57 men, mean age 40.8 [SD 6.6] years) never treated with antihypertensive treatment were included. At the beginning and after one year, blood pressure biochemical profile and urinary albumin excretion (UAE) were measured. After the initial evaluation, 53 patients received angiotensin converting enzyme inhibitors (ACEi) and 53 beta-blockers (BB). Hydrochlorothiazide was added to achieve the blood pressure target < 140/90 mmHg. RESULTS: The average of UAE was 32.1 (43.1) mg/24 h, and 41 (39%) patients had microalbuminuretics. After 12 months of treatment, a significative fall of systolic BP (-20.6 [8.03] mmHg, p < 0.001), and diastolic BP (-14.18 [10.34] mmHg, p < 0.001) were observed, whereas baseline glucose increases (3.08 [11.07] mg/dl, p = 0.006). The changes of UAE were only related with the baseline UAE values. Neither, age, sex, baseline diastolic BP and changes in diastolic BP were significantly related with the changes in UAE. In spite of similar mean BP reduction (medial BP 17.4 [10.9] vs 14.8 [10.4] mmHg), UAE only was reduced in patients treated with ACEi (LogUAE: 0.203 [0.872] mg/24 h; p < 0.04). In addition, in patients treated with BB a significative increase in baseline glucose (4.4 [12.3] mg/dl; p = 0.013) and uric acid (1.18 [4.18]; p = 0.031) were observed. CONCLUSIONS: In patients with essential hypertension, changes in microalbuminuria depends of the initial UAE values and the kind of antihypertensive treatment. ACEi produced higher UAE reduction and lower derangement of the glucose metabolism than BB.