[Structure and metric properties of a questionnaire to measure disability in mobility activities in patients with chronic obstructive pulmonary disease (DIAMO-COPD questionnaire)]. / Estructura y propiedades métricas de un cuestionario para medir discapacidad en las actividades de movilidad en pacientes con enfermedad pulmonar obstructiva crónica (cuestionario DIAMO-EPOC).

OBJECTIVE: The aim of this study was to adapt a disability questionnaire in mobility activities (DIAMO-EPOC) incorporating scales based on the conceptual framework of the International Classification of Functioning, Disability and Health, and to examine its structure, reliability and validity in a cohort of patients with COPD. METHODS: A total of 137 patients with stable COPD were recruited. Two scales of 4 items each were designed and their structure was verified by exploratory factor analysis and multitrait scaling analysis. Additionally, reliability indices (internal consistency and test-retest) were calculated. Construct validity was analysed by known groups and convergence-divergence. RESULTS: The questionnaire had 2 scales, with 4 items each, corresponding to the domains of the International Classification of Functioning, Disability and Health "change and maintain the position of the body" and "walk and move". The reliability and internal consistency of the scales were acceptable and the test-retest was excellent with an ICC of 0.86 and 0.94, respectively. The scales showed a moderate association with dyspnoea, health status and muscle strength and a different score among participants with different physical performance in the Short Physical Performance Battery. CONCLUSIONS: The 2 scales of the DIAMO-EPOC questionnaire are one-dimensional and have a solid internal consistency, test-retest stability and validity, allowing the identification of specific areas of limited mobility in patients with COPD.

Code stroke in Asturias.

BACKGROUND: Intravenous thrombolysis with alteplase is an effective treatment for ischaemic stroke when applied during the first 4.5 hours, but less than 15% of patients have access to this technique. Mechanical thrombectomy is more frequently able to recanalise proximal occlusions in large vessels, but the infrastructure it requires makes it even less available. METHODS: We describe the implementation of code stroke in Asturias, as well as the process of adapting various existing resources for urgent stroke care in the region. By considering these resources, and the demographic and geographic circumstances of our region, we examine ways of reorganising the code stroke protocol that would optimise treatment times and provide the most appropriate treatment for each patient. RESULTS: We distributed the 8 health districts in Asturias so as to permit referral of candidates for reperfusion therapies to either of the 2 hospitals with 24-hour stroke units and on-call neurologists and providing IV fibrinolysis. Hospitals were assigned according to proximity and stroke severity; the most severe cases were immediately referred to the hospital with on-call interventional neurology care. Patient triage was provided by pre-hospital emergency services according to the NIHSS score. CONCLUSIONS: Modifications to code stroke in Asturias have allowed us to apply reperfusion therapies with good results, while emphasising equitable care and managing the severity-time ratio to offer the best and safest treatment for each patient as soon as possible.

[Assessment of a Tiapride solution for its administration through continuous intravenous perfusion]. / Estudio de estabilidad de tiaprida en disolución para administración en perfusión intravenosa continua.

OBJECTIVES: Tiapride is a substituted benzamide classified as an atypical neuroleptic. To our knowledge, there are no published data on its stability prepared as a continuous intravenous infusion. The current study analysed its stability in two different infusion solutions and concentrations over 48 hours. METHOD: Triplicate samples of tiapride were prepared in 0.9% sodium chloride and in 5% dextrose solutions at final concentrations of 1 and 2 mg/ml. Samples were collected in glass bottles without photoprotection and at room temperature (25 ± 2 °C). Sampling times at 0, 1, 3, 6, 12, 24 and 48 hours included a visual inspection for colour changes and appearance of precipitation as well as pH determination. Tiapride was quantified at selected times by mass spectrometry using high-performance liquid chromatography. Concentration values in the samples corresponding to 0 hours were given a reference value of 100%. Concentrations in subsequent samples greater than 90% were considered stable. RESULTS: No colour change or precipitation was observed during the study period. pH values ranged between 0.1 and 0.4 units. At 48 hours, the concentration of remaining tiapride in sodium chloride 1 mg/ml and 2 mg/ml was 93.8% and 91.6%, respectively. That in 5% dextrose 1 mg/ml and 2 mg/ml was 96.8% and 94.1%, respectively. CONCLUSION: Dilutions of tiapride in 0.9% sodium chloride and in 5% dextrose solution, at concentrations of 1 mg/ml and 2 mg/ml, in glass bottles and at room temperature were stable both physically and chemically during 48 hours.

[Review of 22 patients with 22q11.2 deletion syndrome: phenotype spectrum]. / Revisión de 22 casos de deleción 22q11.2: espectro fenotípico.

INTRODUCTION: The 22q11.2 deletion syndrome is a contiguous gene deletion syndrome with an incidence rate of 1/4,000-6,000 live births. The most specific clinical features are: congenital conotruncal heart diseases, palate anomalies, hypocalcaemia, immunity and learning problems, and a characteristic facial phenotype. The objective of this work is to review the presenting phenotype and clinical features of children with 22q11.2 deletion syndrome as a guide for early diagnosis. PATIENTS AND METHODS: Retrospective study of 22 patients with 22q11.2 deletion syndrome diagnosed at our hospital in the time period 2004-2007. Variables analyzed: incidence, sex, age at diagnosis, presenting phenotype, clinical features, positive family history, mortality and natural history. RESULTS: From a total of 22 patients, 63 % were males, and the median age at diagnosis was of 4.5 years. Presenting pheno-type: congenital heart disease, milestones delay, velopharyngeal incompetence, hypocalcaemia, and mental retardation/psychiatric disturbances. CLINICAL FEATURES: congenital heart disease (84 %), velopharyngeal incompetence (47 %), milestones delay and learning disabilities (79 %). All of the deletions were de novo, except in one case where the deletion was present as mosaicism in the father. Three patients died, due to congenital heart disease. CONCLUSIONS: Clinical expression is widely variable, although a characteristic phenotype exists. Patients with heart disease are diagnosed earlier than other patients with unusual presenting phenotype such as congenital dysphagia. It is important to recognize less common phenotypes at early ages in order to provide multidisciplinary monitoring and accurate genetic counselling.

Short, highly efficient syntheses of protected 3-azido- and 4-azidoproline and their precursors.

[structure: see text] An improved synthesis of protected cis- and trans-3-azido-L-proline and cis- and trans-4-azido-L- and -D-proline is reported. These compounds have been synthesized from the corresponding hydroxyproline precursors using diphenylphosphoryl azide under Mitsunobu conditions. Short, highly efficient syntheses of these precursors are described, based on a new lactone-opening reaction and p-nitrobenzoate hydrolysis under very mild conditions.

Mild and selective sodium azide mediated cleavage of p-nitrobenzoic esters.

[reaction: see text] A mild and selective cleavage of p-nitrobenzoic esters by sodium azide in methanol is reported. This new methodology is mild enough for use with acid- or base-sensitive compounds. No elimination byproducts are formed. Fmoc- and trifluoroacetyl-amino protecting groups, benzyl esters, and ethyl esters remain unaffected. Less reactive compounds are discussed in terms of steric factors, and yields are increased by altering the azide solvation.

Angiotensin converting enzyme and endothelial nitric oxide synthase DNA polymorphisms and late onset Alzheimer's disease.

OBJECTIVES: Several lines of evidence suggest that the endothelial constitutive nitric oxide synthase (ecNOS) and angiotensin converting enzyme (ACE) may have a role in Alzheimer's disease. ACE is widely expressed in the brain, and a DNA polymorphism at the ACE gene has been linked to the risk for late onset Alzheimer's disease. Nitric oxide (NO) production by microglial cells, astrocytes, and brain microvessels is enhanced in patients with Alzheimer's disease. There is a growing evidence that NO is involved in neuronal death in Alzheimer's disease, and the oxidative stress caused by NO in the brain could be a pathogenic mechanism in Alzheimer's disease. The objective was to determine if two DNA polymorphisms at the ecNOS and ACE genes that have been linked with different levels of enzyme expression, have some effect on the risk of developing late onset Alzheimer disease. METHODS: A total of 400 healthy controls younger than 65 years and 350 patients with Alzheimer's disease (average age 72 years) were genotyped for the ACE and ecNOS polymorphisms. To define a possible role for these polymorphisms in longevity 117 healthy controls older than 85 years were also analysed. Genomic DNA was obtained and amplified by polymerase chain reaction, and genotypes were defined following a previously described procedure. Gene and genotype frequencies between patients and controls were compared statistically. RESULTS: Gene and genotype frequencies for the ecNOS and ACE polymorphisms did not differ between both groups of healthy controls (<65 years and >85 years). EcNOS gene and genotype frequencies were similar between patients and controls. There was a slight but significantly increased frequency of the ACE-I allele among patients with Alzheimer's disease compared with controls (p=0.03; OR=1.28, 95%CI= 1.04;1.58). CONCLUSIONS: The ACE-I allele was associated with a slightly increased risk of developing late onset Alzheimer's disease.

[Frequency of the APOE-4 allele in Alzheimer's disease and its variation with age in Asturias (Spain)]. / Frecuencia del alelo APOE-4 en la enfermedad de Alzheimer en la población asturiana y su variación con la edad.

BACKGROUND: Patients with late-onset Alzheimer's disease show a higher frequency of the APOE-4 than controls. The usefulness of the APOE genotyping in the diagnosis of the disease is controversial. Recently, an age dependent prevalence of APOE-4 in Alzheimer's disease has been described, with a maximum frequency for patients with an age at onset between 65 and 80 years. Additionally, the APOE-4 frequency in healthy controls is similar among the different age-groups, including healthy octogenarians. These data suggest that APOE-4 determines when and not who will develop the disease. PATIENTS AND METHODS: The APOE genotype was defined following a previously described PCR-protocol. We analysed 120 patients with clinically defined probable Alzheimer's disease and 250 controls from the same Caucasian population (Austrias, Northern Spain). RESULTS: We found a significantly higher frequency of the APOE-4 in patients, compared to controls (p = 0.00001). The prevalence of this allele was 65% among patients with an age at onset 66-70, falling to 36% and 18% in patients younger than 65 and older than 80 years, respectively. The average age (SD) at onset did not differ between the E-44 (69 years), E-34 (73 years) and E-33 (73 years). APOE-4 frequency was similar between the different age-groups of controls, including healthy octogenarians. CONCLUSIONS: In Asturias, APOE genotyping can not be used for the presimptomatic diagnosis of Alzheimer's disease. However, individuals carrying this allele would have a higher probability of developing the disease at an age between 65 and 80 years if they are predisposed (genetically and/or environmentally) to the disease.

Association between an alpha(2) macroglobulin DNA polymorphism and late-onset Alzheimer's disease.

An association between a five-base-pair deletion/insertion DNA polymorphism at the alpha(2) macroglobulin gene (A2M) and late-onset Alzheimer's disease (LOAD) has been recently described. We developed a PCR assay to analyze this polymorphism in 190 LOAD patients (older than 65 years) and 400 controls from Spain. Controls were stratified into three groups: <65 years (n = 200), 65 to 80 years (n = 100), and 81 years or older (n = 100). We found a significantly higher frequency of carriers of the D allele in patients older than 81 years compared to controls older than 81 years (p = 0.0012). In addition, the frequency of the D allele was significantly lower in controls older than 81 years compared to controls younger than 65 (p = 0.048). Our work suggests that the D allele confers an age-dependent increased risk to develop late-onset Alzheimer's disease.

Perineurioma (storiform perineurial fibroma) of the kidney in a child.

Perineurioma is an extremely rare benign tumor of the peripheral nervous system composed exclusively of perineurial cells. Imaging findings of this tumor are non-specific and the diagnosis is based on histologic studies. We report a case of perineurioma of the kidney in a 7-year-old girl discovered incidentally during the evaluation of a urinary tract infection. This is the first case of renal perineurioma reported in a child. We present the ultrasound and computed tomography findings of this histologically confirmed neoplasm.

[Intercritical SPECT in drug-resistant partial epilepsy with normal MRI: a study of 33 cases]. / SPECT intercrítica en la epilepsia focal farmacorresistente con RM normal: estudio de 33 casos.

We made a prospective study of the intercritical changes in cerebral perfusion using SPECT with 99mTc-HMPAO in 33 adult patients with focal epilepsy which was resistant to polypharmacy and showed normal MR, to evaluate the relationship between these changes and the clinico-electrical focus (FCE) and the clinical features of epilepsy. All SPECT studies (100%) showed one or more areas of hypoperfusion. There was good topographical relationship between the perfusion defects and FCE which coincided exactly in 15 patients (45.4%); was acceptable with FCE identification but with associated defects in 12 (36.4%) and poor, bearing no relation to each other in 6 (18.2%). There was no correlation between a good, acceptable or poor relationship of SPECT-FCE and the age of the patient, time-course of the illness, number of crises, number of drugs or type of treatment given. There were more cases showing poor relationship amongst the pure temporal lobe foci (p < 0.05), but when these were considered together with the fronto-temporal cases, no difference was seen when compared with the extra-temporal cases. There was a tendency to greater secondary generalization of the crises in the group showing a good relationship. There were more cases of a clinical history of previous CNS diffuse lesions (anoxia, trauma or meningitis) amongst those with a poor relationship (83%) but not amongst those with a good relationship (20%, p < 0.05), or an acceptable relationship (25%, p < 0.05). This would seem to suggest that the anomalies found were more a result of the cause of the epilepsy than of the repetition of crises. SPECT should be included in the diagnostic algorithms of focal epilepsy with normal.

[Prognostic factors of supratentorial cerebrovascular accidents]. / Factores pronósticos en los accidentes cerebrovasculares supratentoriales.

Our aim was to delimit prognostic factors in supratentorial stroke based on data obtained upon hospitalization. We studied two series of patients, the first being 150 with brain infarct and the second 135 having intracerebral haemorrhage. We analyzed: age, Glasgow and Canadian scales, glucose and urgence haemogram and the size of the lesion across its greatest diameter using computerized tomography (CT). Follow-up time was until death or one year after the stroke. Those who lived longer than one year after were subclassified according to the Rankin scale as < 3 and > or = 3. There was a significant difference between those who survived for less than one month and those surviving more than one year: their age (p < 0.01), average score on the scale (p < 0.001) and size of infarct (p < 0.05) or haematoma (p < 0.001). The Rankin subgroups < 3 and > or = 3 also differed significantly with regard to age. Noteworthy were the unfavourable data: Glasgow < 10 points and Canadian < 5 points, in infarcts > 6 cm and haematomas > 4 cm in diameter. We comment on other evolutionary variables which may influence prognostic assessment such as clinical deterioration or CT sensitivity of the infarct depending on the carry-out time.

CCB, a novel specific kappa opioid agonist, which discriminates between opioid and sigma 1 recognition sites.

CCB, 6,11-Dimethyl-1,2,3,4,5,6-hexahydro-3-([2'-methoxycarbonyl-2'-(4- chlorophenyl)cyclopropyl]methyl)-2,6-methano-3-benzazocin-8-ol, displays specificity and very high affinity for kappa opioid receptor types (Ki = 0.41 +/- 0.19 nM). In contrast to other kappa opioid agonists, CCB is also selective with respect to sigma 1 sites (Ki = 1,050 +/- 55 nM). CCB displays antinociceptive and sedative effects in the mouse comparable to those of U50,488H and morphine. Naltrexone fully antagonizes these effects. The sedative effects of CCB are blocked in mice pretreated with naltrexone or nor-BNI. CCB and U50,488H produce a superimposable diuresis in rats. Naltrexone and nor-BNI, both are effective in antagonizing the effect. CCB does not produce any stereotyped behavior or ataxia in the behavioral assay in doses up to 40 mg/kg s.c. These findings suggest that CCB might be a useful tool to investigate the physiological role of kappa opioid receptors.

[Janz's juvenile myoclonic epilepsy: a little-known frequent syndrome. A study of 85 patients]. / La epilepsia mioclónica juvenil de Janz: un síndrome frecuente poco conocido. Estudio de 85 pacientes.

BACKGROUND: Juvenile myoclonic epilepsy (JME) constitutes 10% of all epilepsies. Despite this syndrome being well defined, its diagnosis is usually delayed. The aim of this study was to analyze the clinical and electroencephalographic characteristics to facilitate guidelines to contribute to its recognition. METHODS: From January 1986 to July 1993 the clinical and EEG data of 85 patients with JME were prospectively studied. In 68 cases (80%) the polygraphic study of sleep was also analyzed during a nap period. RESULTS: The series included 44 males and 41 females of a mean age of 28 years (range: 13-63). Fifty-six percent of the cases showed family history of epilepsy and/or febrile convulsions. All the patients had myoclonic crisis with the age of 15 being the mean age of initiation (range: 8-27). Eighty-seven percent also had generalized tonic-clonic crisis and 18% typical absences. Myoclonias were presented daily up the administration of adequate treatment in 60% of the cases with 21% having myoclonic status. The mean interval from the initiation of the myoclonic crisis to diagnosis of JME was of 10.6 years. On monotherapy with valproic acid and following a mean follow up period of 23.8 months, 86% of the patients remained free of crisis. Nonetheless, the rate of recurrence was 100% in the 19 patients who discontinued the treatment. Surveillance EEG was normal on some occasion in 88% of the cases. The most characteristic paroxysms were the following: wave-point at 4-5 Hz and generalized rapid wave-polypoint. Light stimulation provoked a paroxysmal response in one third of the cases. Sleep EEG was abnormal in all the patients. An activation of the paroxysms during non-REM sleep in 78% of the cases and on waking up in 25%. CONCLUSIONS: Juvenile myoclonic epilepsy is a well defined syndrome. Its diagnosis is based on directed anamnesis allowing myoclonic jerks to be collected which often remain unperceived, and EEG exploration with sleep tracing in which the characteristic outbreaks of wave-point or generalized rapid wave-polypoints may be discovered.