Photo-bioconvection: towards light control of flows in active suspensions.

The persistent motility of individual constituents in microbial suspensions represents a prime example of the so-called active matter systems. Cells consume energy, exert forces and move, overall releasing the constraints of equilibrium statistical mechanics of passive elements and allowing for complex spatio-temporal patterns to emerge. Moreover, when subject to physico-chemical stimuli their collective behaviour often drives large-scale instabilities of a hydrodynamic nature, with implications for biomixing in natural environments and incipient industrial applications. In turn, our ability to exert external control of these driving stimuli could be used to govern the emerging patterns. Light, being easily manipulable and, at the same time, an important stimulus for a wide variety of microorganisms, is particularly well suited to this end. In this paper, we will discuss the current state, developments and some of the emerging advances in the fundamentals and applications of light-induced bioconvection with a focus on recent experimental realizations and modelling efforts. This article is part of the theme issue 'Stokes at 200 (part 2)'.

On the fate of sinking diatoms: the transport of active buoyancy-regulating cells in the ocean.

Diatoms are one of the most abundant, diverse and ecologically relevant phytoplanktonic group, contributing enormously to global biogeochemical processes like the carbon and silica cycles. This large success has been partly attributed to the mechanical and optical properties of the silica shell (the frustule) that envelops their body. But since they lack motility it is difficult to conceive how they cope with the fast-fluctuating environment they live in and where distributions of resources are very heterogeneous and dynamical. This pinpoints an important but yet poorly understood feature of diatoms physiology: buoyancy regulation that helps them controlling their sinking speed and position in the water column. While buoyancy regulation by light and nutrients availability has been well studied, the effect of hydromechanical stress via fluid shear has been rather overlooked when considering diatoms dynamics. Here, we aim to start filling this gap by first presenting direct experimental evidences for buoyancy control in response to hydro-mechanical stress and then review recent theoretical models where simple couplings between local shear and buoyancy control always result in heterogeneous cell distributions, specific accumulation regions within complex flows and increased sedimentation times to the depths, features of direct ecological relevance. We conclude by suggesting future experiments aiming to unveil such coupling and therefore gain better understanding on the fate of these fascinating microorganisms in their natural habitat. This article is part of the theme issue 'Stokes at 200 (part 2)'.

[Mammographic and ultrasonographic BIRADS classification and its correlation with histopathologic findings]. / Clasificación mastográfica y ultrasonográfica del BIRADS y su correlación con los hallazgos histopatológicos.

BACKGROUND: Screening programs for breast cancer include self and clinical examination and Imaging studies to obtain the BIRADS (Breast Imaging Reporting and Data System) grade has been described as an important tool. In México, breast cancer is the leading death cause from malignancy in women and thus an early detection and prompt treatment is an important public health concern OBJECTIVE: To compare the BIRADS classification with histopathological findings and cases of malignancy. METHODS: This is a retrospective, observational and descriptive study about of the correlation between histopathological reports and BIRADS classification. RESULTS: Records of 1551 patients were reviewed, of which only 176 met the inclusion criteria. There was a predominance of fibrocystic condition. 44 patients had cancer, with varying degrees of detection according to each category of the classification where BIRADS 5 corresponded to 100% of the malignant cases. CONCLUSION: Consistent with the results reported by other authors, highlighting some situations like BIRADS 4C (where there was a slight difference compared to literature) and the BIRADS 5 in which a detection of 100% of cases of cancer was achieved.

ATP5H/KCTD2 locus is associated with Alzheimer's disease risk.

To identify loci associated with Alzheimer disease, we conducted a three-stage analysis using existing genome-wide association studies (GWAS) and genotyping in a new sample. In Stage I, all suggestive single-nucleotide polymorphisms (at P<0.001) in a previously reported GWAS of seven independent studies (8082 Alzheimer's disease (AD) cases; 12 040 controls) were selected, and in Stage II these were examined in an in silico analysis within the Cohorts for Heart and Aging Research in Genomic Epidemiology consortium GWAS (1367 cases and 12904 controls). Six novel signals reaching P<5 × 10(-6) were genotyped in an independent Stage III sample (the Fundació ACE data set) of 2200 sporadic AD patients and 2301 controls. We identified a novel association with AD in the adenosine triphosphate (ATP) synthase, H+ transporting, mitochondrial F0 (ATP5H)/Potassium channel tetramerization domain-containing protein 2 (KCTD2) locus, which reached genome-wide significance in the combined discovery and genotyping sample (rs11870474, odds ratio (OR)=1.58, P=2.6 × 10(-7) in discovery and OR=1.43, P=0.004 in Fundació ACE data set; combined OR=1.53, P=4.7 × 10(-9)). This ATP5H/KCTD2 locus has an important function in mitochondrial energy production and neuronal hyperpolarization during cellular stress conditions, such as hypoxia or glucose deprivation.

Occurrence of antibiotics and antibiotic-resistant bacteria (ARB) in the Nervión river.

The main hydrometeorological, microbiological and physico-chemical characteristics of the Nervión river were monitored during a year, including 10 antibiotics and the presence of bacteria resistant to these antibiotics among faecal coliforms (FC) and total aerobic bacteria at 22 °C (TAB22). The characteristics of the river water were variable without a clear seasonal component, strongly influenced by rainfall, with a good quality for drinking water production throughout the year according to the physico-chemical parameters. The antibiotic resistant bacteria isolated from the water of the Nervión river were especially resistant to ß-lactams and macrolide antibiotics, highlighting the absence of resistance to derivatives of tetracyclines among strains of TAB22. A third of the isolated strains were multi-resistant to antibiotics with a seasonal component in its presence, with multi-resistant FC more abundant during summer and multi-resistant TAB22 more abundant during winter. The presence of antibiotics in the waters of the Nervión river was not very significant, with total absence of ß-lactams, minocycline and ciprofloxacin. Erythromycin and clarithromycin can be considered ubiquitous with mean concentrations of 2.5 ± 2.3 ngL-1 and 5.7 ± 4.6 ngL-1 respectively, and the presence of sulfamethoxazole and trimethoprim was also noticeable with maximum concentrations of 78.3 ngL-1 for sulfamethoxazole. Dilution due to the increase of rainfall was observed for several analysed antibiotics, but without significant seasonal differences.

Evaluation of oxidant-antioxidant balance in patients on maintenance haemodialysis: a comparative study of dialyzers membranes.

BACKGROUND: Haemodialysis (HD) exacerbates oxidative stress (OS). The polymethyl-methacrylate (PMMA)-BK-F membrane ameliorates OS and inflammation markers compared to polyacrylonitrile (PAN/AN69) and cellulose membranes. This may be due to the size of pore radius, high flux or other specific properties of PMMA membranes. AIM: To compare OS and inflammatory status in HD-treated end stage renal disease patients with membranes of different pore size radius and flux. METHODS: 47 patients of both sexes were studied. The HD membranes with which the patients were normally treated were changed to BK-P or B-3 membranes for 6 months. Intracellular and extracellular components of the oxidant-antioxidant balance (OAB), C-reactive protein (CRP), beta2-micro-globulin (beta2mu-globulin), albumin and transferrin were measured. RESULTS: A significant decrease in red cell membrane thiobarbituric acid reacting substances and an increase in cytosolic superoxide dismutase (SOD) and plasma total antioxidant substances were observed in all patients after 6 months of treatment with BK-P and B-3 membranes except SOD and CRP in patients previously dialysed with triacetate cellulose membranes. Albumin and transferrin remained unmodified. beta2mu-globulin significantly decreased after treatment with PMMA membranes. CONCLUSION: BK-P and B-3 HD membranes improved the OAB, beta2mu-globulin and CRP compared to PAN/AN69 and cellulose diacetate membranes.

GAB2 gene does not modify the risk of Alzheimer's disease in Spanish APOE 4 carriers.

OBJECTIVES: The genetic basis of Alzheimer's disease (AD) is being analyzed in multiple whole genome association studies (WGAS). The GAB2 gene has been proposed as a modifying factor of APOE epsilon 4 allele in a recent case-control WGAS conducted in the US. Given the potential application of these novel results in AD diagnostics, we decided to make an independent replication to examine the GAB2 gene effect in our series. DESIGN: We are conducting a multicenter population-based study of AD in Spain. PARTICIPANTS: We analyzed a total of 1116 Spanish individuals. Specifically, 521 AD patients, 475 controls from the general population and 120 neurologically-normal elderly controls (NNE controls). METHODS: We have genotyped GAB2 (rs2373115 G/T) and APOE rs429358 (SNP112)/rs7412 (SNP158) polymorphisms using real time-PCR technologies. RESULTS: As previously reported in Spain, APOE epsilon 4 allele was strongly associated with AD in our series (OR=2.88 [95% C.I. 2.16- 3.84], p=7.38E-11). Moreover, a large effect for epsilone 4/epsilone 4 genotype was also observed (OR=14.45 [95% C.I., 3.34-125.2], p=1.8E-6). No difference between the general population and the NNE controls series were observed for APOE genotypes (P > 0.61). Next, we explored GAB2 rs2373115 SNP singlelocus association using different genetic models and comparing AD versus controls or NNE controls. No evidence of association with AD was observed for this GAB2 marker (p > 0.17). To evaluate GAB2-APOE genegene interactions, we stratified our series according to APOE genotype and case-control status, in accordance with the original studies. Again, no evidence of genetic association with AD was observed in any strata of GAB2-APOE loci pair (p > 0.34). CONCLUSION: GAB2 rs2373115 marker does not modify the risk of Alzheimer's disease in Spanish APOE epsilon 4 carriers.

Design and validation of a scale to assess preferences of type 2 diabetic patients towards different nutritional supplements.

OBJECTIVES: To design and validate a scale to evaluate preferences of type 2 diabetic patients towards nutritional supplements (Madrid scale) and to discover those taste attributes that are more discriminating. CONTEXT: ambulatory patients with type 2 diabetes mellitus. MATERIALS AND METHODS: 18 controls and 106 type 2 diabetic patients received 2 of the 7 stimuli studied (6 nutritional supplements and a differential salty stimulus) and then completed both scales and a criterion question. Two weeks later, 30 diabetic patients received a retest. The psychometric properties of the Madrid scale were studied and the relative importance of each stimuli attribute was assessed. RESULTS: Feasibility: The Madrid scale consists of 8 questions and is completed in less than five minutes; Dimensionality: A single dimension which explains 45.1% of the variance. Reliability: Cronbach's , 0.806; intraclass correlation coefficient, 0.835 (95% confidence interval: 0.653-0.922). Concurrent validity: Correlation indexes of the corrected total score with the criterion question and the Modified Wine-Tasting Scale, 0.731 (p < 0.0005) and 0.774 (p < 0.0005), respectively. The scale discriminated between subjects younger and older than 75 years and between supplements and the differential stimulus. Preferences: Glucerna SR chocolate, Glucerna SR strawberry, Glucerna SR vanilla, Diasip vanilla, Clinutren vanilla and Resource diabet vanilla. CONCLUSION: The Madrid scale has adequate psychometric properties for its use in research and daily clinical practice.

[Antiretroviral drug toxicity in human immunodeficiency virus infected children]. / Toxicidad de fármacos antirretrovirales en niños infectados por el virus de la inmunodeficiencia humana.

Paediatric Human Immunodeficiency Virus infection (HIV) nowadays is a chronic disease with an excellent long term prognosis, but lifelong combined antiretroviral treatment is required. However, an improved quality of life in this population is limited by adverse drug effects. The highest risk of treatment toxicity is developing a complete metabolic syndrome including: Hyperlipemia, lipodystrophy, insulin resistance, lactic acidosis, osteopenia, hypertension, and specific system and organ toxicity, such as the kidney, liver, CNS or bone marrow. The risk of cardiovascular disease adult life and also definitive bone mass damage are the most significant metabolic costs that have to paid for increased survival. Most of these toxicities were able to be adequately treated but, pharmacological interferences, patient intolerance and the high number of drugs are the problems that limit the adherence to treatment, which is essential for a good therapeutical efficacy. In this article, we present four HIV paediatric patients who presented with almost the whole range of metabolic toxicities, and a practical overview of therapeutical management.

[Exposure to multiresisant tuberculosis: study and follow-up of nine children]. / Exposición a tuberculosis multirresistente: estudio y seguimiento de nueve niños.

A world increase in multidrug-resistant tuberculosis (MDR-TB) has been reported over the last few years. A larger number of diagnoses are being seen in Spain, due to the increase of immigration from high endemic TB countries. Articles published on this are anecdotal in children, and there is no clear directives for treatment of MDR-TB, or latent tuberculosis infection (ITBL) or on prophylaxis after exposure to active pulmonary MDR-TB. We present the initial management and progression of nine children after close contact exposure to an Ecuadorian woman diagnosed with active pulmonary TB, resistant to Isoniazid, Rifampicin and Pyrazinamide.

Intracellular acidification associated with changes in free cytosolic calcium. Evidence for Ca2+/H+ exchange via a plasma membrane Ca(2+)-ATPase in vascular smooth muscle cells.

The purpose of this study was to define the mechanism whereby agonists that increase free cytosolic calcium (Cai2+) affect intracellular pH (pHi) in smooth muscle. Rat aortic vascular smooth muscle cells grown on coverslips were loaded with BCECF/AM or fura-2/AM for continuous monitoring of pHi or Cai2+, respectively, in a HCO3-/CO2- containing medium. Recovery from rapid increases in Cai2+ produced by 1 microM angiotensin (Ang) II (delta Cai2+ -229 +/- 43 nM) or 1 microM ionomycin (delta Cai2+ -148 +/- 19 nM) was accompanied by a fall in pHi (delta pHi, -0.064 +/- 0.0085 P < 0.01, and -0.05 +/- 0.012 pH units, P < 0.01, respectively). Neither the fall in pHi nor the rise in Cai2+ elicited by Ang II was prevented by pretreatment with agents which block the action of this agonist on pHi via the stimulation of the Cl/HCo3 exchangers (DIDS, 50 microM) or the Na+/H+ antiporter (EIPA, 50 microM). In the presence of DIDS and EIPA, Ang II produced a fall in pHi (delta pHi, -0.050 +/- 0.014, P < 0.01) and a rise in Cai2+ (delta Ca2+ 252 +/- 157 nM, P < 0.01). That the change in pHi was secondary to changes in Cai2+ was inferred from the finding that, when the rise in Cai2+ elicited by Ang II was prevented by preincubation with a Ca2+ buffer, BAPTA (60 microM), the fall in pHi was abolished as well (delta pHi, 0.0014 +/- 0.0046). The pHi fall produced by Ang II and ionomycin was prevented by cadmium at a very low concentration (20 nM) which is known to inhibit plasma membrane Ca(2+)-ATPase activity (delta pHi -0.002 +/- 0.0006 and -0.0016 pH units, respectively). Cadmium also blunted Cai2+ recovery after Ang II and ionomycin. These findings suggest that the fall in pHi produced by these agents is due to H+ entry coupled to Ca2+ extrusion via the plasma membrane Ca(2+)-ATPase. Our results indicate that agonists that increase Cai2+ cause intracellular acidification as a result of Ca2+/H+ exchange across the plasma membrane. This process appears to be mediated by a plasma membrane Ca(2+)-ATPase which, in the process of extruding Ca2+ from the cell, brings in [H+] and thus acidifies the cell.

WITHDRAWN: Tacrine for Alzheimer's disease.

BACKGROUND: Tacrine is one of the first drugs to be widely marketed for the loss of memory and intellectual decline in Alzheimer's disease, often accompanied by abnormal behaviour and physical decline. The alleged success of tacrine in the treatment of these symptoms has been heralded as confirmation of the cholinergic theory of Alzheimer's disease. The efficacy of tacrine for symptoms of dementia remains controversial. This is reflected by the low rate of prescription of tacrine in countries where it is approved and the lack of approval by several regulatory authorities in Europe and elsewhere. The uncertainty about the efficacy of tacrine is due to the difficulties in interpretation of the results from the clinical trials. The reasons for this are the small effects of tacrine compared to placebo for all outcomes; the high incidence of adverse events; the lack of benefit observed in several trials; the use of cross-over designs and their associated methodological problems in a disease like dementia; the use of different measurement scales to assess outcome in different trials; and the problem of high dropout rates. OBJECTIVES: To determine the clinical efficacy of tacrine for the symptoms of Alzheimer's disease. SEARCH STRATEGY: The Cochrane Dementia Group Register of Clinical Trials was searched using the terms 'tacrine', 'tetrahydroaminoacridine' and 'THA' (see the Group's search strategy for full details). SELECTION CRITERIA: All unconfounded, double-blind, randomized trials in which treatment with tacrine was administered for more than a day and compared to placebo in patients with dementia of the Alzheimer's type. DATA COLLECTION AND ANALYSIS: Data were extracted independently by two reviewers, pooled if appropriate and possible, and the pooled odds ratios (95%CI) or the average differences (95%CI) were estimated. Where possible, intention-to-treat data were used. MAIN RESULTS: This review produced no clear results. The results were compatible with tacrine producing improvement, no change or even harm for those with Alzheimer's disease. It was not possible to use many of the published results in a combined analysis. For measures of overall clinical improvement, the intention-to-treat analyses failed to detect any difference between tacrine and placebo (OR 0.87; 95%CI 0.61 - 1.23). Behavioural disturbance, as measured by the Alzheimer's Disease Assessment Scale-noncognitive, failed to detect any difference between tacrine and placebo (SMD -0.04; 95%CI -0.52 - 0.43). For cognition function, the effect of tacrine was not statistically significantly different from placebo for the MiniMental State Examination score (0-30; high =good) (SMD 0.14; 95%CI -0.02 - 0.30) and was barely statistically significantly in favour of treatment for the Alzheimer's Disease Assessment Scale-cognitive scale (SMD -0.22; 95%CI -0.32 - -0.13). Adverse events were not reported in a systematic way in the different trials, making formal comparison difficult. Raised serum liver enzymes was the major reason for withdrawal. The odds ratio for withdrawal due to an adverse event was significantly different from one, the control group experienced fewer events (OR 5.7; 95%CI 4.1-7.9). Gastrointestinal side effects (diarrhoea, anorexia, dyspepsia and abdominal pain) were the other major cause of adverse events and for withdrawal, and the odds ratio for withdrawal was also significantly different from one in favour of the control group (OR 3.8; 95%CI 2.8-5.1). No deaths were reported in any of the studies during the trial period, up to six months. AUTHORS' CONCLUSIONS: This review provides no convincing evidence that tacrine is a useful treatment for the symptoms of Alzheimer's disease. However, as so few trials presented data in a format suitable for pooling, the results of this review may be modified when further data from all relevant trials are included. There is an urgent need for the independent evaluation of the data already existing in the trials but not accessible through published or grouped data. An independent meta-analysis of the individual-patient data is required. The results and conclusions of this update are unaltered by further searching as the additional studies do not add any further valid/eligible data.

Metrifonate for Alzheimer's disease.

BACKGROUND: Metrifonate is a long-acting irreversible cholinesterase inhibitor, originally used to treat schistosomiasis. Its potential to enhance central nervous system cholinergic neurotransmission led to clinical trials for the treatment of people with Alzheimer's disease (AD). Although low incidence of serious side effects occurred during short-term use as an antihelmintic, in studies of the treatment of AD extending over 6 months, 20 patients experienced respiratory paralysis and problems with neuromuscular transmission. These findings have led to a halt to trials of metrifonate for AD and Bayer, the pharmaceutical company, has withdrawn its FDA application. OBJECTIVES: 1) To establish the efficacy of metrifonate for patients with Alzheimer's disease, in terms of cognition, global impression, functional activity, non cognitive symptoms, rate of institutionalization and mortality.2) Assess the safety and tolerability of metrifonate. SEARCH STRATEGY: The Cochrane Dementia and Cognitive Improvement Group's Specialized Register was searched on 5 December 2005 using the term metrifonat*. This Register is regularly updated with records from all major health care databases (MEDLINE, EMBASE, CINAHL, PsycINFO) and many trials databases. One of the authors (LS), as member of the Metrifonate Study Group has had the opportunity to contact other metrifonate trialists to obtain data from potentially non published data of metrifonate clinical trials. SELECTION CRITERIA: All unconfounded, randomized double-blind clinical controlled trials comparing metrifonate to placebo in people with AD. DATA COLLECTION AND ANALYSIS: Data were extracted by the two reviewers, cross-checked, and pooled when appropriate and possible. MAIN RESULTS: Most studies assessed changes in cognitive function, global function, activities of daily living, behavioural problems, severity of disease and adverse events. Occasionally the results were not reported in sufficient detail to allow extraction of data for the meta-analyses. The treatment regimens were varied: loading doses were used in some trials. The range of maintenance doses and studies were not pooled unless the treatment regimens were considered comparable. The lengths of treatment varied from 6 to 26 weeks and studies were not pooled unless the treatment duration was similar. The results are derived from the ITT populations. Metrifonate at various doses, fixed and loading doses, was associated with significant cognitive improvement compared to placebo, except for weekly doses where there was no difference from placebo: MMSE (metrifonate 60-80 mg/day with initial loading at 26 weeks; metrifonate 50 mg/day fixed dose with no initial loading at 26 weeks MD 1.85, 95% CI 1.06 to 2.64, p<0.00001); ADAS-Cog (metrifonate 60-80 mg/day with initial loading at 26 weeks MD -3.24, 95% CI -4.40 to -2.08, p<0.00001)In most trials, there was improvement in clinical global impression: CIBIC-Plus (metrifonate 30-55 mg/day, approximately 0.65 mg/kg body weight, with initial loading at 26 weeks MD -0.25, 95% CI -0.41 to -0.09 p=0.002; metrifonate 50 mg/day fixed dose with no initial loading at 26 weeks MD -0.20, 95% CI -0.39 to -0.01, p=0.04). There were generally-significant drug-placebo differences in activities of daily living but this often depended on sample size and the characteristics of the instrument used: DAD (metrifonate 30-55 mg/day, 0.65 mg/kg body weight, with initial loading at 26 weeks MD 2.72, 95% CI 0.66 to 4.77, p=0.01; metrifonate 50 mg/day fixed dose with no initial loading at 26 weeks MD 4.07, 95% CI 0.29 to 7.85, p=0.03)Also there were differences associated with metrifonate compared with placebo for different doses of metrifonate in scores on a behavioural symptom scale, caregiver burden scale, and severity of disease scale. Adverse events occurring more often with metrifonate included abdominal pain, bloating, bradycardia, diarrhoea, leg cramps, nausea and rhinitis and were described as mostly mild and transient, but occasionally moderately severe, and infrequently severe and serious. Analysis of the number of patients suffering at least one mild, moderate, severe or serious adverse event before the end of treatment showed that there was usually no difference between placebo and metrifonate. AUTHORS' CONCLUSIONS: Metrifonate given once per day appears to be related to clinical response in cognition, global improvement, and activities of daily living in patients with mild to moderate Alzheimer's disease. Tolerability is good with adverse events as expected from a cholinesterase inhibitor, but with a low incidence of neuromuscular dysfunction and respiratory failure, too low to be detected in this review. It has been withdrawn from further development.

[Guidelines of the Spanish Society of Nephrology. Clinical practice guidelines for peritoneal dialysis]. / Guías Sociedad Española de Nefrología. Guías de práctica clínica en diálisis peritoneal.

In Spain and in each of its autonomous communities, the dialysis treatment of chronic renal disease stage 5 is totally covered by public health. Peritoneal dialysis, in any of its modalities, is established as the preferred home dialysis technique and is chosen by high percentage of patients as their choice in dialysis treatment. The Spanish Society of Nephrology has promoted a project of creation of performance guides in the field of peritoneal dialysis, entrusting a work group composed of members of the Spanish Society of Nephrology a with the development of these guides. The information offered is based on levels of evidence, opinion and clinical experience of the most relevant publications of the topic. In these guides, after defining the concept of << peritoneal dialysis>>, the obligations and responsibilities of the sanitation team of the peritoneal dialysis unit are determined, and protocols and performance procedures that try to include all the aspects that concern the patient with chronic renal disease in substitute treatment with this technique are developed. They propose prescription objectives based on available clinical evidence and, lacking this, on the consensus of the experts' opinions. The final aim is to improve the care and quality of the of the patient in peritoneal dialysis, optimizing in this way the survival of the patient and of the technique. In Spain, as in other neighbouring countries, peritoneal dialysis has an incidence and prevalence that is much lower than that of hemodialysis, ranging in the last evaluation by the Spanish Society of Nephrology between 5 and 24% in the different autonomous communities. The great majority of peritoneal dialysis units form part of the public network of the Spanish state, with special representation as a Satellite Unit or Concerted Center related to the public hospital of reference, on which it must depend.

[Vascular access guidelines for hemodialysis]. / Guías de acceso vascular en hemodiálisis.

Quality of vascular access (VA) has a remarkable influence in hemodialysis patients outcomes. Dysfunction of VA represents a capital cause of morbi-mortality of these patients as well an increase in economical. Spanish Society of Neprhology, aware of the problem, has decided to carry out a revision of the issue with the aim of providing help in comprehensión and treatment related with VA problems, and achieving an homogenization of practices in three mayor aspects: to increase arteriovenous fistula utilization as first vascular access, to increment vascular access monitoring practice and rationalise central catheters use. We present a consensus document elaborated by a multidisciplinar group composed by nephrologists, vascular surgeons, interventional radiologysts, infectious diseases specialists and nephrological nurses. Along six chapters that cover patient education, creation of VA, care, monitoring, complications and central catheters, we present the state of the art and propose guidelines for the best practice, according different evidence based degrees, with the intention to provide help at the professionals in order to make aproppiate decissions. Several quality standars are also included.

Terminal-restriction fragment length polymorphism (T-RFLP) screening of a marine archaeal clone library to determine the different phylotypes.

T-RFLP clone characterization (screening) was optimized for a fast and basepair-accurate characterization of clones from marine Archaea collected from the Eastern Mediterranean Sea. Because of the high sensitivity of T-RFLP fingerprinting, a protocol was developed where 10 initial PCR cycles gave detectable terminal fragments from clones. Additionally, forward and reverse primers for PCR were individually labeled and detected simultaneously to assess the suitability of the forward and reverse fragments for T-RFLP screening. Based on independent restriction digests with the tetrameric restriction enzymes HhaI, RsaI and HaeIII to characterize the 49 archaeal clones in our library, the clones were grouped into 13 T-RFLP operational taxonomic units (OTUs). Reverse fragments generally gave less heterogeneous fragments in size. The accuracy of T-RFLP screening was evaluated by sequencing representative clones. Closely related clones ( approximately 97% similarity) could only be resolved with multiple restriction digests where forward and reverse fragments were included in the analysis. All fragments from the clone library were detected in the T-RFLP fingerprint from the complex archaeal community. We found representatives of marine group I, II and III Archaea. Thus, the recently discovered low abundant marine group III Archaea could be clearly differentiated from the other clones in our library and comprised a considerable fraction of the clone library ( approximately 12%). Therefore, our T-RFLP screening approach proved successful in characterizing novel archaeal sequences from the marine environment.

Tacrine for Alzheimer's disease.

OBJECTIVES: To determine the clinical efficacy of tacrine for the symptoms of Alzheimer's disease. SEARCH STRATEGY: The Cochrane Dementia Group Register of Clinical Trials was searched using the terms 'tacrine', 'tetrahydroaminoacridine' and 'THA' (see the Group's search strategy for full details). SELECTION CRITERIA: All unconfounded, double-blind, randomized trials in which treatment with tacrine was administered for more than a day and compared to placebo in patients with dementia of the Alzheimer's type. DATA COLLECTION AND ANALYSIS: Data were extracted independently by two reviewers, pooled if appropriate and possible, and the pooled odds ratios (95%CI) or the average differences (95%CI) were estimated. Where possible, intention-to-treat data were used. MAIN RESULTS: This review produced no clear results. The results were compatible with tacrine producing improvement, no change or even harm for those with Alzheimer's disease. It was not possible to use many of the published results in a combined analysis. For measures of overall clinical improvement, the intention-to-treat analyses failed to detect any difference between tacrine and placebo (OR 0.87; 95%CI 0. 61 - 1.23). Behavioural disturbance, as measured by the Alzheimer's Disease Assessment Scale-noncognitive, failed to detect any difference between tacrine and placebo (SMD -0.04; 95%CI -0.52 - 0. 43). For cognition function, the effect of tacrine was not statistically significantly different from placebo for the MiniMental State Examination score (0-30; high =good) (SMD 0.14; 95%CI -0.02 - 0.30) and was barely statistically significantly in favour of treatment for the Alzheimer's Disease Assessment Scale-cognitive scale (SMD -0.22; 95%CI -0.32 - -0.13). Adverse events were not reported in a systematic way in the different trials, making formal comparison difficult. Raised serum liver enzymes was the major reason for withdrawal. The odds ratio for withdrawal due to an adverse event was significantly different from one, the control group experienced fewer events (OR 5.7; 95%CI 4.1-7.9). Gastrointestinal side effects (diarrhoea, anorexia, dyspepsia and abdominal pain) were the other major cause of adverse events and for withdrawal, and the odds ratio for withdrawal was also significantly different from one in favour of the control group (OR 3.8; 95%CI 2. 8-5.1). No deaths were reported in any of the studies during the trial period, up to six months. REVIEWER'S CONCLUSIONS: This review provides no convincing evidence that tacrine is a useful treatment for the symptoms of Alzheimer's disease. However, as so few trials presented data in a format suitable for pooling, the results of this review may be modified when further data from all relevant trials are included. There is an urgent need for the independent evaluation of the data already existing in the trials but not accessible through published or grouped data. An independent meta-analysis of the individual-patient data is required. The results and conclusions of this update are unaltered by further searching as the additional studies do not add any further valid/eligible data.

Nimodipine for primary degenerative, mixed and vascular dementia.

BACKGROUND: Dementia is an age-related condition in which Alzheimer's disease (AD) and cerebrovascular disease account for the bulk of cases. The role played by calcium in regulating brain functions is well known - the calcium ion links membrane excitation to subsequent intracellular enzymatic response. Change in calcium homeostasis is one important effect of aging with repercussions on higher cortical functions. Nimodipine is an isopropyl calcium channel blocker which can easily cross the blood brain barrier. Its primary action is to reduce the number of open channels, thus restricting influx of calcium ions into the cell. The usefulness of nimodipine in patients with Alzheimer's disease and vascular dementia and unspecified dementia is still controversial with mixed results. In spite of the uncertainties about its efficacy in dementia, nimodipine is currently a frequently prescribed drug for cognitive impairment and dementia in several European countries. This review will be conducted in two phases; the current review is based on evidence from published data only. The second phase will be based on individual-patient data analysed centrally and added to this review in due course. OBJECTIVES: To determine the clinical efficacy of nimodipine for the symptoms of dementia, either unclassified or according to the major subtypes - Alzheimer's disease, vascular, or mixed Alzheimer's and vascular dementia. SEARCH STRATEGY: The Cochrane Dementia Group Register of Clinical Trials was searched using the terms 'nimodipine' and 'isopropyl (2-methoxy-ethyl) 1,4-dihydro-2, 6-dimethyl-4-(3-nitrophenyl)-3, 5-pyridinedicarboxylate'. SELECTION CRITERIA: All unconfounded, double-blind, randomised trials in which treatment with nimodipine was administered for more than a day and compared to placebo in patients with dementia, either unclassified or according to the major subtypes - Alzheimer's disease, vascular, or mixed Alzheimer's and vascular dementia. DATA COLLECTION AND ANALYSIS: Data were extracted independently by the reviewers and the odds ratio (95%CI) or the average difference (95%CI) were estimated. Both intention-to-treat and on-treatment results were extracted. MAIN RESULTS: This review produced no clear results. Many of the data published were not capable of being sensibly pooled. The data were compatible with nimodipine producing improvement, no change or even harm for those with Alzheimer's disease, vascular dementia, or mixed Alzheimer's and vascular dementia. It was not possible to use many of the published results in a combined analysis. For measures of overall clinical improvement, the intention-to-treat analysis, based on one study only, failed to detect any difference between nimodipine and placebo (OR 0.53; 95%CI 0.25 - 1.13). An on-treatment analysis, based on one study only, produced a statistically significant difference in favour of nimodipine (SMD 4.4; 95%CI 3.9 - 5.0). For cognitive function, the effect of nimodipine was statistically significantly different from placebo for the Mini Mental State Examination score (0-30; high =good) (SMD 0.9; 95%CI 0.59 - 1.22) and there was a statistically significant effect in favour of treatment for the Wechsler Memory Scale (SMD 0.47; 95%CI 0.17 - 0.77). These analyses were based only on those who completed the study and not intention-to-treat analyses. There were no results presented in a form suitable for pooling for functional autonomy, behaviour, quality of life dependency (eg institutionalization), effect on carer, death, acceptability of treatment (as measured by withdrawal rate, safety (as measured by the incidence of adverse effects, including side effects, leading to withdrawal). REVIEWER'S CONCLUSIONS: This review provides no convincing evidence that nimodipine is a useful treatment for the symptoms of dementia, either unclassified or according to the major subtypes - Alzheimer's disease, vascular, or mixed Alzheimer's and vascular dementia. (ABSTRACT TRUNCATED)

Nimodipine for primary degenerative, mixed and vascular dementia.

BACKGROUND: Dementia is an age-associated syndrome most commonly due to Alzheimer's disease (AD) and/or cerebrovascular disease. Calcium has an important role in regulating brain functions. Calcium ions link membrane excitation to subsequent intracellular molecular responses. Age-associated changes in calcium homoeostasis have possible repercussions on higher cortical functions. Nimodipine is an isopropyl calcium channel blocker which readily crosses the blood-brain barrier. Its primary action is to reduce the number of open calcium channels in cell membranes, thus restricting influx of calcium ions into cells. The usefulness of nimodipine in patients with Alzheimer's disease and vascular dementia and unspecified dementia is still controversial. In spite of the uncertainties about its efficacy in dementia, nimodipine is currently frequently prescribed for cognitive impairment and dementia in several continental European countries. OBJECTIVES: To assess the clinical efficacy of nimodipine for the manifestations of dementia, in unclassified disease and in the major subtypes - Alzheimer's disease, cerebrovascular disease, and mixed Alzheimer's and cerebrovascular disease. SEARCH STRATEGY: The Cochrane Dementia and Cognitive Improvement Group's Specialized Register - which contains reports of trials from all major medical databases and many trial databases - was last searched on 3 August 2001 using the term 'nimodipin*'. SELECTION CRITERIA: All unconfounded, double-blind, randomized trials in which treatment with nimodipine was administered for more than a day and compared with placebo in patients with dementia, of unclassified type or attributable to Alzheimer's disease, cerebrovascular disease, or mixed Alzheimer's and cerebrovascular disease. DATA COLLECTION AND ANALYSIS: Data were extracted independently by the reviewers and the odds ratio (95%CI) or the average difference (95%CI) were estimated. Both intention-to-treat and on-treatment results were extracted. MAIN RESULTS: Fourteen trials were included which tested two treatment regimes, 90 and 180 mg/day of nimodipine for 12 and 24 weeks. Two trials included only patients with Alzheimer's disease (AD), 9 trials included only patients with cerebrovascular dementia (CVD), and three trials included patients with AD, CVD and mixed disease. Available outcome data from 9 trials (2492 patients) cover the domains of cognitive function, activities of daily living, global clinical state, safety and tolerability. By pooling available data from all trials, whatever the diagnosis of the patients included, this review found benefit associated with nimodipine (90 mg/day at 12 weeks) compared with placebo on the SCAG scale ( WMD -7.59, 95% CI -9.87 to -5.31, P<0.00001) on clinical global impression (WMD -0.87, 95% CI -1.07 to -0.67, P<0.00001) and cognitive function (SMD 0.61, 95% CI 0.42 to 0.81, P<0.00001) but not on scales assessing activities of daily living. When the AD trials and the VD trials were pooled separately similar significant results were found for the 90mg/day dose of nimodipine at 12 weeks. Drop-out rates were low in the trials, affecting similar proportions of treatment and placebo groups. Nimodipine is well tolerated with a low rate of adverse effects similar to that associated with placebo. There were slightly more adverse cerebrovascular events, and adverse events due to blood problems, associated with placebo than with nimodipine, and adverse autonomic events were slightly more common with nimodipine than with placebo. REVIEWER'S CONCLUSIONS: Nimodipine can be of some benefit in the treatment of patients with features of dementia due to unclassified disease or to Alzheimer's disease, cerebrovascular disease, or mixed Alzheimer's and cerebrovascular disease. It appears to be well tolerated with few side effects. Data were not available from several trials, a total of more than 500 patients. A meta-analysis of individual patient data from all trials is desirable. Dementia is a chronic disorder and the short-term benefits of nimodipine demonstrated in the trials reviewed do not justify its use as a long-term anti-dementia drug. New research must focus on longer term outcomes.