Early Cerebellar Network Shifting in Spinocerebellar Ataxia Type 6.

Spinocerebellar ataxia 6 (SCA6), an autosomal dominant degenerative disease, is characterized by diplopia, gait ataxia, and incoordination due to severe progressive degeneration of Purkinje cells in the vestibulo- and spinocerebellum. Ocular motor deficits are common, including difficulty fixating on moving objects, nystagmus and disruption of smooth pursuit movements. In presymptomatic SCA6, there are alterations in saccades and smooth-pursuit movements. We sought to assess functional and structural changes in cerebellar connectivity associated with a visual task, hypothesizing that gradual changes would parallel disease progression. We acquired functional magnetic resonance imaging and diffusion tensor imaging data during a passive smooth-pursuit task in 14 SCA6 patients, representing a range of disease duration and severity, and performed a cross-sectional comparison of cerebellar networks compared with healthy controls. We identified a shift in activation from vermis in presymptomatic individuals to lateral cerebellum in moderate-to-severe cases. Concomitantly, effective connectivity between regions of cerebral cortex and cerebellum was at its highest in moderate cases, and disappeared in severe cases. Finally, we noted structural differences in the cerebral and cerebellar peduncles. These unique results, spanning both functional and structural domains, highlight widespread changes in SCA6 and compensatory mechanisms associated with cerebellar physiology that could be utilized in developing new therapies.

A survey of Italian and Spanish neonatologists and paediatricians regarding awareness of the diagnosis of FAS and FASD and maternal ethanol use during pregnancy.

BACKGROUND: Ethanol is the most widely used drug in the world and a human teratogen whose consumption among women of childbearing age has been steadily increasing. There are no Italian or Spanish statistics on ethanol consumption during pregnancy nor any information regarding prevalence of fetal alcohol syndrome (FAS) and fetal alcohol spectrum disorders (FASD). There is also a reasonable suspicion that these two diseases are underdiagnosed by professionals from the above-reported countries. The objectives of this study were: 1) to evaluate the experience, knowledge and confidence of Italian and Spanish neonatologists and paediatricians with respect to the diagnosis of FAS and FASD, and 2) to evaluate professionals awareness of maternal drinking patterns during pregnancy. METHODS: A multiple-choice anonymous questionnaire was e-mailed to Italian neonatologists registered in the mailing list of the corresponding Society and administered to Italian and Spanish paediatricians during their National Congress. RESULTS: The response rate was 16% (63/400) for the Italian neonatologists of the National Society while a total of 152 Spanish and 41 Italian paediatricians agreed to complete the questionnaire during National Congress. Over 90% of the surveyed physicians declared that FAS is an identifiable syndrome and over 60% of them identified at least one of the most important features of FAS. Although over 60% Italian responders and around 80% Spanish responders were aware that ethanol use in pregnancy is dangerous, approximately 50% Italian responders and 40% Spanish ones allowed women to drink sometimes a glass of wine or beer during pregnancy.Neonatologists and paediatricians rated confidence in the ability to diagnosis FAS and FASD as low, with over 50% responders feeling they needed more information regarding FAS and FASD identification in newborn and child. CONCLUSIONS: Italian and Spanish neonatologists and paediatricians do not feel confident about diagnosing FAS and FASD. More training is needed in order to accurately diagnose ethanol use during pregnancy and correctly inform pregnant women on the consequences on the newborn.

Placental chemical elements concentration in small fetuses and its relationship with Doppler markers of placental function.

INTRODUCTION: In this study, we aimed at quantifying placental concentrations of 22 chemical elements in small fetuses (SGA) as compared with normally grown fetuses (AGA), and to assess the relationship with Doppler markers of placental function. METHODS: Prospective cohort study, including 71 SGA fetuses (estimated fetal weight < 10th percentile) and 96 AGA fetuses (estimated fetal weight > 10th percentile), recruited in the third trimester of gestation. The placental concentration of 22 chemical elements was determined by inductively coupled plasma optical emission spectrophotometer (ICP-OES, ICAP 6500 Duo Thermo): aluminum (Al), beryllium (Be), bismuth (Bi), calcium (Ca), cadmium (Cd), cobalt (Co), chrome (Cr), copper (Cu), magnesium (Mg), manganese (Mn), molybdenum (Mo), nickel (Ni), phosphorus (P), lead (Pb), rubidium (Rb), sulfur (S), strontium (Sr), titanium (Ti), thallium (Tl), antimony (Sb), selenium (Se), and zinc (Zn). Placental function was assessed by measuring the following fetal-maternal parameters: Uterine artery Pulsatility Index (UtA PI), Umbilical artery Pulsatility Index (UA PI) and Middle Cerebral artery Pulsatility Index (MCA PI). The association between the chemical elements concentration and study group and the association with Doppler measures were evaluated. RESULTS: SGA was associated with significantly (p < 0.05) lower concentrations of Al (AGA 21.14 vs SGA 0.51 mg/kg), Cr (AGA 0.17 vs SGA 0.12 mg/kg), Cu (AGA 0.89 vs SGA 0.81 mg/kg), Mg (AGA 0.007 vs SGA 0.006 g/100g), Mn (AGA 0.60 vs SGA 0.47 mg/kg), Rb (AGA 1.68 vs SGA 1.47 mg/kg), Se (AGA 0.02 vs SGA 0.01 mg/kg), Ti (AGA 0.75 vs SGA 0.05 mg/kg) and Zn (AGA 9.04 vs SGA 8.22 mg/kg). Lower placental concentrations of Al, Cr, Mn, Se, Ti were associated with abnormal UtA, UA and MCA Doppler. DISCUSSION: Lower placental concentrations of Al, Cr, Cu, Mn, Rb, Se, Ti and Zn are associated with SGA fetuses and abnormal fetal-maternal Doppler results. Additional studies are required to further understand how chemical elements affect fetal growth and potentially find strategies to prevent SGA.

Onychomycosis by Chaetomium spp.

Onychomycosis is one of the most common infections of the nail. It can be caused by dermatophytes, Candida species and other fungi. Although moulds can cause onychomycosis, they account for a minority of cases, mainly great toenail onychomycosis. We describe a case of an 11-year-old girl who developed an onychomycosis by Chaetomium species in second and third toenails.

[Necrotizing systemic sarcoidosis with pulmonary and central nervous system involvement]. / Sarcoidosis sistémica necrotizante con afectación pulmonar y del sistema nervioso central.

Sarcoidosis is a multisystemic disease which diagnosis depends on the presence of nonnecrotizing granulomas in the biopsy. However there are variants such as necrotizing sarcoidal granulomas or nodular sarcoidosis which have atypical findings and make difficult the differential diagnosis with other infectious processes. We describe a case of a man who develops granulomas with extensive necrosis in a systemic sarcoidosis that affected the lung and the central nervous system. This finding made us to make the diagnosis of tuberculosis and delay the specific treatment.

Ethical problems related to information and pharmaceutical care in Spain.

This paper represents a reflection on the limits and objectives of the information pharmacists should offer in pharmacies. The obligation of a pharmacist to follow the patient's therapeutic progress makes it necessary to integrate this figure into an ethical-legal framework and to define the objective of the health-related information offered, taking into account the patient's welfare and constitutional rights.

Estudio cuantitativo y cualitativo sobre las interacciones farmacológicas en farmacias de la Región de Murcia / Quantitative and qualitative study on pharmacological interactions in pharmacies in the Region of Murcia

JUSTIFICACIÓN: las interacciones farmacológicas son un problema muy frecuente en la actualidad. La farmacia puede ser un lugar estratégico donde detectar e intervenir frente a dichas interacciones.OBJETIVOS: los objetivos del estudio son evaluar las interacciones farmacológicas más frecuentes y más graves desde un punto de vista cuantitativo y realizar un estudio cualitativo sobre el punto de vista de los farmacéuticos respecto a las interacciones, la manera de detectarlas e intervenirlas y su opinión sobre los programas informáticos de detección.MATERIALES Y METODOS: se ha recogido, en una farmacia de Murcia, información sobre las prescripciones de 167 pacientes crónicos y polimedicados con receta electrónica, lo que nos ha permitido evaluar las interacciones presentes en la medicación de los pacientes, así como su gravedad y frecuencia. Además, se ha desarrollado una entrevista semiabierta a 10 farmacéuticos de la Región de Murcia. Con ello, se pretende conocer su percepción sobre la importancia de las interacciones, el procedimiento a seguir en la detección y manejo de las interacciones y la opinión que tienen sobre los programas informáticos como herramienta en la detección.RESULTADOS: se han detectado 577 interacciones en 1330 medicamentos que tenían prescritos 167 pacientes. Las interacciones se han producido sobre todo por diuréticos (17,76 %), antidiabéticos (15,34 %), inhibidores de la bomba de protones (8,49 %) y β-bloqueantes (7,11 %). Concretamente, los fármacos que más interaccionan son hidroclorotiazida (7,37 %), metformina (6,33 %), omeprazol (6,24 %), furosemida (6,07 %) y bisoprolol (5,03 %). Las interacciones que más se han repetido son las de omeprazol-hidroclorotiazida (6,4 %), sacarosa-metformina (6,4 %), metformina- bisoprolol (2,8 %) y la de omeprazol-furosemida (1,7 %). (AU)

Estudio sobre prevalencia de patologías crónicas en mayores de 50 años y adherencia al tratamiento mediante sistemas de dispensación personalizada / Study on the prevalence of chronic pathologies in the over 50s and adherence to treatment through personalised dispensing systems

JUSTIFICACIÓN: la atención farmacéutica ha sufrido un gran auge estas últimas décadas, debido al aumento de pacientes que padecen enfermedades crónicas, y al hecho de que las farmacias comunitarias son el punto de información sanitario más accesible y cercano para la población.OBJETIVOS: los objetivos del estudio consisten en la evaluación de la prevalencia de patologías crónicas en pacientes mayores de 50 años, así como el análisis de la adherencia al tratamiento mediante el uso de sistemas de dispensación personalizada (SDP) en una farmacia de Beniel, Región de Murcia.MATERIALES Y METODOS: en este trabajo se ha realizado un estudio a cuarenta participantes del municipio de Beniel a los cuales se les ha ofrecido el servicio de dispensación personalizada y el servicio de seguimiento farmacoterapéutico desde la farmacia. Además, se ha evaluado cuáles son las enfermadas crónicas más prevalentes en el municipio.RESULTADOS Y DISCUSIÓN: la enfermedad crónica con mayor prevalencia en Beniel es la hipertensión arterial (100 % de los encuestados), lo que coincide con los datos publicados por el Ministerio de Sanidad en los Informes Anuales de Salud. Por el contrario, la tercera enfermedad crónica más frecuente en el municipio de Beniel es la diabetes, de forma diferente a los datos nacionales que la establecen como la novena enfermedad más frecuente. Se han comparado los valores sociodemográficos en las patologías de depresión y ansiedad crónica, donde se ha visto reflejado una diferencia notable en hombres y mujeres, siendo estas últimas las más afectadas. Destaca el gran número de pacientes en tratamiento con Inhibidores de la bomba de protones (IBP) y antiagregantes plaquetarios.CONCLUSIONES: la población de Beniel no presenta grandes diferencias respecto a las patologías crónicas más frecuentes a nivel nacional. (AU)

Molecular cloning and characterization of a maize transglutaminase complementary DNA.

Two related complementary DNA clones, TGZ15 and TGZ21, encoding active maize transglutaminase (TGase) have been isolated for the first time in plants by molecular cloning (Patent Pending PCT/ES03/00247). Southern and northern blot analyses indicate that the two cDNAs probably corresponded to two different single-copy genes in the maize genome. Northern blot analyses revealed that the transcript is expressed preferentially in young leaves and differentiated embryogenic maize callus. This expression is dependent on light exposure time. TGase activity of the proteins encoded by clones TGZ15 and TGZ21 was detected in bacterial extracts overexpressing them, using two enzymatic assays. TGase activity was significantly higher than that of the empty-phagemid bacterial extracts. As in other TGases, this activity was inhibited by monodansyl cadaverine (MDC), GTP and the absence of exogenous Ca(2+). Likewise, light-stimulated Ca(2+)-dependent TGase activity was detected in thylakoids and grana of maize chloroplast, which was inhibited by MDC, GTP, DIECA and Diuron.

Purification and peptidase activity of a bacteriolytic extracellular enzyme from Pseudomonas aeruginosa.

A bacteriolytic enzyme excreted by Pseudomonas aeruginosa Paks I was purified: samples were found to be homogeneous by gel filtration chromatography, ion exchange chromatography using CM-cellulose, immunoelectrophoresis, PAGE and SDS-PAGE. The molecular weight of the lytic enzyme was estimated to be 15,000-19,000. The enzyme was active on Gram-positive bacteria with glycine-containing interpeptide bridges in their murein layers. In addition, this lytic enzyme showed peptidase activity catalysing the hydrolysis of pentaglycine peptides into tri- and diglycine peptides.

Prevention of graft-versus-host disease in high risk patients by depletion of CD4+ and reduction of CD8+ lymphocytes in the marrow graft.

From March 1994 to September 1997, 30 patients with hematological malignancies (12 ANLL, 10 CML, four ALL and four multiple myeloma) received HLA-identical allogeneic bone marrow transplants with the marrow graft selectively depleted of CD4+ lymphocytes and the CD8+ cell content adjusted to 1x10(6)/kg. Total depletion of CD4+ and partial depletion of CD8+ lymphocytes was carried out by an immunomagnetical method. All patients were considered as having high risk for developing GVHD by at least one of the following criteria: patient age >35 years; donor age >35 years; donor multiparity or marrow from an unrelated donor. Twenty-four cases received marrow from an identical sibling and six from an unrelated donor. In order to assess the role of methotrexate (MTX) in addition to cyclosporin A (CsA) after transplant, patients were randomly assigned to received either CsA alone (n = 15) or CsA plus a short course of MTX (n = 15). No case of primary graft failure was observed, but two patients developed late graft failure. Six patients presented grade II acute GVHD and no case of severe III-IV GVHD was seen. The actuarial probability of developing grade II-IV acute GVHD was 25.9+/-9.6% for the entire population. Patients receiving post-transplant CsA + MTX had significantly less probability of acute GVHD than those receiving CsA exclusively (6.7+/-6.4% vs. 50.5+/-17.8%, P = 0.03) and the schedule of post-transplant immunosuppression was the only factor associated with the incidence of acute GVHD in a multivariate analysis. The actuarial incidence of chronic GVHD for the entire population was 31.8+/-12.5, and there was no significant difference between both groups with additional prophylaxis. Four patients with CML and three with ANLL relapsed: the actuarial probability of remaining in complete remission for all patients was 53.6+/-17.3%. For patients with acute leukemia, the probability of remaining in complete remission did not differ significantly between those transplanted in first complete remission and those receiving a transplant in more advanced phases of the disease (87.5+/-11.6% vs. 72.9+/-16.5%; P = 0.44). The incidence of mixed chimerism assessed by PCR was 34%. Nineteen patients are alive between 2 and 43 months post-transplant, the probability of overall survival being 57.8+/-10.4%. Our data indicate that this method of selective T cell depletion is very effective in preventing acute GVHD in high risk patients, particularly when used in combination with post-transplant CsA + MTX.

Absence of detectable PML-RAR alpha fusion transcripts in long-term remission patients after BMT for acute promyelocytic leukemia.

Twenty patients with APL in long-term remission after BMT were analyzed for the presence of the PML-RAR alpha fusion gene by RT-PCR. Ten patients had undergone autologous BMT (six of them peripheral blood stem cell transplantation) and 10 allogeneic BMT. A total of 60 samples were examined by two different protocols. Of the eight patients studied just before conditioning, five showed PML-RAR alpha transcript prior to transplantation. Three of them were in CR and became PCR negative early post-transplantation. The other two patients, that were not in CR before transplant, remained PCR positive, relapsed early post-transplant and died. In the remaining patients no PML-RAR alpha transcripts were visible throughout their post-BMT courses. Our data show that long-term remission after BMT in APL patients is associated with eradication of cells carrying the PML-RAR alpha transcript, and that continued positivity of this test predicts subsequent relapse. The fact of the disappearance of PML-RAR alpha transcript early after BMT in patients previously positive suggest that transplant is capable of curing APL mainly through antileukemic action of the conditioning regimen and therefore, transplantation must be indicated in CR patients if a positive RT-PCR remains after treatment with ATRA plus chemotherapy.

Autologous peripheral blood stem cell transplantation (PBSCT) mobilized with G-CSF in AML in first complete remission. Role of intensification therapy in outcome.

In order to determine if peripheral blood stem cells (PBSC) collected after priming with G-CSF in AML in first complete remission (CR) can be used for autologous transplantation and to evaluate the efficacy of early intensification therapy as in vivo purging, we studied 35 consecutive patients with AML in first CR. After standard induction and consolidation chemotherapy, 24 of them were treated with one (10 patients) or two (14 patients) cycles of high-dose cytarabine plus etoposide prior to PBSC collection. G-CSF was used as the priming agent. Of the 35 patients scheduled for peripheral blood stem cell transplantation (PBSCT), three relapsed before transplantation, and the 32 remaining underwent PBSCT. High-dose therapy consisted of either total body irradiation plus cyclophosphamide or busulphan plus cyclophosphamide. The median number of CD34+ cells infused was 3.24 x 10(6)/kg (range 0.15-14). The median times to reach a PMN count of 0.5 x 10(9)/l and a platelet count of 50 x 10(9)/l were 12 (8-28) and 30 (11-345) days, respectively. There was no transplant-related mortality. Twelve patients relapsed between 2 and 21 months post-PBSCT. With a median follow-up of 28 months, actuarial disease-free survival (DFS) is 52.41 +/- 9% in the intent-to-treat group and 57.4 +/- 9.8% in patients who underwent PBSCT. The probability of DFS is significantly higher for patients who receive early intensification therapy prior to both PBSC collection and PBSCT as compared with patients that do not: 68.8 +/- 10.27% vs 35.5 +/- 12.6%, P = 0.0418. These results indicate the feasibility of PBSCT in AML using G-CSF-mobilized PBSC. The use of intensification treatment as 'purging in vivo' prior both to collection of PBSC and PBSCT significantly reduces the risk of relapse in this group of patients.

Prognostic indicators of herpetic keratitis. Analysis of a five-year observation period after corneal ulceration.

Clinical features of 152 patients with herpetic keratitis after a five-year observation period were analyzed. When compared with dendritic ulceration, geographic ulcers that had been symptomatically present for a longer time were more likely to have been treated with a topical steroid and took longer to heal. After treatment of the corneal ulceration, 40% of the patients experienced a recurrent herpetic ulcer, 25% experienced disciform or irregular stromal keratouveitis, 5% experienced ocular hypertension, and 6% had a decrease in visual acuity caused by corneal scarring. Recurrent ulcerative herpetic keratitis occurred more frequently in men and in patients who entered the study with a history or previous herpetic ulceration.

A protease with staphylolytic activity from Pseudomonas aeruginosa PAKS I.

The supernatant from broth cultures of Pseudomonas aeruginosa PAKS I contains two different enzymes with staphylolytic activity. One of them, namely staphylolytic enzyme, seems to be specific for glycine-rich cross-links present in the cell wall of different Gram-positive bacteria and has been previously characterized. In addition to the staphylolytic activity, the second protein which we propose to be a staphylolytic protease, has proteolytic activity against casein. This enzyme is approximately 33 kDa, has an isoelectric point ranging from 7.3 to 8.1 and an optimum pH value of 8.0 for casein hydrolysis. Staphylolytic protease was detected in the extracellular medium after 12 h of cell growth. Immunocytochemical studies suggest that the protease is located within the periplasmic space of P. aeruginosa.

Rational acyclovir therapy in herpetic eye disease.

Acyclovir has been widely used against the various manifestations of eye disease due to herpes simplex since it first became generally available in the UK nearly five years ago. This paper discusses the rational indications for its use, through considerations of its pharmacology and pharmacokinetics, and through results of the many clinical trials that have been carried out to investigate its effects since its clinical efficacy was first demonstrated in 1979.

Acycloguanosine: antiviral activity in the rabbit cornea.

We describe experiments, using the multiple microinoculation technique, to produce superficial herpes simplex keratitis in the rabbit cornea, which showed a potent antiviral effect of acycloguanosine.

Acanthamoeba keratitis.

We report on four patients seen during the past two years who had acanthamoeba keratitis. One is described in detail. We believe that acanthamoebic eye infection is not rare. An immunofluorescent technique for localisation of amoebae and cysts is described. Our patients' response to propamidine and dibromopropamidine therapy was complicated by problems of toxicity.

Spontaneous intracorneal haemorrhage.

We describe the unusual complication of spontaneous intracorneal haemorrhage in a patient who used an extended-wear contact lens. This was severe enough to cause corneal blood staining and ulceration which required surgical intervention.