[Glaucoma: pharmacological implications]. / Glaucoma: implicaciones farmacológicas.

Glaucoma is the first cause of irreversible blindness worldwide. Its prevalence in our country is 2%; half of patients remain undiagnosed. Certain drugs can trigger and/or exacerbate glaucoma; hence the importance of having knowledge of these drugs by Primary Care physician. In addition, the drugs used in the treatment of glaucoma, even topically, can have systemic side effects that should be also know to the Primary Care physician. An adequate knowledge of all the drug groups and the prescribing of the appropriate drug in patients with risk factors and underlying pathology, will enable the Primary Care physician to optimise the risk/benefit ratio in the therapeutic management of these patients. An update is presented on this ophthalmological disease, with special attention to its implications for pharmacological treatments.

Asynchronous non-invasive brain-actuated control of an intelligent wheelchair.

In this paper we present further results of our asynchronous and non-invasive BMI for the continuous control of an intelligent wheelchair. Three subjects participated in two experiments where they steered the wheelchair spontaneously, without any external cue. To do so the users learn to voluntary modulate EEG oscillatory rhythms by executing three mental tasks (i.e., mental imagery) that are associated to different steering commands. Importantly, we implement shared control techniques between the BMI and the intelligent wheelchair to assist the subject in the driving task. The results show that the three subjects could achieve a significant level of mental control, even if far from optimal, to drive an intelligent wheelchair.

[Management of Descemet's membrane rupture by intracameral injection of SF6 in acute hydrops]. / Tratamiento de la rotura de la membrana de Descemet mediante SF6 intracamerular en hydrops agudo.

CASE REPORT: Hydrops occurring in the eye secondary to keratoconus, grade 4. It was managed by sulfur hexafluoride (SF6) gas injected into the anterior chamber, with an early resolution of corneal edema obtained. DISCUSSION: Intervention with intracameral SF6 injection has proven to be a safe and effective therapy for early reduction of corneal edema in an eye with Descemet's membrane detachment and acute hydrops (Arch Soc Esp Oftalmol 2009; 84: 533-536).

A brain-actuated wheelchair: asynchronous and non-invasive Brain-computer interfaces for continuous control of robots.

OBJECTIVE: To assess the feasibility and robustness of an asynchronous and non-invasive EEG-based Brain-Computer Interface (BCI) for continuous mental control of a wheelchair. METHODS: In experiment 1 two subjects were asked to mentally drive both a real and a simulated wheelchair from a starting point to a goal along a pre-specified path. Here we only report experiments with the simulated wheelchair for which we have extensive data in a complex environment that allows a sound analysis. Each subject participated in five experimental sessions, each consisting of 10 trials. The time elapsed between two consecutive experimental sessions was variable (from 1h to 2months) to assess the system robustness over time. The pre-specified path was divided into seven stretches to assess the system robustness in different contexts. To further assess the performance of the brain-actuated wheelchair, subject 1 participated in a second experiment consisting of 10 trials where he was asked to drive the simulated wheelchair following 10 different complex and random paths never tried before. RESULTS: In experiment 1 the two subjects were able to reach 100% (subject 1) and 80% (subject 2) of the final goals along the pre-specified trajectory in their best sessions. Different performances were obtained over time and path stretches, what indicates that performance is time and context dependent. In experiment 2, subject 1 was able to reach the final goal in 80% of the trials. CONCLUSIONS: The results show that subjects can rapidly master our asynchronous EEG-based BCI to control a wheelchair. Also, they can autonomously operate the BCI over long periods of time without the need for adaptive algorithms externally tuned by a human operator to minimize the impact of EEG non-stationarities. This is possible because of two key components: first, the inclusion of a shared control system between the BCI system and the intelligent simulated wheelchair; second, the selection of stable user-specific EEG features that maximize the separability between the mental tasks. SIGNIFICANCE: These results show the feasibility of continuously controlling complex robotics devices using an asynchronous and non-invasive BCI.

Lipolysis, proteolysis, physicochemical and sensory characteristics of different types of Spanish ostrich salchichon.

The objective of this study was to compare three different types of salchichon: made of ostrich meat, made of ostrich meat and lean pork, and made of ostrich meat and pork belly, from physicochemical and sensory viewpoints. To evaluate the intensity of lipolysis and proteolysis produced during the ripening process, the profile and content of free fatty acids, the degree of rancidity, the non-protein, water-soluble and aminoacidic nitrogen content were determined. In addition, the composition of the fermented sausages (pH, a(w), moisture, fat, protein, ash, sodium chloride and sodium nitrite content) was analysed. From a sensory viewpoint, the organoleptic characteristics of the different types of salchichon were studied using free choice profiling. The fermented sausages had varying characteristics depending on their formulation (ostrich meat or ostrich meat plus pork) and all of them were well accepted by the panelists. This study helps characterise the different types of ostrich salchichon made in Spain.

Molecular and clinical characterisation of three Spanish families with maternally inherited non-syndromic hearing loss caused by the 1494C->T mutation in the mitochondrial 12S rRNA gene.

Mutations in the 12S rRNA gene of the mitochondrial genome are responsible for maternally inherited non-syndromic hearing loss (NSHL), and for increased susceptibility to the ototoxicity of aminoglycoside antibiotics. Among these mutations, 1555A-->G is the most prevalent in all populations tested so far. Recently, the 1494C-->T mutation was reported in two large Chinese pedigrees with maternally inherited NSHL. In this study, sequencing of the 12S rRNA gene in a Spanish family with maternally inherited NSHL showed the presence of the 1494C-->T mutation. An additional screening of 1339 unrelated Spanish patients with NSHL allowed the authors to find two other families with the mutation. Audiological data were obtained from 17 confirmed 1494C-->T carriers, which showed that the hearing loss was sensorineural, bilateral and symmetrical, with a remarkable variability in age of onset and severity. Three carriers were asymptomatic. Three affected carriers had a history of treatment with aminoglycoside antibiotics. The mitochondrial genome of one affected person from each of these three families was entirely sequenced, and it was established that they belong to different mitochondrial haplogroups (H, U5b, U6a). The study results further support the pathogenic role of 1494C-->T on hearing, and show that this mutation can be found in different Caucasian mitochondrial DNA backgrounds.

Detection of hepatitis E virus in patients sera in southern Spain.

The aim of the present study was to detect acute Hepatitis E virus (HEV) infection in patients with abnormal alanine transaminase (ALT) in which other viral hepatitis infections had been excluded in southern Spain, an area adjacent to regions where this disease is endemic. Of 336 sera tested 30 (8.92%) were positive for IgM antibodies against HEV (anti-HEV IgM) and 7 (2.08%) were negative in a repeated assay. Immunoblot analysis (IBA) was applied to the 37 positive sera in the first assay; its results were positivity for 26 (7.73%), ambiguous for 5 and negative for 6 sera. Amplification of ORF1 and ORF2 of HEV by means of nested RT-PCR was carried out with the 37 sera that were either positive or ambiguous by ELISA; a positive result was obtained only with one serum for the ORF2 protein. IgM antibodies against the HEV ORF2 protein could be a useful marker in the diagnosis of acute infection and a substitute for the determination of viral RNA in serum; this is of both diagnostic and epidemiological importance as it would allow the patients transmitting the infection to be recognized by means of a simple determination of antibodies. The sequence of the ORF2 fragment of HEV occurring in samples taken from both humans and animals amplified in this study has considerable homology with the sequences of HEV strains/isolates of European origin. These results demonstrate that an autochthonous HEV circulates in Spain.

Mutation screening of USH3 gene (clarin-1) in Spanish patients with Usher syndrome: low prevalence and phenotypic variability.

Usher syndrome type III is an autosomal recessive disorder clinically characterized by the association of retinitis pigmentosa (RP), variable presence of vestibular dysfunction and progressive hearing loss, being the progression of the hearing impairment the critical parameter classically used to distinguish this form from Usher syndrome type I and Usher syndrome type II. Usher syndrome type III clinical subtype is the rarest form of Usher syndrome in Spain, accounting only for 6% of all Usher syndrome Spanish cases. The gene responsible for Usher syndrome type III is named clarin-1 and it is thought to be involved in hair cell and photoreceptor cell synapses. Here, we report a screening for mutations in clarin-1 gene among our series of Usher syndrome Spanish patients. Clarin-1 has been found to be responsible for the disease in only two families: the first one is a previously reported family homozygous for Y63X mutation and the second one, described here, is homozygous for C40G. This accounts for 1.7% of Usher syndrome Spanish families. It is noticeable that, whereas C40G family is clinically compatible with Usher syndrome type III due to the progression of the hearing loss, Y63X family could be diagnosed as Usher syndrome type I because the hearing impairment is profound and stable. Thus, we consider that the progression of hearing loss is not the definitive key parameter to distinguish Usher syndrome type III from Usher syndrome type I and Usher syndrome type II.

Progresión de la poliquistosis renal autosómica dominante. Influencia de polimorfismos de genes de sintasa endotelial del óxido nítrico (ecNOS) y del sistema renina-angiotensina / Progression of autosomic dominant polycystic kidney disease. Influence of endothelial NO synthase (ecNOS) and renin angiotensin system gene polymorphisms

Glomerular filtration rate decline (GFRd) is variable in autosomic dominant polycystic kidney disease (ADPKD). In 88 ADPKD patients, GFRd was assessed by 1/S(Cr) and compared with the association to AT1A1166C (AT1R), AGTM235T (angiotensinogen) and ecNOSGlu298Asp (NO endothelial synthase) polymorphisms. Age at S(Cr) values of 2 and 6 mg/dl were assumed as beginning of progressive phase (A2) and end-stage-renal disease (A6), respectively. Polymorphisms were studied by PCR-RFLP. The group as a whole showed GFRd (ml/min/year) of 6.9+/-0.5; A2 and A6 of 48.9+/-1.3 and 55.0+/-1.4 years and mean arterial pressure of 111.2+/-1.2 mmHg. When A6 was considered, two populations were defined (< or = and > 55 years). In < or = 55 (assumed as PKD1 phenotype) (n=42), A2 and A6 of the AT1 1166CC genotype were 36.0+/-1.2 and 41.4+/-0.9 years vs AA-AC (42.8+/-1.0 and 47.5+/-0.8, p<0.001). A2 and A6 of the ecNOS298Asp/Asp genotype were 34.8+/-1.5 and 41.1+/-0.6 years vs. Glu/Glu-Glu/Asp (42.4+/-0.9 and 47.1+/-0.8, p<0.02). In AGT235TT genotype, GFRd was 12.4+/-2.2 ml/min/year vs MM-MT (7.9+/-0.7, p<0.03). This difference was also observed when all ADPKD patients were considered (TT: 11.02+/-1.5 vs. MM-MT: 6.44+/-0.5 ml/ min/year, p<0.003). AT1 1166CC and ecNOS 298Asp/Asp are associated with earlier A2 and A6 whereas AGT 235TT induce twofold increase in GFRd, suggesting that RAS and ecNOS are involved in ADPKD progression.

La velocidad de progresión (VdP) de la poliquistosis renal autosómica dominante (PQRAD) es variable.Estudiamos la asociación de los polimorfismos AGTM235T (angiotensinógeno), AT1A1166C(ATR1) y ecNOSGlu298Asp (NO sintasa endotelial) con la VdP en 88 pacientes. VdP fue estimada por 1/Crplvs edad. Consideramos edades de Crpl 2 y 6 mg/dl como comienzo de progresión (E2) y arribo a insuficienciarenal crónica terminal (E6), respectivamente. Los polimorfismos se estudiaron por PCR-RFLP. El grupo en sutotalidad presentó VdP (ml/min/año) de 6.9±0.5, E2 y E6 de 48.9±1.3 y 55.0±1.4 años y tensión arterial media(TAM) de 111.2±1.2 mmHg. Según E6 observamos dos grupos (≤ y > a 55 años). En ≤ 55 (fenotipo PKD1,n=42), E2 y E6 del genotipo CC de AT1A1166C fueron 36.0±1.2 y 41.4±0.9 años vs. AA-AC (42.8±1.0 y 47.5±0.8, p < 0.001). E2 y E6 del genotipo ecNOS298Asp/Asp fueron 34.8±1.5 y 41.1±0.6 años vs. Glu/Glu-Glu/Asp (42.4±0.9 y 47.1±0.8, p < 0.02). En el genotipo AGT235TT, la VdP fue 12.4±2.2 ml/min/año vs. MM-MT (7.9±0.7, p < 0.03). Esta diferencia también se observó cuando analizamos todos los pacientes PQRAD (TT: 11.02±1.5 vs. MM-MT: 6.44±0.5 ml/min/año, p < 0.003). Los genotipos AT1 1166CC y ecNOS 298Asp/Asp anticipan E2 y E6 mientras que AGT235TT duplica VdP, sugiriendo la participación del sistema renina angiotensina y NO sintasaendotelial en la progresión de la PQRAD.

Is the predictive power of previous fractures for new spine and non-spine fractures associated with biochemical evidence of altered bone remodelling? The EPOS study. European Prospective Osteoporosis Study.

BACKGROUND: In the European Prospective Osteoporosis Study (EPOS), a past spine fracture increased risk of an incident fracture 3.6 - 12-fold even after adjusting for BMD. We examined the possibility that biochemical marker levels were associated with this unexplained BMD-independent element of fracture risk. METHODS: Each of 182 cases in EPOS of spine or non-spine fracture that occurred in 3.8 years of follow-up was matched by age, sex and study centre with two randomly assigned never-fractured controls and one case of past fracture. Analytes measured blind were: osteocalcin, bone-specific alkaline phosphatase, total alkaline phosphatase, serum creatinine, calcium, phosphate and albumin, together with the collagen cross-links degradation products serum CTS and urine CTX. Most subjects also had bone density measured by DXA. RESULTS: Cases who had recent fractures did not differ in marker levels from cases who had their last fracture more than 3 years previously. No statistically significant effect of recent fracture was found for any marker except osteocalcin, which was 17.6% lower in recent peripheral cases compared to unfractured controls (p<0.05) and this was independent of BMD. CONCLUSION: Past fracture as a risk indicator for future fracture is not strongly mediated through increased bone turnover.

Expression of proinflammatory cytokines and their inhibitors during the course of spontaneous bacterial peritonitis.

The aim of this work was the evaluation, in cirrhotic patients with noninfected ascites and with spontaneous bacterial peritonitis (SBP), of serum and ascitic fluid levels of proinflammatory cytokines [interleukin (IL) 1-beta, tumor necrosis factor alpha (TNF-alpha), and IL6] and antiinflammatory compounds [IL10, soluble IL-1 receptor antagonist (sIL-1Ra), soluble receptors of TNF p55 and p75 (sTNFR55 and sTNFR75), and soluble receptor of IL6 (sIL6R)], as well as their relationship with the outcome of the infection in those with SBP. These molecules were assayed by ELISA in noninfected cirrhotic controls (n = 15), patients with SBP (n = 32), and healthy controls (n = 20). Serum levels of IL6 and of the majority of antiinflammatory mediators, sIL1Ra, sTNFR75, and sIL6R, were higher in control cirrhotic patients compared to healthy subjects. SBP was associated with significantly elevated ascitic fluid levels of every one of the proinflammatory cytokines compared to those in cirrhotic controls. Also, serum levels of IL10 and both TNF receptors and ascitic fluid levels of sIL1Ra and sTNFR55 were higher in patients with SBP compared to cirrhotic controls. Ascitic fluid levels of proinflammatory cytokines decreased rapidly after resolution of the infection; however, nonsignificant changes were detected in ascitic fluid concentrations of antiinflammatory molecules. Thus, elevated levels of antiinflammatory compounds both in noninfected cirrhotic patients and in patients with SBP suggest a regulatory control of the inflammatory process by these molecules in liver cirrhosis patients.

Serial analysis of serum and ascitic fluid levels of soluble adhesion molecules and chemokines in patients with spontaneous bacterial peritonitis.

The aim of this work was the evaluation of serum and ascitic fluid levels of chemokines (IL-8, growth-regulated oncogene (Gro-alpha), and monocyte chemotactic protein-1 (MCP-1)), and of soluble adhesion molecules (P-selectin, E-selectin, L-selectin, intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1)) in patients with spontaneous bacterial peritonitis (SBP). These compounds were serially analysed in serum and ascitic fluid by ELISA in patients with SBP (n = 20), non-infected cirrhotic controls (n = 12), and healthy controls (n = 15). Infected and non-infected cirrhotic patients showed significantly higher serum levels of adhesion molecules. SBP was associated with significantly higher serum and ascitic fluid levels of IL-8, Gro-alpha and ICAM-1 and with ascitic fluid concentrations of MCP-1. Significantly elevated serum levels of both ICAM-1 and VCAM-1 were detected in patient non-survivors after SBP. Thus, higher ascitic fluid levels of chemokines could be implicated in the peritoneal infiltrate in patients with SBP. Prognostic significance can be attributed to serum levels of ICAM-1 and VCAM-1 in these patients.

Detection of hepatitis G virus (HGV) RNA and antibodies to the HGV envelope protein E2 in a cohort of hemodialysis patients.

An analysis of the evolution of hepatitis G virus (HGV) infection markers was performed for a cohort of 58 hemodialyzed patients. During follow-up (4.88 +/- 0.42 years), a group of these patients cleared their antibodies against the envelope protein E2 with (4 of 29 cases; 13.8%) or without (9 of 29 cases; 31%) the reappearance of viremia. This finding implies a temporally limited protection in patients previously infected with HGV.

Antiemetic efficacy of ondansetron in laparoscopic cholecystectomy. A randomized, double-blind, placebo-controlled study.

OBJECTIVE: to assess the effectiveness of ondansetron in preventing postoperative nausea and vomiting after elective laparoscopic cholecystectomy, and the effect of this anesthetic on hospital stay. METHODS: this randomized, double-blind, placebo-controlled study was done in the General Surgery Service of the Getafe University Hospital. Patients who were scheduled for laparoscopic cholecystectomy to treat uncomplicated cholelithiasis, and who had an ASA status of I-II, were recruited. Before surgery the patients received either ondansetron 4 mg or placebo intravenously. This study was approved by the local ethics committee. RESULTS: 56 patients were included, 29 in the ondansetron group and 27 in the placebo group. In the latter, 4 patients were later excluded because of conversion to open surgery. Postoperative nausea and emetic episodes were experienced by 7% of the patients in the ondansetron group and 47% in the placebo group (p = 0.0007). Oral intake started 7 h after surgery in the ondansetron group and 11 h after surgery in the placebo group (p = 0.04), with a mean difference of 4 h. Hospital stay was 30 h and 48 h respectively (p = 0.01), with a mean difference of 18 h. CONCLUSION: ondansetron given prior to surgery at a dose of 4 mg prevents postoperative nausea and vomiting after laparoscopic cholecystectomy, and reduces hospital stay.

Relationship of hepatitis C viremia to HIV state and to infection by specific hepatitis C genotypes.

AIMS/BACKGROUND: This study was undertaken to examine the relationship of hepatitis C (HCV) viremia to human immunodeficiency virus (HIV) infection and to investigate the evidence of infection by specific hepatitis C genotypes. PATIENTS AND METHODS: The analysis of HCV viremia was performed by reverse transcription-polymerase chain reaction in serum samples from 186 patients' selected by their positivity for anti-HCV antibodies. All samples were tested for HIV infection. In those patients with sera positivity for HCV RNA, isolates were genotyped by line probe assay. In those patients whose sera were negative for HCV RNA, antibodies specific for genotypes implicated in past HCV infection were detected by ELISA. RESULTS: HCV RNA was detected in 117 patients with anti-HCV antibodies (62.9%). There was no statistically significant association between HCV RNA and HIV positivity (Odds ratio, O.R.: 1.75, Confidence interval 95%, C.I.: 0.92-3.33, p = 0.095). A positive association was demonstrated between infection by HCV genotype 3 and HCV viremia (O.R.: 10.67, C.I.: 1.51-458.05, p = 0.015) in HIV-infected patients, as well as between infection by HCV genotype 1 and HCV viremia (O.R.: 4.71, C.I.: 1.65-13.75, p = 0.002) in HIV-non infected individuals. In both groups, a negative association was observed between past HCV infection by multiple genotypes and HCV viremia (HIV-infected patients, O.R.: 0.10, C.I.: 0.00-1.11, p = 0.033. HIV-non infected patients, O.R.: 0.05, C.I.: 0.00-0.41, p = 0.001). CONCLUSIONS: Infection by specific HCV genotypes (type 3 in HIV-infected patients and by type 1 in HIV-non infected ones) implies a higher risk of HCV viremia, whereas multiple HCV types infection is negatively associated with this probability. HIV coinfection does not influence the probability of HCV viremia.

[Octreotide and a serotonin-secreting glomus tumor]. / Octreótido y tumor glómico secretor de serotonina.

Glomus tumors arise in the chemical receptors of vessels in the tympanic and jugular regions. Clinical signs depend on location, the structures invaded and a tumor's ability to secrete active amines and peptides. A 44-year-old woman was scheduled for excision of a serotonin-secreting tympanic glomus tumor. Urinary excretion of 5-hydroxyindolacetic acid (5-HIA) in urine over the previous 24 hours was 80 mg (normal < 10 mg). The patient received oral diazepam, ranitidine, intravenous diphenhydramine and subcutaneous octreotide (150 micrograms). Anesthesia was induced with propofol, alfentanil and vecuronium. The tumor produced an episode of bronchospasm and cutaneous rubor during surgical manipulation of the tumor. Airway pressure increased to 42 cmH2O and SpO2 decreased to 89%. Hypotension and bradycardia appeared. Once it was suspected that the symptoms stemmed from tumoral secretion of active substances, 20 micrograms of intravenous octreotide was administered. The bronchospasm decreased and hemodynamic changes were resolved in three minutes, with no recurrence of symptoms. The patient received 100 micrograms of octreotide subcutaneously every 8 hours throughout the 72 postoperative hours. Urinary excretion of 5-HIA was 12 mg on the fifth day and the patient was released without having experienced complications. Appropriate preoperative preparation is important in patients with such tumors, as are early detection of respiratory and hemodynamic changes that may occur during surgery and correct perioperative treatment. Octreotide, a longer-lasting somatostatin analogue, has facilitated the handling of such cases.

[Impossibility of intubation due to angioedema secondary to an angiotensin-converting enzyme inhibitor]. / Imposibilidad de intubación por angioedema secundario a IECA.

Angioedema secondary to treatment of one year's duration with angiotensin converting enzyme inhibitor (ACEI) (lisinopril) in a 56-year-old man scheduled for elective cardiac surgery led unexpectedly to impossible intubation. Surgical access (tracheostomy) was required when airway control was threatened. We review the clinical course, etiology and treatment of angioedema secondary to ACEI therapy. This is a life threatening complication which, though rare, is becoming increasingly frequent with increased use of such drugs.