[Acquired hemophilia A revealing lung cancer]. / Une hémophilie A acquise ayant révélé un cancer du poumon.

Acquired hemophilia A (AHA) is a rare disease, defined by the production of anti-factor VIII antibodies causing disordered hemostasis. It is idiopathic in 50% of cases, but sometimes associated with solid tumors. We report a case where AHA led to the diagnosis of lung cancer. CASE REPORT: An 82-year-old man with spontaneous hematomas on his trunk and extremities, and isolated prolongation of activated partial thromboplastin time was admitted to the emergency room. A severely reduced factor VIII level and a high factor VIII inhibitor title confirmed the diagnosis of AHA. Thoracic computed tomography scan found a suspect lung nodule and biopsy was consistent with a primary lung adenocarcinoma. The patient received recombinant factor VIII, immunosuppressive therapies, and finally lung stereotactic radiotherapy. Thirty months after diagnosis, the patient is in complete remission both from AHA and from his lung cancer. CONCLUSIONS: Acquired hemophilia A is a rare but potentially severe disease, which may be idiopathic or linked to a solid tumor. The severity of AHA depends on both the volume of hemorrhage and the presence of associated diseases.

Impact of a stewardship program on bacteraemia in adult inpatients.

OBJECTIVE: Bloodstream infections (BSIs) are associated with considerable morbidity and mortality among inpatients. The aim of this study was to evaluate the impact of a stewardship program on clinical and antimicrobial therapy-related outcomes in patients with bacteraemia. METHODS: Single-centre, before-and-after quasi-experimental study in adult inpatients. Over 1 January 2013 to 31 June 2013 all patients aged 18 years or older with a bacteraemia (interven-tion group, N=200) were compared to a historical cohort (1 Janu-ary 2012 to 31 December 2012) (control group, N=200). RESULTS: Following blood culture results and adjusting for potential confounders, the stewardship program was associated with more changes to antibiotic regimens (adjusted odds ratio [ORa]: 4.6, 95% CI 2.9, 7.4), more adjustments to antimicrobial therapy (ORa: 2.4, 95% CI 1.5, 3.8), and better source control in the first five days (ORa 1.6, 95% CI: 1.0, 2.7). In the subgroup that initially received inappropriate empiric treatment (n=138), the intervention was associated with more antibiotic changes (OR: 3.9, 95% CI: 1.8, 8.5) and a better choice of definitive antimicrobial therapy (OR 2.3 95% CI: 1.2, 4.6). There were also more antibiotic changes in the subgroups with both Gram-negative (OR: 2.8, 95% CI: 1.6, 4.9; n=217) and Gram-positive (OR: 4.6, 95% CI: 1.8, 9.9; n=135) bacteraemia among those receiving the intervention, while the Gram-positive subgroup also received more appropriate definitive antimicrobial therapy (OR: 3.9, 95% CI: 1.8, 8.8). CONCLUSIONS: The stewardship program improved treatment of patients with bacteraemia and appropriateness of therapy.

Implementation and assessment of a fast-track programme to improve communication between primary and specialized care in patients with suspected cancer: how to shorten time between initial symptoms of cancer, diagnosis and initiation of treatment.

PURPOSE: This study aims to asses a cancer fast-track programme (CFP) to shorten the time since a patient with suspicion of cancer is referred by the primary care (PC) physician to the specialized medical team. METHODS: Guidelines for main suspected tumours were designed to help PC physicians to detect and rapidly refer cases to the CFP oncology coordinator, who sent them to the appropriate department to accelerate diagnosis, staging and therapy. All patients analysed in this report were referred from June 2009 to July 2012. RESULTS: A total of 897 suspected cancer cases were submitted and finally 705 were studied. In 205 (29 %) a cancer diagnosis was confirmed within 23 days (median). Therapy was initiated within 46 days after referral (median). Early diagnoses with a potential curative approach were made in 166 (82 %). CONCLUSIONS: This CFP decreased the waiting time for cancer diagnosis, by improving communication between PC physician and specialized care teams. Most patients included in this program could get therapy with curative intent.

[Emergent drugs (III): hallucinogenic plants and mushrooms]. / Drogas emergentes (III): plantas y hongos alucinógenos.

An increase in the consumption of vegetable substances with a hallucinogenic effect has been observed. Some of these substances are associated with ancestral religious ceremonies, while many of them are legal or are partially regulated. Salvia divinorum is a powerful kappa receptor agonist, with dissociative and hallucinogenic properties, which start quickly and have a short duration. Kratom (Mytragyna speciosa) has mitragynine as its principal alkaloid, with stimulating effects at low doses (coke-like effect), and sedative effects (opiate-like effect) at high doses. Several deaths from its consumption have been detected. The consumption of hallucinogenic mushrooms appears in cyclic form, although there has been increase in their online offer. They are consumed in search of their hallucinogenic effects, above all those belonging to the family of psilocybes, which contain tryptamines with a hallucinogenic effect similar to LSD. Peyote (Lophophora psilocybes), a cactus rich in mescaline (trimetoxifeniletilamina), produces hallucinations of the five senses, and forms part of the religious culture of the North American Indians. Daturas, which are ubiquitous, produce anticholinergic symptoms and effects on the central nervous system (delirium, hallucinations, etc.), due to their high atropine and scopolamine content. Other substances used for their hallucinogenic effects include the drink known as ayahuasca, and seeds for preparing infusions like Ololiuqui, Morning Glory (Ipomoea violacea), Hawaian Baby Woodrose (Argyreia nervosa), Syrian Rue (Peganum harmala) and Iboga Rootbark (Tabernanthe iboga).

Mapping the core of the Arabidopsis circadian clock defines the network structure of the oscillator.

In many organisms, the circadian clock is composed of functionally coupled morning and evening oscillators. In Arabidopsis, oscillator coupling relies on a core loop in which the evening oscillator component TIMING OF CAB EXPRESSION 1 (TOC1) was proposed to activate a subset of morning-expressed oscillator genes. Here, we show that TOC1 does not function as an activator but rather as a general repressor of oscillator gene expression. Repression occurs through TOC1 rhythmic association to the promoters of the oscillator genes. Hormone-dependent induction of TOC1 and analysis of RNA interference plants show that TOC1 prevents the activation of morning-expressed genes at night. Our study overturns the prevailing model of the Arabidopsis circadian clock, showing that the morning and evening oscillator loops are connected through the repressing activity of TOC1.

[Emergent drugs (I): smart drugs]. / Drogas emergentes (I): las "smart drugs"

In recent years, a series of new drugs, known as smart drugs or legal highs, have gaining in popularity. They are easily obtainable through online shops. This is happening amongst younger segments of the population and is associated with recreational consumption, at weekends. In general, they are synthetic derivatives of natural products. There has been hardly any clinical research into them and they are not detectable in hospital laboratories. Three of these products, BZP (1- benzylpiperazine), mefedrone (4-methylmethcathinone) and Spice are probably the most widely used in Europe. The first two are consumed as an alternative to ecstasy and cocaine and are characterized by their producing a clinical profile of a sympathetic mimetic type; on occasion, they have serious consequences, with convulsions and even death. Spice (a mixture of herbs with synthetic cannabinoids such as JWH-018, JWH-073 and CP 47497-C8) is giving rise to profiles of dependence and schizophrenia. Although the emergent drugs have an aura of safety, there is an increasing amount of experience on their secondary effects.

Pharmacokinetic monitoring of antiepileptic drugs.

Monitoring plasma levels of antiepileptic drugs for the treatment and prophylaxis of epilepsy is one of the strategies enabling clinical results to improve by reducing adverse affects and increasing effectiveness. The objective of this article is to review the basic aspects in the monitoring of antiepileptic drugs using a consensus document prepared and endorsed by the pharmacokinetics and pharmacogenetics working group (PK.gen) of the Sociedad Española de Farmacia Hospitalaria (Spanish Society of Hospital Pharmacists).

Double-balloon enteroscopy: a descriptive study of 50 explorations.

AIM: To evaluate the utility of double-balloon enteroscopy for small-bowel disease. DESIGN: A prospective study of 50 consecutive enteroscopies performed from December 2004 to July 2005 to analyze diagnoses and treatments. PATIENTS: 44 patients (33 had undergone a previous capsule endoscopy) with indications for obscure digestive hemorrhage, angiodysplasia, Peutz-Jeghers syndrome, ulcer, suspected Crohn's disease, tumors, and refractory celiac disease. RESULTS: We carried out enteroscopy studies in 44 patients by the oral route and, in 6 additional patients, by both the oral and anal routes. We reached the ileon with the oral route in all cases but one (jejunal stenosis), and in 4 cases out of 7 with the anal route, with an average duration of 73 minutes. We found angiodysplasia in 19 cases, as well as NSAID-related enteropathy, Crohn's disease, diverticulosis, and Waldenström's disease. We performed biopsies in 31% of cases with diagnoses of adenocarcinoma, lymphangiectasia secondary to tumor in celiac disease, and Whipple's disease. We treated 19 patients with angiodysplasia (1 to 20 synchronous lesions) with argon, and 4 patients with polyps using polipectomy (sporadic polyps or Peutz-Jeghers syndrome). A retained capsule in one patient with stenosis was removed. CONCLUSIONS: Double-balloon enteroscopy is a useful and effective technique in the diagnosis and treatment of small intestine diseases, thus complementing capsule endoscopy. More studies are needed to analyze its impact on the management of this condition.

A shortened, 2-hour rifampin test: a useful tool in Gilbert's syndrome.

INTRODUCTION: Diagnosis of Gilbert's disease often involves unnecessary testing and patient anxiety. Rifampin test can support the diagnosis; it has been described in short series and lacks standardization in dose, collection times, result presentation and interpretation. Our objective was to compare the response to oral rifampin in a series of patients with Gilbert's disease, 2 and 4 h after drug administration. PATIENTS AND METHODS: Eighty-nine patients with Gilbert's disease (elevated total bilirubin with no hepatopathy or hemolysis) were recruited. After a basal blood collection, 900 mg rifampin were administered per os and new samples were drawn 2 and 4 h later. Total and esterified bilirubin were measured in every sample. Haptoglobin concentration was also analyzed. RESULTS: When expressed as relative increase with respect to basal values, variations observed 2 h after rifampin intake were all above 15%. A significant correlation (r = 0.902; p = 0.000) was found between relative increases 2 and 4 h after drug administration. No significant variations were found in haptoglobin concentrations. CONCLUSION: Rifampin test is useful in diagnosing Gilbert's disease, but variations in total bilirubin concentrations (basal and post-rifampin) make that no absolute cut-off value can be used. Correlation between 2- and 4-h relative increases suggests that a shortened version could simplify the test.

[Translation and adaptation in the Spanish environment of the Altman Self-Rating Mania Scale]. / Traducción y adaptación de la Altman Self-Rating Mania Scale al ámbito español.

INTRODUCTION: The aim of the present study is the translation, adaptation and validation in the Spanish environment of a self-rating of mania scale, the Altman Self-Rating Scale for Mania (ASRM), to fulfill a need in our environment in the self-rating of mania. METHODS: The scale was translated, and then a back translation was done. This was sent to the author of the original scale. The scale was administered to a sample of 74 patients with bipolar disorder, divided into two groups, one formed by patients with acute mania (n=35) and the other one constituted by asymptomatic patients (n=39). Concurrently we applied the Clinician Administered Rating Scale for Mania (CARS-M) and the Numeric Evaluation Scale (NES). RESULTS: High internal consistency, high and significant correlation with the CARS-M mania sub-scale, as well as with the NES and very significant differences between the two groups in the scale score were found. The ROC curve indicates excellent adjustment of the scale, when discriminating among bipolar patients with and without manic symptoms. The factorial analysis provided a single factor that accounts for 62% of the total variance. CONCLUSIONS: The Altman Self-Rating Mania Scale is shown to be a reliable and valid self-rating instrument to assess the presence and intensity of manic symptoms. It makes it possible to carry out simple and quick assessments of the patient's state, can be used for research as clinical objectives and can also be a screening instrument.

Norfloxacin decreases bacterial adherence of quinolone-resistant strains of Escherichia coli isolated from patients with cirrhosis.

BACKGROUND: Long-term administration of norfloxacin is recommended for secondary prophylaxis of spontaneous bacterial peritonitis in cirrhosis, but it may be associated with the development of quinolone-resistant bacteria in stools. However, these bacteria rarely cause infections. AIM: To assess bacterial adherence of either quinolone-sensitive or -resistant Escherichia coli obtained from stools of cirrhotic patients, as one of the main virulence factors, and its variations when sub-minimum inhibitory concentration of norfloxacin were added to the medium. METHODS: E. coli strains were co-cultured with oral epithelial cells obtained from patients in presence/absence of norfloxacin. Bacterial adherence was measured as percentage of cells exhibiting positive adherence and the number of bacteria attached to epithelial cells. RESULTS: 37 sensitive and 22 resistant E. coli strains were studied. Bacterial adherence was similar in both series (78% vs. 81%, P = N.S.), and these percentages were similarly and significantly reduced when subminimum inhibitory concentration of norfloxacin was added to the culture medium (P < 0.001). CONCLUSIONS: Bacterial adherence of E. coli obtained from patients with cirrhosis is unrelated to the sensitivity/resistance to quinolones, and is similarly reduced in both cases when subminimum inhibitory concentration of norfloxacin is added to the medium.

Molecular characterization of a cryptic 2q37 deletion in a patient with Albright hereditary osteodystrophy-like phenotype.

The Albright hereditary osteodystrophy-like (AHO-like) syndrome was recently defined as a rare dysmorphic syndrome including brachymetaphalangism and mental retardation. This phenotype occurs in Albright hereditary osteodystrophy (AHO) but unlike it, the level of the Gs alpha protein activity is not reduced. To date 59 patients with these clinical and biochemical features have been reported, and for the majority of them (57/59) a cytogenetically visible 2q37 deletion has been observed. We report a new case of typical AHO-like syndrome with normal karyotype. Using the polymorphic marker D2S125 we found a loss of heterozygosity suggestive of a de novo 2q37 deletion of maternal origin. This hypothesis was confirmed by FISH analysis with a subtelomeric 2q probe containing the D2S90 marker. Genotypic analysis allowed us to map the proximal breakpoint of the subtelomeric deletion within an interval delimited by D2S2338 (present) and D2S2253 (deleted). This 2q subtelomeric deletion as small as 4 Mb is to date the smallest one observed in association with a typical AHO-like phenotype, and allows us to move the centromeric boundary of the AHO-like critical region by 750 kb towards the 2q telomere.

Treatment response in relation to inflammatory and axonal surrogate marker in multiple sclerosis.

BACKGROUND: This study aimed to investigate if treatment response could retrospectively be related to inflammatory or axonal pathology as measured by plasma surrogate markers. METHODS: In this 1-year observational study 30 multiple sclerosis (MS) patients with relapsing-remitting disease were treated with intramuscular IFNbeta-1a or subcutaneous IFNbeta-1b. Responders and nonresponders were defined according to clinical and magnetic resonance imaging criteria. The control group consisted of 14 healthy subjects. Plasma levels of surrogate markers for inflammation (nitric oxide metabolites (NOx)), astrocytic activation (S100B) and axonal damage (NfH(SM135)) were measured using standard assays. RESULTS: There were 11 nonresponders and 19 responders to IFNbeta treatment. Median S100B levels were elevated in a higher proportion of treatment responders (63%, 42.9 pg/mL) compared to nonresponders (18%, 11.7 pg/mL, P < 0.05, Fisher's exact test) and controls (0%, 2 pg/mL, P < 0.001). Levels of NOx were found to be more frequently elevated in nonresponders (72%, 39 microM) compared to healthy controls (0%, 37 microM, P < 0.05). Levels of NfH(SM135) were more frequently elevated in responders (58%, 300 pg/mL, P < 0.001) and nonresponders (72%, 500 pg/mL, P < 0.001) compared to controls (0%, 4.5 pg/mL). CONCLUSION: Patients with relapsing-remitting MS who had surrogate marker supported evidence for astrocytic activation responded more frequently to treatment with IFNbeta.

Respiratory diseases in French cork workers.

A cross-sectional study on suberosis was conducted in the Champagne-Ardenne County, France, to determine the prevalence of respiratory symptoms, the level of pulmonary function, and the presence of precipitins against Penicillium frequentans. Thirteen of the 33 workers exposed to cork dust had respiratory symptoms excluding hypersensitivity pneumonitis. The respiratory symptoms were not correlated with tobacco habits or duration of exposure. The levels of pulmonary function were not significantly impaired. No precipitin arc against Penicillium frequentans was found in the sera of exposed workers. The varied symptomatology of suberosis may point to several different diseases, each with its own determining factor. In the present study, exposure to weak humidity and low level of cork dust were related to asthma and chronic bronchitis only, excluding hypersensitivity pneumonitis.