Capillary malformation-arteriovenous malformation syndrome: a multicentre study.

BACKGROUND: Capillary malformation-arteriovenous malformation (CM-AVM) syndrome is a rare syndrome with characteristic skin lesions that are associated with fast-flow vascular malformations (FFVMs) in one-third of patients. Few case series have been described, and none in Spain. AIM: To identify the prevalence of dermatological parameters, FFVMs and associated features in a large series of patients with CM-AVM. METHODS: We conducted an observational study of patients with CM-AVM syndrome diagnosed in 15 Spanish hospitals over 3 years. The main clinical, radiological, genetic findings and associated diseases were analysed. RESULTS: In total, 64 patients were assessed. In 26.5% of cases, the diagnosis was incidental. In 75% of patients, there was one significantly larger macule, which we termed the 'herald patch'. FFVMs were detected in 34% of the patients, with 30% located on the skin, 7.8% in the brain and in 1.5% in the spine. There was a positive family history in 65% of the 64 patients. Genetic analysis was performed for RASA1 mutations in 57 patients, of whom 42 (73%) had a positive result. All 4 patients tested for EPHB4 mutations had a positive result. No tumour lesions were detected in the series, except for five infantile haemangiomas. CONCLUSIONS: Our data on clinical lesions, associated FFVM, family history and genetics are similar to those previously published in the literature. An extensive data analysis failed to demonstrate any statistically significant association between the presence of an FFVM and any clinical, familial or genetic parameter that could predict its onset, although a link between the presence of a herald patch on the midline face and the presence of a brain FFVM was observed. We did not detect any genotype-phenotype correlation.

Sturge-Weber Syndrome: A Review. / Síndrome de Sturge-Weber: revisión.

Sturge-Weber syndrome is a sporadic congenital neurocutaneous disorder caused by a somatic activating mutation in GNAQ; it affects 1 in every 20,000 to 50,000 newborns. It is characterized by a facial Port-wine stain, leptomeningeal angiomatosis, and glaucoma. Seizures are the most common neurological manifestation and typically present in the first months of life. Glaucoma may be present at birth or develop later. Neuroimaging studies show leptomeningeal angiomatosis, supporting diagnosis. Standard treatment for Sturge-Weber syndrome includes laser treatment for the Port-wine stain, anticonvulsants, and medical or surgical treatment for the glaucoma. Prognosis depends on the extent of leptomeningeal involvement and the severity of the glaucoma.

Capillary malformation-arteriovenous malformation syndrome: a report of 2 cases, diagnostic criteria, and management.

Capillary malformation-arteriovenous malformation syndrome is a rare type of vascular malformation first described in 2003. It is an autosomal dominant inherited disorder that has been reported in association with heterozygous mutations in the RASA1 gene, which encodes the protein RASp21. The clinical picture is characterized by multiple small capillary malformations which are associated with either arteriovenous malformations or arteriovenous fistulas in both the affected individual and other members of their family. We describe 2 new familial cases of this syndrome that were clinically and genetically diagnosed and studied in our hospital.

Unmet needs in patients with moderate-to-severe plaque psoriasis treated with methotrexate in real world practice: FirST study.

BACKGROUND: Methotrexate (MTX) is frequently used in the treatment of moderate-to-severe psoriasis, however, there is limited data on health-related quality-of-life (HRQoL), psoriasis clinical outcomes and hepatic fibrosis in MTX-treated patients in routine clinical practice. OBJECTIVES: To investigate the impact of moderate-to-severe psoriasis in MTX-treated patients in Spain regarding to HRQoL, psoriasis clinical data and risk of hepatic fibrosis. METHODS: Observational, non-interventional, cross-sectional, retrospective, multicentre study, performed in Spain in moderate-to-severe plaque psoriasis patients treated with MTX > 16 weeks prior to inclusion. RESULTS: Despite ongoing treatment, 17.1% of 457 evaluable patients reported moderate-to-extreme impact on HRQoL (DLQI > 5); 21.4% BSA > 5 and 35.2% moderate-to-severe pruritus (VAS ≥ 4). Persistent severe psoriasis (PASI ≥ 10 and/or DLQI ≥ 10) was observed in 10.7%. Hepatic steatosis was identified in 64.1% of patients (HSI ≥ 36) and 37.2% of the patients were at-risk of advanced fibrosis which was associated to the MTX treatment duration. CONCLUSIONS: The study identified unmet needs in moderate-to-severe plaque psoriasis patients treated with MTX, revealing a significant proportion of sub-optimally controlled patients in terms of HRQoL and different domains of the disease. This study also found patients at-risk of advanced fibrosis, with evidence suggesting a correlation between longer exposures to MTX and higher risk of advanced fibrosis.

Low serological positivity in patients with histology compatible with celiac disease in Perú.

OBJECTIVE: To study the frequency of positive serology for celiac disease (CD) in patients with duodenal biopsies suggestive of this disease. MATERIAL AND METHODS: Cross sectional study. We included patients with duodenal biopsies histologically compatible with CD and antigliadin, antiendomysial and IgA antitransglutaminase antibodies. We defined a "case" of CD if there was a positive biopsy and either antiendomisial or antitransglutaminase positive antibodies. RESULTS: Thirty one patients were included in our study. Six were antiendomysial positive and 5 antitransglutaminase positive while the antigliadin was positive in 14 cases. Therefore, out of 31 patients only 10 had a serology compatible with CD and only one had positive both antibodies, antiendomysial and antitransglutaminase. CONCLUSIONS: a) We have found that most of the duodenal biopsies compatible with CD are not diagnosed with positive serology; and b) we found a low correlation between serological diagnostic tests.

Bone density and fragility fractures in patients with developmental disabilities.

UNLABELLED: We investigated prior fractures, osteoporosis risk factors, and bone mineral density (BMD) in 107 institutionalized adults with developmental disabilities. We found a very high prevalence of BMD in the osteoporotic range and a significant correlation between lower BMD and prior fragility fractures. INTRODUCTION: The purpose of this study was to investigate factors contributing to osteoporosis and fragility fractures among developmentally disabled adults. METHODS: Adults from a residential center participated in a prospective study in which bone mineral density (BMD) at the forearm and heel were measured with a portable X-ray densitometer. Prior fragility fractures were identified from chart review. RESULTS: Among 107 participants, 84 (78.5%) had a measurement within the osteoporotic range. The heel was more severely abnormal (mean T-score -3.1 +/- 1.5) than the forearm (-1.6 +/- 1.3, p < .0.0001). Radiographically confirmed prior fragility fractures (17 [16.3%]) were associated with lower heel (p = 0.0155) and forearm (p = 0.0172) T-scores. In multiple regression analysis, there were independent associations between forearm BMD and prior fragility fractures (p = 0.0126) and between heel BMD and prior fragility fractures (p = 0.0291). The odds ratio for prior fracture increased by 2.02 (95% CI 1.12-3.64) for each standard deviation (SD) decrease in heel T-score and by 2.39 (95% CI 1.08-5.32) for each SD decrease in forearm T-score. CONCLUSIONS: We found a very high prevalence of osteoporotic BMD measurements in institutionalized adults with developmental disabilities. Lower heel and forearm BMD measurements were significantly and independently associated with prior fragility fractures in this population.

Efalizumab treatment of psoriasis vulgaris: a cohort study in outpatient clinical practice.

BACKGROUND: Efalizumab is approved by the European Medicines Evaluation Agency for the treatment of adult patients with moderate to severe plaque psoriasis who fail to respond to, have a contraindication for, or cannot tolerate other systemic therapies. OBJECTIVES: To evaluate the efficacy and safety of efalizumab treatment in daily practice at a dermatology department in a teaching hospital in Barcelona, Spain. METHODS: A cohort study was carried out for patients treated with efalizumab for at least 3 months between May 2005 and July 2007. In total, 31 patients [21 men, 10 women; mean psoriasis and severity index (PASI) 12.9] were treated with efalizumab. Data were collected prospectively, including PASI, and recorded at the start of treatment and at follow-up visits with a frequency of at least every 3 months. RESULTS: At the end of the study period, efalizumab treatment was ongoing in 18 of the 31 patients (58.1%), and 7 of these patients had been treated for > or = 24 months. At week 12, 67.7% of the patients treated with efalizumab had achieved an improvement of 50% in PASI (PASI 50), 41.9% reached PASI 75, and 16.1% reached PASI 90 (intention to treat and as-treated analyses). In all, 19 patients (61.3%) received treatment for > or = 24 weeks. At week 24, 89.5% of these patients reached PASI 75, and 26.3% reached PASI 90 (as-treated analysis). During efalizumab treatment, mainly mild adverse effects were reported, including transient papular or circinate exacerbations of psoriasis, which were seen in five patients (16.1%). Rebounds (defined as PASI > or = 125% of baseline, leading to erythroderma in two patients) occurred in 7/31 patients (22.6%); this occurred while on treatment in 5/11 nonresponding patients (45.5%) and after discontinuation of treatment in 2/20 patients with good response (10.0%). CONCLUSION: Efalizumab is an effective and safe treatment for psoriasis in most patients of a high need population in routine practice, and provides maintained improvement in 'responders'. Combination treatment was transiently used in 48.4% of patients to optimize therapeutic results. Special consideration must be given to possible rebound in patients with an inadequate response or after discontinuation of treatment.

Tellurium causes dose-dependent coordinate down-regulation of myelin gene expression.

Exposure of developing rats to a diet containing elemental tellurium systemically inhibits cholesterol synthesis at the level of squalene epoxidase. At high tellurium exposure levels (> 0.1% in the diet), there is an associated segmental demyelination of the PNS. Low levels of dietary tellurium (0.0001%) led to in vivo inhibition of squalene epoxidase activity in sciatic nerve, and inhibition increased with increasing exposure levels. With increasing dose and increasing exposure times, there was an increasing degree of demyelination and increasing down-regulation of mRNA levels for myelin P0 protein, ceramide galactosyltransferase (rate-limiting enzyme in cerebroside synthesis), and HMG-CoA reductase (rate-limiting enzyme in cholesterol synthesis). Because these were all down-regulated in parallel, we conclude there is coordinate regulation of the entire program for myelin synthesis in Schwann cells. An anomaly was that at early time points and low tellurium levels, mRNA levels for HMG-CoA reductase were slightly elevated, presumably in response to tellurium-induced sterol deficits. We suggest the eventual down-regulation relates to a separate mechanism by which Schwann cells regulate cholesterol synthesis, related to the need for coordinate synthesis of myelin components. Levels of mRNA for the low-affinity nerve growth factor receptor (indicator of alterations in axon-Schwann cell interactions) and for lysozyme (marker for phagocytic macrophages) were both up-regulated in a dose- and time-dependent manner which correlated with the presence of segmental demyelination. Levels of mRNA coding for myelin-related proteins were down-regulated at low tellurium exposure levels, without demyelination or up-regulation of nerve growth factor receptor. This suggests the down-regulation is related to the tellurium-induced cholesterol deficit, and not to the loss of axonal contact associated with early stages of demyelination or to the entry of activated macrophages.

Changes in antibiotic sensitivity patterns of Gram-negative bacilli in burns.

Sensitivity tests with 12 antibiotics on 1,018 strains of Gram-negative bacilli isolated in a burns unit between 1969 and 1971 showed some important differences from results in similar tests on a series of strains isolated between 1965 and 1967. These changes included the emergence of a large proportion of kanamycin-resistant strains of Klebsiella aerogenes, Proteus mirabilis, and Escherichia coli and of smaller proportions of trimethoprim- and gentamicin-resistant strains; also the complete replacement of Proteus mirabilis with dissociated resistance to ampicillin by strains showing linked resistance to ampicillin and carbenicillin. The probable relationship of these changes to the emergence of an R factor determining resistance to tetracycline, kanamycin, carbenicillin, ampicillin, and cephaloridine in Enterobacteria and Pseudomonas aeruginosa is discussed.

The effects of erythromycin on theophylline elimination in normal males.

The effects of three erythromycin preparations on theophylline elimination kinetics were examined in 23 male subjects. Subjects received 6 mg/kg of the theophylline elixir orally and elimination kinetics were determined. The population was then randomized to receive either a lactose placebo, erythromycin base, erythromycin stearate, or erythromycin ethylsuccinate. Each 250-mg preparation was given four times a day for six days. On day seven, a repeat kinetic study was performed. The mean theophylline half-life of controls was 7.8 +/- 2.6 hours. The half-life increased significantly in all erythromycin treatment groups. The increase for the base, stearate, and ethylsuccinate groups was 51.7, 21.3, and 60.3 per cent, respectively. The total body theophylline clearance decreased significantly in all treatment groups. This was not associated with biochemical evidence of hepatitis. Three of four smokers who received erythromycin manifested no increase in theophylline half-life, in contrast to one of 13 nonsmokers. There was no difference in the percentage theophylline bound to serum protein for any of the erythromycin treatment groups or controls as determined by ultracentrifugation.

Vaccination against 77 capsular types of Klebsiella aerogenes with polyvalent Klebsiella vaccines.

A method is described for producing monovalent and polyvalent vaccines from culture filtrates of Klebsiella aerogenes. With a single injection, each monovalent vaccine protected mice against lethal intraperitoneal challenge by more than 30 capsular types; and polyvalent vaccines containing 2-12 monovalent components protected against 46-61 of the 77 capsular types of K. aerogenes. One vaccine with 12 components, administered in two doses, induced full protection against 71 types and protected half of the mice challenged with the other six types.

A new polyvalent Pseudomonas vaccine.

This paper describes the preparation, chemical characterisation and immunogenic properties of a new polyvalent pseudomonas vaccine. New cultural methods were devised which allowed a build-up of the immunogen in the cell wall of the bacteria, and mild extraction techniques were used to remove the immunogens from the cell wall of living bacteria without apparent physical or chemical change which might affect immunogenicity. The polyvalent vaccine comprised 16 component vaccines, each a lipid-protein-carbohydrate complex extracted from one of the 16 different serotypes of Pseudomonas aeruginosa. Single injections into mice of each of the 16 component vaccines induced protection against several strains of homologous serotypes within 3 days of vaccination. The polyvalent vaccine induced similar protection against several strains of each of the 16 serotypes. We would like to thank R. E. Dyster, K. Digby and J. Simmonds for their technical assistance.

Characterisation of mouse monoclonal antibodies produced by immunisation with a single serotype component of a polyvalent Pseudomonas aeruginosa vaccine.

Mouse monoclonal antibodies raised by immunisation with a protective antigen extract from Pseudomonas aeruginosa serotype 1 varied in immunoglobulin isotype, in passive protective properties against infection by homologous P. aeruginosa serotype 1, and in cross-reactions in ELISA against antigen preparations from 15 other P. aeruginosa serotypes. All monoclonal antibodies with specificity in ELISA for the immunising antigen gave some degree of protection to mice against lethal infection by the homologous P. aeruginosa serotype. The IgG antibodies were more protective than the IgM antibodies.

Timing of maintenance phenytoin therapy after intravenous loading dose.

The specific timing of maintenance phenytoin therapy in children has not been addressed. Prevention of a subtherapeutic phenytoin level is important for seizure control. We devised a protocol using an 18 mg/kg loading dose of phenytoin with serial levels (obtained after 2,6,12 hours) and analyzed the results in 20 consecutive patients. A therapeutic level (greater than 10 micrograms/ml) was present in all patients at 2 hours, in 16 of 20 at 6 hours, and in 10 of 20 at 12 hours. The patients were divided into 2 groups by the 12-hour levels: group I: therapeutic level; and group II: subtherapeutic level. The mean 2-hour level in group I was 22.7 micrograms/ml versus 15.6 micrograms/ml in group II (P less than 0.001). The mean decline in plasma concentration in individual patients was 0.7 micrograms/ml/hr in group I versus 1.02 micrograms/ml/hr in group II (P less than 0.05). We now use the 2-hour level to decide the timing of maintenance phenytoin therapy and have devised an equation to estimate the duration of the therapeutic range. Phenytoin can be administered at 12 hours when the 2-hour level is satisfactory or earlier when the 2-hour level indicates that a subtherapeutic level will occur.

Blind nasotracheal intubation in the presence of facial trauma.

Blind nasotracheal intubation (BNTI) is an effective procedure for the intubation of trauma patients. The presence of major facial trauma has been considered a relative contraindication due to the perceived risk of intracranial placement. The purpose of the present study was to assess the risk of intracranial placement in patients with facial fractures who undergo BNTI. The records of 311 patients with facial fractures were reviewed for methods of intubation and complications. Eighty-two patients underwent BNTI. There were no cases of intracranial placement, significant epistaxis requiring nasal packing, esophageal intubation, or osteomyelitis. Three patients (4%) developed sinusitis and eight (10%) developed aspiration pneumonia. We conclude that the presence of facial trauma does not appear to be a contraindication to BNTI.