SPG7 mutational screening in spastic paraplegia patients supports a dominant effect for some mutations and a pathogenic role for p.A510V.

Mutations in the SPG7 gene were initially reported in patients with autosomal recessive hereditary spastic paraplegia (HSP). Recent works suggested a dominant effect for some SPG7 mutations. To characterize the SPG7 mutational spectrum in a large cohort of Spanish HSP patients, we sequenced the whole SPG7 gene in a total of 285 Spastic Paraplegia patients. Large gene rearrangements were also ascertained in some patients. We found a total of 14 SPG7 mutations (12 new) in 14 patients; 2 were large deletions. All the mutation carriers had an adult onset age but only five (35%) had a complicated phenotype. We identified a single mutation in 13 patients. Familial analysis suggested a dominant inheritance for one (p.Leu78*) of these mutations. Carriers of the rare p.A510V variant were significantly more frequent in patients vs healthy controls (3% vs 1%), suggesting a pathogenic role for this SPG7 variant. We reported a high frequency of patients with only one SPG7 mutation, and a putative pathogenic role for the p.A510V variant.

[Patient exposure to electromagnetic fields in magnetic resonance scanners: a review]. / Exposiciones a pacientes por campos electromagnéticos en equipos de imagen por r esonancia magnética. Revisión.

The use of non-ionizing electromagnetic fields in the low frequency end of the electromagnetic spectrum and static fields, radiofrequencies (RF), and microwaves is fundamental both in modern communication systems and in diagnostic medical imaging techniques like magnetic resonance imaging (MRI). The proliferation of these applications in recent decades has led to intense activity in developing regulations to guarantee their safety and to the establishment of guidelines and legal recommendations for the public, workers, and patients. In April 2012 it was foreseen that the European Parliament and Council would approve and publish a directive on the minimum health and safety requirements regarding the exposure of workers to the risks arising from electromagnetic fields, which would modify Directive 2004/40/EC. New studies related to the exposure to electromagnetic radiation and its impact on health published in recent years have led to a new postponement, and it is now foreseen that the directive will come into effect in October 2013. One of the most noteworthy aspects of the new version of the directive is the exclusion of the limits of occupational exposure to electromagnetic fields in the clinical use of MRI. In exchange for this exception, physicians and experts in protection against non-ionizing radiation are asked to make additional efforts to train workers exposed to non-ionizing radiation and to establish mechanisms to guarantee the correct application of non-ionizing electromagnetic fields in patients, along similar lines to the principles of justification and optimization established for ionizing radiation. On the basis of the most recently published studies, this article reviews some safety-related aspects to take into account when examining patients with MRI with high magnetic fields.

[Safe use of magnetic resonance imaging: practical recommendations for personnel]. / Utilización segura de la resonancia magnética. Recomendaciones prácticas para el personal que trabaja con resonancia magnética.

MRI is a powerful diagnostic imaging tool and its use has increased significantly in hospitals all over the world. Due to the technical particularities of MRI, all staff members dealing with the scanner need to have adequate knowledge of how it works and of aspects related to safety. The European parliament and council's directive on minimum health and safety requirements for workers dealing with electromagnetic fields (EMF) 2004/40/CE represents a threat to the clinical development and healthcare use of MRI. The efforts of the Alliance for MRI led to a postponement of the European parliament's decision, first until April 2012 and finally until October 2013. The purpose of this article is to define and propose a set of practical rules to ensure the protection of workers involved with MRI scanners. It also aims to define our position with respect to UE directive (2004/40/CE).

Toxicity of cadmium in musculoskeletal diseases.

Epidemiological studies have reported that exposure to toxic metals like cadmium (Cd) may promote the development of musculoskeletal diseases, such as osteoporosis, rheumatoid arthritis (RA), and osteoarthritis (OA), among others. The objective of this review is to summarize the molecular mechanisms of inflammation and oxidative stress activated by Cd at the bone level, particularly in osteoporosis, RA, and OA. Cadmium can increase bone resorption, affect the activity of osteoclasts and calcium (Ca) absorption, and impair kidney function, which favors the development of osteoporosis. In the case of RA, Cd interferes with the activity of antioxidant proteins, like superoxide dismutase (SOD) and catalase (CAT). It also promotes an inflammatory state, inducing the process of citrullination, which affects the proteins of immune response. On the other hand, accumulation of Cd in the tissues and blood of smokers has been related to the development of some musculoskeletal diseases. Therefore, knowing the negative impact of Cd toxicity at the articular level can help understand the damage mechanisms it produces, leading to the development of such diseases.

A research model--forecasting incident rates from optimized safety program intervention strategies.

UNLABELLED: INTRODUCTION/PROBLEM: Property damage incidents, workplace injuries, and safety programs designed to prevent them, are expensive aspects of doing business in contemporary industry. The National Safety Council (2002) estimated that workplace injuries cost $146.6 billion per year. Because companies are resource limited, optimizing intervention strategies to decrease incidents with less costly programs can contribute to improved productivity. METHOD: Systematic data collection methods were employed and the forecasting ability of a time-lag relationship between interventions and incident rates was studied using various statistical methods (an intervention is not expected to have an immediate nor infinitely lasting effect on the incident rate). RESULTS/SUMMARY: As a follow up to the initial work, researchers developed two models designed to forecast incident rates. One is based on past incident rate performance and the other on the configuration and level of effort applied to the safety and health program. Researchers compared actual incident performance to the prediction capability of each model over 18 months in the forestry operations at an electricity distribution company and found the models to allow accurate prediction of incident rates. IMPACT ON INDUSTRY: These models potentially have powerful implications as a business-planning tool for human resource allocation and for designing an optimized safety and health intervention program to minimize incidents. Depending on the mathematical relationship, one can determine what interventions, where and how much to apply them, and when to increase or reduce human resource input as determined by the forecasted performance.

Abnormal cochlea linked to deafness in transgenic mice expressing human cytokeratin K8.

The cytokeratin intermediate filaments have a relevant role in the proliferation and differentiation processes of epithelial cells. To provide information about the role of K8 cytokeratin during the auditory receptor differentiation, two groups of adult mice were used: TGK8-4 transgenic and control animals. The TGK8-4 transgenic mice contained 12 kb of K8 human cytokeratin (HK8) locus (Casanova et al., 1995, 1999). The functional activity of the auditory receptor was analyzed by auditory thresholds. Morphological studies demonstrate that the auditory receptors of the TGK8-4 transgenic mice are highly immature. Immunocytochemical studies were made by using two monoclonal antibodies: CAM 5-2 (recognizing K8 human cytokeratin) and Troma-1 (recognizing both mouse and human K8 cytokeratin). These demonstrated significant differences between the auditory receptors of the transgenic mice and the control mice. These functional and morphological differences clearly suggest that K8 cytokeratin has a relevant role during the differentiation and tridimensional organization of the sensory and the supporting cells of the auditory receptor.

Augmented thromboxane generation by mesenteric arteries from pancreatectomized diabetic dogs is coincident with the vascular tone enhancement evoked by Na arachidonate and prostacyclin.

We studied the relationships between arachidonic acid (AA) metabolism and contractile responses to Na arachidonate (NaA) and the prostaglandins (PGs) in mesenteric arteries isolated from sham-operated and totally pancreatectomized dogs. PGE2 and PGF2 alpha produced a similar dose-dependent relaxation of mesenteric arteries from normal and diabetic dogs. On the contrary, NaA and prostacyclin (PGI2) enhanced the resting basal tone of arteries from pancreatectomized animals but depressed it in arteries from intact normal control or from sham-operated groups. Inhibitors of thromboxane A2 (TXA2) biosynthesis abolished in vitro the vasoconstricting effect of NaA and PGI2 in diabetics whereas inhibitors of PGI2 biosynthesis blocked the vasodilating influence of NaA in normal mesenteric vessels. Additionally, antagonists of cyclooxygenase activity prevented both the vasoconstricting and the vasodilating actions of NaA in normal and in diabetic arteries, respectively, as well as the PGI2 tone enhancement in vessels from diabetics. In arteries from pancreatectomized animals treated with insulin, PGI2 induced a biphasic (constriction and relaxation) effect of a magnitude between that of effects seen in normal controls or sham-operated and those in untreated diabetic animals. The basal radioconversion of exogenous [1-14C]AA, showed that mesenteric arteries from diabetic dogs generated more TXB2 than did vessels from intact normal control or sham-operated dogs. Moreover, in the presence of exogenous PGI2, the vascular production of TXB2 from AA in the diabetic group was significantly greater than that of preparations not exposed to PGI2. The % conversion of AA into PGI2 (assessed as 6-oxo-PGF1 alpha) was similar in normal controls, in sham-operated and in diabetic vessels. Insulin given in vivo abolished the greater basal conversion of AA into TBX2 by mesenteric arteries from diabetic dogs and significantly attenuated the enhanced prostacyclin-evoked generation of thromboxane. The present results strongly suggest that the abnormal constricting response evoked by NaA and PGI2 in mesenteric arteries from diabetic dogs could be related to the generation of TXA2 by vessel walls.

13C-urea breath test for the diagnosis of Helicobacter pylori infection before treatment: is citric acid necessary?

AIM: 13C-urea breath test is one of the best methods for the diagnosis of Helicobacter pylori infection. Although a citric acid solution is generally used prior to urea intake, the superiority of this strategy has not been sufficiently demonstrated. Thus, our aim was to compare 13C-urea breath test with and without citric acid solution, to evaluate whether 13C-urea breath test can also achieve favourable results when the test meal is omitted. METHODS: 13C-urea breath test with and without citric acid were compared prospectively in 53 subjects without prior Helicobacter pylori eradication therapy prescription. Basal samples and at 15', 30', and 45' after taking 100 mg of 13C-urea were obtained. The gold standard for Helicobacter pylori diagnosis was the 13C-urea breath test result with citric acid at 30', and "Delta Over Baseline" values >5 at that time were considered positive. RESULTS: The prevalence of Helicobacter pylori infection was 68%. Mean Delta Over Baseline values with citric acid at 15', 30' and 45' were: 29.6+/-39, 30.8+/-37 and 24.6+/-27; whereas respective values without citric acid were lower: 14.9+/-22, 12.2+/-17 and 10D+/-13 (p

Transient congenital hypoparathyroidism and 22q11 deletion.

CATCH-22 syndrome represents a spectrum of abnormalities associated with microdeletions of chromosome 22q11. We report a patient with transient congenital hypoparathyroidism, with severe neonatal hypocalcemia and spontaneous resolution in infancy, tetralogy of Fallot and thymic hypoplasia. Genetic confirmation of chromosome 22q11 deletion was made. Newborns with congenital hypoparathyroidism need genetic analysis and examination for anomalies associated with CATCH-22 syndrome.

[Spontaneous mediastinal hemorrhage: a study of 2 cases]. / Hemorragia mediastínica espontánea: estudio de 2 casos.

The clinical symptoms of two cases of spontaneous mediastinal hemorrhage, a rare entity of unknown etiology, are presented. In both cases the evolution was acute with initial symptomatology similar to that observed in the upper caval vein syndrome. The appearance of a large hematoma in the cervical-thoracic region constituted the outstanding clinical symptom. Imaging techniques provided the second key to diagnosis, which was made following the exclusion of the other causes of bleeding in the mediastinum. Given the apparent stability of the lesion and the absence of hemodynamic changes, treatment should only be symptomatic.

[Olfactory esthesioneuroblastoma: scintigraphic expression of somatostatin receptors]. / Estesioneuroblastoma olfatorio: expresión gammagráfica de receptores de somatostatina.

Esthesioneuroblastoma is an uncommon tumor originating in the upper nasal cavity and constitutes 3% of all intranasal neoplasms. Few references exist about the expression of somatostatin receptors in these tumors. Our case demonstrates a good correlation between the somatostatin receptor scintigraphy and magnetic resonance imaging.

[Merkel cell carcinoma. Utility of scintigraphy with 111In-DTPA-pentetreotide]. / Carcinoma de células de Merkel. Utilidad de la gammagrafía con 111In-DTPA-pentetreotido.

Merkel cell carcinoma (MCC) is an unusual malignant primary skin tumor, having a high incidence of local recurrent, and regional and distant metastasis. Due to its capacity to express somatostatin receptors, it can be detected in vivo with 111In-pentetreotide scintigraphy (Ostreoscan). We present a case of a MCC whose scintigraphy revealed regional metastases of a primary frontal cutaneous tumor that had been removed previously. The results verified a good correlation with clinical, radiological an histopathological findings.

[Thrombophlebitis of the cavernous sinus secondary to polysinusitis. Report of a new case]. / Tromboflebitis del seno cavernoso secundaria a polisinusitis. Aportación de un nuevo caso.

Cavernous sinus thrombophlebitis syndrome is uncommon nowadays. Despite the wide range of antimicrobial agents it carries a high mortality. The disease frequently arises from infection of face, mouth, nose and paranasal sinuses, reaching the cavernous sinus by venous spread. Involvement of adjacent anatomic structures accounts for most of the clinical findings. Meningeal involvement, bilateral orbital edema and ocular cranial nerves palsy are very helpful in the differential diagnosis. Streptococcus spp., Staphylococcus spp., Haemophilus influenzae and anaerobic organisms are considered to be the most frequent etiological agents. In the present paper we report a case of cavernous sinus thrombophlebitis following left side polysinusitis. The patient presented with the main clinical features of the syndrome along with Streptococcus equisimilis and Fusobacterium necrophorum bacteremia. Urgent surgery of infected sinuses and appropriate antibiotic therapy led to a favorable outcome. The patient made and excellent progress and was discharged completely recovered two weeks after admission.

Hepatocytes display a compensatory survival response against cadmium toxicity by a mechanism mediated by EGFR and Src.

Although the liver is a cadmium-target organ, hepatocyte response involved in its toxicity is not yet elucidated. A link between this heavy metal treatment and Stat3 signaling pathways was examined in primary mouse hepatocytes. We provided evidence of a novel link among NADPH oxidase and Stat3 signaling, mediated by Src, EGFR, and Erk1/2. Cadmium activates NADPH oxidase. ROS produced by this oxidase activates Src, enable that in turn, transactivates EGFR that activates Stat3 in tyrosine, allowing its dimerization. Also, ROS from NADPH oxidase favors ERK1/2 activation that phosphorylates Stat3 in serine, resulting in a compensatory or adaptive survival response such as production of metallothionein-II in short Cd exposure times. However, after 12h CdCl2 treatment, cell viability diminished in 50%, accompanied by a drastic decrease of metallothionein-II production, and an increase in p53 activation and the pro-apoptotic protein Bax.