Recurrent Syncope due to Esophageal Squamous Cell Carcinoma

Syncope is caused by a wide variety of disorders. Recurrent syncope as a complication of malignancy is uncommon and may be difficult to diagnose and to treat. Primary neck carcinoma or metastases spreading in parapharyngeal and carotid spaces can involve the internal carotid artery and cause neurally mediated syncope with a clinical presentation like carotid sinus syndrome. We report the case of a 76-year-old man who suffered from recurrent syncope due to invasion of the right carotid sinus by metastases of a carcinoma of the esophagus, successfully treated by radiotherapy. In such cases, surgery, chemotherapy or radiotherapy can be performed. Because syncope may be an early sign of neck or cervical cancer, the diagnostic approach of syncope in patients with a past history of cancer should include the possibility of neck tumor recurrence or metastasis and an oncologic workout should be considered.     

Cytopathological and chemico‐physical analyses of smears of mucosa surrounding oral piercing

Oral Diseases (2010) 16 , 160–166 Objective: The aim of this comparative study was to analyze cytopathologically and chemico‐physically the mucosa surrounding oral piercing to correlate results with adverse tissue signs. Materials and methods: The tongue superficial mucosa of 15 young subjects (control group) and the superficial mucosa surrounding oral piercing of 15 young subjects (test group, TG) were smeared on slides, Papanicolaou stained and analyzed under the optical microscope. Some smears were prepared for (back‐scattered) scanning electron microscope (SEM) and X‐ray microanalysis to study piercing fragments. Results: Smears of TG displayed a variable extent of bacterial cytolysis of epithelial cells, fungi, hyperkeratosis, parakeratosis, granulocyte infiltration, calcium formations and bacterial flora; the four last statistically significant (P < 0.05). Foreign bodies surrounded by keratinocytes were detected under both light and SEM. X‐ray microanalyses highlighted piercing alloy aggression, ion release and an inverse gradient of ion concentration inside keratinocytes. Conclusions: The pathological findings in smears correlated with adverse effects of oral piercing. Ion release may be related to direct toxic effects and belated reactions because of metal sensitization. A strict regulation of piercing is warranted.     

Characterization of a novel SCN5A mutation associated with Brugada syndrome reveals involvement of DIIIS4-S5 linker in slow inactivation

OBJECTIVE: Mutations in SCN5A, the gene encoding the alpha-subunit of the cardiac sodium channel (Na(v)1.5), have been associated with various inherited arrhythmia syndromes, including Brugada syndrome (BrS). Here, we report the functional consequences of a novel missense SCN5A mutation, G1319V, identified in a BrS patient. The G1319V mutation is located in the loop connecting transmembrane segments 4 and 5 in domain III (DIIIS4-S5), a region so far considered to be exclusively involved in fast inactivation. METHODS: Whole-cell mutant (G1319V) and wild-type (WT) sodium currents (I(Na)) were studied in the Human Embryonic Kidney cell line (HEK-293) transfected with Na(v)1.5 alpha-subunit cDNA (WT or mutant) together with hbeta(1)-subunit cDNA, using the patch-clamp technique. RESULTS: Maximal peak I(Na) and persistent sodium current were similar in WT and channel G1319V channels. The G1319V mutation shifted the potential of half-maximal (V(1/2)) activation towards more positive potentials (+3.7 mV), thereby increasing the degree of depolarization required for activation. The V(1/2) of inactivation of G1319V channels was shifted by -6.0 mV compared to WT, resulting in a reduced channel availability. The change in the steady-state inactivation was completely due to a negative shift (-6.8 mV) of the voltage-dependence of slow inactivation, while the voltage-dependence of fast inactivation was unaffected. The fast component of recovery from inactivation of G1319V channels was slowed down. Finally, the G1319V mutation caused a two-fold increase in the propensity of the channels to enter the slow inactivated state. Reduction in I(Na) peak amplitude on repetitive depolarizations at short interpulse intervals (40 ms) was significantly more pronounced in G1319V compared to WT. Accordingly, carriers of the G1319V mutation showed marked QRS widening upon increases in heart rate during exercise testing, pointing to enhancement of slow inactivation. CONCLUSIONS: We identified the DIIIS4-S5 linker as a new region involved in slow inactivation of Na(v)1.5. The biophysical alterations of the G1319V mutation all contribute to a reduction in I(Na), in line with the proposed mechanism underlying BrS.     

Cell death and impairment of glucose-stimulated insulin secretion induced by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in the beta-cell line INS-1E

The aim of this research was to characterize 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) toxicity on the insulin-secreting beta-cell line INS-1E. A sharp decline of cell survival (below 20%) was observed after 1 h exposure to TCDD concentrations between 12.5 and 25 nM. Ultrastructurally, beta-cell death was characterized by extensive degranulation, appearance of autophagic vacuoles, and peripheral nuclear condensation. Cytotoxic concentrations of TCDD rapidly induced a dose-dependent increase in intracellular calcium concentration. Blocking calcium entry by EGTA significantly decreased TCDD cytotoxicity. TCDD was also able to rapidly induce mitochondrial depolarization. Interestingly, 1 h exposition of INS-1E cells to very low TCDD concentrations (0.05-1 nM) dramatically impaired glucose-stimulated but not KCl-stimulated insulin secretion. In conclusion, our results clearly show that TCDD exerts a direct beta-cell cytotoxic effect at concentrations of 15-25 nM, but also markedly impairs glucose-stimulated insulin secretion at concentrations 20 times lower than these. On the basis of this latter observation we suggest that pancreatic beta-cells could be considered a specific and sensitive target for dioxin toxicity.     

Localization of a glutathione-dependent dehydroascorbate reductase within the central nervous system of the rat

In this study, we describe for the first time the occurrence, within the central nervous system of the rat, of a dehydroascorbate reductase analogous to the one we recently described in the liver. Dehydroascorbate reductase plays a pivotal role in regenerating ascorbic acid from its oxidation product, dehydroascorbate. In a first set of experiments, we showed that a dehydroascorbate reductase activity is present in brain cytosol; immunoblotting analysis confirmed the presence of an immunoreactive cytosolic protein in selected brain areas. Immunotitration showed that approximately 65% of dehydroascorbate reductase activity of brain cytosol which was recovered in the ammonium sulphate fraction can be attributed to this enzyme. Using immunohistochemistry, we found that a variety of brain areas expresses the enzyme. Immunoreactivity was confined to the gray matter. Amongst the several brain regions, the cerebellum appears to be the most densely stained. The enzyme was also abundant in the hippocampus and the olfactory cortex. The lesion of norepinephrine terminals following systemic administration of DSP-4 markedly decreased immunoreactivity in the cerebellum. Apart from the possible co-localization of the enzyme with norepinephrine, the relative content of dehydroascorbate reductase in different brain regions might be crucial in conditioning regional sensitivity to free radical-induced brain damage. Given the scarcity of protective mechanisms demonstrated in the brain, the discovery of a new enzyme with antioxidant properties might represent a starting-point to increase our knowledge about the antioxidant mechanisms operating in several central nervous system disorders.     

Effect of ethanol chronic use on hepatotoxicity in rats exposed to tetrachloroethylene.

Tetrachloroethylene, an industrial halogenated solvent, shows several toxic effects. Also at hepatic level this substance can induce a damage but this effect is present only after high exposure, but such high levels have not been found in work environments. Using Wistar rats, we wanted to check whether the chronic administration of ethyl alcohol can modify the action of tetrachloroethylene. Tetrachloroethylene was administered by aerosol and alcohol at the concentration of 15% in drinking water. We observed an increase in plasma triglycerides, and evident histological alteration as a result of steatosis, in rats drinking alcohol as compared to a control group; the administration of tetrachloroethylene to rat drinkers of alcohol did not cause an increase in plasma triglycerides and steatosis as compared to rat drinkers of alcohol, but on the contrary we observed a decrease in alcohol-induced liver damage.     

Complementary medicine: use and attitudes among GPs

BACKGROUND: Information about use and attitudes of GPs towards complementary medicine is required in order to inform the debate about its place within mainstream medicine. There is evidence that public use of complementary medicine is particularly high in the South-West of England. OBJECTIVE: This study aimed to determine the use of, and attitudes towards, complementary medicine among GPs. METHODS: A questionnaire survey was performed of all primary care physicians working in the health service in Devon and Cornwall. RESULTS: Replies were received from 461 GPs, a response rate of 47%. A total of 314 GPs (68%, range 32-85%) had been involved in complementary medicine in some way during the previous week. One or other form of complementary medicine was practised by 74 of the respondents (16%), the two most common being homoeopathy (5.9%) and acupuncture (4.3%). In addition, 115 of the respondents (25%) had referred at least one patient to a complementary therapist in the previous week, and 253 (55%) had endorsed or recommended treatment with complementary medicine. Chiropractic, acupuncture and osteopathy were rated as the three most effective therapies, and the majority of respondents believed that these three therapies should be funded by the health service. A total of 176 (38%) of respondents reported adverse effects, most commonly after manipulation. CONCLUSION: Over two-thirds of the GPs in Devon and Cornwall who responded to the survey had been involved with complementary medicine in some way during the previous week. This figure is higher than the national average. The majority of respondents believed that acupuncture, chiropractic and osteopathy were effective and should be funded by the NHS.