The effects of cisapride on gastric and oesophageal emptying in dystrophia myotonica

The effects of cisapride on gastric emptying, oesophageal emptying, and gastrointestinal symptoms were evaluated in 10 patients with dystrophia myotonica who had delayed gastric emptying of the solid and/or liquid component of a meal. A double isotope technique was used to measure gastric emptying and oesophageal emptying was measured as the time taken for a bolus of the solid meal to enter the stomach. Gastrointestinal symptoms were assessed by a questionnaire. Gastric and oesophageal emptying and gastrointestinal symptoms were measured before and when each subject had taken cisapride (10 mg, q.i.d., p.o.) for 4 weeks. Cisapride improved solid gastric emptying, and there was a non-significant trend for improved liquid emptying. Cisapride had no effect on oesophageal emptying. Upper gastrointestinal symptoms were less after cisapride and there was an increased frequency of bowel actions. No side effects were reported. These results indicate that gastroparesis is a treatable cause of morbidity in dystrophia myotonica.     

Permanent Atrial Pacing in Cardiac Transplant Patients

Thirteen out of 223 consecutive cardiac transplant patients required permanent pacemaker implantation; 11 for sinus node dysfunction and 2 for complete AV block. Patients with sinus node dysfunction were considered for AAIB mode pacemakers if they had intact AV conduction defined as a Wenckebach point of > 120 beats/min. Ten of 11 patients with sinus node dysfunction had a single atrial lead placed. Atrial lead placement was most easily accomplished with a straight, active fixation lead and the use of manually curved stylets to find an optimal position in the donor atrium, although active fixation leads with a preformed atrial J were used as well. Two leads dislodged requiring revision. In contrast, only 1 of 250 atrial leads implanted in nontranspianted hearts dislodged (P < 0.0001). Transvenous endomyocardial biopsies have not caused atrial lead dislodgment. Most transplant recipients requiring permanent pacing have intact AV nodal function and require only atrial pacing. Atrial lead dislodgment requiring lead revision occurs more frequently in heart transplant recipients than in native hearts. Use of a straight active fixation lead with a munually formed curve in the stylet is useful in order to find the optimal position for pacing.     

Erythromycin resistant propionibacteria in antibiotic treated acne patients: association with therapeutic failure

Erythromycin resistant (EmR) propionibacteria were isolated from the skin surface of 51% of patients treated with oral erythromycin and 42% of patients treated with topical clindamycin compared with 3% of untreated control subjects (P less than 0.001). Amongst the topical clindamycin-treated patients, there was a higher incidence of EmR propionibacterial carriage in those patients who had previously been treated with oral erythromycin (64%) than in patients with no known previous exposure to erythromycin (20%; 0.01 greater than P greater than 0.001). Patients responding to oral erythromycin treatment carried EmR propionibacteria less frequently (24%) than patients who were not responding or who had relapsed (70%; P less than 0.001). These observations suggest that the use of oral erythromycin and/or topical clindamycin encourages the development of resistant propionibacteria and that the emergence of resistant strains is associated with therapeutic failure in erythromycin-treated patients. In total 63 resistant isolates were obtained from 52 subjects. There were 42 strains of Propionibacterium acnes, 16 strains of Propionibacterium granulosum and five strains of Propionibacterium avidum. The majority of isolates were inducibly or constitutively resistant to macrolide (e.g. erythromycin), lincosamide (e.g. clindamycin) and streptogramin B type antibiotics. Therefore, the isolates are phenotypically indistinguishable from the majority of EmR bacteria in which resistance is due to methylation of 23S ribosomal RNA.     

Is adenoidectomy in children safer with laryngeal mask airway or with tracheal intubation?

Adenoidectomy in paediatric outpatient surgery is assumed to require tracheal intubation (TT). The laryngeal mask airway (LMA) commonly used for general paediatric surgery has never been previously studied for adenoidectomy. We therefore prospectively compared in a randomized manner, the incidence of complications with TT and LMA in 56 children undergoing adenoidectomy. Preoperative, intraoperative and the lowest SPO₂ values after removal of either TT or LMA were recorded. The respiratory complications, cough, stridor and/or laryngospasm, were recorded intraoperatively and after removal of the airway device. The oxygen saturation levels were significantly higher in the laryngeal mask airway group both intraoperatively and after removal of the respiratory device (P<0.05). The incidence of respiratory complications was lower in the LMA group. In conclusion we have shown that the laryngeal mask airway with a flexometallic tube is a satisfactory alternative to tracheal intubation for outpatient paediatric adenoidectomy.     

The Diverse Role of Selenium within Selenoproteins: A Review

Selenium functions within mammalian systems primarily in the form of selenoproteins. Selenoproteins contain selenium as selenocysteine and perform a variety of physiological roles. Eleven selenoproteins have been identified: cellular or classical glutathione peroxidase; plasma (or extracellular) glutathione peroxidase; phospholipid hydroperoxide glutathione peroxidase; gastrointestinal glutathione peroxidase; selenoprotein P; types 1, 2, and 3 iodothyronine deiodinase; selenoprotein W; thioredoxin reductase; and selenophosphate synthetase. Of these, cellular and plasma glutathione peroxidase are the functional parameters used for the assessment of selenium status. Glutathione peroxidases catalyze the reduction of peroxides that can cause cellular damage. Thioredoxin reductase provides reducing power for several biochemical processes and defends against oxidative stress. Selenoprotein P appears to play a role in oxidant defense. Selenoprotein W may play a role in oxidant defense and be involved with muscle metabolism. Thyroid deiodinases function in the formation and regulation of active thyroid hormone. Selenophosphate synthetase is an enzyme required for the incorporation of selenocysteine into selenoproteins. In addition, a protein in the sperm mitochondrial capsule, which is vital to the integrity of sperm flagella, may be a unique selenoprotein. Recommended intakes, food sources, and status assessment of selenium, as well as selenium's role in health and disease processes, are reviewed.     

Entrainment Onset in a Pacemaker Model of Reentrant Ventricular Tachycardia: Insight into Localization of Critical Elements of a Reentrant Circuit

We investigated entrainment in a pacemaker model of reentrant ventricular tachycardia (VT) created in the intact dog heart using a VAT pacemaker with both electrodes on the ventricular epicardium. This produced an incessant wide QRS tachycardia originating from the pacing site with a cycle length equal to the conduction time between the sensing and pacing site plus the pacemaker AV delay. The conduction time between entrainment sites and the critical elements of the reentrant pathway (sensing and pacing sites) was determined by pacing at a comparable cycle length during sinus rhythm. Entrainment was achieved in 12 tachycardias with pacing at 1-4 sites at cycle lengths 10-100 msec shorter than tachycardia and confirmed by constant QRS fusion, progressive QRS fusion, and coupling of the first nonpaced QRS or intracardiac electrogram at the entraining cycle length. By least squares regression, the timing of entrainment onset (first reset of pacing or sensing site electrogram) measured by the prematurity of the local electrogram at the entraining site was highly correlated to the shortest conduction time between the entraining site and the circuit (F value of 84.7 and R = 0.752 [P less than 0.001]). Therefore, the timing of entrainment onset maybe useful in predicting the conduction time from the entraining site to critical elements of a reentrant circuit and may assist in localization of the reentrant pathway.     

Dual Variation in SCN5A and CACNB2b Underlies the Development of Cardiac Conduction Disease without Brugada Syndrome

Background: Inherited loss of function mutations in SCN5A have been linked to overlapping syndromes including cardiac conduction disease and Brugada syndrome (BrS). The mechanisms responsible for the development of one without the other are poorly understood. Methods: Direct sequencing was performed in a family with cardiac conduction disease. Wild‐type (WT) and mutant channels were expressed in TSA201 cells for electrophysiological study. Green fluorescent protein (GFP)‐fused WT or mutant genes were used to assess channel trafficking. Results: A novel SCN5A mutation, P1008S, was identified in all family members displaying first‐degree atrioventricular block, but not in unaffected family members nor in 430 reference alleles. Peak P1008S current was 11.77% of WT (P < 0.001). Confocal microscopy showed that WT channels tagged with GFP were localized on the cell surface, whereas GFP‐tagged P1008S channels remained trapped in intracellular organelles. Trafficking could be rescued by incubation at room temperature, but not by incubation with mexiletine (300 μM) at 37°C. We also identified a novel polymorphism (D601E) in CACNB2b that slowed inactivation of L‐type calcium current (I_Ca,L), significantly increased total charge. Using the Luo‐Rudy action potential (AP) model, we show that the reduction in sodium current (I_Na) can cause loss of the right ventricular epicardial AP dome in the absence but not in the presence of the slowed inactivation of I_Ca,L. Slowed conduction was present in both cases. Conclusions: Our results suggest genetic variations leading to a loss‐of‐function in I_Na coupled with a gain of function in I_Ca,L may underlie the development of cardiac conduction disease without BrS. (PACE 2010; 33:274–285)     

MATRIX METALLOPROTEINASE-2 (72 kD TYPE IV COLLAGENASE) EXPRESSION OCCURS IN THE EARLY STAGE OF HUMAN MELANOCYTIC TUMOUR PROGRESSION AND MAY HAVE PROGNOSTIC VALUE

Matrix metalloproteinase-2 (MMP-2), a member of the matrix metalloproteinase family, participates in degradation of the pericellular and extracellular matrix during neoplastic growth and metastasis. Experimental data have substantiated its role in melanoma invasion, but there is no information at present concerning its expression in histological specimens from human melanocytic tumours. This study describes the occurrence and immunolocalization of MMP-2 in human melanocytic lesions, defining distinct steps in melanoma progression. Paraffin-embedded sections from 118 melanocytic lesions were immunostained using a specific antibody to 72 kD type IV collagenase. The material included 34 common naevocellular naevi, 14 dysplastic naevi, 21 in situ melanomas, 20 primary malignant melanomas, and 29 melanoma metastases. Intracytoplasmic MMP-2 immunoreactive protein was found in the ‘naevocytic nests’ of common naevi, in junctional naevus cells, and in melanoma cells. The surrounding normal skin stained negatively, except for occasional macrophages, sweat glands, and hair follicles. The number of MMP-2-positive cells increased with decreasing architectural organization and increasing atypia in the melanocytic lesions. The MMP-2 positivity in the primary and subcutaneous melanoma lesions correlated with later haematogenous metastasis. The data suggest that MMP-2 expression is an early event in melanocytic tumour progression, but is nevertheless prognostic for haematogenous metastasis in melanoma.