Electrophysiological and antiarrhythmic effects of the atrial selective 5-HT(4) receptor antagonist RS-100302 in experimental atrial flutter and fibrillation.

BACKGROUND: Stimulation of 5-HT(4) receptors increases atrial chronotropic and inotropic responses. Whether other electrophysiological effects are produced is unknown. In humans and swine, 5-HT(4) receptors are present only in atrium. Therefore, the effects of a novel 5-HT(4) receptor antagonist, RS-100302, and the partial agonist cisapride on atrial flutter and fibrillation induced in swine were studied to delineate the role of the 5-HT(4) receptor in modulating atrial electrophysiological properties and the antiarrhythmic potential of RS-100302. METHODS AND RESULTS: In 17 anesthetized, open-chest, juvenile pigs, atrial flutter or fibrillation was induced by rapid right atrial pacing with or without a right atrial free wall crush injury, respectively. Atrial effective refractory period (ERP), conduction velocity, wavelength, and dispersion of refractoriness were determined during programmed stimulation via a 56-electrode mapping plaque sutured to the right atrial free wall. Ventricular electrophysiological parameters were also measured. All electrophysiological parameters were measured at baseline and after infusion of RS-100302 and cisapride. In the atrium, RS-100302 prolonged mean ERP (115+/-8 versus 146+/-7 ms, P<0.01) and wavelength (8.3+/-0.9 versus 9.9+/-0.8 cm, P<0.01), reduced dispersion of ERP (15+/-5 versus 8+/-1 ms, P<0.01), and minimally slowed conduction velocity (72+/-4 versus 67+/-5 cm/s, P<0.01). These effects were all partially reversed by cisapride. RS-100302 produced no ventricular electrophysiological effects. RS-100302 terminated atrial flutter in 6 of 8 animals and atrial fibrillation in 8 of 9 animals and prevented reinduction of sustained tachycardia in all animals. CONCLUSIONS: The electrophysiological profile of RS-100302 suggests that it may have atrial antiarrhythmic potential without producing ventricular proarrhythmic effects.

Congenital infantile fibrosarcoma.

Infantile fibrosarcoma is a rare tumour in the paediatric age group. It occurs mainly in children below the age of 5 years. About 200 cases have been reported in the literature so far, very few of them in new-borns. We present here a case of infantile fibrosarcoma in a 27-day-old baby.

Malignant lymphoma of the gastrointestinal tract.

AIMS: The gastrointestinal tract (GIT) is the most common site of extra-nodal lymphoma. Most of these lymphomas arise from mucosa associated lymphoid tissue (MALT). We attempt in this study to define the natural history and treatment outcome of this type of lymphoma. METHODS: We carried out a retrospective study of patients presenting at our centre with histopathological diagnosis of primary GIT lymphoma between 1990 and 1994. RESULTS: Equal numbers of cases of stomach and small bowel lymphoma were found. Vomiting and feeling of fullness were the two most common presenting symptoms. Large cell type and high grade tumours were found to be the commonest histological types. All the patients were treated with surgery followed by chemotherapy. A 5-year disease-free survival (DFS) rate of 73%) was observed with a confidence interval of 0.65-1.35. Survival in stomach cancer was 73.5% (95% CI 0.26-1.74) while it was 76.4% in small bowel tumours (95% CI 0.54-1.46). The difference in survival was not statistically significant. CONCLUSIONS: Although there is no consensus regarding treatment of primary GI lymphoma, surgery and adjuvant chemotherapy yield good survival.

Transcatheter cryoablation of ventricular myocardium in dogs.

INTRODUCTION: Surgical cryoablation, a highly effective technique used during antiarrhythmic surgery, produces voluminous, histologically uniform and discreet myocardial lesions. In contrast, radiofrequency (RF) catheter ablation, which as a result of its less invasive nature has largely supplanted antiarrhythmic surgery, produces smaller, histologically heterogeneous myocardial lesions. Since small lesion size and heterogeneity may reduce antiarrhythmic efficacy, we sought to reproduce the large, histologically homogeneous lesions created by surgical cryoablation, using a catheter cryoablation system (Cryogen, Inc., San Diego, CA) in the canine ventricle. METHODS AND RESULTS: In seven dogs, nineteen ventricular lesions (two right and seventeen left) were created with a 10F cryoablation catheter with either a 2 or 6 mm tip. In one dog AV node ablation was also performed. For each 'freeze', catheter tip nadir temperature, lesion width, depth, and transmurality were recorded, and lesion volume calculated. Average tip nadir temperature was -79.6+/-4.9 degrees C. Cooler nadir tip temperature was associated with deeper (p=.007) and more voluminous lesions (p=.042), and a greater likelihood of lesion transmurality (p=.034). Average lesion volume was 500+/-356 mm(3). No other variables predicted lesion volume or transmurality. Histologically, the catheter cryoablation lesions were sharply demarcated and homogeneous. The single freeze performed at the AV junction produced complete AV block. One complication, catheter rupture following its repetitive use, resulted in a coronary air embolus and death. CONCLUSION: Catheter cryoablation of canine ventricular myocardium produced voluminous, discrete, transmural lesions, which might be effective for ablation of ventricular tachycardia. Lesion volume and transmurality were dependent on catheter tip nadir temperature.

Nasopharyngeal presentation of renal cell carcinoma.

In this case report, we present a 50-year- old woman, who presented with severe headache as her only presenting clinical symptom due to nasopharyngeal mass. Histo-pathological evaluation of the biopsy from nasopharyngeal mass revealed clear cell carcinoma. On further evaluation, an asymptomatic mass was detected in the left kidney. The metastatic lesion was treated with palliative radiotherapy. A search of the literature revealed no reports of such unusual metastasis in the nasopharynx from a primary carcinoma of the renal origin.

Scalp metastasis from squamous cell carcinoma of the cervix.

We describe a 45-year-old woman with squamous cell carcinoma of the cervix stage IIB, who was initially treated with radical radiotherapy. The patient developed multiple scalp metastases 8 months following her treatment. The scalp was involved in the disease as the sole anatomic site of distant cutaneous metastasis. The scalp lesions were treated with palliative radiotherapy. A search of the literature revealed only two cases of such distant metastatic involvement of the scalp from cervical cancer.

Primary rhabdomyosarcoma of the larynx.

Sarcomas constitute fewer than 1% of the head and neck cancers. They represent less than 1% of laryngeal cancers. Primary rhabdomyosarcoma of the larynx is an extremely rare malignancy. The available literature on this medical oddity is in the form of isolated case reports only. The purpose of this article is to add another case of primary rhabdomyosarcoma of a rare site, the larynx, of which only 36 cases have so far been reported in the world literature. The present patient, an eighteen-year-old boy is only the third case being reported from India among all reported cases of rhabdomyosarcoma of the larynx in the world literature.

Assessment of glutathione-S-transferase and glutathione reductase in patients with squamous-cell carcinoma of buccal mucosa.

Serum and tumor cytosolic levels of glutathione-S-transferase (GST) and glutathione-reductase (GR) activity were determined spectrophotometrically. The levels were correlated with clinicopathological criteria and a tobacco-associated protein band (T band) found in serum. The results showed significantly decreased mean serum GST levels (p < 0.02) in cancer patients as compared with controls. However, mean serum GR levels were significantly higher in patients than in controls (p < 0.01). T-band-positive patients showed low GST and low GR activity as compared with T-band-negative patients. Tumor cytosolic-enzyme levels of GST and GR activity were significantly higher (p < 0.0003 and p < 0.0001, respectively) than in corresponding adjacent noncancerous mucosa. Tumour cytosolic GST and GR activity showed significant association with clinicopathologic criteria, e.g., stage, histologic grade and nodal involvement. T-band-negative patients showed significantly higher levels of GST (p < 0.0001) than did T-band-positive patients. Low levels of cytosolic GST may be associated with increased susceptibility towards carcinogen-induced damage. The results suggest that the presence of T band in the sera may be associated with a high-risk phenotype due to decreased detoxification ability.