Valvular heart disease in Antiphospholipid antibody syndrome: Isolated Tricuspid stenosis

Antiphospholipid antibody syndrome (APLS) is a rare disorder characterized by a hypercoagulable state. Manifestations include arterial or venous thrombosis, recurrent fetal wastage, coronary artery disease, valvular heart disease, dilated cardiomyopathy, pulmonary artery hypertension, and intracardiac thrombus. Most commonly mitral valve is affected followed by aortic and then tricuspid valve. In this report, a rare case of spontaneous aortic thrombosis with tricuspid stenosis uncomplicated by other valve lesions is presented with clinical and echocardiographic studies and computed tomographic images.     

Altered steady state pharmacokinetics of levofloxacin in adult cystic fibrosis patients receiving calcium carbonate.

BACKGROUND: Levofloxacin is used in adult patients with cystic fibrosis but its pharmacokinetics is not well characterized in this population. Patients with cystic fibrosis use calcium routinely to prevent osteoporosis. A slower intestinal transit time is common in cystic fibrosis implying that the standard 2-h spacing of minerals and levofloxacin to prevent a chelation interaction may be insufficient. The objectives of this study were to characterize the steady state pharmacokinetics of oral levofloxacin 750 mg with and without 2-h spaced calcium carbonate in patients with cystic fibrosis compared to matched healthy volunteers. METHODS: In an open-label, randomized, cross-over study of five patients with cystic fibrosis and five age, sex, race, and serum creatinine matched healthy volunteers received 750 mg of oral levofloxacin alone daily for 5 days and the same dose of levofloxacin with 2-h spaced calcium carbonate supplementation 500 mg po thrice daily with meals in random sequence. Blood was collected for plasma assay of levofloxacin pre-dose, 0.5, 1, 1.5, 2, 4, 8, 12, and 24h after the fifth levofloxacin dose. RESULTS: There was no significant interaction in healthy volunteers, however, when cystic fibrosis patients were given levofloxacin with 2-h spaced calcium, the maximum plasma concentration (Cmax) decreased by 19% and time to Cmax increased by 37% (p<0.05). This difference in peak concentrations resulted in a lack of bioequivalence (Cmax geometric mean ratio 81.6%, 90% confidence intervals: 71.8%, 91.4%) even when levofloxacin and calcium supplements were spaced by the standard 2h administration instruction in patients with cystic fibrosis. CONCLUSIONS: These results indicate that multivalent cations such as calcium should be maximally separated from oral levofloxacin administration in adult patients with cystic fibrosis to prevent this drug interaction, thereby better optimizing antibiotic efficacy and decreasing the potential for resistance development.     

Quality of life in patients with seasonal affective disorder: summer vs winter scores.

OBJECTIVE: To compare perceived quality of life (QoL) in patients diagnosed with seasonal affective disorder (SAD) during the winter and summer months. METHODS: Twenty-six patients who were enrolled in an ongoing multicentre study in Canada completed 2 measures of QoL (the 20-item Medical Outcomes Study Short-Form General Health Survey [SF-20] and the Quality of Life Enjoyment and Satisfaction Questionnaire, [Q-LES-Q]) during the winter, when suffering from depression, and again during the summer months. RESULTS: Both general and health-related QoL scores were significantly improved in patients with SAD during the summer months, with scores for the most part falling within normal range. CONCLUSIONS: Perceived QoL in patients with SAD is markedly impaired during the winter months but shows a substantial rebound during the summer months. The findings of this study provide further evidence that SAD is a distinct diagnostic entity.     

Preparation, characterization and in vitro release kinetics of clozapine solid lipid nanoparticles.

Clozapine, a lipophilic antipsychotic drug, has very poor oral bioavailability (<27%) due to first pass effect. Solid lipid nanoparticle (SLN) delivery systems of clozapine have been developed using various triglycerides (trimyristin, tripalmitin and tristearin), soylecithin 95%, poloxamer 188 and charge modifier stearylamine. Hot homogenization of melted lipids and aqueous phase followed by ultrasonication at temperature above the melting point of lipid was used to prepare SLN dispersions. Particle size and zeta potential were measured by photon correlation spectroscopy (PCS) using Malvern Zetasizer. Process and formulation variables have been studied and optimized. Differential scanning calorimetry (DSC) and powder X-ray diffraction (PXRD) studies were performed to characterize state of drug and lipid modification. In vitro release studies were performed in 0.1 N HCl, double-distilled water and phosphate buffer, pH 7.4, using modified Franz diffusion cell. Stable SLN formulations of clozapine having mean size range of 60-380 nm and zeta potential range of -23 to +33 mV were developed. More than 90% clozapine was entrapped in SLN. DSC and PXRD analysis showed that clozapine is dispersed in SLN in an amorphous state. The release pattern of drug is analyzed and found to follow Weibull and Higuchi equations.     

Effects of sirsasana (headstand) practice on autonomic and respiratory variables.

The present study had two aims: (1) To assess heart rate variability (HRV) along with non-specific autonomic measures (used in earlier studies), before and after two minutes of the head stand. (2) To compare changes in two categories of subjects, i.e., those who practiced the headstand in a traditional way (without any support) and those who used the support of the wall (a present day adaptation). The subjects were forty male volunteers (age range 19 to 36 years), with twenty subjects under each category. The following changes were significant after the practice, compared to values at baseline. (i) Both categories had an increase in the power of the low frequency component (LF) and a decrease in the high frequency component (HF) of the HRV spectrum, increased LF/HF ratio, and decreased heart rate. (ii) Subjects who practiced the head stand with the support of a wall showed reduced finger plethysmogram amplitude suggesting increased sympathetic vasomotor tone. (iii) Practicing the headstand without support was associated with an increase in the skin conductance level, suggestive of increased sympathetic sudomotor tone. Hence, both categories showed similar changes in the HRV components though changes in sympathetic vasomotor and sudomotor activity were different. These changes suggest sympathetic activation, irrespective of the method of practice.     

Intraoral Tumor of Chievitz in a Child

Juxtaoral organs known as organs of Chievitz are intramuscular embryonic structures found close to the angle of the mandible near the insertion of the pterygomandibular raphae. They are considered of neuroepithelial origin with no known function. We describe the first tumor of the organ of Chievitz which presented intraorally in a child. Immunohistochemically, the Chievitz nests showed positive reaction for vimentin, cytokeratins, and epithelial membrane antigen and ultrastructurally demonstrated cytoplasmic processes and intermediate filament bundles. These observations, together with light microscopic features, suggest that the epithelial nests of the organ of Chievitz are meningothelial rather than neuroepithelial. Received December 18, 1996; accepted March 13, 1997.     

Case report and literature review: primary cutaneous carcinosarcoma

Carcinosarcomas are rare but aggressive neoplasms commonly described in organs such as the breast, urinary bladder, uterus, liver, and lungs. Histopathologically, they are characterized by the presence of malignant epithelial and mesenchymal components. The exact histogenesis of carcinosarcomas remains unknown and is debated in the literature. Primary carcinosarcomas of the skin are uncommon. To our knowledge, 20 cases of primary cutaneous carcinosarcoma have been described in the world literature. Most of these tumors were seen on the head and neck region of older individuals, both male and female. Microscopically, the more common carcinoma component is a squamous cell carcinoma followed by basal cell carcinoma, whereas the most common sarcoma component is an osteosarcoma. We report an example of this rare entity and speculate on its histogenesis in the skin.     

Malignant progression of B16 melanoma cells induced in vitro by growth factors produced by highly malignant cells

Four mouse B16 melanoma subclones (G3.15, G3.5, G3.12 and G3.26) exhibit progressively greater growth capacity in vitro and in vivo. Previously, non-metastatic G3.15 cells were sequentially converted, in monolayer cultures, to the moderately-metastatic G3.5 cells, and then to a highly-metastatic G3.5^* phenotype. Both conversions were induced by hypoxia followed by confluence, and also occurred in tumors. G3.5^* cells were comparable with, yet distinguishable from, G3.12 cells in being growth-autonomous in culture. In this study, the presumption that rapidly-growing G3.26 cells represented the ultimate progression step in this clonal system was examined. Both G3.12 and G3.5^* cells converted in vitro to the G3.26 phenotype during growth in serum-free medium conditioned by G3.26 cell growth. By selective filtration of conditioned medium and characterization of the stability of growth- and conversion-promoting activities, three distinct activities were found to promote a two-step G3.12 to G3.26 phenotype conversion: (1) a < 10 kDa filtrate stimulated slight attachment and proliferation of G3.12 cells, effects that were reversible, partly attributable to accumulated lactate, and fully mimicked by medium acidification to pH 6.5; (2) medium acidification, together with a heat- and acid-stable but partially trypsin-sensitive > 10 kDa activity, induced G3.12 G3.5^* conversion that resulted in acquisition of growth autonomy; and (3) a heat-, acid- and trypsin-sensitive > l0 kDa activity induced G3.5^* G3.26 conversion, characterized by anchorage-independent growth in soft agar, and potent lung colonization following intravenous injection. Phenotype analysis of G3.12 tumors and lung metastases revealed that G3.5^*-like cells were regularly present in tumors and metastases, whereas G3.26-like cells occurred almost exclusively in large lung metastases. While G3.12 cells might convert to G3.5^* cells in order to disseminate, G3.26 cells are apparently not involved in metastatic spread but probably account for the rapid growth of established metastases.