A mathematical model for irrigated epicardial radiofrequency ablation

A mathematical model for epicardial radiofrequency ablation using an electrode irrigated by saline is proposed. Saline flow profiles are derived using thin film theory, and heat convection due to blood flow is also included in the model. Results from a computer implementation of the model using a finite element method suggest that transmural ablation lesions can be made in 4-mm-thick tissue. Effects of parameters such as tissue and saline layer thickness, irrigation rate, blood flow rate, and applied power are investigated. Saline is found to irrigate as well as ablate. Rise in saline temperature and consequent ablation by saline is more pronounced as saline layer becomes thicker. Electrode tip temperatures as much as 40 °C lower than maximum tissue temperature were found in simulations. © 2002 Biomedical Engineering Society. PAC2002: 8754Br, 8719Pp, 0270Dh, 8710+e     

Modulation of action potential firing by iberiotoxin and NS1619 in rat dorsal root ganglion neurons

The present study investigated the effects of iberiotoxin (IbTx), a peptide toxin blocker of large-conductance Ca(2+)-activated K(+) (BK(Ca)) channels and NS1619, a BK(Ca) channel opener, on action potential firing of small and medium size afferent neurons from L6 and S1 dorsal root ganglia of adult rats. Application of IbTx (100 nM) reduced whole-cell outward currents in 67% of small and medium size neurons. Analysis of action potential profile revealed that IbTx significantly prolonged the duration of action potential and increased firing frequency of afferent neurons. IbTx did not significantly alter the resting membrane potential, threshold for action potential activation and action potential amplitude. The benzimidazolone NS1619 (10 microM) increased opening activity of a Ca(2+)-dependent channel as assessed by single channel measurements. In contrast to IbTx, NS1619 reversibly suppressed action potential firing, attributable to increases in threshold for evoking action potential, reduction in action potential amplitude and increases in amplitude of afterhyperpolarization. The effect of NS1619 on neuronal firing was sensitive to IbTx, indicating the attenuation of neuronal firing by NS1619 was mediated by opening BK(Ca) channels. NS1619 also reduced neuronal hyperexcitability evoked by 4-aminopyridine (4-AP), a transient-inactivated K(+) channel (A-current) blocker, in an IbTx-sensitive manner.These results indicate that IbTx-sensitive BK(Ca) channels exist in both small and medium diameter dorsal root ganglion (DRG) neurons and play important roles in the repolarization of action potential and firing frequency. NS1619 modulates action potential firing and suppresses 4-AP-evoked hyperexcitability in DRG neurons, in part, by opening BK(Ca) channels. These results suggest that opening BK(Ca) channels might be sufficient to suppress hyperexcitability of afferent neurons as those evoked by stimulants or by disease states.     

Pharmacology of human sulphonylurea receptor SUR1 and inward rectifier K(+) channel Kir6.2 combination expressed in HEK-293 cells

1. The pharmacological properties of K(ATP) channels generated by stable co-expression of the sulphonylurea receptor SUR1 and the inwardly rectifying K(+) channel Kir6.2 were characterized in HEK-293 cells. 2. [(3)H]-Glyburide (glibenclamide) bound to transfected cells with a B(max) value of 18.5 pmol mg(-1) protein and with a K(D) value of 0.7 nM. Specific binding was displaced by a series of sulphonylurea analogues with rank order potencies consistent with those observed in pancreatic RINm5F insulinoma and in the brain. 3. Functional activity of K(ATP) channels was assessed by whole cell patch clamp, cation efflux and membrane potential measurements. Whole cell currents were detected in transfected cells upon depletion of internal ATP or by exposure to 500 microM diazoxide. The currents showed weak inward rectification and were sensitive to inhibition by glyburide (IC(50)=0.92 nM). 4. Metabolic inhibition by 2-deoxyglucose and oligomycin treatment triggered (86)Rb(+) efflux from transfected cells that was sensitive to inhibition by glyburide (IC(50)=3.6 nM). 5. Diazoxide, but not levcromakalim, evoked concentration-dependen decreases in DiBAC(4)(3) fluorescence responses with an EC(50) value of 14.1 microM which were attenuated by the addition of glyburide. Diazoxide-evoked responses were inhibited by various sulphonylurea analogues with rank order potencies that correlated well with their binding affinities. 6. In summary, results from ligand binding and functional assays demonstrate that the pharmacological properties of SUR1 and Kir6.2 channels co-expressed in HEK-293 cells resemble those typical of native K(ATP) channels described in pancreatic and neuronal tissues.     

Cowden syndrome - Report of two cases

Two cases of Cowden syndrome with typical features are presented. In addition to the cutaneous lesions like facial trichilemmomas, oral mucosal fibromas, acrokeratosis verruciformis and palmo plantar hyperkeratosis, the first patient had follicular carcinoma of thyroid, fibrocystic disease of the breasts and ovarian teratoma and second patient had a cerebellar hamartoma (Lhermitte Duclos syndrome) which is a rare entity.     

Transfer of heritable properties by cell cybridization: Specificity and the role of selective pressure

Enucleated chloramphenicol (CAP) resistant mouse L-cells (LEA-2A) were fused with the mouse hepatoma cells (BW1J). The resultant cybrids expressed CAP resistance (the property used in selection of the cybrids), and also expressed the hepatic-specific functions of the BW1J parent. Hybrids between these same cells, on the other hand, exhibited chloramphenicol resistance and extinction of the hepatoma-specific properties. Cybrids were also prepared between enucleated rat hepatoma cells (FT-2) and mouse erythroleukemia cells (C19TK). The resultant cybrids selected in tyrosine-free medium expressed phenylalanine hydroxylase, an enzyme normally expressed only in the FT-2 cells. By immunotitration studies, the enzyme appeared to be the result of activation of the previously silent gene of the C19TK cells. These cybrids, however, did not express any other liver-specific functions present in the FT-2 cytoplast donor. These experiments suggest that the transfer of heritable properties by cell cybridization is selection specific and that activation or extinction observed in hybrids may not occur in cybrids of the same cells.Visiting Scientist on leave from the Diabetes Branch, NIAMDD, National Institutes of Health, Bethesda, Maryland 20205.     

Papillary carcinoma arising in a thyroglossal duct cyst

A 21-year-old lady was admitted with a one year history of painless swelling in the neck. The clinical features and radiological findings suggested a thyroglossal duct cyst. Histology of the excised duct cyst showed papillary carcinoma. Ultrasound examination of the thyroid gland was normal. The patient is on regular follow-up and is well two years following surgery.     

Recombinant immunotoxins containing anti-Tac(Fv) and derivatives of Pseudomonas exotoxin produce complete regression in mice of an interleukin-2 receptor-expressing human carcinoma

Anti-Tac(Fv)-PE40 is a recombinant single-chain immunotoxin composed of the variable domains of the monoclonal antibody anti-Tac, which binds to the p55 subunit of the interleukin-2 receptor (IL-2R), and a truncated form of Pseudomonas exotoxin (PE), which does not bind to the PE receptor (Chaudhary et al, Nature 339:394, 1989). Whereas its cytotoxic activity toward autoimmune and malignant target cells has been established, its efficacy in vivo remains unknown. To establish an animal model, we produced ATAC-4 cells by transfecting the gene encoding the low-affinity IL-2R (p55) into A431 epidermoid carcinoma cells. ATAC-4 cells contained low-affinity IL-2Rs (2 x 10(5)/cell) and formed tumors in nude mice. In tissue culture, protein synthesis in ATAC-4 cells was inhibited 50% (IC50) at 0.06 ng/mL (0.9 pmol/L) of anti-Tac(Fv)-PE40. IC50s for the derivatives anti-Tac(Fv)-PE38, which is missing PE amino acids 365-380, and anti-Tac(Fv)-PE38KDEL, which contains the same deletion plus the KDEL carboxyl terminus, were 0.04 and 0.025 ng/mL, respectively. All the agents produced complete tumor regressions in ATAC-4 tumor-bearing mice and anti-Tac(Fv)-PE38KDEL had significant antitumor activity at 1% of the LD50. The dose limiting toxicity of anti-Tac(Fv)-PE38KDEL was from hemorrhagic liver necrosis, which was observed at approximately 55% of the LD50.     

Reversible “Pulvinar sign” in Wernicke's encephalopathy

Young onset dementia is a challenge. We describe a case, where a patient presented with psychosis, dementia and MRI showing pulvinar sign, all of this typical of variant Cruetzfelt Jacob disease (CJD). Subsequent investigations lead to the diagnosis of a treatable illness and patient was improved and MRI sign reversed, underlining again the importance of search needed for treatable diseases in any “typical” case of fatal illness.