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Biomedical subjects

P Kamath

Publications and source records attributed to P Kamath.

10 recordsLinked to original sources

Evidence-based practice. A philosophical and political analysis: some matters for consideration by professional practitioners.

This paper evaluates the concept of evidence-based practice (EBP) and appraises critically the implementation process of the EBP initiative, noting its consonance with the aspirations of the dominant political culture and offering a critique of the inherent contradictions and ethical dilemmas associated with it. A critical evaluation of the implications for practitioners and service users is offered and the authors argue that while the concept of EBP is a laudable one, there is a need to exercise caution about uncritical acceptance and evidence that a more eclectic and less reductionist approach to EBP is essential for quality service development.

Diffusion of Innovation↗

Percutaneous transvenous mitral commissurotomy using Inoue balloon in children less than 12 years.

Rheumatic mitral stenosis in some parts of the world afflicts even young children. Percutaneous transvenous mitral commissurotomy (PTMC) using Inoue balloon in these children is not well reported. Forty-five children (aged 7-12 years, mean 11.0 +/- 1.2 years) with severe rheumatic mitral stenosis (mitral valve area [MVA] 0.64 +/- 0.14 cm2) underwent PTMC. The pulmonary artery wedge pressure (PAW) decreased from 24.3 +/- 8.6 to 14.7 +/- 7.2 mmHg (P < 0.0001) and mean diastolic gradient decreased from 24.3 +/- 7.7 to 7.9 +/- 5.9 mmHg with the final MVA of 1.63 +/- 0.45 cm2 (P < 0.0001). Complications included significant mitral regurgitation (MR) in three children and atrial shunting in two patients. No procedural death, systemic embolism, and cardiac tamponade were encountered. Twenty-four children had maximum balloon size (MBS) same as recommended balloon size (RBS) derived according to the height (group I) and 21 children had MBS 1-3 mm less than RBS (group II). Despite the lesser maximum balloon size, the final results were comparable in both groups (MVA group 1.66 +/- 0.44 vs. group II 1.61 +/- 0.48 P = NS). The incidence of significant MR (2 and 1 in group I and group II, respectively) was similar. On follow-up of 20.4 +/- 16.3 months (range 3-56 months), one child developed restenosis. We conclude that PTMC is safe and effective in children less than 12 years of age. However, the smaller balloon size than the RBS derived from height may be equally effective and possibly safer.

Balloon Occlusion↗

Effectiveness of three ribozymes for cleavage of an RNA transcript from human papillomavirus type 18.

We tested three hammerhead ribozymes for their ability to bind and cleave RNA transcripts derived from the E6 and E7 genes of human papillomavirus (HPV) type-18. Targets were located at nucleotides (nt) 123, 309, and 671 of the viral transcript. In vitro each ribozyme hybridized to its target site when the ribozyme:target ratio was 20:1 or greater and achieved maximal hybridization within 1 hour. HPV RNA from the HeLa cervical cancer cell line was cleaved effectively by each ribozyme. When HPV RNA and a ribozyme were expressed simultaneously in Escherichia coli, each ribozyme produced a significant reduction in the intracellular concentration of HPV RNA. In each assay the ribozyme directed to nt 309 was the most effective. A noncatalytic antisense molecule was used as a control and did not digest HPV RNA or reduce its concentration. The data imply that three different ribozymes each have potential for use in gene therapy of human tumors that express HPV-18 but that the ribozyme targeted to nt 309 is likely to be most effective.

Base Sequence↗

Papillomaviruses as targets for cancer gene therapy.

Gene therapy of human cancer is likely to be most effective when it is directed at targets that are expressed in cancer cells but are lacking from other cells. Human papillomaviruses can provide such targets, since these viruses are present in many cervical and oral cancers, and are likely to be etiological agents of the tumor. Continued expression of human papillomavirus genes is probably necessary for the growth of these cancers, and effective gene therapy could consist of antisense or ribozyme molecules directed against these genes. Some human papillomavirus gene products are antigenic, and immunotherapy based upon these antigens might prove clinically beneficial. Human papillomaviruses have specific promoters, are linked to toxin genes, the toxin may be selectively expressed by tumor cells where the virus genes are active. Thus, there are several approaches for the development of specific gene therapy for human cancers that contain human papillomaviruses.

Adult↗

Emergency transcatheter balloon recanalization of acutely thrombosed modified Blalock-Taussig shunts.

BACKGROUND: Modified Blalock-Taussig shunts are used to palliate a variety of cyanotic heart diseases associated with reduced pulmonary blood flow. Acute shunt thrombosis in patients with shunt-dependent pulmonary blood flow can result in life-threatening hypoxia. We describe our experience of emergency transcatheter recanalization in 5 severely hypoxic children with acute shunt occlusion. METHODS AND RESULTS: Five patients with ages ranging between 5 and 24 months (median 11 months) and weight ranging from 4 to 8 kg (median 5 kg) presented with severe hypoxia, acidosis and hypotension following acute occlusion of modified Blalock-Taussig shunts placed 11 days to 12 months ago. As severe hypoxia (saturation range 3 5%-5 0%), acidosis and a state of shock in all the patients increased the risk for a redo surgical procedure, they were taken up for emergency transcatheter recanalization within 2-6 hours of hospitalization. This was done by positioning a Judkin's right coronary catheter at the mouth of the thrombosed shunt, crossing the shunt with a guidewire and serial dilatations with coronary and/or peripheral angioplasty balloons to the size of the graft. This technique was immediately successful in 4 of the 5 patients, thereby avoiding a repeat palliative operation. In 2 patients with residual stenosis, stents were used to restore luminal patency. One patient with acute stent thrombosis was managed successfully with local delivery of thrombolysis for 36 hours, which resulted in good luminal patency. At follow-up after 6 and 12 months, the shunts in both the stented patients are patent, with an oxygen saturation of 78% and 80%, respectively. In 2 other patients who had undergone plain balloon angioplasty, the shunts remained patent for 11 days (died of bronchopneumonia and septicemia) and 3 months, respectively. The procedure was unsuccessful in one very sick patient in whom the shunt had a tortuous course. CONCLUSIONS: Transcatheter recanalization of an acutely thrombosed Blalock-Taussig shunt is feasible. It can offer satisfactory short-term palliation in selected patients. Stents may play a role in patients with residual narrowing after dilatation. The procedure can be expeditiously accomplished in an emergency situation in a severely hypoxic child and may be a realistic alternative to surgery or thrombolysis.

Anastomosis, Surgical↗

Brugada syndrome.

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Adult↗

Effects on tumor cells of ribozymes that cleave the RNA transcripts of human papillomavirus type 18.

Many human cervical and oral carcinomas express RNA of human papillomaviruses, and the RNA transcript provides a potential target for gene therapy of these carcinomas. Three hammerhead ribozymes that were targeted to RNA of human papillomavirus type 18 (HPV-18) were cloned into a plasmid expression vector. Each plasmid was then transfected into the HPV-18-expressing cell line. HeLa, or the non-HPV-expressing oral cancer cell line, Tu167. None of the ribozymes had any effect on the phenotype of Tu167 cells. In contrast, each ribozyme affected the phenotype of HeLa cells, causing reduced growth rates, increased serum dependency, and reduced focus formation in soft agar. A molecule that had the same antisense sequences as a ribozyme but lacked the catalytic sequences affected the HeLa cell phenotype to a much lesser extent. The effects of two of the ribozymes could be attributed in part to an increased intracellular concentration of the tumor suppressor protein p53. The most effective ribozyme was targeted to nucleotide 309 in the HPV-18 transcript, but each of the three ribozymes appears to have potential for gene therapy of cancers that express HPV-18.

Base Sequence↗