Safety and efficacy of multipolar pulmonary vein ablation catheter vs. irrigated radiofrequency ablation for paroxysmal atrial fibrillation: a randomized multicentre trial.

AIMS: The current challenge in atrial fibrillation (AF) treatment is to develop effective, efficient, and safe ablation strategies. This randomized controlled trial assesses the medium-term efficacy of duty-cycled radiofrequency ablation via the circular pulmonary vein ablation catheter (PVAC) vs. conventional electro-anatomically guided wide-area circumferential ablation (WACA). METHODS AND RESULTS: One hundred and eighty-eight patients (mean age 62 ± 12 years, 116 M : 72 F) with paroxysmal AF were prospectively randomized to PVAC or WACA strategies and sequentially followed for 12 months. The primary endpoint was freedom from symptomatic or documented >30 s AF off medications for 7 days at 12 months post-procedure. One hundred and eighty-three patients completed 12 m follow-up. Ninety-four patients underwent PVAC PV isolation with 372 of 376 pulmonary veins (PVs) successfully isolated and all PVs isolated in 92 WACA patients. Three WACA and no PVAC patients developed tamponade. Fifty-six percent of WACA and 60% of PVAC patients were free of AF at 12 months post-procedure (P = ns) with a significant attrition rate from 77 to 78%, respectively, at 6 months. The mean procedure (140 ± 43 vs. 167 ± 42 min, P<0.0001), fluoroscopy (35 ± 16 vs. 42 ± 20 min, P<0.05) times were significantly shorter for PVAC than for WACA. Two patients developed strokes within 72 h of the procedure in the PVAC group, one possibly related directly to PVAC ablation in a high-risk patient and none in the WACA group (P = ns). Two of the 47 patients in the PVAC group who underwent repeat ablation had sub-clinical mild PV stenoses of 25-50% and 1 WACA patient developed delayed severe PV stenosis requiring venoplasty. CONCLUSION: The pulmonary vein ablation catheter is equivalent in efficacy to WACA with reduced procedural and fluoroscopy times. However, there is a risk of thrombo-embolic and pulmonary stenosis complications which needs to be addressed and prospectively monitored. CLINICALTRIALSGOV IDENTIFIER: NCT00678340.

Targeting renin-angiotensin system in malignant hypertension in atypical hemolytic uremic syndrome.

Hypertension is common in hemolytic uremic syndrome (HUS) and often difficult to control. Local renin-angiotensin activation is believed to be an important part of thrombotic microangiopathy, leading to a vicious cycle of progressive renal injury and intractable hypertension. This has been demonstrated in vitro via enhanced tissue factor expression on glomerular endothelial cells which is enhanced by angiotensin II. We report two pediatric cases of atypical HUS with severe refractory malignant hypertension, in which we targeted the renin-angiotensin system by using intravenous (IV) enalaprilat, oral aliskiren, and oral enalapril with quick and dramatic response of blood pressure. Both drugs, aliskiren and IV enalaprilat, were effective in controlling hypertension refractory to multiple antihypertensive medications. These appear to be promising alternatives in the treatment of severe atypical HUS-induced hypertension and hypertensive emergency.

Eculizumab for atypical hemolytic-uremic syndrome in India: First report from India and the challenges faced.

Much progress has been made in understanding the pathophysiology and treatment of atypical hemolytic uremic syndrome (aHUS). Plasma therapy is the mainstay of treatment for aHUS. The availability of the first effective anti-complement therapeutic agent, eculizumab, has dramatically changed the outlook of this disease. However, its use in clinical practice raises important questions, such as who should receive the drug, when to start such therapy, and is it safe to stop treatment once the disease is controlled. We describe here for the 1st time in India, use of eculizumab in a 12-year-old boy with aHUS. We also describe in this report challenges faced in procuring the drug, and an ideal, evidence-based method of treating aHUS in children.

Cytogenetic analysis of a gossypol-induced murine myxosarcoma.

Cytogenetic analysis of gossypol acetate-induced murine myxosarcoma demonstrated a stemline of 78 chromosomes and the presence of three marker (M) chromosomes produced by robertsonian translocation. Tumor cells at passage 1 that contain chromosomes M1 and M2 were nontumorigenic, whereas cells at passage 3 were tumorigenic in syngeneic mice and showed M1, M2, and M3. The presence of M3 has been implicated to be responsible for the tumorigenic phenotype.

Specific chromosomal defects associated with ultraviolet radiation-induced cutaneous tumors in Monodelphis domestica (Marsupialia, mammalia).

Cytogenetic analysis of eight ultraviolet radiation (UVR)-induced cutaneous tumors and one spontaneously transformed fibroblast cell line of Monodelphis domestica showed that two of the tumor cell lines were of murine origin and that the remaining six marsupial tumor cell lines had hyperdiploid stemline numbers ranging from 21 to 31. Each tumor cell line showed structural and numerical abnormalities. The single transformed fibroblast cell line also showed a hyperdiploid chromosome number with structural and numerical defects. All M. domestica tumor cell lines and the fibroblast line showed a common structural abnormality: deletion of the short arm (p) of a chromosome 1. In some cell lines, the short arm of chromosome 1 was replaced by a translocation with the X chromosome. We suggest, based on the Giemsa-banding homology of chromosome 1p in M. domestica and human chromosome 6q involved in melanomas, that marsupial chromosome 1p may harbor tumor suppressor gene(s) that are associated with UVR-induced cutaneous tumors.

Genetic susceptibility, somatic mosaicisms and predisposition to human cancer.

We herein propose that specific chromosomal aberrations associated with specific neoplasms are not necessarily inherited as a constitutional trait. High-risk individuals may have a tendency to undergo specific somatic mutations or chromosomal rearrangements at a relatively low frequency in all tissues as mosaicism. This may potentiate the development of specific somatic cancers. Our hypothesis may be applicable to both hereditary and sporadic types of neoplasms.

Cytogenetic characterization of two human milk-derived cell line (HBL-100) passages differing in tumorigenicity.

Using the trypsin-Giemsa staining technique, cytogenetic analysis was done to determine the karyotypic characteristics in cells from the early nontumorigenic passage 12 and the late tumorigenic passage 147 of the human breast milk-derived cell line HBL-100. Acquisition of exclusive marker chromosomes in the late passage of HBL-100 may be responsible for the tumorigenic behavior of these cells in athymic nude mice.

An osteosarcoma cell line with hypodiploid chromosome number and complex structural anomalies.

Giemsa-banding analysis performed on a newly established metastatic osteosarcoma cell line (SP-388) that was passaged through the nude mouse revealed a hypodiploid stemline number of 39 chromosomes. This cell line showed both numerical and structural abnormalities, including the abnormally banded region in certain marker chromosomes. Chromosomes 3, 15, 17 and the X were the most frequently absent elements of this tumor. Segments of chromosomes 3, 15 and X could not be identified even in rearranged chromosomes (Ml to M15). We suggest that more cases of osteosarcoma should be studied so that specific primary and secondary chromosomal anomalies can be identified in human osteosarcoma.

High frequency of telomeric association in a family with multiple congenital neoplasia.

Chromosomal analysis of the peripheral blood cultures of a married couple whose second pregnancy gave birth to twin daughters with multiple congenital malignancies revealed normal karyotypes of 46,XX and 46,XY, respectively. However, in the father's blood, 23.3% of metaphases showed telomere-telomere associations involving single-single and double-double chromatids. Such associations were not observed in the metaphases of the mother. We speculate from these observations that the father's genotype may somehow be responsible for the congenital malignancies in their twin daughters.

Molecular inclusion of rofecoxib with cyclodextrin: pharmacological properties in laboratory animals.

Rofecoxib is practically insoluble in water and its prolonged use is associated with the incidence of side effects like gastrointestinal perforations, ulcerations and bleeding. Therefore, an attempt has been made to improve the aqueous solubility of the drug by making an inclusion complex using dimethyl-beta-cyclodextrin (DIMEB). The complexes were prepared by kneading and by the spray drying method. The prepared complexes showed better anti-inflammatory activity and decreased ulcerogenic potential than the pure drug.

Methemoglobinemia due to quinine causing severe acute kidney injury in a child.

Congenital methemoglobinemia is a rare condition resulting from a deficiency of nicotinamide adenine dinucleotide-cytochrome b5 reductase. Acquired methemoglobinemia may result due to certain drugs, chemicals and food items. Information on epidemiological determinants from India is sparse. This report describes methemoglobinemia in a 4-year-old child after parenteral administration of quinine causing acute kidney injury. This case emphasizes the need of awareness of potential adverse events of antimalarial drugs. Prompt management of methemoglobinemia is essential to avoid potential life-threatening complications.

Epidemiological study of a large cluster of fungaemia cases due to Kodamaea ohmeri in an Indian tertiary care centre.

While performing molecular confirmation of phenotypically identified Candida tropicalis isolates, we re-identified a few isolates as Kodamaea ohmeri. This led us to the present epidemiological investigation of K. ohmeri fungaemia cases. All phenotypically identified C. tropicalis blood isolates during October 2008 through to December 2009 at our advanced paediatric centre were included for molecular identification by sequencing of the internal transcribed spacer and D1/D2 regions of rDNA. After identifying a large cluster K. ohmeri fungaemia cases, a case-control study was carried out retrospectively to analyse potential risk factors for K. ohmeri fungaemia. Molecular typing of the isolates was performed using a fluorescent amplified fragment length polymorphism (FAFLP) technique. The antifungal susceptibility testing was performed as per the M27-A3 protocol of CLSI. Thirty-eight (25.7%) of 148 phenotypically identified C. tropicalis isolates were confirmed as K. ohmeri by sequencing and FAFLP. By case-control analysis, piperacillin-tazobactam was significantly associated with the K. ohmeri fungaemia. The FAFLP analysis showed that all K. ohmeri isolates had >92% similarity. The azoles and echinocandins had good in vitro activity against K. ohmeri, though 86.8% of the isolates had MIC of 1 mg/L for amphotericin B. The response to antifungal therapy could be evaluated in 27 patients and 70.4% of patients recovered after antifungal therapy. The present study reports the largest cluster of K. ohmeri fungaemia from a single centre. The study also stresses the need for accurate identification of clinical yeast isolates.

India--workshops on "HIV/AIDS: the law and ethics".

The Lawyers Collective HIV/AIDS Unit is a non-governmental organization providing legal aid, advice, and support to people with HIV/AIDS in India. This article summarizes a series of workshops on "HIV/AIDS: The Law and Ethics" organized by the Unit to empower people with HIV/AIDS and educate the Indian judiciary.

A high-resolution G-banding idiogram of Rattus norvegicus chromosomes.

G-banded karyotypes of Rattus norvegicus fibroblast cells at the late prophase, prometaphase, early metaphase, mid and late metaphase, and diagrammatic representation of the banding patterns at the 450-band level are presented. High-resolution G-banded rat chromosomes were prepared following the actinomycin D pretreatment technique. Silver-stained nucleolus organizer regions (Ag-NORS) were found in chromosome pairs 3, 11 and 12 of the rat karyotype.

Multiple polyposis coli associated with Gardner's syndrome and chromosomal mosaicism: a family analysis.

A family in which the proband (father) has multiple polyposis coli associated with Gardner's syndrome and his only son, also with multiple polyps, has been studied cytogenetically. The karyotypes of the proband and the son have shown deletion in the short arm of one chromosome 12 in a small percentage of cells. Normal cells and cells with a deletion of a 12p were noted, not only in the lymphocytes, but also in the skin fibroblast culture of the son. The karyotypes of the asymptomatic mother and their unaffected daughter were considered to be normal.

Ag-NOR staining in the Bennett wallaby, Macropus rufogriseus: evidence for dosage compensation.

Silver staining of cells in metaphase and interphase nuclei of both sexes of the Bennett wallaby, Macropus rufogriseus, has shown that (1) the nucleolus organizer region (NOR) is located only on the X chromosome (single Ag-NOR); (2) both X chromosomes in the female cells stain with silver; (3) the amounts of silver staining of metaphase chromosomes and interphase nuclei of both sexes are very similar; (4) the single X chromosome is hyperactive in male cells to equalize the expression of rRNA genes in the female cells with two X chromosomes; and (5) the mechanism of dosage compensation for rRNA genes in this species is similar to that reported for Drosophila salivary gland cells.

Telomeric association: another characteristic of cancer chromosomes?

Telomeric associations between single chromatids and double chromatids of nonhomologous normal human chromosomes and altered markers were observed in two morphologically distinct squamous-cell carcinoma lines derived from a surgical specimen. Chromosomes 2, 3, 5, and 16 were associated by their telomeric ends more frequently than other chromosomes.