Mouse lymphoma thymidine kinase gene mutation assay: follow-up International Workshop on Genotoxicity Test Procedures,New Orleans,Louisiana, April 2000

The Mouse Lymphoma Assay (MLA) Workgroup of the International Workshop on Genotoxicity Test Procedures held a second harmonization meeting just prior to the U.S. Environmental Mutagen Society Meeting in New Orleans, LA, in April 2000. The discussion focused on several important aspects of the MLA, including: 1) cytotoxicity measures and their determination, 2) use of a 24-hr treatment, 3) the ability of the assay to detect aneugens, and 4) concentration selection. Prior to the meeting the group developed Microsoft Excel Workbooks for data entry. Ten laboratories entered their data into the workbooks (primarily as coded chemicals). The Excel Workbooks were used to facilitate data analysis by generating an extensive set of graphs that were evaluated by the meeting participants. Based on the Workgroup's previous agreement that a single cytotoxicity measure should be established for both the microwell and soft agar versions of the assay, the Workgroup analyzed the submitted data and unanimously agreed that the relative total growth (RTG) should be used as the cytotoxicity measure for concentration selection and data evaluation. The Workgroup also agreed that the various cytotoxicity measures should be calculated using the same methods regardless of whether the soft agar or microwell version of the assay was used. In the absence of sufficient data to make a definitive determination, the Workgroup continued to endorse the International Committee on Harmonization recommendation for the use of 24-hr treatment and made some specific 24-hr treatment protocol recommendations. The Workgroup recognized the ability of the MLA to detect at least some aneugens and also developed general guidance and requirements for appropriate concentration selection.     

Successful pregnancy in a patient with a 46,XY karyotype

OBJECTIVE: To report a case of successful pregnancy in a patient with 46,XY karyotype with primary ovarian failure. DESIGN: Case report. SETTING: Fertility Research Center, G.G. Hospital, Chennai, Tamil Nadu, India. PATIENT(S): A 27-year-old woman with hypoplastic uterus, normal fallopian tubes on both sides, and gonadal dysgenesis. INTERVENTION(S): Chromosomal analysis, diagnostic laparoscopy, donor oocyte program, gamete intrafallopian transfer, and gonadectomy. MAIN OUTCOME MEASURE(S): Response to hormone replacement therapy and the probability of achieving a pregnancy by a tubal procedure. RESULT(S): Treatment was successful, and the patient delivered a live baby. CONCLUSION(S): A hypoplastic uterus of patients with the 46,XY karyotype can be stimulated by the use of cyclical steroid therapy to accommodate pregnancy and facilitate tubal procedures in patients with normal fallopian tubes.     

Prevalence of asymptomatic recurrences of atrial fibrillation after successful radiofrequency catheter ablation

INTRODUCTION: The long-term efficacy of radiofrequency catheter ablation of atrial fibrillation (AF) has been based on patient-reported symptoms suggestive of AF. However, asymptomatic recurrences of AF may remain undetected. The aim of this study was to determine the prevalence of asymptomatic recurrences of AF after an apparently successful catheter ablation procedure for AF. METHODS AND RESULTS: Among 244 consecutive patients (mean age 53 +/- 11 years) who underwent a pulmonary vein isolation procedure for symptomatic paroxysmal AF and who reported no symptoms of recurrent AF at > or =6 months after the procedure, 60 patients with a history of > or =1 episode of AF per week were asked to participate in this study. Preablation, these patients had experienced 19 +/- 13 episodes of AF per month. The patients were provided with a patient-activated transtelephonic event recorder for 30 days, a mean of 642 +/- 195 days after the ablation procedure, and were asked to record and transmit recordings on a daily basis and whenever they felt palpitations. Seven patients (12%) felt palpitations during the study, although they had not experienced symptoms previously. Each of these 7 patients had an episode of AF documented with the event monitor during symptoms. In these 7 patients, the mean number of episodes per month decreased from 19 +/- 14 preablation to 3 +/- 1 postablation (P < 0.001). Among the 53 asymptomatic patients, an episode of AF was captured in 1 (2%) patient during the study period. CONCLUSION: Asymptomatic recurrences of AF after an apparently successful catheter ablation procedure for symptomatic paroxysmal AF are infrequent.     

Gene therapy in cardiovascular diseases

Established modalities of treatment for obstructive coronary artery disease include medical therapy, bypass surgery and percutaneous coronary intervention. Similarly, conventional treatment of congestive heart failure is also limited to medical therapy, temporary assist devices and transplantation. A significant subset of patients with severe symptomatic coronary artery disease and end stage heart failure is not eligible for these traditional methods of treatment. In spite of maximal medical and revascularization therapy, these patients may not get adequate symptomatic benefit. After a decade of investigations, gene therapy has emerged as a promising therapeutic option for this group of patients. This review discusses newer modalities of therapy for this subset, including therapeutic angiogenesis with growth factors and cell transplantation.     

Neonatal tetanus: Observations on antenatal immunization,natal and immediate post-natal factors

The objective is to study the present status of the antenatal immunization with tetanus toxoid and the natal and immediate postnatal factors among the cases of neonatal tetanus and the changes over time. Retrospective analysis of 61 case records of Neonatal Tetanus (NNT) during 1987–88 and prospective study of 19 cases of 1989 was done. The number of cases have decreased considerably from 88 in 1984 to 19 in 1989. 80% of cases were from residents outside the city. Antenatal checkup improved from 37.7% in 1987 to 73.7% in 1989. The proportion of mothers of NNT cases who received = >2 doses have increased from 19.7% in 1987–88 to 31.6% in 1989. In the year 1989, 21% and 10.5% have received the I and II doses of TT respectively at the 9th month of pregnancy, the value of which is doubtful. Majority (73.7%) were domiciliary deliveries conducted by dhais and this has not changed over the years. The importance of antenatal booking, immunization at the appropriate time, hygienic obstetric and cord care are stressed.     

An acute,epitope‐specific modification in the dopamine transporter associated with methamphetamine‐induced neurotoxicity

Preclinical studies demonstrate that repeated, high‐dose methamphetamine administrations rapidly decrease plasmalemmal dopamine uptake, which may contribute to aberrant dopamine accumulation, reactive species generation, and long‐term dopaminergic deficits. The present study extends these findings by demonstrating a heretofore unreported, epitope‐specific modification in the dopamine transporter caused by a methamphetamine regimen that induces these deficits. Specifically, repeated, high‐dose methamphetamine injections (4 × 10 mg/kg/injection, 2‐h intervals) rapidly decreased immunohistochemical detection of striatal dopamine transporter as assessed 1 h after the final methamphetamine exposure. In contrast, neither a single high dose (1 × 10 mg/kg) nor repeated injections of a lower dose (4 × 2 mg/kg/injection) induced this change. The high‐dose regimen‐induced alteration was only detected using antibodies directed against the N‐terminus. Immunohistochemical staining using antibodies directed against the C‐terminus did not reveal any changes. The high‐dose regimen also did not alter dopamine transporter expression as assessed using [¹²⁵I]RTI‐55 autoradiography. These data suggest that the repeated, high‐dose methamphetamine regimen alters the N‐terminus of the dopamine transporter. Further, these data may be predictive of persistent dopamine deficits caused by the stimulant. Future studies of the signaling cascades involved should provide novel insight into potential mechanisms underlying the physiological and pathophysiological regulation of the dopamine transporter. Synapse, 2016. © 2016 Wiley Periodicals, Inc. Synapse 70:139–146, 2016. © 2016 Wiley Periodicals, Inc.