The efficacy of amiodarone for ventricular arrhythmias can be predicted with clinical electrophysiological studies

We report five cases of dysfunction of the sinus node in patients suffering from familial amyloidosis with polyneuropathy. The implantation of a pacemaker resulted in symptomatologic relief in all.     

An exploratory qualitative study of women's perceptions of risk management options for familial ovarian cancer: implications for informed decision making

OBJECTIVE: Women who are at increased risk of familial ovarian cancer face complex decisions about strategies for managing their risk due to a lack of evidence regarding the benefits of ovarian cancer screening (OCS) and prophylactic surgery. At present, there is a limited understanding of women's attitudes towards these options. METHOD: In-depth interviews were conducted to explore perceptions of ovarian cancer screening and prophylactic oophorectomy (PO) in 10 women who were newly identified as being at increased risk of familial ovarian cancer. RESULTS: The study findings highlight the gaps in women's knowledge about risk management options. Although most women derived considerable reassurance from ovarian screening, many were not aware of the limitations of the screening process or the likelihood of receiving false positive results. Areas in which women's knowledge about prophylactic oophorectomy could be improved include the practicalities of surgery, the risks and benefits of HRT given postsurgically, the limitations of surgery in removing risk, and the absence of concrete information on which to base surgical decisions. In particular, women who were not previously aware of their increased risk may need additional psychological support and preparation. CONCLUSIONS: The present study raises serious questions about the extent to which women are making informed decisions about familial ovarian cancer risk management strategies. Suggestions are made for improving the information and support provided to women and for large-scale prospective research.     

Phase 2 study of BCNU and temozolomide for recurrent glioblastoma multiforme: North American Brain Tumor Consortium study

The purpose of this study was to evaluate the activity, measured in terms of progression-free survival (PFS) and response rates, of 1,3-bis(chloro-ethyl)-1-nitrosourea (BCNU) plus temozolomide in adult patients with recurrent glioblastoma multiforme. The phase 2 dose and schedule for this trial was BCNU 150 mg/m(2) i.v. followed in 2 h by temozolomide 550 mg/m(2) as a single oral dose. Treatment was repeated every 6 weeks for up to 8 cycles unless tumor progression was documented. The primary end point was PFS at 6 months (PFS-6). Response was a secondary end point, measured by MR imaging, neurological status, and steroid requirements prior to each 6-week cycle. The median age of eligible patients was 53, and 89.5% had no prior chemotherapy. All patients were evaluable for toxicity and time to progression. The PFS-6 was 21%. Overall survival was 68% at 6 months and 26% at 1 year. The MRI response for 36 patients was 2 partial responses, 2 minor responses, 19 cases of stable disease, and 13 immediate progressions. Median survival was 34 weeks, and median PFS was 11 weeks. Toxicity was primarily myelosuppression; no toxic deaths occurred. Historical phase 2 study data in this patient population show a PFS-6 of 15%. Recent data for use of temozolomide alone have shown a PFS-6 of 21%. We conclude that BCNU plus temozolomide when used in these doses and schedule has only modest activity, with significant toxicity, and appears to be no more effective than single-agent temozolomide.     

Relating testosterone levels and free play social behavior in male and female preschool children

This study assessed potential relationships between a series of behavioral measures seen in the interactions of preschool children with their peers (particularly aggressive behavior) and testosterone levels. 28 boys and 20 girls of preschool age were videotaped in free play interactions. Their behavior was then evaluated with particular emphasis on aggression and affiliation in play and social interactions. Testosterone levels were measured using radioimmunoassay in saliva samples. Correlation analysis revealed a positive relationship in boys between testosterone and giving and receiving aggression in the context of 'social interactions' (serious aggression), but not in the context of play (playful aggresstion). Testosterone can be a useful biological marker for serious aggression (and behavioral patterns reflecting different levels of sociability) in preschool boys.     

Population pharmacokinetics and exploratory pharmacodynamics of ifosfamide according to continuous or short infusion schedules: an n = 1 randomized study

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT
• The optimal infusion duration for ifosfamide remains to be determined.
• No differences according to time of infusion have been identified in traditional pharmacokinetic endpoints, such as area under the curve.
• The impact on pharmacodynamics has never been modelled or correlated with pharmacokinetics.
WHAT THIS STUDY ADDS
• The pharmacokinetics and pharmacodynamics of ifosfamide and its main metabolites can both be modelled with no influence of infusion duration.
• Pharmacodynamic modelling (renal and haematological toxicity) allows further simulations of new schedules with favourable toxicity profiles.  

AIMS

To model the pharmacokinetics and pharmacodynamics of ifosfamide and its key metabolites. The pharmacodynamic parameters included were renal toxicity and myelosuppression measured using urinary β₂-microglobulin (BMG) and absolute neutrophil count (ANC), respectively.  

METHODS

Seventeen patients were enrolled into an n  = 1 randomized trial during two consecutive cycles of ifosfamide 9 g m⁻² during each cycle given by a 3 h or 72 h infusion. Data were analyzed using NONMEM.  

RESULTS

Ifosfamide and metabolite concentration–time profiles were described by a one-compartment open-model with auto-induction of clearance. BMG and ANC time-courses were related to ifosfamide concentration via indirect response models.  

CONCLUSIONS

This modelling allowed the simulation of weekly schedules of flat doses with favourable myelotoxic profiles.