Catechol oxidation by peroxidase-positive astrocytes in primary culture: an electron spin resonance study.

In rodents, chronic estrogenization has been shown to induce degeneration of dendrites and myelin figures in the hypothalamic arcuate nucleus adjacent to peroxidase-positive astrocyte processes. Because in this brain region estradiol is metabolized to 2-hydroxyestradiol (catecholestrogen), we hypothesized that the latter may be oxidized by the astrocytic peroxidase activity to cytotoxic ortho-semiquinones as occurs in peripheral tissues. Cysteamine induces nonenzymatic peroxidase activity in cultured astroglia identical to that observed in vivo. Using electron spin resonance, we demonstrate robust peroxidase-catalyzed oxidation of 2-hydroxyestradiol and dopamine by cysteamine-pretreated astrocyte cultures relative to untreated controls. These results implicate the peroxidase-positive astrocytes in the pathogenesis of estradiol-related hypothalamic damage, parkinsonism, and other free-radical-related neurologic disorders.     

Retrospective review of pemetrexed with or without platinum in malignant mesothelioma: The Australian 'Special Access Scheme' experience

Background: Pemetrexed and cisplatin have recently been shown to significantly improve survival compared with cisplatin alone. However, there are only limited data reflecting teaching hospital experience outside a clinical trial. Pemetrexed has only been available in Australia on a restricted basis since 2002. We reviewed our experience of patients treated on the Australian ‘Special Access Scheme’ at three major thoracic oncology units. Methods: Charts were reviewed for all patients enrolled on the scheme. Data was extracted on age, World Health Organization (WHO) performance status, histology, prior therapy, time from diagnosis to starting pemetrexed, chemotherapy (pemetrexed alone or with a platinum), cycle number, response rate, actuarial progression‐free and overall survival. Doses were cisplatin 75 mg/m² or carboplatin AUC = 5 and pemetrexed 500 mg/m² every 21 days. Results: 52 patients (32 male and 20 female) were reviewed. Median age was 58 years and 88% were WHO 0–1. Histology included 54% epithelial, 17% biphasic (epithelial and sarcomatoid) and 21% undefined. The median time from diagnosis to administration of pemetrexed was 145 days. Sixty‐five percent had minimal surgical intervention with video assisted thoracoscopy, pleurodesis and biopsy, while 19% had received prior palliative radiation. Seventy‐one percent were chemotherapy naïve, the remaining 29% having received previous platinum and/or gemcitabine regimens. Twenty‐three percent had pemetrexed alone, 35% in combination with carboplatin and 42% with cisplatin. The median number of cycles was 4 (range 1–13). The response rate was 33%. No toxicity was observed in 20% grade 3–4 toxicity in 10% (majority nausea/vomiting). The median progression‐free and overall survival times from starting pemetrexed were 184 days and 298 days, respectively. Conclusions: Pemetrexed‐based regimens are safe and effective in a community setting in malignant mesothelioma.     

How Can and Do Australian Doctors Promote Physical Activity?

Background.Physical inactivity is recognized as an important public health issue. Yet little is known about doctors' knowledge, attitude, skills, and resources specifically relating to the promotion of physical activity. Our survey assessed the current practice, perceived desirable practice, confidence, and barriers related to the promotion of physical activity in family practice.Methods.A questionnaire was developed and distributed to all 1,228 family practitioners in Perth, Western Australia.Results.We received a 71% response (n= 789). Family practitioners are most likely to recommend walking to sedentary adults to improve fitness and they are aware of the major barriers to patients participating in physical activity. Doctors are less confident at providing specific advice on exercise and may require further skills, knowledge, and experience. Although they promote exercise to patients through verbal advice in the consultation, few use written materials or referral systems.Conclusions.There are significant differences between self-reports of current practice and perceived desirable practice in the promotion of physical activity by doctors. Future strategies need to address the self-efficacy of family physicians and involve resources of proven effectiveness. The potential of referral systems for supporting efforts to increase physical activity by Australians should be explored.     

Rotational tomography of the normal and reconstructed middle ear in temporal bones: an experimental study

Imaging is an essential diagnostic tool in reconstructive middle ear surgery, especially in pre-operative planning. Due to ongoing improvement of imaging quality and development of new imaging techniques like e.g. rotational tomography (RT) post-operative follow-up and immediate evaluation of surgical results may become more important. The aim of this experimental study was to evaluate RT as a new tool for postoperative determination of middle ear anatomy and implant position in temporal bones. RT was performed in ten temporal bone specimen after insertion of different middle ear prostheses concerning material, shape and length (PORP; TORP; Stapes piston). An implantable hearing device (Symphonix Soundbridge®) was also implanted and visualized. For comparison some specimen additionally underwent conventional computed tomography (CT), including the newest technology. Characterization of anatomical structures of the temporal bone using RT was of comparable quality to conventional CT-scans in all investigated specimen while requiring approximately 30% of the CT’s irradiation exposure. Unlike CT the RT showed almost no problems due to metallic artefacts of the implanted prostheses. Furthermore RT enabled a 3-dimensional view of the temporal bone and angle determination of inserted prostheses towards the tympanic membrane and/or the malleus handle. Detailed imaging of the prostheses allowed determination of shape, material and localization within the specimen’s reconstructed middle ear. The new imaging technique of RT allows precise presentation of anatomical structures and middle ear implants in temporal bones. Following these experimental results it will be our future work to evaluate this method in clinical practise.     

Testicular dysgenesis and mental retardation in two incompletely masculinized XY-siblings.

Aberrations of fetal sexual development were studied in two retarded phenotypic female 46,XY dysgonadal sisters from a consanguineous marriage. Endocrine evaluation revealed an inadequate response of plasma-testosterone to human chorionic gonadotropin (hCG) stimulation and a normal response to adrenocorticotropic hormone (ACTH) administration. At exploratory laparotomy dysgenetic testes and remnants of the Müllerian and of the Wolffian duct were found. Loss of testicular function, resulting in male pseudohermaphroditism (MPH), can occur at different times during intrauterine development, resulting in a variety of clinical manifestations. A thorough evaluation is warranted in all patients in order to reach a correct diagnosis which is of importance for appropriate gender assignment and genetic counseling.