An Update on Tamoxifen and the Chemo-Preventive Potential of Vitamin E in Breast Cancer Management.

Breast cancer (BC) is the most common female cancer in terms of incidence and mortality worldwide. Tamoxifen (Nolvadex) is a widely prescribed, oral anti-estrogen drug for the hormonal treatment of estrogen-receptor-positive BC, which represents 70% of all BC subtypes. This review assesses the current knowledge on the molecular pharmacology of tamoxifen in terms of its anticancer and chemo-preventive actions. Due to the importance of vitamin E compounds, which are widely taken as a supplementary dietary component, the review focuses only on the potential importance of vitamin E in BC chemo-prevention. The chemo-preventive and onco-protective effects of tamoxifen combined with the potential effects of vitamin E can alter the anticancer actions of tamoxifen. Therefore, methods involving an individually designed, nutritional intervention for patients with BC warrant further consideration. These data are of great importance for tamoxifen chemo-prevention strategies in future epidemiological studies.

Lasers and laser-like devices: part one.

Lasers have been used in dermatology for nearly 50 years. Through their selective targeting of skin chromophores they have become the preferred treatment for many skin conditions, including vascular malformations, photorejuvenation and acne scars. The technology and design of lasers continue to evolve, allowing greater control of laser parameters and resulting in increased safety and efficacy for patients. Innovations have allowed the range of conditions and the skin types amenable to treatment, in both general and cosmetic dermatology, to expand over the last decade. Integrated skin cooling and laser beam fractionation, for example, have improved safety, patient tolerance and decreased downtime. Furthermore, the availability and affordability of quality devices continues to increase, allowing clinicians not only to access laser therapies more readily but also to develop their personal experience in this field. As a result, most Australian dermatologists now have access to laser therapies, either in their own practice or within referable proximity, and practical knowledge of these technologies is increasingly required and expected by patients. Non-laser energy devices utilising intense pulsed light, plasma, radiofrequency, ultrasound and cryolipolysis contribute to the modern laser practitioners' armamentarium and will also be discussed.

Ice anaesthesia in procedural dermatology.

This article presents findings from a survey of Australian dermatologists who were questioned about their preferred pain control methods when carrying out injectable procedures. We also present, what is to the best of our knowledge, the first proof-of-concept experiment exploring the relationship between ice-to-skin contact time and skin surface temperature, using both ice wrapped in latex and ice wrapped in aluminium foil. Of 79 dermatologists 32 responded to the survey (41% response rate): 31 (97%) injected botulinum toxin type A (BTA) for dynamic lines, 26 (81%) injected BTA for hyperhidrosis, and 24 (75%) injected skin fillers. Ice anaesthesia was the most common method of pain control (75%) followed by use of topical anaesthesia (50%) such as EMLA, compound agents and lignocaine 4%. Ice wrapped in latex or latex-like material was the most common ice packaging used by those surveyed and the median ice-to-skin contact time was 10 s. The ice experiment results indicated that ice wrapped with aluminium foil was equivalent to ice wrapped in latex for short contact times (< 20 s), but more effective at reducing skin temperature with longer contact times (> 20 s). These findings will be of relevance to cosmetic and paediatric dermatologists or any area of procedural medicine where effective non-injectable pain control is required.

Subcutaneous injection of kisspeptin-54 acutely stimulates gonadotropin secretion in women with hypothalamic amenorrhea, but chronic administration causes tachyphylaxis.

BACKGROUND: Kisspeptin is a critical regulator of normal reproductive function. A single injection of kisspeptin in healthy human volunteers potently stimulates gonadotropin release. However, the effects of kisspeptin on gonadotropin release in women with hypothalamic amenorrhea (HA) and the effects of repeated administration of kisspeptin to humans are unknown. AIM: The aim of this study was to determine the effects of acute and chronic kisspeptin administration on gonadotropin release in women with HA. METHODS: We performed a prospective, randomized, double-blinded, parallel design study. Women with HA received twice-daily sc injections of kisspeptin (6.4 nmol/kg) or 0.9% saline (n = 5 per group) for 2 wk. Changes in serum gonadotropin and estradiol levels, LH pulsatility, and ultrasound measurements of reproductive activity were assessed. RESULTS: On the first injection day, potent increases in serum LH and FSH were observed after sc kisspeptin injection in women with HA (mean maximal increment from baseline within 4 h after injection: LH, 24.0 +/- 3.5 IU/liter; FSH, 9.1 +/- 2.5 IU/liter). These responses were significantly reduced on the 14th injection day (mean maximal increment from baseline within 4 h postinjection: LH, 2.5 +/- 2.2 IU/liter, P < 0.05; FSH, 0.5 +/- 0.5 IU/liter, P < 0.05). Subjects remained responsive to GnRH after kisspeptin treatment. No significant changes in LH pulsatility or ultrasound measurements of reproductive activity were observed. CONCLUSION: Acute administration of kisspeptin to women with infertility due to HA potently stimulates gonadotropin release, but chronic administration of kisspeptin results in desensitization to its effects on gonadotropin release. These data have important implications for the development of kisspeptin as a novel therapy for reproductive disorders in humans.

The relationship of in vivo 31P MR spectroscopy to histology in chronic hepatitis C.

Liver biopsy remains the gold standard for characterizing diffuse liver disease and is associated with significant morbidity and, rarely, mortality. Our aim was to investigate whether a noninvasive technique, in vivo phosphorus 31 ((31)P)-magnetic resonance spectroscopy (MRS), could be used to assess the severity of hepatitis C virus (HCV)-related liver disease. Fifteen healthy controls and 48 patients with biopsy-proven HCV-related liver disease were studied prospectively. Based on their histologic fibrosis (F) and necroinflammatory (NI) scores, patients were divided into mild hepatitis (F or= 4/18), and cirrhosis (F = 6/6). Hepatic (31)P MR spectra were obtained using a 1.5-T spectroscopy system. Quantitation of the (31)P signals was performed in the time domain using the Advanced MAgnetic RESonance algorithm. There was a monotonic increase in the mean +/- 1 standard error phosphomonoester (PME) to phosphodiester (PDE) ratios for the control, mild disease, moderate disease, and cirrhosis groups: 0.15 +/- 0.01, 0.18 +/- 0.02, 0.25 +/- 0.02, 0.38 +/- 0.04, respectively (ANOVA, P <.001). An 80% sensitivity and specificity was achieved when using a PME/PDE ratio less than or equal to 0.2 to denote mild hepatitis and a corresponding ratio greater than or equal to 0.3 to denote cirrhosis. No other significant spectral changes were observed. In conclusion, (31)P MRS can separate mild from moderate disease and these 2 groups from cirrhosis. The ability to differentiate these populations of patients has therapeutic implications and (31)P MRS, in some situations, would not only complement a liver biopsy but could replace it and be of particular value in assessing disease progression.