An open-label, noncomparative phase II trial to evaluate the efficacy and safety of docetaxel in combination with gefitinib in patients with hormone-refractory metastatic prostate cancer

BACKGROUND: Prostate cancer is the most common type of cancer in men, however, therapeutic options are limited. 50-90% of hormone-refractory prostate cancer cells show an overexpression of epidermal growth factor receptor (EGFR), which may contribute to uncontrolled proliferation and resistance to chemotherapy. In vitro, gefitinib, an orally administered tyrosine kinase inhibitor, has shown a significant increase in antitumor activity when combined with chemotherapy. PATIENTS AND METHODS: In this phase II study, the safety and efficacy of gefitinib in combination with docetaxel, a chemotherapeutic agent commonly used for prostate cancer, was investigated in patients with hormone-refractory prostate cancer (HRPC). 37 patients with HRPC were treated continuously with gefitinib 250 mg once daily and docetaxel 35 mg/m2 i.v. for up to 6 cycles. PSA response, defined as a =50% decrease in serum PSA compared with trial entry, was the primary efficacy parameter. PSA levels were measured at prescribed intervals. RESULTS: The response rate and duration of response were consistent with those seen with docetaxel monotherapy. The combination of docetaxel and gefitinib was reasonably well tolerated in this study. CONCLUSION: Future studies should investigate whether patients with specific tumor characteristics, e.g. EGFR protein overexpression, respond better to gefitinib than patients without, leading to a more customized therapy option.

Randomised controlled trials of homeopathy in hyperactive children: treatment procedure leads to an unconventional study design. Experience with open-label homeopathic treatment preceding the Swiss ADHD placebo controlled, randomised, double-blind, cross-over trial

BACKGROUND: Treatment of patients with attention deficit hyperactivity disorder (ADHD) with homeopathy is difficult. The Swiss randomised, placebo controlled, cross-over trial in ADHD patients (Swiss ADHD trial) was designed with an open-label screening phase prior to the randomised controlled phase. During the screening phase, the response of each child to successive homeopathic medications was observed until the optimal medication was identified. Only children who reached a predefined level of improvement participated in the randomised, cross-over phase. Although the randomised phase revealed a significant beneficial effect of homeopathy, the cross-over caused a strong carryover effect diminishing the apparent difference between placebo and verum treatment. METHODS: This retrospective analysis explores the screening phase data with respect to the risk of failure to demonstrate a specific effect of a randomised controlled trial (RCT) with randomisation at the start of the treatment. RESULTS: During the screening phase, 84% (70/83) of the children responded to treatment and reached eligibility for the randomised trial after a median time of 5 months (range 1-18), with a median of 3 different medications (range 1-9). Thirteen children (16%) did not reach eligibility. Five months after treatment start, the difference in Conners Global Index (CGI) rating between responders and non-responders became highly significant (p = 0.0006). Improvement in CGI was much greater following the identification of the optimal medication than in the preceding suboptimal treatment period (p < 0.0001). CONCLUSIONS: Because of the necessity of identifying an optimal medication before response to treatment can be expected, randomisation at the start of treatment in an RCT of homeopathy in ADHD children has a high risk of failure to demonstrate a specific treatment effect, if the observation time is shorter than 12 months.

Change in pain severity with open label venlafaxine use in patients with a depressive symptomatology: an observational study in primary care

PURPOSE: Venlafaxine has shown benefit in the treatment of depression and pain. Worldwide data are extensively lacking investigating the outcome of chronic pain patients with depressive symptoms treated by venlafaxine in the primary care setting. This observational study aimed to elucidate the efficacy of venlafaxine and its prescription by Swiss primary care physicians and psychiatrists in patients with chronic pain and depressive symptomatology. SUBJECTS AND METHODS: We studied 505 patients with depressive symptoms suffering from chronic pain in a prospective naturalistic Swiss community based observational trial with venlafaxine in primary care. These patients have been treated with venlafaxine by 122 physicians, namely psychiatrists, general practitioners, and internists. RESULTS: On average, patients were treated with 143+/-75 mg (0-450 mg) venlafaxine daily for a follow-up of three months. Venlafaxine proved to be beneficial in the treatment of both depressive symptoms and chronic pain. DISCUSSION: Although side effects were absent in most patients, physicians might have frequently omitted satisfactory response rate of depression by underdosing venlafaxine. Our results reflect the complexity in the treatment of chronic pain in patients with depressive symptoms in primary care. CONCLUSION: Further randomized dose-finding studies are needed to learn more about the appropriate dosage in treating depression and comorbid pain with venlafaxine.

On-chip non-invasive and label-free cell discrimination by impedance spectroscopy

OBJECTIVES: Many flow-cytometric cell characterization methods require costly markers and colour reagents. We present here a novel device for cell discrimination based on impedance measurement of electrical cell properties in a microfluidic chip, without the need of extensive sample preparation steps and the requirement of labelling dyes. MATERIALS AND METHODS, RESULTS: We demonstrate that in-flow single cell measurements in our microchip allow for discrimination of various cell line types, such as undifferentiated mouse fibroblasts 3T3-L1 and adipocytes on the one hand, or human monocytes and in vitro differentiated dendritic cells and macrophages on the other hand. In addition, viability and apoptosis analyses were carried out successfully for Jurkat cell models. Studies on several species, including bacteria or fungi, demonstrate not only the capability to enumerate these cells, but also show that even other microbiological life cycle phases can be visualized. CONCLUSIONS: These results underline the potential of impedance spectroscopy flow cytometry as a valuable complement to other known cytometers and cell detection systems.

Understanding Michigan nonindustrial private forest landowners attitudes and knowledge about forest management

Approximately one-fourth of the non-industrial private forestland (NIPF) owners in the state of Michigan, who collectively own approximately 50% of the private forested land, have conducted commercial timber harvest in recent years. Previous studies indicated that NIPFs preferred to manage their forest for a sustained yield of high-quality timber, but were limited to even-aged regeneration treatments or conversion for uneven-aged silviculture due to previous cuttings. Improved knowledge about NIPF’s intentions and forest management behavior could be useful for successful implementation of sustained yield management. This study’s objective was to identify more active NIPF’s attitudes towards timber management, their forest management practices and whether their forest management behavior leads or leads not to q management for sustained yield. Active NIPF’s intentions to harvest timber for biofuels and its suitability with NIPF’s forest management behavior will be discussed. Phone interviews of 30 NIPFs who have experience with commercial timber harvests were conducted between August and October 2011. All interviews were recorded, transcribed, and analyzed for identifying NIPF’s motivations, attitudes, forest management behavior and forestry related knowledge. Interviewees, whether consciously or not, tended to manage their land for a sustained yield and they would be willing to harvest timber for biofuels facility as long as it benefits landowners management goals.

Balancing wildlife and bioenergy values on private forestlands in the eastern Upper Peninsula of Michigan

There is interest in developing a reliable, sustainable, domestic U.S. biofuels industry. A domestic biofuels industry has the potential to provide economic, environmental, and national security benefits on a local, regional, national, and global level. The Mascoma Corporation plans to develop a cellulosic ethanol facility in Michigan’s eastern Upper Peninsula. The primary feedstock of the plant site would be trees sourced within a 150 mile supply radius. In the eastern Upper Peninsula, this radius encompasses Alger, Chippewa, Delta, Luce, Mackinac, and Schoolcraft counties. In these six counties there are 1,320,500 acres of NIPF (non-industrial private forestlands). These acres account for 40% of the total timberland in these six counties. Thus it is likely that in order for the successful implementation of a cellulosic ethanol facility the support of local NIPF owners will be necessary. This thesis presents research on how eastern Upper Peninsula forest landowners think about and manage their land. It is based on 48 in-depth interviews with these landowners. The goal was to determine how landowner values and beliefs, on a variety of issues including wildlife management, land management, biofuels development, and climate change, are expressed through both their current management decisions, and possibly their future land management decisions. Some of the values articulated by the landowners in this study included biodiversity protection, conservation of healthy game populations, and the production of high-value timber. Understanding the values and beliefs of landowners in the eastern Upper Peninsula of Michigan is critical for successfully developing a sustainable regional woody bioenergy.