Phase 2 study of T138067-sodium in patients with malignant glioma: Trial of the National Cancer Institute of Canada Clinical Trials Group

We studied the activity of T138067-sodium in patients with malignant gliomas. T138067-sodium is a unique new chemotherapy agent that inhibits microtubule formation by binding irreversibly and specifically to beta(1), beta(2)and beta(4) isotypes of 3-tubulin, causing cell arrest at G(2)/M and inducing apoptosis. Patients with recurrent anaplastic astrocytoma or glioblastoma multiforme were treated intravenously with 330 mg/m(2) of T138067-sodium weekly. Treatment was continued until the patient experienced either unacceptable toxicity or progressive disease. Patients had to have histologically proven glioma, have bidimensionally measurable disease at least 1 cm x 1 cm, and have received no more than one prior adjuvant chemotherapy. No chemotherapy or radiotherapy for recurrent disease was permitted. Nineteen patients entered the trial. One patient was found to be ineligible. There were two patients with anaplastic astrocytoma and 16 with glioblastoma multiforme. Only two patients had received prior adjuvant chemotherapy. The first seven patients had full pharmacokinetic sampling. No dose-limiting toxicity was seen, and pharmacokinetic results were consistent with those from nonglioma patients. The most common drug-related effects were fatigue (33%), nausea (28%), neutropenia (28%), and anorexia (17%). No patients stopped the study because of toxicity. No responses were seen in the 15 eligible patients who completed at least one cycle. Three patients had stable disease with a median duration of 2.6 months. Our results suggest that given in this dose and schedule T138067-sodium does not have activity in this population of anaplastic astrocytoma and glioblastoma multiforme.     

The changing discourse on population and development: toward a new political demography

The United Nations (UN) Millennium Project is an independent advisory body commissioned by UN Secretary General Kofi Annan to advise the United Nations on strategies for achieving the Millennium Development Goals (MDGs)–the set of internationally agreed-upon targets for reducing poverty, hunger, disease, illiteracy, environmental degradation, and discrimination against women by 2015. The Millennium Project presented its findings to the Secretary General in January of 2005 in a report entitled Investing in Development: A Practical Plan to Achieve the Millennium Development Goals. The report is expected to play a central role in the high-level Summit of the UN General Assembly on the Millennium Development Goals in September 2005. The March 2005 issue of Studies included a commentary by Barbara Crossette that addressed the question of why the Millennium Development Goals do not include a reproductive health goal. In this special section, six scholars and policymakers in the fields of population and reproductive health reflect on the context, scope, and significance of the treatment of reproductive health and rights within the Millennium Development Goals. The opening commentary from Stan Bernstein, a participant in the UN Millennium Project, provides historical context. In the four alphabetically arranged essays that follow, Alaka Malwade Basu, Mahmoud Fathalla, Adrienne Germain and Ruth Dixon-Mueller, and Steven W. Sinding offer critical analyses of the MDG-reproductive health nexus. Included after the commentaries are three excerpts from the full report of the Millennium Project and a chapter from a Millennium Project Task Force report calling for the guarantee of sexual and reproductive health and rights. All of the Millennium Project documents can be found at 〈 http://www.unmillenniumproject.org 〉.     

Can women's autonomy impede male involvement in pregnancy health in Katmandu, Nepal?

Women's empowerment programs focus primarily on increasing the decision-making power of women, while male involvement/couple-friendly programs emphasize communication and negotiation within couples in making decisions. In-depth-interviews and focus group discussions were conducted to investigate patterns of household decision-making and the context of male involvement behaviors in Katmandu, Nepal. A questionnaire focusing on household decision-making and husbands' roles during pregnancy was administered to 592 pregnant women receiving antenatal services at a large maternity hospital. Multivariate regression techniques were used to compare male involvement behaviors across varying levels of women's autonomy, represented by different decision-making patterns. Higher women's autonomy, as measured by her sole final decision-making power, was associated with significantly lower male involvement in pregnancy health. After adjustment for other covariates, each additional decision in which a woman had final say was associated with a significantly lower likelihood of her husband accompanying her to antenatal care (OR=0.70, p<0.01). Conversely, joint decision-making between the husband and wife was associated with significantly higher levels of male involvement in pregnancy health. For each additional decision made jointly with husbands, women were more likely to discuss health with their husbands (OR=1.47, p<0.001), to make birth preparations (OR=1.19, p<0.05), and to experience a high level of male involvement (OR=1.29, p<0.05). The positive associations between joint decision-making and male involvement imply that couple communication and shared negotiation strategies can improve health practices. These results indicate that programs intended to increase women's empowerment and/or women's health must consider the dynamics and ramifications of including or excluding males in their efforts. Involving husbands and encouraging couples' joint decision-making in reproductive and family health may provide an important strategy in achieving both women's empowerment and women's health goals.     

Third Prize: Comparison of radical nephrectomy, laparoscopic microwave thermotherapy, cryotherapy, and radiofrequency ablation for destruction of experimental VX-2 renal tumors in rabbits

BACKGROUND AND PURPOSE: Currently available minimally invasive renal tumor-ablation procedures include cryotherapy, radiofrequency ablation, and microwave thermotherapy. In this study, we investigated the ability of these three approaches to destroy experimental renal tumors in rabbits. The mechanism of potential tumor metastasis was also explored. MATERIALS AND METHODS: The VX-2 tumor line is an aggressive rabbit epidermoid tumor with a high metastatic potential. An initial experiment comparing cooled-tip microwave thermotherapy with cryotherapy and radical nephrectomy for treatment of small VX-2 tumors revealed that all microwave-treated rabbits had local recurrence and that several also had diffuse intraperitoneal carcinomatosis. In view of these results, a second experiment was performed in which 45 New Zealand White rabbits were implanted laparoscopically with VX-2 xenografts underneath the kidney capsule and divided into five groups of 9 each. The test groups were microwave thermotherapy with a 3.5-mm cooled-tip probe, microwave thermotherapy with a 3.5-mm noncooled- tip probe, radiofrequency ablation with a 1.5-mm cooled-tip probe, radiofrequency ablation with a 1.5- mm non-cooled tip probe, and cryotherapy with a 2.3-mm cryoprobe. The control groups were five rabbits that were not treated, five rabbits with tumors that had the tumor pierced with a probe but were untreated, and five rabbits that underwent nephrectomy after piercing of the tumor. Treatment was initiated 5 days after tumor implantation. One month later, all animals were euthanized and autopsied. RESULTS: At 5 days after tumor implantation, laparoscopic inspection revealed no visible peritoneal metastases. At 1 month, in the cooled and non-cooled microwave-thermotherapy groups, carcinomatosis occurred in five and six of nine animals, respectively. In comparison, carcinomatosis was detected in two of nine animals in the cryotherapy group at autopsy. With respect to cooled and non-cooled radiofrequency ablation, carcinomatosis was observed in four of nine rabbits in each group. In the control groups, none of the animals with unpierced tumors exhibited carcinomatosis, while carcinomatosis was seen in two of the five rabbits with tumor violated by piercing and in three of the five rabbits that underwent immediate nephrectomy after piercing of the tumor. CONCLUSION: Carcinomatosis occurred most frequently in animals treated with microwave thermotherapy, followed by radiofrequency ablation, and lastly cryoablation. The simple act of piercing a highly aggressive tumor can result in local spread. More disconcerting, and less well understood, is why certain ablative modalities appear to increase the rate of intraperitoneal spread.     

Long-term success of sinus augmentation using a synthetic alloplast: a 20 patients, 7 years clinical report

An adverse architecture of the maxillary sinus is no longer a contraindication for implant placement. Grafting the sinus has become an accepted treatment modality. Techniques for lifting the sinuses are well documented and numerous articles have been published. The main difference between the multitude of articles seems to be the graft material used. After having used different grafts, with varying success, this article reflects the authors' impressions on one particular grafting material, a composite synthetic bone substitute. The objective of this clinical study was to evaluate the effectiveness, reliability and predictability of that synthetic graft material (Bioplant HTR). After treating 20 patients (22 sites, 56 implants), and after a follow-up period as long as 7 years, it was clinically and radiographically observed that achieved results are enhanced if this synthetic graft material is used and that its use enhances sinus augmentation outcome and predictability. It provides the patient with the benefits of implant-supported restorations in a simple, quick, cost-effective, predictable, and secure manner.     

Effects of aspirin, clopidogrel and dipyridamole administered singly and in combination on platelet and leucocyte function in normal volunteers and patients with prior ischaemic stroke

The aim of this study was to assess whether triple antiplatelet therapy is superior to dual and mono therapy in attenuating platelet and leucocyte function. Aspirin (A), clopidogrel (C), and dipyridamole (D) were administered singly and in various combinations (A, C, D, AC, AD, CD, ACD), each for two weeks (without washout) to 11 healthy subjects and to 11 patients with previous ischaemic stroke in two randomised multiway crossover trials. At the end of each two-week period platelet aggregation, platelet-leucocyte conjugate formation and leucocyte activation were measured ex vivo blinded to treatment. Platelets were stimulated with collagen; additional measurements were made with adenosine diphosphate (ADP), platelet activating factor (PAF), adrenaline and the combination of, ADP, PAF and adrenaline. Results show that in the presence of collagen, ACD was superior to all antagonists or combinations, except AC, in reducing aggregation, platelet-leucocyte conjugate formation, and monocyte activation (all p<0.05). ACD was also more potent than other treatments, except AC, in inhibiting the aggregation and platelet-monocyte conjugate formation induced by the combination of ADP, PAF and adrenaline. The effects were similar in both volunteers and stroke patients. No serious adverse events or major bleeding events occurred. Triple antiplatelet therapy did not appear to be more effective than combined aspirin and clopidogrel in moderating platelet and leucocyte function. Any additional clinical benefit provided by dipyridamole may be through other mechanisms of action.