Role of chemotherapy in dedifferentiated liposarcoma of the retroperitoneum: defining the benefit and challenges of the standard.

Benefit from chemotherapy for well-differentiated/de-differentiated (WD/DD) liposarcomas has been reported to be minimal, however traditional response criteria may not adequately capture positive treatment effect. In this study, we evaluate benefit from first-line chemotherapy and characterize imaging response characteristics in patients with retroperitoneal (RP) WD/DD liposarcoma treated at The University of Texas MD Anderson Cancer Center. Response was assessed using RECIST (Response Evaluation Criteria in Solid Tumors) and an exploratory analysis of vascular response was characterized. Among 82 patients evaluable for response to first-line therapy, 31 patients received neoadjuvant chemotherapy for localized/locally advanced disease; 51 received chemotherapy for unresectable recurrent/metastatic disease. Median overall survival from the start of chemotherapy was 29 months (95% CI 24-40 months). Response rates by RECIST: partial response (PR) 21% (17/82), stable disease (SD) 40%, and progression (PD) 39%. All RECIST responses were in patients receiving combination chemotherapy. A qualitative vascular response was seen in 24 patients (31%). Combination chemotherapy yields a response rate of 24% and a clinical benefit rate (CR/PR/SD > 6 months) of 44%, higher than previously reported in DD liposarcoma. A higher percentage of patients experience a vascular response with chemotherapy that is not adequately captured by RECIST in these large heterogeneous tumors.

Review of NMDA antagonist-induced neurotoxicity and implications for clinical development.

NMDA receptor antagonists have been investigated for many years as therapeutic agents for the treatment of neurological disorders such as stroke, epilepsy, pain and Parkinson's disease. It has been discovered, however, that many of these compounds cause adverse behavioral (psychotomimetic) effects and can produce neurotoxicity characterized by neuronal vacuolization, induction of heat-shock protein, neuronal/axonal degeneration and regional brain cell death in several animal species. It is unknown whether NMDA antagonists induce neurotoxicity in humans. The mechanism of NMDA antagonist-induced neurotoxicity is not completely known, but some evidence suggests disinhibition of GABAergic inputs to the affected neurons. Several classes of compounds have been shown to prevent NMDA antagonist-induced neurotoxicity. The extent of neurotoxicity produced by NMDA antagonists is affected by many factors, including type of antagonist, dose, length of exposure, age, sex and species. While there are no published regulatory guidelines regarding how NMDA antagonist compounds should be evaluated, sponsors and investigators of these compounds should make every effort to assess the potential for neurotoxicity. NMDA receptor antagonists, as well as other CNS-active compounds need to be analyzed for neurotoxicity through careful experimental design, adequate tissue sampling and through the use of a sensitive method of detection.

Mammography screening in single older African-American women: a study of related factors.

OBJECTIVE: Using baseline data from an intervention study, we examined cognitive, psychological, social and medical care factors in relation to the use of a mammogram in the preceding year among single African-American women aged 65 and older. METHODS: Study subjects were 325 African-American women aged 65 and older who were divorced, widowed, separated or never-married, and lived in ten public housing complexes in Nashville, Tennessee. In-person interviews were conducted to collect information on breast screening behavior, knowledge and attitude, social network and activities, emotional and psychological symptoms and signs, and medical care use. RESULTS: Compared with those who had not had a mammogram in the preceding year, women who had had a mammogram in the preceding year were three times more likely to have a regular doctor (95% confidence interval [CI] 1.4-5.0) and about six times more likely to have a doctor's recommendation for a mammogram (95%CI 3.4-11.1). In addition, they were more likely to: (a) have attended a meeting on breast health or received educational materials on breast cancer; (b) agree that a woman needs a mammogram even though she has no breast problem; (c) agree that a woman can have breast cancer without having symptoms; (d) have living children and grandchildren; and (e) attend social activities more frequently. CONCLUSIONS: While access to regular medical care and receiving a physician's recommendation are strongly associated with mammography among these older, single African-American women, education on breast health and social networks also appear to be influential.

Recruiting elderly African-American women in cancer prevention and control studies: a multifaceted approach and its effectiveness.

Barriers to engaging African Americans as research participants may be accentuated among older single African-American women partly because of financial, social, physical, and cognitive factors. This article shows our multifaceted strategies and experiences in the recruitment of single African-American women aged 65 and older in a cancer prevention and control study. The study was conducted in 10 public housing complexes in Nashville, Tennessee. Out of 367 eligible women, 325 participated in the study, resulting in a rate of 89%. The result suggests that a strategy, which targets the cultural, perceptive, and cognitive characteristics of the population, was effective for increasing the enrollment of study subjects in this population. Because the single constitute 75% of African-American women aged 65 and older; and the incidence and mortality of cancer are especially high in elderly African Americans, our experiences are encouraging for cancer prevention and control research in the population.

Remifentanil versus alfentanil as analgesic adjuncts during placement of ophthalmologic nerve blocks.

BACKGROUND AND OBJECTIVES: Short-acting opioids are often used prior to the placement of ophthalmologic nerve blocks. This study examines whether remifentanil would provide superior analgesia compared with alfentanil, without oversedation or prolonged recovery when given either as a single dose over 30 seconds or as a single dose followed by a continuous infusion, in a dose ratio of 1:7 (remifentanil:alfentanil). METHODS: Seventy-nine ASA I-III patients scheduled for elective ophthalmologic surgery participated in this multicenter, double-blind study. Patients were randomized into three groups: remifentanil (remifentanil 1 microg/kg and placebo infusion); remifentanil infusion (remifentanil 1 microg/kg and infusion of 0.2 microg/kg/min); and alfentanil (alfentanil 7 microg/kg and placebo infusion). Supplemental doses of the respective opioid were given as needed. RESULTS: Seventy-seven percent of patients in the remifentanil group were pain-free at the time of the block placement compared with 44% in the alfentanil group (P < .05). Eighty percent of patients in the remifentanil infusion group were pain-free. Although the occurrence of respiratory depression (14%) was higher in the remifentanil infusion group, it was short-lived (< or = 5 minutes) and resolved spontaneously. More than 89% of patients were awake and alert prior to surgery, and > or = 85% bypassed the phase I recovery area. Nausea and vomiting were rare. CONCLUSIONS: Remifentanil 1 microg/kg results in superior analgesia compared with alfentanil 7 microg/kg when used during the placement of ophthalmologic nerve blocks. The combination of a single dose of remifentanil followed by a continuous infusion was equally effective but resulted in a higher incidence of respiratory depression.

Intracranial pressure and hemodynamic effects of remifentanil versus alfentanil in patients undergoing supratentorial craniotomy.

Remifentanil hydrochloride is an ultra-short-acting esterase metabolized mu-opioid receptor agonist. The purpose of this study was to provide preliminary information regarding the effects of this drug on intracranial pressure (ICP) and mean arterial pressure (MAP) in patients scheduled for craniotomy. Twenty-six patients undergoing excision of supratentorial space-occupying lesions were anesthetized with 0.3-0.8 vol% isoflurane in a 2:1 mixture of nitrous oxide:oxygen. Ventilation was adjusted to provide a Paco2 of < 30 mm Hg. After the first burr hole was drilled, patients (n = 5-6 per group) were administered an intravenous infusion of study drug (placebo, remifentanil 0.5 micrograms/kg or 1.0 micrograms/kg, or alfentanil 10 micrograms/kg or 20 micrograms/kg) over 1 min. Epidural ICP and MAP values were recorded at baseline, at completion of infusion, and every minute for the next 10 min. Blood study drug concentrations were measured immediately after completion of infusion. Neither opioid caused a significant increase in ICP. Both drugs were associated with a dose-dependent decrease in MAP. Remifentanil was 31 times more potent than alfentanil for effects on MAP. We conclude that remifentanil produces similar cerebral perfusion pressure effects as does alfentanil.