Using a modified nominal group technique as a curriculum evaluation tool

The modified nominal group technique (NGT) is a useful and practical course evaluation tool that complements existing methods such as evaluation forms, surveys, pretests and posttests, focus groups, and interviews. The NGT's unique contribution to the evaluation process is the semi-quantitative, rank-ordered feedback data obtained on learners' perceptions of a course's strengths and weaknesses. In this paper, we demonstrate through a worked example how to use a modified NGT as a course evaluation tool in medical education.     

Improving the effectiveness of adjuvant psychological treatment for women with breast cancer: the feasibility of providing online support

Many well-designed studies have shown psychosocial treatments for cancer to be efficacious for improving patients' quality of life, but the actual impact of these treatments may be limited by low rates of participation. Web-based treatment formats could improve effectiveness by increasing availability and accessibility. Two phases of a feasibility study are reported in this article. In the first phase, we sought to assess internet access and perceived interest in online support among 136 women with breast cancer (June-October, 1999). Levels of interest in participating in an online psychosocial treatment were associated with age, outcome expectancy, and barriers to using the internet but not stage or time since diagnosis. In the second phase, we document accrual rates among several methods of recruitment during a randomized trial (February-December, 2001) and report changes over time in internet access. Recruitment rates were substantially higher when a study representative was available in clinic to provide information about the treatment than for all other methods of recruitment. Access to the internet increased between 1999 (63%) and 2001 (70%) and varied across age groups. These results suggest that internet-based psychosocial treatments, with notable limitations, are feasible for increasing the impact of psychosocial care.     

Phase II study of weekly docetaxel alone or in combination with trastuzumab in patients with metastatic breast cancer

This study was designed to determine the efficacy and toxicity of weekly docetaxel in metastatic breast cancer when given alone (for HER2/neu negative disease) or with trastuzumab (for HER2/neu overexpressing disease). Patients with metastatic breast carcinoma received docetaxel given on 2 different schedules (group 1A, 33 mg/m2 weekly [n = 21]; group 1B, 40 mg/m2 weekly for 3 weeks with 1 week off [n = 14]). Patients with HER2/neu overexpressing disease also received trastuzumab 4 mg/kg on day 1, then 2 mg/kg on days 8 and 15 of each 28-day cycle (group 2). Fifty-two patients were treated with docetaxel alone (group 1A/B, n = 35) or in combination with trastuzumab (group 2, n = 17). Prior taxane therapy given every 3 weeks had been used for metastatic disease in 19 of 35 patients (54%) in group 1A/B and in 2 of 17 patients (12%) in group 2. The mean delivered dose intensity of docetaxel was 29 mg/m2 per week. Partial response occurred in 7 of 35 patients (21%; 95% exact binomial confidence interval [CI], 9%-38%) treated with docetaxel alone, including 3 of 19 taxane-pretreated patients (16%) and 4 of 16 taxane-naive patients (25%). Partial response occurred in 10 of 17 patients (59%; 95% CI, 34%-82%) treated with docetaxel/trastuzumab. The most common grade 3/4 toxicities, occurring in more than or equal to 10% of patients, included neutropenia (21%), pulmonary toxicity (12%), and hyperglycemia (10%). The median times to disease progression were 4.5 months (95% CI, 2.5-6.5 months) in the docetaxel group and 8.5 months (95% CI, 4.5-12.5 months) in the docetaxel/trastuzumab group. Weekly docetaxel/trastuzumab is an effective regimen for patients with HER2/neu overexpressing metastatic breast cancer. Weekly docetaxel may be effective in as many as 20% of patients who had progressive disease after treatment with taxanes given every 3 weeks.     

Future directions with angiogenesis inhibitors in colorectal cancer

The recent US Food and Drug Administration's approval of bevacizumab has reinvigorated antiangiogenic research and has moved colorectal cancer to the forefront of study for the most promising drug candidates in this class. Predicting future directions in this field requires a return to the challenges of the past. Antiangiogenic drugs have necessitated new study design paradigms and imaging techniques in the assessment of drug activity and in dose selection. The success of bevacizumab and the promise of vatalanib (PTK787/ZK222584) and the cyclooxygenase-2 inhibitors also illustrate the importance of these adaptations. A better understanding of the determinants of response to antiangiogenic agents and their mechanisms of action, especially in combination with cytotoxic drugs, is crucial to future drug development.     

Impairment of radial maze delayed nonmatching after lesions of anterior thalamus and parahippocampal cortex

This study compared the effects of lesions damaging hippocampus-related pathways in anterior thalamus (AT) and parahippocampal (PH) cortex on allocentric spatial memory. Rats were trained to perform radial maze delayed nonmatching (DNM) with random selection of arms to prevent egocentric solutions. After experimental treatment (control, excitotoxic AT, radiofrequency PH, or combined AT-PH lesions), rats were retrained for 30 sessions from 2 to 8 weeks after surgery. Results showed comparable impairments for AT and PH lesions that added without interaction in the combined AT-PH group. During chronic recovery, the AT-PH group exhibited delay-dependent deficits comparable to previous results for hippocampal lesions. Thus, AT and PH lesions appear to have separate effects that together disrupt hippocampus-dependent spatial memory.     

Effects of antenatal corticosteroids on regional brain and non-neural tissue water content in the ovine fetus

OBJECTIVE: We examined the effects of maternal corticosteroid administration on water content in regional tissue in ovine fetuses at 60%, 80%, and 90% of gestation. METHODS: After catheters were placed in the fetuses, the ewes were given four 6-mg doses of dexamethasone or placebo injections 12 hours apart over 48 hours. Water content of fetal tissue was determined 18 hours after the last injection was given to the ewes. Tissue water was determined by wet-to-dry weight ratio in brain (cerebral cortex, caudate nucleus, cerebellum, midbrain, and medulla) and non-neural tissues (kidney, liver, muscle, and skin) at each gestational age. RESULTS: Water content (P <.05) in brain regions was lower in fetuses from dexamethasone-treated than placebo-treated ewes at 60% but not 80% or 90% of gestation and in non-neural tissues at each gestational age. CONCLUSIONS: Maternal treatment with a corticosteroid regimen similar to that used in the clinical setting was associated with small decreases in brain water content early but not later in gestation. This corticosteroid treatment regimen was also associated with decreased regional non-neural tissue water content at 60%, 80%, and 90% of gestation.     

Cell death in MMTV-c-myc transgenic mouse mammary tumors may not be typical apoptosis

Enforced expression of c-myc has been shown to serve as an apoptotic stimulus in cultured cells. Prior studies have also demonstrated that several tissues expressing c-myc transgene display a large number of dead cells, although a morphologic or biochemical verification of apoptosis in these tissues has actually not been presented. In the present study, we examined the morphologic properties of cell death in the mammary tumors developed from MMTV-c-myc transgenic mice. We found that c-myc-expressing mammary tumor cells exhibited malformation of mitochondria, characterized by an amorphous matrix with very few cristae. The mitochondria were also frequently degenerated by lysis of the matrix and cristae. The protein level of cytochrome c was much lower in the areas of c-myc-expressing tumor cells compared with the adjacent tumor foci, which was previously shown to have decreased expression of c-myc, reduced frequencies of cell death, and increased frequencies of proliferating cells. In the c-myc-expressing tumor areas, there were many dying or dead cells organized in clusters, termed "dead cell islands." These cells exhibited shrinkage, DNA breakage as indicated by a positive TUNEL staining, and nuclear localization of apoptosis-inducing factor, but a lack of typical apoptotic morphology, such as nuclear condensation and formation of cell membrane blebs and apoptotic bodies. Many macrophages infiltrated into these dead cell islands, engulfing the dying or dead tumor cells. In the total tumor tissue, the protein level of caspase-3 was very low, and the poly(ADP)-ribose polymerase was present mainly as the unprocessed, inactive form. Collectively, these results suggest that programmed cell death in the c-myc transgenic mammary tumor tissue may not be typical apoptosis and may involve a caspase-independent mechanism.     

Degeneration of mammalian PNS and CNS axons is accelerated by incubation with protein synthesis inhibitors

Protein synthesis inhibitors (PSIs) increase the rate of degeneration, as measured by compound action potential (CAP) conduction, in segments of rat PNS and CNS axons. Sciatic axonal segments maintained in vitro in Krebs at 37-38 degrees C generate CAPs for 24 h compared to 8 h for axons exposed to Krebs containing two PSIs, 100 microM anisomycin and/or 35 microM cycloheximide. Spinal axonal segments at 37-38 degrees C generate CAPs for 3 h compared to 2 h for axons exposed to Krebs containing PSIs. While cooling (6-9 degrees C) slows degeneration rate, cooled sciatic axons exposed to PSIs exhibit lower peak CAPs compared to cooled control segments (P<0.005).