Differential modulation of signaling pathways and apoptosis of ras-transformed 10T1/2 cells by the depsipeptide FR901228

(E)-(1S,4S,10S,21R)-7-[(Z)-ethylidene]-4,21-diisopropyl-2-oxa-12,13-dithia-5,8,20,23-tetraazabicyclo[8,7,6]-tricos-16-ene-3,6,9,19,22-pentanone (FR901228), a natural anticancer depsipeptide, induces apoptosis of ras-transformed 10T1/2 cells whereas it induces growth arrest of nontransformed counterpart cells in G0/G1 phase of the cell cycle. Our study of the effect of FR901228 treatment on intracellular signaling pathways reveals a discriminating activity of FR901228 to regulate signaling cascades differently in ras-transformed 10T1/2 cells and nontransformed counterpart cells. Induction of apoptosis of ras-transformed cells by FR901228 correlates with suppression of the extracellular signal-regulated kinase (ERK) signaling pathway through reduction of Raf expression and deactivation of Mek and Erk, inhibition of the phosphoinositide-3 kinase (PI3-K) pathway indexed by suppression of Akt activity, suppression of p38 activity, and activation of caspase-3. Expression of p21(Cip1) is not induced in ras-transformed cultures undergoing apoptosis induced by FR901228. In contrast, FR901228 induces p21(Cip1) expression in nontransformed counterpart cultures growth-arrested in G0/G1 that is also accompanied by moderate induction of the kinase activities of Raf, Mek, Erk, and Akt, but not accompanied by activation of caspase-3 or changes in p38 activity. Our study indicates a potential value of FR901228 in the treatment of cancer cells involving aberrant regulation of Ras through preferential induction of the caspase cascade and suppression of the ERK, PI3-K, and p38 pathways.     

Colchicine-induced rhabdomyolysis

OBJECTIVE: To report a case of rhabdomyolysis occurring during treatment with colchicine. CASE SUMMARY: A 44-year-old African American man was admitted to the hospital due to persistent diarrhea, vomiting, and diffuse weakness. Past medical history was significant for renal failure requiring peritoneal dialysis, gout, and a new skin lesion. Approximately 2 months prior to admission, he had been started on colchicine and allopurinol. Creatine kinase concentration on admission was >14 000 U/L. Liver function tests were elevated 5 times the upper limit of normal. Colchicine was discontinued on admission. Creatine kinase concentrations decreased significantly, and strength and ambulation improved throughout hospitalization. DISCUSSION: Colchicine was thought to be the causative factor for rhabdomyolysis in conjunction with chronic renal failure and elevated liver function tests. After discontinuation of colchicine, creatinine kinase concentrations declined and the patient's ability to walk improved. Limited case reports of colchicine-induced rhabdomyolysis have been published. CONCLUSIONS: Chronic renal failure in conjunction with elevated liver function tests appear to increase the possibility of colchicine-induced toxicity, specifically, rhabdomyolysis.     

Celecoxib to decrease urinary retention associated with prostate brachytherapy

PURPOSE: To retrospectively evaluate the effect of celecoxib in preventing urinary retention following prostate brachytherapy. MATERIALS AND METHODS: Between December 1997 and November 2001, 149 patients underwent a prostate implant. Medical records were reviewed to identify those who had acute urinary retention after the procedure. Urinary retention was scored based on replacement of the urinary catheter and the number of calls to the clinic and/or unscheduled clinic visits within 1 month after the implant. RESULTS: The use of celecoxib was associated with a decreased need for replacement of the catheter (p=.04) and decreased number of calls to the clinic and/or unscheduled clinic visits (p=.002). No patient who was given celecoxib for 1 week before brachytherapy required a urinary catheter compared to 14 (of 120) who did not receive celecoxib. CONCLUSIONS: The use of celecoxib appears to result in decreased urinary retention following prostate brachytherapy.     

Partial breast brachytherapy after lumpectomy: low-dose-rate and high-dose-rate experience

PURPOSE: The use of partial breast brachytherapy (PBB) after lumpectomy for selected patients with early-stage breast cancer reduces the adjuvant radiotherapy treatment time to <1 week. Despite the advantages of accelerated treatment, maintaining an acceptable cosmetic outcome is important. In a cohort of patients who received low-dose-rate (LDR) or high-dose-rate (HDR) PBB after lumpectomy, the clinical characteristics and treatment parameters were analyzed to identify predictors for an unfavorable cosmetic outcome. METHODS AND MATERIALS: Early-stage breast cancer patients with clear resection margins and 0-3 positive lymph nodes were eligible for PBB. Uniform guidelines for target definition and brachytherapy catheter placement were applied. The HDR PBB dose was 34 Gy in 10 fractions within 5 days, and the LDR dose was 45 Gy given at a rate of 50 cGy/h. The end points included incidence of radiation recall reaction, telangiectasias, and cosmetic-altering fibrosis. RESULTS: Between 1995 and 2000, 44 patients with early-stage breast cancer received PBB without adjuvant external beam radiotherapy after lumpectomy (31 HDR PBB, 13 LDR PBB). After a median follow-up of 42 months (range 18-86), all patients remained locally controlled. The overall rate of good/excellent cosmetic outcome was 79.6% overall and 90% with HDR PBB. Radiation recall reactions occurred in 43% of patients (6 of 14) who received adriamycin. LDR PBB and adriamycin were significant predictors for late unfavorable cosmetic changes in univariate analysis (p = 0.003 and p = 0.005, respectively). CONCLUSION: Although a high rate of local control and good/excellent cosmetic outcome is provided with HDR PBB, the risk of unfavorable cosmetic changes when treated with both LDR PBB and adriamycin is noteworthy. This suggests that HDR PBB is preferred in patients for whom adriamycin is indicated.     

Use of the think-aloud method to identify factors influencing purchase of bread and cereals by low-income African American women and implications for whole-grain education

The think-aloud method was used to determine factors influencing bread and cereal purchase by low-income African American women that have implications for whole-grain education. Women (N=70) were audiotaped as they thought aloud while purchasing groceries. Because bread and cereal account for the majority of whole-grain products consumed, transcribed verbalizations regarding purchase of bread and cereals were analyzed using content analysis procedures. Cost, preferences, eating and buying habits, and nutrition were the most important factors that influenced purchase. Nutrition issues included a general desire to eat healthy foods and specific concerns about fat, calcium, and calories, but no mention of wanting to purchase whole-grain products. Whole-grain education should focus on identification of whole-grain products, health benefits, and low-cost and tasty whole-grain options for mothers and children.     

Applying the theory of planned behavior to promotion of whole-grain foods by dietitians

The objective of this preliminary study was to apply the theory of planned behavior to explain dietitians’ intentions to promote whole-grain foods. Surveys were mailed to a random national sample of registered dietitians to assess knowledge and attitudinal, normative, and control beliefs regarding intention to promote whole-grain foods, with a 39% return rate (n=776, with 628 usable surveys from those working in direct patient care). About half of the respondents had a master’s degree, and 58% had substantial experience in the dietetics field. The theory of planned behavior explained intention to promote whole grains to a moderate extent (df=3, F=74.5, R²=0.278, P<.001). Most were positive about the health benefits, and few perceived barriers to promotion. However, many had low levels of knowledge and self-efficacy regarding ability to help clients consume more whole-grain foods. Continuing education for dietitians should use strategies that enhance self-efficacy regarding ability to promote whole-grain foods.     

Extratympanic electrocochleography: diagnostic and predictive value

OBJECTIVE: To define the clinical value of extratympanic electrocochleography (ECoG) in the diagnosis of Meniere's disease. STUDY DESIGN: Retrospective case review. SETTING: An otology/neurotology referral center. PATIENTS: A group of 252 patients with symptoms consistent with Meniere's disease and 20 normal-hearing control subjects. INTERVENTION: All patients underwent audiologic testing and extratympanic ECoG at the time of initial evaluation and, when possible, following treatment. MAIN OUTCOME MEASURES: Audiologic thresholds and summating and action potential ratios (SP:AP). RESULTS: Patients were classified into definite, probable, possible, and bilateral Meniere's disease groups according to American Academy of Otolaryngology-Head and Neck Surgery (AAO-HNS) guidelines. The definite Meniere's group demonstrated an elevated SP:AP ratio in 74% of cases, the possible Meniere's group in 64%, and the bilateral group demonstrated elevated ratios in both ears in 66%. Contralateral ears produced elevated ratios in 42% for unilateral cases, whereas 40% of these ears reported at least one contralateral symptom. All 40 control ears were normal (SP:AP > or = 0.50). Results statistically correlated (p = 0.004) with the Meniere's staging system set forth in the 1995 AAO-HNS guidelines. No correlation was found between ECoG results and disease duration. Although 72% of the 86 follow-up patients reported complete or substantial vertigo control, changes from initial ECoG results did not specifically correlate to vertigo, tinnitus, or aural fullness improvement. CONCLUSIONS: Extratympanic ECoG can be useful in the diagnosis of Meniere's disease, lending promise to possible cases where objective audiologic data are lacking. Each testing center should study its own results to establish meaningful parameters and confidence levels.     

Antenatal corticosteroids for preterm birth

A single course of antenatal corticosteroids is a rare example of a treatment that yields both a health benefit and a cost savings. This article reviews the history and background of antenatal corticosteroids, its use in clinical practice and the controversy today regarding the use of multiple courses of antenatal corticosteroids.