FOLFCIS Treatment and Genomic Correlates of Response in Advanced Anal Squamous Cell Cancer

Background

Treatment of advanced anal squamous cell cancer (SCC) is usually with the combination of cisplatin and 5-fluorouracil, which is associated with heterogeneous responses across patients and significant toxicity. We examined the safety and efficacy of a modified schedule, FOLFCIS (leucovorin, fluorouracil, and cisplatin), and performed an integrated clinical and genomic analysis of anal SCC.

Etomidate for Rapid-sequence Intubation in Young Children: Hemodynamic Effects and Adverse Events

OBJECTIVES: Physicians commonly use etomidate for adult rapid-sequence intubation (RSI), but the manufacturer does not recommend its use for children under 10 years of age due to a lack of data. The authors present their experience with etomidate for pediatric RSI in order to further develop its risk-benefit profile in this age group. METHODS: Trained abstractors reviewed the medical records for all children under 10 years old who received etomidate for RSI between July 1996 and April 2001. RESULTS: 105 children, with an average age of 3 (+/-2.9) years, received a median dose of 0.32 (+/-0.12) mg/kg of etomidate. The systolic blood pressure increased an average of 4 mm Hg (95% CI = -3.3 to 9.2); the diastolic blood pressure increased 7 mm Hg (95% CI = -3.1 to 11) within 10 minutes of receiving etomidate. The heart rate increased an average of 10 beats/min (95% CI = 4.0 to 17.4). Complications included three patients who vomited within 10 minutes of etomidate administration. There were no cases of documented myoclonus, status epilepticus, or new-onset seizures. Thirty-eight patients received corticosteroids during the hospital course, none for suspected adrenal insufficiency. Three patients died, all from severe brain injury. CONCLUSIONS: In children less than 10 years old, etomidate seems to produce minimal hemodynamic changes, and appears to have a low risk of clinically important adrenal insufficiency, myoclonus, and status epilepticus. The association between etomidate and emesis (observed in less than 3% of enrolled patients) remains unclear. For clinical situations in which minimal blood pressure changes during RSI are critical, etomidate appears to have a favorable risk-benefit profile for children under 10 years old.     

Satellite cells express distinct patterns of myogenic proteins in immature skeletal muscle.

Satellite cells are the myogenic cells lying between the myofiber sarcolemma and basal lamina. The objective of this study was to determine the expression patterns of MyoD, myogenin, and Pax7 within the satellite cell population in the growing rat soleus and extensor digitorum longus (EDL) muscles. Secondly, the expression of the myogenic markers was also studied within the interstitial cell compartment and myonuclei. It was discovered that the soleus contained a higher number of Pax7, MyoD, or myogenin-positive nuclei compared with the EDL. Similarly, myogenin was expressed at a lower level in the myonuclei of the soleus compared with the EDL, and myogenin was expressed at a higher level in the interstitial compartment of the soleus compared with the EDL. When interstitial nuclei, myonuclei, and double-labeled nuclei were used in the estimate of the satellite cell population, it was discovered that approximately of 13% of the myofibers in a transverse section of the soleus muscle and 4.1% of EDL myofibers exhibit a labeled satellite cell nucleus. Overall, results from this study suggest that expression patterns of these markers vary predictably among muscles with different growth dynamics and phenotypic characteristics.     

OVERHEATING IN BED AS AN IMPORTANT FACTOR IN MANY COMMON DERMATOSES

Background. Extensive questioning of patients with a wide variety of skin disorders led to the impression that nocturnal overheating was probably an important factor in the initiation and the perpetuation of many skin disorders. Methods. In order to test the hypothesis, 12 “clean-skinned” subjects (6M/6F) aged 18 to 45 years were monitored electronically every 30 seconds during an 8 hour sleep period (2300 to 0700 hours), sleeping under a standard 10 tog duvet. Results. All the subjects were too hot by 3 to 4°C. All showed changes in their EEG patterns with reduced REM sleep, increased awakenings, and all showed changes in their sleep stage patterns. In addition, they all showed evidence of increased sweating in the “heat-sink” area. Conclusions. The mechanisms where by such changes could be implicated in the precipitation and perpetuation of skin disease are discussed. “Lifestyle” modification as a very effective, noninvasive, therapeutic regime is recommended. Further research along these lines would probably be very valuable and instructive.     

The direct enhancement of positive palatability by chlordiazepoxide is antagonized by Ro 15-1788 and CGS 8216

In a previous study, it was found that positive, palatability-dependent consummatory reactions in rats to intraorally infused tastes were facilitated by chlordiazepoxide (10 mg/kg). In contrast, the rats' more neutral or aversive reactions to these tastes were not facilitated by chlordiazepoxide. This suggested that chlordiazepoxide might selectively enhance the positive palatability of tastes. This effect was replicated in the present experiment, and in addition, the benzodiazepine antagonists Ro 15-1788 and CGS 8216 were found to counteract the enhancement of positive ingestive reactions produced by chlordiazepoxide. These antagonist effects generally suggest that the benzodiazepine receptor complex may be involved in making tastes more palatable after chlordiazepoxide administration.     

Conservative surgery and radiation therapy in black women with early stage breast cancer. Patterns of failure and analysis of outcome.

Between 1977 and 1986, 75 black and 615 white women with American Joint Committee (AJC) Stages I and II breast cancer were treated with excisional biopsy, axillary dissection, and radiation therapy for breast conservation. Cyclophosphamide, methotrexate, and 5-fluorouracil, with and without prednisone and tamoxifen, was given to 92% of premenopausal, 83% of perimenopausal, and 63% of postmenopausal node-positive women; 20 of 106 (19%) postmenopausal node-positive women received tamoxifen only. The clinical characteristics of the similarly treated patients were compared. The 5-year actuarial local only first failure rate was 5% for black women and 6% for white women (P = 0.53). Regional only failure as the first site of failure was 9% for blacks versus 1% for whites (P = 0.002), with regional recurrence as any component of first failure being 16% for blacks and 4% for whites (P = 0.001). The supraclavicular fossa was identified as the primary site of regional recurrence in black patients with either pathologically positive or negative axillae. Distant metastases as the only site of first failure were significantly greater in the black population with a 20% 5-year actuarial failure rate versus 11% in white patients (P = 0.01). The 5-year actuarial overall survival for the black patients was 82% versus 91% for the white patients (P = 0.01), with no-evidence-of-disease (NED) survival being 64% and 83% (P = 0.0002) and relapse-free survival (RFS) being 61% and 77% (P = 0.01), respectively. Black patients younger than 40 years of age or with pathologically positive axillary nodes had significantly worse NED, RFS, and overall survival compared with similarly staged white patients. Cosmetic results were analyzed at 3 and 5 years after completion of therapy. Although significantly fewer black patients had an excellent-to-good cosmetic result at 3 years compared with white patients, the results were not significantly different at 5 years. These results show that appropriately selected black patients with early stage breast cancer have excellent local control after conservative surgery and radiation therapy and should continue to be offered breast preservation as an alternative to mastectomy. Patterns of failure, however, demonstrated higher regional and distant recurrence rates and lower NED, RFS, and overall survival rates in most subsets of black patients reviewed.