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.     

Localization of Apaf1 gene expression in the early development of the mouse by means of in situ reverse transcriptase-polymerase chain reaction.

Apoptosis is an essential ubiquitous process that controls the duration of the life span of cells, thus playing a crucial role in morphogenetic, histogenetic, and phylogenetic developmental processes. Apaf1 (apoptosis protease activating factor 1) is one of the central mediators of the intrinsic apoptotic pathway and a part of the apoptosome, which activates procaspase-3 and promotes cell death. Gene knockout of Apaf1 in mice leads to late embryonic lethality with malformations such as the persistence of interdigital webs and hyperplasia of brain and retina. Therefore, Apaf1 is generally believed to play a crucial role in developmental apoptosis and have a widespread expression. However, its pattern of expression in early development remains unknown. To specify whether Apaf1 indeed plays this key role, we investigated the pattern of gene expression for Apaf1 in mouse embryos on day 7, 9, and 12 of development. Our results show, that gene expression for Apaf1 first occurs within the embryo between day 7 and 9 of development, becoming more widespread toward day 12 and then includes structures, such as yolk sac, mesenchyme, cartilage, heart anlage, otic vesicle, peridermis, and anlagen of the spinal ganglia and vertebral bodies. Our results also show that gene expression for Apaf1 is not ubiquitous in early mouse development. This finding indicates that cell death processes are independent of or less dependent on Apaf1 during this time. Of interest, an active gene expression for Apaf1 is also present in organ anlagen such as heart or intestine, in which no obvious phenotype is seen after Apaf1 deletion. This finding suggests a possible role for Apaf1 in such anlagen as a putative alternative compensatory pathway, which could be switched on in the case of defects in the mediators that are normally involved in such organs.     

Sildenafil Prevents Cardiovascular Changes after Bone Marrow Fat Embolization in Sheep

Background: Sudden, intraoperative cardiovascular deterioration as a result of pulmonary embolization of bone marrow fat is a potentially fatal complication during total hip and knee arthroplasty, intramedullary nailing, and spine surgery. Anesthetic management is challenging in the presence of increased right ventricular afterload due to pulmonary hypertension. Selective pulmonary vasodilation may be an appropriate prophylactic or therapeutic measure. The effect of sildenafil (phosphodiesterase inhibitor) on cardiovascular deterioration after bone marrow fat embolization was therefore investigated.

Methods: Bone cement (polymethylmethacrylate) was injected into three lumbar vertebrae in 12 sheep. Invasive blood pressures and heart rate were recorded continuously until 60 min after the last injection. Cardiac output and arterial and mixed venous blood gas variables were measured at selected time points. Before the first cement injection, 6 animals received a bolus injection (0.7 mg/kg) of sildenafil, with continuous infusion (0.2 mg [middle dot] kg-1 [middle dot] h-1) thereafter. Postmortem lung and kidney biopsies were taken for semiquantitative analysis of intravascular fat.

Results: Fat embolism was associated with a transient increase (21 +/- 7mmHg) in pulmonary arterial pressure. A transient decrease in arterial blood pressure and temporary increases in central venous pressure and dead space were also observed. No significant changes in any cardiovascular variable were observed after fat embolism in the sildenafil group. There was significantly (P < 0.05) less intravascular fat in the lungs of the sildenafil (median count of 5 emboli per microscopic view) compared with the control group (median count of 1).     

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.     

Head-to-head comparison of retropubic, perineal and laparoscopic radical prostatectomy

OBJECTIVE: As more patients are diagnosed with prostate cancer at an early stage, it is becoming increasingly important to refine the technique of surgical excision. For this purpose we have generated objective data comparing three different surgical approaches used by three experienced surgeons. METHODS: We prospectively compared three contemporary personal series of 50 consecutive radical prostatectomy (RP) patients. The health-related quality of life was evaluated preoperatively and in months 1, 3, 6, 12 and 24. RESULTS: Considering in turn the patients undergoing retropubic, perineal and laparoscopic RP, the median procedure time was 2 h and 27 min, 1 h and 50 min and 4 h, with a transfusion rate of 2, 0 and 8%, respectively. In the perineal group there were more wound infections. Median catheter drainage was 7, 10 and 7 days and zero, 13 and one patients needed reinsertion of a catheter. Early continence varied considerably, with 57.4, 11.4 and 6.3% of patients pad-free after 1 month, but there were no differences in social continence (zero or one pad) with 97.8, 97.8 and 91.9% after 2 years. The Litwin score for incontinence (preoperative minus postoperative) was -24, -41 and -63% after 1 month and -13, +3 and -29% after 2 years. Twenty-nine, five and 15 patients had a preoperative five-item version of International Index of Erectile Function (IIEF-5) score of > or = 17 points and a nerve-sparing procedure. After 2 years, 48.1, 0 and 0% had an IIEF-5 score of > or = 17 points without the use of phosphodiesterase type 5 (PDE-5) inhibitors, but when including patients using inhibitors there were no significant differences. CONCLUSIONS: A comparison of morbidity, short-term convalescence and long-term side-effects of different surgical techniques is strongly biased by both the preoperative status of patients and the skill of the surgeons. Overall, we found some differences in the short-term results (e.g. early continence) and comparable long-term results.