Smoking delays chondrogenesis in a mouse model of closed tibial fracture healing.

Smoking delays the healing process and increases morbidity associated with many common musculoskeletal disorders, including long bone fracture. In the current study, a murine model of tibial fracture healing was used to test the hypothesis that smoking delays chondrogenesis after fracture. Mice were divided into two groups, a nonsmoking control group and a group exposed to cigarette smoke for 1 month prior to surgical tibial fracture. Mice were euthanized at 7, 14, and 28 days after surgery. The outcomes measured were immunohistochemical staining for type II collagen protein expression as a marker of cartilage matrix and proliferating cell nuclear antigen (PCNA) staining to measure proliferation at the site of injury. Toluidine blue staining and histomorphometry were used to quantify areas of cartilaginous and noncartilaginous fracture callus. Radiographs were analyzed for evidence of remodeling after injury. At day 7 after injury, mice exposed to cigarette smoke had a smaller fracture callus with less cartilage matrix compared to controls. Proliferation was present at high levels in both groups at this time point, but proliferating cells had a more immature morphology in the smoking group. At day 14, chondrogenesis was more active in smokers compared to controls, while a higher percentage of bone was present in the control animals. At day 28, X-ray analysis revealed a larger fracture callus remaining in the smoking animals. Together, these findings show that the chondrogenic phase of tibial fracture healing is delayed by smoking. This study represents, to our knowledge, the first analysis of molecular and cellular mechanisms of healing in a smoking mouse fracture model.     

Factors affecting early and long-term outcomes after completion pneumonectomy

Objective: To identify factors that affect operative mortality and morbidity and long-term survival after completion pneumonectomy. Methods: We retrospectively reviewed the charts of consecutive patients who underwent completion pneumonectomy at our cardiothoracic surgery department from January 1996 to December 2005. Results: We identified 69 patients, who accounted for 17.8% of all pneumonectomies during the study period; 22 had benign disease and 47 malignant disease (second primary lung cancer, n = 19; local recurrence, n = 17; or metastasis, n = 11). There were 50 males and 19 females with a mean age of 60 years (range, 29–80 years). Postoperative mortality was 12% and postoperative morbidity 41%. Factors associated with postoperative mortality included obesity (p = 0.005), coronary artery disease (p = 0.03), removal of the right lung (p = 0.02), advanced age (p = 0.02), and renal failure (p < 0.0001). Preoperative renal failure was the only significant risk factor for mortality by multivariate analysis (p = 0.036). Bronchopleural fistula developed in seven patients (10%), with risk factors being removal of the right lung (p = 0.04) and mechanical stump closure (p = 0.03). Overall survival was 65% after 3 years and 46% after 5 years. Long-term survival was not affected by the reason for completion pneumonectomy. Conclusion: Although long-term survival was acceptable, postoperative mortality and morbidity rates remained high, confirming the reputation of completion pneumonectomy as a challenging procedure. Significant comorbidities and removal of the right lung were the main risk factors for postoperative mortality. Improved patient selection and better management of preoperative renal failure may improve the postoperative outcomes of this procedure, which offers a chance for prolonged survival.     

Fentanyl is more effective than remifentanil at preventing increases in cerebral blood flow velocity during intubation in children

PURPOSE: Controlling the cerebral and systemic hemodynamic responses to laryngoscopy and tracheal intubation may play a role in determining clinical outcome in pediatric neurosurgical patients. This study compared the effects of remifentanil and fentanyl on cerebral blood flow velocity (CBFV) and hemodynamic profile during laryngoscopy and tracheal intubation in children under sevoflurane anesthesia. METHODS: Sixty healthy children aged two to six years undergoing dental surgery under general anesthesia were enrolled. Each child was randomly assigned to receive a remifentanil or fentanyl infusion, at a rate of 0.75, 1.0, or 1.5 microg x kg(-1) x min(-1) after induction of anesthesia with 2% sevoflurane. Middle cerebral artery blood flow velocity was measured by transcranial Doppler (TCD) sonography. Once a baseline set of hemodynamic variables and TCD measurements were recorded, the opioid infusion was started. Measurements were taken at two-minute intervals, starting four minutes prior to laryngoscopy until four minutes following naso-tracheal intubation. RESULTS: Remifentanil caused a more significant decrease in mean arterial pressure and CBFV prior to tracheal intubation than did fentanyl (P < 0.001). During laryngoscopy and for two minutes following tracheal intubation, CBFV increased in all remifentanil groups (P < 0.05), whereas it remained stable in all fentanyl groups. CONCLUSION: This study suggests that fentanyl was more effective than remifentanil at preventing increases in CBFV during and immediately following laryngoscopy and tracheal intubation in children undergoing sevoflurane anesthesia. Fentanyl also seemed to provide a more stable hemodynamic profile prior to laryngoscopy and tracheal intubation when compared to remifentanil.     

Immunophenotyping of childhood acute lymphoblastic leukemia in Saudi Arabia: Second look

Geographical variations in the incidence of disease are of considerable theoretical and practical importance. It has been claimed that the distribution of acute lymphoblastic leukemia (ALL) phenotypes in Saudi Arabia is different from that recorded in the Western literature. One hundred and twelve (112) patients under 15 years of age, diagnosed as ALL between January 1992 and May 1994 had immunophenotypes performed on their blast cells. Common ALL (cALL) together with pre-B-ALL, formed 86.5% of the total; B-cell 3%, T-cell 6% and null cell 4.5%. These figures are not significantly different from the Western literature. A previous claim from this institution in 1990, that both null and B-cell ALL were significantly increased compared with elsewhere, is not supported by the present figures. Age and sex distribution, and FAB classification, L1 77%, L2 20% and L3 3%, were also of the same order as described elsewhere and, in particular, there was no increase in the frequency of L3 subtype.     

Human papillomavirus infection in Egyptian esophageal carcinoma: correlation with p53, p21, mdm2, C-erbB2 and impact on survival

The etiological role of human papillomavirus (HPV) in esophageal carcinoma (EC) in relation to p53, mdm2, p21(waf), c-erbB2 and the overall survival (OS) rate was investigated. Tumor and normal tissues from 50 EC were evaluated by polymerase chain reaction and InnoLiPA for HPV. Single strand conformation polymorphism/sequencing were used to detect p53 gene mutations. Immunohistochemistry was performed to determine p53, mdm2, p21(waf)and c-erbB2 expression. Human papillomavirus was detected in 54% of tumors and in 24% of normal tissues. p53, mdm2 and c-erbB2 overexpression was detected in 68%, 70% and 60% of tumors and in 14%, 16% and 10% of normal samples, whereas loss of p21(waf) was evident in 64% of tumors. p53 mutations were detected in 20% of cases. Exon 8 and 5 showed the highest mutation rate (40% each), followed by exons 6 and 7 (10% each). There was a significant correlation between HPV and p53, mdm2, c-erbB2 overexpression. The OS was significantly associated with overexpression of p53 and loss of p21(waf). Human papillomavirus infection is frequent in Egyptian EC. Both p53-dependent and p53-independent pathways seem to be involved in HPV-associated EC. mdm2 and c-erbB2 are possible targets for HPV in the p53-independent pathway. However, only advanced stage and aberrant expression of p53 and p21(waf) are independent prognostic markers.