Expression of epithelial matrix molecules collagen and laminin and corresponding integrins in chronic wounds

Re-epithelialization of cutaneous wounds is a coordinated process of proliferation and migration of keratinocytes at the wound edge. The study objective was to identify the differences in epidermal morphology, keratinocyte proliferation and matrix molecules (laminin 1, laminin 5, type IV collagen) and their specific integrin (α3, α6) expression in biopsies of meshed split thickness grafted and chronic wounds. The mean mitotic index of keratinocytes (ratio of cell cycle associated antigen Ki-67 expressing keratinocytes to basal keratinocytes) was highest in chronic wounds (38.7%) compared to acute wounds (22.25%, range 5.7% to 54%). The mean thickness of the hyper-proliferative epithelium at the wound edge of chronic wounds was 0.69 mm compared to 0.15 mm at the wound margin of split thickness grafted wounds. Both chronic wounds and skin grafted wounds exhibited strong laminin 5 immunoreactivity at the basal side of the epithelium, which extended under the most forward keratinocytes. Laminin 1 and type IV collagen immunoreactivity did not extend to the wound margin in either skin grafted or chronic wounds. In both transplanted skin and chronic wounds, the integrin sub-units α3 and α6 exhibited a strong pericellular immunoreactivity on the leading keratinocytes of the wound margin. Our data demonstrates that the proliferation of keratinocytes and the expression of associated integrins are not impaired in chronic wounds. Presented at the 33rd Congress of the Association of German Plastic Surgeons, Germany, 18–21 September, 2002.     

Treatment of dyskeratosis congenita with Granulocyte Colony-Stimulating Factor and Erythropoietin

Aplastic anaemia is both frequent and difficult to manage in patients with dyskeratosis congenita (DC). We recently treated a 23-year-old male for a year with granulocyte colony-stimulating factor (G-CSF) and erythropoietin (Ep), with an excellent neutrophil response, and a transient effect on haemoglobin levels. G-CSF alone or combined with other cytokines may provide at least a partial effect in pancytopenic patients with DC.     

Are positive axillary nodes in breast cancer markers for incurable disease?

OBJECTIVE: This study was designed to determine if resection of positive regional nodes in patients with breast cancer provided a group of cured patients. SUMMARY BACKGROUND DATA: Previous studies of long-term follow-up of patients with breast cancer have demonstrated that 30% of patients with positive nodes may be alive at 10 or 20 years. Randomized, prospective studies have not shown a difference in survival between modified radical and total mastectomy. METHODS: The authors analyzed the statistical basis of randomized, prospective studies of breast cancer. Patients from University and Kings County Hospital with breast cancer were observed (n = 1024) and the 10-year survival curves were analyzed. Data from the Surveillance, Epidemiology, and End Results (SEER) program were evaluated to determine the prognosis of patients with positive-node breast cancer who survived 10 and 15 years. RESULTS: The authors found that no current randomized study of primary treatment of breast cancer has the power to determine the advantage of one treatment over another if the primary cancer is treated. Additionally, evaluation of the patients in this study demonstrated that those with regional disease usually had a recurrence by 7 years; however, at 10 years, 30% are still alive and have the same prognosis as patients with negative-node breast cancer. CONCLUSIONS: Regional breast cancer is a curable disease in some resected patients.     

Phase II trial of piroxantrone in metastatic breast cancer

Summary Thirty-two eligible patients with advanced metastatic breast cancer who had received no more than 1 prior chemotherapy regimen for metastatic disease (16 had received prior doxorubicin) were treated with piroxantrone at a dose of 120 mg/m² intravenously every 21 days. In the twenty-seven patients evaluable for response, two partial responses were seen. Toxicities observed were primarily hematologic with grade 3 or greater granulocytopenia occurring in 34% of the patients. One patient developed symptomatic congestive heart failure at a total cumulative dose of 960 mg/m². We conclude that piroxantrone given at this dose and schedule has minimal activity in patients with metastatic breast cancer.     

A Thalamic Contribution to Arousal-induced, Non-photic Entrainment of the Circadian Clock of the Syrian Hamster

It is well established that the circadian clock of the suprachiasmatic nuclei (SCN) is entrained by light. More recently, the potent effects of arousing, non-photic cues on the clock have been recognized. The neural mediators of non-photic entrainment are yet to be identified. To examine the contribution of the thalamic intergeniculate leaflet (IGL) and its NPY-immunopositive projection, the geniculo-hypothalamic tract to non-photic entrainment by arousal, male Syrian hamsters received lesions of the IGL (IGLX) which ablated NPY-immunoreactivity in the SCN. Their circadian responses to both photic and non-photic cues were then tested. Lesions resulted in a delay in the timing of activity onset following lights out, but had no effect on the behavioural or cellular circadian responses to phase-advancing light pulses presented at circadian time (CT) CT19 (where CT12 represents the time of activity onset). Injection with a benzodiazepine (chlordiazepoxide, 100 mg/kg) at CT6 suppressed wheel-running, increased general locomotion of intact controls and induced large phase advances of the circadian rhythm of wheel-running. Chlordiazepoxide also inhibited wheel-running in lesioned animals, but there was no significant increase in general locomotion and the lesioned animals did not phase advance. Serial arousal by injection of saline at intervals of 23.5 h for 6 days entrained the circadian rhythm of wheel-running of intact hamsters and was associated with an increase in general locomotor activity. Entrainment by serial arousal was abolished by IGLX. However, the lesioned animals did show a clear behavioural response to every presentation of the non-photic cue. These results show that the IGL is a necessary component of the neural pathways mediating both arousal- and benzodiazepine-induced non-photic entrainment.