Hyponatraemia and hypothyroidism in a previously irradiated case of carcinoma of the tongue

A case of squamous cell carcinoma of the tongue was complicated by post operative hyponatraemia. The criteria for the syndrome of inappropriate secretion of anti diuretic hormone, [ADH] (SIADH) were met but the patient remained hyponatraemic despite adequate treatment. The patient had previously received radical external radiotherapy to the neck and was found to be profoundly hypothyroid. Correction of the hypothyroid state led to clinical and biochemical recovery. The frequency of post-irradiation hypothyroidism and the possible mechanisms of hypothyroid-induced hyponatraemia are discussed.     

Lack of apoptosis in the hypoxic brain of a rat model mimicking cyanotic heart disease

OBJECTIVE: To assess the effect of chronic hypoxia on brain neuronal apoptosis, an animal model mimicking cyanotic heart disease was utilized. METHODS: Rats were placed in an hypoxic environment at birth and oxygen levels were maintained at 10% in an air-tight Plexiglass chamber. Controls remained in room air. Animals were sacrificed and the brains were harvested at 1 and 4 weeks, respectively. RESULTS: Significant polycythemia developed in the hypoxic rats at 1 and 4 weeks. Indexed brain mass to body weight was significantly increased in the hypoxic groups by 18% (p < 0.01) and 38% (p < 0.01) as compared to controls at 1 and 4 weeks, respectively. There was no difference in the number of apoptotic neurons between the chronically hypoxic rats and controls, as assayed by TUNEL labelling and Hoechst staining. The role of the sphingolipid ceramide was then examined because of its reported role in stress response, growth suppression and apoptosis. It was found that the brain ceramide accumulation was not significantly different in the hypoxic and control groups at 1 and 4 weeks. CONCLUSION: A protective adaptive response to chronic hypoxia in the neonatal brain may exist.     

Development and physical characterization of a periodontal bioadhesive gel of metronidazole

To develop a localized drug delivery system that offers prolonged administration of metronidazole into the periodontal pocket, muccoadhesive gel formulations containing 5% w/w metronidazole were prepared using the bioadhesive polymers: carboxymethylcellulose, methylcellulose, hydroxyethylcellulose, polyvinylpirrolidone, and carbopol. Increased concentrations of the polymers decreased the drug release rate and enhanced syringeability, yield value, and adhesiveness but decreased the spreadability. The bioadhesive properties of the gels were affected by pH and Ca 2+ concentration. The gel containing 20% hydroxyethylcellulose, 20% polyvinylpirrolidone, and 1% carbopol exhibited zero-order drug release kinetics and suitable physical properties for drug delivery to the periodontal pocket.     

Prevention of secondary lymphedema

After some preliminary remarks upon pathophysiologic and anatomo-surgical aspects, the main complications of axillary lymph-nodal dissection for breast cancer treatment are reported. The role of surgical technique is particularly underlined and also the importance of proper management of wound and surgical drainage post-operatively are pointed out. Author describes, finally, the necessity of an adequate knowledge of lymphatic drainage not only of mammary region, but also of surrounding area, in order to prevent lesions to lymphatic pathways, particularly to those draining upper arm at the same site of breast cancer.     

Etoposide, ifosfamide and cisplatin (VIP) plus concurrent radiation therapy for previously untreated limited small cell lung cancer (SCLC): a Hoosier Oncology Group (HOG) phase II study

Results of a previous Hoosier Oncology Group (HOG) study revealed a small survival advantage for VIP versus etoposide and cisplatin (EP) for patients with extensive stage small cell lung cancer (SCLC). This phase II study evaluated VIP with concurrent thoracic radiotherapy in patients with limited stage SCLC. Eligible patients had a Karnofsky Performance Score > or = 50, no prior chemotherapy or radiotherapy, and adequate end organ function. Fifty-three patients were entered. Radiotherapy was given as a daily fraction of 1.8 Gy, five fractions per week for 5 weeks for a total dose of 45 Gy, beginning on day 1 of VIP. The first 13 patients received etoposide 75 mg/m(2), cisplatin 20 mg/m(2), and ifosfamide 1.2 g/m(2) on days 1-4 with Mesna every 3 weeks for four cycles unless the patient demonstrated disease progression or undue toxicity. Excessive toxicity was seen in the first 13 patients; therefore, VIP was modified by deleting the 4th day for all subsequent patients. The major toxicity in this trial was myelosuppression. Grade 3/4 anemia, granulocytopenia, and thrombocytopenia occurred in 38, 75, and 34% of patients, respectively. There were four treatment-related deaths [three patients (23%) on the 4-day regimen and one patient (2.5%) on the 3-day regimen]. Twenty-five patients (47.2%) achieved a CR and 11 patients (20.8%) had a PR for an overall response rate of 68%. Minimum follow up for all patients is 5 years. Overall, 46 of 53 patients have died. Median, 1, 2 and 5 year overall survival for the entire group is 15.1 months, 69.8, 35.9, and 13.2, respectively. The results of this phase II trial of VIP with concurrent early thoracic radiotherapy failed to demonstrate a superior response rate over other series utilizing EP. In addition, treatment-related morbidity and mortality appears to be unacceptably high with the VIP regimen.     

Carboplatin plus paclitaxel and sequential radiation followed by consolidation carboplatin and paclitaxel in patients with previously untreated locally advanced NSCLC. A Hoosier Oncology Group (HOG) phase II study

Chemoradiation is standard treatment for patients with unresectable locally advanced non-small cell lung cancer (NSCLC). However, local and distant relapse rates remain high. It has been postulated that the addition of consolidation chemotherapy might further decrease the systemic relapse rate. We performed this phase II study to evaluate the toxicities and activity of two cycles of paclitaxel and carboplatin administered prior to and following thoracic radiation in patients with locally advanced, inoperable NSCLC. From April to December 1997, 25 patients were entered on study. Twenty-three patients were eligible and received paclitaxel 225 mg/m(2) intravenously over 3 h followed by carboplatin at an AUC (6) on days 1 and 22. Radiation consisted of 60 Gy given over 6 weeks beginning on day 43. Patients with non-progressive disease received two additional cycles of consolidation carboplatin and paclitaxel. Four of 23 patients progressed during induction chemotherapy. There were seven PR's and 11 had SD after induction chemotherapy. Following radiation, the response changed to 11 PR, four SD, and three had progressive disease. Of the 15 patients eligible to receive consolidation chemotherapy, three were excluded due to a poor performance status. Twelve patients were treated with consolidation chemotherapy with further improvement in two patients (SD to PR, PR to CR). All 12 patients who received consolidation chemotherapy developed grade 3 or 4 neutropenia, including three patients with neutropenic fever. The overall response rate was 52.1%. The median survival, 1-, and 2-year survival was 10.5 months, 45, and 17%, respectively. In conclusion, consolidation chemotherapy was associated with significant hematologic toxicity without an obvious improvement in survival in comparison to other studies utilizing chemoradiation alone.     

The value of platinum compounds in non-small-cell lung cancer

The value of platinum compounds has come into question with the advent of newer chemotherapy agents in the management of patients with advanced non-small-cell lung cancer. These newer agents, which include the taxanes, topoisomerase I inhibitors, gemcitabine, and vinorelbine, appear to have higher single-agent response rates and more favorable toxicity profiles when compared to the platinum compounds. However, the toxicity of the platinum compounds is now minimized with the advent of more effective antiemetics. In addition, phase III clinical trials have demonstrated that the strategy of cisplatin dose intensity and prolonged duration of therapy with platinum compounds does not improve overall survival; therefore, moderate doses of cisplatin and a shorter duration of therapy can be given to further decrease toxicity. Furthermore, while phase II trials utilizing nonplatinum-based combination chemotherapy appear to demonstrate superior response rates and survival in comparison to platinum-based doublets, results of phase III trials have demonstrated no improvement in survival. Platinum combination chemotherapy remains the standard approach for stage IV non-small-cell lung cancer. More substantial advances will likely be made with novel molecular targeted therapy, such as the epidermal growth factor receptor inhibitors, which demonstrate synergy with the platinum compounds.