Randomized double-blind placebo-controlled trial of bestatin in patients with resected stage I squamous-cell lung carcinoma

BACKGROUND: Bestatin is a potent aminopeptidase inhibitor that has immunostimulant and antitumor activity. We conducted a prospective randomized, double-blind, placebo-controlled trial to determine whether postoperative adjuvant treatment with bestatin could prolong the survival of patients with completely resected stage I squamous-cell lung carcinoma. METHODS: Patients with confirmed, resected stage I squamous-cell lung carcinoma were randomly assigned to receive either bestatin (30 mg) or placebo daily by mouth for 2 years. We assessed whether bestatin treatment was associated with overall survival and 5-year cancer-free survival and assessed its safety. All statistical tests were two-sided. RESULTS: From July 8, 1992, through March 30, 1995, 402 patients were entered in the study, 202 in the bestatin group and 198 in the placebo group. The median follow-up for surviving patients was 76 months (range = 58-92 months). The 5-year overall survival was 81% in the bestatin group and 74% in the placebo group for a difference of 7% (95% confidence interval [CI] = -1.4% to 15.0%). The 5-year cancer-free survival was 71% in the bestatin group and 62% in the placebo group for a difference of 9% (95% CI = -0.7% to 17.8%). Overall survival (P =.033, log-rank test) and cancer-free survival (P =.017, log-rank test) were statistically significantly different by Kaplan-Meier analysis. Few adverse events were observed in either group. CONCLUSIONS: Survival was statistically significantly better for patients with completely resected stage I squamous-cell lung carcinoma who were treated with bestatin as a postoperative adjuvant therapy than for those who received a placebo. This result requires confirmation in other phase III trials.     

Granulocyte transfusions: efficacy in treating fungal infections in neutropenic patients following bone marrow transplantation

Background: A retrospective study was conducted to evaluate the efficacy of granulocyte transfusions in neutropenic patients with fungal infections following bone marrow transplantation. Study Design and Methods: Systemic fungal infection was detected in 87 patients during the first 100 days following bone marrow transplantation; 50 received granulocytes in addition to appropriate antifungal agents. The median age was 17 years in the transfused patients (range, 1.5–57) and 35 years in the nontransfused patients (range, 0.8–50). Granulocyte transfusions were given on a daily to twice-daily basis. To evaluate their responses, patients were categorized by infection type (candidal [n = 38] vs. noncandidal [n = 49]) and site (fungemia alone [n = 30] vs. invasive infection [n = 57]). Resolution of infection was defined as the resolution of signs and symptoms and negative cultures and/or histopathology. Results: No benefit of granulocyte transfusions could be shown in the resolution of infection in patients with either invasive noncandidal infection (29% in the transfused patients vs. 23% in the nontransfused patients, p > 0.1) or candidal sepsis (56% vs. 50%, p > 0.1). Among patients with delayed marrow recovery, no difference was seen in the resolution of infection in the transfused (25.9%) and nontransfused (50%) patients (p > 0.1); nor was any difference between the transfused and nontransfused patients evident in the duration of febrile episode associated with the fungal infection. Granulocyte transfusions were well tolerated, with the only complications being fever in 12 patients (24%), chills in 10 (20%), and respiratory distress in 2 (4%). Despite attempts to stratify by infection type, invasiveness, and marrow recovery, it was not possible to show any benefit of granulocyte transfusions in this group. Conclusions: It is likely that only through a prospective randomized trial can the question of the efficacy of granulocyte transfusions in treating fungal infections be conclusively answered.     

A DOUBLE-BLIND,COMPARATIVE STUDY OF DOTHIEPIN AND CLOMIPRAMINE IN THE TREATMENT OF MAJOR DEPRESSIVE ILLNESS

Dothiepin, a well-established antidepressant, has been compared with clomipramine in a single-blind study which demonstrated that dothiepin was better tolerated but there was no difference in efficacy. The present study was performed to recent European guidelines on good clinical practice using a randomised, double-blind, parallel-group methodology. One hundred and one patients suffering from major depressive disorder as defined by DSM-III-R were randomised to receive either clomipramine (25-150 mg daily) or dothiepin (75-150 mg daily) for up to six weeks. The clomipramine group comprised 51 patients, the dothiepin group 50 patients. At baseline, both groups had a mean age of 41-43 years and gave similar mean scores on the Hamilton Depression Rating Scale (23.5 for clomipramine, 23.6 for dothiepin). At endpoint it was reduced in both groups but there were no significant differences between the groups (mean change from baseline for the clomipramine and dothiepin groups was -14.6 and -14.1 respectively). Thirty-one clomipramine patients and 41 dothiepin patients completed six weeks' treatment. Withdrawal from treatment (20 patients for clomipramine, nine for dothiepin) was significantly different (p=0.0105). When reasons for withdrawal were analysed, 13 clomipramine patients and two dothiepin patients withdrew because of adverse events, this difference being significant (p=0.002). Thus both treatments were effective in treating patients suffering from major depressive disorder, but patients receiving dothiepin suffered fewer adverse events and were more likely to complete their treatment.     

Sulfonated biochar catalyst derived from eucalyptus tree shed bark: synthesis,characterization and its evaluation in oleic acid esterification

Herein, fatty acid (oleic acid, OA) was upgraded to fatty acid methyl ester (FAME) via esterification reaction using sulfonated biochar obtained from eucalyptus tree shed bark as solid acid catalyst. Under the optimal esterification conditions (i.e., at 65 °C for 2 h using a methanol/OA molar ratio of 10 : 1 with a catalyst dosage of 4 wt%), the FAME yield was 97.05 ± 0.28% when a solid acid catalyst prepared by loading 6 g of p-Toluenesulfonic acid (p-TSA) on 2 g of activated biochar (p-TSA₃/ABC) was used. The remarkable performance of the p-TSA₃/ABC could be attributed to its high acidity (468.8 μmol g⁻¹) and dominance of the SO₃H acid site on the catalyst surface. Experimental findings showed that the p-TSA₃/ABC was relatively stable due to its highly functionalized structure. The catalyst was recycled for five successive cycles and exhibited no dramatic decrease in catalytic activity.

Herein, fatty acid (oleic acid, OA) was upgraded to fatty acid methyl ester (FAME) via esterification reaction using sulfonated biochar obtained from eucalyptus tree shed bark as solid acid catalyst.     

Polymorphisms in CYP2A13 and UGT1A7 genes and head and neck cancer susceptibility in North Indians

Oral Diseases (2010) 16 , 760–768 Objectives: To examine role of genetic variants of CYP2A13 and UGT1A7 genes, involved in activation and detoxification of tobacco carcinogens, with risk of head and neck cancer as well as to assess the potential modifying role of gene‐gene and gene‐environment interactions. Methods: 203 head and neck cancer patients and 201 healthy controls were genotyped for functional polymorphisms of CYP2A13 and UGT1A7 genes using polymerase chain reaction‐restriction fragment length polymorphism, denaturing high‐performance liquid chromatography and sequencing. Results: We identified two novel polymorphisms T478C and T494C in CYP2A13 gene which were associated with significantly reduced risk of cancer (OR 0.37; 95% CI 0.19–0.71; P < 0.05). A CYP2A13 haplotype carrying variant alleles of T478C/T494C was found to be associated with reduced risk of head and neck cancer (OR 0.42; 95% CI 0.22–0.78; P = 0. 005). Mutant ‘T’ allele of CYP2A13 C578T polymorphism was found to be present in cancer patients only. A sevenfold increased risk of cancer was observed in smokers with UGT1A7 low activity genotypes (OR 7.01; 95% CI 1.02–48.37; P < 0.05). UGT1A7 haplotype carrying C allele (T622C) showed 10‐fold increased risk of cancer (OR 10.12; 95% CI 1.29–79.4; P < 0.05). Conclusion: Interplay between genetic variants of CYP2A13 and UGT1A7 genes and smoking may modulate susceptibility to head and neck cancer.