Antagonistic selection between adult thorax and wing size in field released Drosophila melanogaster independent of thermal conditions.

Attempts to explain size variation in Drosophila and other small insects often focus on the larval stage and association between development time and size, but patterns are also influenced by direct selection on size-related traits in the adults. Here we use multiple field releases of Drosophila melanogaster to test the association between size and one component of field fitness, the ability of Drosophila to locate resources for feeding and breeding. We find antagonistic selection between wing length and thorax length in both males and females, such that capture at baits is higher for flies with relatively larger thorax lengths and smaller wings. However flies with large wings relative to thoraces disperse further as reflected in the longer distances moved to baits. These patterns did not depend strongly on weather conditions, suggesting that selection on adult size is at least partly independent of temperature. Antagonistic selection between size traits can generate changes in size along gradients if the distribution of resources in the environment varies and selects for different dispersal patterns, particularly as dispersal is relatively higher under warmer conditions.

Randomized comparative study of fleroxacin and chloramphenicol in typhoid fever.

This study compared fleroxacin, 400 mg daily for 7 or 14 days, with chloramphenicol, 50 mg/kg per day for 14 days, for the treatment of patients with typhoid fever in a multicenter study. A total of 184 patients were randomly assigned to the three treatment groups. Efficacy was determined by culture of blood and stool, overall clinical response, and time to defervescence. Safety was assessed by occurrence of adverse events and laboratory abnormalities. A total of 97 patients were evaluable for efficacy, 28 in the fleroxacin 7-day group, 35 in the fleroxacin 14-day group, and 34 in the chloramphenicol group. All showed rapid defervescence with high cure rates. Bacteriologic cure rates were 96% in the fleroxacin 7-day group, 97% in the fleroxacin 14-day group, and 85% in the chloramphenicol group. Clinical cure rates were 83-100% with fleroxacin and 82% with chloramphenicol. The time to defervescence was shorter for patients treated with fleroxacin than for those treated with chloramphenicol. All three treatment regimens were well tolerated. Fleroxacin, 400 mg daily for 7 days, appears to be satisfactory for the treatment of typhoid fever and compares favorably with the standard 14-day therapy with chloramphenicol.

Clinical evaluation of fleroxacin in the treatment of bone and joint infections.

The objective of this open label, non-comparative study was to evaluate the efficacy and safety of fleroxacin 400mg administered orally once daily to patients with acute osteomyelitis and/or acute septic arthritis. Nineteen patients (10 males and 9 females) were evaluable for the analysis of clinical efficacy and safety. Of these, 7 (36.8%) had osteomyelitis and 12 (63.2%) had septic arthritis. Bacteriological cures were reported in 6 of 7 patients (85.7%) with osteomyelitis and in 8 of 11 patients (72.7%) with septic arthritis. The median duration of treatment for the clinical cures in osteomyelitis and septic arthritis were 29.5 days and 46 days respectively. The eradication rate for the most common pathogens, Salmonella enteritidis and Staphylococcus aureus were 77.7% and 80.0%, respectively. The clinical response was cure in 4 of 7 patients (57.1%) evaluable for osteomyelitis, and in 9 of 12 patients (75.0%) evaluable for septic arthritis at the three-month follow-up after treatment. Adverse reactions were minimal. It is concluded that fleroxacin appears to be an effective and safe in the treatment of acute osteomyelitis and acute septic arthritis.

Combination of recombinant interferon alpha-2a and vinblastine in advanced renal cell cancer.

Among 40 evaluable patients with metastatic renal cell cancer treated by high-dose interferon alpha-2a in combination with vinblastine, the authors have observed a 42.5% response rate. The 8 months' median duration of remissions is relatively short but some patients experience very long remissions, lasting many months after discontinuation of therapy. The survival of responding patients is significantly longer than the survival of nonresponders. The diverging results of other studies of the same combination are discussed; its efficacy is certainly dependent on the type of interferon, on the dose actually administered, and on the compliance to this often poorly tolerated treatment.

Treatment of advanced malignant melanoma with interferon alpha and etretinate.

The combination of recombinant human interferon alpha A 9 MU daily intramuscularly and etretinate 50 mg daily orally was given to 25 patients with progressive advanced, metastatic melanoma. The treatment was well tolerated. Partial responses were seen in three (12%) patients lasting from 2 to 8 months. A further partial response was seen in one of three patients when they were given vindesine and DTIC whilst they continued receiving interferon and etretinate.

[Treatment of metastatic renal adenocarcinomas with combined recombinant alpha-2a interferon and vinblastine]. / Traitement des adénocarcinomes rénaux métastatiques par l'association interféron recombinant alpha-2a et vinblastine.

The results of treatment of metastatic renal cell carcinoma have so far been very poor. Many phase II studies have shown that interferon alpha therapy is active in a significant proportion of patients (approximately 10 to 15% complete and partial remission). In the hope of improving these results we have conducted a phase I-II study of the combination of interferon alpha-2a and vinblastine in 21 patients with metastatic renal cell cancer. Side-effects were pronounced and the mean tolerated doses were 12.5 x 10(6) U/m2 interferon alpha three times per week and 0.10 mg/kg vinblastine once every three weeks. We observed a 43% response rate, with 1 complete remission, 8 partial remissions, 4 stabilizations and 8 progressions. These very encouraging results need to be confirmed by large scale studies.

Further experience with recombinant interferon alfa-2a with vinblastine in metastatic renal cell carcinoma: a progress report.

Thirty-three patients with measurable metastatic renal cell carcinoma were entered into 2 consecutive phase II protocols using interferon alfa-2a. In protocol I, 20 patients were treated with interferon alfa-2a at a dose of 36 X 10(6) IU i.m. t.i.w. Vinblastine was also given to 18 of these patients at a dose of 0.10-0.15 mg/kg i.v. every 2-3 weeks, depending on the blood cell count. In protocol 2, 13 patients received interferon alfa-2a at a dose of 18 X 10(6) i.m. t.i.w. with stepwise dose escalations of 3 X 10(6) IU being given every 2 weeks to 8 patients. Vinblastine, at a dose of 0.1 mg/kg every 3 weeks, was also given to 12 patients in protocol 2. Partial responses were seen in a total of 9 evaluable patients (lung, 5; lymph nodes, 2; liver, 1; and bone, 1), comprising 6 of 18 from protocol 1 and 3 of 13 from protocol 2. The median response duration was 89 days (range 91-540). No clinical parameter could be identified which was predictive for response. The subjective toxicity (flu-like symptoms and muscle pain) was considerable and necessitated dose reduction in 19 patients from protocol 1. The dose schedule of protocol 2 was tolerated better even after slight dose escalation. The considerable interpatient variation in toxicity, however, made any demonstration of a clear dose-toxicity relationship impossible. High dose interferon treatment of metastatic renal cell carcinoma combined with vinblastine results in a 33% response rate (95% confidence interval: 11-55%).(ABSTRACT TRUNCATED AT 250 WORDS)

Recombinant interferon alfa-2a with or without vinblastine in metastatic renal cell carcinoma.

Twenty patients with measurable metastatic renal cell carcinoma (RCC) were were treated with interferon alfa-2a (Roferon-A), 36 X 10(6)U intramuscularly 3 times weekly, alone (2 patients) or in combination with vinblastine, 0.10-0.15 mg/kg intravenously every 2 to 3 weeks. Objective responses in the lung, bone, liver, and lymph node metastases were seen in 6 of 18 evaluable patients. Dose reduction of interferon alfa-2a was necessary in 19 of the 20 patients due to intolerable flu-like side effects and fatigue. Bone marrow suppression and increase of gamma-GT represented the most often observed objective toxicity. The preliminary results of this combination treatment in RCC are promising and warrant randomized studies exploring the role of vinblastine. The dose of interferon alfa-2a should be reduced by 50% to avoid excessive toxicity and to maximize patient compliance.