Phase I evaluation of diaziquone in childhood cancer

Summary We conducted a phase I clinical study of aziridinylbenzoquinone (Diaziquone, AZQ) given as a 4 hour infusion weekly × 4. Forty-five children with recurrent acute leukemia and 33 children with various advanced solid tumors participated. Severe myelosuppression was the dose limiting toxic effect, occurring in all patients at the upper dose levels. Gastrointestinal and hepatic toxicities were infrequent and not severe. No allergic reactions occurred. Objective tumor regression was noted in 3 of 25 patients with a CNS tumor and in 6 of 45 patients with acute leukemia. For phase II trials the recommended dosage of Diaziquone given by this schedule is 18 mg/M²×4 for patients with a solid tumor, and is 30 mg/M²/week × 4 for children with acute leukemia.     

Ritanserin in the treatment of alcohol dependence – a multi-center clinical trial

Four hundred and twenty-three alcohol dependent subjects were enrolled into a 12-week randomized, double-blind, placebo-controlled study to determine the safety and efficacy of the 5-HT₂ receptor antagonist, ritanserin (2.5 mg/day or 5 mg/day), in reducing alcohol intake and craving. All subjects received 1 week of single-blind placebo prior to randomization into the 11-week double-blind phase. Additionally, all subjects received weekly individual sessions of manual-guided cognitive-behavioral therapy. Comparing the single-blind period with endpoint, there was approximately a 23% reduction in drinks/day; 34% fall in the total number of drinking days/week; 22% decrease in drinks/drinking day; and a 37% diminution in alcohol craving for all treatment groups. All treatment groups experienced a beneficial clinical outcome as assessed by the Clinical Global Impression Scale. There was, however, no significant difference between treatment groups on any of these measures of alcohol drinking, craving, or clinical outcome. Subjects were of relatively high social functioning at baseline, and this did not change significantly during treatment. Treatment groups did not differ significantly on either medication compliance or reported adverse events. Ritanserin treatment was associated with a dose-related prolongation of subjects’ QTc interval recording on the electrocardiogram. These results suggest that alcohol dependent subjects can show marked clinical improvement within a structured alcohol treatment program. These findings do not support an important role for ritanserin in the treatment of alcohol dependence. Received: 30 April 1996/Final version: 3 July 1996     

Practice setting and physician influences on judgments of colon cancer treatment by community physicians.

OBJECTIVE. This article compares judgments about the treatment of Dukes' B2 and C colon cancer made by general surgeons to those of internists and family practitioners. Physician and practice variables were specialty, affiliation with a Community Clinical Oncology Program (CCOP) hospital, time in practice, professional centrality (level of participation in cancer information networks), solo practice, and number of colon cancer patients. DATA COLLECTION METHODS. Data are combined from national probability samples of CCOP- and non-CCOP-affiliated physicians. This study focused on 1,138 internists, family physicians, and general surgeons who participated in decision making for patients diagnosed with Dukes' B2 or C stage colon cancer. Judgments were elicited using brief vignettes. METHODS OF ANALYSIS. Judgments of adjuvant therapy are classified as (a) consistent with the National Institutes of Health Consensus Conference recommendations (experimental for Dukes' B2, accepted for Dukes' C); (b) accepted treatment for both stages; or (c) experimental for both stages. Multinomial logit analyses were used to examine the association of practice setting and physician characteristics to judgments of treatment. RESULTS. Surgeons and CCOP-affiliated physicians were more likely to endorse the NIH consensus conference position. Surgeons, younger physicians, and those in group practice were more likely to approve of chemotherapy for both cancer stages. The most common position (chemotherapy experimental) was more likely from nonsurgeons, solo practitioners, and non-CCOP physicians. CONCLUSION. Physician and practice setting characteristics, including organized structures such as the CCOP, are possible mediating structures that can facilitate dissemination of standards of treatment.     

Agenesis of the Gallbladder Revisited Laparoscopically

Gallbladder agenesis is an extremely rare disease. Necropsy incidence has been reported to be 0.016%. Failure lo locate the gallbladder at the time of a planned cholecystectomy can be very challenging. We report such a case during a laparoscopic cholecystectomy. The indication for surgery in these patients are complaints of gallbladder symptoms along with a false-positive ultrasound study. During exploration, an abnormal location of the gallbladder has to be excluded. Ectopic gallbladder locations include intrahepatic, lesser omentum, retroperitoneal, retrohepatic, within the falciform ligament, retroduodenal, and retrohepatic areas. Thorough exploration and cholangiography are essential. Embryologically, the gallbladder and cystic duct arise from the caudal portion of the hepatic bud. All of the previously reported cases of gallbladder agenesis have shown an absence of both the gallbladder and cystic duct. We report an embryological oddity wherein a patent cystic duct was found along with an agenetic gallbladder. This is the first case report of this finding, along with this being the first absent gallbladder discovered laparoscopically.     

Managing asthma in accident and emergency departments: an assessment in non teaching hospitals

Background: The management and follow-up of asthma patients presenting at Accident and Emergency (A&E) departments have mostly been studied in children's hospitals or specialised teaching hospitals. Aims: To study the adequacy of assessment, treatment and follow-up of patients presenting at A&E departments in non-teaching hospitals. Methods: A twenty-five per cent sample of presentations to A&E departments in all public hospitals in the Illawarra for one year was selected for a case note audit. Information on demographics, assessment, management and referral was extracted from the A&E case notes and medical records of cases with documentation of a final diagnosis of asthma. Chi square and Fischer's Exact tests were used for comparisons among hospitals. Results: Of 359 presentations with a final diagnosis of asthma, 88% were self referred and only 5% were first presentations. Objective measures of airways obstruction was not documented in 34% of admissions and 48% of nonadmissions. There was no documented follow-up in 28% of cases. The assessment and management of asthma in A&E was significantly poorer in smaller hospitals. Conclusion: Evidence of high use of A&E as a primary care facility by asthma patients was found in the study. There is a need to implement protocols to optimise assessment and treatment of asthma in smaller hospitals. (Aust NZ J Med 1993; 23: 672–677.).     

Induction of endothelium-dependent relaxation in the rat aorta by IRL 1620, a novel and selective agonist at the endothelin ETB receptor.

1. The effects of a novel and selective agonist at the endothelin ETB receptor, IRL 1620 (Suc-[Glu9, Ala11,15] endothelin-1 (8-21)), were examined in the isolated aorta of the rat. 2. IRL 1620 (1-300 nM) changed neither the resting tone nor the cytosolic Ca2+ level ([Ca2+]i) of the aorta without endothelium. In the presence of endothelium, however, IRL 1620 increased endothelial [Ca2+]i with little effect on the muscle tone. In the absence of external Ca2+, IRL 1620 still induced a transient increase in endothelial [Ca2+]i. 3. Noradrenaline (100 nM) increased both muscle [Ca2+]i and tension. IRL 1620 (1-300 nM) relaxed the muscle with an increase in endothelial [Ca2+]i only in the presence of endothelium. An inhibitor of nitric oxide synthase, 100 microM NG-monomethyl-L-arginine, inhibited the relaxant effect of IRL 1620 but not the increase in endothelial [Ca2+]i. 4. In resting and noradrenaline-stimulated aorta, the effects of IRL 1620 were inhibited by a selective antagonist of the ETB receptor, IRL 1038 (0.3-3 microM), although a selective antagonist of the ETA receptor, BQ-123 (3 microM), was ineffective. Verapamil (10 microM) did not alter the effects of IRL 1620. 5. A muscarinic receptor agonist, carbachol (1 microM), also induced endothelium-dependent relaxation with an increase in endothelial [Ca2+]i. However, the effects of carbachol were not inhibited by the ETB antagonist, IRL 1038 (3 microM).(ABSTRACT TRUNCATED AT 250 WORDS)     

Problems and solutions of pedicle screw plate fixation of lumbar spine

Fifty-seven patients with low back pain and sciatica of various causes were reviewed with reference to problems associated with pedicle plate fixation of the lumbar spine. Eleven percent of patients had neurologic problems postoperatively and 3.5% (two patients) had severe sensory impairments. All patients had this complication in the early phases of the study. Of 297 screws, 17 broke, ie, 5.7%. These breakages occurred in 12 of 57 patients (21%). In patients with spondylolisthesis, the degree of slip correction averaged 53% postoperatively, which decreased to 35% at the 1-year follow-up. Slip angle was maintained after correction. Pedicle screw plate fixation is an effective form of immobilization of the lumbar spine used in achieving arthrodesis. The surgeon must be fully trained in methodology. It is recommended that screw and plate materials be improved to prevent screw breakage.