Absorption, Metabolism, and Excretion of N,N-Diethyl-m-toluamide Following Dermal Application to Human Volunteers

The absorption, metabolism, and excretion of N,N-diethyl-m-toluamide(DEET) in male human volunteers following dermal applicationof |¹⁴C|DEET was studied. DEET was applied to two groups ofsix volunteers either as the undiluted technical grade materialor as a 15% solution in ethanol. The material was applied overa 4 x 6-cm area on the volar surface of the forearm and wasleft in contact with the skin for 8 hr, then rinsed off theskin. Application sites also were tape stripped at 1, 23, and45 hr after rinsing. Serial blood samples and all urine andfeces were collected for 5 days after application. Aliquotsof these materials were analyzed for total radioactivity inorder to define absorption and excretion patterns. Urine samplesalso were analyzed by HPLC to characterize the metabolic profileand/or to identify metabolites. Absorption of DEET as evidencedby plasma radioactivity occurred within 2 hr after dose application.Elimination of radioactivity from plasma was rapid and quantifiablelevels of radioactivity were observed in plasma for only 4 hrafter the end of the 8-hr exposure period. Urine was the principalroute of excretion of radioactivity and accounted for an averageof 5.61 and 8.33/ of the applied dose in the undiluted DEETand 15/ DEET in ethanol groups, respectively. Excretion of radioactivityin the feces was less than 0.08/ of the applied dose in bothgroups. DEET did not accumulate in the superficial layers ofthe skin as evidenced by low amounts of radioactivity in thetape strippings. The major fraction of the applied radioactivitywas recovered in the skin rinses. Absorbed DEET was completelymetabolized and six major metabolites were observed in urine.Two major urinary metabolites tenta tively were identified.Based upon the percentage of applied dose recovered in the excreta,dermal absorption of DEET ranged from 3 to 8% with a mean of5.6/ in the volunteers applied undiluted technical grade DEET.The corresponding values for the volunteers applied 15/ DEETin ethanol were 4 to 14/ and 8.4/, respectively.     

The influence of HLA-matched sibling donor availability on treatment outcome for patients with AML: an analysis of the AML 8A study of the EORTC Leukaemia Cooperative Group and GIMEMA

To determine whether patients with a HLA-identical sibling donor have a better outcome than patients without a donor, an analysis on the basis of intention-to-treat principles was performed within the framework of the EORTC-GIMEMA randomized phase III AML 8A trial. Patients in complete remission (CR) received one intensive consolidation course. Patients with a histocompatible sibling donor were then allocated allogeneic bone marrow transplantation (alloBMT), the patients without a donor were randomized between autologous BMT (ABMT) and a second intensive consolidation (IC2). 831 patients <46 years old and alive >8 weeks from diagnosis were included. HLA typing was performed in 672 patients. AlloBMT was performed during CR1 in 180 (61%) out of 295 patients with a donor. Another 38 patients were allografted: five in resistant disease, 14 during relapse and 19 in CR2. ABMT was performed in 130 (34%) out of 377 patients without a donor in CR1, in six (2%) patients during relapse and in 38 (10%) patients during CR2. The disease-free survival (DFS) from CR for patients with a donor was significantly longer than for patients without a donor (46% v 33% at 6 years; P = 0.01, RR 0.78, 95% confidence interval 0.63–0.96). The overall survival from diagnosis for patients with a donor was longer, but not statistically significant, than for patients without a donor (48% v 40% at 6 years; logrank P = 0.24). When patients were stratified according to prognostic risk groups, the same trend in favour of patients with a donor was seen for survival duration and the DFS remained significantly longer for this group of patients.     

Utilization of radiotherapy for rectal cancer in Greater Western Sydney 1994–2001

Background and purpose: Despite evidence for the efficacy of radiotherapy in stages II and III rectal cancer, utilization rates remain low. The aim of this study is to examine patient, provider and service factors affecting utilization of radiotherapy in rectal cancer patients. Materials and methods: Patients with a diagnosis of curable rectal cancer were identified from the colorectal tumor databases of three Sydney Area Health Services between 1994 and 2001. Data were collected on tumor characteristics such as site and stage, provider factors such as type of surgery and surgeon caseload, and patient factors including socioeconomic status and access to radiotherapy. Results: Thirty‐five percent of stage II and 57% of stage III rectal cancer patients received radiotherapy. Independent determinants of utilization were age less than 70 years (odds ratio, 2.96; 95% confidence interval, 1.75–5.03), high‐volume surgeons (OR, 1.95; 95% CI, 1.17–3.24), stage III disease (OR, 2.06; 95% CI, 1.25–3.41) and abdominoperineal resections (OR, 3.67; 95% CI, 1.94–6.94). Conclusion: Radiotherapy utilization rates remain low. Age, and being referred to a surgeon with a high caseload, has a greater impact on radiotherapy utilization than other provider, socioeconomic or service factors.     

A "new" phenotype confirming a relationship between Cra and Tca

The red cells of two sisters had very weak Cra and Tca antigens and reacted only weakly with the antibody of the Cr(a-) Tc(a-)person, Inab. Both sisters had an antibody, named anti-Dra, to a high frequency antigen absent from their own cells and Inab cells but present on Cr(a- ) Tc(a+) and on Cr(a+) Tc(a-) cells. This is the third example in which both Cra and Tca antigens are either absent or show weakened expression on the red cells, but the first case in which the unusual phenotype is shown to be inherited.     

Relationships Between Histological and Functional Indices of Acute Chemically Induced Nephrotoxicity

Relationships Between Histological and Functional Indices ofAcute Chemically Induced Nephrotoxicity. Miyajima, H., Hewitt,W.R., Côté, M.G., and Plaa, G.L. (1983). Fundam.Appl. Toxicol. 3: 543–551. Acute renal injury was producedin rats with K₂Cr₂O₇ (5–40 mg/kg, sc) HgCl₂ (0.5–5.0mg/kg, sc) or cephaloridine (0.5–3.0 g/kg, sc). Histological(percentage of normal, degenerated or necrotic cells) and functionalindices (relative kidney weight, renal cortical slice accumulationof organic ions, and blood urea nitrogen content) were evaluated48 hours later. The relative sensitivity of each of these indiceswas determined for each nephrotoxicant. Renal cortical accumulationof organic ions appeared to be the most sensitive of the functionalparameters. A quantitative histological evaluation was foundto be as sensitive an indicator of nephrotoxicity as organicion accumulation. Alterations in each of the functional indiceswere significantly correlated with changes in renal histology.     

Dose-Dependent Cytotoxicity of Chlorinated Hydrocarbons in Isolated Rat Hepatocytes

Dose-Dependent Cytotoxicity of Chlorinated Hydrocarbons in IsolatedRat Hepatocytes. DAHLSTROM-KJNG, L., COUTURE, J., LAMOUREUX,C, VAILLANCOURT, T., AND PLAA, G. L. (1990). Fundam. Appl. Toxicol.14, 833–841. The aim was to determine if isolated suspendedhepatocytes could differentiate between the effects of fourchlorinated hydrocarbons that are hepatotoxic In vivo and fourthat are not. Membrane integrity was assessed by measuring alanineaminotransferase (ALT) release after 30- to 180-min incubationsin vitro. From the results, the chlorinated hydrocarbons fellinto three groups: tetrachloroethylene and 1,1,2,2-tetrachloroeth-anewere the most potent cytotoxicants; CCl₄, 1,1,2-trichloroethane,and trichloroethylene exhibited intermediate cytotoxicity; andlow cytotoxicity was observed with CHCl₃, 1,1,1 -trichlo-roethane,and 1,1-dichloroethylene. Cytotoxicity ranking correlated poorlywith the reported In vivo hepatotoxicity of these agents. Theeffect of adding SKF-525A on the cytotoxicity of tetrachloroethyleneand CCI4 was also assessed. In addition, hepatocytes from ratspretreated with 2,5-hexanedione were used to determine if theywere more susceptible to the effects of CHCl₃, CCl₄ or tetrachloroethylene.SKF-525A decreased the cytotoxicity of both CO, and tetrachloroethylene,whereas pretreatment with 2,5-hexanedione enhanced their effect.The effects of both SKF-525A and 2,5-hexanedione on CCl in vitroare consistent with In vivo findings. However, tetrachloroethyleneis not hepatotoxic In vivo, suggesting that SKF-525A might actby stabilizing plasma membranes rendering the hepatocyte moreresistant to lysis. Overall, the results cast doubts on theuse of ALT release from isolated hepatocytes as an appropriatein vitro model for assessing hepatotoxic properties of chlorinatedhydrocarbons.     

The effect of dental education and dental treatment on the dental status of a handicapped population: a longitudinal study

Thirty-nine patients, aged 3 to 22, who have handicapping conditions were examined twice in a range of 1 1/2 years to determine oral hygiene level, periodontal treatment needs, and level of caries. During this period, each patient was given periodontal treatment, including scaling, caries treatment, and oral health education, which also was given to hospital staff members. Findings showed a slight increase in the DMF rate, a minor improvement in oral hygiene, and a significant reduction in periodontal treatment needs. The results showed that without cooperation of the staff members, a dental education program would not succeed in this setting.     

DDIR Versus VVIR Pacing in Patients with Paroxysmal Atrial Tachyarrhythmias

Patients with sinus node dysfunction (SND) in particular those with tachycardia-bradycardia syndrome and patients undergoing atrioventricular nodal ablation procedures for refractory paroxysmal atrial tachyarrhythmias (PAT), are candidates for single chamber (VVIR mode) or dual chamber rate responsive (DDIR mode) systems. To evaluate the benefits and disadvantages of each pacing mode we retrospectively analyzed 33 patients with a history of frequent PAT who received a VVIR (22 patients); or a DDDR pacemaker (11 patients) programmed to the DDIR mode. The mean follow-up time was 25 and 18 months, respectively. Preimplant left atrial diameter was significantly smaller in the DDIR group. Chronic atrial fibrillation developed in 54% of the VVIR patients and 27% of the DDIR group, but this difference was not significant. Complications of patients with VVIR pacemakers included new mitral and tricuspid insufficiency, stroke, pacemaker inlolerance and aggravated congestive heart failure. Patients with DDIR pacemakers had a lower incidence of symptoms and complications. However, this group received more antiarrhythmic medication, required a closer follow-up, and their pacemakers needed frequent reprogramming. Our findings suggest that VVIR is a poor choice for patients with SND, congestive heart failure, and PAT, and that DDIR may be an acceptable alternative.