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.     

Comments on adequacy, nutrition and survival with peritoneal dialysis and haemodialysis

Summary: This paper summarizes the status of the worldwide peritoneal dialysis population at the end of 1994. Relative mortality risks on peritoneal dialysis and haemodialysis are compared. Clearance targets for continuous ambulatory peritoneal dialysis are discussed.     

Cryoballoon Pulmonary Vein Isolation with Real-Time Recordings from the Pulmonary Veins

Introduction: Cryoballoon (CB) ablation represents a novel technology for pulmonary vein isolation (PVI). We investigated feasibility and safety of CB-PVI, utilizing a novel spiral catheter (SC), thereby obtaining real-time PV potential registration.
Methods: Following double transseptal puncture, a Lasso catheter (Biosense Webster, Diamond Bar, CA, USA) and the 28 mm CB were positioned within the left atrium. A novel SC (Promap, ProRhythm Inc., Ronkonkoma, NY, USA) was inserted through the lumen of the CB allowing PV signal registration during treatment. Time to PV conduction block was analyzed. If no stable balloon position was obtained, the SC was exchanged for a regular guide wire and PV conduction was assessed after treatment by Lasso catheter.
Results: In 18 patients, 39 of 72 PVs (54%) were successfully isolated using the SC. The remaining 33 PVs were isolated switching to the regular guide wire. Time to PV conduction block was significantly shorter in PVs in which sustained PVI was achieved as compared to PVs in which PV conduction recovered within 30 minutes (33 ± 21 seconds vs 99 ± 65 seconds). In 40 PVs, time to PV conduction block was not obtained because of: (1) PVI not being achieved during initial treatment; (2) a distal position of the SC; or (3) isolation with regular guide wire. No procedural complications occurred.
Conclusion: Visualization of real-time PV conduction during CB PVI is safe, feasible, and allows accurate timing of PVI onset in a subset of PVs. Time to PV conduction block predicts sustained PVI. However, mechanical properties of the SC need to be improved to further simplify CB PVI.     

Esophageal Endoscopy Results After Pulmonary Vein Isolation Using the Single Big Cryoballoon Technique

Esophageal Effects of Single Big Cryoballoon PVI. Introduction: Reversible esophageal thermal lesions after cryoballoon pulmonary vein isolation (CB‐PVI) have been reported when using variable balloon sizes. The aim of this study was to investigate (1) the incidence of esophageal thermal lesions, and (2) esophageal temperature changes associated with CB‐PVI using the single big cryoballoon technique. Methods and Results: Thirty‐eight patients with atrial fibrillation underwent successful CB‐PVI using only the 28 mm cryoballoon. Luminal esophageal temperature (LET) was continuously monitored by 3 thermocouples. Fluoroscopic distance from cryoballoon to esophagus probe was retrospectively evaluated in RAO 30° and LAO 40° projections. All patients underwent postprocedural esophageal endoscopy. Average minimal LET was lower during freezing at inferior PVs, when compared to superior PVs: 35.4 ± 0.9 (range: 32.6 to 37.4; RSPV); 31.5 ± 7.5 (2.5 to 37.6; RIPV); 32.9 ± 5.2 (8.5 to 36.5; LSPV); and 30.3 ± 8.4°C (?6 to 36.7°C; LIPV); P = 0.001. We found steep temperature gradients over distance (1) from the cryoballoon center (LETs < 10°C confined to a distance of < 15 mm in both RAO 30° and LAO 40° projections), and (2) along the esophagus long axis, underscoring the need for multiple measurement sites. None of the patients showed esophageal thermal lesions at endoscopy after 3 ± 1 (range 1–7) days. No AEF occurred during a follow‐up of 125 ± 78 days. Conclusion: In a cohort of AF patients treated by the single big cryoballoon technique, CB‐PVI was not associated with thermal esophageal lesions. (J Cardiovasc Electrophysiol, Vol. 21, pp. 869‐874, August 2010)     

Corticosterone Modulates Acute Toxicity of 2,3,7,8-Tetrachlorodibenzo-p-1 dioxin (TCDD) in Male Sprague--Dawley Rats

Corticosterone Modulates Acute Toxicity of 2,3,7,8-Tetrachlorodibenzo-p-dioxin(TCDD) in Male Sprague-Dawley Rats.GORSKI, J. R., ROZMAN, T.,GREIM, H., AND ROXMAN, K. (1988). Fundam Appl. Toxicol 11, 494-502.Bilateral adrenalectomy or adrenal demedullation was performedon male Sprague-Dawley rats by established surgical techniques.Subsequently, the dose-response (mortality and mean time todeath) to TCDD was determined in adrenalecto-mized (10, 20,40 µg/kg TCDD ip in 95:5 corn oil: acetone) or demedullated(15, 30, 60 µg/kg TCDD) rats. Adrenalectomy drasticallyincreased mortality and greatly shortened mean time to deathafter dosing with TCDD. More importantly, adrenalectomized TCDD-treatedrats died 3 of hypoglycemic shock without losing much body weightConversely, adrenal demedullation had no effect on mortalityor mean time to death caused by TCDD when compared to non-demedullatedTCDD-treated controls. Thus, it was concluded that the factors)modulating the acute toxicity of TCDD resides in the adrenalcortex and not in the medulla. Administration of corticosterone(25 ngjµl in drinking water) to adrenalectomized ratsreturned the toxicity of TCDD to levels seen in nonadrenalectomizedrats suggesting that this hormone is another key 3 factor (inaddition to the thyroid hormones) in the modulation of the acutetoxicity of TCDD. Corticosterone supplementation (25, 50, or100 µg/) to nonadrenalectomized rats, or to thy- roidectomized-adrenalectomizedrats (25 µg/ml), resulted in no additional beneficialeffect indicating that a factoids) other than thyroid hormonesand corticosterone is also involved in the 14 acute toxicityof TCDD     

Dialysis-related amyloidosis: Pathogenetic aspects and therapeutic considerations

Summary: Beyond renal transplantation and the provision of symptomatic relief, approaches to treat dialysis-related amyloidosis (DRA), an important long-term complication in patients on regular dialysis, must be based on the knowledge of the underlying pathogenetic process. Retention of beta₂-microglobulin (β₂m) is the prerequisite; biochemical alterations of β₃₂m increasing its amyloidogenicity, and local predisposing tissue factors together with age appear to be relevant. A growing body of evidence points toward the importance of pro-inflammatory effects of dialysis (blood-membrane interactions, pyrogen-related priming of cytokine producing mononuclear cells) in the development of DRA. Advanced glycation endproduct formation (AGE-β₂m) may represent a central element in the pathogenesis of DRA. For non-transplant therapy of DRA, the main goals must be the optimization of β₂m removal (high-flux haemodialysis, haemofiltration, especially pre-dilution haemofiltration) and reduction of pro-inflammatory effects of dialysis (use of non-complement activating biocompatible membranes, pyrogen free dialysate). At least patients at high risk for DRA should be treated according to these guidelines.     

REQUIREMENTS FOR PROTEIN AND ESSENTIAL AMINO ACIDS IN EARLY INFANCY1Studies with a Soy-Isolate Formula

Thirteen normal female infants were observed from 8 through 111 days of age while receiving a diet providing 1.62 g of protein per 100 kcal, almost entirely from soy-isolate. Clinical observations, growth rates and serum concentrations of albumin were similar to those of female infants fed milk-based formulas providing greater intakes of protein. On the basis of these findings, it is assumed that the requirements for protein and essential amino acids of these infants were no greater than the amounts consumed. Reasons for preferring to express requirements for proteins and amino acids per unit of calorie intake rather than per unit of body weight are presented. The preliminary estimates of requirements presented here are believed applicable when the diet is adequate in total calories and non-nitrogenous essential nutrients, nitrogen is provided primarily in the form of whole proteins, and protein intakes do not greatly exceed the requirement. For reasons discussed, the approach is likely to yield estimates of requirements for some amino acids that are substantially greater than the true requirements. Nevertheless, our estimates of requirements for isoleucine and methionine are distinctly less than those reported by Holt & Snyderman. We conclude that the estimates of Holt & Snyderman from studies of infants fed mixtures of amino acids are less relevant than our estimates to circumstances in which whole proteins are fed in amounts that do not greatly exceed the requirement for protein.