Transcatheter Electrical Ablation of Accessory Pathways in Children

Supraventricular tachycardia (SVT), the most common sustained symptomatic arrhythmia of childhood, is often supported by a manifest or concealed accessory pathway. Permanent interruption of the accessory pathway usually requires surgical division. Recent experience with electrical ablation of posterior septal pathways in adults prompted us to apply the technique to children. Six children, ages 8 to 15 years, underwent a complete electrophysiological study followed by transcatheter electrical ablation. Five of the 6 children, 3 with a right posterior septal and 2 with a left posterior septal pathway, were approached with the ablation catheter at the os of the coronary sinus. In the remaining patient, a left lateral pathway was mapped with an electrode catheter in the coronary sinus and then approached with the ablation catheter through the patent foramen into the left atrium. Two patients are asymptomatic 18-24 months postablation; one patient had return of anomalous conduction between 7 and 21 days after ablation. Two patients had transient interruption of anomalous conduction, whereas one patient experienced no effect. We conclude that in carefully selected patients, transcatheter electrical ablation offers an alternative to surgery for permanent interruption of an accessory pathway.     

Reduction in toxicity of organic priority pollutants by pilot-scale conventional wastewater treatment process

Static acute toxicity tests with fathead minnows,Daphnia magna, and rainbow trout were used to demonstrate the effectiveness of a pilot-scale conventional wastewater treatment system in detoxifying a raw municipal wastewater that continuously received a mixture of 22 organic priority pollutants. Wastewater from the City of Cincinnati (Ohio) was added to two parallel pilot-scale (control and experimental) conventional activated-sludge wastewater treatment systems. The effect of chlorination on the acute toxicity of effluent from the experimental system was also investigated. The system typically reduced the organic priority pollutants by 89 to >99%, and both systems provided excellent treatment of conventional pollutants. Even though toxicity reduction as high as 90% was achieved, significant toxicity was present in the experimental effluent. The study clearly supports the premise that organism responses should be considered, in addition to chemical and conventional pollutant characterization, to determine the quality of a wastewater discharge.     

Fatal Toxic Epidermal Necrolysis Related to Lamotrigine Administration

Toxic epidermal necrolysis (TEN) and Stevens-Johnson syndrome (SJS) are severe life-threatening dermatologic conditions. To date, eight cases of TEN and one of SJS related to lamotrigine administration have been reported in the literature. Most patients were also taking concomitant valproic acid. It was hypothesized that valproic acid may interfere with glucuronidation of lamotrigine, leading to increased serum lamotrigine levels, or perhaps alter the drug's metabolism, resulting in accumulation of a toxic intermediate metabolite. Ultimately, this may possibly predispose a patient to increased dermatologic reactions, including TEN. A 54-year-old man developed TEN 4 weeks after beginning lamotrigine for complex partial seizures related to a glioblastoma multiforme brain tumor. The patient had also been taking concomitant allopurinol and captopril for more than 4 years with no complications, and valproic acid 3 months before the cutaneous event. Despite aggressive intensive care management, the patient died 17 days from the onset of symptoms due to multiple organ failure. Administration of lamotrigine, especially in combination with valproic acid, may lead to the development of TEN.     

Propofol Fails to Attenuate the Cardiovascular Response to Rapid Increases in Desflurane Concentration

Background: A rapid increase in desflurane concentration to greater than 1 MAC transiently increases heart rate, arterial blood pressure, and circulating catecholamine concentration. Because propofol decreases sympathetic outflow, it was hypothesized that propofol would blunt these responses.

Methods: To test this hypothesis, five healthy male volunteers were studied three times. After induction of anesthesia with 2 mg *symbol* kg sup -1 propofol, anesthesia was maintained with 4% end-tidal desflurane in oxygen (0.55 MAC) via an endotracheal tube for 32 min. On separate occasions, in random order, either no propofol or 2 mg *symbol* kg sup -1 propofol was administered either 2 or 5 min before increasing end-tidal desflurane concentration from 4% to 8%.

Results: Without propofol pretreatment, the increase to 8% desflurane transiently increased heart rate (from 63+/-3 beats/min to 108 +/-5 beats/min, mean+/-SEM; P < 0.01), mean arterial pressure (from 73+/-1 mmHg to 118+/-6 mmHg; P < 0.01), and epinephrine concentration (from 14+/-1 pg *symbol* ml sup -1 to 279+/-51 pg *symbol* ml sup -1; P < 0.05). There was no significant change in norepinephrine concentration (from 198+/-37 pg *symbol* ml sup -1 to 277+/-46 pg *symbol* ml sup -1). The peak plasma epinephrine concentration was attenuated by each propofol pretreatment (158+/-35 pg *symbol* ml sup -1, propofol given 2 min before, and 146 + 41 pg *symbol* ml sup -1, propofol given 5 min before; P < 0.05), but neither propofol pretreatment modified the cardiovascular or norepinephrine responses.     

Food Restriction during Organogenesis in Rabbits: Effects on Reproduction and the Offspring

Food Restriction during Organogenesis in Rabbits: Effects onReproduction and the Offspring. PETRERE, J. A., ROHN, W. R.,GRANTHAM, L. E., II, AND ANDERSON, J. A. (1993). Fundam. Appl.Toxicol. 21, 517–522. To assess the effects of markedly restricted food intake versusad libitum feeding or a slightly restricted feeding regimenduring the period of organogenesis we fed groups of 16–18pregnant rabbits Purina Certified High Fiber Chow ad libitum,150 g/day, 75 g/day, or 15 g/day on Gestation Days 6 to 18 inclusive.Prior to and after organogenesis the animals were provided foodad libitum (ad lib). Clinical observations, body weights, andfood and water consumption were recorded daily. On GestationDay 30 each doe was euthanatized and necropsied, and maternaland fetal data were collected. Each fetus was examined for external,visceral, and skeletal variations and malformations. Ossificationparameters were also evaluated. Statistical analyses were conductedin two ways, first comparing the restricted groups to the adlib group and second comparing the 15 and 75 g/day groups tothe 150 g/day group. During Days 6–18, the 15 and 75 g/daygroups had significantly decreased weight gain (actual weightloss), compared to the groups fed 150 g/day or ad lib. Waterconsumption was also significantly decreased in the 15 g/daygroup during this period, compared to the ad lib group. Whenfood was provided ad lib on Days 19–30 to the restrictedgroups, weight gain was significantly higher in the 15 and 75g/day groups than the group previously given 150 g/day and thead lib group. There were no differences in water consumptionduring that period. Abortion occurred in three 15 g/day animals.Pregnancy rate and numbers of corpora lutea, implantation sites,live and dead fetuses and resorptions, pre- and postimplantationloss, and placental weights were similar among groups. Fetalsex ratio and survival at term were comparable between the adlib group and the restricted groups. In the 15 g/day group,mean fetal weights were lower than those in the 150 g/day andthe ad lib groups. None of the fetuses from food-restricteddoes had external or visceral malformations, whereas two littermatesfrom the ad lib group had malformations of the heart or gallbladder.Except for a significant increase in the percentage of litterswith external or visceral variations in the 15 g/day group comparedto the 150 g/day group, there were no significant differencesbetween groups in the incidences of variations or malformations.Our findings agree with those in the literature in that abortionis increased and fetal weights are reduced when maternal foodintake is severely restricted during organogenesis. Contraryto a previous report also using 15 g/day during organogenesis[R. L. Clark, R. T. Robertson, C. P. Peter, J. A. Bland, T.E. Nolan, L. Oppenheimer, and D. L. Bokelman (1986). Fundam.Appl. Toxicol. 7, 292–286], we did not have an increasedincidence of fetal malformations. This study indicates thatthe influence of reduced food intake and body weight loss duringorganogenesis is equivocal in the induction of teratogenicityin rabbits.     

Recovery and Kinetic Characteristics of Desflurane and Sevoflurane in Volunteers after 8-h Exposure, including Kinetics of Degradation Products

Background: Desflurane and sevoflurane permit speedier changes in anesthetic partial pressures than do older halogenated anesthetics. The authors determined the kinetic characteristics of desflurane and sevoflurane and those of compound A [CH2 F-O-C(= CF2)(CF3)], a nephrotoxic degradation product of sevoflurane.

Methods: Volunteers received 1.25 minimum alveolar concentration of desflurane or sevoflurane, each administered for 8 h in a fresh gas inflow of 2 l/min. Inspired (FI) and end-tidal (FA) concentrations of anesthetic and compound A were measured during administration, and FA relative to FAO (the last end-tidal concentration during administration) during elimination. The indices of recovery were also measured.

Results: The ratio FI /FA rapidly approached 1.0, with values greater for sevoflurane (desflurane 1.06 +/- 0.01 vs. sevoflurane 1.11 +/- 0.02, mean +/- SD). The ratio FA /FI for compound A was approximately 0.8. The FA /FAO ratio decreased slightly more rapidly with desflurane than with sevoflurane, and objective measures indicated faster recovery with desflurane: The initial response to command (14 +/- 4 min vs. 28 +/- 8 min [means +/- SD]) and orientation (19 +/- 4 vs. 33 +/- 9 min) was quicker, and recovery was faster as defined by results of the Digit Symbol Substitution, P-deletion, and Trieger tests. Desflurane produced less vomiting (1 [0.5, 3]; median [quartiles] episodes) than did sevoflurane (5 [2.5, 7.5] episodes). The FA /FAO ratio for compound A decreased within 5 min to a constant value of 0.1.     

Flow Cytometric Measurement of DNA Index and BrdUrd Labeling Index in Endoscopic Biopsy Specimens of Colorectal Carcinoma

We compared values of the DNA Index (DI) and bromodeoxyuridine (BrdUrd) labeling index (BULI) of biopsy specimens with those of resected specimens from 12 patients with colorectal cancer, to evaluate the cell cycle by flow cytometry (FCM). From each patient, 4 biopsy specimens were endoscopically removed. Also, small pieces of tissue, 0.5 cm in diameter, were taken from 4 different sites of the resected tumor. Both kinds of specimens were labeled in vitro with BrdUrd. Their DI and BULI values were evaluated from the DNA/BrdUrd bivariate scatter diagram by FCM. It was found that the coefficients of variation (CVs) for endoscopic biopsy specimens were siginificantly lower than those for resected specimens, 4.2 ± 1.3 (Mean ± S. D.) and 5.4 ± 1. 7, respectively. In 8 cases without intratumoral DI heterogeneity, there was a good correlation in the values of DI between the biopsy and resected specimens (r = 0.99, p < 0.01). A significant correlation was also found in the BULI values between the two types of specimens (r = 0.73, p < 0.01). These results suggested that 4 biopsy specimens were enough to estimate DI and BULI by FCM and that DI and BULI values determined by flow cytometry could be useful for decision-making about the therapeutic modality for preoperative patients.     

Efficacy and safety of monoclonal antibody purified factor IX concentrate in haemophilia B patients undergoing surgical procedures

The present study summarizes results of the efficacy and safety of monoclonal antibody (MAb) purified factor IX concentrate [Mononine® Coagulation Factor IX (Human), Centeon L.L.C., King of Prussia, PA, USA] for surgical prophylaxis in 74 patients with mild, moderate or severe haemophilia B who underwent a total of 81 different operative interventions. Surgical procedures included joint replacement/arthroplasty ( n = 12), gastrointestinal (GI) or rectal surgery ( n = 6), synovectomy/osteotomy ( n = 8), hernia repair ( n = 4), central catheter insertion ( n = 3), ENT surgery ( n = 4), dental procedures ( n = 14), biopsies ( n = 2), gynaecological procedures ( n = 4), ophthalmological surgery ( n = 4), spinal surgery ( n = 4), urogenital surgery ( n = 2), other orthopaedic surgery ( n = 4) or other miscellaneous procedures ( n = 10). All patients demonstrated haemostasis rated as 'excellent' by the investigators. No patients experienced clinically evident thromboembolic complications during treatment with MAb factor IX. These results, from a large and varied random group of patients, demonstrate that this highly purified factor IX concentrate is safe and effective for surgical prophylaxis in patients with haemophilia B, including those patients who have experienced thromboembolic complications during prior treatment with prothrombin complex concentrates.