Acute, subchronic, and mutagenicity studies with norbornene fluoroalcohol

The object of this study was to evaluate the toxicity of norbornene fluoroalcohol (NBFOH), which is used as an intermediate in the production of fluorinated monomers and polymers. NBFOH was evaluated for acute oral, dermal, and inhalation toxicity, dermal sensitization using the Local Lymph Node Assay (LLNA), mutagenesis by the Ames assay, and subchronic toxicity in a 4-week inhalation rat study. NBFOH demonstrated slight acute toxicity in oral, dermal, and inhalation studies. Approximate lethal doses of 3400 and > 5000 mg/kg for the oral and dermal routes, respectively, and an approximate lethal concentration of 4300 mg/m(3) were determined. NBFOH demonstrated moderate skin irritation, was a severe eye irritant, produced dermal sensitization, but did not cause bacterial mutagenicity either in the presence or absence of S9 activation. Male and female rats were exposed nose only to airborne NBFOH at levels of 0, 410, 1400, and 1500 mg/m(3), 6 h/day, 5 days/week for 4 weeks with clinical and histopathology specimens collected 1 day after the final exposure. Due to the vapor pressure of NBFOH, the 1500 mg/m(3) atmosphere was 27% aerosol and 73% vapor; the 1400 mg/m(3) atmosphere was 5% aerosol and 95% vapor, and the 410 mg/m(3) level was only vapor. No test substance-related mortality or clinical signs of toxicity were observed over the course of the study, and male rats demonstrated significant weight loss and decreased food consumption at 1400 mg/m(3). Male rats from the 1500 mg/m(3) group demonstrated an 11% increase in prothrombin time that was significantly higher than the control value. Examination of fluoride in the urine did not demonstrate a concentration-response relationship, with minimal elevations observed in male rats at all exposure levels and sporadic increases in females. Both male and female rats exposed to 1400 mg/m(3) or greater had squamous metaplasia of the laryngeal mucosa and degeneration of the nasal olfactory and respiratory mucosa. Based on the above findings, NBFOH demonstrates the potential to produce allergic contact dermatitis, and subchronic inhalation studies indicate a no-observed-adverse-effect-level (NOAEL) of 410 mg/m(3).     

Efficacy of unilateral nerve sparing in radical perineal prostatectomy

AIM: We determine the efficacy of unilateral nerve-sparing radical perineal prostatectomy in preserving the sexual function. PATIENTS AND METHODS: Ninety-two patients with histologically confirmed unilateral prostate cancer were scheduled for contralateral nerve preservation. The perioperative morbidity was assessed using the patients' chart reviews. Postoperative health-related quality of life, urinary continence, and potency were evaluated prospectively with questionnaires provided before surgery and then after 6, 12, and 24 months. RESULTS: Unilateral nerve preservation was performed in 88 of the 92 patients. Due to extensive scarring or prostatic size, the procedure was terminated as regular radical prostatectomy in 4 other patients. The perioperative complication rate was low and of minor significance, except in 1 patient who experienced a significant myoglobulinuria due to a prolonged procedure. Blood transfusions were necessary in 5 (5.4%) patients. Ureteral reimplantation was performed in 1 patient because of ureteral stricture. Positive surgical margins were present in 12 (18%) of 67 pT2 patients and in 8 (35%) of 23 pT3 patients. A proportion of 48% (15/31) of the patients followed for more than 24 months and who had a good erectile function prior to surgery reported unassisted sexual intercourse. However, only 4 of these patients were completely satisfied with all aspects of sexual performance, as asked in a short version of the International Index of Erectile Function questionnaire. CONCLUSIONS: Unilateral nerve-sparing radical perineal prostatectomy is technically feasible and yields excellent results in terms of potency preservation for prostates <60 ml. However, the quality of erections is decreased, even in patients with erections sufficient for intercourse. Hence, appropriate sexual counseling in conjunction with medical therapy should be offered to all patients.     

Impact of intraoperative duodenal feeding on the oxygen balance of the splanchnic region in severely burned patients

Enteral feeding causes an increase of intestinal oxygen demand depending on the amount administered. The aim of this study presented was to evaluate, whether intraoperative duodenal feeding might put patients at risk developing splanchnic O(2)-imbalance due to an intraoperatively compromised intestinal perfusion based on stress and unrecognized hypovolemia. In 18 severely burned patients, the CO(2)-gap between the arterial and gastric CO(2), as a parameter for the intestinal O(2)-balance, was measured during the first operation. All operations were performed on day 3-5 after admission and lasted for 4-5h. Half of the patients (nine patients) were fed intraoperatively, whereas in the other nine patients feeding was suspended beginning 1h prior to surgery until 6h after surgery. CO(2)-gap measurements were carried out prior to surgery, hourly during the operation and 5h postoperatively. Measurements 3 and 4h after beginning of the operation revealed significantly higher CO(2)-gap values in the fasting group. All other measurements showed no significant difference between both groups. Therefore, intraoperative enteral nutrition, at least in the early postburn phase, is not only necessary for reducing caloric deficits, but also seems to have a protective effect on gut oxygen balance.     

Fatal measles encephalopathy with retinopathy during cytotoxic chemotherapy

A 14-year-old boy receiving post-operative cytotoxic chemotherapy for a testicular rhabdomyosarcoma developed a fatal encephalopathy associated with retinal changes 2 months after an episode of acute measles. Post-mortem histological examination showed intranuclear inclusion bodies in the neurons and glial cells, but inflammatory cell infiltrations were absent. Electron-microscopic and immunofluorescent studies revealed intracellular masses of paramyxovirus nucleocapsid-like structures, which had the morphological and antigenic properties of measles virus. Recent reports have emphasized the possibility of occurrence of a similar encephalopathy in treated childhood leukaemia. It is evident, however, that this potentially fatal complication must be borne in mind when measles is contracted during any form of cytotoxic treatment or immunosuppression. Retinal changes may be of value for the diagnosis during life. We propose the designation “measles encephalopathy during immunosuppression” (MEI) for this condition.     

Pitfalls of and controversies in cluster randomization trials

It is now well known that standard statistical procedures become invalidated when applied to cluster randomized trials in which the unit of inference is the individual. A resulting consequence is that researchers conducting such trials are faced with a multitude of design choices, including selection of the primary unit of inference, the degree to which clusters should be matched or stratified by prognostic factors at baseline, and decisions related to cluster subsampling. Moreover, application of ethical principles developed for individually randomized trials may also require modification. We discuss several topics related to these issues, with emphasis on the choices that must be made in the planning stages of a trial and on some potential pitfalls to be avoided.     

Electroencephalographic correlate of juvenile Huntington's disease

The spectrum of clinical disease in juvenile Huntington's disease differs from that seen in adults. Younger patients often present with seizures, dystonia and rigidity. The mechanism and type of seizures, timing of onset and electrographic features have not been well characterized in either adults or children. We describe the electroencephalographic findings observed in a young child with Huntington's disease who presented with motor regression and seizures. Recordings demonstrated bilateral posterior quadrant epileptiform discharges and occipital intermittent rhythmic delta activity, generally considered a nonspecific abnormality. These findings have not been reported in adult or juvenile Huntington's disease. Its presence in proximity to bilateral posterior spikes suggests that occipital intermittent rhythmic delta activity is an epileptiform abnormality, on a continuum with the posterior spike-and-wave discharges. Intermittent rhythmic delta activity can occur secondary to either the subcortical gray-matter disease or the associated seizure disorder. Huntington's disease should be considered in the differential diagnosis of young children who present with seizures and developmental regression.