Cardiotoxicity of chlorodibromomethane and trichloromethane in rats and isolated rat cardiac myocytes

The cardiovascular effects were investigated after acute and subacute treatment with chlorodibromomethane (CDBM; 0.4 to 3.2 mmol/kg p.o.), trichloromethane (TCM; 0.31 and 1.25 mmol/kg p.o.) and mixtures of CDBM and TCM (acute, 0.8 mmol CDBM/kg + 1.25 mmol TCM/kg p.o.; subacute, 0.4 mmol CDBM/kg + 0.31 mmol TCM/kg p.o.) in conscious and urethane anaesthetized male Wistar rats (n = 6-10 per treatment). Furthermore it was observed whether cardiovascular responses were modified in CDBM or TCM treated rats after administration of exogenous catecholamines (epinephrine, 1 microg/kg; norepinephrine, 2 microg/kg) and underpinned with in vitro alterations of Ca2+ dynamics in cardiac myocytes. The present findings demonstrated that single and subacute oral administration of CDBM or TCM and mixtures of CDBM and TCM resulted in arrhythmogenic and negative chronotropic and dromotropic effects in conscious and urethane anaesthetized rats. The atrioventricular conduction time and the intraventricular extension time were extended. A slight shortening of the repolarization velocity was observed. The myocardial contractility was depressed and the heart was sensitized to the arrhythmogenic effects of epinephrine. After catecholamine injection the adrenergic cardiovascular responses in urethane anesthetized rats were modified: increased hypertensive epinephrine and norepinephrine action as well as augmentation of negative chronotropic and negative dromotropic cardiac effects of catecholamines were observed. The positive inotropic adrenergic response was diminished. The present in vivo findings, myocardial depression after acute CDBM treatment, as determined by different indices of contractility, correlate well with the observed inhibitory actions of CDBM on Ca2+ dynamics in isolated cardiac myocytes. All cardiovascular alterations found after CDBM or TCM treatment were not intensified after treatment with mixtures of CDBM and TCM. The effects observed were distinctly stronger after TCM (1.25 and 0.31 mmol/kg) treatment compared to CDBM (0.8 and 0.4 mmol/kg) treatment.     

Nonsyndromic cleft lip and palate: no evidence of linkage to HLA or factor 13A

Nonsyndromic cleft lip with or without cleft palate (CLP) is a common craniofacial anomaly, the etiology of which is not known. Population studies have shown that a large proportion of cases occur sporadically. Recently, segregation analyses applied to CLP families have demonstrated that an autosomal dominant/codominant gene(s) may cause clefting in cases. Associations of autosomal dominant CLP and nonsyndromic cleft palate (CP) with HLA and F13A genes on chromosome 6p have been suggested previously. Linkage to these two areas on chromosome 6p were tested in 12 autosomal dominant families with CLP. With a LOD score of -2 or less for exclusion, no evidence of linkage was found to four chromosome 6p markers. Multipoint analysis showed no evidence of a clefting locus in this region spanning 54 cM on chromosome 6p in these CLP families.     

Safety of silver oxide-impregnated silastic tympanostomy tubes

Otorrhea occurs after the insertion of tympanostomy tubes in as many as 50% of ears. Although topical antibiotic solutions minimize otorrhea in the immediate postoperative period, recurrent otorrhea is sometimes a clinical problem. The antimicrobial effects of silver oxide when impregnated into a tympanostomy tube may decrease the incidence of recurrent otorrhea. This study demonstrates that silver oxide-impregnated silicone elastomer is well tolerated within the middle ear of gerbils when implanted for 1 year, and the tissue reaction is no more than silicon elastomer without silver oxide. When applied directly to the round window of guinea pigs, there was no evidence of ototoxicity of silver oxide as measured by electrocochleography (N-1 thresholds) and cytocochleography (hair cell counts). These animal studies indicate that silver oxide-impregnated silicone elastomeric tympanostomy tubes may be used safely in clinical trials to determine efficacy.     

Collective doses to man from dumping of radioactive waste in the Arctic Seas

A box model for the dispersion of radionuclides in the marine environment covering the Arctic Ocean and the North Atlantic Ocean has been constructed. Collective doses from ingestion pathways have been calculated from unit releases of the radionuclides 3H, 60Co, 63Ni, 90Sr, 129I, 137Cs, 239Pu and 241Am into a fjord on the east coast of NovayaZemlya. The results show that doses for the shorter-lived radionuclides (e.g. 137Cs) are derived mainly from seafood production in the Barents Sea. Doses from the longer-lived radionuclides (e.g. 239Pu) are delivered through marine produce further away from the Arctic Ocean. Collective doses were calculated for two release scenarios, both of which are based on information of the dumping of radioactive waste in the Barents and Kara Seas by the former Soviet Union and on preliminary information from the International Arctic Sea Assessment Programme. A worst-case scenario was assumed according to which all radionuclides in liquid and solid radioactive waste were available for dispersion in the marine environment at the time of dumping. Release of radionuclides from spent nuclear fuel was assumed to take place by direct corrosion of the fuel ignoring the barriers that prevent direct contact between the fuel and the seawater. The second scenario selected assumed that releases of radionuclides from spent nuclear fuel do not occur until after failure of the protective barriers. All other liquid and solid radioactive waste was assumed to be available for dispersion at the time of discharge in both scenarios. The estimated collective dose for the worst-case scenario was about 9 manSv and that for the second scenario was about 3 manSv. In both cases, 137Cs is the radionuclide predicted to dominate the collective doses as well as the peak collective dose rates.     

Anxiety and depression in adolescent cancer: findings in patients and parents at the time of diagnosis

Adolescent cancer is uncommon and presents an exceptional stress for the young patient and their parents. The emotional needs of adolescents with cancer are a major factor in the recommendation for the establishment of adolescent cancer units in major cancer centres in the U.K. However, there have been no prospective, longitudinal studies assessing the psychological impact of a diagnosis of cancer on the adolescent patient and their family. In 1994 we began a longitudinal study of the emotional impact of the diagnosis of cancer in patients and their families presenting to an adolescent cancer unit and of the coping strategies they employ. This first report presents the results of the study at the time of diagnosis in 42 adolescents, 34 mothers and 27 fathers. The Beck Depression Inventory (BDI) was used to assess depression and anxiety levels were measured using Spielberger's State Trait Anxiety Inventory (STAI). Adolescents and their parents completed the questionnaires on first admission to the adolescent cancer unit. The median time since cancer diagnosis was approximately 3 weeks. To provide normative data for the U.K. adolescent population, control values were obtained from 173 pupils of the same age and background. The results showed that, contrary to expectation, adolescents with cancer were no more anxious or depressed than the control adolescent population. Nevertheless, a substantial minority of patients and controls had elevated anxiety or depression scores. Girls were significantly more anxious (P = 0.011) and depressed (P < 0.0001) than boys. Mothers were the most anxious family members and were significantly more anxious than fathers (P = 0.038). Parental anxiety scores, especially mothers, were much higher than reported norms. There was no significant difference between mothers' and fathers' depression scores. Although at the time of diagnosis adolescent cancer patients are not more anxious or depressed than their healthy peers, many adolescents without cancer are anxious or depressed. Staff on adolescent cancer units should therefore be aware of the frequency of emotional disturbance in this population. Mothers are the most anxious family members. Although the findings are relatively reassuring at the time of diagnosis, follow-up data from this cohort will show whether anxiety and depression change with treatment involving intensive chemotherapy, surgery and radiotherapy and will indicate the coping strategies which patients and their families adopt in dealing with both the disease and its treatment.     

Activation of coagulation and fibrinolysis in open and laparoscopic cholecystectomy

BACKGROUND: Activation of coagulation and fibrinolysis occurs as a stress response to surgery and may predispose the patient to thromboembolic complications. Other components of the surgical stress response (cytokine release, neurohumoral response, etc.) have been shown to differ between laparoscopic and open cholecystectomy, and the aim of this study was to investigate the effects of laparoscopic and open surgery on the coagulation and fibrinolytic pathways. METHODS: Fourteen patients undergoing laparoscopic cholecystectomy and 12 patients undergoing open cholecystectomy had blood taken in the perioperative period for fibrinopeptide A (FPA) prothrombin fragment F1.2, antithrombin 3, tissue plasminogen activator (tPA) and its fast-acting inhibitor plasminogen activator inhibitor-1 (PAI-1 antigen and activity), and the euglobulin clot lysis time (ECLT). RESULTS: The only significant differences between the two groups occurred 6 h after surgery when the ECLT was longer (p < 0.005; Mann Whitney), and PAI-1 antigen and activity were higher (p < 0.01 and p < 0.001, respectively; Mann Whitney) after open cholecystectomy than laparoscopic cholecystectomy. CONCLUSIONS: Other changes in fibrinolysis and coagulation were similar for open and laparoscopic cholecystectomy. With respect to hemostasis, laparoscopic cholecystectomy does not increase the risk of thromboembolic complications compared to the conventional procedure.