Evaluation of agonists and antagonists acting at Group I metabotropic glutamate receptors in the thalamus in vivo.

Recordings were made from single neurones in the ventrobasal thalamus of anaesthetised rats in order to evaluate the properties of several agonists and antagonists of Group I mGlu receptors. The selective mGlu1 receptor antagonist LY367385 was found to reduce excitatory responses to iontophoretically applied ACPD and DHPG whereas the mGlu5 agonist CHPG was resistant to antagonism. The antagonists LY367366 and LY393053 reduced responses to all three agonists, but without reducing responses to NMDA or AMPA. Although AIDA was also found to reduce mGlu agonist-evoked responses, this antagonist also produced significant reductions in responses to NMDA and AMPA. These data suggest that there are functional mGlu1 and mGlu5 receptors in the thalamus. Furthermore, LY367385 is a useful tool for investigating mGlu1 functions whereas LY367366 and LY393053 have a broader spectrum of action. The usefulness of AIDA as an antagonist in physiological experiments would appear to be limited by its effects against NMDA and AMPA.     

Chlorpyrifos: a ten-year US poison center exposure experience

We performed a retrospective review of data based on poison center exposure inquiries related to chlorpyrifos (CP) and the corresponding poison center-determined medical outcomes reported to the Toxic Exposure Surveillance System (TESS) of the American Association of Poison Control Centers. Ten y (1985-1994) of TESS data were obtained. Medical outcomes representing all inquiries, accidental/unintentional inquiries, and intentional/suicidal inquiries were tabulated. Published TESS data was also tabulated to allow comparison of CP exposure inquiries to all non-pharmaceutical and insecticides/pesticides exposure inquiries for like time periods. Frequency of antidote use, product sales data, CP-related fatality reports, and pertinent issues related to telephone derived surveillance data were also reviewed; 36, 183 CP exposure inquiries were identified. Of all CP exposure inquiries, 27, 473 (75.9%) were assessed as having no significant health consequences; 4,511 (12.5%) outcomes were judged unrelated and 2,980 (8.2%) were unable to be followed. Reported significant medical outcomes for the remaining exposure inquiries were moderate 1,092 (3.0%), major 119 (0.3%) and death 8 (0.02%). Considering only calls with outcomes judged causally related to CP, where a given level of effect could reasonably be determined, 95.8% (27,473/28,692) of these calls resulted in no significant health effects. Use of antidotes specific to organophosphates were infrequent [atropine, 1.0% (385) and 2-PAM, 0.5% (177) of all cases respectively]. Despite the number of reported CP exposure inquiries, relatively few resulted in outcomes of consequence. TESS data suggested that the majority of patients undergoing medical evaluation and/or treatment after a suspected CP exposure do not require specific antidotes. TESS data serves as a useful first step in evaluating product safety. Assessment of product toxicity requires additional investigation of reported adverse effects and circumstances related to the incident.     

Outcome of children with respiratory symptoms without objective evidence of asthma: a two-year, prospective, follow-up study

This study evaluated the outcome of 33 children with asthma-like symptoms without objective evidence of asthma, and the role of certain factors in predicting the development of clinical asthma in these children. Data on symptom histories, lung functions (flow-volume spirometry, free running test and methacholine inhalation challenge test) and atopic sensitization (skin prick tests and markers of eosinophilic inflammation) were collected twice with an interval of 2 y, and the diagnoses were re-evaluated after the follow-up period. Based on the results, it was concluded that one-third of the children with prolonged or recurrent lower airway symptoms, such as cough or wheeze, either have mild asthma or will develop asthma in the near future. Children who had a significant response [≥ 10% fall in forced expiratory volume in 1 s (FEV1)] in the free running test formed a risk group for active asthma, whereas other baseline characteristics seemed not to predict the outcome.     

Randomized trial examining cerebral haemodynamics following artificial or animal surfactant

To determine the effects of animal and artificial surfactants on cerebral haemodynamics, 20 premature babies receiving mechanical ventilation were randomized to receive Curosurf or Exosurf surfactant. Anterior cerebral artery blood flow velocity (CABFV) was measured using Doppler ultrasound before and up to 2 h after treatment. Following animal surfactant there was a rapid reduction in CABFV (median -36%, range -43% to +8%, p < 0:01), whereas artificial surfactant resulted in a slower rise which was less marked (median +20%, range -7% to +62%, p < 0:05). There were no significant changes in blood pressure. Two hours after administration, the oxygenation index (OI) improved significantly only in babies receiving animal surfactant. In this group there was a significant association between the change in CABFV at 1 min and the change in OI at 2 h ( r = 0:66, p < 0:05). Animal surfactant produces rapid improvements in ventilation which are associated with marked alterations in cerebral haemodynamics.     

Recurrent primary vulvovaginal malignant melanoma arising in melanoma in situ– the natural history of lesions followed for 23 years

Multifocal melanoma and melanoma in situ of the vulva and vagina are uncommon lesions, and our understanding of their natural history is limited. Vulvovaginal melanoma appears to be biologically different from cutaneous melanoma and has more in common with mucosal melanoma. A 60-year-old woman presented in 1977 with a pigmented vulvar lesion. Histologic examination revealed melanoma in situ associated with focal invasive melanoma. She re-presented with recurrent primary melanomas arising in melanoma in situ in 1990 and 1998 and died of widespread metastatic melanoma in 2000. Melanoma in situ of the vulva and vagina is rare and appears to have a relatively slow but definite progression to invasive melanoma. All suspicious pigmented lesions in this region should be biopsied, and if multifocal in situ melanoma is identified, vulvo(vagin)ectomy should be considered.     

Atrioesophageal Fistula After Cryoballoon Pulmonary Vein Isolation

Atrioesophageal Fistula After Cryoballoon PV Isolation . The risk of atrioesophageal fistula after cryoballoon pulmonary vein isolation is thought to be much lower than after radiofrequency ablation, seeing that no data exist on this complication so far. We report for the first time on the occurrence of an atrioesophageal fistula 4 weeks after cryoballoon ablation at the site of the left inferior pulmonary vein. We suggest that even when using cryothermal ablation technique, an imaging modality to assess the proximity of esophagus and left atrium should be routinely performed to avoid this fatal complication. (J Cardiovasc Electrophysiol, Vol. 23, pp. 1254–1257, November 2012)