Early developmental 2,3,7,8-tetrachlorodibenzo-p-dioxin exposure decreases chick embryo heart chronotropic response to isoproterenol but not to agents affecting signals downstream of the beta-adrenergic receptor.

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) causes cardiovascular toxicity in laboratory animals, including alteration in several processes in which beta-adrenergic receptor (beta-AR) signaling plays important roles. Thus, our laboratory investigated the effects of TCDD on beta-AR expression and signal transduction. Fertile chicken eggs were injected with vehicle (corn oil), 0.24 or 0.3 pmol TCDD/g egg on incubation day 0 (D0) or D5. On D10, heart function was assessed by ECG in ovo. Exposure to TCDD increased the incidence of arrhythmias and decreased the positive chronotropic responsiveness of the heart to isoproterenol. The reduced beta-AR responsiveness was, in part, independent of any overt morphological changes in the heart as chick embryos exposed to TCDD on D5 displayed an intermediate responsiveness to beta-AR agonist in the absence of the dilated cardiomyopathy observed in chick embryos exposed to TCDD on D0. TCDD did not decrease the chronotropic response of the heart to agents that stimulate signals downstream of the beta-AR. In fact, TCDD-exposed embryos were more sensitive than controls to forskolin, increasing heart rates (HR) 21.8 +/- 3.5 beats per min (bpm) above baseline versus control values at 6.3 +/- 2.7 bpm above baseline. TCDD exposure also augmented the negative chronotropic response of the heart to verapamil, decreasing HR -23.2 +/- 7.4 bpm relative to baseline versus control embryos at -12.7 +/- 5.9 bpm below baseline. Finally, the mean cardiac beta1-AR mRNA expression in D10 embryos was not significantly altered by exposure to TCDD on D0. These findings establish that a functional end point of the developing chick heart is sensitive to TCDD exposure and that the TCDD-induced reduction in beta-AR responsiveness may result from alterations in signal transduction upstream of adenylyl cyclase.     

Emergency Preparedness for Health Professionals in a Statewide AHEC Program: the first two years.

In 2003 through 2005, the California Statewide Area Health Education Centers (AHEC) Program developed an educational delivery system, through partnerships with six AHECs and state organizations concerned with emergency preparedness, to train for public health emergency preparedness the health professionals who practice primarily in the state's medically underserved areas. Four educational modules--General Emergency Preparedness, Bioterrorism, Chemical and Radiologic Agents, and Emerging Infections--were developed and delivered by a trained, multidisciplinary, community-based faculty. The authors discuss the organization, partnerships, curriculum, faculty, characteristics of trainees, outcomes of the program, effects for AHECs, and the evaluation used to commit the organization and program process to the intended program objectives during the two-year period. Over 9,000 health professionals attended one or more of the 462 educational presentations. Approximately one third of attendees were physicians, and 82% of the learners were from sites that typically care for the underserved. Important to the success of the program (which still continues in a revised form) were the types of partnerships, an orientation of the curriculum to all-hazards disaster preparedness, the delivery of educational sessions at clinical sites, and the increased capacities of community AHECs to facilitate continuing professional education. The challenges were the diminished role of a key partner organization, uncertainties within the funding agency, and the widespread geographic area to address.     

Increasing synchronization may promote seizure termination: evidence from status epilepticus.

OBJECTIVE: To test whether increasing synchronization of neuronal activity might be causally related to seizure termination. METHODS: Neuronal synchronization was assessed by the relative changes of the eigenvalue spectrum of the equal-time correlation matrix computed from a short window sliding along multi-channel EEGs, recorded with either intracranial or surface electrodes. RESULTS: Synchronization dynamics of six status epilepticus EEG recordings from six patients were assessed. In all six recordings EEG synchronization fluctuated around relatively low levels during ongoing epileptiform activity. Synchronization only persistently increased before, or in one case, at the end of status epilepticus. Ongoing seizure activity stopped without pharmacological intervention in one patient. In four of the five other cases, the persistent increase of synchronization followed administration of anticonvulsant drugs. CONCLUSIONS: Our findings support the hypothesis that increasing synchronization of neuronal activity may be considered as an emergent self-regulatory mechanism for seizure termination. SIGNIFICANCE: The traditional concept is challenged that increasing neuronal synchronization during epileptic seizures is always pathological and should be suppressed. On the contrary, our findings imply that therapeutic interventions to increase synchronization during seizures might be beneficial.     

Identification of Risk Factors for Postoperative Nausea and Vomiting in the Perianesthesia Adult Patient

Postoperative nausea and vomiting (PONV) is a common and potentially debilitating complication of surgery. The preoperative assessment of PONV using established risk assessment tools enables the identification of patients at risk and potentially decreases the incidence of PONV in adult surgical patients. The identification of risk factors associated with PONV and the factors that are independent predictors of PONV preoperatively can facilitate the effective prophylactic treatment and management of PONV in adult surgical patients.     

Body composition of patients on a very low-protein diet: a two-year survey with DEXA.

BACKGROUND: It has been reported that patients on a very-low-protein diet (VLPD) maintain a satisfactory nutritional status because of a conserved adaptive metabolic response. However, only few studies have examined the course of nutritional status and body composition in the long term (2 years). METHODS: Thirteen stable patients (8 men; age, 55 +/- 12 years; glomerular filtration rate (GFR), 15 +/- 5 mL/min) receiving a VLPD (0.3 g/kg/day protein) supplemented with amino acids and ketoanalogues (SVLPD) were studied for 2 years. A joint visit with a physician and a dietitian and routine blood and urine analyses were performed every month. Dual-energy x-ray absorptiometry (DEXA), which was used to assess modification of body composition, and GFR (urinary 51Cr-EDTA) and urinary urea and creatinine excretion, which were used to assess nutritional status and compliance to the diet, were assessed every 3 months. RESULTS: GFR, albumin, and prealbumin levels remained stable. Urea urinary excretion decreased at 3 months and then slightly increased at 2 years, but the calculated protein intake remained low at 0.38 +/- 0.1 g/kg/day. Energy intake remained close to 30 kcal/kg/day. No significant change was observed for total fat mass or percent fat mass. After an initial decrease, lean body mass stabilized at 6 months and then increased significantly from 6 to 24 months (P =.02, paired t-test); the mean increase during this period was of 2 kg, that is, 4.6%. Urinary creatinine excretion showed the same profile. Total bone mass, lumbar or hip site bone mass, and Z-score significantly decreased from T0 to 1 and 2 years (P <.05). CONCLUSION: This study confirms that a supplemented VLPD is nutritionally safe for a long period, but attention must be paid to bone mass.     

Effects of different perfusates on functional parameters of isolated perfused dog kidneys.

BACKGROUND: The isolated perfused canine kidney has been established as a valid model for conducting both renal physiology and transplantation research. This model is of particular importance for developing new strategies to improve graft function after renal transplantation. In the present study, a newly developed method using isolated haemoperfused porcine kidneys was adapted for use in canine kidneys. In contrast to haemoperfusion, synthetic perfusion media can be standardized and can prevent the initiation of blood-mediated reperfusion reactions. Thus, an additional aim was to determine whether blood could be replaced by synthetic cell-free perfusion solutions. METHODS: Canine kidneys (n = 30) were harvested from donors euthanized in veterinary practices for causes unrelated to the present study. The kidneys were isolated and perfused with autologous blood or cell-free synthetic electrolyte buffer (Tyrode solution). During perfusion, we monitored renal perfusate flow (RPF), glomerular filtration rate (GFR), electrolyte and glucose reabsorption, oxygen consumption and urine concentration. RESULTS: Changes in perfusion medium did not affect the RPF. In contrast, GFR, urine concentration and oxygen consumption were significantly higher, whereas fractional excretion of sodium and glucose were significantly lower in blood- than in Tyrode-perfused kidneys. CONCLUSIONS: This system offers a simple model for studying whole-organ functional alterations after acute renal ischaemia. Renal function indicators were below values reported during in vivo physiological conditions. These functions were better conserved when kidneys were perfused with autologous blood than with Tyrode.     

Acquired dyschromatopsia in combined exposure to solvents and alcohol

Hypothesis: Does occupational exposure to solvents in combination with alcohol intake give rise to acquired color vision defects? Method: A total of 138 individuals exposed to solvents (toluene, xylene, trichloroethylene, tetrachloroethylene) were examined using Lanthony’s D-15 test and compared with 100 nonexposed controls. The extent of color vision loss was quantitatively assessed based on Bowman’s color confusion index (CCI). A cumulative exposure index was calculated from the hours of exposure per day and the years of exposure. In 30 persons who were exposed to trichloroethylene and tetrachloroethylene, urinary trichloroacetic acid was assessed as a parameter of exposure. Alcohol intake was calculated as based on interviews of patients in grams of ethyl alcohol per week. Results: Individuals who consumed more than 250 g alcohol/week and were simultaneously exposed to solvents showed a significantly elevated CCI (P = 0.0044). No significant correlation emerged between trichloroacetid acid excretion in the urine or the cumulative exposure index and the CCI. Conclusion: The combination of alcohol intake and occupational exposure to solvents discloses the risk of acquired subclinical color vision defects.     

Postictal Language Dysfunction in Patients with Right or Bilateral Hemispheric Language Localization

Summary: Purpose : As shown previously, when temporal lobe complex partial seizures (TLCPS) originate from the language dominant hemisphere, patients cannot read a test phrase correctly within 60 s of the end of the ictal discharge. We wished to assess whether postictal language testing results discordant with this pattern identified patients with non-left (right hemisphere or mixed) language dominance.
Methods : Since 1988, all patients undergoing video/EEG monitoring at our institution have been given a test phrase to read aloud as soon as a seizure is detected. Inclusion criteria for this study were (a) postictal language testing within 60 s of seizure end for at least one TLCPS, (b) >90% seizure reduction after anterior temporal lobectomy with 2-year minimum follow- follow- up, and (c) language localization by either intracarotid amobarbital test (IAT) or direct electrical stimulation of left hemisphere cortex.
Results : Two hundred twenty-four seizures in 64 patients were analyzed. Discordant postictal language patterns were noted in 10 of 11 patients with IAT documented non-left language dominance and in 15 of 53 with left dominance (p = 0.006; sensitivity 90.9%, specificity 71.7%).
Conclusions : Postictal language testing accurately identifies patients with non-left language dominance and may be useful in selecting appropriate patients for IAT.