Mechanism of action of the epileptogenic drug pentylenetetrazol on a cloned neuronal potassium channel

The action of the epileptogenic agent pentylenetetrazol (PTZ) on a cloned potassium channel of the rat brain was studied. The Kv1.1 channel was expressed in oocytes ofXenopus laevis and potassium currents were investigated in outside-out and inside-out membrane patches. The results show that PTZ increased the multi-channel potassium currents at strongly negative potentials and decreased them at potentials positive to −35 mV both in outside-out and inside-out membrane patches. The extent and manner of PTZ action, the concentration dependence as well as the onset and time course of the PTZ effect were the same both in outside-out and inside-out membrane patches. The single-channel potassium currents showed an increase in open probability and frequency of opening and a decrease in close time at −50 mV and vice versa at 0 mV with application of PTZ. The amplitude of single-channel current, the open time and the latency to the first channel opening remained almost unchanged under PTZ. The results indicate that PTZ acts via the cell membrane and influences the membrane-associated part of the potassium channel. Thereby, PTZ accelerates the transition from the inactivated to the open state of the channel at strongly negative potentials and reduces it at slightly negative and positive potentials. This mechanism may be the basis for a gate function which is in favour of the development of epileptic discharges.     

Evaluation of postsurgical crestal bone levels adjacent to non‐submerged dental implants

In most of the studies on long-term radiographic evaluations of crestal bone levels adjacent to dental implants, no baseline radiographs taken immediately post-surgically had been obtained.The aim of this study was to test the reproducibility of a simple radiographic method for linear measurements of changes in bone levels and to evaluate changes in crestal bone levels adjacent co non-submerged ITI® implants 1 year following the surgical procedure. From 128 patients enrolled in a clinical and radiographic longitudinal study 40 patients also had radiographs taken immediately postsurgically. They were, however, not obtained as “identical” images. The radiographs were mounted onto slides and projected on a screen. Mesially and distally from 57 implants triplicate linear measurements of the distance implant shoulder to bone crest were taken, using known dimensions of the implants as internal reference distances. The median difference of 213 (out of 228 possible) duplicate measurements was 0.00 mm (ranging from ?1.72 mm to +1.47 mm when comparing the second co the third reading). Some 81% of the double measurements were within ±0.5 mm and the precision was 0.30 mm. In the immediate postoperative radiographs the median mesial bone level was located at 2.07 mm (distally 2.19 mm) from the implant shoulder. A statistically significant amount of bone loss in the first year was observed mesially (median=?0.78 mm) and distally (0.85 mm)(Wilcoxon matched pairs signed rank test ±0.001). No statistically significant influence of the implant location, the implant length, type of the implant (screw; cylinder) was observed (Kruskal-Wallis P>0.05).The age of the patients was not correlated significantly to the amount of bone loss observed. In conclusion, methodological limitations existed when evaluating linear bone changes in non-identical radiographs using reference dimensions of the implants. The amount of postsurgical bone loss estimated in other studies was confirmed when using an immediate postoperative radiograph as a baseline.     

Lack of Nonshivering Thermogenesis in Infants Anesthetized with Fentanyl and Propofol

Background: Sweating, vasoconstriction, and shivering have been observed during general anesthesia. Among these, vasoconstriction is especially important because-once triggered-it minimizes further hypothermia. Surprisingly, the core-temperature plateau associated with vasoconstriction appears to preserve core temperature better in infants and children than adults. This observation suggests that vasoconstriction in anesthetized infants may be accompanied by hypermetabolism. Consistent with this theory, unanesthetized infants rely on nonshivering thermogenesis to double heat production when vasoconstriction alone is insufficient. Accordingly, the authors tested the hypothesis that intraoperative core hypothermia triggers nonshivering thermogenesis in infants.

Methods: With Ethics Committee approval and written parental consent, the authors studied six infants undergoing abdominal surgery. All were aged 1 day to 9 months and weighed 2.4-9 kg. Anesthesia was maintained with propofol and fentanyl. The infants were mechanically ventilated and allowed to cool passively until core (distal esophageal) temperatures reached 34-34.5 degrees Celsius. Oxygen consumption-the authors' index of metabolic rate- was recorded throughout cooling. Because nonshivering thermogenesis triples circulating norepinephrine concentrations, arterial blood was analyzed for plasma catecholamines at [nearly equal] 0.5 degrees Celsius intervals. Thermoregulatory vasoconstriction was evaluated using forearm - fingertip, skin-surface gradients, with gradients exceeding 4 degrees Celsius, indicating intense vasoconstriction. The patients were subsequently rapidly rewarmed to 37 degrees Celsius. Regression analysis was used to correlate changes in oxygen consumption and plasma catecholamine concentrations with core temperature.

Results: All patients were vasoconstricted by the time core temperature reached 36 degrees Celsius. Further reduction in core temperature to 34-34.5 degrees Celsius did not increase oxygen consumption. Instead, oxygen consumption decreased linearly. Hypothermia also failed to increase plasma catecholamine concentrations.     

Prevention of hepatitis B virus recurrence after liver transplantation

Abstract:  Liver transplantation for hepatitis B virus (HBV)-related liver disease has changed from a contraindication to outcomes comparable with non-HBV-related liver transplantations during the last two decades. Mainly the implementation of immunoprophylaxis with hepatitis B immunoglobulin (HBIG) and the use of nucleoside analogs such as lamivudine and adefovir account for this dramatic change. The standard of care in most centers today consists of lamivudine treatment in replicating hepatitis B pre-orthotopic liver transplantation (OLT) and a combination regimen of lamivudine and HBIG post-OLT. With adefovir, a potent antiviral drug became available in recent years that allows for the treatment of patients with lamivudine-resistant tyrosine-methionine-aspartate-aspartate (YMDD)-mutant HBV. In the transplantation setting, first studies indicate that a triple prophylactic therapy consisting of lamivudine, adefovir, and HBIG will become the standard of care for YMDD-mutant-related hepatitis B. With new drugs emerging for the treatment of chronic HBV, there is optimism for new options also in the transplant setting.     

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.     

Role of DAT‐SPECT in the diagnostic work up of Parkinsonism

The diagnosis of idiopathic Parkinson's disease (PD) can be achieved with high degrees of accuracy in cases with full expression of classical clinical features. However, diagnostic uncertainty remains in early disease with subtle or ambiguous signs. Functional imaging has been suggested to increase the diagnostic yield in parkinsonian syndromes with uncertain clinical classification. Loss of striatal dopamine nerve terminal function, a hallmark of neurodegenerative Parkinsonism, is strongly related to decreases of dopamine transporter (DAT) density, which can be measured by single photon emission computed tomography (SPECT). The use of DAT‐SPECT facilitates the differential diagnosis in patients with isolated tremor symptoms not fulfilling PD or essential tremor criteria, drug‐induced, psychogenic and vascular Parkinsonism as well as dementia when associated with Parkinsonism. This review addresses the value of DAT‐SPECT in early differential diagnosis, and its potential as a screening tool for subjects at risk of developing PD as well as issues around the assessment of disease progression. © 2007 Movement Disorder Society