Early and widespread engagement of the cerebellum during hippocampal epileptiform activity Format: Brief Communication.

Despite research illustrating the cerebellum may be a critical circuit element in the epilepsies, remarkably little is known about cerebellar engagement during seizures. We therefore implemented a novel method for repeated imaging of the cerebellum in awake, chronically epileptic animals. We found widespread changes in cerebellar calcium signals during behavioral seizures and during hippocampal seizures that remained electrographic only, arguing against cerebellar modulation simply reflecting motor components. Moreover, even brief interictal spikes produced widespread alterations in cerebellar activity. Changes were noted in the anterior and posterior cerebellum, along the midline, and both ipsilaterally and contralaterally to the seizure focus. Remarkably, changes in the cerebellum also occurred prior to any noticeable change in the hippocampal electrographic recordings, suggesting a special relationship between the cerebellum and hippocampal epileptiform activity. Together these results underscore the importance of the cerebellum in epilepsy, warranting a more consistent consideration of the cerebellum when evaluating epilepsy patients.

Supplemented phase diagrams for vitrification CPA cocktails: DP6, VS55 and M22.

DP6, VS55 and M22 are the most commonly used cryoprotective agent (CPA) cocktails for vitrification experiments in tissues and organs. However, complete phase diagrams for the three CPAs are often unavailable or incomplete (only available for full strength CPAs) thereby hampering optimization of vitrification and rewarming procedures. In this paper, we used differential scanning calorimetry (DSC) to measure the transition temperatures including heterogeneous nucleation temperatures (Thet), glass transition temperatures (Tg), rewarming phase crystallization (devitrification and/or recrystallization) temperatures (Td) and melting temperatures (Tm) while cooling or warming the CPA sample at 5 °C/min and plotted the obtained transition temperatures for different concentrations of CPAs into the phase diagrams. We also used cryomicroscopy cooling or warming the sample at the same rate to record the ice crystallization during the whole process, and we presented the cryomicroscopic images at the transition temperatures, which agreed with the DSC presented phenomena.

Two-year vascular hospitalisation rates and associated costs in patients at risk of atherothrombosis in France and Germany: highest burden for peripheral arterial disease.

OBJECTIVES: To obtain Western European perspectives on the economic burden of atherothrombosis in patients with multiple risk factors only (MRF), cerebrovascular disease (CVD), coronary artery disease (CAD), and in the under-evaluated group of patients with peripheral arterial disease (PAD), we examined vascular-related hospitalisation rates and associated costs in France and Germany. DESIGN: The prospective REACH Registry enrolled 4693 patients in France, and 5594 patients in Germany (from December 2003 until June 2004). METHODS: For each country, 2-year rates and costs associated with cardiovascular events and vascular-related hospitalisations were examined for patients with MRF, CVD, CAD, and PAD. RESULTS: Two-year hospitalisation costs were highest for patients with PAD (3182.1€ for France; 2724.4€ for Germany) and lowest for the MRF group (749.1€ for France; 503.3€ for Germany). Peripheral revascularizations and amputations were the greatest contributors to costs for all risk groups. Across all PAD subgroups, peripheral procedures constituted approximately half of the 2-year costs. CONCLUSION: Hospitalisation rates and costs associated with atherothrombotic disease in France and Germany are high, especially so for patients with PAD.

Use of FT-NIR transmission spectroscopy for the quantitative analysis of an active ingredient in a translucent pharmaceutical topical gel formulation.

The objective of this study was to demonstrate the use of transmission Fourier transform near-infrared (FT-NIR) spectroscopy for quantitative analysis of an active ingredient in a translucent gel formulation. Gels were prepared using Carbopol 980 with 0%, 1%, 2%, 4%, 6%, and 8% ketoprofen and analyzed with an FT-NIR spectrophotometer operated in the transmission mode. The correlation coefficient of the calibration was 0.9996, and the root mean squared error of calibration was 0.0775%. The percent relative standard deviation for multiple measurements was 0.10%. The results prove that FT-NIR can be a good alternative to other, more time-consuming means of analysis for these types of formulations.

Alcohol use and abuse in random samples of physicians and medical students.

BACKGROUND: This study sought to resolve conflicting views about whether physicians are especially prone to alcohol abuse. METHODS: Using an anonymous, mailed questionnaire on substance use, we surveyed 500 physicians, 510 pharmacists, and 974 of their students. The physicians and pharmacists were selected randomly from the state society's membership lists, and students selected were from local school lists. Follow-up surveys were sent to nonresponders at two-week intervals. RESULTS: The physicians and medical students did not drink especially heavily and were no more vulnerable to alcoholism than were their counterparts in pharmacy and other professions. Physicians differed from pharmacists in their style of drinking (greater frequency, smaller quantity), but not in total amount of alcohol consumed. Drinking habits among physicians were not associated with medical specialty or type of practice, but were positively related to gender (males drank more than females) and to age (older doctors were more apt to qualify as heavy drinkers than were younger doctors). CONCLUSIONS: Physicians were no more likely to abuse substances nonmedically than were other professionals. Any group in which alcohol use is nearly universal incurs a risk of abuse and impairment that cannot be ignored.

Risk factors of drug impairment in random samples of physicians and medical students.

The prevalence of hypothesized risk factors of drug impairment is estimated and correlated with drug use in random samples of physicians and medical students. Substantial percentages of both physicians and medical students reported access to drugs, family histories of substance abuse, stress at work and home, emotional problems, and sensation seeking. Each of these factors correlated with drug use in physicians or medical students, and analysis suggested that in most cases the hypothesized risk factors were more likely to be causes rather than consequences of drug use.

Use and abuse of controlled substances by pharmacists and pharmacy students.

The use of controlled substances by samples of pharmacists and pharmacy students in one New England state was surveyed. A questionnaire was sent in November 1984 to a sample of 510 pharmacists randomly selected from the membership list of the state's pharmaceutical association and to a sample of 470 students from the state's pharmacy schools; 76% and 67% of the eligible pharmacists and students responded, respectively. The questionnaire elicited information about the respondents' use of controlled substances for self-treatment and recreation, as well as the instrumental use of stimulants to enhance performance. Almost half of the pharmacists (46%) and two thirds of the students (62%) reported using a controlled substance at some time without a prescription; 19% and 41%, respectively, used one within the past year. Whereas students used the drugs most often for recreation (57% ever, 36% currently), use by pharmacists was more equally divided among self-treatment (29% ever, 13% currently), recreation (29% ever, 9% currently), and instrumental purposes (21% ever). The drugs most often used were marijuana, stimulants (especially cocaine by students), tranquilizers, and opiates. Drug use was generally limited in amount, but 18% of the pharmacists and 35% of the students who ever used a drug either became dependent or were at risk of drug abuse. Current drug use was most strongly associated with age, non-attendance at religious services, student access, year in school, and citizenship. The findings of this study suggest the need for continued development of impaired pharmacist committees and drug abuse prevention programs for pharmacists and pharmacy students.

Psychoactive drug use among practicing physicians and medical students.

We surveyed random samples of 500 practicing physicians and 504 medical students in a New England state during 1984-1985; 70 percent of the physicians and 79 percent of the students responded. Fifty-nine percent of the physicians and 78 percent of the students reported that they had used psychoactive drugs at some time in their lives. In both groups, recreational use most often involved marijuana and cocaine, and self-treatment most often involved tranquilizers and opiates. In the previous year, 25 percent of the physicians had treated themselves with a psychoactive drug, and 10 percent had used one recreationally. Although most of the use was experimental or infrequent, 10 percent of the physicians reported current regular drug use (once a month or more often) and 3 percent had histories of drug dependence. More physicians and medical students had used psychoactive drugs at some time than had comparable samples of pharmacists and pharmacy students. The results suggest a need for renewed professional education about the risks of drug misuse.

Analysis of salsolinol and salsoline in biological samples using deuterium-labelled internal standards and gas chromatography--mass spectrometry.

Salsolinol and salsoline were labelled with deuterium using an acidic exchange reaction in 2HCl--2H2O. Two deuterium atoms were incorporated in both compounds. The deuterium-labelled salsolinol and salsoline were used as internal standards to determine picomol amounts of the corresponding unlabelled compound in the urine, cerebrospinal fluid, brain and liver. The salsolinol was purified on alumina and salsoline collected in the effluent. The compounds were analysed as their pentafluoropropionyl derivatives by gas chromatography on a 1% OV-17 column and were selectively detected with electron-impact mass spectrometry at the molecular ions M+ and M+--15. With human urine the precision of the methods were +/- 4.9% (coefficient of variation, n = 10) for salsolinol and +/- 2.2% for salsoline at a level of 0.100 nmol/ml. Administration of salsolinol to rats intraperitoneally (0.4 mmol/kg) resulted in levels of 1--2 nmol/g in striatum and limbic forebrain after 2 h, whereas the corresponding liver values were about 550 nmol/g. Control animals showed salsolinol values in liver of about 2 nmol/g and in striatum and limbic forebrain 1 nmol/g tissue.

Salsolinol and salsoline in cerebrospinal lumbar fluid of alcoholic patients.

Analyses of salsolinol and salsoline in human lumbar cerebrospinal fluid and urine have been performed by gas chromatography mass spectrometry. Twelve male alcoholic inpatients have been investigated. On the first sampling occasion patients were still intoxicated after a heavy alcohol debauch and on the second sampling occasion they had been inpatients and off alcohol for one week. Urine and lumbar cerebrospinal fluid was collected in a uniform way. In urine salsolinol and salsoline was found in all cases. In cerebrospinal fluid salsolinol was found in totally six subjects--one at the first sampling occasion only, four at both and one subject at the last sampling occasion only. Salsoline was found in nine patients--six in both sampling occasions and three only during intoxication. There was a wide interindividual variation and no statistical significant difference in the levels between the first and second sampling in CSF or urine.