The impact of a hybrid online and classroom-based course on palliative care competencies of family medicine residents.

The University of Calgary offers a palliative care course that involves both classroom- and web-based learning for rural-based family medicine residents. This study assessed the impact of the course on palliative care-related competencies for two classes: 2004 and 2005. Instruments were developed to evaluate pre- versus post-course changes in knowledge (15-item quiz), attitudes (12-item survey), self-perceived comfort levels (19-item survey) and skills (3 long Objective Structured Clinical Examination stations (OSCEs), with accompanying standardised score sheets). In all, 16 and 20 residents participated in the 2004 and 2005 classes, respectively. Internal reliability values were acceptable to very good (Knowledge Quiz, Kuder-Richardson 20 = 0.5; Attitude Scale, alpha = 0.68-0.78; OSCE score sheets, alpha = 0.63-0.89; Self-Perceived Comfort Survey, alpha = 0.89-0.92). Inter-rater reliability values of the OSCE score sheets were alpha = 0.87 to 0.92. There was a significant improvement in the pre- versus post-course performances in OSCE 2 for 2004 and 2005 (P = 0.01; P = 0.01; d = 1.42 and 1.94, respectively). Despite statistically insignificant changes in the other OSCEs, acceptable to large effect sizes were noted (d = 0.4-1.34) for OSCE 1 in 2004 and OSCEs 3 in 2004 and 2005. Knowledge improved significantly pre-versus post-course in 2004 and 2005 (t = 4.44 and 8.99; d = 2.29 and 2.24, respectively). Significant improvements and large effect sizes were noted in the comfort scales, but a ceiling effect was noted in the communication subscale. This hybrid course resulted in significant improvements across four domains, knowledge, attitudes, self-perceived comfort scale, and skills, in 2 consecutive classes.

SEARCH: a system for evaluation and archiving of radiation accidents based on case histories.

Overexposure of humans to ionizing radiation has occurred worldwide in the past and will surely occur again in the future. In order to allow an effective radiation accident management, it is consequently necessary to be prepared for such emergency situations and to improve means and ways to help people suffering from radiation-induced health impairments. Such approaches should rely on knowledge and experience gained from previous radiation incidents. A prerequisite for any scientific evaluation and comparison of information related to radiation accidents is to collect data in a standardized way. Therefore, the SEARCH database (System for Evaluation and Archiving of Radiation accidents based on Case Histories) has been developed in our department and implemented as an Oracle 8.0 database containing to date more than 800 case histories. The use of this registry is so far limited to active contributors and requires each contributor to sign a cooperation agreement. More information is available under http://www.faw.uniulm.de/radmed/.

[Cardiac side effects and ECG changes with lamotrigine?--A clinical study]. / Kardiale Nebenwirkungen und EKG-Veränderungen unter Lamotrigin?--Eine klinische Untersuchung.

After a patient treated with lamotrigine (LTG) had suffered from thoracal pain and repolarisation deficiencies in the electrocardiogram (ECG), we prospectively investigated 20 patients with localization-related epilepsies to assess cardiovascular side effects of LTG. During the study, LTG was added to a stable dosage of one to three first line antiepileptic drugs (AED). Physical examinations and ECG recordings were performed regularly. Clinical cardial side effects did not occur. Only in single ECG traces of six patients non specific abnormalities were seen. Only in one patient, the abnormalities (supraventricular extrasystoles and a first grade atrioventricular block) unequivocally appeared initially under LTG. However, in the same patient two later ECG recordings under higher LTG dosages were normal. The statistical analysis of the ventricular activation times did not reveal any significant changes under LTG (p = 0.05) with the exception of an extended PQ time when comparing a patient group before LTG (n = 11) with another patient group under LTG (n = 11). Since this observation was not confirmed by the statistical analysis of a third patient group (n = 10) with ECG data prior to and under LTG, we believe that the statistically significant changes mentioned above were based mainly on structural differences between the patient groups and not on true LTG effects. Our results do not give evidence for an elevated risk of clinically relevant cardial side effects under LTG.

Do local vasomotor effects elicit the motor deficits induced by intrathecally applied substance P antagonists in the rat?

The intrathecal application of the substance P (SP) antagonists [D-Pro2,D-Trp7,9]SP (DPDT) and [D-Arg1, D-Pro2, D-Trp7,9, Leu11]SP (DAPTL) to the lumbar region of intact, freely moving rats produced laming of the hindlimbs at doses of 0.375 nmol and above, and 1.5 nmol and above, respectively. In addition, the administration of DPDT (doses of 25 and 0.18 nmol) and DAPTL (25 and 0.6 nmol) produced a powerful constriction of the dorsal median spinal vein (DMSV) in decerebrated, unanaesthetised rats. Intrathecal SP (25 or 1.0 nmol) had a similar action on the spinal circulation to DPDT and DAPTL, though laming was first observed at doses of 30 nmol and higher. This suggests that intrathecally applied SP antagonists do not elicit laming by causing an obstruction of the venous drainage of the spinal cord. Disturbances of the spinal circulation could, however, influence the results of behavioural or physiological experiments in which SP or its analogues are administered intrathecally.

Pituitary dwarfism in mice persistently infected with lymphocytic choriomeningitis virus.

Most strains of mice injected intracerebrally with lymphocytic choriomeningitis virus grow to adulthood maintaining a persistent virus infection associated with chronic virus-induced immune complex disease. However, mice on a k background are highly susceptible to neonatal infection and develop the clinical syndrome of pituitary dwarfism and hypoglycemia. Examination of pituitary tissue fails to reveal morphologic alteration by light and electron microscopy. Within the pituitary, viral antigens are exclusively distributed within the cells of the adenohypophysis. Using ultrastructural colloidal gold-labeling techniques, we demonstrate the presence of mature virus particles budding from the surface of growth hormone containing cells from the pituitary. This study indicates that persistent lymphocytic choriomeningitis virus infection of the growth hormone cells in susceptible mice is associated with pituitary dwarfism without producing visible structural damage.

Virus-induced alterations in homeostasis: alteration in differentiated functions of infected cells in vivo.

The noncytopathic lymphocytic choriomeningitis virus displays a tropism for the anterior lobe of the murine pituitary gland. Virus replicates in cells that make growth hormone. This results in a diminished synthesis of growth hormone with a concomitant clinical picture of retarded growth and hypoglycemia. However, there is no morphologic evidence of either cell necrosis or inflammation in the anterior lobe of the pituitary. Hence, during infection in vivo, a noncytopathic virus may turn off the "differentiation" or "luxury" function of a cell while not killing that cell (loss of vital function). This is turn can disrupt homeostasis and cause disease. This model illustrates a novel way whereby viruses may cause disease.

Transfer of synaptic vesicle antigens to the presynaptic plasma membrane during exocytosis.

We have utilized immunofluorescence techniques to look for synaptic vesicle antigens on the plasma membrane of resting and active nerve terminals. Rabbit antiserum was raised against purified cholinergic synaptic vesicles from the electric organ of Narcine brasiliensis, a marine electric ray. Antibodies to synaptic vesicles were shown to bind selectively to nerve terminals in cryostat sections of frog nerve-muscle preparations. Binding was demonstrated indirectly by using fluorescein-labeled goat anti-rabbit antibodies. Structures in cross sections that bound antiserum were identified as nerve terminals because of their size, shape, and position and because they coincided with sites that bound rhodamine-conjugated alpha-bungarotoxin and had acetylcholine esterase activity. Presumably, sectioning gave antibodies access to binding sites within the nerve terminal. However, when antibodies to synaptic vesicles were added to the bathing medium of intact neuromuscular preparations prior to sectioning, antibody binding was marginal or undetectable, suggesting that few vesicle antigens were normally accessible on the outer surface of resting nerve terminals. When intact preparations were stimulated to release their vesicular acetylcholine by the addition of 1 mM LaCl3, antibody binding to the intact nerve terminals became striking. These findings suggest that the synaptic vesicle membrane and the synaptic terminal plasma membrane differ in composition. They also provide further support for the exocytotic hypothesis of neurotransmitter release, which predicts that vesicle markers should be exposed on the outside of nerve terminals when vesicles fuse with the plasma membrane during stimulation.

[Studies of lipase-induced fat necrosis in rats (author's transl)]. / Untersuchungen zur lipaseinduzierten Fettgewebsnekrose bei der Ratte.

Disseminated fat necrosis can be produced by intraperitoneal injection of porcine pancreatic lipase. They get detecable by intravital staining with Phosphine 3R about 15 min after injection. The earliest fine structural findings are spotty destruction of the pinocytic invaginations and vesicles, combined with alterations of the cell membrane. Later there is a complete destruction and disintegration of the cytoplasm and its organels as well as the nucleus, whereas the cell membrane partly remains visible. At the same time the central lipid droplet shows cloudy disintegration and clumping as well as cristalline and granular structures. In the beginning the necrosis is limited to single cells. Later the adjacent fat cells also undergo necrosis, even when the applicated lipase has been removed after 30 min. In light microscopic studies fat necrosis are detectable 30 min after the application of lipase. During the first 48 hours they get demarcated by leucocytes. In the following days resorption and organisation take place. Lipolytic drugs facilitate the development of fat necrosis, whereas antilipolytic drugs inhibit it. In starvation the number of fat necrosis rises, after feeding it decreases. In the diurnal rhythm there is a maximum after midnight and a minimum in the early afternoon. The results support the hypothesis that pancreatic lipase only attacks fat cells, which are lipolytically active.