[Abortive course of malignant hyperthermia following preclinical induction of general anesthesia using succinylcholine]. / Abortiver Verlauf einer malignen Hyperthermie nach präklinischer Narkoseinduktion mit Succinylcholin.

In a 59-year-old woman with a perforating eyeball injury to the right eye, the emergency physician induced a preclinical general anesthesia with propofol, fentanyl and the depolarizing muscle relaxant succinylcholine. Anesthesia was maintained using propofol and remifentanil infusion throughout the preoperative period and the subsequent surgical procedure. Postoperatively, isolated rhabdomyolysis with an increase in serum creatine kinase to >20,000 U/l was observed. The diagnosis of malignant hyperthermia (MH) susceptibility could be confirmed in the patient 4 months after the acute event by the in vitro contracture test and detection of the MH causative mutation p.Val4849Ile in exon 101 of the ryanodine receptor gene. Due to the variable expression, for a long time MH often remained unrecognized. Warning symptoms, such as unspecific tachycardia or masseter spasm following succinylcholine injection, should alert emergency physicians to include MH susceptibility in the differential diagnostics. With an estimated genetic MH prevalence of 1:2000-3000, individuals with known or so far unrecognized MH disposition are likely to be among patients treated in the preclinical setting. If a person develops MH symptoms after exposure to triggering agents, immediate hospital admission is essential in order to initiate guideline-conform treatment without further delay because preclinically the life-saving causal measures are not possible due to the lack of supply of dantrolene.

[Prevalence and risk factors of atrial fibrillation in Germany : data from the Gutenberg Health Study]. / Prävalenz und Risikofaktoren von Vorhofflimmern in Deutschland : Daten aus der Gutenberg Health Study.

Atrial fibrillation (AF) is a disease with increasing clinical and public health importance. We describe the prevalence of AF, the current distribution of AF risk factors and their importance in a general population. The distribution of AF risk factors and the medicinal treatment were determined among 10,000 individuals in the population-based Gutenberg Health Study (median age 56 years and 49% women). Individuals with AF (n=309, 3.1%) had a higher median age (67 years) and significantly more risk factors. A large percentage of individuals with AF were taking antithrombotic medication (84% with a CHAD2DS2-VASc score of ≥3). Multiple logistic regression analysis showed that male gender (odds ratio, OR 2.07, 95% CI: 1.59-2.71), age (OR 1.09, 95% CI: 1.07-1.11), body mass index (OR 1.04, 95% CI: 1.02-1.07), prevalent cardiovascular disease (OR 3.06, 95% CI: 2.26-4.11) and heart failure (OR 3.11, 95% CI: 1.92-4.97) were the strongest predictors of AF. The full model explained 18% (Nagelkerke's determination coefficient R(2)) of the variation in AF prevalence. The addition of echocardiographic variables in a subgroup analysis with 5.000 participants increased the explained variation to 23%. AF is a common disease in the general population. Important risk factors for AF, apart from age and male gender, were cardiovascular disease, in particular heart failure, hypertension and increased body mass index. Awareness for AF in the population and medical community needs to be improved.

Sevoflurane is less sensitive than halothane for in vitro detection of malignant hyperthermia susceptibility.

BACKGROUND: Sevoflurane is a known triggering agent of malignant hyperthermia (MH). The present study analyzed different effects of sevoflurane on skeletal muscle of MH susceptible and nonsusceptible individuals in vitro and compared the results to the standardized test protocol with halothane and caffeine. A potential influence of a present ryanodine receptor type 1 (RyR1) mutation was investigated. METHODS: Muscle bundles of 24 MH-susceptible patients with or without an RyR1 mutation, 35 MH-nonsusceptible and 10 MH-equivocal patients were exposed either to sevoflurane 8 vol% bolus or increasing doses of 2, 4, 6, and 8 vol%. In MH-positive patients, a screening for mutations in the RyR1 gene was performed. RESULTS: The in vitro parameters initial length, weight, predrug resting tension, and predrug twitch height did not differ between the groups. Sevoflurane caused significant contractures in MH-susceptible but not in MH-nonsusceptible muscle after increasing doses [1.4 (0.3-6.0) vs. 0 (0-0) mN] and after bolus application [6.9 (2.4-21.4) vs. 0 (0-0) mN]. However, only 50% of the susceptible patients developed contractures ≥ 2 mN after increasing concentrations while 83% did so after rapid bolus administration. Presence of an RyR1 mutation was detected in 36% of the examined MH-positive patients but had no influence on developing contractures. CONCLUSION: Sevoflurane-induced contractures do not reliably detect MH susceptibility on an individual level. Therefore, sevoflurane is no suitable alternative for diagnostic use. Mutation-specific effects regarding contracture sizes after incubation with sevoflurane, halothane, or caffeine were not found.

Temporal-spatial expression and novel biochemical properties of the memory-related protein KIBRA.

The ability of the mammalian brain to store and recall information is based on synaptic plasticity due to constant remodeling of synaptic contacts. Although various classes of proteins such as neurotransmitter receptors, cytoskeletal components and protein kinases were already identified as modulators of memory formation, their specific interactions and crosstalks are still poorly understood. Genetic variants of the scaffolding protein KIBRA (kidney brain) a substrate of the memory-related protein kinase C zeta and component of the neuronal cytoskeleton, were recently shown to be associated with human memory performance. However, the function of KIBRA on the cellular and physiological level is still unclear. To gain more insights into the temporal and spatial expression of KIBRA, we performed in situ hybridization assays and immunohistological staining of human and rodent (rat) brain. Our data demonstrate that KIBRA is mainly expressed in memory-related regions of the brain (hippocampus, cortex) but is also found in the cerebellum and the hypothalamus. In primary hippocampal neurons, KIBRA displays a somatodendritic distribution and an enrichment at the postsynaptic density. Binding studies further show that KIBRA is able to form head-to-tail homodimers and that dimerization is mediated by the internal C2-like domain. Our data indicate that KIBRA is involved in brain development and memory formation as a postsynaptic scaffold protein connecting cytoskeletal and signaling molecules.

Neuromuscular reaction to paired stimuli.

A modification of the twin pulse method is described, by which the nerve tested is stimulated at one proximal site percutaneously and the neuromuscular response to it is derived from a dependent muscle. An electronic subtraction procedure provides separation of the conditioned muscle action potential for measurement by means of a microcomputer. Several parameters were determined in the conditioned action potential and compared to the same criteria in an unconditioned single action potential. Changes of the conditioned action potential were measured at fixed stimulus intervals between 2 and 6 msec. Preliminary normal ranges interindividually and intraindividually were established. Their dependency on skin surface temperature was determined. In polyradiculoneuropathy, the data for motor nerve conduction velocity were characteristically pathologic, and neuromuscular reaction to paired stimuli data deviated minimally from normal. In vincristine neuropathy, motor nerve conduction velocity was normal, but neuromuscular reaction to paired stimuli data fell outside the normal range early in the clinical course. Since polyradiculoneuropathy is a primary demyelinating and remyelinating process and vincristine neuropathy is an example of axonal degeneration, neuromuscular reaction to paired stimuli can facilitate the differential diagnosis in polyneuropathy. Furthermore, this method seems apt to quantify axonal degeneration. In a mixed form of polyneuropathy, peroneal muscular atrophy, motor nerve conduction velocity, as well as neuromuscular reaction to paired stimuli, were abnormal, the latter resulting in abnormally high relative amplitudes. In muscle disorders such as Duchenne muscular dystrophy, neuromuscular reaction to paired stimuli data was abnormal, contrasting experiments using double stimulation of the diseased muscle itself.