[Telephone enquiries on the topic of malignant hyperthermia: Evaluation of the content and subsequent diagnostic results at the MH Center Leipzig]. / Telefonische Anfragen zum Thema maligne Hyperthermie: Auswertung der Inhalte und der resultierenden Diagnostikergebnisse am MH-Zentrum Leipzig.

BACKGROUND: Malignant hyperthermia (MH) is an autosomal dominant metabolic myopathy. The in vitro contracture test (IVCT) is still considered to be the gold standard for diagnosing a disposition for MH. However, advances in genetic testing for MH disposition have supplemented or even replaced the invasive procedure of the IVCT. Information about MH can be obtained by either contacting the hotline for MH as a nationwide 24 h/7 days a week service or one of the regional MH centers. METHODS: The protocols of telephone conversations concerning MH at the MH Center University Leipzig were retrospectively analyzed. Data were collected from January 2011 to March 2015. Additionally, the results of the IVCT and genetic testing evolving from the counseling interviews were examined. RESULTS: A total of 205 telephone calls were documented during the period in question and an IVCT was performed as a consequence of 112 of the telephone calls. The IVCT resulted in 27 individuals being identified as MH susceptible which was subsequently diagnosed in 15 individuals with known familial MH disposition and 12 individuals were identified as new index patients. In 24 individuals a total of 13 different mutations were detected and of these 4 mutations were causative concerning MH. Of the 205 telephone calls 131 were private and 74 of medical professional origin. Among the private enquiries MH disposition within the family was a frequent reason for contacting the MH Center (61.8%). Conversations relating to MH-like symptoms during general anesthesia were carried out with 35.1% of medical doctors and with 22.9% of private callers. Advice about neuromuscular symptoms of unknown genesis was given to 15.3% of private individuals and to 24.3% of medical doctors. Overall MH topics were discussed with 23% (N = 17) of the medical profession and approximately half of these were anesthesiologists (N = 8). Not a single call was documented for the treatment of a suspected MH crisis. CONCLUSION: Private individuals and families affected by a MH disposition often showed good compliance with respect to counseling and diagnostics for MH and contacted the MH center more often than medical doctors. A more comprehensive cooperation with the medical profession is preferable and necessary to obtain a systematic and broad synopsis of characteristic and uncharacteristic signs and symptoms of MH. The telephone conversations analyzed as well as the diagnostic results (IVCT and genetic testing) underline that MH disposition is still a current and relevant topic.

Pharmacokinetics and clinical toxicity of prilocaine and ropivacaine following combined drug administration in brachial plexus anesthesia.

OBJECTIVE: Local anesthetics (LA) are often administered in combination for regional anesthesia in order to obtain the specific advantages (onset and duration of effect) of each drug. However, few data on the safety of such combinations are available and consequently plasma concentrations possibly associated with toxicity and interactions between the specific anesthetics are not sufficiently established. We measured pharmacokinetics and toxicity parameters of prilocaine and ropivacaine after combined use as single doses in brachial plexus blockade. METHODS: In an open clinical study using a combined dose regime (300 mg prilocaine followed immediately by 75 mg ropivacaine) total plasma concentrations of prilocaine and ropivacaine were measured serially in 60 patients using a gas-chromatographic method. The data were analyzed regarding a relationship with central nervous and cardiovascular toxicity. RESULTS: Following the administration in combination prilocaine and ropivacaine were rapidly absorbed. Mean prilocaine peak plasma concentrations (mean Cmax = 1.51 microg/ml) were measured between 15 and 30 min after injection. Highest ropivacaine plasma concentrations (mean Cmax = 1.12 microg/ml) were seen between 30 min and 1 hour after injection (calculated mean tmax = 44 min). One of 59 patients showed signs of myoclonus which were suspected of being due to intravascular injection. There was no relevant cardiovascular toxicity observed in terms of changes in the QRS complex, PQ interval prolongation, AV dissociation, occurrence of extrasystoles or sinus arrest. The pharmacokinetics of combined administration did not differ from those of prilocaine and ropivacaine given alone. CONCLUSION: The use of a combined prilocaine/ ropivacaine (300 mg/75 mg) dose regimen in patients given single dose for brachial plexus blockade can generally be regarded as safe with regard to peak plasma concentrations and cardiovascular toxicity and this holds true for patients with a higher perioperative risk profile (ASA III grading, American Society of Anesthesiologists). The considerable inter-individual variation in LA peak plasma concentrations observed in our patients and the one case of suspected accidental intravascular injection, highlight the necessity of adequate monitoring of the patients undergoing LA injections.

A space-variant filter model of texture segregation: parameter adjustment guided by psychophysical data.

This article presents a space-variant version of a standard spatial filter model of texture segregation of the "back-pocket" type (i.e., two filter layers with an intermediate pointwise nonlinearity). The model was tested with psychophysical data from experiments with line textures in which target lines differed in orientation from background lines. The textures were presented briefly and then masked. Segregation performance was evaluated along the horizontal meridian up to retinal eccentricities of about 10 deg. Data are reported from two experiments with different line densities (Kehrer 1989) and two experiments with different orientation contrasts between target lines and background lines (Kehrer 1990). Segregation performance proved to depend strongly on these texture variations, and it peaked several degrees from fixation in all cases. The filter model provided satisfactory predictions of experimental data when model parameters were adjusted appropriately. It is concluded (1) that filter models defined in strictly spatial terms (i.e., without temporal properties) offer a sufficient framework to account for the psychophysical data and (2) that the particular course of the performance curve (i.e., the performance peak outside the central region) must be attributed to the characteristics of second-layer filters.

Mutation screening in the ryanodine receptor 1 gene (RYR1) in patients susceptible to malignant hyperthermia who show definite IVCT results: identification of three novel mutations.

BACKGROUND: The ryanodine receptor of the skeletal muscle (RYR1) seems to be of outstanding importance in the pathogenesis of malignant hyperthermia (MH). It has been shown that point mutations in the RYR1 gene are strongly associated with the MH phenotype. A correctly determined phenotype is the basic prerequisite for adequate genetic MH screening. In this study we examined only those MH susceptible patients for the presence of potential RYR1 mutations who showed strong pathological muscle responses in the in vitro contracture test (IVCT). METHODS: A total of 56 MHS index patients who complied with the following IVCT criteria were included in the molecular genetic investigation: Contracture forces > or =4 mN at a caffeine concentration of 2.0 mmol/l and > or =8 mN at a halothane concentration of 0.44 mmol/l. DNA sequences of exons 2, 6, 9, 11, 12, 14, 15, 17, 39, 40, 45, 46, 102 of the RYR1 gene were analysed by the direct sequencing technique. Furthermore, if an MH mutation was identified in an index patient, all relatives were screened for their family specific RYR1 defect. RESULTS: In 39 index patients an RYR1 mutation was detected: Arg163Cys (n = 2), Asp166Asn (n = 1), Gly341Arg (n = 2), Arg401His (n = 2), Arg614Cys (n = 12), Asp2129Glu (n = 1),Vol2168Met (n = 1), Thr2206Met (n = 9), Ala2428Thr (n = 1), Gly2434Arg (n = 2), Arg2435His (n = 1), Arg2452Trp (n = 1), Arg2454His (n = 4). Three new RYR1 mutations were identified. We found a potential MH mutation in a further 130 relatives of the 39 index patients. Thirty-seven individuals were classified as MHS exclusively by molecular genetic techniques and did not have to undergo the IVCT. CONCLUSIONS: The ascertained high rate of successful MH mutation screening (69.64%) is obviously associated with the more clearly defined MHS diagnosis in the IVCT. According to the EMHG guidelines for the molecular genetic detection of MH susceptibility, a positive MH disposition could be determined in numerous persons by a less invasive technique.

Learning to ignore the mask in texture segmentation tasks.

Although traditionally texture segmentation has been regarded as an automatic, preattentive process, participants confronted with texture segmentation in experimental settings (i.e., with brief presentation time and subsequent masking) are initially unable to perform the task. According to perceptual learning concepts, participants must learn to fine-tune their sensory channels before perception improves under restricted viewing conditions. The present article proposes an alternative perspective that emphasizes the role of the mask. Four experiments showed that the amount of observed learning depends on the structural and temporal homogeneity or heterogeneity of the mask. The authors suggest that learning consists of separating the task-relevant signal stemming from the texture from the task-irrelevant signal of the mask and of ignoring the mask.

Automaticity and attention: investigating automatic processing in texture segmentation with event-related brain potentials.

The present article deals with the question of automaticity and/or plasticity of processes in early vision. The detection of irregularities in an otherwise homogeneous surrounding, as studied in texture segmentation tasks, is considered an example of an automatic process in the processing of visual information. Participants in texture segmentation experiments are usually instructed to respond to the texture stimuli, i.e. attention is completely allocated towards them. Automaticity, however, would imply that processing takes also place when no attention is allocated to the texture stimuli and participants, e.g. perform another primary task. We investigated the automaticity of texture segmentation by recording Event-related potentials which allow to investigate processing also when no overt response is given. Three experiments investigated the role of attention in texture segmentation by varying task relevance of the texture stimuli. Participants had to either discriminate homogeneous or inhomogeneous textures or had to perform a different primary task of varying complexity. Two components were found to be sensitive to texture segmentation, a posterior N2 and a positivity within the P3 time interval. Both components were also observed when texture segmentation was task-irrelevant. However, while the posterior N2 was not affected by the complexity of the primary task and thus showed some degree of automaticity, the P3 was found to be dependent on the attentional resources left over by the primary task.

Feature localization and identification.

Theories on visual search differ substantially with respect to the relationship they assume between localization and identification processes. The aim of the present study was to rigorously compare the alternative theoretical notions on how localization and identification processes are related. In two experiments, participants searched for a target with a unique line orientation among distractors containing another orientation. Localization and identification performance were measured in combination, as function of display size and target eccentricity. To compare the alternative theories, formal binomial models were developed and compared with respect to their goodness of fit to the individual data. The formal analyses showed that the model assuming identification processes to be conditioned on localization processes provided the best fit to the individual data. Furthermore, maximum likelihood estimates of the parameter corresponding to identification processes were differently affected by display size than identification performance was. The results were discussed in terms of their implication for current theories on visual search.

High-flux hemodialysis without hemoperfusion is effective in acute valproic acid overdose.

OBJECTIVE: To report a case of valproic acid overdose treated successfully with high-flux hemodialysis without the addition of charcoal hemoperfusion. CASE SUMMARY: A 25-year-old white woman with a history of multiple suicide attempts and schizophrenia presented after ingesting an unknown amount of valproic acid. She became comatose and developed hypotension and lactic acidosis as valproic acid concentrations increased to > 1200 micrograms/mL (therapeutic concentration 50-100). High-flux hemodialysis was performed for four hours; the calculated elimination rate constant (kel) during the procedure was 0.2522 h-1 with a half-life (t1/2) of 2.74 hours compared with posthemodialysis kel of 0.0296 h-1 and t1/2 of 23.41 hours, suggesting that high-flux hemodialysis effectively eliminates valproic acid. The patient's hemodynamic status and mental function improved in conjunction with the acute reduction in valproic acid concentrations. Her subsequent hospital course was complicated only by transient thrombocytopenia. DISCUSSION: Most literature reports of valproic acid overdose have described the use of charcoal hemoperfusion alone or in combination with hemodialysis to accelerate valproic acid clearance at toxic concentrations. However, the pharmacokinetic properties of valproic acid indicate that hemodialysis alone would be effective therapy for an acute valproic acid overdose. CONCLUSIONS: We suggest that toxic concentrations of valproic acid can be effectively reduced with high-flux hemodialysis without the addition of charcoal hemoperfusion and its attendant risks.

Congenital transmission of visceral leishmaniasis (Kala Azar) from an asymptomatic mother to her child.

In this article, we report the case of a 16-month-old German boy who was admitted to the Children's Hospital of Stuttgart with a 4-week history of intermittent fever, decreased appetite, weakness, fatigue, and difficulty sleeping. He was healthy at birth and remained so for the first 15 months of his life. On admission, physical examination showed enlarged cervical, axillary, and inguinal lymph nodes, as well as hepatosplenomegaly. Laboratory data revealed pancytopenia, elevated liver function tests, and hypergammaglobulinemia. Blood, stool, and urine culture results were negative. Viral infections and rheumatologic and autoimmune disorders were ruled out, but a positive titer for Leishmania antibodies was noted. In a liver and bone marrow biopsy, the amastigote form of the parasite could not be seen in cells. The promastigote form of Leishmania was found and the diagnosis of visceral leishmaniasis was made by combining the cultures of both the liver and the bone marrow biopsy material in 5 mL 0.9% saline on brain heart infusion agar, supplemented with defibrinated rabbit blood and incubated at 25 to 26 degrees C for 5 days. The parasite was identified by Southern blot analysis as Leishmania infantum. Specific therapy with the antimonial compound sodium stibogluconate with a dose of 20 mg/kg body weight was begun immediately. Within 4 days, the patient became afebrile. The side effects of treatment, including erosive gastritis, cholelithiasis, worsening hepatosplenomegaly, elevation of liver enzymes, pancreatitis, and electrocardiogram abnormalities, necessitated the discontinuation of treatment after 17 days. On discharge 4 weeks later, the patient was stabilized and afebrile with a normal spleen, normal complete blood count, normal gammaglobulins, and decreasing antibody titers to Leishmania. During the next 24 months, the patient experienced intermittent episodes of abdominal pain, decreased appetite, recurrent arthralgia, and myalgia. But at his last examination in January 1998, he was well; all symptoms mentioned above had disappeared. Because the child had never left Germany, nonvector transmission was suspected and household contacts were examined. His mother was the only one who had a positive antibody titer against Leishmania donovani complex. She had traveled several times to endemic Mediterranean areas (Portugal, Malta, and Corse) before giving birth to the boy. But she had never been symptomatic for visceral leishmaniasis. Her bone marrow, spleen, and liver biopsy results were within normal limits. Culture results and polymerase chain reaction of this material were negative. A Montenegro skin test result was positive, indicating a previous infection with Leishmania. Western blot analysis showed specific recognition by maternal antibodies of antigens of Leishmania cultured from the boy's tissue. Visceral leishmaniasis is endemic to several tropical and subtropical countries, but also to the Mediterranean region. It is transmitted by the sand fly (Phlebotomus, Lutzomyia). Occasional nonvector transmissions also have been reported through blood transfusions, sexual intercourse, organ transplants, excrements of dogs, and sporadically outside endemic areas. Only 8 cases of congenital acquired disease have been described before 1995, when our case occurred. In our patient, additional evaluation showed that the asymptomatic mother must have had a subclinical infection with Leishmania that was reactivated by pregnancy, and then congenitally transmitted to the child. Visceral leishmaniasis has to be considered in children with fever, pancytopenia, and splenomegaly, even if the child has not been to an endemic area and even if there is no evidence of the disease in his environment, because leishmaniasis can be transmitted congenitally from an asymptomatic mother to her child.

[Diagnosis of disposition for malignant hyperthermia--an updated review based on 1,001 studies]. / Diagnostik der Disposition zur Malignen Hyperthermie--eine aktualisierte Ubersicht auf der Basis von 1001 Untersuchungen.

The in vitro contracture test (IVCT) based on European Malignant Hyperpyrexia Group criteria including the linked quality guarantee is carried out in 6 centres in Germany. Due to the genetic heterogeneity of malignant hyperthermia. This test remains the existing standard, despite intensive search for less invasive diagnostic methods. The test is necessary for clarification of narcosis incidents and diagnosis of individual disposition of MH-afflicted families. The analysis of 11 years of experience with 1.001 investigations in the Leipzig centre focuses on characteristic problems. It indicates, that severe courses with resulting fatality (37 cases in the whole observation period in the centre district had a decreasing tendency. Independently thereof the rate of demands for diagnostics remains constant at 125 per year. Apparently MH related incidents are under better control now. Of the requested diagnostics 85% are related to anaesthesia incidents, 15% to other MH related problems [myopathies, unexplained fever attacks]. Of the patients tested 59.7% were MH-negative (MHN), 33.7% MH-positive (MHS) and 6.3% were equivocally positive (MHE). A parallel part of the study regarding IVCT and histology/morphometry in 230 consecutive examinations did not show any correlation. Ultrastructural investigations accordingly are carried out only if there is suspicion of myopathy. Differentiation of the in vitro threshold values shows a relation to the patients' risks. Low threshold values were detected in persons diagnosed as MHS from families with MH related deaths: one man diagnosed MHS died from an anaesthesia-unrelated MH crisis. In a parallel test of MH-positive muscles with new inhalational narcotics (sevoflurane, desflurane), a strong correlation to triggering of contracture by halothane was detected. In contrast, no information about a false negative result exists at this time. MH manifestation was observed postoperatively only in one patient 1337 patients MHS, 63 MHE). However, in 3 cases cardio-circulatory arrests occurred under local anaesthesia without further consequences. The analysis documents the safety of IVCT and the clarity of its results. IVCT is the base for an improved communication with patients and colleagues.

Peripheral and foveal segmentation of angle textures.

Studies of the effects of retinal eccentricity on the visual segmentation of textures are presented. The textures used in these studies were composed of angle elements. These were presented tachistoscopically to college students in three different experiments. Results showed that there were different relationships between segmentation performance and eccentricity, depending on the width of the angles used in the background and target texture. One major difference was that peak performance was found in the fovea in some conditions, and in peripheral areas in other conditions. Performance in the fovea and the periphery seemed to be determined by qualitatively different features. It was assumed that an appropriate explanation is that the system-internal representation of a specific stimulus within the early visual system differs as a function of the retinal location at which it is projected. Thus, the critical features discriminating between target and background texture have to be sought in the system-internal representation of the stimulus instead of in the stimulus itself. The data show that a relatively exact system-internal representation of the stimulus is present in the fovea, where performance is determined by angle width. In the periphery, in contrast, angles seem to be represented as "blobs," and performance is determined by the orientation of the blobs' main axes.

[The prognostic relevance of preoperative pulmonary function tests]. / Die prognostische Relevanz präoperativer Lungenfunktionsdiagnostik.

At Leipzig University, preoperative pulmonary function testing has been performed for about 3 years in order to detect and classify patients at high pulmonary risk. During the postoperative period, the risk of developing pulmonary complications is particularly high due to factors influencing respiratory mechanics such as the supine position, pain, residual effects of narcotic drugs, etc. It has often been emphasised that an underlying ventilatory disturbance such as obstructive lung disease or smoking may enhance the postoperative pulmonary risk, although the extent of the influence of preoperative pulmonary diseases on the postoperative complication rate is still controversial. The prediction of postoperative lung function from preoperative spirometric values is complicated by factors such as patient cooperation, pulmonary complications secondary to aspiration, infection, peritonitis, etc., and by differing and therefore non-comparable postoperative care. For this reason, the criteria for assessing pulmonary risk vary widely. METHODS. We examined 339 patients (mean age 59.3 years) preoperatively by quiet and forced spirometry; in most cases we also measured airway resistance and functional residual capacity. We estimated the postoperative lung function using the quadrant scheme of Miller and compared this risk class with our spirometric diagnosis and the postoperative clinical course. RESULTS. According to our results, Miller's classification seems inadequately differentiated for patients with mild to moderate ventilatory disturbances. A relatively high percentage of these patients were considered to have normal postoperative lung function. Some patients with severely diminished pulmonary function were classified as having sufficient postoperative lung function. The number and severity of pulmonary complications also corresponded better with the spirometric diagnosis, which was made using all spirometric parameters and not only vital capacity (VC) and 1-s forced expiratory volume (FEV1). We found that the percentage of primary respiratory complications increased with deterioration of the preoperative spirometric values. To provide a prognostic model combining both the advantages of using only a few parameters (FEV1, VC) and appropriate risk assessment, we propose a modification of the Miller scheme consisting of five risk classes. The analysis of the respiratory therapy regimen was unsatisfactory because of discrepancies between the predicted pulmonary risk, the use of respiratory therapy, and the occurrence of pulmonary complications. CONCLUSIONS. For minimising perioperative pulmonary complications, respiratory care (prophylaxis and therapy) adequate for the functional risk of the patient is necessary. We assume that intensive pre- and postoperative respiratory care and therapy in patients with underlying reductions in ventilatory function can help to avoid or reduce respiratory complications. The modification of Miller's scheme proposed after evaluating the postoperative course of our patients provides a differentiated prognostic model that allows the establishment of an appropriate and economical therapeutic regimen of perioperative pulmonary care.

Adverse clinical events in dependent long-term nursing home residents.

OBJECTIVE: To assess the occurrence, type, and burden of adverse clinical events (ACE) among residents of chronic facilities. An ACE is any acute or subacute change in health status suggesting acute or subacute illness. DESIGN: Survey with face-to-face functional assessment and 3-month retrospective chart review. STUDY POPULATION: One hundred six continuing-care residents with a minimum length of stay of 4 months at an Italian chronic care facility. MEASUREMENTS: Functional assessment and chart review-based classification of ACE burden on care management according to a clinical-functional Severity Rating Scale. MAIN RESULTS: Functional dependence, dementia and concurrent clinical problems were common. Two hundred seventy-three ACEs were detected. Eighty-nine percent of residents experienced at least one ACE. Only 21% of ACEs could be managed by simple medical intervention and monitoring within 1 day; in 23% there was need for more complex care management; 7% of the latter ACEs resulted in residual (new) functional impairment. Cardiovascular and gastrointestinal systems were most commonly involved in ACEs. Neurological ACEs were the most frequent category leading to new functional impairment (22%). ACE occurrence/burden was higher in male residents (P < 0.01) and strongly associated with the number of concurrent medical problems (P < 0.001). Neither cognitive nor functional dependence levels were related to ACE occurrence. CONCLUSIONS: This description of the burden on care management resulting from acute and subacute changes in clinical and functional status of chronic patients emphasizes the continuing and unpredictable nature of medical attention required in a nursing home or chronic care facility. ACEs occur far more frequently among the elderly than is generally recognized. Thus a high level of medical and nursing skill is necessary in chronic care facilities.

Risk reduction in sexual behavior: a condom giveaway program in a drug abuse treatment clinic.

Just before and 4 months after initiation of a condom giveaway program, a questionnaire regarding sexual behavior and condom acquisition was administered to 103 men attending an outpatient drug abuse treatment clinic. Jars filled with a variety of condoms were placed in every clinic room. Condom taking varied as a function of room. Sixty percent of the subjects reported taking condoms. At follow-up, clients reported increases in condom possession and in use of condoms for vaginal intercourse.

[A new emphasis on the diagnosis of malignant hyperthermia using the in vitro contracture test?]. / Neue Akzente bei der Maligne-Hyperthermie-Diagnostik mittels in-vitro-Kontrakturtest?

In accordance with the protocol of the European Malignant Hyperpyrexia Group, an account is given of the experience regarding establishment of the "in vitro contracture test" for diagnosis and exclusion of malignant hyperpyrexia disposition at the University Clinic of Leipzig. Since its commencement in 1986 these diagnostic possibilities are being increasingly utilized, and--basing on 76 MH manifestations and suspected cases--324 persons have been examined until now. Besides the representation of the methodical features (e.g. performance of biopsy in tranquanalgesia in children), emphasis was on the safety of executing this test (attaining higher specificity, total absence of MH manifestations). The epidemiological study of the results shows the varying knowledge of physicians and the interference by insufficient investigation alternatives in individual areas. On the basis of the results, the use of the in vitro contracture test is recommended in all MH suspected cases by the authorized and qualified regional centres.

Cognitive deficits associated with human immunodeficiency virus encephalopathy.

The encephalopathy associated with direct nervous system infection by the human immunodeficiency virus (HIV) has been recognized as one of the major debilitating aspects of the acquired immunodeficiency syndrome (AIDS) and of pre-AIDS conditions. A comprehensive neuropsychological examination of symptomatic HIV-infected subjects without opportunistic cerebral disease demonstrated a distinctive pattern of cognitive deficits marked by prominent attentional impairment. Evidence of organizational and reasoning impairments also was observed, but language, visual-spatial, and memory consolidation abilities were relatively preserved. The findings suggest a profile of impairment similar to other cognitive syndromes involving dysfunction of predominantly anterior brain structures and projections and suggest a rationale for psychostimulant drug treatment.