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Background: The prehospital stroke scale B-FAST (Gaze deviation, Face paresis, Arm weakness, Visual loss and Speech disruptions ) was implemented in the Emergency Medical Services (EMS) in the Western Norway Regional Health Trust (1,1 million catchment population; eight primary stroke centres (PSC) ; two comprehensive stroke centres (CSC)) in 2019 to detect acute ischaemic stroke (AIS) patients with large vessel occlusion (LVO). Prehospital presence of gaze deviation (B-symptom)and at least one FAST symptom, may lead to PSC bypass and proceed directly to a CSC. The aim of the study was to investigate the sensitivity of the B-FAST scale detecting LVO in the prehospital setting. Methods: Retrospective study including patients with at least one B-FAST symptom at EMS arrival. We obtained patient data from all code red stroke dispatches from Emergency Medical Communication Centres (EMCC) and local endovascular treatment (EVT) registries in the period August-December 2020. Variables collected were clinical features, CT examination and reperfusion treatment. Definition of prehospital positive B-FAST was presence of Gaze deviation (B-symptom)and at least one FAST symptom at EMS arrival. Results: We collected data on 643 patients, 59 were diagnosed with a LVO stroke at hospital arrival. In the LVO group, 7 of 59 patients presented with prehospital positive B-FAST, resulting in a sensitivity of 12 %. EVT was performed in 38/59 (64%) cases. Two patients were false negative and positive predictive value was 78%. Specificity was 99% and negative predictive value 83%. Median transfer delay for patients initially admitted to a PSC before transfer to a CSC, was 130 min (IQR 60-167 min). Conclusion: The use of B-FAST by EMS personnel for identification of AIS patients with LVO has a low sensitivity, but presence of gaze deviation predicts LVO stroke with high certainty. more...

Deep brain stimulation of the subthalamic nucleus (STN-DBS) is an effective treatment for Parkinson's disease (PD). The long-term benefit in PD patients with STN-DBS in comparison to medical treatment (MT) alone has not yet been demonstrated conclusively.ObjectivesTo judge the long-term outcome of patients with STN-DBS.MethodsTo assess the evolution of PD symptoms and health-related quality of life (HRQoL) after deep brain stimulation (DBS) surgery, we conducted a cross-sectional analysis of 115 patients with STN-DBS with rater-based scales and self-reported questionnaires. In addition, we screened records of all our STN-DBS patients (2001–2019, n = 162 patients) for the onset of the morbidity milestones (falls, hallucinations, dementia, and nursing home placement) to assess disability-free life expectancy.ResultsIn the first year of STN-DBS, levodopa equivalent dose was reduced and motor function improved. Nonmotor symptoms and cognition remained stable. These effects were similar to previous studies. Morbidity milestones occurred 13 ± 7 years after diagnosis. Motor function, cognition, and HRQoL significantly worsened after the occurrence of any milestone, confirming the clinical relevance of these milestones. After onset of the first milestone, mean survival time was limited to 5 ± 0.8 years, which is comparable with patients with PD but without STN-DBS.ConclusionsOn average, PD patients with STN-DBS live with their disease for a longer time, and morbidity milestones occur later in the disease course than in PD patients with MT. As judged by morbidity milestones, morbidity remains compressed into the final 5 years of life in PD patients with STN-DBS. more...

Triage describes the assignment of resources based on where they can be best used, are most needed, or are most likely to achieve success. Triage is of particular importance in time-critical conditions such as acute ischemic stroke. In this setting, one of the goals of triage is to minimize the delay to endovascular thrombectomy (EVT), without delaying intravenous thrombolysis or other time-critical treatments including patients who cannot benefit from EVT. EVT triage is highly context-specific, and depends on availability of financial resources, staff resources, local infrastructure, and geography. Furthermore, the EVT triage landscape is constantly changing, as EVT indications evolve and new neuroimaging methods, EVT technologies, and adjunctive medical treatments are developed and refined. This review provides an overview of recent developments in EVT triage at both the pre-hospital and in-hospital stages. We discuss pre-hospital large vessel occlusion detection tools, transport paradigms, in-hospital workflows, acute stroke neuroimaging protocols, and angiography suite workflows. The most important factor in EVT triage, however, is teamwork. Irrespective of any new technology, EVT triage will only reach optimal performance if all team members, including paramedics, nurses, technologists, emergency physicians, neurologists, radiologists, neurosurgeons, and anesthesiologists, are involved and engaged. Thus, building sustainable relationships through continuous efforts and hands-on training forms an integral part in ensuring rapid and efficient EVT triage. more...

Careful brain monitoring saves lives and is beneficial to patients' health. Nevertheless, Norway lacks guidelines for brain monitoring in hospitals.

Risk factors for early bleeding complications after lung transplantation are not well described. Our aim was to evaluate coagulation test results and the use of extracorporeal membrane oxygenation as risk factors for bleeding after lung transplantation. We analyzed a single-center cohort of bilateral lung transplants between January 2009 and August 2015. Predictors of severe postoperative bleeding (bleeding requiring reoperation within 48 h of transplantation) were assessed using multivariable logistic regression. The effect of bleeding on survival was assessed using a Cox proportional-hazards model. Twenty-nine (4.5%) of 641 patients experienced severe postoperative bleeding. Postoperative fibrinogen levels (OR = 0.99, 95% CI 0.98-0.995, P = 0.001; per mg/dl increase) and pre- and postoperative use of extracorporeal membrane oxygenation (OR = 14.41% 95% CI 5.4-40.19, P < 0.001 and OR = 4.25, 95% CI 1.0-11.09, P = 0.002, respectively) were associated with an increased risk of severe postoperative bleeding. Severe postoperative bleeding was associated with decreased survival within 60 days after transplantation (adjusted HR = 5.73, 95% CI 2.52-13.02, P < 0.001). Low postoperative fibrinogen levels, and pre- and postoperative use of extracorporeal membrane oxygenation were risk factors for bleeding after lung transplantation. more...

Ziel dieser Studie war die Erfassung der Konsistenz der Diagnostik und der psychopharmakologischen Behandlung an Schizophrenie und wahnhaften Storungen erkrankter Menschen im Alter. Ein weiterer Aspekt war, signifikante klinische Unterschiede oder auch Gemeinsamkeiten zu erfassen zwischen den betreuten Patientengruppen, welche die Kriterien nach ICD 10 fur Schizophrenie (F20), anhaltend wahnhafte Storung (F22) und schizoaffektive Storung (F25) erfullen. Retrospektive Analyse unter Verwendung der schriftlichen und elektronischen Krankenakten einer akut versorgenden Abteilung fur Alterspsychiatrie und Alterspsychotherapie. Im Untersuchungszeitraum wurden konsekutiv 210 Patienten uber 65 Jahre in die Studie aufgenommen (F20 – 64 Patienten, F22 – 78 Patienten, F25 – 64 Patienten, 4 Patienten verstarben). Wenn man davon absieht, dass viele Patienten ohne Diagnose zugewiesen wurden, ist die diagnostische Zuordnung der Einweiser, vor allem durch Arzte fur Allgemeinmediziner, zu Gruppe F20 und F25 sehr konsistent. In der Gruppe der F22-Diagnosen wurde fast die Halfte der Zugewiesenen falschlicherweise als F20-Diagnose eingewiesen. Die Patienten, die sich in der Gruppe F22 befanden, bildeten eine heterogene Gruppe, ein Sammelbecken unterschiedlicher Untergruppen, die als gemeinsame Eigenschaft an einer wahnhaften Storung litten. Sie unterschieden sich zu den anderen zwei Gruppen durch folgende Merkmale: Sie waren alter oder auch hochaltrig, meist erstmals stationar in Behandlung und hatten in der Folge weniger Wiederaufnahmen. Sie litten haufiger sowohl unter psychiatrischen, als auch unter somatischen Komorbiditaten, des Weiteren fanden sich altgewordene Menschen mit einer Grenz- oder Minderbegabung. Die Patienten in der Gruppe F20 und F25 unterschieden sich vorwiegend nur durch die psychiatrische Medikation, in der Gruppe der F25 wurden signifikant mehr Mood-Stabilizer verschrieben. Alle drei Gruppen nahmen sehr haufig Beruhigungsmittel tagsuber ein sowie Schlafmittel, uberwiegend wurden atypische Antipsychotika verordnet. Die Einweisungsdiagnosen von Patienten mit langjahrigen Erkrankungen des schizophrenen Formenkreises stimmten uberwiegend mit den diagnostischen Kriterien uberein, viel schwieriger gestaltete sich fur die Einweiser die Zuordnung der Patienten mit erstmals aufgetretener wahnhafter Symptomatik. Die Patienten, die der diagnostischen Gruppe Schizophrenie zugeordnet wurden, unterschieden sich erheblich von den Patienten der Gruppe mit wahnhaften Storungen. more...

Cognitive impairments in individuals with alcohol dependence may interfere with the progress of treatment and contribute to the progression of the disease. This study aimed to determine whether cognitive remediation (CR) therapy applied during treatment for alcohol dependence improves cognitive functioning in alcohol-dependent inpatients. A secondary aim was to evaluate whether the benefits of CR generalize to noncognitive clinically meaningful outcomes at the end of inpatient treatment.Forty-one alcohol-dependent patients entering inpatient treatment for alcohol dependence were randomly assigned to receive conventional treatment (n = 21) or an additional 12 sessions of computer-assisted CR focusing on cognitive enhancement in attention/executive function and memory domains (n = 20). Assessments of cognitive abilities in these domains as well as of psychological well-being and alcohol craving were conducted at baseline (at the beginning of inpatient treatment) and after CR (at the end of treatment).Results indicated that, relative to patients completing conventional treatment, those who received supplemental CR showed significant improvement in attention/executive function and memory domains, particularly in attention (alertness, divided attention), working memory, and delayed memory (recall). In addition, patients receiving CR during alcohol-dependence treatment showed significantly greater improvements in psychological well-being (Symptom Checklist-90-Revised) and in the compulsion aspect of craving (Obsessive Compulsive Drinking Scale-German version).CR during inpatient treatment for alcohol dependence is effective in improving cognitive impairments in alcohol-dependent patients. The benefits generalize to noncognitive outcomes, demonstrating that CR may be an efficacious adjunctive intervention for the treatment of alcohol dependence. more...

Background: Osteoporosis is regularly mentioned as a consequence of alcoholism. Ethanol′s direct effect on bone-modeling cells as well as alcoholism-related “life-style factors” such as malnutrition, lack of exercise, hormonal changes, and liver cirrhosis are discussed as potential causative factors. Methods: In a cross-sectional study, we have examined 57 noncirrhotic alcoholic patients (37 male, 20 female) aged 27 to 50 years. Patients suffering from comorbid somatic diseases and with co-medication known to have an influence on bone mineral density (e.g., glucocorticoids, heparin, anticonvulsant agents, oral contraceptives) were excluded. We determined bone mineral density (BMD) by dual x-ray absorptiometry (DXA) in the lumbar spine (L1–L4) and the proximal right femur (femoral neck, total hip) as well as parameters of bone metabolism. Results: In males but not females, BMD was significantly reduced in the lumbar region, as well as in the proximal femur (femoral neck, total hip). Nine male patients (24.3% of men) and 1 female patient (5% of women) had low BMD (defined as Z-score ≤ −2.0). As expected, there was a positive correlation between body mass index (BMI) and BMD. Alcohol-related factors (e.g., duration of abuse, consumed amount of alcohol per day) as well as smoking were not associated with a significant effect on BMD. All of the 20 women examined showed elevated estradiol levels, which may have served as a protective factor. In this study, 75.7% of the men and 90% of the women had vitamin D insufficiency or deficiency (plasma levels of 25-hydroxy-vitamin D more...

The objective of this study was to survey the consistency of the clinical diagnostics and the psychopharmacological treatment of schizophrenia and delusional disorders suffered by older persons. A further aspect was to record significant clinical differences and also similarities between the patient groups in care, matching with the criteria of ICD 10 for schizophrenia (F20), persistent delusional disorders (F22) and schizoaffective disorder (F25).Retrospective analysis with reference to the manually and electronically recorded patient medical records of an acute case care ward for geriatric psychiatry and psychotherapy.During the assessment period 210 patients over the age of 65 years were included consecutively in the study (F20 - 64 patients, F22 - 78 patients, F25 - 64 patients, 4 patients died). Ignoring the fact that many of the patients were admitted without a diagnosis, the diagnostic classification of the referring doctor, above all those made by general practitioners, proved to be very consistent for the groups F20 and F25. In the group F22 diagnoses, however, up to almost one half of the referred patients were incorrectly admitted with an F20 diagnosis. The patients included in group F22 formed a heterogeneous group, or a melting pot for various sub-groups, with the common shared characteristic of being comprised of persons suffering from a delusional disorder. These differed from the other two groups in the following attributes: the patients were either older or very old persons, they were mostly receiving inpatient treatment for the first time and subsequently had fewer re-admissions. They also suffered more frequently from both psychiatric and somatic comorbidities; furthermore they included elderly people who had suffered from learning deficiencies or borderline intellectual deficiencies throughout their earlier lives. The patients in groups F20 and F25 differed primarily only in terms of their psychiatric medication, with significantly more mood stabilizer prescribed in the F25 group. Patients in all three groups frequently received tranquilisers during the day and sedatives in the evening, atypical antipsychotics were prescribed in the great majority of cases.The referral diagnoses of patients suffering from many years of schizophrenic type illnesses were largely in compliance with the diagnostic criteria, a much more difficult issue for the referring doctors was the allocation of patients with a first occurrence of delusional symptoms. Those patients who were allocated to the diagnostic group schizophrenia differed significantly from patients from the group with delusional disorders. more...

Background: Prior research indicates that chronic alcoholism is accompanied by olfactory deficits. These have been suggested to reflect dysfunctions in olfactory brain regions. The present study investigated the role of neurocognitive functioning in tests (executive function and memory) sensitive to the functional integrity of brain areas that are crucial to olfactory processing in patients with alcohol dependence. Methods: Performance on olfactory functions (detection threshold, quality discrimination, identification), executive function (Wisconsin Card Sorting Test), and memory (German version of the California Verbal Learning Test) was assessed in 32 alcohol-dependent patients and 30 healthy comparison subjects, comparable in age, gender, and smoking status. Results: Compared with controls, alcohol-dependent patients were impaired in all 3 domains, olfactory functions, executive function, and memory. In patients, olfactory discrimination ability was positively correlated with executive function performance. Regression analyses conducted to clarify the relation between group (patients vs controls), executive function, memory, and olfactory functions indicated that group was the only significant predictor of olfactory detection threshold and identification, and both group and executive function were found to be the significant predictors of olfactory discrimination. Conclusions: Olfactory deficits in alcohol dependence appear to be associated with prefrontal cognitive dysfunction. Results indicate that olfactory quality discrimination deficits are related to executive function impairment. These findings add to the available research on frontal lobe dysfunction in alcoholism, suggesting that alcohol-related olfactory discrimination deficits may be associated with impairment in the functional integrity of the prefrontal lobe. more...

In diesem Artikel wird versucht, ein flexibles und gemeindenahes Versorgungssystem fur Alkohol- und Medikamentenabhangige auf der Basis neuerer Erkenntnisse epidemiologischer und Therapieforschung zu entwerfen. Besonderes Augenmerk wird dabei auf bisher wenig beachtete Personengruppen und Betreuungsangebote gelegt, insbesondere auf gemeindenahe ambulante Therapiemoglichkeiten fur sozial noch gut integrierte Personen und Angebote fur comorbide bzw. chronisch mehrfachgeschadigte Abhangigkeitskranke. more...

In this study we evaluated whether our efforts to promote evidence-based guidelines for the psychopharmacological treatment of patients with schizophrenia have led to measurable changes of treatment practice in our hospital by investigating three primary hypotheses: 1) Polypharmacy has become less common in recent years, 2) Conventional neuroleptics have been replaced by second generation antipsychotics; and 3) Dosing regimes have changed towards lower doses. We have therefore collected data from the clinical records of all in-patients with ICD-9/ICD-10 diagnoses of schizophrenia hospitalized at the Department of Psychiatry of the Medical University Innsbruck in the years 1989, 1995, 1998 and 2001. Data from 1989 to 1998 showed a significant decrease in the use of two or more antipsychotics given simultaneously. Contrary to our hypothesis, there was a significant increase in polypharmacy between 1998 and 2001. The predominant use of second generation antipsychotics became standard in schizophrenia treatment. In this context the decrease of concomitant anticholinergic medication is notable. Doses of conventional antipsychotics like haloperidol as well as doses of risperidone decreased whereas doses of other second generation antipsychotics increased. All in all, the pharmacological management of schizophrenia patients is increasingly in tune with current treatment guidelines. more...

Aims: Prior studies indicate that alcohol-dependent patients have impaired olfactory sensitivity, odor quality discrimination and identification ability. However, olfactory functioning with regard to the immediate, perception driven odor associations is unknown. Therefore, this study assessed olfactory judgements in nonamnesic and nondemented patients with alcohol dependence. Methods: Thirty alcohol-dependent patients and 30 healthy control subjects, well matched for gender, age and smoking status, and screened for olfactory sensitivity, were asked to rate intensity, familiarity, edibility and pleasantness of 16 odors using visual rating scales. Results: Compared with controls, patients showed lower scores in odor familiarity and impaired edibility judgements. These impairments were observed bilaterally, were present independently of age, gender, general mental abilities and length of abstinence, and not attributable to smoking or impaired olfactory sensitivity. No differences between groups were found in odor intensity and pleasantness judgements. Conclusion: These results extend prior findings of alcohol-related olfactory deficits, indicating impairments in olfactory processes of odor familiarity and edibility in alcohol-dependent patients. Although the basis of these deficits is still unknown, our finding of a distinct pattern of olfactory functional, with spacing of perception of pleasantness and familiarity, suggests that there is no generalised olfactory impairment but that, neural olfactory networks may be affected differently. ( Received 28 May 2004; first review notified 27 July 2004; in revised form 18 August 2004; accepted 6 September 2004 ) more...

Background: Preincisional and postoperative Transcutaneous Electrical Nerve Stimulation (TENS) has shown an opioid sparing effect in the treatment of postoperative pain after major spine surgery. The aim of this study was to test the effect of TENS applied intraoperatively on intraoperative demand for fentanyl. Methods: Forty-eight patients scheduled for dorsal lumbar fusion were enrolled and divided into two groups by random numbers. Group A received TENS preoperatively, intra-operatively and postoperatively. Group B received this treatment pre- and postoperatively only. Fentanyl was given during surgery if systolic blood pressure and or heart rate increased 15% over baseline level. Bispectral index (BIS) was maintained between 40 and 50. The total amount of fentanyl administered intra-operatively was recorded. Physician-determined analgesics were given postoperatively to achieve a visual analogue pain score below 3. The total amount of analgesics given, postoperative nausea and vomiting, and stomachache up to the seventh day after surgery were recorded. Results: The two groups were comparable on demographic variables. The intra-operative demand for fentanyl differed significantly between A versus B. (P>0.0000001). No significant differences were detected in total amount of administered analgesics, postoperative nausea and vomiting, nor stomachache up to the seventh postoperative day. Conclusion: Intra-operative TENS reduces intra-operative demand for fentanyl during major spinal surgery. This may be considered especially important in patients who suffer from obstructive sleep apnea syndrome. more...

In summary, both mu-receptor and combined mu/kappa-receptor opioids impair thermoregulatory control. Alfentanil, a pure mu-receptor agonist slightly increased the thresholds for sweating and markedly decreased the thresholds for vasoconstriction and shivering. However, the vasoconstriction-to-shivering range remained normal during alfentanil administration as it does during general anesthesia. Meperidine, a combined mu- and kappa-receptor agonist, also slightly increased the threshold for sweating and reduced the thresholds for vasoconstriction. However, meperidine reduced the shivering threshold twice as much as the vasoconstriction threshold, thus significantly increasing the vasoconstriction-to-shivering range. Furthermore, shivering during meperidine administration, once triggered, was of low intensity suggesting that the drug also decreased the gain of shivering. The special antishivering action of meperidine appears to result, at least in part, from its kappa-receptor activity. more...

Storungen durch psychotrope Substanzen sind heute eine der am houfi gsten in der Psychiatrie vorkommenden Krankheitsgruppen. Psychotrope Substanzen sind Stoff e unterschiedlicher chemischer Herkunft, die auf verschiedenen somatischen und psychischen Ebenen Wirkungen entfalten. Ihre Einnahme hat vegetative, aff ektive, kognitive, wahrnehmungsverondernde und damit auch verhaltensspezifi sche Reaktionen zur Folge. more...

The clinical diagnostic criteria for dementia with Lewy bodies (DLB) have a low sensitivity, and there are no generally accepted biomarkers to distinguish DLB from other dementias. Our aim was to identify biomarkers that may differentiate DLB from Alzheimer's disease (AD).We performed a systematic literature search for studies of EEG, imaging techniques and genetic and CSF markers that provide sensitivity and specificity in the identification of DLB.The best evidence was for scintigraphy of the striatal dopamine transporter system using FP-CIT SPECT. Several small scintigraphy studies of cardiovascular autonomic function using metaiodobenzylguanidine SPECT have reported promising results. Studies exploring innovative techniques based on CSF have reported interesting findings for the combination of amyloid beta (abeta) isoforms as well as alpha-synuclein, and there are interesting results emerging from preliminary studies applying proteomic techniques. Data from studies using structural MRI, perfusion SPECT, genetics and EEG studies show differences between DLB and AD but only at a group level.Several potential biomarkers for the differential diagnosis of probable DLB and AD have shown good diagnostic accuracy in the research setting. Data from large multicentre studies and from studies with autopsy confirmation exist for scintigraphy of the dopamine transporter system. Future studies should explore its value in possible DLB and for clinical management and health economics. more...

We previously described the expression of melanoma-associated endogenous retrovirus (MERV) proteins and viral particles in human melanomas and metastases. The objective of the present study was to determine whether a humoral immune response to MERV proteins occurs in melanoma. Candidate B-cell epitopes on MERV proteins were predicted using bioinformatic screening. The reactivity of MERV peptides corresponding to the predicted epitopes with antibodies prevalent in sera of melanoma patients was analyzed. An immunodominant peptide located in the env protein of MERV was identified. Subsequent analyzes using 81 samples from stage I to stage IV melanoma patients and 95 sera from healthy subjects revealed statistically significant differences in seroprevalence of antibodies in melanoma sera samples when compared with reference samples from healthy subjects. The prevalence of anti-MERV antibodies in melanoma patient sera was confirmed by immunofluorescence on env-transfected cells. These data indicate the potential of this candidate peptide as target for diagnosis and immunotherapy. (Cancer Res 2006; 66(3): 1658-63) more...

The aim of this paper is to outline a future community-based treatment system for persons with alcohol- and substance-related disorders. Current knowledge about epidemiology and treatment outcome will be presented, followed by a description of a network of treatment and support facilities, focusing at treatment possibilities currently not sufficiently supported by the public, especially community-based outpatient treatment for socially well integrated persons and offerings for comorbid or multiple disabled substance-dependent patients. more...

Background: Various olfactory deficits have been reported in the alcohol-induced amnestic syndrome (Korsakoff's syndrome). Less is known about olfactory functioning in nonamnesic and nondemented alcoholic patients. Methods: Olfactory performance of 30 alcohol-dependent patients was assessed unirhinally using the Sniffin’ Sticks (threshold, discrimination, identification, composite TDI score) and compared with that of 30 healthy controls, matched for sex, age, and smoking status. Results: Patients showed significantly reduced olfactory sensitivity (higher threshold), discrimination, and identification compared with controls. No group differences were observed in laterality. Identification and discrimination group differences remained significant after controlling for differences in sensitivity. Olfactory deficits in patients were present independent of age, gender, and duration of abstinence ( more...

In a multibunch collider scheme deterioration of the beam due to long range wakefields is a severe problem to be overcome. While, in principle, it is possible to couple selectively to dangerous Higher Order Modes (HOMs) a different way is to prevent coherent excitation of these wakes by means of modifying a constant gradient accelerator tube such that a structure detuned with respect to HOM modes is obtained. Since the phenomenon of longer interacting dipole modes which are trapped completely in an inner part of the accelerating structure has, to our knowledge, never been studied experimentally-even theoretically it was not notorious-it was decided to design and build a test structure with the characteristics mentioned above. First results of measurements and numerical predictions are presented. more...

Two major routes of preprotein targeting into mitochondria are known. Preproteins carrying amino-terminal signals mainly use Tom20, the general import pore (GIP) complex and the Tim23–Tim17 complex. Preproteins with internal signals such as inner membrane carriers use Tom70, the GIP complex, and the special Tim pathway, involving small Tims of the intermembrane space and Tim22–Tim54 of the inner membrane. Little is known about the biogenesis and assembly of the Tim proteins of this carrier pathway. We report that import of the preprotein of Tim22 requires Tom20, although it uses the carrier Tim route. In contrast, the preprotein of Tim54 mainly uses Tom70, yet it follows the Tim23–Tim17 pathway. The positively charged amino-terminal region of Tim54 is required for membrane translocation but not for targeting to Tom70. In addition, we identify two novel homologues of the small Tim proteins and show that targeting of the small Tims follows a third new route where surface receptors are dispensable, yet Tom5 of the GIP complex is crucial. We conclude that the biogenesis of Tim proteins of the carrier pathway cannot be described by either one of the two major import routes, but involves new types of import pathways composed of various features of the hitherto known routes, including crossing over at the level of the GIP. more...

The aim of this study was to evaluate the frequency and course of sexual disturbances associated with clozapine and haloperidol and their potential influence on compliance with medication regimens in patients with schizophrenia.The authors prospectively investigated 153 patients with schizophrenia who received clozapine (N = 100) or haloperidol (N = 53) in a drug monitoring program.The frequency of sexual disturbances was lower in female patients than in male patients. There was no statistically significant difference between the patients taking haloperidol and those taking clozapine in the frequency of these disturbances. Clozapine plasma levels had a significant effect on diminished sexual desire and functional disturbances in male patients. Functional disturbances and diminished sexual desire did not have any influence on compliance in patients taking either haloperidol or clozapine.There was no statistically significant difference between haloperidol and clozapine in regard to their propensity to induce sexual side effects. more...

Two hundred thirty-eight patients treated with either haloperidol or clozapine were investigated to shed more light on the incidence and severity of antipsychotic-induced liver enzyme increase. Serum glutamic-pyruvic transaminase (SGPT) increase was most frequently seen in both treatment groups. When analyzing the incidence rates for patients with increased liver enzyme values (serum glutamic-oxaloacetic transaminase, SGPT, gamma-glutamyl transpeptidase) that were higher than twice the upper limit of the normal range, clozapine-treated patients showed an SGPT increase (37.3%) significantly more frequently than patients treated with haloperidol (16.6%). Both patients with higher clozapine plasma levels and male patients were at a higher risk for an SGPT increase. At least 60% of the increase of the different enzymes remitted within the first 13 weeks of treatment. In general, the authors conclude that clozapine-induced liver enzyme elevation seems to be a common and mostly transient phenomenon. (J Clin Psychopharmacol 1997;17:314-317). more...

The core temperature triggering thermoregulatory action defines the threshold for that response. Elevated core temperatures trigger sweating and active pre-capillary vasodilation whereas progressively lower temperatures trigger arterio-venous shunt vasoconstriction and shivering. Temperatures between the sweating and vasoconstriction thresholds, which do not trigger thermoregulatory responses, identify the interthreshold range (1). more...

Meperidine, which binds both mu and kappa opioid receptors, is reportedly more effective in treating shivering than are equianalgesic doses of morphine (a nearly pure mu-receptor agonist). Furthermore, butorphanol, a kappa-receptor agonist/antagonist, treats shivering better than does fentanyl, which mostly binds mu receptors. These data indicate that much of meperidine's special antishivering activity may be mediated by its kappa activity. Accordingly, the authors tested the hypothesis that the antishivering activity of meperidine will be minimally impaired by low-dose naloxone (blocking most mu-receptors), but largely prevented by high-dose naloxone (blocking all mu and most kappa receptors).Twelve volunteers each participated on 2 days. On both days, shivering was induced by central venous infusion of cold fluid. Twenty minutes later, six volunteers were given a placebo infusion of saline on one day, or an infusion of 0.5 microgram.kg-1.min-1 naloxone hydrochloride ("low-dose," designed to block mu receptors) on the other. The second group of six volunteers was given a saline bolus and infusion on one day, or a bolus of 11.5 micrograms/kg naloxone hydrochloride followed by an infusion of naloxone at 5 micrograms.kg-1.min-1 ("high-dose," designed to block both mu and kappa receptors) on the other day. The infusions were continued for the duration of the study. The order of the treatment days (saline vs. naloxone) was randomly assigned, and the study was double blinded. Fifteen minutes after the test infusion was started, all 12 volunteers were given an intravenous bolus of 1 mg/kg meperidine hydrochloride. Pupillary diameter and light reflex amplitude were used to quantify opioid-receptor agonist activity; shivering intensity was evaluated using oxygen consumption.Administration of naloxone alone did not alter oxygen consumption, pupil size, or the pupillary light reflex. No pupillary constriction was detected in either group when naloxone and meperidine were combined; in contrast, meperidine alone decreased pupil size and amplitude of the light reflex 30%. The meperidine bolus decreased oxygen consumption nearly to control values when the volunteers were given saline placebo. Combined administration of meperidine and low-dose naloxone also significantly reduced oxygen consumption, but the reduction and the duration of the reduction was less than during saline. When the volunteers were given high-dose naloxone, meperidine only slightly reduced oxygen consumption, and the values rapidly returned to premeperidine levels.These data indicate that the antishivering property of meperidine is not fully mediated by mu-receptors. Although meperidine has well-known nonopioid actions, stimulation of kappa receptors seems a likely alternative explanation for much of the drug's antishivering action. more...

Reportedly, during spinal anesthesia, the shivering threshold is reduced approximately 1 degree C but the vasoconstriction threshold remains normal. Such divergence between the shivering and vasoconstriction thresholds is an unusual pattern of thermoregulatory impairment and suggests that the mechanisms of impairment during regional anesthesia may be especially complex. Accordingly, we sought to define the pattern of thermoregulatory impairment during spinal anesthesia by measuring response thresholds. Seven healthy women volunteered to participate on two study days. On one day, we evaluated thermoregulatory responses to hypothermia and hyperthermia during spinal anesthesia; on the other day, responses were evaluated without anesthesia. Upper body skin temperature was kept constant throughout the study. The volunteers were warmed via the lower body and cooled by central venous infusion of cold fluid. The core temperatures triggering a sweating rate of 40 g.m-2 x h-1, a finger flow of 0.1 mL/min, and a marked and sustained increase in oxygen consumption were considered the thermoregulatory thresholds for sweating, vasoconstriction, and shivering, respectively. Spinal anesthesia significantly decreased the thresholds for vasoconstriction and shivering, and the decrease in each was approximately 0.5 degree C. The range of temperatures not triggering thermoregulatory responses (those between sweating and vasoconstriction) was 0.9 +/- 0.6 degree C during spinal anesthesia. The synchronous decrease in the shivering and vasoconstriction thresholds during spinal anesthesia is consistent with thermoregulatory impairment resulting from altered afferent thermal input. more...

The hypothesis that forced-air warming preserves core temperature better than circulating-water mattresses was tested in: (a) 16 adults undergoing major maxillofacial surgery, including radical node resection and flap reconstruction; (b) 53 adults undergoing hip arthroplasty, having approximately 25% of their body surface area available for warming; (c) 20 infants undergoing minor maxillofacial surgery; and (d) 10 young children undergoing pelvic or femoral osteotomies. Patients having each type of surgery were randomly assigned to forced-air warming (approximately 40 degrees C) or conductive warming using a full-length circulating-water mattress at 40 degrees C. Forced-air warming was applied to the legs of the adults undergoing maxillofacial surgery and to one arm, the shoulders, and the neck in the adults undergoing hip arthroplasty; a U-shaped, tubular forced-air cover was positioned around the pediatric patients. Core temperatures increased in all patients given forced-air warming and decreased or remained constant in those without active warming. Furthermore, we needed to decrease the temperature of the warmer from high to medium (approximately 37 degrees C) in most patients assigned to forced-air warming to prevent hyperthermia. After 15 h of anesthesia, rectal temperatures in the adults undergoing maxillofacial surgery were 3.4 degrees C higher in the forced-air group (P < 0.01). After 4 h of anesthesia, esophageal temperatures had increased 0.8 +/- 0.5 degrees C in the patients warmed with forced-air and decreased 0.8 +/- 0.3 degrees C in those warmed by circulating-water mattresses (P < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS) more...

Schon kurz nach der Markteinfuhrung von Clozapin machten Norris et al. [6] auf eine vermehrte Gewichtszunahme aufmerksam. Wahrend der letzten Jahre beschrieben immer mehr Autoren diese Nebenwirkung. Bisher existiert jedoch nur eine Studie, welche den Unterschied zu Standardneuroleptika untersucht [4]. Diese Arbeitsgruppe beschreibt eine signifikant grosere Gewichtszunahme bei mit Clozapin behandelten Patienten im Vergleich zu Fluphenazin. more...