[Treatment of acute myocardial infarction: a matter of time].
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Angioplasty, Balloon, Coronary↗
Biomedical subjects
C Kaiser
Publications and source records attributed to C Kaiser.
Mortality from epilepsy in an onchocerciasis-endemic area in West Uganda.
Mortality from epilepsy was investigated in a rural area of West Uganda where epilepsy is found to be closely linked to onchocerciasis. Thirty-three female and 28 male patients (age range 4-58 years, median 15 years) were identified in a population-wide prevalence survey and were followed from June 1994 to March 2001 (observation period 3,929 person-months). Patients had continuing access to antiepileptic drug (AED) treatment with phenobarbital. Eighteen patients died during the period of observation, corresponding to a standardised mortality ratio (SMR) of 7.2 (95% CI 4.4-11.6; P<0.0001). Adherence to treatment was considered good in 36 of 56 patients receiving regular AEDs, with a SMR of 7.4 in this group compared with a SMR of 8.0 for those 20 patients considered poorly adherent. These findings show high mortality in patients with onchocerciasis-associated epilepsy despite regular AED treatment. Epilepsy appears to have a dramatic impact on this community with high Onchocerca volvulus infestation. If the suspected causal relationship between epilepsy and infection with O. volvulus could be confirmed, this would further underline the importance of sustained control efforts against onchocerciasis.
Adolescent↗
[Tasks and development of health services research. A comparison between the USA, UK, Australia and Germany].
Given the fact that health services research has become increasingly popular in Germany during the last 5 years this article focuses on the status quo of this research field in a multinational comparison. An overview of the health services research situation in the USA, UK, Australia and Germany is given by considering development status, definition and future challenges. This overview shows that health services research is by now regarded as an essential field in these countries. Despite clear distinctions in research tradition and research infrastructure there are cross-national themes and challenges regarding research questions and organisation of research. The common challenges of the future are probably the enhancement of research capacities, the further development of adequate research methods and the question of translating research results into practice. All countries concur that the cooperation between stakeholders of the health services research field needs to be strengthened.
Australia↗
Selection bias of elderly patients with chronic angina referred for catheterization.
BACKGROUND: Registry patients are generally older and more sick than patients enrolled in trials questioning the generalizability of trial results. We assessed whether such a selection bias also exists in elderly patients with chronic angina referred for catheterization. METHODS AND RESULTS: All 119 patients age>or=75 years with Trial of Invasive versus Medical Therapy in the Elderly (TIME) inclusion but no major exclusion criteria referred for catheterization during the TIME trial inclusion period in four TIME centers were registered and followed-up for one year. Registry patients differed from the 188 trial patients in the same hospitals in that they were younger, somewhat more frequently male, with less antianginal drugs and studied more often after acute chest pain at rest but with more comorbidities than study patients. Left ventricular ejection fraction and vessel disease were similar. One year mortality was 11.4% in registry and 9.6% in invasive TIME patients but differences disappeared after adjustment for baseline differences. Symptomatic status after one year was similar too. CONCLUSIONS: In elderly patients with chronic angina, a bias in the selection for invasive management exists which seems different from that reported in younger patient settings. After adjustment for these selection factors, however, one-year outcome was remarkably similar in registry and trial patients.
Aged↗
[The technique of outflow tract reconstruction in patients with tetralogy of Fallot influence the morbidity 3 decades after repair].
The purpose of this study was to examine long-term results of different surgical techniques in patients with tetralogy of Fallot considering their morbidity. We analyzed the data of 74 patients 24.5 +/- 3 years after surgical repair in childhood to evaluate their clinical status, maximal exercise capacity, medication and frequency of reoperations. We compared two groups of patients according to the surgical techniques employed: 1) TAP group (Trans anular Patch, n = 41) in which ventricular septal defects were closed with a Dacron patch, the right ventricular outflow was reconstructed by resection of the partial extension of the infundibular septum and transanular patch repair was performed because of hypoplastic pulmonary valve. 2) nonTAP group (33) in which no transanular patch repair was necessary. Most of the patients described their health as "good". 94% of the nonTAP group and 71% of TAP group were in NYHA class I. The rest were in NYHA class II. Despite the good clinical classification we found a reduced cardiopulmonary exercise capacity in all patients. More than 50% in the TAP group took medicine because of congestive heart failure and/or arrhythmia, which was present 3-times more often compared with the nonTAP group. Furthermore, 50% of TAP group patients had at least one reoperation during the follow- up: by comparison 5-times more often than the nonTAP group. These data show that the long-term outcome and morbidity of the patients after repair is closely related to the type of the surgical technique employed.
Adolescent↗
Expression of a foot-and-mouth disease virus immunodominant epitope by a filamentous bacteriophage vector.
We described the construction of a recombinant filamentous phage displaying on its surface the immunodominant site of VP1 protein of foot-and-mouth disease virus (FMDV). The coding sequence was inserted at the amino-terminus of the major coat protein pVIII via a spacer. The hybrid phage proved to be antigenic as it was recognized by polyclonal and monoclonal anti FMDV sera. In two experiments involving immunisation of guinea-pigs with the recombinant phage, a low antibody response was generated. This suggests a possible role for phage displayed peptides in inducing anti FMDV immunity and the possibility of further development is discussed.
Amino Acid Sequence↗
Abortifacient and endocrine effects of metergoline in beagle bitches during the second half of gestation.
The purpose of this study was to investigate the abortifacient effects of high doses of metergoline when administered to pregnant beagle bitches during the second half of gestation and to define the endocrine effects of this treatment as represented by plasma progesterone and estradiol concentrations. Previously, metergoline had been shown to be incompletely luteolytic and induced abortion in only one of eight pregnant bitches when 0.4-0.5 mg/kg were administered twice daily for 5 days from Days 18 to 20 of diestrus. Nine pregnancies in six beagle bitches were used for the present study. Three bitches were treated in each of two consecutive pregnant cycles. Metergoline was administered at a dose of 0.6 mg/kg per os twice daily, starting on Day 28 after the cytological onset of diestrus. Abortion was induced in eight of the nine treated pregnancies and started after 3-23 days of treatment (mean 12.5 days, S.D. 6.4 days). The abortions were completed within 0.5-8 days (mean 2.2 days, S.D. 2.7 days). There were no side effects associated with metergoline treatment and none of the abortions was associated with complications that required intervention. In the single bitch that did not abort, an ovarian granulosa cell tumor was discovered when the single fetus had to be removed surgically at term. Plasma progesterone concentrations declined after the start of metergoline administration in all pregnancies but levels below 4.8 nmol/l were required for successful abortions. Plasma estradiol concentrations showed a tendency to decline and fluctuate concurrently with the plasma progesterone levels. However, suppression of plasma estradiol concentrations by metergoline was not as complete as the suppression of progesterone and did not seem a prerequisite for abortion. The hormone profiles and treatment period required for abortion tended to be similar for both cycles of the three bitches that were treated during two consecutive pregnancies. This suggests a bitch effect on the factors that determine the efficacy of metergoline to induce abortion. The large variation and length of the treatment period that was required until abortion commenced was probably related to the relatively early start of treatment compared to other studies. The results of this investigation suggest that, similar to other prolactin suppressing ergot derivatives, metergoline causes complete luteolysis and can be used to reliably induce abortion only during the last 3 weeks of gestation.
Abortifacient Agents↗
[Which patients with acute coronary syndrome without ST segment elevation should be handled invasively/interventionally when?].
Until recently the therapeutic approach in patients with acute coronary syndrome without ST-segment elevation focused on medical stabilization. Usually cardiac catheterization and revascularisation were performed later only if the stabilized patient had provoked ischemia. Since angioplasty became safer with the introduction of coronary stents, and since new potent antithrombotic agents (i.e. tienopyridines or glycoprotein-receptorIIb/IIIa-antagonists) have been developed, early angioplasty has become much more effective. Moreover major progress has been made in risk-stratification, which allow an individual therapeutic strategy for each patient according to his risk-status. We discuss the most important randomised clinical trials comparing a conservative versus an invasive strategy and introduce a new algorithm for risk-stratification und therapy in acute coronary syndromes without ST-elevation.
Angina, Unstable↗
Crystal structure of sorbitol dehydrogenase.
Sorbitol dehydrogenase (SDH) is a distant relative to the alcohol dehydrogenases (ADHs) with sequence identities around 20%. SDH is a tetramer with one zinc ion per subunit. We have crystallized rat SDH and determined the structure by molecular replacement using a tetrameric bacterial ADH as search object. The conformation of the bound coenzyme is extended and similar to NADH bound to mammalian ADH but the interactions with the NMN-part have several differences with those of ADH. The active site zinc coordination in SDH is significantly different than in mammalian ADH but similar to the one found in the bacterial tetrameric NADP(H)-dependent ADH of Clostridiim beijerinckii. The substrate cleft is significantly more polar than for mammalian ADH and a number of residues are ideally located to position the sorbitol molecule in the active site. The SDH molecule can be considered to be a dimer of dimers, with subunits A-B and C-D, where the dimer interactions are similar to those in mammalian ADH. The tetramers are composed of two of these dimers, which interact with their surfaces opposite the active site clefts, which are accessible on the opposite side. In contrast to the dimer interactions, the tetramer-forming interactions are small with only few hydrogen bonds between side-chains.
Animals↗
The transcriptional program of a human B cell line in response to Myc.
The proto-oncogene c-myc (myc) encodes a transcription factor (Myc) that promotes growth, proliferation and apoptosis. Myc has been suggested to induce these effects by induction/repression of downstream genes. Here we report the identification of potential Myc target genes in a human B cell line that grows and proliferates depending on conditional myc expression. Oligonucleotide microarrays were applied to identify downstream genes of Myc at the level of cytoplasmic mRNA. In addition, we identified potential Myc target genes in nuclear run-on experiments by changes in their transcription rate. The identified genes belong to gene classes whose products are involved in amino acid/protein synthesis, lipid metabolism, protein turnover/folding, nucleotide/DNA synthesis, transport, nucleolus function/RNA binding, transcription and splicing, oxidative stress and signal transduction. The identified targets support our current view that myc acts as a master gene for growth control and increases transcription of a large variety of genes.
B-Lymphocytes↗
A current review of olanzapine's safety in the geriatric patient: from pre-clinical pharmacology to clinical data.
OBJECTIVE: Olanzapine (OLZ) is unique among currently available antipsychotic medications in its antagonism of a range of receptor systems including dopamine, norepinephrine, serotonin, acetylcholine, and histamine. Olanzapine's mechanistic complexity provides a broad efficacy profile in patients with schizophrenia and acute, pure or mixed mania. Patients experience symptomatic relief of mania, anxiety, hallucinations, delusions, and agitation/aggression and reduced depressive, negative, and some cognitive symptoms. This paper will review the safety profile of OLZ, focusing on the elderly, where data are available. METHOD: Preclinical and clinical studies of OLZ are reviewed, with emphasis on its possible effects on the cholinergic system and the histamine H(1) receptor. Weight change and related metabolic considerations, cardiac and cardiovascular safety, and motor function during treatment with OLZ are also reviewed. RESULTS AND CONCLUSION: In vitro receptor characterization methods, when done using physiologically relevant conditions allow accurate prediction of the relatively low rate of anticholinergic-like adverse events, extrapyramidal symptoms, and cardiovascular adverse events during treatment with OLZ. Currently available clinical data suggest olanzapine is predictably safe in treating adult patients of any age with schizophrenia and acute bipolar mania, as well as in treatment of patients with some types of neurodegenerative disorders.
Adverse Drug Reaction Reporting Systems↗
Early clinical experience with the 6 French Angio-Seal device: immediate closure of femoral puncture sites after diagnostic and interventional coronary procedures.
The objective of this study was to assess the early safety and efficacy of the novel 6 Fr Angio-Seal device for routine clinical use after diagnostic cardiac catheterization and coronary angioplasty. In a prospective study, we used the 6 Fr Angio-Seal device in 180 consecutive patients (131 male, 49 female, mean age 60.7 years) for closure of femoral arterial puncture sites immediately after diagnostic (n = 108) or interventional (n = 72) coronary procedures independent of the coagulation status. All patients were monitored for 24 hr after the procedure and followed for 30 days. The closure device was successfully deployed in 95.4% after diagnostic catheterization versus 98.6% after coronary angioplasty (P = 0.963). Immediate hemostasis was achieved in 91.5% versus 90.1% of the patients (P = 0.993). Major complications were observed 1.9% versus 2.8% of the patients (P = 0.885). During 30-day follow-up, no late events or complications were reported. The 6 Fr Angio-Seal device is a safe and effective device that allows for immediate closure of femoral puncture sites after both diagnostic and interventional procedures with a low rate of major complications.
Adult↗
Prospective comparison of admission computed tomographic scan and plain films of the upper cervical spine in trauma patients with altered mental status.
OBJECTIVE: The accurate evaluation of patients with multiple injuries is logistically complex and time sensitive, and must be cost-effective. We hypothesize that computed tomographic (CT) scan of the upper cervical spine (occiput to C3 [Co-C3]) would add little to the initial evaluation of patients with multiple injuries who have altered mental status. METHODS: The study consisted of a prospective, unblinded, consecutive series. Patients met entry criteria if they had sustained a blunt mechanism of injury and had an altered mental status requiring CT scan of two or more body systems. All patients received CT scan of Co-C3 with 2-mm cuts and subsequent reconstructions as well as five-view cervical spine plain films. Cervical spine injury was defined as any radiographically identified fracture or subluxation that required treatment. Patients were excluded if they died or were cleared clinically before plain film series were obtained. CT scan of Co-C3 and cervical spine films were reviewed by two different attending radiologists. RESULTS: Of the 2,690 consecutive admissions between December 1998 and November 1999, 1,356 patients met entry criteria. Seventy patients (5.2%) had a total of 95 injuries to the upper cervical spine. CT scan of Co-C3 identified 67 of 70 patients and plain films identified 38 of 70 patients with injuries to the upper cervical spine. Twelve patients (17%) had neurologic deficits attributable to Co-C3 injuries. Three patients had false-negative CT scans of Co-C3, and one patient was quadriplegic. There were 32 patients with false-negative plain films, including four patients with motor deficits (one with quadriplegia). Use of the guidelines developed by the Eastern Association for the Surgery of Trauma identified all patients with upper cervical spine injuries; to date, no patient in the study group was readmitted or has initiated a lawsuit for missed injury of the upper cervical spine. CONCLUSION: CT scan of Co-C3 was superior to plain films in the early identification of upper cervical spine injury. Plain films failed to identify 45% of upper cervical spine injuries; four of these missed injuries resulted in motor deficits. Our study supports the practice guidelines developed by the Eastern Association for the Surgery of Trauma for clearance of the upper cervical spine in patients with altered mental status, as all patients with injuries were identified using these guidelines.
Adolescent↗
Thinking about p24 proteins and how transport vesicles select their cargo.
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Animals↗
Clinical and electro-clinical classification of epileptic seizure in west Uganda.
When compared to that of industralised countries, the prevalence of epilepsy in developing countries has generally been found to be higher and in some areas extremely high rates of up to 57 cases per 1000 inhabitants have been reported. The reasons for this difference are still widely unknown and detailed epidemiological as well as clinical data are scarce, especially from rural Africa. The present study was conducted in western Uganda, in an area of high epilepsy prevalence, known to be endemic for onchocerciasis. The seizures of all 91 epilepsy patients diagnosed in this area over the period of two years were classified according to the criteria of the International League against Epilepsy. Based on seizure description alone, the predominant seizure was classified as generalised in 57 patients (63%), as partial in 22 (24%) and unclassified in 12 (13%). An EEG record was analysed in 55 out of 91 patients, showing focal epileptiform activity (EA) in 12, multifocal EA in 9 and primarily generalised EA in 6 patients. When in addition to clinical information, the EEG results in the 27 patients with EA were taken in consideration for seizure classification, the proportion of partial seizures increased to 78% (n = 21); inversely the proportion of generalised seizures fell to 22% (n = 6). The predominance of partial seizures would be compatible with a localised brain lesion as a frequent cause for epileptic seizures in the study area. The findings further corroborate recent observations from several African countries of an association between epilepsy and onchocerciasis.
Adolescent↗
Suppression of Raf-1 kinase activity and MAP kinase signalling by RKIP.
Raf-1 phosphorylates and activates MEK-1, a kinase that activates the extracellular signal regulated kinases (ERK). This kinase cascade controls the proliferation and differentiation of different cell types. Here we describe a Raf-1-interacting protein, isolated using a yeast two-hybrid screen. This protein inhibits the phosphorylation and activation of MEK by Raf-1 and is designated RKIP (Raf kinase inhibitor protein). In vitro, RKIP binds to Raf-1, MEK and ERK, but not to Ras. RKIP co-immunoprecipitates with Raf-1 and MEK from cell lysates and colocalizes with Raf-1 when examined by confocal microscopy. RKIP is not a substrate for Raf-1 or MEK, but competitively disrupts the interaction between these kinases. RKIP overexpression interferes with the activation of MEK and ERK, induction of AP-1-dependent reporter genes and transformation elicited by an oncogenically activated Raf-1 kinase. Downregulation of endogenous RKIP by expression of antisense RNA or antibody microinjection induces the activation of MEK-, ERK- and AP-1-dependent transcription. RKIP represents a new class of protein-kinase-inhibitor protein that regulates the activity of the Raf/MEK/ERK module.
3T3 Cells↗
Latent membrane protein 1 of Epstein-Barr virus interacts with JAK3 and activates STAT proteins.
Latent membrane protein 1 (LMP1) acts like a permanently activated receptor of the tumor necrosis factor (TNF)-receptor superfamily and is absolutely required for B cell immortalization by Epstein-Barr virus. Molecular and biochemical approaches demonstrated that LMP1 usurps cellular signaling pathways resulting in the induction of NF-kappaB and AP-1 via two C-terminal activating regions. We demonstrate here that a third region encompassing a proline rich sequence within the 33 bp repetitive stretch of LMP1's C-terminus is required for the activation of Janus kinase 3 (JAK3). The interaction of LMP1 and JAK3 leads to the enhanced tyrosine auto/transphosphorylation of JAK3 within minutes after crosslinking of a conditional NGF-R:LMP1 chimera and is a prerequisite for the activation of STAT transcription factors. These results reveal a novel activating region in the LMP1 C-terminus and identify the JAK/STAT pathway as a target of this viral integral membrane protein in B cells.
Amino Acid Sequence↗
LMP1 signal transduction differs substantially from TNF receptor 1 signaling in the molecular functions of TRADD and TRAF2.
The Epstein-Barr virus latent membrane protein 1 (LMP1) binds tumor necrosis factor receptor (TNFR)-associated factors (TRAFs) and the TNFR-associated death domain protein (TRADD). Moreover, it induces NF-kappaB and the c-Jun N-terminal kinase 1 (JNK1) pathway. Thus, LMP1 appears to mimick the molecular functions of TNFR1. However, TNFR1 elicits a wide range of cellular responses including apoptosis, whereas LMP1 constitutes a transforming protein. Here we mapped the JNK1 activator region (JAR) of the LMP1 molecule. JAR overlaps with the TRADD-binding domain of LMP1. In contrast to TNFR1, LMP1 recruits TRADD via the TRADD N-terminus but not the TRADD death domain. Consequently, the molecular function of TRADD in LMP1 signaling differs from its role in TNFR1 signal transduction. Whereas NF-kappaB activation by LMP1 was blocked by a dominant-negative TRADD mutant, LMP1 induces JNK1 independently of the TRADD death domain and TRAF2, which binds to TRADD. Further downstream, JNK1 activation by TNFR1 involves Cdc42, whereas LMP1 signaling to JNK1 is independent of p21 Rho-like GTPases. Although both LMP1 and TNFR1 interact with TRADD and TRAF2, the different topologies of the signaling complexes correlate with substantial differences between LMP1 and TNFR1 signal transduction to JNK1.
Antigens, CD↗