RESUMO
BACKGROUND: Melatonin, which plays an important role for regulation of circadian rhythms and the sleep/wake cycle has been linked to the pathophysiology of major depressive and bipolar disorder. Here we investigated melatonin levels in cerebrospinal fluid (CSF) and serum of depression and bipolar patients to elucidate potential differences and commonalities in melatonin alterations across the two disorders. METHODS: Using enzyme-linked immunosorbent assays, CSF and serum melatonin levels were measured in 108 subjects (27 healthy volunteers, 44 depressed and 37 bipolar patients). Covariate adjusted multiple regression analysis was used to investigate group differences in melatonin levels. RESULTS: In CSF, melatonin levels were significantly decreased in bipolar (P<0.001), but not major depressive disorder. In serum, we observed a significant melatonin decrease in major depressive (P=0.003), but not bipolar disorder. No associations were found between serum and CSF melatonin levels or between melatonin and measures of symptom severity or sleep disruptions in either condition. CONCLUSION: This study suggests the presence of differential, body fluid specific alterations of melatonin levels in bipolar and major depressive disorder. Further, longitudinal studies are required to explore the disease phase dependency of melatonin alterations and to mechanistically explore the causes and consequences of site-specific alterations.
Assuntos
Transtorno Bipolar/fisiopatologia , Ritmo Circadiano/fisiologia , Transtorno Depressivo Maior/fisiopatologia , Melatonina/sangue , Melatonina/líquido cefalorraquidiano , Adulto , Transtorno Bipolar/diagnóstico , Transtorno Bipolar/metabolismo , Estudos de Casos e Controles , Transtorno Depressivo Maior/diagnóstico , Transtorno Depressivo Maior/metabolismo , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Masculino , Melatonina/metabolismo , Pessoa de Meia-Idade , Análise de RegressãoRESUMO
Antibiotic resistance is an unsolved healthcare problem with increasing impact on patient management in the last years. In particular, multidrug resistance among Gram-negative bacterial strains has become the most pressing challenge. In order to deliver the most efficacious antimicrobial therapy with minimum delay, rapid diagnostic tests are required in order to detect multidrug resistant pathogens early during infection. In line with these efforts, we have developed a mass spectrometry-based assay for the rapid determination of ampicillin and cefotaxime resistance. The assay quantifies beta-lactamase activities towards ampicillin and cefotaxime within a turnaround time of 150 min, which is substantially faster than classical susceptibility testing.
Assuntos
Antibacterianos/metabolismo , Cefotaxima/metabolismo , Cromatografia Líquida/métodos , Escherichia coli/efeitos dos fármacos , Escherichia coli/enzimologia , Espectrometria de Massas/métodos , beta-Lactamases/análise , Ampicilina/metabolismo , Técnicas Bacteriológicas/métodos , Humanos , Fatores de Tempo , Resistência beta-LactâmicaRESUMO
BACKGROUND: Acute ischemic stroke patients may occasionally suffer from concomitant acute coronary syndrome (ACS). Troponin I and T are established biomarkers to detect ACS. Recently introduced high-sensitive cardiac troponin (hs-TNI and hs-TNT) assays are increasingly used to identify ACS in stroke patients even without signs or symptoms of ACS. These new test systems very often detect elevated values of hs-troponin, although clinical relevance and consequences of elevated hs-TNI values in these patients are unclear so far. PATIENTS AND METHODS: We examined hs-TNI values in 834 consecutive ischemic stroke patients admitted to our Comprehensive Stroke Center during a 1-year period. hs-TNI was measured immediately after admission and after 3 h if initial hs-TNI was elevated above the 99th percentile of normal values (>0.045 ng/ml). Patients with elevated values were divided into two groups: (1) constant and (2) dynamic hs-TNI values. The dynamic approach was defined as a 30% rise or fall of the hs-TNI value above the critical value within 3 h. All patients received stroke diagnostic and continuous monitoring according to international stroke unit standards, including a 12-lead ECG, blood pressure, body temperature and continuous ECG monitoring, as well as regular 6-hourly neurological and general physical examination (including NIHSS scores). The cardiologists - as members of the Stroke Unit team - evaluated clinical symptoms/examination, as well as laboratory, echocardiographic and ECG findings for the diagnosis of ACS. RESULTS: 172/834 (20.6%) patients showed elevated hs-TNI levels on admission. Patients with elevated hs-TNI values exhibited a significantly (p < 0.001) increased rate of hypertension (89 vs. 77.2%), history of stroke (24.4 vs. 14.8%), history of coronary artery disease (65.7 vs. 34.1%), history of myocardial infarction (22.1 vs. 7.6%), heart failure (12.8 vs. 5.7%) and atrial fibrillation (44.2 vs. 23.6%). 82/136 patients showed constant and 54/136 patients dynamic hs-TNI values: among the latter, 5 patients were diagnosed with ST segment elevation myocardial infarction (STEMI) and 24 with non-STEMI (NSTEMI). CONCLUSION: Our data demonstrate that hs-TNI was elevated in about 20.6% of acute ischemic stroke patients but therapeutically relevant ACS was diagnosed only in the dynamic group. hs-TNI elevations without dynamic changes may occur in stroke patients without ACS due to different reasons that stress the heart. Therefore, we suppose that hs-TNI is a sensitive marker to detect high-risk patients but serial measurements are mandatory and expert cardiological workup is essential for best medical treatment and to accurately diagnose ACS in acute ischemic stroke patients.
Assuntos
Síndrome Coronariana Aguda/diagnóstico , Infarto do Miocárdio/diagnóstico , Acidente Vascular Cerebral/sangue , Troponina I/sangue , Síndrome Coronariana Aguda/sangue , Idoso , Idoso de 80 Anos ou mais , Angiotensina Amida , Biomarcadores/sangue , Eletrocardiografia/métodos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/sangue , Medição de Risco , Fatores de Risco , Acidente Vascular Cerebral/diagnóstico , Troponina T/sangueRESUMO
Early targeted antimicrobial therapy helps decrease costs and prevents the spread of antimicrobial resistance, including in Escherichia coli, the most frequent Gram-negative bacterium that causes sepsis. Therefore, rapid susceptibility testing represents the major prerequisite for knowledge-based successful antimicrobial treatment. To accelerate testing for antibiotic susceptibility, we have developed a new mass spectrometry-based assay for antibiotic susceptibility testing (MAAST). For proof of principle, we present an ampicillin susceptibility test for E. coli with a turnaround time of 90 min upon growth detection.
Assuntos
Resistência a Ampicilina , Ampicilina/farmacologia , Antibacterianos/farmacologia , Escherichia coli/efeitos dos fármacos , Espectrometria de Massas/métodos , Humanos , Testes de Sensibilidade Microbiana/métodos , Fatores de TempoRESUMO
OBJECTIVES: The new immunochemistry cobas e 801 module (Roche Diagnostics) was developed to meet increasing demands on routine laboratories to further improve testing efficiency, while maintaining high quality and reliable data. DESIGN AND METHODS: During a non-interventional multicenter evaluation study, the overall performance, functionality and reliability of the new module was investigated under routine-like conditions. It was tested as a dedicated immunochemistry system at four sites and as a consolidator combined with clinical chemistry at three sites. RESULTS: We report on testing efficiency and analytical performance of the new module. Evaluation of sample workloads with site-specific routine request patterns demonstrated increased speed and almost doubled throughput (maximal 300 tests per h), thus revealing that one cobas e 801 module can replace two cobas e 602 modules while saving up to 44% floor space. Result stability was demonstrated by QC analysis per assay throughout the study. Precision testing over 21â¯days yielded excellent results within and between labs, and, method comparison performed versus the cobas e 602 module routine results showed high consistency of results for all assays under study. In a practicability assessment related to performance and handling, 99% of graded features met (44%) or even exceeded (55%) laboratory expectations, with enhanced reagent management and loading during operation being highlighted. CONCLUSION: By nearly doubling immunochemistry testing efficiency on the same footprint as a cobas e 602 module, the new module has a great potential to further consolidate and enhance laboratory testing while maintaining high quality analytical performance with Roche platforms.
Assuntos
Técnicas Eletroquímicas/instrumentação , Medições Luminescentes/instrumentação , Técnicas Eletroquímicas/métodos , Humanos , Imunoensaio/instrumentação , Imunoensaio/métodos , Imunoquímica , Medições Luminescentes/métodosRESUMO
A unique feature of human soft tissue liposarcoma is a stable (12;16)(q13;p11) translocation observed mainly in myxoid and roundcell liposarcomas. This translocation results in FUS/CHOP fusion transcripts with a corresponding oncogenic protein. We hypothesised that genes downstream of FUS/CHOP might serve as attractive candidates for novel tumour associated antigens. Among a panel of analysed genes, only pentraxin related gene (PTX3) demonstrated high expression in liposarcomas as compared to normal tissues. The analysis of RNA and protein expression demonstrated concordant results. However, the level of RNA and protein overexpression did not correlate in all cases. Finally, PTX3 expression was not related to presence of a FUS/CHOP fusion transcript within the liposarcoma tissues. PTX3 has been associated with adipocyte differentiation and now, additionally, is characterised by a markedly increased expression in human soft tissue liposarcoma. This finding mandates further research efforts to clarify the exact role of PTX3 in liposarcoma oncogenesis.
Assuntos
Proteína C-Reativa/metabolismo , Lipossarcoma/genética , Proteínas de Neoplasias/metabolismo , Componente Amiloide P Sérico/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Western Blotting , Estudos de Coortes , Feminino , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Proteínas de Fusão Oncogênica/metabolismo , Proteína FUS de Ligação a RNA/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Fator de Transcrição CHOP/metabolismo , Translocação GenéticaRESUMO
Ductal pancreatic adenocarcinoma is a dismal disease, having the worst prognosis of all solid tumors. While genomics and transcriptomics have provided a wealth of data, no contribution has been made to clinical medicine in terms of diagnostic or prognostic markers. Hope lies in yet another novel technology, proteomics. Conceptually, proteomics bears the advantage of incorporating both posttranslational modifications as well as host factors. This is thought to be important in factors influencing survival such as chemoresistance. This tutorial review discusses the state of the art in pancreatic cancer proteomics in light of technical developments. At this moment, proteomics is still at the beginning in clinical application. First results, however, suggest some hope for the development of a new understanding of the molecular biology in pancreatic cancer yielding into very specific markers of disease or allowing a rational and individualized therapy.
Assuntos
Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/metabolismo , Biomarcadores Tumorais/metabolismo , Perfilação da Expressão Gênica/métodos , Proteínas de Neoplasias/metabolismo , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/metabolismo , Proteoma/metabolismo , Antineoplásicos/uso terapêutico , Sistemas de Liberação de Medicamentos/métodos , Resistencia a Medicamentos Antineoplásicos , Perfilação da Expressão Gênica/tendências , Mapeamento de Peptídeos/métodos , Mapeamento de Peptídeos/tendênciasRESUMO
High demands on freedom from germs are made on auditory ossicles to be used as implants. Postoperative infections often result from the existence of germ-contaminated ossicles. That is why we undertook microbiological examinations, using three frequently applied preserving methods for auditory ossicles kept for tympanoplasties. The results of the examinations were: Disinfection by Cialit (often used in clinical practice) produced unsatisfactory results. Disinfection by ethyl alcohol (70 per cent) and a subsequent treatment with thiomersal-Ringer's solution (0.4 per cent) yielded satisfactory results. Disinfection by preservation with an aqueous solution of formalin and subsequent treatment with Cialit proved most effective. None of the applicated germs could be regrown.
Assuntos
Técnicas Bacteriológicas , Desinfecção/métodos , Ossículos da Orelha/transplante , Esterilização/métodos , Preservação de Tecido/métodos , Animais , Ossículos da Orelha/microbiologia , Suínos , TimpanoplastiaRESUMO
Efficacy of and tolerance to 0.25 mg brotizolam and 2.0 mg flunitrazepam were compared over a period of 6 days in ambulatory patients complaining of sleep disturbance. The study was double-blind and randomised with a parallel group design. Both drugs improved sleep. More patients assessed sleep latency as shorter during the first night of ingestion with flunitrazepam than with brotizolam, but assessments were comparable over the next 5 days. The number of patients who considered that the frequency of nocturnal awakenings was less did not differ significantly between drugs. Tolerance to brotizolam (0.25 mg) was assessed more favourably than with flunitrazepam (2.0 mg). The study suggests that brotizolam (0.25 mg) is indicated for patients who have difficulty in falling asleep and staying asleep, and who must preserve their alertness during the early part of the next day. Flunitrazepam (2.0 mg) is equally effective, but at this dose there is a higher incidence of adverse effects.
Assuntos
Azepinas/uso terapêutico , Flunitrazepam/uso terapêutico , Hipnóticos e Sedativos/uso terapêutico , Transtornos do Sono-Vigília/tratamento farmacológico , Adulto , Idoso , Ensaios Clínicos como Assunto , Método Duplo-Cego , Tolerância a Medicamentos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Distribuição AleatóriaRESUMO
Efficacy and tolerability of brotizolam (0.25 and 0.5 mg) were compared over a 6-day period with nitrazepam (5.0 mg) in middle-aged patients (less than 65 years) with sleep disturbances requiring medication. The study was double-blind and randomised with a cross-over design. Each preparation reduced sleep onset latency and frequency of awakenings, and improved quality and duration of sleep as well as subjective condition on awakening. Brotizolam 0.25 mg was found to be equally effective as 0.5 mg, and so the lower dose is recommended for the middle aged.
Assuntos
Azepinas/uso terapêutico , Hipnóticos e Sedativos/uso terapêutico , Nitrazepam/uso terapêutico , Transtornos do Sono-Vigília/tratamento farmacológico , Adolescente , Adulto , Idoso , Ensaios Clínicos como Assunto , Método Duplo-Cego , Tolerância a Medicamentos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Distribuição AleatóriaRESUMO
Efficacy of and tolerance to 0.25 mg brotizolam and 0.25 mg triazolam were compared in hospitalised patients (aged 20 to 69 years) with sleep difficulties. Over 6 days there were no differences in efficacy and tolerance. The physicians reported the effectiveness of the drugs as good-to-satisfactory in 88.6% with brotizolam and 92.0% with triazolam. The patients reported with both drugs reduced time to fall asleep, less awakenings, increased duration of sleep and improved condition on awakening.