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1.
Eur J Surg Oncol ; 50(7): 108421, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38870573

ABSTRACT

BACKGROUND: The aim of this study was to analyze four pre-operative physical frailty indicators from a geriatric assessment (GA) independently and combined in a physical frailty index, in their ability to predict postoperative 30 d-complications. MATERIALS AND METHODS: In this secondary analysis of data from the published PERATECS study (ClinicalTrials.gov: NCT01278537), the predictive value of four physical frailty indicators from a defined GA battery was examined with univariable and multivariate logistic regression models in a sample of 493 onco-geriatric surgical patients. The primary endpoint was incidence of major (Clavien-Dindo ≥ grade 2 [CD ≥ 2]) complications within 30 postoperative days. Predictors of the first model included self-reported exhaustion (SRE), body mass index (BMI), Timed Up-and-Go (TUG) and handgrip strength (HGS) independently, and a second model combined these four items as a Physical Frailty Index (4i-PFI). Both regression models were adjusted for age, gender, American Society of Anesthesiologists (ASA) status, tumor sites, duration of surgery time and Mini Nutritional Assessment (MNA) score. RESULTS: A total of 233 patients (47 %) developed CD ≥ 2 complications. In addition to ASA score, length of surgery, and gynecological and upper gastrointestinal tumor sites, the first model showed that SRE (OR 1.866) predicted CD ≥ 2 complications, but not TUG, BMI and HGS. In the second model, the 4i-PFI predicted CD ≥ 2 complications (OR pre-frail = 1.808, frail = 3.787). CONCLUSIONS: Physical frailty indicators as SRE revealed a better ability to predict CD ≥ 2 complications than BMI, TUG and HGS. However, prediction of CD ≥ 2 complications was enhanced when these parameters were combined in a novel 4i-PFI.


Subject(s)
Frailty , Geriatric Assessment , Hand Strength , Neoplasms , Postoperative Complications , Self Report , Humans , Female , Male , Aged , Postoperative Complications/epidemiology , Frailty/epidemiology , Neoplasms/surgery , Incidence , Fatigue/epidemiology , Fatigue/etiology , Aged, 80 and over , Body Mass Index , Frail Elderly
2.
Front Med (Lausanne) ; 8: 613951, 2021.
Article in English | MEDLINE | ID: mdl-33842496

ABSTRACT

Objective: To analyze continuous 1- or 2-channel electroencephalograms (EEGs) of mechanically ventilated patients with coronavirus disease 2019 (COVID-19) with regard to occurrence of epileptiform potentials. Design: Single-center retrospective analysis. Setting: Intensive care unit of Hannover Medical School, Hannover, Germany. Patients: Critically ill COVID-19 patients who underwent continuous routine EEG monitoring (EEG monitor: Narcotrend-Compact M) during sedation. Measurements and Main Results: Data from 15 COVID-19 patients (11 men, four women; age: 19-75 years) were evaluated. Epileptiform potentials occurred in 10 of 15 patients (66.7%). Conclusions: The results of the evaluation regarding the occurrence of epileptiform potentials show that there is an unusually high percentage of cerebral involvement in patients with severe COVID-19. EEG monitoring can be used in COVID-19 patients to detect epileptiform potentials.

3.
BMC Res Notes ; 13(1): 161, 2020 Mar 18.
Article in English | MEDLINE | ID: mdl-32188509

ABSTRACT

OBJECTIVE: This study aimed to investigate the association of anesthetists' academic and educational status with self-confidence, self-rated knowledge and objective knowledge about rational antibiotic application. Therefore, anesthetists in Germany were asked about their self-confidence, self-rated knowledge and objective knowledge on antibiotic therapy via the Multiinstitutional Reconnaissance of practice with Multiresistant bacteria (MR2) survey. Other analysis from the survey have been published elsewhere, before. RESULTS: 361 (52.8%) questionnaires were completed by specialists and built the study group. In overall analysis the Certification in Intensive Care (CIC) was significantly associated with self-confidence (p < 0.001), self-rated knowledge (p < 0.001) and objective knowledge (p = 0.029) about antibiotic prescription. Senior consultant status was linked to self-confidence (p < 0.001) and self-rated knowledge (p = 0.005) but not objective knowledge. Likewise, working on Intensive Care Unit (ICU) during the last 12 months was significantly associated with self-rated knowledge and self-confidence (all p < 0.001). In a logistic regression model, senior consultant status was not associated with any tested influence factor. This analysis unveiled that CIC and working on ICU were more associated with anesthesiologists' self-confidence and self-rated knowledge than senior consultant status. However, neither of the characteristics was thoroughly associated with objective knowledge.


Subject(s)
Anesthesiologists/statistics & numerical data , Anti-Bacterial Agents/therapeutic use , Attitude of Health Personnel , Health Knowledge, Attitudes, Practice , Intensive Care Units/statistics & numerical data , Adult , Female , Germany , Health Care Surveys , Humans , Male , Middle Aged
4.
J Clin Anesth ; 61: 109632, 2020 May.
Article in English | MEDLINE | ID: mdl-31668693

ABSTRACT

BACKGROUND: Postoperative delirium (POD) is a common complication after surgery. OBJECTIVE: We sought to determine the association between preoperative anticholinergic load calculated using the anticholinergic drug scale (ADS) and POD in cancer patients over 65 years of age. DESIGN: A retrospective sub-investigation of a randomised controlled interventional trial. SETTING: Two tertiary university hospitals. PATIENTS: Overall, patients aged 65 years and older scheduled for surgical treatment of gastrointestinary, genitourinary or gynaecological cancers. MAIN OUTCOME MEASURES: The primary outcome was the interaction between anticholinergic drug scale and occurrence of postoperative delirium. Patient clinical parameters and ADS scores were assessed preoperatively. POD screening was conducted for a total of 7 days following surgery using validated measures. Independent associations between ADS and POD were assessed using multivariate logistical regression analyses. RESULTS: A total of 651 patients (mean age, 71.8 years; 68.5% males) were included. Of those, 66 patients (10.1%) developed POD. The ADS score was independently associated with the occurrence of POD (higher ADS per point OR 1.496; 95% CI 1.09-2.05; p = 0.01). Additionally, age (per year OR 1.06; CI 95% CI 1.01-1.11; p = 0.03) and ASA state (OR 2.16; 95% CI 1.22-3.83; p = 0.01), as well as stay on ICU (yes vs. no OR 2.8; 95% CI 1.57-4.998; p < 0.01), were independently associated with POD. CONCLUSIONS: ADS assessment according to chronic medication use is a cost-effective, non-invasive method of identifying elderly cancer patients at risk for POD. TRIAL REGISTRY: www.clinicaltrials.gov. Identifier NCT01278537. Ethics: IRB of Charité University-Medicine Berlin, Germany; EA2/241/08.


Subject(s)
Cholinergic Antagonists , Delirium , Aged , Cholinergic Antagonists/adverse effects , Delirium/chemically induced , Delirium/diagnosis , Delirium/epidemiology , Female , Humans , Male , Postoperative Complications/chemically induced , Postoperative Complications/epidemiology , Prospective Studies , Retrospective Studies , Risk Factors
5.
J Perianesth Nurs ; 33(3): 281-289, 2018 Jun.
Article in English | MEDLINE | ID: mdl-29784257

ABSTRACT

PURPOSE: This study aimed to determine the effect of patient empowerment on acute postoperative pain. This research was part of the Patient Empowerment and Risk-Assessed Treatment to Improve Outcome in the Elderly After Onco-Surgery Trial. DESIGN: This research was a prospective randomized controlled interventional study. METHODS: Patients who underwent gynecologic onco-surgery were included in this analysis of demographic data, basic characteristics, pain intensity by numeric rating scale, and mode of pain therapy. The intervention included provision of detailed information booklet and patient diary. FINDINGS: Ninety-one patients were enrolled (treatment group, n = 51; control group, n = 40). With the same medications, pain on the first postoperative day was significantly less severe in the treatment group than in the control group (P = .03). On multivariate logistic regression, patient empowerment had a significant effect on pain intensity (odds ratio, 3.46; 95% confidence interval, 1.35 to 8.86; P = .01). The number needed to treat to decrease pain from severe to mild (numeric rating scale, 5 to 10 to 0 to 4) was 4.35. CONCLUSIONS: Patient empowerment significantly reduces postoperative pain in elderly patients undergoing gynecologic cancer surgery.


Subject(s)
Gynecologic Surgical Procedures/adverse effects , Pain, Postoperative/drug therapy , Power, Psychological , Aged , Analgesics, Opioid/administration & dosage , Female , Humans , Pain Management/methods , Pain, Postoperative/prevention & control , Prospective Studies
6.
J Geriatr Oncol ; 9(1): 53-59, 2018 01.
Article in English | MEDLINE | ID: mdl-28888555

ABSTRACT

OBJECTIVE: To investigate the prognostic value of elements of the Geriatric Assessment, in particular the Timed Up and Go (TUG) Test and the Barthel Index of Activities of Daily Living (ADL) for one-year post-operative mortality in elderly patients with cancer. MATERIALS AND METHODS: This prospective cohort study included patients 65years of age or older undergoing elective major surgery for cancer between June 2008 and June 2010. Preoperative functional status was measured by the TUG Test and the Barthel Index of ADL Cognitive state was assessed by the Mini Mental State Examination (MMSE). Complications were recorded prospectively. The degree of resection was noted. RESULTS: Data from 131 patients (56% women; median age, 71years) were analysed at 1year of follow-up. Mortality after 1year was 28.2%. Twenty-nine patients (22.3%) were dependent in ADLs, and 43 (35.2%) impaired in TUG. Thirteen patients (10.7%) were both, dependent in ADLs and impaired in TUG. Short-term complications after surgery occurred in 66% of patients, and major complications occurred in 29%. Patients who were dependent in ADLs and impaired in TUG had significantly higher 1-year mortality (OR, 4.5; 95% CI, 1.21-18.25; p=0.034). Lower scores on the MMSE (OR, 0.64; 95% CI, 0.43-0.95; p=0.048) and incomplete surgical resection (OR, 3.25; 95% CI, 1.15-9.20; p=0.026) were independently associated with higher 1-year mortality. CONCLUSION: Functional assessments, such as ADL and TUG scores, as well as mild cognitive impairment, are predictors of long-term outcome in elderly cancer patients. TRIAL REGISTRATION: German Clinical Trials Register (DRKS 00005150).


Subject(s)
Cognitive Dysfunction/epidemiology , Gastrointestinal Neoplasms/mortality , Geriatric Assessment/methods , Urogenital Neoplasms/mortality , Activities of Daily Living , Aged , Aged, 80 and over , Comorbidity , Female , Gastrointestinal Neoplasms/psychology , Gastrointestinal Neoplasms/surgery , Humans , Kaplan-Meier Estimate , Male , Mental Status and Dementia Tests , Postoperative Complications/epidemiology , Prospective Studies , Urogenital Neoplasms/psychology , Urogenital Neoplasms/surgery
7.
BMC Anesthesiol ; 16(1): 108, 2016 11 08.
Article in English | MEDLINE | ID: mdl-27821065

ABSTRACT

BACKGROUND: Currently there is no ARDS definition or classification system that allows optimal prediction of mortality in ARDS patients. This study aimed to examine the predictive values of the AECC and Berlin definitions, as well as clinical and respiratory parameters obtained at onset of ARDS and in the course of the first seven consecutive days. METHODS: The observational study was conducted at a 14-bed intensive care unit specialized on treatment of ARDS. Predictive validity of the AECC and Berlin definitions as well as PaO2/FiO2 and FiO2/PaO2*Pmean (oxygenation index) on mortality of ARDS patients was assessed and statistically compared. RESULTS: Four hundred forty two critically-ill patients admitted for ARDS were analysed. Multivariate Cox regression indicated that the oxygenation index was the most accurate parameter for mortality prediction. The third day after ARDS criteria were met at our hospital was found to represent the best compromise between earliness and accuracy of prognosis of mortality regarding the time of assessment. An oxygenation index of 15 or greater was associated with higher mortality, longer length of stay in ICU and hospital and longer duration of mechanical ventilation. In addition, non-survivors had a significantly longer length of stay and duration of mechanical ventilation in referring hospitals before admitted to the national reference centre than survivors. CONCLUSIONS: The oxygenation index is suggested to be the most suitable parameter to predict mortality in ARDS, preferably assessed on day 3 after admission to a specialized centre. Patients might benefit when transferred to specialized ICU centres as soon as possible for further treatment.


Subject(s)
Critical Care/standards , Respiratory Distress Syndrome/mortality , Breath Tests , Critical Illness/mortality , Female , Hospital Mortality , Humans , Male , Middle Aged , Oxygen/blood , Prognosis , Respiratory Distress Syndrome/blood , Respiratory Distress Syndrome/diagnosis , Risk Factors , Severity of Illness Index
8.
PLoS One ; 10(9): e0137824, 2015.
Article in English | MEDLINE | ID: mdl-26378939

ABSTRACT

PURPOSE: This randomized controlled, clinical prospective interventional trial was aimed at exploring the effect of patient empowerment on short- and long-term outcomes after major oncologic surgery in elderly cancer patients. METHODS: This trial was performed from February 2011 to January 2014 at two tertiary medical centers in Germany. The study included patients aged 65 years and older undergoing elective surgery for gastro-intestinal, genitourinary, and thoracic cancer. The patients were randomly assigned to the intervention group, i.e. patient empowerment through information booklet and diary keeping, or to the control group, which received standard care. Randomization was done by block randomization in blocks of four in order of enrollment. The primary outcome were 1,postoperative length of hospital stay (LOS) and 2. long-term global health-related quality of life (HRQoL) one year postoperatively. HRQoL was assessed using the EORTC QLQ C30 questionnaire. Secondary outcomes encompassed postoperative stress and complications. Further objectives were the identification of predictors of LOS, and HRQoL at 12 months. RESULTS: Overall 652 patients were included. The mean age was 72 ± 4.9 years, and the majority of patients were male (68.6%, n = 447). The ^median of postoperative length of stay was 9 days (IQR 7-14 day). There were no significant differences between the intervention and the control groups in postoperative LOS (p = 0.99) or global HRQoL after one year (women: p = 0.54, men: p = 0.94). While overall complications and major complications occurred in 74% and 24% of the cases, respectively, frequency and severity of complications did not differ significantly between the groups. Patients in the intervention group reported significantly less postoperative pain (p = 0.03) than the control group. Independent predictors for LOS were identified as severity of surgery, length of anesthesia, major postoperative complications, nutritional state, and pre-operative physical functional capacity measured by the Timed Up and Go-test by multiple robust regressions. CONCLUSION: Patient empowerment through information booklet and diary keeping did not shorten the postoperative LOS in elderly onco-surgical patients, but improved quality of care regarding postoperative pain. Postoperative length of stay is influenced by pre-operative nutritional state, pre-operative functional impairment, severity of surgery, and length of anesthesia. TRIAL REGISTRATION: Clinicaltrials.gov. Identifier NCT01278537.


Subject(s)
Patient Education as Topic , Patient Participation/methods , Perioperative Care/methods , Quality of Health Care , Quality of Life , Aged , Female , Gastrointestinal Neoplasms/surgery , Germany , Humans , Length of Stay , Male , Pain, Postoperative , Postoperative Complications , Prospective Studies , Surveys and Questionnaires , Tertiary Care Centers , Thoracic Neoplasms/surgery , Treatment Outcome , Urogenital Neoplasms/surgery
9.
PLoS One ; 9(1): e85456, 2014.
Article in English | MEDLINE | ID: mdl-24465568

ABSTRACT

OBJECTIVE: Aim of this study was to evaluate the association between preoperative health-related quality of life (HRQoL) and mortality in a cohort of elderly patients (>65 years) with gastrointestinal, gynecological and genitourinary carcinomas. DESIGN: Prospective cohort pilot study. SETTING: Tertiary university hospital in Germany. PATIENTS: Between June 2008 and July 2010 and after ethical committee approval and written informed consent, 126 patients scheduled for onco-surgery were included. Prior to surgery as well as 3 and 12 months postoperatively all participants completed the EORTC-QLQ-C30 questionnaire (measuring self-reported health-related quality of life). Additionally, demographic and clinical data including the Mini Mental State Examination (MMSE) were collected. Surgery and anesthesia were conducted according to the standard operating procedures. Primary endpoint was the cumulative mortality rate over 12 months after one year. Changes in Quality of life were considered as secondary outcome. RESULTS: Mortality after one year was 28%. In univariable and multivariable logistic regression analysis baseline HRQoL self-reported cognitive function (OR per point: 0.98; CI 95% 0.96-0.99; p = 0.024) and higher symptom burden for appetite loss (per point: OR 1.02; CI 95% 1.00-1.03; p = 0.014) were predictive for long-term mortality. Additionally the MMSE as an objective measure of cognitive impairment (per point: OR 0.69; CI 95% 0.51-0.96; p = 0.026) as well as severity of surgery (OR 0.31; CI 95% 0.11-0.93; p = 0.036) were predictive for long-term mortality. Global health status 12 months after surgery was comparable to the baseline levels in survivors despite moderate impairments in other domains. CONCLUSION: This study showed that objective and self-reported cognitive functioning together with appetite loss were prognostic for mortality in elderly cancer patients. In addition, impaired cognitive dysfunction and severity of surgery were predictive for one-year mortality whereas in this selected population scheduled for surgery age, gender, cancer site and metastases were not.


Subject(s)
Neoplasms/mortality , Neoplasms/surgery , Quality of Life , Aged , Aged, 80 and over , Female , Humans , Logistic Models , Male , Mortality , Preoperative Period , Prognosis , Surveys and Questionnaires
10.
Chronobiol Int ; 29(4): 430-42, 2012 May.
Article in English | MEDLINE | ID: mdl-22515562

ABSTRACT

In Djungarian hamsters (Phodopus sungorus) bred at the authors' institute, a certain number of animals show activity patterns incompatible with proper entrainment of their endogenous circadian pacemaker to the environmental light-dark (LD) cycle. Even though the activity-offset in these animals is stably coupled to "light-on," activity-onset is increasingly delayed, leading to a compression of the activity time (α). If α falls below a critical value, the circadian rhythm in these so called delayed activity-onset (DAO) hamsters starts to free-run and finally breaks down. Animals then show an arrhythmic activity pattern (AR hamsters). Previous studies revealed the mechanisms of photic entrainment have deteriorated (DAO) or the suprachiasmatic nucleus (SCN) does not generate a rhythmic signal (AR). The aim of the present study was to investigate the consequences that these deteriorations have upon photoperiodic time measurement. Animals were bred and kept under standardized housing conditions with food and water ad libitum and a 14L/10D (long day, LD) regimen. Locomotor activity was recorded continuously using passive infrared motion detectors. Body mass, testes size, and fur coloration were measured weekly or biweekly to further quantify the photoperiodic reaction. In a first experiment, adult male wild-type (WT), DAO, and AR hamsters were transferred initially to a 16L/8D cycle. After 3-4 wks, the light period was shortened symmetrically by 8 h. After 14 wks, none of the DAO and AR hamsters, and only 1 of 8 WT hamsters showed short-day (SD) traits. Therefore, in a second experiment, hamsters were transferred to SD conditions (8L/16D cycle) for 8 wks directly from standard LD conditions. In 6 of 7 WT hamsters, activity time expanded, body mass and testes size decreased, and fur coloration changed from summer to winter pelage. In contrast, none of the DAO and AR hamsters displayed an SD response. In a third experiment, DAO and AR hamsters were kept in constant darkness (DD) for 8 and 14 wks. After 8 wks, DAO hamsters showed a similar photoperiodic reaction to WT hamsters that had been kept for 8 wks under SD conditions. However, the level of adaptation was still less compared to WT hamsters, but this difference was not apparent after 14 wks. In contrast, AR animals did not display any photoperiodic reaction, even after 14 wks in DD. Type VI phase response curves (PRCs) were constructed to better understand the mechanism behind the SD response. In WT hamsters, the photosensitive phase, where light pulses induce phase shifts, was lengthened in SD condition. In DAO hamsters, in contrast, the PRCs were similar under LD and SD conditions with a compressed photosensitive phase corresponding to α. Also, "light-on" induced only weak phase advances of activity-onset, insufficient to compensate for the long endogenous period. The results show that physiological mechanisms necessary for seasonal adaptation are working in DAO hamsters and that it is the inadequate interaction of the LD cycle with the SCN that prevents the photoperiodic reaction. AR hamsters, on the other hand, are incapable of measuring photoperiodic time due to a complete disruption of circadian rhythmicity.


Subject(s)
Behavior, Animal , Circadian Rhythm , Motor Activity , Phodopus/physiology , Photoperiod , Seasons , Adaptation, Physiological , Animals , Biological Clocks , Cricetinae , Female , Male , Phenotype , Photic Stimulation , Suprachiasmatic Nucleus/physiology , Time Factors
11.
Crit Care ; 15(3): R151, 2011 Jun 21.
Article in English | MEDLINE | ID: mdl-21693012

ABSTRACT

INTRODUCTION: Impact of gender on severe infections is in highly controversial discussion with natural survival advantage of females described in animal studies but contradictory to those described human data. This study aims to describe the impact of gender on outcome in mixed intensive care units (ICUs) with a special focus on sepsis. METHODS: We performed a prospective, observational, clinical trial at Charité University Hospital in Berlin, Germany. Over a period of 180 days, patients were screened, undergoing care in three mainly surgical ICUs. In total, 709 adults were included in the analysis, comprising the main population ([female] n = 309, [male] n = 400) including 327 as the sepsis subgroup ([female] n = 130, [male] n = 197). RESULTS: Basic characteristics differed between genders in terms of age, lifestyle factors, comorbidities, and SOFA-score (Sequential Organ Failure Assessment). Quality and quantity of antibiotic therapy in means of antibiotic-free days, daily antibiotic use, daily costs of antibiotics, time to antibiotics, and guideline adherence did not differ between genders. ICU mortality was comparable in the main population ([female] 10.7% versus [male] 9.0%; P = 0.523), but differed significantly in sepsis patients with [female] 23.1% versus [male] 13.7% (P = 0.037). This was confirmed in multivariate regression analysis with OR = 1.966 (95% CI, 1.045 to 3.701; P = 0.036) for females compared with males. CONCLUSIONS: No differences in patients' outcome were noted related to gender aspects in mainly surgical ICUs. However, for patients with sepsis, an increase of mortality is related to the female sex.


Subject(s)
Intensive Care Units/trends , Sepsis/mortality , Sepsis/therapy , Sex Characteristics , Aged , Female , Hospital Mortality/trends , Humans , Longitudinal Studies , Male , Middle Aged , Prospective Studies , Treatment Outcome
13.
Brain Res ; 1343: 14-9, 2010 Jul 09.
Article in English | MEDLINE | ID: mdl-20452333

ABSTRACT

Exposure to Gamma-aminobutyric-acid (GABA)(A)-receptor agonists and N-Methyl-D-Aspartate (NMDA)-antagonists has been demonstrated to induce neurodegeneration in newborn rats. Exogenous erythropoietin (EPO) protects against NMDA antagonist-mediated neuronal death. In this study we evaluated whether EPO is also effective in limiting neurodegeneration of the GABA(A)-mimetic agent propofol in newborn rats. 6 day old rats were randomized to one of four groups and treated with intraperitoneal applications of 3 x 30 mg/kg propofol at 0, 90 and 180 min, propofol in combination with 5000 IU/kg rEPO, propofol in combination with 20,000 IU/kg rEPO or sham injections of PAD II solution as controls. After 24h, brains of the animals were histopathologically examined and a summation score of degenerated cells was calculated for every brain. Propofol increased neuronal degeneration scores from 16,090+/-4336 to 28,860+/-6569 (p<0.01). This effect was completely abolished by low-dose rEPO (14,270+/-4542, p<0.001 versus propofol only; p>0.05 versus controls). In contrast, high-dose rEPO was not protective (23 930+/-8896, p>0.05 versus propofol only). Propofol may cause neuronal death in newborn rat brains, which is prevented by low-dose rEPO but not high-dose rEPO.


Subject(s)
Erythropoietin/administration & dosage , Hypnotics and Sedatives/antagonists & inhibitors , Neuroprotective Agents/pharmacology , Propofol/antagonists & inhibitors , Age Factors , Animals , Animals, Newborn , Dose-Response Relationship, Drug , Drug Interactions/physiology , Erythropoietin/therapeutic use , Hypnotics and Sedatives/toxicity , Injections, Intraperitoneal , Nerve Degeneration/chemically induced , Nerve Degeneration/drug therapy , Nerve Degeneration/prevention & control , Neuroprotective Agents/therapeutic use , Propofol/toxicity , Rats , Treatment Outcome
14.
Biomol NMR Assign ; 3(1): 141-4, 2009 Jun.
Article in English | MEDLINE | ID: mdl-19636966

ABSTRACT

Mutations in the PKD2 gene lead to the development of polycystic kidney disease (PKD). The PKD2 gene codes for polycystin-2, a cation channel with unknown function. The cytoplasmic, C-terminal domain interacts with a large number of proteins including mDia1, alpha-actinin, PIGEA-14, troponin, and tropomyosin. The C-terminal fragment polycystin-2 (680-796) consisting of 117 amino acids contains a putative calcium binding EF-hand. It was produced in Escherichia coli and enriched uniformly with (13)C and (15)N. The backbone and side chain resonances were assigned by multidimensional NMR methods, the obtained chemical shifts are typical for a partially folded protein. The chemical shifts obtained are in line with the existence of two paired helix-loop-helix (HLH) motifs.


Subject(s)
Cytosol/chemistry , Magnetic Resonance Spectroscopy/methods , Protein Serine-Threonine Kinases/chemistry , TRPP Cation Channels/chemistry , Amino Acid Sequence , Carbon Isotopes/chemistry , Molecular Sequence Data , Nitrogen Isotopes/chemistry , Protein Structure, Tertiary , Protein Subunits , Protons , Pyruvate Dehydrogenase Acetyl-Transferring Kinase
15.
Eur J Anaesthesiol ; 26(7): 597-602, 2009 Jul.
Article in English | MEDLINE | ID: mdl-19522051

ABSTRACT

BACKGROUND AND OBJECTIVE: Commonly used anaesthetics can cause neurodegeneration in the developing brain. Sevoflurane, a widely used substance in paediatric anaesthesia, has not been analysed thus far. This study was carried out to investigate the effects of sevoflurane on neuronal cell viability. METHODS: Primary cortical neuronal cultures were prepared from Wistar rat embryos (E18), kept in 100 microl Gibco-Neurobasal-A medium and exposed to 4 and 8 Vol.% sevoflurane for up to 48 h. Cell viability was assessed using the methyltetrazolium assay and was related to untreated controls. To evaluate the role of gamma-aminobutyric acid type A receptors, untreated cells were preincubated with the receptor antagonists gabazine or picrotoxin and were subsequently exposed to 8 Vol.% sevoflurane and the receptor antagonist. Cell viability was assessed and compared with that of sevoflurane-treated controls. RESULTS: Up to 6 (8 Vol.%) and 12 h (4 Vol.%) of exposure to sevoflurane, cell viability was equal when compared with untreated controls. Only longer exposure times led to significantly lowered cell viability. After 12 h of exposure, no significant differences in cell viability were found between these two series. Cell viability of cultures treated with sevoflurane and the receptor antagonists showed no significant differences when compared with sevoflurane-exposed controls. CONCLUSION: These results suggest that sevoflurane does not cause neurodegeneration in primary cortical neurons of the rat following clinically relevant exposure times and concentrations.


Subject(s)
Anesthetics, Inhalation/adverse effects , Cell Survival/drug effects , Methyl Ethers/adverse effects , Neurons/drug effects , Anesthetics, Inhalation/administration & dosage , Animals , Cells, Cultured , Cerebral Cortex/cytology , Cerebral Cortex/drug effects , Dose-Response Relationship, Drug , GABA Antagonists/pharmacology , Methyl Ethers/administration & dosage , Neurons/metabolism , Picrotoxin/pharmacology , Pyridazines/pharmacology , Rats , Rats, Wistar , Receptors, GABA-A/drug effects , Receptors, GABA-A/metabolism , Sevoflurane , Time Factors
16.
J Biol Chem ; 284(36): 24372-83, 2009 Sep 04.
Article in English | MEDLINE | ID: mdl-19546223

ABSTRACT

The PKD1 and PKD2 genes are the genes that are mutated in patients suffering from autosomal dominant polycystic kidney disease. The human PKD2 gene codes for a 968-amino acid long membrane protein called polycystin-2 that represents a cation channel whose activity can be regulated by Ca(2+) ions. By CD, fluorescence, and NMR spectroscopy, we have studied a 117-amino acid-long fragment of the cytoplasmic domain of polycystin-2, polycystin-2-(680-796) that was proposed to contain a Ca(2+)-binding site. NMR structure determination reveals the existence of two Ca(2+)-binding sites in polycystin-2-(680-796) arranged in a typical and an atypical EF-hand motif. In the absence of Ca(2+) the protein forms a dimer that is dissociated by Ca(2+) binding. This dissociation may be related to the Ca(2+) inactivation observed earlier. The calcium affinity of the protein was determined by fluorescence and NMR spectroscopy. At 293 K, the K(D) values for the high and low affinity sites are 55 mum and 179 mum, respectively.


Subject(s)
Calcium/chemistry , Protein Multimerization , TRPP Cation Channels/chemistry , Amino Acid Motifs/genetics , Binding Sites/genetics , Calcium/metabolism , Circular Dichroism , Humans , Mutation , Nuclear Magnetic Resonance, Biomolecular , Polycystic Kidney, Autosomal Dominant/genetics , Polycystic Kidney, Autosomal Dominant/metabolism , Protein Binding/genetics , Protein Structure, Tertiary/genetics , Spectrometry, Fluorescence , TRPP Cation Channels/genetics , TRPP Cation Channels/metabolism
17.
Crit Care ; 12(1): R9, 2008.
Article in English | MEDLINE | ID: mdl-18218076

ABSTRACT

INTRODUCTION: Hyperglycaemia following aneurysmal subarachnoid hemorrhage (SAH) is associated with complications and impaired neurological recovery. The aim of this study was to determine the effect of insulin treatment for glucose control on cerebral metabolism in SAH patients. METHODS: This prospective, nonrandomized study was conducted in 31 SAH patients in an intensive care unit (age 52 +/- 10 years, World Federation of Neurological Surgeons grade 2.9 +/- 1.6). A microdialysis catheter was inserted into the vascular territory of the aneurysm after clipping. Blood glucose levels above 140 mg/dl were treated with intravenous insulin and the microdialysates were analyzed hourly for the first 12 hours of infusion. RESULTS: No hypoglycaemia occurred. Twenty-four patients were treated with insulin for glucose control. Higher age and World Federation of Neurological Surgeons score were risk factors for need for insulin treatment (P < 0.05). Although blood glucose remained stable after initiation of insulin infusion, insulin induced a significant decrease in cerebral glucose at 3 hours after onset of the infusion until the end of the observation period (P < 0.05), reflecting high glucose utilization. The lactate:pyruvate ratio and glutamate did not increase, excluding ischaemia as possible cause of the decrease in glucose. Glycerol tended toward higher values at the end of the observation period (9 to 12 hours), reflecting either tissue damage after SAH or the beginning of cellular distress after insulin infusion. CONCLUSION: Higher SAH grade was among the risk factors for need for insulin. Intensive glycaemic control using insulin induced a decrease of cerebral glucose and a slight increase in glycerol, though blood glucose remained normal. Future studies might detect relevant metabolic derangements when insulin treatment starts at low cerebral glucose levels, and may allow us to design a strategy for avoidance of insulin-induced metabolic crisis in SAH patients.


Subject(s)
Blood Glucose/drug effects , Brain/metabolism , Hyperglycemia/etiology , Hypoglycemic Agents/therapeutic use , Insulin/therapeutic use , Intracranial Aneurysm/complications , Subarachnoid Hemorrhage/complications , Brain/drug effects , Female , Humans , Hyperglycemia/drug therapy , Hypoglycemic Agents/pharmacology , Insulin/pharmacology , Intracranial Aneurysm/blood , Intracranial Aneurysm/metabolism , Male , Microdialysis , Middle Aged , Prospective Studies , Subarachnoid Hemorrhage/blood , Subarachnoid Hemorrhage/etiology
18.
Arch Kriminol ; 220(1-2): 25-35, 2007.
Article in German | MEDLINE | ID: mdl-17879704

ABSTRACT

Autosomal STR typing alone seems to be no sufficient tool for resolving deficiency cases (e.g. cases of questioned paternity or half-sibships). Therefore, we investigated whether the additional analysis of RFLP single locus probes can improve the solution of such complicated kinship cases. We analyzed 207 children and men from 101 families using the AmpFlSTRIdentifiler multiplex PCR kit and three RFLP single locus probes. A comparison between each child and all unrelated men resulted in 11,023 man / child pairs. Less than three excluding STRs were found in 125 child / unrelated man pairs (1.13%). Additional analysis of RFLP results reduced the number of ambiguous cases to 35. Half-sibling pairs were simulated using STR results from 20 cases with high paternity probabilities (group 1) and relatively low paternity probabilities (group 2). Using a commercially available computer program we calculated probabilities for 778 half-sibling pairs. In 35 pairs (4.49%) half-sibling probabilities over 90.0% could be calculated. Additional investigation of RFLP single locus probes did not lead to a more reliable evaluation of these results. The combined investigation of autosomal STRs and RFLP single locus probes can satisfactorily solve deficient paternities but does not contribute to the solution of questioned half-sibships.


Subject(s)
DNA Fingerprinting , Microsatellite Repeats/genetics , Paternity , Polymerase Chain Reaction , Polymorphism, Restriction Fragment Length , Adult , Child , Computer Simulation , Female , Humans , Male , Predictive Value of Tests , Siblings , Software
19.
J Cancer Res Clin Oncol ; 129(9): 503-10, 2003 Sep.
Article in English | MEDLINE | ID: mdl-12884027

ABSTRACT

BACKGROUND: The number of axillary lymph-node metastases is not only a function of disease progression in primary breast cancer, but is also influenced by the intra-mammary location of the tumor. Nevertheless, the prognostic role of the tumor site is discussed controversially. The objective of this study was to analyze the impact of primary-tumor location on axillary lymph-node involvement, relapse, and mortality risk by univariate and multivariate analysis, in patients both with and without systemic and loco-regional treatment. METHOD: Retrospective analysis was conducted on 2,414 patients at the I. Frauenklinik, Ludwig-Maximilians University, Munich and Berlin-Charlottenburg, who underwent R(0) resection of the primary tumor and systematic axillary lymph-node dissection (at least five lymph nodes resected) for UICC I-III-stage breast cancer. Patients with unknown tumor site, multifocal tumor spread, central tumor location, or tumor location within 15 degrees of the border between outer and inner quadrants were excluded from the study. Median observation time was 6.7 years. RESULTS: The primary tumor site was within or between the medial quadrants of the breast in 33.6% of the patients ( n=810) and in the lateral hemisphere of the breast in 66.4% ( n=1,604). Tumor size, histopathological grading, and estrogen receptor status were balanced between patients with lateral and medial tumor location. Metastatic axillary lymph-node involvement was significantly associated with a lateral tumor location ( P<0.0001). The mean number of axillary lymph-node metastases was increased by 29% in cases with lateral tumor location (2.2 vs 1.7, P=0.003). In a multivariate logistic regression analysis allowing for tumor location, estrogen receptor status, grading and tumor size, tumor location was confirmed as a significant risk factor ( P=0.02) for axillary lymph-node involvement. Tumor location, however, did not correlate with either disease-free survival (DFS) or overall survival (OS), by univariate (DFS: P=0.41; OS: P=0.57) or by multivariate analysis (DFS: P=0.16; OS: P=0.98). CONCLUSION: We conclude that there is no sufficient evidence to support any independent prognostic significance of intra-mammary tumor location in early breast cancer. However, medial tumor location may lead to the underestimation of axillary lymph-node involvement.


Subject(s)
Breast Neoplasms/pathology , Lymph Nodes/pathology , Analysis of Variance , Breast Neoplasms/mortality , Breast Neoplasms/therapy , Female , Humans , Lymphatic Metastasis , Middle Aged , Multivariate Analysis , Neoplasm Recurrence, Local/diagnosis , Prevalence , Prognosis , Survival Analysis , Time Factors
20.
Anesthesiology ; 96(3): 588-94, 2002 Mar.
Article in English | MEDLINE | ID: mdl-11873032

ABSTRACT

BACKGROUND: Unconscious processing of words during general anesthesia has been suggested after surgery with several tests of implicit memory. Patients can neither recall those words nor do they have explicit memories of other intraoperative events. It is unclear to what degree information is processed during general anesthesia and which tests are best suited to detect implicit memory. In the current study, a lexical decision paradigm not previously used to demonstrate implicit memory during anesthesia was used. METHODS: Sixty patients undergoing lumbar disc surgery were assigned to receive isoflurane infusion- or propofol infusion-based anesthesia combined with alfentanil infusions and a nitrous oxide-oxygen mixture. A control group of 10 medical students listened to tapes without receiving anesthesia. Two tapes, each containing a list of 30 low-frequency German nouns repeated for 15 min, were prepared, with half of the patients listening to tape A and the other half listening to tape B during the operation. Exposure time was 15 min from the time of skin incision onward. In the test phase, approximately 7 h later, words from lists A and B plus 60 nonwords were presented in random order by a computer program. Subjects were asked to indicate, by pressing one of two response buttons, whether the spoken word was or was not a legal German word (lexical decision). RESULTS: A recognition test revealed chance recognition for words presented during anesthesia. Lexical decision responses, however, were slightly faster to primed (previously presented) words than to unprimed (not previously presented) words when the entire group of patients was tested, suggesting a small implicit memory effect, which barely failed to reach the significance level. When the two medication groups were tested separately, no significant implicit memory effect could be ascertained statistically. The effects of previous exposure were much more pronounced in the control group. CONCLUSIONS: Balanced anesthesia techniques with isoflurane or propofol lead to only a minimal, statistically borderline implicit memory effect in the lexical decision paradigm.


Subject(s)
Anesthesia, Inhalation , Anesthesia, Intravenous , Anesthetics, Inhalation , Anesthetics, Intravenous , Memory/drug effects , Propofol , Acoustic Stimulation , Adult , Alfentanil , Cognition/drug effects , Female , Humans , Intervertebral Disc/surgery , Intraoperative Period/psychology , Male , Mental Processes/drug effects , Mental Recall/drug effects , Mental Recall/physiology , Nitrous Oxide , Orthopedic Procedures , Sample Size
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