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2.
J Thromb Haemost ; 4(12): 2547-52, 2006 Dec.
Article in English | MEDLINE | ID: mdl-17002662

ABSTRACT

BACKGROUND: Platelet hyperfunction contributes to acute coronary syndromes (ACS). Thus, we hypothesized that platelet function under high shear stress predicts recurrent ACS during long-term follow-up of ACS patients. PATIENTS AND METHODS: Consecutive ACS patients (n = 208) were prospectively followed-up for an average of 28 months. Platelet function was measured with the platelet function analyzer (PFA-100; Dade Behring, Marburg, Germany) at baseline for collagen/adenosine diphosphate closure times (CADP-CT) and for collagen/epinephrine closure times (CEPI-CT) after infusion of a uniform dose of 250 mg aspirin. RESULTS: Of the conventional risk factors, only the prevalence of diabetes was higher in ACS patients with re-events. However, use of clopidogrel and use of beta blockers were also slightly lower in patients with re-events (P < 0.05). The unadjusted risk hazard ratio (HR) for re-events was 3.3 [95% confidence interval (95% CI): 1.4-7.4; P = 0.005] in those patients with the shortest CADP-CT values (lowest quartile). Similarly, the risk was 2.0-fold higher (95% CI: 1.1-3.6; P = 0.02) in ACS patients with CEPI-CT < 300 s as compared with CEPI-CT >or = 300 s. Inclusion of diabetes, clopidogrel and beta blockers in a multivariate Cox regression model enhanced the predictive value of CEPI-CT (HR: 2.7). Inclusion of von Willebrand factor levels did not alter the HR for recurrent ACS (HR: 2.1; 95% CI: 1.1-5.2; P = 0.03) for CEPI-CT < 300 s, but reduced the HR for CADP-CT (HR: 2.8, 95% CI: 0.8-9.8; P = 0.11). CONCLUSION: Shortened CT values reflect biologically relevant platelet hyperfunction in patients with ACS because they predict recurrent ACS.


Subject(s)
Coronary Disease/blood , Coronary Disease/prevention & control , Platelet Activation , Acute Disease , Adrenergic beta-Antagonists/therapeutic use , Aspirin/pharmacology , Clopidogrel , Coronary Disease/drug therapy , Coronary Disease/etiology , Coronary Disease/mortality , Diabetes Complications/blood , Female , Follow-Up Studies , Humans , Kaplan-Meier Estimate , Male , Middle Aged , Odds Ratio , Platelet Activation/drug effects , Platelet Aggregation Inhibitors/pharmacology , Platelet Aggregation Inhibitors/therapeutic use , Platelet Function Tests , Predictive Value of Tests , Proportional Hazards Models , Prospective Studies , Recurrence , Research Design , Risk Assessment , Stress, Mechanical , Syndrome , Ticlopidine/analogs & derivatives , Ticlopidine/therapeutic use , Time Factors , von Willebrand Factor/metabolism
3.
Presse Med ; 34(15): 1059-64, 2005 Sep 10.
Article in French | MEDLINE | ID: mdl-16334880

ABSTRACT

OBJECTIVE: The purpose of this project was to study the clinical feasibility of videophone-based communication between patients in their homes, and the care teams who work in the Home Hospitalization department (HH). METHODS: This pilot study of videophone users compared them with a group of control patients also in HH. They came from either the adult, maternity or pediatric departments. Patients who met the inclusion criteria and consented to participate in the study were randomly assigned to one of two groups: those who had a videophone installed in their homes (telemedicine group), and those who received the standard HH care (control group). Sixteen patients in the telemedicine group were matched with 16 from the control group, according to age, Karnofsky Index score, and the reason for HH admission. RESULTS: The mean videophone call lasted six minutes, and patients averaged 23 calls each over the study period (0.7 calls per patient per working day). The videophone enabled better follow-up of wounds: for example, the nurse could transmit photos from the patient's home for real-time coordination. It was also useful for following patients suffering from pain, for technical nursing care, and for educating patients and their caregivers. Anxiety (measured with the Hospital Anxiety and Depression Scale) diminished during the study period for the telemedicine patients, compared with the control group (p=0.048). Within the telemedicine group, all patients and their families were very satisfied or satisfied with their care and with the communication (15/15), although the staff's level of satisfaction was slightly lower (14/16); there were no significant differences between groups. CONCLUSION: The ViSaDom program indicates that videophone communication is feasible and acceptable and could be a useful tool for improving the quality, efficiency and effectiveness of care.


Subject(s)
Home Care Services, Hospital-Based , Telemedicine , Activities of Daily Living , Adult , Aged , Aged, 80 and over , Data Interpretation, Statistical , Depression/diagnosis , Depression/etiology , Female , Hospital Departments , Hospitalization , Hospitals, University , Humans , Karnofsky Performance Status , Male , Middle Aged , Patient Education as Topic , Pilot Projects , Telemedicine/ethics , Telemedicine/instrumentation , Telemedicine/legislation & jurisprudence , Telephone , Time Factors
4.
Diabet Med ; 22(1): 56-60, 2005 Jan.
Article in English | MEDLINE | ID: mdl-15606692

ABSTRACT

AIM: The presence of a transcapillary arterial-interstitial gradient for glucose (AIG(glu)) in skeletal muscle may be interpreted as a consequence of intact cellular glucose uptake. We hypothesized that the AIG(glu) decreases in Type 2 diabetes mellitus as a consequence of insulin resistance, whereas it remains intact in Type 1 diabetes. METHODS: Glucose concentrations were measured in serum and interstitial space fluid of skeletal muscle during an oral glucose tolerance test (OGTT) in patients with Type 1 and Type 2 diabetes and in young and middle-aged healthy volunteers, using microdialysis. RESULTS: The area under the curve for glucose in serum (AUC(SE)) was higher than in interstitial space fluid of skeletal muscle (AUC(MU)) in healthy young (AUC(SE) = 1147 +/- 332 vs. AUC(MU) = 633 +/- 257 mM/min/ml; P = 0.006), healthy middle-aged volunteers (AUC(SE) = 1406 +/- 186 vs. AUC(MU) = 1048 +/- 229 mM/min/ml; P = 0.001) and in Type 1 diabetic patients (AUC(SE) = 2273 +/- 486 vs. AUC(MU) = 1655 +/- 178 mM/min/ml; P = 0.003). In contrast, in Type 2 diabetic patients AUC(SE) (2908 +/- 1023 mM/min/ml) was not significantly different from AUC(MU) (2610 +/- 722 mM/min/ml; P = NS). CONCLUSION: The present data indicate that AIG(glu) is compromised in Type 2 diabetes in contrast to Type 1 diabetes where it appears to be normal. Because no changes in muscle blood flow were detected, insulin resistance appears to be the main cause for the observed decreased AIG(glu) in skeletal muscle in Type 2 diabetic patients.


Subject(s)
Diabetes Mellitus, Type 1/metabolism , Diabetes Mellitus, Type 2/metabolism , Glucose/pharmacokinetics , Muscle, Skeletal/metabolism , Adolescent , Adult , Area Under Curve , Extracellular Fluid/metabolism , Humans , Insulin Resistance , Microdialysis , Middle Aged
5.
Eur J Clin Invest ; 33(2): 141-6, 2003 Feb.
Article in English | MEDLINE | ID: mdl-12588288

ABSTRACT

BACKGROUND: Transcapillary insulin transfer is considered a rate-limiting step in insulin action at supraphysiological insulin concentrations. However, it remains unclear whether this concept also applies for physiological conditions. MATERIALS AND METHODS: In the present study we set out to characterize transcapillary insulin transfer by measuring insulin concentrations in plasma and interstitial space fluid of skeletal muscle during an oral glucose tolerance test and euglycaemic hyperinsulinaemic clamp conditions, respectively. For this purpose we employed in vivo microdialysis of skeletal muscle in conjunction with an ultrasensitive insulin assay in eight healthy lean male volunteers (aged 25 +/- 1 years). RESULTS: Insulin concentrations at baseline were 48 +/- 8 pmol x L(-1) in plasma and 19 +/- 4 pmol x L(-1) in the interstitium (P = 0.002). The mean interstitium to plasma ratio at baseline was 0.48 +/- 0.09 pmol x L(-1). During the oral glucose tolerance test the interstitium to plasma ratio remained unchanged (0.43 +/- 0.12, P = NS vs. baseline), but was significantly reduced during euglycaemic hyperinsulinaemic clamp conditions at steady-state hyperinsulinaemia (0.12 +/- 0.01, P = 0.01 vs. baseline). CONCLUSION: In summary there is a substantial transcapillary insulin gradient in healthy human skeletal muscle under baseline and glucose-stimulated conditions. Our findings support the hypothesis of a saturable transcapillary insulin transport representing a partly rate-limiting step for insulin action.


Subject(s)
Capillary Permeability , Insulin/metabolism , Muscle, Skeletal/blood supply , Adult , Capillaries/metabolism , Cross-Over Studies , Glucose Clamp Technique , Glucose Tolerance Test , Humans , Insulin/blood , Insulin Resistance , Male , Microdialysis
6.
Antimicrob Agents Chemother ; 47(1): 371-4, 2003 Jan.
Article in English | MEDLINE | ID: mdl-12499216

ABSTRACT

We investigated the distribution of the broad-spectrum antibiotic fosfomycin in infected soft tissue of patients with uncomplicated cellulitis of the lower extremities or diabetic foot infection using in vivo microdialysis. Our findings suggest that fosfomycin exhibits good and similar penetration into the fluid in the interstitial space in inflamed and noninflamed soft tissue in patients.


Subject(s)
Cellulitis/metabolism , Diabetic Foot/metabolism , Fosfomycin/pharmacokinetics , Area Under Curve , Female , Fosfomycin/blood , Half-Life , Humans , Male , Microdialysis , Middle Aged , Tissue Distribution
7.
J Neural Transm Suppl ; (62): 293-301, 2002.
Article in English | MEDLINE | ID: mdl-12456072

ABSTRACT

Alzheimer's disease (AD) is a neurodegenerative disorder for which there is no cure or effective treatment. One of the major neuropathological signatures of AD is the deposition of amyloid plaques in the brain of affected people. Although the role of these structures in the pathogenesis of the disease is not fully understood, recent findings have provided evidence that amyloid may be a key player in the disease. Therefore, preventing and reversing cerebral amyloid deposition have become an attractive therapeutic strategy for AD. We have engineered synthetic beta-sheet breaker peptides to bind soluble amyloid peptide and prevent and reverse its conversion to the beta-sheet rich aggregated structure, precursor of the amyloid plaques. Results in vitro, in cell culture and in vivo suggest that beta-sheet breaker peptides might be candidates for an AD-therapy focused to reduce amyloid deposition.


Subject(s)
Alzheimer Disease/drug therapy , Amyloid/chemistry , Amyloid/drug effects , Protein Structure, Secondary/drug effects , Aged , Amino Acid Sequence , Amyloid beta-Peptides/chemistry , Drug Design , Humans , Molecular Sequence Data , Peptide Fragments/chemistry
8.
Clin Pharmacol Ther ; 70(6): 532-9, 2001 Dec.
Article in English | MEDLINE | ID: mdl-11753269

ABSTRACT

OBJECTIVE: Patients with peripheral arterial occlusive disease are prone to soft tissue infections and frequently require antibiotics. To date, however, it is not known whether improvement of arterial blood flow by angioplasty of stenosis increases antibiotic concentrations in ischemic lesions. PATIENTS AND METHODS: All patients were scheduled to undergo elective percutaneous transluminal angioplasty (n = 10). Following a single, 400-mg dose of ciprofloxacin, drug concentrations in plasma, ischemic and healthy soft tissue; arterial peak systolic velocity; and ankle-brachial pressure index were assessed before and after angioplasty. Unbound ciprofloxacin concentrations were measured at the site of infection with use of in vivo microdialysis. RESULTS: Angioplasty increased peak systolic velocity and ankle-brachial pressure index compared with baseline (P <.002). Before angioplasty area under concentration-time curve (AUC(0-300)) values for ciprofloxacin were lower in ischemic tissue than in healthy tissue, with median values of 7.1 mg.h/L (range, 3.5-13.0) and 11.3 mg.h/L (range, 3.4-19.0), respectively (P =.03). After angioplasty AUC(0-300) values were identical in ischemic and healthy adipose tissue; median AUC(0-300) values were 8.0 mg.h/L (range, 4.0-20.7) and 8.5 mg.h/L (range, 4.4-22.9), respectively (P =.7). A combined in vivo pharmacokinetic/in vitro pharmacodynamic simulation based on tissue concentration data indicates that this difference in pharmacokinetics is also reflected in antimicrobial effect. CONCLUSION: Antibiotic concentrations are reduced significantly in ischemic lesions compared to those of healthy adipose tissue in patients with peripheral arterial occlusive disease. From the present data it might be speculated that improvement of arterial blood flow at the affected extremity is associated with increased cure rates of soft tissue infections in these patients.


Subject(s)
Angioplasty , Anti-Infective Agents/pharmacokinetics , Arterial Occlusive Diseases/metabolism , Ciprofloxacin/pharmacokinetics , Adipose Tissue/metabolism , Aged , Aged, 80 and over , Anti-Infective Agents/adverse effects , Anti-Infective Agents/pharmacology , Area Under Curve , Arterial Occlusive Diseases/surgery , Chromatography, High Pressure Liquid , Ciprofloxacin/adverse effects , Ciprofloxacin/pharmacology , Female , Half-Life , Hemodynamics/physiology , Humans , Ischemia/metabolism , Male , Microbial Sensitivity Tests , Microdialysis , Middle Aged , Vascular Surgical Procedures
9.
FEBS Lett ; 509(3): 451-6, 2001 Dec 14.
Article in English | MEDLINE | ID: mdl-11749972

ABSTRACT

A hallmark event in transmissible spongiform encephalopathies is the conversion of the physiological prion protein into the disease-associated isoform. A natural polymorphism at codon 129 of the human prion gene, resulting in either methionine or valine, has profound influence on susceptibility and phenotypic expression of the disease in humans. In this study, we investigated the local propensity of synthetic peptides, corresponding to the region of the polymorphism and containing either methionine or valine, to adopt a beta-sheet-rich structure similar to the pathological protein. Circular dichroism studies showed that the methionine-containing peptide has a greater propensity to adopt a beta-sheet conformation in a variety of experimental conditions. The higher beta-sheet tendency of this peptide was also associated with an increased ability to aggregate into amyloid-like fibrils. These results suggest that methionine at position 129 of the prion protein increases its susceptibility to switch to the abnormal conformation, in comparison with the presence of valine at the same position.


Subject(s)
Polymorphism, Genetic/genetics , Prions/chemistry , Prions/genetics , Amyloid/genetics , Amyloid/metabolism , Amyloid/ultrastructure , Circular Dichroism , Genetic Predisposition to Disease/genetics , Humans , Microscopy, Electron , Peptide Fragments/chemical synthesis , Peptide Fragments/chemistry , Peptide Fragments/ultrastructure , Prion Diseases/genetics , Prion Diseases/metabolism , Prions/ultrastructure , Protein Isoforms/chemistry , Protein Isoforms/genetics , Protein Structure, Secondary , Time Factors
10.
Crit Care Med ; 29(2): 385-91, 2001 Feb.
Article in English | MEDLINE | ID: mdl-11246321

ABSTRACT

OBJECTIVE: Current guidelines for adjusting antimicrobial therapy regimens commonly are based on drug concentrations measured in plasma. In septic patients, however, the interstitial space of soft tissues in addition to the central compartment represents the target site of infection. We thus hypothesized that one explanation for therapeutic failure during antibiotic treatment might be the inability to achieve effective antimicrobial concentrations in the interstitial space fluid of soft tissues. This is corroborated by the fact that piperacillin, a frequently administered beta-lactam antibiotic, often fails to be effective despite documented susceptibility of the causative pathogen in vitro. DESIGN: Prospective comparative study of two groups. SETTING: The intensive care unit and research ward of an university hospital. SUBJECTS: Six patients with septic shock and a control group of six gender- and age-matched healthy volunteers. INTERVENTIONS: To measure piperacillin penetration into the interstitial space fluid of skeletal muscle and subcutaneous adipose tissue, we employed microdialysis after a single intravenous administration of 4.0 g of piperacillin to patients and healthy volunteers. Piperacillin concentrations were assayed by using reversed-phase high-pressure liquid chromatography. MEASUREMENTS AND MAIN RESULTS: In septic shock patients, interstitial piperacillin concentrations in skeletal muscle and subcutaneous adipose tissue were five- to ten-fold lower than corresponding free plasma concentrations (p <.03). Mean piperacillin concentrations in subcutaneous adipose tissue never exceeded 11 microg/mL, which is below the minimal inhibitory concentration for a range of relevant pathogens in patients with septic shock. CONCLUSION: The results of the present study demonstrate that in septic shock patients, piperacillin concentrations in the interstitial space may be subinhibitory, even though effective concentrations are attained in plasma. The lack of success of antimicrobial therapy in these patients thus might be attributable to inadequate target site penetration of antibiotics.


Subject(s)
Adipose Tissue/drug effects , Anti-Bacterial Agents/pharmacokinetics , Anti-Bacterial Agents/therapeutic use , Drug Delivery Systems/adverse effects , Muscle, Skeletal/drug effects , Piperacillin/pharmacokinetics , Piperacillin/therapeutic use , Shock, Septic/drug therapy , Adipose Tissue/chemistry , Aged , Anti-Bacterial Agents/analysis , Anti-Bacterial Agents/blood , Case-Control Studies , Chromatography, High Pressure Liquid , Drug Delivery Systems/standards , Drug Monitoring , Female , Humans , Infusions, Intravenous , Male , Microbial Sensitivity Tests , Microdialysis , Middle Aged , Muscle, Skeletal/chemistry , Piperacillin/analysis , Piperacillin/blood , Practice Guidelines as Topic , Prospective Studies , Shock, Septic/metabolism , Shock, Septic/microbiology , Time Factors , Tissue Distribution , Treatment Failure
11.
Sante Publique ; 13(3): 263-76, 2001 Sep.
Article in French | MEDLINE | ID: mdl-11826845

ABSTRACT

The authors describe the utilisation of a quality assessment tool for palliative care administered at home. The questionnaire entitled Support Team Assessment Schedule (STAS) was translated from English for this study. It was then utilised comparatively with different quality of life evaluation instruments. Only the results of the STAS are described here. The approach allows for the unresolved problems in the care to come to the surface week after week. The STAS comprises nine items pertaining to the patient and his/her family, and seven items concerning the services provided. The study exhibits the results of 107 evaluations completed from 50 patients stricken with cancer or AIDS in an advanced phase. The availability of this auto clinical audit tool, employable at home or in a hospital, constitutes an essential initial step in the field of French-speaking clinical evaluation of palliative care.


Subject(s)
Acquired Immunodeficiency Syndrome/psychology , Attitude to Health , Home Care Services/standards , Neoplasms/psychology , Palliative Care/psychology , Palliative Care/standards , Quality Assurance, Health Care/methods , Quality of Life , Surveys and Questionnaires/standards , Translating , Acquired Immunodeficiency Syndrome/therapy , Adult , Aged , Communication , Family/psychology , Female , France , Humans , Male , Medical Audit , Middle Aged , Needs Assessment , Neoplasms/therapy , Professional-Patient Relations
12.
Antimicrob Agents Chemother ; 44(10): 2728-32, 2000 Oct.
Article in English | MEDLINE | ID: mdl-10991852

ABSTRACT

Fosfomycin is a broad-spectrum antibiotic which is established as therapy for uncomplicated lower urinary tract infections. In addition, preliminary data indicate that fosfomycin has a potential role in the treatment of soft tissue infections. However, the use of fosfomycin has not been established for this condition, and it is unclear whether the level of fosfomycin penetration into human soft tissues is high enough to eradicate relevant pathogens. To better characterize the antibiotic potential of fosfomycin, we applied a combined in vivo pharmacokinetic-in vitro pharmacodynamic model to human volunteers. For this purpose fosfomycin concentrations in vivo in the fluid of the interstitial space of human soft tissues were measured by microdialysis following intravenous infusion of 4 or 8 g of fosfomycin (n = 6). Subsequently, bacterial isolates with relevance for soft tissue infections were exposed to concentrations according to the in vivo pharmacokinetic profile in the interstitial space fluid obtained by microdialysis. Our experiments indicated a high degree of soft tissue penetration for fosfomycin, with ratios of the area under the concentration-time curve from 0 to 8 h for muscle (AUC(0-8(muscle)))/AUC(0-8(serum)) of 0.48+/-0.08 and 0.53+/-0.04 and ratios of AUC(0-8(adipose tissue))/AUC(0-8(serum)) of 0.74+/-0.12 and 0.71+/-0.11 following administration of 4 and 8 g, respectively. In corresponding in vitro simulation experiments with selected isolates of Staphylococcus aureus, Enterobacter cloacae, and Serratia marcescens for which MICs were 16 microg/ml, organisms were undetectable after a single dosing interval. Fosfomycin exhibits a strong ability to penetrate into the fluid of the interstitial space of soft tissues and reaches levels sufficient to substantially inhibit the growth of relevant bacteria at the target site. We therefore conclude that fosfomycin might qualify as an alternative candidate for the therapy of soft tissue infections.


Subject(s)
Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/pharmacokinetics , Extracellular Space/metabolism , Fosfomycin/pharmacology , Fosfomycin/pharmacokinetics , Adipose Tissue/metabolism , Adipose Tissue/microbiology , Adult , Anti-Bacterial Agents/administration & dosage , Area Under Curve , Cross-Over Studies , Extracellular Space/microbiology , Fosfomycin/administration & dosage , Humans , Infusions, Intravenous , Male , Microbial Sensitivity Tests , Microdialysis , Models, Biological , Muscle, Skeletal/metabolism , Muscle, Skeletal/microbiology
13.
Life Sci ; 66(10): PL147-54, 2000.
Article in English | MEDLINE | ID: mdl-10714896

ABSTRACT

The paracrine renin-angiotensin-system (RAS) is increasingly recognized to play an important role in the regulation of both, regional vascular tone and regional glucose metabolism. To date, however, a selective investigation of paracrine RAS effects in an in vivo clinical setting was beyond technical reach. We here set out to selectively study the metabolic effects of paracrine RAS inhibition at different levels in healthy volunteers (n = 8). For this purpose bradykinin, enalaprilate and losartan were administered locally to the interstitial space fluid in skeletal muscle by means of reverse microdialysis and transcapillary glucose transport was measured simultaneously. During reverse microdialysis with bradykinin and enalaprilate a significant decrease in arterial-interstitial-gradient for glucose (AIG(glu)) was observed (from 1.49 +/- 0.08 mM to 0.12 +/- 0.63 mM (p = 0.018) for bradykinin and from 1.5 +/- 0.07 mM to 0.24 +/- 0.67 mM (p = 0.043) for enalaprilate). In contrast, losartan had no effect on AIG(glu). The changes in transcapillary glucose transport during bradykinin and enalaprilate administration were accompanied by significant increases in interstitial lactate levels which was most pronounced for bradykinin (from 0.14 +/- 0.01 mM to 0.40 +/- 0.07 mM, p = 0.018). We conclude that paracrine angiotensin-converting-enzyme (ACE) inhibition but not angiotensin II (AT-II) receptor blockade decreases AIG(glu) and facilitates transcapillary glucose transport due to an increase in interstitial bradykinin concentration. These results support the concept that blood pressure control with ACE-inhibitors but not with AT-II-receptor-antagonists has beneficial long term metabolic consequences in hypertensive, hyperinsulinemic subjects.


Subject(s)
Angiotensin II/metabolism , Angiotensin Receptor Antagonists , Angiotensin-Converting Enzyme Inhibitors/pharmacology , Capillaries/metabolism , Glucose/metabolism , Adult , Biological Transport , Bradykinin/physiology , Enalapril/pharmacology , Humans , Hyperinsulinism/chemically induced , Losartan/pharmacology , Male , Receptors, Angiotensin/metabolism
14.
Stroke ; 30(8): 1598-603, 1999 Aug.
Article in English | MEDLINE | ID: mdl-10436107

ABSTRACT

BACKGROUND AND PURPOSE: The prediction of neurological outcome in comatose cardiac arrest survivors has enormous ethical and socioeconomic implications. The purpose of the present study was to investigate the prognostic relevance of the time course of serum neuron-specific enolase (NSE) as a biochemical marker of hypoxic brain damage. METHODS: Serial analysis of serum NSE levels was performed in 56 patients resuscitated from witnessed, nontraumatic, normothermic, in- or out-of-hospital cardiac arrest. The neurological outcome was evaluated with the use of the cerebral performance category (CPC) within 6 months after restoration of spontaneous circulation (ROSC). The Mann-Whitney U test was used to compare patients with good (CPC 1 to 2) and bad (CPC 3 to 4) neurological outcome. The diagnostic performance at different time points after ROSC was described in terms of areas under receiver operating characteristic curves according to standard methods. RESULTS: Patients with a bad neurological outcome (CPC 3 to 4) had significantly higher NSE levels than those with a good neurological outcome at 12 (P=0.004), 24 (P=0.04), 48 (P<0.001), and 72 hours (P<0.001) after ROSC. The maximum NSE level measured within 72 hours after ROSC was also significantly higher in patients with a bad neurological outcome (P<0.001). The NSE value at 72 hours after ROSC was the best predictor of neurological outcome (area under the curve=0.92+/-0.04). In addition, we also found a significant difference in the time course of NSE concentrations during the first 3 days after ROSC. CONCLUSIONS: Serum NSE levels are valuable adjunctive parameters for assessing neurological outcome after cardiac arrest.


Subject(s)
Brain Ischemia/enzymology , Heart Arrest/enzymology , Phosphopyruvate Hydratase/blood , Resuscitation , Adolescent , Adult , Aged , Biomarkers/blood , Brain/blood supply , Brain/metabolism , Brain Ischemia/etiology , Female , Follow-Up Studies , Heart Arrest/complications , Heart Arrest/therapy , Humans , Hypoxia/enzymology , Hypoxia/etiology , Male , Middle Aged , Predictive Value of Tests , Prospective Studies , Radioimmunoassay , Treatment Outcome
15.
Intensive Care Med ; 25(6): 620-4, 1999 Jun.
Article in English | MEDLINE | ID: mdl-10416916

ABSTRACT

OBJECTIVE: To characterize the effect of the phosphodiesterase inhibitor (PDEI) milrinone in adult patients with a non-hyperdynamic condition during the course of the systemic inflammatory response syndrome (SIRS) or sepsis when compared with patients with congestive heart failure (CHF). PDEIs are potent inhibitors of cytokine production and expression. We hypothesized that there might be an outstanding beneficial effect of PDEIs in the setting of SIRS/sepsis. DESIGN: Prospective, open labeled, protocol-driven pilot study. PATIENTS: Nine patients with a nonhyperdynamic hemodynamic condition during SIRS/sepsis (group 1) and seven patients with CHF (group 2) requiring inotropic support. All patients were having heart disease. All patients had a combination of various catecholamines at the time of inclusion in the study and had received fluid resuscitation to an extent that left ventricular stroke work index (LVSWI) did not increase further. INTERVENTION: Milrinone infusion at a rate of 0.5 microg/kg per min in addition to preexisting catecholamine therapy. MEASUREMENTS AND RESULTS: Measurements of cardiac index (CI; thermodilution) and calculation of vascular resistance and LVSWI was done every 8 h for at least 40 h during milrinone infusion. CI and LVSWI significantly increased in both groups (p < 0.001 and p = 0.006, respectively). There were no significant differences between groups in these parameters (p > 0.11 and p > 0.13, respectively). The LVSWI increase occurred while there was a decrease in pulmonary capillary wedge pressure, suggesting a true and comparable improvement in cardiac function relatively independent of loading conditions. Preexisting catecholamines had to be increased in both groups (NS). Milrinone had to be discontinued in one patient due to hypotension. CONCLUSION: Milrinone administration is feasible in selected patients with a non-hyperdynamic condition during SIRS/sepsis and with preexisting heart disease. Under the conditions of this study, milrinone was no better in terms of CI and LVSWI maintenance in septic cardiac dysfunction when compared with CHF. These results do not necessarily extend to other cohorts with no preexisting heart disease.


Subject(s)
Cardiotonic Agents/therapeutic use , Heart Failure/drug therapy , Milrinone/therapeutic use , Sepsis/drug therapy , Systemic Inflammatory Response Syndrome/drug therapy , Adult , Aged , Female , Heart Failure/physiopathology , Hemodynamics/physiology , Humans , Male , Middle Aged , Pilot Projects , Prospective Studies , Sepsis/physiopathology , Statistics as Topic , Systemic Inflammatory Response Syndrome/physiopathology
16.
Wien Klin Wochenschr ; 111(4): 157-60, 1999 Feb 26.
Article in English | MEDLINE | ID: mdl-10192149

ABSTRACT

We report the case of a 42 years old, non-immunocompromised native Austrian living in Vienna. He presented at home with severe dyspnea and had to be intubated immediately. Shortly after hospital admission, he developed severe adult respiratory distress syndrome (ARDS) and septic shock with massive, bilobar patchy to confluent infiltrations and a need for norepinephrine. A CT-scan revealed severe loss of functional lung tissue with areas of consolidation and multiple communicating cystic spaces. Air leaking into the mediastinum through fistulas produced pneumomediastinum, pneumoperitoneum, and a massive soft tissue emphysema. Bronchoalveolar lavage performed within the first 24 hours of admission revealed + of acid-fast bacilli. Even though appropriate tuberculostatic medication was started immediately, the patient succumbed the next day to ARDS due to massive tuberculous pneumonia and miliary disease (Sepsis tuberculosis gravissima).


Subject(s)
Respiratory Distress Syndrome/pathology , Shock, Septic/pathology , Tuberculosis, Miliary/pathology , Tuberculosis, Pulmonary/pathology , Adult , Austria , Fatal Outcome , Humans , Lung/pathology , Male , Tomography, X-Ray Computed
17.
J Hypertens ; 16(2): 251-5, 1998 Feb.
Article in English | MEDLINE | ID: mdl-9535154

ABSTRACT

OBJECTIVE: To evaluate the course of blood pressure within 12 h of a hypertensive urgency with or without oral antihypertensive treatment prior to discharge of patients from hospital. DESIGN: A prospective, double-blinded, placebo-controlled and randomized clinical trial. SETTING: Department of Emergency Medicine in a 2000-bed inner city hospital. PATIENTS: Forty patients successfully treated for a hypertensive urgency with intravenous administration of urapidil. INTERVENTIONS: We administered 60 mg urapidil orally or placebo prior to discharge of patients from hospital and evaluated the course of blood pressure within 12 h of the urgency by use of an ambulatory blood pressure measurement unit. MAIN OUTCOME MEASURES: Mean systolic and diastolic blood pressures within the first 12 h of a hypertensive urgency and the number of hypertensive and hypotensive episodes. RESULTS: Mean systolic and diastolic blood pressures were significantly lower in members of the urapidil group than they were in members of the placebo group (132 +/- 14 versus 147 +/- 18 mmHg, P = 0.003; 79 +/- 12 versus 87 +/- 14 mmHg, P = 0.047, respectively). The number of hypotensive episodes was similar for these two groups (three versus one, P = 0.32), whereas the number of hypertensive episodes was significantly lower for the urapidil group (13 versus 34, P = 0.001). CONCLUSIONS: Oral medication with urapidil prior to discharge results in lower overall blood pressure levels and reduces the risk of hypertensive episodes recurring within 12 h of a hypertensive urgency. Therefore, we recommend this therapeutic approach for patients with hypertensive urgencies, who are treated with an intravenous antihypertensive drug.


Subject(s)
Antihypertensive Agents/therapeutic use , Blood Pressure/drug effects , Hypertension/drug therapy , Hypertension/physiopathology , Piperazines/therapeutic use , Administration, Oral , Aged , Antihypertensive Agents/administration & dosage , Antihypertensive Agents/adverse effects , Double-Blind Method , Emergencies , Female , Heart Rate/drug effects , Humans , Injections, Intravenous , Male , Middle Aged , Piperazines/administration & dosage , Piperazines/adverse effects , Prospective Studies , Time Factors
18.
J Thorac Imaging ; 12(2): 150-8, 1997 Apr.
Article in English | MEDLINE | ID: mdl-9179827

ABSTRACT

Spiral computed tomography (CT) has shown promising results in the detection of acute pulmonary embolism. The aim of this study was to investigate whether the severity of acute pulmonary embolism could be quantitatively assessed with spiral CT examinations and to test the potential clinical impact of this information. In a consecutive series of 123 patients screened with spiral CT for suspected acute pulmonary embolism, 31 patients (25%) had evidence of emboli. The severity of pulmonary arterial obstruction in those 31 spiral CT examinations was evaluated by two independent observers using angiographic scores previously described by Walsh (29) and Miller (30), adapted to the needs of spiral CT. Clinical patient subgroups were defined according to oxygen saturation, heart rate, and echocardiographic signs of right ventricular strain. CT severity scores were then correlated to each other and to clinical parameters using the Spearman rank test. Interobserver agreement was calculated using the analysis of variance. Both modified Walsh and Miller scores were readily reproducible and showed interobserver agreements of 0.85 and 0.96, respectively (p = 0.001). Patients with mild and marked clinical abnormalities showed statistically significant differences between CT severity scores. Differences between severity scores of patients with moderate and marked clinical abnormalities were somewhat significant. No significant mean severity score differences were seen between patients with mild and moderate clinical abnormalities. Although correlations of severity scores and detailed clinical parameters within the defined subgroups were moderate to poor, threshold scores greater than 10 (Miller) and greater than 11 (Walsh) always indicated marked clinical abnormalities. The modified scores presented in this study constitute a readily reproducible method for the quantitative assessment of acute pulmonary embolism severity on spiral CT examinations.


Subject(s)
Angiography/instrumentation , Pulmonary Embolism/diagnostic imaging , Tomography, X-Ray Computed/instrumentation , Acute Disease , Adult , Aged , Aged, 80 and over , Echocardiography , Female , Heart Rate/physiology , Humans , Male , Middle Aged , Predictive Value of Tests , Pulmonary Embolism/classification , Ventilation-Perfusion Ratio/physiology , Ventricular Function, Right/physiology
19.
Clin Nucl Med ; 22(2): 97-100, 1997 Feb.
Article in English | MEDLINE | ID: mdl-9031766

ABSTRACT

The authors report two patients without coronary artery disease who experienced asystole during the IV infusion of dipyridamole on routine TI-201 myocardial perfusion imaging and review the literature for possible explanations of this rare side effect. Until now, this side effect was only reported in patients with coronary artery disease or beta-blocker therapy. Yet, the cases lacked both concomitant factors and autonomic dysregulation is suggested as a cause for asystole.


Subject(s)
Dipyridamole/adverse effects , Heart Arrest/chemically induced , Vasodilator Agents/adverse effects , Adrenergic beta-Antagonists/therapeutic use , Angina Pectoris/diagnosis , Autonomic Nervous System Diseases/complications , Bradycardia/chemically induced , Coronary Circulation , Coronary Disease/complications , Dipyridamole/administration & dosage , Electrocardiography/drug effects , Exercise Test , Follow-Up Studies , Heart/diagnostic imaging , Humans , Infusions, Intravenous , Male , Middle Aged , Radionuclide Imaging , Radiopharmaceuticals , Thallium Radioisotopes , Vasodilator Agents/administration & dosage
20.
Rev Epidemiol Sante Publique ; 45(5): 429-37, 1997 Oct.
Article in French | MEDLINE | ID: mdl-9446148

ABSTRACT

BACKGROUND: The case management approach is increasing in the elderly population. The organizations which support case management agencies now require an economic assessment. This paper presents a methodology and its test at four experimental sites, in order to measure the costs and the effectiveness of the case management and the willingness to pay of potential users of this procedure. METHODS: Costs were measured from the data collected in 4 agencies. Effectiveness was assessed on the basis of a statistical analysis of 247 care plans, and a survey among health care and social professionals, elderly people and their relatives. A mail survey was used to get data on the willingness to pay. RESULTS: The average cost of the case management was 24.50 F. Effectiveness included several dimensions: management of the available resources according to the patient's incapacity situation, effective implementation of the care plan, and collective learning leading to reduce inter-professional disagreements. Analysis of the willingness to pay indicated that Social Security and local authorities intended to be the main co-payers of case management. CONCLUSIONS: The standard framework of economic analysis is not appropriate for an assessment of case management. New instruments are proposed and results have to be validated by further research.


Subject(s)
Aged , Case Management , Case Management/economics , Case Management/standards , Cost-Benefit Analysis , Costs and Cost Analysis , Evaluation Studies as Topic , Health Personnel , Humans , Social Security
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