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Biomedical subjects

Jan de Gans

Publications and source records attributed to Jan de Gans.

At least 19 recordsLinked to original sources
PubMed2007

Procoagulant and fibrinolytic activity in cerebrospinal fluid from adults with bacterial meningitis.

OBJECTIVES: This study investigated levels of coagulation and fibrinolysis factors in cerebrospinal fluid (CSF) from adults with bacterial meningitis in relation to development of brain infarction. METHODS: CSF was collected from 92 adults with community-acquired bacterial meningitis, who participated in the prospective Dutch Meningitis Cohort Study; 8 patients with viral meningitis and 9 healthy control subjects. Levels of proteins involved in the coagulation cascade were determined by means of immunoassays. RESULTS: Bacterial meningitis was accompanied by local activation of coagulation, as shown by significantly higher CSF soluble tissue factor (P<0.001) and prothrombin fragment F1+2 concentrations (P<0.001) as compared to viral meningitis patients and controls. This was accompanied by a significantly higher D-dimer formation (P<0.001). In addition, in bacterial meningitis fibrinolysis was attenuated, since CSF plasminogen activator inhibitor (PAI)-1 levels were significantly higher as compared to the controls (P=0.02). In patients with bacterial meningitis who developed brain infarction, CSF PAI-1 levels were higher than in those without infarction (P=0.04). CONCLUSIONS: Activation of coagulation and attenuation of fibrinolysis in the CSF are important features of bacterial meningitis; the net effect on fibrin turnover may contribute to the development of brain infarction.

Adolescent↗
PubMed2006

Attenuated cerebrospinal fluid leukocyte count and sepsis in adults with pneumococcal meningitis: a prospective cohort study.

BACKGROUND: A low cerebrospinal fluid (CSF) white-blood cell count (WBC) has been identified as an independent risk factor for adverse outcome in adults with bacterial meningitis. Whereas a low CSF WBC indicates the presence of sepsis with early meningitis in patients with meningococcal infections, the relation between CSF WBC and outcome in patients with pneumococcal meningitis is not understood. METHODS: We examined the relation between CSF WBC, bacteraemia and sepsis in a prospective cohort study that included 352 episodes of pneumococcal meningitis, confirmed by CSF culture, occurring in patients aged >16 years. RESULTS: CSF WBC was recorded in 320 of 352 episodes (91%). Median CSF WBC was 2530 per mm3 (interquartile range 531-6983 per mm3) and 104 patients (33%) had a CSF WBC <1000/mm3. Patients with a CSF WBC <1000/mm3 were more likely to have an unfavourable outcome (defined as a Glasgow Outcome Scale score of 1-4) than those with a higher WBC (74 of 104 [71%] vs. 87 of 216 [43%]; P < 0.001). CSF WBC was significantly associated with blood WBC (Spearman's test 0.29), CSF protein level (0.20), thrombocyte count (0.21), erythrocyte sedimentation rate (-0.15), and C-reactive protein levels (-0.18). Patients with a CSF WBC <1000/mm3 more often had a positive blood culture (72 of 84 [86%] vs. 138 of 196 [70%]; P = 0.01) and more often developed systemic complications (cardiorespiratory failure, sepsis) than those with a higher WBC (53 of 104 [51%] vs. 69 of 216 [32%]; P = 0.001). In a multivariate analysis, advanced age (Odds ratio per 10-year increments 1.22, 95%CI 1.02-1.45), a positive blood culture (Odds ratio 2.46, 95%CI 1.17-5.14), and a low thrombocyte count on admission (Odds ratio per 100,000/mm3 increments 0.67, 95% CI 0.47-0.97) were associated with a CSF WBC <1000/mm3. CONCLUSION: A low CSF WBC in adults with pneumococcal meningitis is related to the presence of signs of sepsis and systemic complications. Invasive pneumococcal infections should possibly be regarded as a continuum from meningitis to sepsis.

Adult↗
PubMed2006

Community-acquired Listeria monocytogenes meningitis in adults.

BACKGROUND: Listeria monocytogenes is the third most common cause of bacterial meningitis. METHODS: We prospectively evaluated 30 episodes of community-acquired L. monocytogenes meningitis, confirmed by culture of cerebrospinal fluid specimens, in a nationwide study in The Netherlands. Outcome was graded using the Glasgow outcome score; an unfavorable outcome was defined as a score of 1-4. RESULTS: We found 30 episodes of L. monocytogenes meningitis. All patients were immunocompromised or > 50 years old. In 19 (63%) of 30 patients, symptoms were present for > 24 h; in 8 patients (27%), symptoms were present for > or = 4 days. The classic triad of fever, neck stiffness, and change in mental status was present in 13 (43%) of 30 patients. An individual cerebrospinal fluid indicator of bacterial meningitis was present in 23 (77%) of 30 cases. Gram staining of cerebrospinal fluid samples revealed the causative organism in 7 (28%) of 25 cases. The initial antimicrobial therapy was amoxicillin based for 21 (70%) of 30 patients. The coverage of initial antimicrobial therapy was microbiologically inadequate for 9 (30%) of the patients. The mortality rate was 17% (5 of 30), and 8 (27%) of 30 patients experienced an unfavorable outcome. Inadequate initial antimicrobial therapy was not related to outcome. CONCLUSIONS: In contrast with previous reports, we found that patients with meningitis due to L. monocytogenes do not present with atypical clinical features; however, typical cerebrospinal fluid findings predictive for bacterial meningitis might be absent. A high proportion of patients received initial antimicrobial therapy that did not cover L. monocytogenes.

Adult↗
PubMed2006

Soluble triggering receptor expressed on myeloid cells 1: a biomarker for bacterial meningitis.

OBJECTIVE: To evaluate whether soluble triggering receptor expressed on myeloid cells 1 (sTREM-1) in CSF can serve as a biomarker for the presence of bacterial meningitis and outcome in patients with this disease. DESIGN: Retrospective study of diagnostic accuracy. SETTING AND PATIENTS: CSF was collected from 92 adults with community-acquired bacterial meningitis who participated in the prospective Dutch Meningitis Cohort Study; 8 patients with viral meningitis and 9 healthy control subjects. RESULTS: CSF sTREM-1 levels were higher in patients with bacterial meningitis (median 82 pg/ml, range 0-988) than in those with viral meningitis (0 pg/ml, 0-48) and controls (0 pg/ml, 0-36). The diagnostic accuracy of sTREM-1 in discriminating between patients with and without bacterial meningitis, expressed as the area under the receiver operating characteristic curve, was 0.82. At a cutoff level of 20 pg/ml the sensitivity was 0.73 and specificity 0.77. In patients with bacterial meningitis CSF sTREM-1 levels were associated with mortality (survivors, median 73 pg/ml, range 0-449 pg/ml; nonsurvivors, 15 pg/ml, 0-988). CONCLUSIONS: Measuring sTREM-1 in CSF may be a valuable new additional approach to accurately diagnose bacterial meningitis and identify patients at high risk for adverse outcome. Therefore a prospective study of sTREM-1 as a biomarker in bacterial meningitis is needed.

Biomarkers↗
PubMed2006

Arthritis in adults with community-acquired bacterial meningitis: a prospective cohort study.

BACKGROUND: Although the coexistence of bacterial meningitis and arthritis has been noted in several studies, it remains unclear how often both conditions occur simultaneously. METHODS: We evaluated the presence of arthritis in a prospective nationwide cohort of 696 episodes of community-acquired bacterial meningitis, confirmed by culture of cerebrospinal fluid, which occurred in patients aged >16 years. The diagnosis of arthritis was based upon the judgment of the treating physician. To identify differences between groups Fisher exact statistics and the Mann-Whitney U test were used. RESULTS: Arthritis was recorded in 48 of 696 (7%) episodes of community-acquired bacterial meningitis in adults. Joint-fluid aspirations were performed in 23 of 48 patients (48%) and joint-fluid cultures yielded bacteria in 6 of 23 patients (26%). Arthritis occurred most frequently in patients with meningococcal meningitis (12%). Of the 48 patients with bacterial meningitis and coexisting arthritis, four died (8%) and 10 (23%) had residual joint symptoms. CONCLUSION: Arthritis is a common manifestation in patients with community-acquired bacterial meningitis. Functional outcome of arthritis in bacterial meningitis is generally good because meningococcal arthritis is usually immune-mediated, and pneumococcal arthritis is generally less deforming than staphylococcal arthritis. Nevertheless, additional therapeutic measures should be considered if clinical course is complicated by arthritis. In patients with infectious arthritis prolonged antibiotic therapy is mandatory.

Adolescent↗
PubMed2006

Dexamethasone and long-term outcome in adults with bacterial meningitis.

OBJECTIVE: This follow-up study of the European Dexamethasone Study was designed to examine the potential harmful effect of adjunctive dexamethasone treatment on long-term neuropsychological outcome in adults with bacterial meningitis. METHODS: Neurological, audiological, and neuropsychological examinations were performed in adults who survived pneumococcal or meningococcal meningitis. RESULTS: Eighty-seven of 99 (88%) eligible patients were included in the follow-up study; 46 (53%) were treated with dexamethasone and 41 (47%) with placebo. Median time between meningitis and testing was 99 months. Neuropsychological evaluation showed no significant differences between patients treated with dexamethasone and placebo. The proportions of patients with persisting neurological sequelae or hearing loss were similar in the dexamethasone and placebo groups. The overall rate of cognitive dysfunction did not differ significantly between patients and control subjects; however, patients after pneumococcal meningitis had a higher rate of cognitive dysfunction (21 vs 6%; p = 0.05) and experienced more impairment of everyday functioning due to physical problems (p = 0.05) than those after meningococcal meningitis. INTERPRETATION: Treatment with adjunctive dexamethasone is not associated with an increased risk for long-term cognitive impairment. Adults who survive pneumococcal meningitis are at significant risk for long-term neuropsychological abnormalities.

Adult↗
PubMed2006

Clinical features, complications, and outcome in adults with pneumococcal meningitis: a prospective case series.

BACKGROUND: Bacterial meningitis is a grave disease of high incidence, especially in less developed countries. Here, we describe its clinical presentation, spectrum of complications, prognostic factors, and outcome in adults with pneumococcal meningitis. METHODS: From October, 1998, to April, 2002, we assessed 352 episodes of community-acquired pneumococcal meningitis, confirmed by culture of cerebrospinal fluid (CSF), which occurred in patients older than 16 years. Predictors for an unfavourable outcome (Glasgow outcome scale score 1-4) were identified by logistic regression with multiple imputation techniques. FINDINGS: 245 (70%) episodes of pneumococcal meningitis were associated with an underlying disorder. Cranial CT was done for 85% of episodes and revealed underlying disorders in 17% (50/299) and meningitis-associated intracranial complications in 39% (117/299). Independent predictors for an unfavourable outcome were a low score on the Glasgow coma scale, cranial nerve palsies, a raised erythrocyte sedimentation rate, a CSF leucocyte count less than 1000 cells per mm(3), and a high CSF protein concentration on admission. Overall in-hospital mortality was 30%. Prevalence of neurological and systemic complications did not differ between patients aged younger than 60 years and those aged 60 years and older; however, systemic complications were the cause of death in 59% (32/54) of fatal episodes in patients aged 60 years and older, whereas neurological complications were the cause of death in 65% (20/31) of fatal episodes in younger patients. INTERPRETATION: Pneumococcal meningitis is associated with high mortality and morbidity rates in adults. Whereas neurological complications are the leading cause of death in younger patients, elderly patients die predominantly from systemic complications.

Adult↗
PubMed2006

Pneumococcal meningitis in adults: new approaches to management and prevention.

Since the virtual eradication of meningitis due to Haemophilus influenzae type B by vaccination in the developed world, pneumococcal meningitis has become the leading cause of bacterial meningitis beyond the neonatal period. Clinical and experimental research has increased our knowledge about the pathophysiology and pathogenesis of the disease over the past decades. Despite the availability of effective antibiotics, supportive care facilities, and recent advances in adjunctive strategies-ie, adjunctive dexamethasone-mortality and morbidity rates associated with pneumococcal meningitis remain unacceptably high. Although preliminary results after the introduction of the pneumococcal conjugate vaccine are promising, the incidence of multidrug-resistant pneumococcal strains is rising worldwide. Here we discuss clinical aspects of pneumococcal meningitis in adults, with focus on pathophysiology, and stress the urgent need for adequate preventive measures and new effective treatments.

Anti-Infective Agents↗
PubMed2006

Drug Insight: adjunctive therapies in adults with bacterial meningitis.

Despite the availability of effective antibiotics, mortality and morbidity rates associated with bacterial meningitis are high. Studies in animals have shown that bacterial lysis, induced by treatment with antibiotics, leads to inflammation in the subarachnoid space, which might contribute to an unfavorable outcome. The management of adults with bacterial meningitis can be complex, and common complications include meningoencephalitis, systemic compromise, stroke and raised intracranial pressure. Various adjunctive therapies have been described to improve outcome in such patients, including anti-inflammatory agents, anticoagulant therapies, and strategies to reduce intracranial pressure. Although a recent randomized trial provided evidence in favor of dexamethasone treatment, few randomized clinical studies are available for other adjunctive therapies in adults with bacterial meningitis. This review briefly summarizes the pathogenesis and pathophysiology of bacterial meningitis, and focuses on the evidence for and against use of the available adjunctive therapies in clinical practice.

Adult↗
PubMed2006

Community-acquired bacterial meningitis in older people.

OBJECTIVES: To describe clinical features of bacterial meningitis in older people. DESIGN: Cohort study. SETTING: Hospitals in the Netherlands. PARTICIPANTS: Patients aged over 16 with community-acquired bacterial meningitis, confirmed using cerebrospinal fluid culture. MEASUREMENTS: Data were collected prospectively. The cohort was dichotomized with respect to age (>or=60 vs 17-59). RESULTS: Two hundred fifty-seven of 696 episodes of community-acquired bacterial meningitis (37%) occurred in elderly patients and 439 (63%) in younger adults. Older people more often presented with the triad of fever, neck stiffness, and altered mental status than younger adults (58% vs 36%; P<.001). In older people, meningitis was due to Streptococcus pneumoniae in 176 episodes (68%). In younger adults, Neisseria meningitidis was the most common pathogen, responsible for 221 episodes (50%). Elderly patients more often developed complications than younger adults (72% vs 57%; P<.001), which resulted in a higher mortality rate (34% vs 13%; P<.001). Older people tended to die more often from cardiorespiratory failure (25% vs 11%; P=.06), whereas younger adults more often died from brain herniation (23% vs 2%; P=.004). CONCLUSION: Elderly patients with bacterial meningitis often present with classic symptoms of bacterial meningitis. Bacterial meningitis within this age group is predominantly due to S. pneumoniae and is associated with high morbidity and mortality rates. Whereas older people die frequently of cardiorespiratory failure, younger adults more often die of brain herniation.

Adolescent↗
PubMed2006

Dexamethasone in adults with community-acquired bacterial meningitis.

Bacterial meningitis in adults is a severe disease with high fatality and morbidity rates. Experimental studies have shown that the inflammatory response in the subarachnoid space is associated with an unfavourable outcome. In these experiments, corticosteroids, and in particular dexamethasone, were able to reduce the inflammatory cascades in the subarachnoid space. The use of corticosteroids as adjunctive therapy in adults with bacterial meningitis has been evaluated in six studies, performed over a time period of 40 years. Most studies on adjunctive dexamethasone therapy in adults with bacterial meningitis were limited by methodological flaws. In 2002, a study with sufficient statistical power to show significant differences was published. This European Dexamethasone Study showed that adjunctive dexamethasone therapy reduced the rate of unfavourable outcomes in adults with bacterial meningitis from 25% to 15%. In this study, adjunctive treatment with dexamethasone was given before or with the first dose of antibacterials, without serious adverse effects. A quantitative review showed a consistent beneficial effect of dexamethasone on mortality and a borderline statistical beneficial effect on neurological sequelae. On the basis of the available evidence, adjunctive dexamethasone therapy should be initiated before or with the first dose of antibacterials and continued for 4 days in all adults with suspected or proven bacterial meningitis, regardless of bacterial aetiology. In patients with both meningitis and septic shock, dexamethasone therapy cannot be unequivocally recommended, but the use of lower doses seems reasonable at present. Since prompt use of dexamethasone and appropriate antibacterials improves the prognosis of adults with bacterial meningitis, hospitals will require protocols to include dexamethasone with the initial antibacterial therapy.

Adult↗
PubMed2005

Dexamethasone and prognostic factors in adults with bacterial meningitis.

OBJECTIVE: To determine the effect of dexamethasone on prognostic factors in adults with bacterial meningitis. DESIGN AND SETTING: A post hoc multivariate analysis of the European Dexamethasone Study. PATIENTS AND PARTICIPANTS: Dexamethasone-treated patients in the European Dexamethasone Study. As internal validation we performed an identical analysis on patients in the placebo group. MEASUREMENTS AND RESULTS: Only focal cerebral abnormalities on admission were predictive for unfavourable outcome in patients treated with early adjunctive dexamethasone (Odds ratio 3.22; 95% confidence interval 1.11-9.35; P=0.03). Other potential prognostic factors failed to achieve statistical significance. An analysis on patients in the placebo group showed prognostic factors comparable with those found in the literature without routine use of dexamethasone. CONCLUSIONS: Routine use of dexamethasone therapy may lead towards new risk stratification in adults with bacterial meningitis.

Adult↗
PubMed2005

Cognitive outcome in adults with moderate disability after pneumococcal meningitis.

OBJECTIVES: To assess cognitive outcome and quality of life in patients with moderate disability after bacterial meningitis as compared to patients with good recovery. METHODS: Neuropsychological evaluation was performed in 40 adults after pneumococcal meningitis; 20 patients with moderate disability at discharge on the glasgow outcome scale (GOS score 4) and 20 with good recovery (GOS score 5). RESULTS: Patients with GOS score 4 had similar test results as compared to patients with GOS score 5 for the neuropsychological domains 'intelligence', 'memory' and 'attention and executive functioning'. Patients with GOS score 4 showed less cognitive slowness than patients with GOS score 5. In a linear regression analysis cognitive speed was related to current intelligence, years of education and time since meningitis. Overall performance on the speed composite score correlated significantly with time since meningitis (-0.62; P<0.001). Therefore, difference between both groups may have been related to a longer time between meningitis and testing for GOS four patients (29 vs. 12 months; P<0.001). CONCLUSIONS: Patients with moderate disability after bacterial meningitis are not at higher risk for neuropsychological abnormalities than patients with good recovery. In addition, cognitive slowness after bacterial meningitis may be reversible in time.

Adolescent↗
PubMed2005

Adjunctive Corticosteroids in Adults with Bacterial Meningitis.

Bacterial meningitis is a complex disorder in which neurologic injury is caused, in part, by the causative organism and, in part, by the host's own inflammatory response. In studies of experimental bacterial meningitis, adjuvant treatment with corticosteroids, specifically dexamethasone, has beneficial effects. On the basis of these experimental studies, several clinical trials were undertaken to determine the effects of adjunctive corticosteroids in patients with bacterial meningitis. On the basis of overall benefit without detrimental effects by subgroup analysis, dexamethasone therapy should be initiated before or with the first dose of antibiotic and should be continued in most patients with community-acquired acute bacterial meningitis. For patients with a low suspicion of meningitis but an urgent need for antibiotics before cerebrospinal fluid can be obtained, we recommend initiation of treatment with dexamethasone, with discontinuation of dexamethasone therapy as soon as the diagnosis has been excluded.

Journal Article↗
PubMed2004

Clinical features and prognostic factors in adults with bacterial meningitis.

BACKGROUND: We conducted a nationwide study in the Netherlands to determine clinical features and prognostic factors in adults with community-acquired acute bacterial meningitis. METHODS: From October 1998 to April 2002, all Dutch patients with community-acquired acute bacterial meningitis, confirmed by cerebrospinal fluid cultures, were prospectively evaluated. All patients underwent a neurologic examination on admission and at discharge, and outcomes were classified as unfavorable (defined by a Glasgow Outcome Scale score of 1 to 4 points at discharge) or favorable (a score of 5). Predictors of an unfavorable outcome were identified through logistic-regression analysis. RESULTS: We evaluated 696 episodes of community-acquired acute bacterial meningitis. The most common pathogens were Streptococcus pneumoniae (51 percent of episodes) and Neisseria meningitidis (37 percent). The classic triad of fever, neck stiffness, and a change in mental status was present in only 44 percent of episodes; however, 95 percent had at least two of the four symptoms of headache, fever, neck stiffness, and altered mental status. On admission, 14 percent of patients were comatose and 33 percent had focal neurologic abnormalities. The overall mortality rate was 21 percent. The mortality rate was higher among patients with pneumococcal meningitis than among those with meningococcal meningitis (30 percent vs. 7 percent, P<0.001). The outcome was unfavorable in 34 percent of episodes. Risk factors for an unfavorable outcome were advanced age, presence of otitis or sinusitis, absence of rash, a low score on the Glasgow Coma Scale on admission, tachycardia, a positive blood culture, an elevated erythrocyte sedimentation rate, thrombocytopenia, and a low cerebrospinal fluid white-cell count. CONCLUSIONS: In adults presenting with community-acquired acute bacterial meningitis, the sensitivity of the classic triad of fever, neck stiffness, and altered mental status is low, but almost all present with at least two of the four symptoms of headache, fever, neck stiffness, and altered mental status. The mortality associated with bacterial meningitis remains high, and the strongest risk factors for an unfavorable outcome are those that are indicative of systemic compromise, a low level of consciousness, and infection with S. pneumoniae.

Acute Disease↗