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Biomedical subjects

J T van Dissel

Publications and source records attributed to J T van Dissel.

At least 37 records · Page 2Linked to original sources

[Predictive value of chills in patients presenting with fever to urgent care department].

OBJECTIVE: To ascertain the correlation between chills, bacteraemia, infection type and clinical progress in patients presenting with fever to the casualty department. DESIGN: Prospective, descriptive. METHOD: Anamnestic, clinical and microbiological data were registered from patients with fever (> 38.2 degrees C rectal) presenting to the Casualty Department of the Leiden University Hospital and the Bronovo Hospital, in the period 1 February 1994-31 July 1995 respectively 1 February 1996-31 July 1997. RESULTS: A total of 764 patients (424 men and 340 women; median age: 66 years) were included in the study. A chill was reported by 270 patients (35%). Bacteria were isolated from the blood culture in the case of 141 patients (18%). The relative risk (RR) for bacteraemia in the case of a chill was 2.8 (95% CI: 2.1-3.8); the positive predictive value of a chill for bacteraemia was 31% and the negative predictive value 89%. For 683 (89%) of the 764 patients the cause of the fever was probably or certainly an infection, which was mostly pulmonary (319 patients; 42%) or urogenital (112 patients; 15%) in origin. The positive predictive value was 24% for patients with respiratory tract infections and 48% for patients with urinary tract infections. Mortality occurred in the case of 62 patients (8%) after a median admission period of 11 days. The patients who died were older than the patients discharged (p < 0.01) and there was a statistically significant correlation between mortality with bacteraemia (RR: 1.1) and serious comorbidity (RR: 6.1). CONCLUSION: There was a strong correlation between the chill indicated in the anamnesis and bacteraemia, especially in patients with a urinary tract infection. Bacteraemia, advanced age and serious comorbidity were unfavourable prognostic factors.

Aged↗

Procalcitonin and other markers of infection. What should be their role in clinical practice?

Clinicians are always faced with a decision when confronted with a febrile patient; they must decide between what is an infectious condition and what is not, and between what merits hospital observation, what requires empirical antibiotic treatment and what needs outpatient follow-up. In this respect, judgement based on medical history and physical examination outweigh the predictive value of various laboratory markers of infection, as the latter generally reflect a nonspecific reaction of the host to widely different infectious and inflammatory stimuli. In the evaluation of specific subgroups of patients, e.g. those in the intensive care unit, laboratory tests should also preferably form a continuum with medical history and physical examination, aimed at clarifying host condition, the setting and the source of a possible infection.

Bacterial Infections↗

[Anthrax due to deliberate infection].

Anthrax is a zoonosis which is particularly prevalent in cattle, goats and sheep and is caused by Bacillus anthracis, a Gram-positive spore forming aerobic microorganism. The endospores can survive outside of the body for many decades. The natural form of anthrax has a cutaneous, pulmonary and intestinal form. The pulmonary form can be rapidly fatal but is difficult to recognise due to an initially non-specific, flu-like clinical picture. As a result of spores being inhaled, a mediastinal lymphadenitis arises from which a systemic disease develops with a violent toxaemia, damage to the vascular endothelium, oedema, internal haemorrhages and circulatory collapse. Anthrax is diagnosed by demonstrating the presence of the bacteria in the cutaneous abnormality, in blood or another sterile body component such as cerebrospinal fluid, by means of a direct preparation, immunofluorescence or surface antigens, molecular diagnostics with PCR, or by means of culturing. B. anthracis is sensitive to quinolones, clindamycin and tetracyclines, and often to penicillin. Although naturally acquired cutaneous anthrax can be effectively treated with a short antibiotic cure, it is nevertheless advised in the USA to complete the full 60-day cure and to regard the cutaneous manifestation as a telltale sign of possible respiratory exposure. Anthrax is not transmitted from one person to another.

Adult↗

The effect of two different dosages of intravenous immunoglobulin on the incidence of recurrent infections in patients with primary hypogammaglobulinemia. A randomized, double-blind, multicenter crossover trial.

BACKGROUND: In patients with hypogammaglobulinemia, substitution with immunoglobulin is the treatment of choice to reduce both frequency and severity of bacterial infections. Even with treatment, however, infections still occur in these patients. OBJECTIVE: To determine whether doubling the standard dose of intravenous immunoglobulin would affect the incidence and duration of infections. DESIGN: Multicenter, double-blind, randomized, crossover study. SETTING: 15 outpatient clinics in the Netherlands. PATIENTS: 43 patients with primary hypogammaglobulinemia, 41 of whom completed the protocol. INTERVENTION: Patients received standard-dose immunoglobulin therapy for 9 months, followed by a 3-month washout period, and high-dose intravenous immunoglobulin therapy for 9 months, or vice versa. MEASUREMENTS: The primary outcome measures were total number and duration of infections. Other measures were periods of fever, hospital admissions, use of antibiotics, absence from school or work, and trough levels of serum immunoglobulin. Side effects from the study medication were also recorded. RESULTS: Compared with the standard dose of intravenous immunoglobulin (adults, 300 mg/kg of body weight every 4 weeks; children, 400 mg/kg every 4 weeks), high-dose therapy (adults, 600 mg/kg every 4 weeks; children, 800 mg/kg every 4 weeks) significantly reduced the number (3.5 vs. 2.5 per patient; P = 0.004) and duration (median, 33 days vs. 21 days; P = 0.015) of infections. Trough levels of IgG increased significantly during high-dose therapy. The incidence and type of side effects did not differ significantly for the two dosages. CONCLUSION: In patients with hypogammaglobulinemia, doubling the standard dose of intravenous immunoglobulin significantly reduced the number and duration of infections.

Adolescent↗

Repeatedly negative tuberculin skin tests followed by active tuberculosis in an immunocompetent individual.

We describe a woman who was repeatedly tuberculin (PPD) skin test negative after exposure to smear-positive tuberculosis (TB), but developed active TB with a positive skin test 7 years later. Molecular epidemiologic evidence is presented that the infection was contracted 7 years previously from the original source case. PPD skin testing is subject to many technical and biological variables and this report underscores that this tool can fail to detect latent TB infection in some cases. The causes of false-negative and false-positive PPD skin test results are reviewed.

Acute Disease↗

Multifocal osteomyelitis caused by nontuberculous mycobacteria in patients with a genetic defect of the interferon-gamma receptor.

We describe three patients with multifocal osteomyelitis caused by Mycobacterium avium and a family history of one or more first degree family members diagnosed with various clinical presentations of infections with nontuberculous mycobacteria. There was a significant delay in the diagnosis and they had a protracted course of their illness, which responded only slowly to prolonged multi-drug treatment. In one patient, additional treatment with interferon-gamma (IFN-gamma) was necessary. Macrophages of these patients had decreased in vitro responsiveness to IFN-gamma. Genomic sequencing revealed that these patients and their affected family members were heterozygous for a previously described dominant negative mutation in the gene encoding the IFN-gamma binding receptor-1 chain. The clinical presentations of the infections with nontuberculous mycobacteria in these families, with spread limited to skin, bone and lymph nodes, is discussed in the light of the immune mechanisms that are responsible for the clearance of otherwise poorly pathogenic environmental mycobacteria.

Adult↗

Persistent airflow limitation in adult-onset nonatopic asthma is associated with serologic evidence of Chlamydia pneumoniae infection.

BACKGROUND: Persistent airflow limitation may develop in patients with asthma, particularly in adults with nonatopic (intrinsic) disease. Although the underlying mechanisms are still unknown, respiratory infections might be involved. OBJECTIVE: We investigated the annual loss of lung function in relation to seropositivity to Chlamydia pneumoniae in different subgroups of patients with severe asthma according to age at onset of asthma and atopic status. METHODS: One hundred one nonsmoking outpatients with a pulmonologist's diagnosis of severe asthma (32 men and 69 women; mean age, 46.0 years; range, 18-75 years) were included in a cross-sectional study. C pneumoniae-specific serum IgG and IgA were measured by means of ELISA. The estimated decline in lung function was calculated from the relationship between postbronchodilator FEV(1)/vital capacity (percent predicted) and the duration of asthma and expressed as the slope of the regression line. RESULTS: Patients with adult-onset nonatopic asthma and positive IgG antibodies to C pneumoniae had a significantly steeper slope of the regression line compared with the other subgroups of asthmatic patients (P =.001), being indicative of a 4-fold greater estimated decline in postbronchodilator FEV(1)/vital capacity (2.3% vs 0.5% predicted per year of asthma duration). CONCLUSION: These results suggest that C pneumoniae infection might promote the development of persistent airflow limitation in patients with nonatopic adult-onset asthma. It remains to be established whether viable pathogens that are accessible for therapeutic intervention are still present in the lower airways.

Adolescent↗

Tuberculin skin testing compared with T-cell responses to Mycobacterium tuberculosis-specific and nonspecific antigens for detection of latent infection in persons with recent tuberculosis contact.

The tuberculin skin test (TST) is used for the identification of latent tuberculosis (TB) infection (LTBI) but lacks specificity in Mycobacterium bovis BCG-vaccinated individuals, who constitute an increasing proportion of TB patients and their contacts from regions where TB is endemic. In previous studies, T-cell responses to ESAT-6 and CFP-10, M. tuberculosis-specific antigens that are absent from BCG, were sensitive and specific for detection of active TB. We studied 44 close contacts of a patient with smear-positive pulmonary TB and compared the standard screening procedure for LTBI by TST or chest radiographs with T-cell responses to M. tuberculosis-specific and nonspecific antigens. Peripheral blood mononuclear cells were cocultured with ESAT-6, CFP-10, TB10.4 (each as recombinant antigen and as a mixture of overlapping synthetic peptides), M. tuberculosis sonicate, purified protein derivative (PPD), and short-term culture filtrate, using gamma interferon production as the response measure. LTBI screening was by TST in 36 participants and by chest radiographs in 8 persons. Nineteen contacts were categorized as TST negative, 12 were categorized as TST positive, and 5 had indeterminate TST results. Recombinant antigens and peptide mixtures gave similar results. Responses to TB10.4 were neither sensitive nor specific for LTBI. T-cell responses to ESAT-6 and CFP-10 were less sensitive for detection of LTBI than those to PPD (67 versus 100%) but considerably more specific (100 versus 72%). The specificity of the TST or in vitro responses to PPD will be even less when the proportion of BCG-vaccinated persons among TB contacts evaluated for LTBI increases.

Adolescent↗

Novel Salmonella enterica serovar Typhimurium protein that is indispensable for virulence and intracellular replication.

Upon contact with host cells, the intracellular pathogen Salmonella enterica serovar Typhimurium promotes its uptake, targeting, and survival in intracellular niches. In this process, the bacterium evades the microbicidal effector mechanisms of the macrophage, including oxygen intermediates. This study reports the phenotypic and genotypic characterization of an S. enterica serovar Typhimurium mutant that is hypersusceptible to superoxide. The susceptible phenotype is due to a MudJ insertion-inactivation of a previously undescribed Salmonella gene designated sspJ that is located between 54.4 and 64 min of the Salmonella chromosome and encodes a 392-amino-acid protein. In vivo, upon intraperitoneal injection of 10(4) to 10(7) bacteria in C3H/HeN and 10(1) to 10(4) bacteria in BALB/c mice, the mutant strain was less virulent than the wild type. Consistent with this finding, during the first hour after ingestion by macrophage-like J774 and RAW264.7 cells in vitro, the intracellular killing of the strain carrying sspJ::MudJ is enhanced fivefold over that of wild-type microorganisms. Wild-type salmonellae displayed significant intracellular replication during the first 24 h after uptake, but sspJ::MudJ mutants failed to do so. This phenotype could be restored to that of the wild type by sspJ complementation. The SspJ protein is found in the cytoplasmic membrane and periplasmic space. Amino acid sequence homology analysis did reveal a leader sequence and putative pyrroloquinoline quinone-binding domains, but no putative protein function. We excluded the possibility that SspJ is a scavenger of superoxide or has superoxide dismutase activity.

Animals↗

Intravitreal vancomycin and gentamicin concentrations in patients with postoperative endophthalmitis.

BACKGROUND/AIMS: To study the intravitreal antibiotic concentrations and the efficacy of an intravitreal dosing regimen to treat patients with postoperative bacterial endophthalmitis. This regimen, based on pharmacokinetic/pharmacodynamic considerations, relies on a repeat antibiotic injection of a lower dose than is generally used. METHODS: In consecutive patients with suspected postoperative endophthalmitis a vitreous biopsy for bacterial culture was taken before 0.2 mg vancomycin and 0.05 mg gentamicin were injected intravitreally. After 3 or 4 days a second biopsy was taken for bacteriological culture and to measure intravitreal vancomycin and gentamicin concentrations, followed by a repeat injection of 0.2 mg vancomycin. RESULTS: 17 patients entered the study. In 11 patients the initial bacterial culture was positive, predominantly coagulase negative staphylococci. All second vitreous biopsies were sterile. Intravitreal vancomycin levels varied between 2.6 and 18.0 microg/ml (mean 10.3 (SD 4.1) microg/ml) after 3 days and between 3.1 and 16.6 microg/ml (mean 7.5 (6.2) microg/ml) after 4 days which is well above the minimal inhibitory concentration for most micro-organisms. Concentrations of intravitreal gentamicin varied between 0.90 and 3.3 microg/ml (mean 1.6 (0.72) microg/ml) after 3 days and between 1.2 and 2.6 microg/ml (mean 1.9 (0.99) microg/ml) after 4 days. CONCLUSION: This dosing regimen resulted both in adequate intravitreal vancomycin and gentamicin levels for over a week as well as in negative second cultures. This study also provides new information on intravitreal vancomycin and gentamicin concentration over time in patients with postoperative endophthalmitis.

Aged↗

Uncommon presentations of tuberculosis: the potential value of a novel diagnostic assay based on the Mycobacterium tuberculosis-specific antigens ESAT-6 and CFP-10.

SETTING: Leiden University Medical Center, Leiden, the Netherlands. OBJECTIVE: To illustrate the potential value of a recently developed diagnostic assay for detection of tuberculosis (TB), based on T cell responses to the early secreted antigenic target 6 kDa protein (ESAT-6) and culture filtrate protein 10 (CFP-10). These antigens are Mycobacterium tuberculosis specific because they are expressed by M. tuberculosis but absent from M. bovis bacille Calmette-Guérin (BCG) and most environmental mycobacteria. In recent studies, the assay had a high sensitivity and specificity for detection of active TB. DESIGN: We describe five patients with uncommon presentations of tuberculosis, in whom the diagnosis was delayed by negative or conflicting results of diagnostic procedures aimed at detection of M. tuberculosis and an uninformative tuberculin skin test. IFN-gamma production in response to ESAT-6 and CFP-10 by peripheral blood mononuclear cells from these patients was evaluated before and during anti-tuberculosis treatment. RESULTS: In all five patients, IFN-gamma responses to ESAT-6 and/or CFP-10 were above the cut-off level defined in a previous study. During treatment, IFN-gamma responses generally increased. CONCLUSION: These results indicate that T cell responses to M. tuberculosis-specific antigens have potential diagnostic value when TB is suspected and the results of other diagnostic tests are inconclusive, especially in BCG-vaccinated individuals.

Adult↗

Endotoxin, cytokines, and procalcitonin in febrile patients admitted to the hospital: identification of subjects at high risk of mortality.

We prospectively examined 464 febrile patients (median age, 61 years) for predictors of in-hospital death, by use of univariate and multivariate logistic regression using clinical data (age, underlying disease, duration of fever, chills, and shock on admission) and plasma endotoxin, TNF-alpha, IL-6, IL-10, and procalcitonin levels. The mortality rate was 4.6-fold higher (95% confidence interval [CI], 1.8-12) in 31 patients with shock on admission, 7 of whom died; the strongest association with mortality was the endotoxin concentration (relative risk, 13.7; 95% CI, 1. 4-136), which predicted 5 of the deaths with a 5% false-positive rate. For 433 patients without shock on admission, mortality (26 deaths) was associated with age and underlying disease: clinical data predicted 30% of the deaths, whereas IL-6 and procalcitonin levels identified an extra 10% with a 5% false-positive rate. When febrile patients are screened on hospital admission to identify those with a high risk for mortality, clinical judgment on the basis of age, underlying disease, and recent history outweighs the predictive value of endotoxin, cytokine, and procalcitonin levels. Only in patients who present with shock will measurement of endotoxin levels help predict those who will likely die at the cost of few false-positive results.

Adolescent↗

Enhanced antibody response to pneumococcal polysaccharide vaccine after prior immunization with conjugate pneumococcal vaccine in HIV-infected adults.

The antibody production by HIV-infected adults after two vaccinations with conjugated pneumococcal vaccine (CPV) and consecutive vaccination with polysaccharide pneumococcal vaccine (PPV) was studied. Thirty days after the second CPV, the geometric mean antibody concentrations (GMC) against pneumococcal polysaccharide serotypes (PPS) 6B, 14 and 19F were significantly lower in the group HIV-infected individuals with <200x10(6)/l CD4(+) T lymphocytes (group 1) than in the group with >/=200x10(6)/l CD4(+) T lymphocytes (group 2) and healthy controls. Thirty days after PPV vaccination the GMC against PPS 6B, 14, 19F and 23F in group 1, and against 6B and 19F in group 2, were significantly lower compared with healthy controls. Both in HIV-infected and in healthy individuals who received CPV and PPV the postvaccination GMC against PPS 14, 19F and 23F were higher compared with historical controls who were not previously immunized with CPV but only received PPV. We conclude that the antibody response to CPV is impaired in HIV-infected individuals. Higher antibody concentrations were achieved in HIV-infected and healthy individuals after sequential vaccination with CPV and PPV compared with PPV vaccination alone.

Adult↗

[From gene to disease; mutations in interleukin-12-receptor-beta 1- and interferon-gamma-receptor-1 lead to nontuberculous mycobacterial infections and salmonellosis].

In patients with severe and relapsing infections with non-tuberculous mycobacteria and Salmonella autosomal recessive as well as dominant-negative mutations are shown in genes for receptors of type-1 cytokines: the IL-12 receptor and the IFN-gamma receptor. In case of an impaired capacity to produce these cytokines or--given an abnormal receptor--to react to them, the cellular immune reaction does not run a normal course and the susceptibility to infection by intracellular pathogens is enhanced.

Immune Tolerance↗

Antibody response after influenza vaccination in HIV-infected individuals: a consecutive 3-year study.

In a consecutive 3-year study the antibody response after immunization with influenza vaccine of a cohort of HIV-infected adults was studied. The haemagglutination-inhibiting (HAI) antibody titres after vaccination correlated with the number of CD4(+) T lymphocytes (p<0.001), the prevaccination antibody titres (p<0.001), and the proliferative response to anti-CD3 (p<0.001). Severely impaired antibody responses were observed in HIV-infected individuals with CD4(+) T-lymphocyte counts < or =100x10(6)/l. Significantly higher prevaccination antibody titres were observed in healthy controls in the 2nd or 3rd year of vaccination, but not in HIV-infected individuals. Annually repeated vaccination of HIV-infected individuals did not lead to higher postvaccination antibody titres. Annual vaccination of HIV-infected individuals with CD4(+) T-lymphocyte counts exceeding 100x10(6)/l seems to be worthwhile, although it may not be expected to render the same level of protection against influenza as in non-infected individuals.

Adult↗