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Biomedical subjects

P Speelman

Publications and source records attributed to P Speelman.

At least 19 recordsLinked to original sources

[Two adult patients with pneumococcal peritonitis].

Two women, aged 31 and 37 years, had abdominal pain and fever several months after giving birth and a few weeks after receiving an intrauterine device. Both patients were admitted and treated under the working diagnosis of pelvic inflammatory disease (PID). They appeared to have pneumococcal adnexitis and pneumococcal peritonitis. Both patients recovered after initiating directed antibiotic treatment. Peritonitis in previously healthy adults is seldom caused by pneumococci. Standard antibiotics that are effective when given empirically for PID may be a suboptimal treatment for pneumococcal peritonitis.

Abdominal Pain↗

[Optimising antibiotic policies in the Netherlands. IX. SWAB guidelines for antimicrobial therapy in adults with acute infectious diarrhoea].

The 'Stichting Werkgroep Antibioticabeleid' (SWAB; Dutch Working Party on Antibiotic Policy) develops evidence-based guidelines for the use of antibiotics in hospitalised adults. This guideline on acute infectious diarrhoea (AID) concerns the antibiotic treatment of acute infectious inflammation of the gastrointestinal tract, manifesting primarily as diarrhoea. AID can be subdivided into community-acquired diarrhoea, traveller's diarrhoea and hospital-acquired (nosocomial) diarrhoea. In the first 2 categories, the need for antibiotic treatment is generally restricted to individuals with severe illness, dysentery or a predisposition to complications. High rates of primary fluoroquinolone resistance can be found in human Campylobacter isolates from the Netherlands and from other parts of the world. Therefore, if antibiotic treatment is necessary for community-acquired AID or AID in travellers returning to the Netherlands, it is advised to use oral azithromycin for 3 days as empirical treatment. If intravenous treatment is necessary, the combination of ciprofloxacin and erythromycin for 5-7 days may be considered. As soon as the identity of the causative organism is known, antimicrobial treatment should be tailored accordingly.

Acute Disease↗

Antimicrobial treatment of infective endocarditis caused by viridans streptococci highly susceptible to penicillin: historic overview and future considerations.

In this article we present the path that led to current concepts regarding antimicrobial treatment of endocarditis caused by viridans streptococci highly susceptible to penicillin. Early treatment trials indicate that some patients with subacute endocarditis can be cured with shorter treatment duration than currently advised by international guidelines. Also, high-dose antibiotics, as recommended today, have a predominantly pharmacokinetic and pharmacodynamic rationale that is based mostly on experimental animal studies. Shortening antimicrobial treatment in select patients with endocarditis would be of great benefit. As yet there are no predictors of cure that can be used to individualize treatment duration in patients with bacterial endocarditis.

Anti-Bacterial Agents↗

[Life-threatening infections with a new strain of Clostridium difficile].

Three men, aged 39, 73, and 66 years, respectively, developed an infection with a new strain ofClostridium difficile, ribotype 027.C.difficile-associated diarrhoea (CDAD) occurred in two patients after multiple abdominal surgery and in the third patient one week after autologous haematopoietic cell transplantation. Within a few days, despite antibiotic therapy, all three patients developed severe (pseudomembranous) colitis with sepsis for which admission to the Intensive Care Unit was required. Two patients underwent (sub)total colectomy and received an intensive course of oral and/or rectal vancomycin. In all patients who develop diarrhoea in hospital, especially during or after treatment with antibiotics or chemotherapeutic agents, an infection with C. difficile ribotype 027 should be suspected. Recent outbreaks of this hypervirulent strain of C. difficile have been reported in Canada, the United States, United Kingdom, and The Netherlands. Demonstration of C. difficile toxin in faeces confirms the clinical suspicion of CDAD and ribotyping of the strain may reveal whether the 027 strain is present. For treatment of these 027 infections, vancomycin is preferred to metronidazole. After a severe course of colitis or in case of recurrence a 'tapering and pulse' course ofvancomycin can be prescribed; alternatively, treatment with bovine antibody-enriched whey may be considered. The introduction of this hypervirulent strain has led to reinforcement of the hygienic measures in accordance with the recommendations of the Dutch Working Party on Infection Prevention and a policy to deter the use of fluoroquinolones.

Adult↗

[Guideline 'Lyme borreliosis'].

Borrelia burgdorferi is the causative bacterial agent of Lyme borreliosis, a tick-transmitted infectious disease. The Dutch Institute for Health Care Improvement (CBO) has now issued a guideline on 'Lyme borreliosis'. Lyme borreliosis is classified as 'early', 'early disseminated', 'late' or as 'post-infectious complaints and symptoms'. Erythema migrans is the most common manifestation of early Lyme borreliosis. Frequent neurological manifestations of 'early disseminated Lyme borreliosis' include meningoradiculitis, meningitis and peripheral facial palsy, but Lyme carditis and arthritis also occur. Late Lyme borreliosis is characterised by skin abnormalities (acrodermatitis chronica atrophicans), chronic neuroborreliosis or chronic arthritis. Confirmation serology with respect to Borrelia is the most commonly used laboratory technique, but in early Lyme borreliosis the immune response may be absent. In addition, the mere presence of antibodies in the serum is no proof of an active infection with Borrelia and serology may yield false-positive reactions. Doxycycline and ceftriaxone are the most commonly used antibiotics in the various stages of Lyme borreliosis. Lyme borreliosis may be prevented by avoiding high-risk areas, keeping the skin covered as much as possible, and inspection of the skin after possible exposure to remove ticks within 24 hours. Laboratory tests after a tick bite are not recommended, nor is prophylactic treatment with antibiotics.

Animals↗

Development and validation of a short questionnaire in community acquired pneumonia.

BACKGROUND: A short but sensitive questionnaire evaluating changes in respiratory symptoms and well being during the treatment of community acquired pneumonia (CAP) is needed. We have developed a measurement and evaluated its psychometric properties in 67 patients admitted with CAP. METHODS: The patients were asked to indicate the presence and severity of dyspnoea, coughing, coughing up sputum, coughing up sputum with ease, the colour of the sputum, fatigue, fitness, and their state of health. The item fatigue showed substantial overlap with fitness and was therefore excluded. The response of the patients to the remaining eight items was used to calculate a CAP score. RESULTS: The percentage of missing data (0.2-1.7%), floor and ceiling effects (0.2/5.5%), internal consistency (Cronbach alpha = 0.87), and the intraclass correlation coefficient for test-retest reproducibility (0.83) met predefined criteria, indicating good acceptability and reliability. Face and clinical validity were satisfactory. Effect sizes under treatment were large, indicating high responsiveness. CONCLUSION: The newly developed CAP score is a simple, reliable, valid, and highly responsive instrument. This makes it scientifically sound and clinically relevant for measuring outcome when evaluating treatment strategies in CAP.

Adult↗

Usefulness of Gram stain for diagnosis of lower respiratory tract infection or urinary tract infection and as an aid in guiding treatment.

During a prospective study of 8 months duration conducted in the Department of Internal Medicine and the Department of Pulmonary Diseases of the Academic Medical Centre, Amsterdam, Gram stainings of sputa and urine were performed for all patients whose clinical symptoms indicated an acute urinary tract infection or pulmonary infection. On the test request, the physician reported which antibiotic treatment he would prescribe if a microscopic examination was not available. The results of the Gram stain were discussed by the microbiologist with the physician, and the antibiotic therapy recommended by the microbiologist was recorded. This recommendation was compared with the antibiotic prescription noted in the patient record 1 day later. Two days after the results of final cultures and susceptibility tests became available, the patient record was again investigated for changes in the antibiotic regimen. Of 57 urine samples and 103 sputa, 27 and 85, respectively, were derived from patients with an infection of the urinary tract or respiratory tract. The results of the Gram stain confirmed the physician's suspicion 91% of the time for urinary tract infections and 81% of the time for pulmonary infections. In 67% of the patients with suspected lower respiratory tract infections and in 58% of patients with suspected urinary tract infections, the antibiotic treatment recommended on the basis of the results of the Gram stain differed significantly from the antibiotic treatment that the physician would have prescribed had a microscopic examination not been performed. The microbiologist's advice on antibiotic treatment was followed in 79% of the cases of respiratory tract infection and in 65% of the cases of urinary tract infection. The antibiotic treatment was adjusted to the final results of culture and antimicrobial susceptibility testing in 54% of the urinary tract infections and in 31% of the respiratory tract infections. The results indicate that the examination of sputa and urine in patients suspected to have an infection of the respiratory tract or urinary tract influences the antibiotic choice considerably.

Anti-Bacterial Agents↗

Reduced interferon-gamma release in patients recovered from Legionnaires' disease.

BACKGROUND: Legionella pneumophila, a Gram negative intracellular pathogen, causes Legionnaires' disease (LD). Interferon (IFN)-gamma is important for host defence against L pneumophila so reduced IFN-gamma production capacity and/or responsiveness might render humans more susceptible to infection with L pneumophila. METHODS: Seventy seven patients who suffered from LD after a point source outbreak one year earlier participated in the study. Whole blood was incubated with non-specific stimuli (lipopolysaccharide (LPS) or interleukin (IL)-12) or specific stimuli (viable or heat killed L pneumophila) to evaluate IFN-gamma production, and with IFN-gamma to evaluate IFN-gamma responsiveness. Expression of complement receptor 3 on monocytes was determined by flow cytometry. Thirty seven companions who were also exposed but had not developed LD served as controls. RESULTS: Patients released less IFN-gamma than controls in response to stimulation with LPS (mean (SE) 393 (58) pg/ml v 914 (178) pg/ml; p=0.001) and IL-12 (96 (14) pg/ml v 177 (41) pg/ml; p=0.058). IFN-gamma responsiveness, measured by release of IFN-gamma inducible protein (IP)-10, tumour necrosis factor alpha, IL-12 production capacity, and monocyte expression of complement receptor 3, did not differ between patients and controls. IFN-gamma release after stimulation with LPS and IP-10 release after stimulation with IFN-gamma were weakly associated with severity of LD in the former patient group (rho=-0.3, p=0.011 and rho=-0.3, p=0.037, respectively). CONCLUSION: These results suggest that impaired IFN-gamma production may contribute to susceptibility to L pneumophila infection.

Aged↗

[Fitz-Hugh-Curtis syndrome: 2 patients with perihepatitis and sepsis].

Two women aged 53 and 22 years presented with abdominal pain and signs of sepsis with metabolic acidosis. The first patient had ecchymoses all over her body, the second patient had an enlarged left kidney with wedge-shaped hypo-intense areas on the CT scan. The clinical condition of both women deteriorated. On laparoscopy perihepatitis with fibrin wires ('violin strings') was seen, pathognomonic for Fitz-Hugh-Curtis syndrome. Upon appropriate antibiotic treatment, both patients fully recovered. Although it is common belief that Fitz-Hugh-Curtis syndrome is caused by local spread from the fallopian tubes into the peritoneal cavity, these presentations suggest a haematogenous spread of Neisseria gonorrhoeae as well as Chlamydia trachomatis in the first case, and C. trachomatis in the second case.

Abdomen↗

TNF-alpha compensates for the impaired host defense of IL-1 type I receptor-deficient mice during pneumococcal pneumonia.

To determine the role of IL-1 in the host defense against pneumonia, IL-1R type I-deficient (IL-1R(-/-)) and wild-type (Wt) mice were intranasally inoculated with Streptococcus pneumoniae. Pneumonia resulted in elevated IL-1alpha and IL-1beta mRNA and protein levels in the lungs. Survival rates did not differ between IL-1R(-/-) and Wt mice after inoculation with 5 x 10(4) or 2 x 10(5) CFU. At early time points (24 and 48 h) IL-1R(-/-) mice had 2-log more S. pneumoniae CFU in lungs than Wt mice; at 72 h bacterial outgrowth in lungs was similar in both groups. Upon histopathologic examination IL-1R(-/-) mice displayed a reduced capacity to form inflammatory infiltrates at 24 h after the induction of pneumonia. IL-1R(-/-) mice also had significantly less granulocyte influx in bronchoalveolar lavage fluid at 24 h after inoculation. Since TNF is known to enhance host defense during pneumonia, we determined the role of endogenous TNF in the early impairment and subsequent recovery of defense mechanisms in IL-1R(-/-) mice. All IL-1R(-/-) mice treated with anti-TNF rapidly died (no survivors (of 14 mice) after 4 days), while 10-day survival in IL-1R(-/-) mice (control Ab), Wt mice (anti-TNF), and Wt mice (control Ab) was 7 of 13, 3 of 14, and 12 of 13, respectively. These data suggest that TNF is more important for host defense against pneumococcal pneumonia than IL-1, and that the impaired early host defense in IL-1R(-/-) mice is compensated for by TNF at a later phase.

Animals↗

CXC chemokine receptor 2 contributes to host defense in murine urinary tract infection.

CXC chemokines have been implicated in the recruitment of neutrophils to sites of infection. To determine the role of CXC chemokines in the host response to urinary tract infection (UTI), female mice were treated with an antibody against the major CXC chemokine receptor in the mouse, CXCR2, before intravesical inoculation with Escherichia coli. Anti-CXCR2 prevented the influx of neutrophils in urine and kidneys. The absence of a neutrophil response only temporarily impaired the clearance of bacteria from the urinary tract, as indicated by 100- and 1000-fold more E. coli colony-forming units in urine and kidneys of anti-CXCR2-treated mice at 24 h, but not at 48 h, after the infection. UTI induced increases in the renal concentrations of the CXCR2 ligands macrophage inflammatory protein-2 and KC, which were not influenced by anti-CXCR2 administration. CXC chemokines play an important role in the development of a local inflammatory response to UTI.

Animals↗

Mice lacking the multidrug resistance protein 1 are resistant to Streptococcus pneumoniae-induced pneumonia.

Leukotrienes (LTs) are considered important for antibacterial defense in the lung. Multidrug resistance protein 1 (mrp1) is a transmembrane protein responsible for the cellular extrusion of LTC(4). To determine the role of mrp1 in host defense against pneumonia, mrp1(-/-) and wild-type mice were intranasally inoculated with Streptococcus pneumoniae. mrp1(-/-) mice displayed a diminished outgrowth of pneumococci in lungs and a strongly reduced mortality. These findings were related to an effect of mrp1 on LT metabolism, because survival was similar in mrp1(-/-) and wild-type mice treated with the 5-lipoxygenase-activating protein inhibitor MK-886. Although LTC(4) levels remained low in the bronchoalveolar lavage fluid of mrp1(-/-) mice, LTB(4) concentrations were higher than in wild-type mice. These elevated LTB(4) concentrations were important for the relative protection of mrp1(-/-) mice, because the LTB(4) antagonist LTB(4)-dimethyl amide abolished their survival advantage. In vitro experiments suggested that the intracellullar accumulation of LTC(4) in mrp1(-/-) mice results in product inhibition of LTC(4)-synthase, diminishing substrate competition between LTA(4)-hydrolase (which yields LTB(4)) and LTC(4)-synthase for the available LTA(4). We conclude that mrp1(-/-) mice are resistant against pneumococcal pneumonia by a mechanism that involves increased release of LTB(4). These results identify mrp1 as a novel target for adjunctive therapy in pneumonia.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

Patients with active tuberculosis have increased expression of HIV coreceptors CXCR4 and CCR5 on CD4(+) T cells.

Expression of human immunodeficiency virus (HIV) coreceptors CXCR4 and CCR5 was found to be elevated on CD4(+) T cells (1) in blood samples obtained from patients with tuberculosis and (2) in blood samples obtained from healthy subjects and stimulated with mycobacterial lipoarabinomannan in vitro. These data suggest that the increase in HIV viremia that occurs in association with tuberculosis may result from up-regulation of CXCR4 and CCR5 on CD4(+) T cells, thereby causing acceleration of HIV infection.

Adult↗

Urine interleukin-8 is a marker for urinary tract infection in postoperative patients.

BACKGROUND: Urine of patients with urinary tract infection (UTI) contains high levels of interleukin (IL)-6 and IL-8. However, knowledge of the kinetics of their release in urine is limited. We therefore compared the appearance of IL-6 and IL-8 in urine after uncomplicated surgery and surgery complicated by UTI. PATIENTS AND METHODS: 165 patients undergoing abdominal surgery who received a urinary catheter were studied. Urine IL-6 and IL-8 were prospectively measured in patients who did (n = 10) or did not (n = 20) develop UTI. Statistical analysis was done by one-way ANOVA and the Mann-Whitney test. RESULTS: Although urine IL-6 increased in the 2 to 4 days preceding the bacteriological documentation of UTI, a similar increase was observed in patients who did not develop UTI. Urine IL-8 was elevated on the day UTI was diagnosed, while remaining low in controls. CONCLUSION: In this patient group with postoperative UTI, urine IL-8 was a better marker for the early host response than urine IL-6.

Abdomen↗

Guidelines for adults on self-medication for the treatment of acute diarrhoea.

Acute uncomplicated diarrhoea is commonly treated by self-medication. Guidelines for treatment exist, but are inconsistent, sometimes contradictory, and often owe more to dogma than evidence. An ad hoc multidisciplinary group has reviewed the literature to determine best practice. In general it is recognized that treatment of acute episodes relieves discomfort and social dysfunction. There is no evidence that it prolongs the illness. Self-medication in otherwise healthy adults is safe. Oral loperamide is the treatment of choice. Older anti-diarrhoeal drugs are also effective in the relief of symptoms but carry the risk of unwanted adverse effects. Oral rehydration solutions do not relieve diarrhoea, and confer no added benefit for adults who can maintain their fluid intake. Probiotic agents are, at present, limited in efficacy and availability. Antimicrobial drugs, available without prescription in some countries, are not generally appropriate for self-medication, except for travellers on the basis of medical advice prior to departure. Medical intervention is recommended for the management of acute diarrhoea in the frail, the elderly (> 75 years), persons with concurrent chronic disease, and children. Medical intervention is also required when there is no abatement of the symptoms after 48 h, or when there is evidence of deterioration such as dehydration, abdominal distension, or the onset of dysentery (pyrexia > 38.5 degrees C and/or bloody stools).

Acute Disease↗

Erythromycin inhibits Pseudomonas aeruginosa-induced tumour necrosis factor-alpha production in human whole blood.

Erythromycin has been shown to be beneficial for panbronchiolitis, a disorder linked to infection with Pseudomonas aeruginosa. Erythromycin, but not the anti-Pseudomonas antibiotics imipenem, ceftazidime, gentamicin and ciprofloxacin, caused a dose-dependent decrease in the production of tumour necrosis factor (TNF)-alpha by whole blood stimulated with heat-killed P. aeruginosa. The release of interleukin (IL)-10, IL-6, interferon-gamma and IL-8 was inhibited only at the highest erythromycin concentration. Inhibition of TNF-alpha production by erythromycin may, at least in part, explain the efficacy of this macrolide during panbronchiolitis despite its lack of activity for P. aeruginosa.

Anti-Bacterial Agents↗

Thalidomide inhibits granulocyte responses in healthy humans after ex vivo stimulation with bacterial antigens.

Ingestion of thalidomide was associated with a reduction in the upregulation of the granulocyte activation marker CD11b and a reduced capacity to release elastase and lactoferrin after stimulation with lipopolysaccharide or lipoteichoic acid. A single oral dose of thalidomide attenuates neutrophil activation upon ex vivo stimulation with bacterial antigens.

Anti-Inflammatory Agents↗