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Biomedical subjects

J W Fijen

Publications and source records attributed to J W Fijen.

17 recordsLinked to original sources
PubMed2002

Monocyte intracellular cytokine production during human endotoxaemia with or without a second in vitro LPS challenge: effect of RWJ-67657, a p38 MAP-kinase inhibitor, on LPS-hyporesponsiveness.

In the present study, we investigated the effect of RWJ-67657, a p38 MAP kinase inhibitor, upon in vivo LPS-induced monocyte cytokine production and upon monocyte LPS-hyporesponsiveness. Thirty minutes before a single injection of LPS (4 ng/kg BW), healthy male volunteers received a single oral dose of RWJ-67657 at increasing dosages (0-1400 mg). Blood samples (pre-medication, 3, 6 and 24 h after LPS) were immediately incubated with LPS (reflecting LPS-hyporesponsiveness) or without LPS (reflecting in vivo monocyte stimulation) for 4 h at 37 degrees C. Following red blood cells lysis and white blood cell permeabilization, cells were labelled with alpha-CD14-FITC and alpha-IL-1beta, alpha-IL-12 or alpha-TNFalpha (PE-labelled), fixed, and analysed using flow cytometry. In vivo LPS injection resulted in an increased percentage of circulating monocytes producing IL-1beta, TNFalpha and IL-12 only at 3 h after the LPS injection. This was dose-dependently inhibited by RWJ-67657 treatment. LPS-hyporesponsiveness to in vitro LPS treatment was most prominent at 3 and 6 h after the in vivo LPS injection; compared with pre-medication monocytes, at these intervals a reduced percentage of monocytes produced IL-1beta, TNFalpha or IL-12 after the in vitro LPS stimulus. At t = 6 h, this LPS-hyporesponsiveness could dose-dependently be inhibited by RWJ-67657 treatment of the volunteers. We therefore conclude that p38 MAP kinase inhibition with RWJ-67657 inhibited monocyte production of cytokines following in vivo LPS injection. Treatment with RWJ-67657 also reversed the LPS-hyporesponsiveness. Whether this result can be extended to the clinical situation remains to be elucidated. Patients with sepsis or an otherwise high risk for multi-organ failure are potential study groups.

Endotoxemia↗
PubMed2001

[Diagnostic image (61). Interpleural placement of a central venous catheter].

In a 41-year-old woman a tunneled central venous catheter was inserted for parenteral nutrition. The antero-posterior chest radiograph suggested a correct position, but the patient developed pleural effusion with dyspnoea. A lateral chest radiograph showed the tip of the catheter in the posterior pleural space.

Adult↗
PubMed2001

[Three patients with massive pulmonary embolism].

Three patients presenting with massive venous pulmonary thrombo-embolism are described, who have been selected from a series of 22 patients treated with thrombolysis during a 6-year period. A 23-year-old female presented with tachycardia and dyspnoea. She had pulmonary angiography following scintigraphy with a perfusion deficit of more than 60%. Thrombolysis resulted in open blood vessels and a disappearance of the complaints. A 51-year-old woman presented with profound hypoxemia, probably due to a patent foramen ovale, with shunting and tachycardia. Perfusion defects on scintigraphy combined with a normal chest radiograph in the absence of pre-existent pulmonary disease established the diagnosis. She responded favourably to intravenous streptokinase. The third patient was an 80-year-old woman with hypertension. She developed dyspnoea, tachycardia and shock following immobilisation due to a fractured hip. Despite an initial improvement on streptokinase, she deteriorated and died from right-sided heart failure. The diagnostic tests should be limited and aimed at ruling out left-sided heart failure and pericardial tamponade. Echocardiography is often diagnostic in these patients. Thrombolysis may be life saving but there are no randomised trials to prove that survival rate is indeed better compared to heparin therapy. Streptokinase is less expensive than alteplase and there is no evidence from trials to suggest that it is inferior to more expensive thrombolytics such as alteplase or urokinase.

Adult↗
PubMed2001

Suppression of the clinical and cytokine response to endotoxin by RWJ-67657, a p38 mitogen-activated protein-kinase inhibitor, in healthy human volunteers.

UNLABELLED: Sepsis resulting in multiorgan failure and death is still a major problem in intensive care medicine, despite extensive attempts to interfere in the supposed underlying mechanism of a deranged immune system. This is not only due to the persistent lacunae in knowledge about the immune system in sepsis but also due to the lack of sufficient instruments for intervention. Inhibitors of the p38 mitogen-activated protein kinase (p38MAPK) have been used to study the signalling pathway of the immune response. In vitro and animal studies have demonstrated that blocking p38MAPK could mitigate the pro-inflammatory response and improve survival after endotoxaemia. Using an endotoxaemia model in healthy human volunteers we evaluated the attenuation of clinical and cytokine response to endotoxin after inhibition of p38MAPK by an oral dose of RWJ-67657, a pyrindinyl imidazole. We measured the clinical parameters temperature, blood pressure and heart rate. The proinflammatory cytokines tumour necrosis factor-alpha, interleukin-6 and interleukin-8 were measured by ELISA at various points during a 24-h period. Drug toxicity was evaluated by routine clinical and laboratory examinations. After a single dose dose of RWJ-67657 the temperature and blood pressure response remained at the basal level. The inhibition of TNF-alpha, IL-6 and IL-8 response was a dose dependent. With the maximum dosage, reduction in peak serum levels of the proinflammatory cytokines was greater than 90%. There was no drug-related toxicity. INTERPRETATION: We conclude that inhibition of p38MAPK by RWJ-67657 might be a tool to intervene in the deranged immune response in sepsis and other inflammatory diseases.

Adult↗
PubMed2000

[Pulmonary hemorrhage with respiratory insufficiency in Henoch- Schoenlein purpura].

A 20-year-old woman presented with abdominal pain, purpura on the extremities, and arthralgia. The diagnosis of Henoch-Schönlein purpura was made based on granular IgA deposits in the vessels in a skin biopsy. Three weeks after onset of these symptoms, she developed glomerulonephritis and diffuse alveolar haemorrhage; she developed respiratory failure and needed mechanical ventilation. She recovered upon treatment with corticosteroids. Diffuse alveolar bleeding has occasionally been reported in adults with Henoch-Schönlein purpura; this is the first report from the Netherlands.

Adult↗
PubMed2000

Antidepressants self-poisoning and ICU admissions in a university hospital in The Netherlands.

OBJECTIVES: Many overdosed patients are admitted to an ICU. Antidepressants are frequently used. We examined clinical end-points of toxicity recorded during admission to our ICU of all antidepressants used in overdose. DESIGN: Single centre; retrospective analysis, 5 consecutive years (1994-1998). SETTING: Intensive and Respiratory Care Unit, Groningen University Hospital. PARTICIPANTS: 86 patients admitted to the ICU because of antidepressant self-poisoning--database of 258 consecutively admitted patients with (auto-)intoxication. RESULTS: Significantly more patients were intoxicated with TCAs (65) compared with SSRIs (20; p < 0.05), despite the fact that the number of prescriptions of antidepressants in the community was greater for SSRIs than for TCAs. Patients intoxicated with TCAs needed significantly more often tracheal intubation (27/65 vs 7/20; p < 0.05), and these individuals had also significantly more often tachycardia (14 vs. 3) and QRS-complex widening (19 vs. 1), compared to those with non-TCA antidepressant intoxication (p < 0.05). CONCLUSIONS: TCA self-poisoning has remained the predominant cause of morbidity among patients with auto-intoxication admitted to our ICU in the previous years. The data from this ICU-population confirm previous evidence that SSRIs are safer in overdose than TCAs. This finding was not explained by more prescriptions in the community of TCAs compared with SSRIs. Physicians should be more reluctant in prescribing TCAs to depressed patients in whom the risk of self-poisoning is difficult to assess.

Adult↗
PubMed1999

Pharmacokinetics of cefpirome in critically ill patients with renal failure treated by continuous veno-venous hemofiltration.

OBJECTIVE: To study the cefpirome pharmacokinetics of patients with sepsis and multiple organ failure treated with CVVH. DESIGN: Measurements of serum and ultrafiltrate (UF) concentrations and in vitro sensitivity testing of isolated micro-organisms. SETTING: University hospital-based, single ICU. PATIENTS: Six critically ill CVVH-dependent patients with sepsis and multiple organ dysfunction syndrome in need of antimicrobial therapy. Age range: 60-75 years; APACHE II score for severity of illness on admission: 19-30. One patient survived. INTERVENTIONS: Cefpirome i.v. was started at 2 g in 30 min, then continued 1 g i.v.b.i.d. MEASUREMENTS: The UF rate was 27 +/- 7 ml/min on day 1 and 34 +/- 2 ml/min on day 2. Serum and ultrafiltrate samples were measured by a validated high performance liquid chromatography assay. Volume of distribution: 23 x 5(SD +/- 4 x 6) l. Total cefpirome clearance was 32 +/- 6 x 3 ml/min; cefpirome CVVH clearance (ClCVVH): 17 +/- 4.2 ml/min; mean serum half-life (t1/2): 8.8 +/- 2.3 h; mass transfer on day 1: 660 +/- 123 mg/12 h (33 +/- 6% of administered dose) and day 2: 642 +/- 66 mg/12 h (64 +/- 7%). Estimated sieving coefficient (ClCVVH/UF rate): 64 +/- 11%. In vitro sensitivity of isolated microbes was excellent except for two non-sensitive enterococci and Candida spp. CONCLUSIONS: The sieving coefficient (64%) indicates that a substantial fraction of the drug is not filtered; clearance by pathways other than CVVH mounted to 50% of the total clearance and increased on day 2, indicating that the dosing schedule used is appropriate for this setting. Cefpirome appeared to be safe in these patients and effective for most of the nosocomial microbial isolates. During more than 90% of the time, serum levels were maintained above killing concentrations for susceptible micro-organisms.

APACHE↗
PubMed1999

Diffuse pulmonary infiltrates in immunocompromised patients.

The differential diagnosis of bilateral interstitial pulmonary infiltrates in immunocompromised patients is very extensive. We describe two immunocompromised patients with diffuse pulmonary infiltrative changes. Bronchoscopic bronchoalveolar lavage after orotracheal intubation using topical anaesthesia combined with mild sedation in an ICU setting is safe in critically ill patients and often yields a conclusive diagnosis.

Acquired Immunodeficiency Syndrome↗
PubMed1999

Non-surgical treatment of purulent pericarditis, due to non-encapsulated Haemophilus influenzae, in an immunocompromised patient.

A 59-year-old woman suffering from rheumatoid arthritis was admitted with pleural empyema and pericarditis due to non-encapsulated H. influenzae, and developed signs of cardiac tamponade. Purulent pericarditis resolved after ultrasound-guided percutaneous aspiration and systemic antimicrobial therapy. Serial echocardiographic examinations showed a slowly vanishing effusion. Long term follow-up revealed no evidence of pericardial constriction. This case illustrates that life-threatening purulent pericarditis in an immunocompromised patient may respond well to non-surgical treatment.

Cardiac Tamponade↗
PubMed1997

[Hypothermia in patients with a high spinal cord lesion].

Two women aged 54 and 69 years with high spinal cord injuries and tetraparesis developed hypothermia (30.4 and 29.4 degrees C, respectively); normalization was accomplished by external heating using insulation blankets. Even moderately lowered environmental temperatures may lead to hypothermia in these patients with abnormal temperature sensation, incapacity to compensate and autonomous dysfunction. The symptoms are aspecific and the differential diagnosis is extensive. Recommendations for prevention of hypothermia include daily measurement of the core temperature, adjustment of the environmental temperature and humidity of the air, adequate closing and avoidance of vasodilator drugs.

Aged↗