105 research outputs found
Infections, coagulation and thrombosis
No full textMatthijs van Wissen bestudeerde bij proefdieren en mensen veranderingen in de bloedstolling tijdens en vlak na virale luchtweginfecties. Ook onderzocht hij of er een verband is tussen luchtweginfecties veroorzaakt door een virus, longembolie en hart- en vaatziekten. Virusinfecties kunnen op verschillende manieren van invloed zijn op diverse onderdelen van de bloedstolling. Luchtweginfecties zijn wellicht een potentiële risicofactor voor het ontwikkelen van trombose. Een griepbesmetting lijkt de kans op een longembolie niet te verhogen
Bioanalysis, metabolism & clinical pharmacology of antiretroviral drugs
No full textThe aims of all studies described in this thesis were to develop new bioanalytical and more patient friendly methods for studying the clinical pharmacology of antiretroviral drugs and to ultimately improve antiretroviral treatment
Through the Eye of the . . . . .
No full textSpeech, Delivered on accepting the endowed chair in
Clinical Virology, in particular, exotic virus infections,
at Erasmus MC, Faculty of Erasmus University Rotterdam
on November 15, 201
Long-term survival with HIV-infection : the reverse side of the medal
No full textThe introduction of highly effective combined antiretroviral therapy (cART) in 1996 resulted in effective, long-term suppression of HIV with consequent recovery of the patient’s immune system. Although the enthusiasm about the effectiveness of current cART remains strong, the ongoing work in the area of HIV disease and treatment complications appears to reflect concerns that these clinical problems will continue to be important and possibly increase over time in the current therapeutic area. There is growing interest in the pathogenesis, treatment and prevention of long-term complications of HIV disease and its therapies. This thesis describes some of the long-term complications of HIV-infection since the introduction of cART. Cardiac and vascular complications are one of the most frequently occurring complications in long-term surviving HIV-infected patients in different ethnical populations. In the first part markers of coagulation, anticoagulation and fibrinolysis are studied to define a possible pathogenic mechanism for the increased risk of cardiovascular disease as a long-term complication in HIV-infected patients. An improvement in markers of inflammation and coagulation after initiation of cART was found. Nevertheless, markers of inflammation and coagulation did not normalize even with undetectable HIV viral load. In the second part of this dissertation the prevalence of human papillomavirus (HPV) infection in the anogenital area and HPV-associated precursor lesions of anogenital malignancies in HIV-infected men and women in the cART era are studied. Non-AIDS defining malignancies have an increasing incidence in the HIV-infected population and are responsible for considerable mortality. These malignancies could be related to co-infection with viruses like the human papillomavirus (HPV) or Epstein-Barr virus. In the second part we observed a generally high HPV prevalence and a high prevalence of cervical and anal dysplasia in both HIV-infected men and women. Screening HIV-infected sexually active women for cervical dysplasia is recommended while screening for anal dysplasia is no common practice. Screening of the HIV-infected population or of certain risk groups, like HIV-infected MSM, for anal dysplasia should become a routine preventive measure. In the third part HIV-related fatigue is studied as another highly prevalent long-term complication of HIV-infection resulting in significant morbidity. In the third part predictors of HIV-related fatigue are studied to guide future treatment strategies for one of the most common debilitating symptoms in chronic HIV-infected patients. In this dissertation, we investigated several aspects of pathophysiology and screening of some of the long-term complications of HIV-infection. It will become more and more important to define which host, viral and environmental risk factors for developing long-term complications are present and relevant in this specific patient population. Risk factors should be integrated into up-to-date guidelines for screening and treatment strategies. Dealing with the reverse side of the medal of prolonged survival due to effective antiretroviral therapy constitutes a present and future challenge for all HIV caregivers
Increased PAI-1 plasma levels and risk of death from dengue: no association with the 4G/5G promoter polymorphism
No full textBackground: Dengue virus infected patients have high plasminogen activator inhibitor type I (PAI-1) plasma concentrations. Whether the insertion/deletion (4G/5G) polymorphism in the promotor region of the PAI-1 gene is associated with increased PAI-1 plasma concentrations and with death from dengue is unknown. We, therefore, investigated the relationship between the 4G/5G polymorphism and PAI-1 plasma concentrations in dengue patients and risk of death from dengue.
Methods: A total of 194 patients admitted to the Dr. Kariadi Hospital in Semarang, Indonesia, with clinical suspected severe dengue virus infection were enrolled. Blood samples were obtained on day of admission, days 1, 2 and 7 after admission and at a 1-month follow-up visit. Plasma concentrations of PAI-1 were measured using a sandwich ELISA kit. The PAI-1 4G/5G polymorphism was typed by allele-specific PCR analysis.
Results: Concentrations of PAI-1 on admission and peak values of PAI-1 during admission were higher than the values measured in healthy controls. Survival was significantly worse in patients with PAI-1 concentrations in the highest tertile (at admission: OR 4.7 [95% CI 0.9–23.8], peak value during admission: OR 6.3 [95%CI 1.3–30.8]). No association was found between the PAI-1 4G/5G polymorphism, and PAI-1 plasma concentrations, dengue disease severity and mortality from dengue.
Conclusion: These data suggest that the 4G/5G polymorphism has no significant influence on PAI-1 concentrations in dengue virus infected patients and is not associated with the risk of death from dengue. Other factors contributing to the variability of PAI-1 plasma concentrations in patients with dengue need to be explored
Impaired Fibrinolysis in the Pathogenesis of Dengue Hemorrhagic Fever
No full textThe mechanisms contributing to bleeding complications in dengue hemorrhagic fever were studied by investigating the pattern of activation of the coagulation and fibrinolytic systems in 50 children with severe dengue hemorrhagic fever. Thirteen patients (26%) died, and activation of coagulation was most pronounced in the deceased group. Fibrinolysis was also activated, but this activation was relatively weak compared with that of coagulation as a result of persistently high plasminogen activator inhibitor levels. Plasminogen activator inhibitor also prevented a switch from the procoagulant to the profibrinolytic state in lethal dengue hemorrhagic fever, which was further enhanced by an acquired protein C deficiency. The present study is the first to demonstrate such a mechanism in a viral infection. This imbalance between coagulation and fibrinolysis may be used as a prognostic marker, but it may also be a target for future therapeutic intervention
Changes in the Plasma Lipid Profile as a Potential Predictor of Clinical Outcome in Dengue Hemorrhagic Fever
No full textIn 50 consecutive children admitted to the intensive care unit with the clinical diagnosis of dengue hemorrhagic fever (DHF)/dengue shock syndrome (grade III or IV), 20 patients with mild DHF (grade I or II), and 20 healthy control patients, the plasma lipid profile was measured. Levels of total plasma cholesterol, high-density lipoprotein, and low-density lipoprotein were significantly decreased in patients with the severest cases, compared with patients with mild DHF and healthy controls. Changes in the plasma lipid profile differentiate between patients with different stages of DHF disease severity and could be used as a potential predictor for clinical outcome
Cytokine patterns during dengue shock syndrome
No full textObjective. To investigate the patterns of tumor necrosis factor-a (TNF-a), interleukin-1b (IL-1b), IL-6, interferon-c (IFN-c) and interleukin-1 receptor antagonist (IL-1Ra) during the course of dengue shock syndrome.
Design. Prospective clinical study.
Setting. Pediatric Intensive Care Unit, Dr. Kariadi Hospital, the university hospital of Diponegoro University, Semarang, Indonesia.
Patients. Fifty children with dengue shock syndrome.
Measurements. The plasma concentration and the ex vivo production, with and without lipopolysaccharide (LPS), of TNF-a, IL-1b and IL-1Ra were measured in duplicate by nonequilibrium radioimmunoassay (RIA); IFN-c and IL-6 were measured by ELISA.
Results. During the acute phase, the plasma concentrations and the ex vivo production without LPS of IL-1Ra were considerably elevated and returned to normal on recovery. However, the ex vivo LPS-stimulated production of the proinflammatory cytokines TNF-a and IL-1b were considerably depressed. Also, these concentrations returned towards normal on recovery. In non-survivors, the plasma concentrations of IL-6 and IL-1Ra were significantly higher than in survivors (p < 0.00001 and p = 0.0005, respectively). In addition, the ex vivo production of IL-1Ra in non-survivors was significantly higher than in survivors, both without LPS stimulation (p = 0.0008) and with LPS (p < 0.004). IL-1Ra was significantly associated with mortality (p = 0.007).
Conclusion. Since IL-1Ra was significantly associated with mortality, this measurement may be used as an index of disease severity in dengue shock syndrome
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