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Biomedical subjects

J L Kimpen

Publications and source records attributed to J L Kimpen.

At least 37 records · Page 2Linked to original sources

Long-term consequences of respiratory syncytial virus (RSV) bronchiolitis.

Despite differences in study design, follow-up studies consistently show that approximately half of the infants with respiratory syncytial virus (RSV) lower respiratory tract infection (LRTI) go on to have recurrent wheezing episodes during childhood. Respiratory symptoms are associated with abnormal lung function, including bronchial hyper-responsiveness. Wheezing symptoms following RSV LRTI gradually decrease, and it appears that during school age airway morbidity is no longer related to RSV LRTI during infancy. Mechanisms underlying the association between RSV LRTI and long-term airway morbidity are poorly understood. On the one hand, abnormal airway function that is congenitally present or acquired before RSV LRTI occurs could be the cause of both RSV LRTI and subsequent recurrent wheezing. On the other hand, it is possible that RSV LRTI causes changes in the lower airways or the immune system that result in long-term airway morbidity. Animal models suggest that RSV infection can promote the development of allergic sensitization, but most studies in humans do not indicate a role for atopy in the development of recurrent wheezing following RSV LRTI.

Animals↗

Differences in antigen-specific T-cell responses between infants with atopic dermatitis with and without cow's milk allergy: relevance of TH2 cytokines.

BACKGROUND: Cow's milk is the most important food antigen in infancy and may lead to acute cutaneous symptoms and atopic dermatitis (AD). The role of circulating allergen-specific T cells in the pathogenesis of food-allergic skin symptoms is still under investigation. OBJECTIVE: This study was designed to analyze the cow's milk protein (CMP)-specific T-cell response at the clonal level in infants with AD and cow's milk allergy (CMA) in comparison with infants with AD without CMA. METHODS: We used an antigen-specific culturing system with autologous B cells as antigen-presenting cells to establish CMP-specific T-cell clones derived from PBMCs in infants with AD. T-cell reactivity, measured by using a lymphocyte stimulation test, and cytokine production, measured by using ELISA, was compared between infants with AD with and without CMA. RESULTS: Both infants with and without allergy to cow's milk had a CMP-specific T helper cell response directed against the major proteins in milk. Analysis of antigen-specific cytokine production showed that this response was T(H)2 skewed in infants with CMA, with production of high levels of IL-4, IL-5, and IL-13. In contrast, infants without CMA had a T(H)1-skewed response, with high levels of IFN-gamma and low levels of IL-4, IL-5, and IL-13. CONCLUSION: These data confirm for the first time at the clonal level that food allergy in infants with AD is associated with production of T(H)2 cytokines by circulating antigen-specific CD4(+) T cells, whereas tolerance to food antigens is associated with low levels of these cytokines. This suggests a key role for the T helper cell-derived T(H)2 cytokines in food allergy-related skin symptoms.

Animals↗

Streptococcus pneumoniae induces secretion of vascular endothelial growth factor by human neutrophils.

Infection by pneumococci causes an acute inflammatory response associated with neutrophil influx, increased vascular permeability, and edema. Vascular endothelial growth factor (VEGF) is one of the most potent regulators of endothelial permeability. In vitro stimulation of neutrophils showed that pneumococci and purified pneumococcal cell wall induce VEGF secretion, independent of the presence of pneumolysin or polysaccharide capsule. The results of this study indicate VEGF is secreted in pneumococcal disease, suggesting a role as a mediator of increased vascular permeability.

Bacterial Capsules↗

Monocyte IL-10 production during respiratory syncytial virus bronchiolitis is associated with recurrent wheezing in a one-year follow-up study.

Respiratory syncytial virus (RSV) bronchiolitis is associated with subsequent recurrent wheezing episodes. To determine whether cytokine responses during infection can be of predictive value for the development of recurrent wheezing, we performed a follow-up study in 50 hospitalized children with RSV bronchiolitis. Monocyte and lymphocyte cytokine responses in vitro were studied during the acute phase of disease, and again during the convalescent phase, 3 to 4 wk later. Monocyte cytokine responses, including interleukin-10 (IL-10), were measured in whole blood cultures, stimulated with lipopolysaccharide and interferon-gamma (LPS + IFN-gamma). In addition, T-cell cytokine responses, including IFN-gamma and IL-4 production, were measured in whole-blood cultures stimulated with phytohemagglutinin (PHA) or alphaCD2 + alphaCD28. Cytokine responses were analyzed in relation to the development of recurrent episodes of wheezing, documented by parents in a diary during a 1-yr follow-up period. IL-10 responses during the acute phase of RSV bronchiolitis were comparable to those in healthy control subjects. During the convalescent phase, IL-10 responses were significantly increased in patients as compared with those in healthy control subjects (p < 0.001). At follow-up, 27 children (58%) had recurrent episodes of wheezing. IL-10 levels, measured during the convalescent phase, were significantly higher in patients who developed recurrent wheezing during the year after RSV bronchiolitis than in patients without recurrent episodes of wheezing (p = 0.006). Moreover, IL-10 responses during the convalescent phase correlated significantly with the number of wheezing episodes (r = 0.42, n = 46, p = 0.004). Interestingly, no association was found between IFN-gamma responses, IL-4 responses, or IFNgamma/IL-4 ratios and recurrent wheezing. We conclude that monocyte IL-10 responses in vitro upon stimulation with nonspecific stimuli may have predictive value for the development of recurrent wheezing after RSV bronchiolitis. Moreover, our results indicate that not only allergen-driven Th2 cytokine responses can lead to asthmatic symptoms but also virus-induced changes in cytokine responses may result in asthmatic symptoms.

Bronchiolitis, Viral↗

Prophylaxis against respiratory syncytial virus in premature infants.

Postconceptional age was studied in 33 mechanically ventilated preterm infants with respiratory syncytial virus (RSV) bronchiolitis. Preterm infants without chronic lung disease had an increased risk of severe RSV infection until a postconceptional age of 44 weeks.

Bronchiolitis, Viral↗

[Heart transplantation in the Netherlands, an option to be considered for 5 children per year on the average].

OBJECTIVE: To assess the number of possible candidates for paediatric cardiac transplantation and the number of available donors. DESIGN: Retrospective. PATIENTS AND METHODS: The population (date of birth 1 January 1980-31 March 1998) of the Department of Paediatric Cardiology of the Wilhelmina Children's Hospital, Utrecht, the Netherlands, was reviewed for possible candidates for cardiac transplantation and the resulting number of candidates was extrapolated to the entire country. Figures of the transplant co-ordination unit of the University Hospital Utrecht over 1993-1997 were obtained, to estimate the number of available donors. Furthermore, an overview was made of the results of paediatric cardiac transplantations reported in centres around the world. RESULTS: A total number of 15 possible candidates could be selected over the studied period. Extrapolated to the entire country, about 5 candidates each year could be expected. Per year 5 donor hearts of children (< 12 yr) and 11 hearts of adult donors with a low body weight (40-65 kg) have been available for paediatric cardiac transplantation. Worldwide 5- and 10-year survival rates reach 60% and 50%, respectively, morbidity seems low and the quality of life can be considered reasonably good. CONCLUSION: The number of expected recipients corresponds with the number of available donors. Together with the promising results reported in transplant centres around the world, this seems to justify the option of paediatric cardiac transplantation for children with end-stage cardiac disease.

Adolescent↗

Primarily infected cephalhematoma and osteomyelitis in a newborn.

Cephalhematomas are subperiosteal blood collections occurring in newborns secondary to trauma at birth. They develop within a few days and are subsequently resorbed. Infection of a cephalhematoma is unusual and caused most often by colonization of the hematoma during bacteremia or by direct inoculation secondary to trauma. Less than 10 patients with primary infection of the hematoma, in the absence of a positive blood culture, complicated by osteomyelitis have been described. We report a newborn with a primarily infected cephalhematoma complicated by parietal bone osteomyelitis.

Birth Injuries↗

[Clinical thinking and decision-making in practice. A child with dyspnea and excess pleural fluid].

Pleural fluid was diagnosed on an X-ray in a 9-month-old boy with acute dyspnoea without fever. Thoracentesis showed exudate and the patient was diagnosed as having empyema and was treated with continuous chest tube drainage and antibiotics. The culture of the pleural fluid was negative. A month after discharge the boy developed recurrent pleural effusion with dyspnoea. A mass in the right hemithorax was found upon additional diagnostic evaluation. Microscopic evaluation of tumour biopsy specimen showed a malignancy. Infantile fibromatosis was diagnosed in a surgical specimen. The patient died after having developed a recurrent tumour. Infectious causes are not likely in a child with pleural fluid without fever. Pleural fluid has to be analysed in transudate or exudate. Exudate requires a complete diagnostic evaluation.

Anti-Bacterial Agents↗

Peripheral blood cytokine responses and disease severity in respiratory syncytial virus bronchiolitis.

The role of cellular immunity in disease severity in respiratory syncytial virus (RSV) bronchiolitis is largely unknown. This study investigated the association between disease severity and systemic cytokine responses in hospitalized ventilated and nonventilated RSV bronchiolitis patients. In whole blood cultures stimulated with phytohaemagglutinin (PHA), lymphoproliferative responses and interferon (IFN)-gamma and interleukin (IL)-4 production during acute illness were measured. In addition, plasma cytokines were measured. Measurements were repeated in the convalescent phase, 3-4 weeks after admission. Fifty patients were included. The median age in ventilaled patients was significantly lower than in nonventilated patients (1 versus 4 months, p<0.05). In comparison with nonventilated patients, the ventilated patients had significantly lower lymphoproliferative responses and a lower production of IFN-gamma and IL-4. In fact, IFN-gamma and IL-4 production in ventilated patients was almost completely undetectable. Plasma IL-8 levels in ventilated patients were significantly higher than in nonventilated patients. In the convalescent phase, lymphoproliferative and cytokine responses as well as plasma IL-8 levels were normal in both patient groups. Since RSV bronchiolitis is associated with the subsequent development of asthma, the possible skewing of the T-helper (Th1/Th2) cytokine balance was investigated. This was found neither in the acute nor in the convalescent phase. In conclusion, the data indicate that depressed lymphocyte function and elevated plasma interleukin-8 levels are markers of severe disease. It is suggested that age and maturation related immune mechanisms could explain the occurrence of severe respiratory syncytial virus bronchiolitis requiring mechanical ventilation in young infants.

Antibodies, Viral↗

Vertebral osteomyelitis associated with cat-scratch disease.

We describe a patient with vertebral osteomyelitis and paravertebral soft-tissue collections associated with cat-scratch disease (CSD). Diagnosis was established on the basis of histologic examination and serological and polymerase chain reaction (PCR) tests. Treatment consisted of administration of antibiotics, and although skeletal lesions were persistently evident on radiography the patient showed complete clinical recovery. In addition, 15 cases of documented osteomyelitis associated with CSD are reviewed.

Cat-Scratch Disease↗

Respiratory viral infection predisposing for bacterial disease: a concise review.

Although bacterial superinfection in viral respiratory disease is a clinically well documented phenomenon, the pathogenic mechanisms are still poorly understood. Recent studies have revealed some of the mechanisms involved. Physical damage to respiratory cells as a result of viral infection may lead to opportunistic adherence of bacteria. Enhanced bacterial adherence by specific mechanisms has been documented for respiratory cells infected with influenza A virus, respiratory syncytial virus and adenovirus in both in vitro and in vivo models. To date, results of various experimental studies indicate that different mechanisms for increased bacterial adherence induced by viruses are operating for specific viral-bacterial combinations. In the present review, a number of key findings obtained during the past two decades is presented and discussed.

Animals↗

[Pertussis in young infants].

Four infants, three girls aged 4 weeks, 2.5 months and 3 months, and a boy aged 2 months, were hospitalized because of severe respiratory distress. Apnoea spells with bradycardia and hypoxia were seen in two of the patients, one showing convulsions as well, and bronchopneumonia in the other two, of whom one eventually died. All suffered from pertussis. During outbreaks of pertussis, infants less than 6 months of age are at highest risk for severe disease. In this age group, however, the clinical signs of pertussis are often atypical. Classical symptoms such as paroxysms of cough and loud whoops may be absent while feeding problems, apnoea, cyanosis and bradycardia may be present. For infants younger than 6 months with signs indicating pertussis hospitalization is indicated. In the current vaccination schedule in the Netherlands infants are vaccinated at 3, 4, 5 and 11 months of age. Starting in 1999 the first vaccination will be administered at the age of 2 months.

Anti-Bacterial Agents↗

[Primary peritonitis due to Streptococcus pneumoniae in childhood].

Three patients, two boys of 5 months and 6 years and one girl aged 4 years, presented with acute abdominal pain, vomiting and fever, suggesting peritonitis. Imaging examinations (abdominal survey roentgenogram and (or) echography), exploratory laparotomy (in two patients) and blood cultures with growth of Streptococcus pneumoniae led to the diagnosis of primary peritonitis. Intravenous antibiotics led to recovery, in one patient complicated by paralytic ileus, which was treated surgically. Primary peritonitis is a rare condition which should be considered in the differential diagnosis of children with an acute abdominal syndrome. Conditions requiring surgery should be excluded by imaging examinations or laparotomy. When the diagnosis is confirmed by paracentesis or laparotomy, antibiotic treatment has to be started.

Abdominal Pain↗

Shift in antibiotic prescribing patterns in relation to antibiotic expenditure in paediatrics.

UNLABELLED: In paediatrics, antibiotics are among the most commonly prescribed drugs. Because of an overall rise in health care costs, lack of uniformity in drug prescribing and the emergence of antibiotic resistance, monitoring and control of antibiotic use is of growing concern and strict antibiotic policies are warranted. Before such a policy can be implemented, detailed knowledge of antibiotic prescribing patterns and related costs is important. In this study a shift of antibiotic prescription patterns over time is described in relation to hospital antibiotic expenditure. CONCLUSIONS: A considerable shift in prescription patterns towards more expensive and broader spectrum antibiotics occurs in paediatrics, carrying a risk for the development of antibiotic resistance among the most prevalent micro-organisms in this age group.

Anti-Bacterial Agents↗

Antibiotic utilisation for hospitalised paediatric patients.

Antibiotics are among the most commonly prescribed drugs in paediatrics. Because of an overall rise in health care costs, lack of uniformity in drug prescribing and the emergence of antibiotic resistance, monitoring and control of antibiotic use is of growing concern and strict antibiotic policies are warranted. Before such policies can be implemented, detailed knowledge of antibiotic prescribing patterns is important. In this combined retrospective and prospective study the utilisation of antibiotics in a paediatric university hospital over three consecutive years has been analysed. Over an 8-week period (1 November-22 December) in 1994, 1995 and 1996 patient charts were reviewed with regard to antibiotic prescription (generic class, dose, duration and indication). A total of 1120 patients were admitted during the study periods. Antibiotics were prescribed at least once for 36% of hospitalised children, although only 12.3% of the patients receiving antibiotics had a proven bacterial infection. During a single hospitalisation 13, 4.7, 2.6, and 2.7% of all children received 2, 3, 4 or more than four antibiotics, respectively. Infants less than 2 years received antibiotics more frequently than older children (25 and 11% respectively, P=0.0256). More children admitted to the intensive care unit received antibiotics compared with patients admitted on medium care units (49.7 and 29.3% respectively, P < 0.0001). They received more often several different antibiotic courses (2.6 courses per patient versus 1.9 courses per patient, P < 0.0001). These children were also given more often intravenous rather than oral antibiotics (P < 0.0001) Significant differences could be found between the generic classes of antibiotics prescribed to children admitted to the intensive care unit and the medium care. However high variability in dose and duration of antibiotic therapy for the same clinical indication was shown. A high percentage of all hospitalised children receive antibiotics. In most cases antibiotics are started on an empirical basis, without proof of a bacterial infection, either before the start of therapy or afterwards. The fact that children admitted to intensive care units and patients of younger age groups are at special risk of receiving multiple courses of antibiotics, together with the knowledge that antibiotic resistance develops in this setting, suggest that strategies to control antibiotic use should focus on these patient populations.

Adolescent↗

T cell subset analysis in peripheral blood of children with RSV bronchiolitis.

Respiratory syncytial virus (RSV) bronchiolitis is partially an immune-mediated disease in which RSV-specific T cells play a predominant role. The peripheral blood T cell response was studied in patients with RSV bronchiolitis in order to detect evidence for T cell redistribution during natural RSV infection and if so, which subsets are involved. 18 patients with RSV bronchiolitis and 13 control patients were studied. The white blood cell count, the number of T cells and T cell subsets in blood on admission and after 1 week were measured. The absolute count of natural killer cells and gamma delta + T cells on admission were significantly lower in RSV patients in comparison with the control group. During the course of RSV bronchiolitis CD8+ T cells and IL-2 receptor-positive T cells increased significantly. In the ventilated patients the total lymphocytes and the number of T cells and several T cell subsets with surface molecules compatible with an activation state of the cell were decreased in comparison with the non-ventilated RSV patients on admission. During RSV bronchiolitis, consistent shifts in T cell subsets can be demonstrated in the peripheral blood compatible with redistribution from the circulation probably towards the lungs. These findings are more pronounced in patients with severe disease.

Antigens, CD↗