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Biomedical subjects

J A Burgers

Publications and source records attributed to J A Burgers.

At least 19 recordsLinked to original sources

[Chronic indwelling pleural catheter for malignant pleural effusion in 25 patients].

OBJECTIVE: To describe the experience with an indwelling pleural catheter in patients with pleuritis carcinomatosa. DESIGN: Prospective follow-up study. METHOD: The placement of an indwelling pleural catheter was considered as a treatment possibility for patients who presented with symptomatic accumulation of pleural fluid that returned following previous drainage or pleurodesis or when the fluid had not been drained off previously but there were strong radiological indications for a 'trapped lung'. The intervention was considered to be contraindicated by the following: dyspnoea that had not been reduced by previous pleural punctures performed for relief, dyspnoea caused by many different factors, a tendency for haemorrhaging that could not be corrected. The drain used was a Pleurx indwelling catheter, a thorax drain that is tunnelled subcutaneously, can remain in situ for a long time and offers the patient the opportunity to drain off fluid himself at any desired moment. RESULTS: In the period September 2003-May 2005, the treatment was considered in 40 patients. Ultimately, the catheter was inserted in 25 patients; the clinical deterioration of most of the other patients was too quick. Of the group, 33 patients (82%) died with a median survival of 70 days. All catheters functioned until they were removed or until the patient died. In 3 patients, the drainage procedure was complicated by empyema and in 1 patient by haemoptysis. From the total number of catheters, 9 were removed while the patient was still alive and in 6 patients, spontaneous pleurodesis occurred following 3, 4, 4, 5, 6, and 8 months respectively. In general, the patients were able to handle the catheter without problems and the symptoms were brought and kept adequately under control. CONCLUSION: The Pleurx indwelling pleural catheter was an efficacious treatment supplement for patients with malignant pleural effusion, in whom the standard pleurodesis was not effective.

Adult↗

Concurrent chemotherapy (carboplatin, paclitaxel, etoposide) and involved-field radiotherapy in limited stage small cell lung cancer: a Dutch multicenter phase II study.

To improve the prognosis of limited stage small cell lung cancer (LS-SCLC) the addition of concurrent thoracic radiotherapy to a platinum-containing regimen is important. In the Netherlands, we initiated a multicenter, phase II study, of the combination of four cycles of carboplatin (AUC 5), paclitaxel (200 mg m(-2)) and etoposide (2 x 50 mg orally for 5 days) combined with 45 Gy (daily fractions of 1.8 Gy). The radiation was given to the involved field and concurrently with the second and third chemotherapy cycle. Patients with a partial or complete response received prophylactic cranial irradiation to a dose of 30 Gy. From January 1999 to December 2001, 37 of the 38 patients with LS-SCLC entered were eligible for toxicity analysis and response. Grade 3 and 4 haematological toxicity occurred in 57% (21/37) with febrile neutropenia in 24% (9/37). There were no treatment-related deaths or other grade 4 toxicity. Grade 3 toxicities were oesophagitis (27%), radiation pneumonitis (6%), anorexia (14%), nausea (16%), dyspnea (19%) and lethargy (22%). The objective response rate was 92% (95% confidence interval (CI) 80-98%) with a median survival time of 19.5 months (95% CI 12.8-29.2). The 1-, 2- and 5-year survival rate was 70, 47 and 27%, respectively. In field local recurrences occurred in six patients. Distant metastases were observed in 19 patients of which 13 in the brain. This study indicates that combination chemotherapy with concurrent involved-field radiation therapy is an effective treatment for LS-SCLC. Despite PCI, the brain remained the most important site of recurrence.

Administration, Oral↗

Occupational asbestos exposure: how to deal with suspected mesothelioma cases--the Dutch approach.

INTRODUCTION: Patients with asbestos-related diseases, such as malignant mesothelioma (MM), are not uniformly treated in Europe when they apply for compensation. In The Netherlands, the Institute of Asbestos Victims (IAV) acts on behalf of patients with a malignant mesothelioma. In the majority of cases, the diagnosis is clear but in some, uncertainty remains. In these cases a specialist opinion of the Mesothelioma Group of the Dutch Thoracic Society (DTS) is required. The process of data handling and final outcome for these patients is discussed and compared with the situation in other European countries. MATERIALS AND METHODS: Dutch patients with a possible malignant mesothelioma and occupational exposure to asbestos presented their cases to the IAV. In 10% of the cases, pathological confirmation of a malignant mesothelioma could not be obtained. These cases were presented to the Mesothelioma Group to obtain a clinical diagnosis based on clinical reports, occupational history, X-ray examination and other factors. Each case was reviewed by three independent pulmonologists experienced in MM. The majority view was binding for acceptance or rejection of the diagnosis. RESULTS: In the period January 2000 until May 2005, the IAV received 1747 cases for compensation. In 161 cases no definitive diagnosis could be made on pathology and were presented to the Mesothelioma Group. Of these cases, 117 (73%) were considered to be compatible with the clinical diagnosis malignant pleural mesothelioma. Forty-four cases (27%) were rejected. In 75% of the cases (112 of 150), the conclusion of the three independent specialists was unanimous; in 11 cases one specialist refrained from a diagnosis. The median time from request to submission of the report was 34 days (range 1-185 days). CONCLUSIONS: Compared with other European countries, this approach, as determined by the IAV and Mesothelioma Group of the DTS, is an effective and rapid way to investigate claims of patients with a possible occupationally related malignant mesothelioma.

Aged↗

[Development in the treatment of malignant mesothelioma].

For many years there has been a search for an effective treatment of malignant pleural mesothelioma. Surgery is of limited applicability and is reserved for special cases, in which it is combined with radiation therapy. In the previous century, many cytostatic agents have been tested, alone or in combination, but the response was limited, the median survival time was unchanged and the toxicity was high. New drugs, including the new antifolates, are being used much more often in the treatment of malignant pleural mesothelioma in combination with a platinum derivative. Cytostatics such as pemetrexed, an antifolate, and to a lesser extent raltitrexed, have shown good response rates and increased survival in phase III studies, but the survival benefit evaporates within 2 years. Inhibitors of angiogenesis and of epidermal growth factor are being tested, but they have shown only limited activity until now. The current studies focus on the use of chemotherapy and biological agents as part of a more complex treatment schedule.

Antimetabolites, Antineoplastic↗

[Problematic cases of mesothelioma reported to the Dutch Institute for Asbestos Victims: evaluation by the Mesothelioma Working Group of the Netherlands Association of Pulmonologists and Specialists in Tuberculosis].

OBJECTIVE: To analyse the assessments of problematic cases reported to the Dutch Institute for Asbestos Victims (IAS) by the Mesothelioma Working Party of the Netherlands Association of Pulmonologists and Specialists in Tuberculosis (NVALT). DESIGN: Descriptive. METHOD: The pathological confirmation of a malignant pleural mesothelioma of occupational origin is difficult in about 10% of the cases. The IAS has requested the Mesothelioma Working Party of the NVALT to review these cases. When no definitive diagnosis can be made on histological or cytological grounds, three pulmonologists reach a conclusion on the basis of correspondence, X-ray examination and other information. RESULTS: In the period January 2000--March 2004 the Working Party evaluated 132 cases, two-thirds of whom (n = 89) were assessed to be compatible with 'malignant pleural mesothelioma' and one-third of whom (n = 43) were felt to be non-compatible. In 69% of the cases (91/132) the conclusions of the three independent specialists were unanimous. The median time from request to report was 25 days (range: 1-185). CONCLUSION: This approach was effective and rapid.

Aged↗

[Bronchoscopy: new diagnostic and therapeutic technology, new indications].

Over the last few years developments have been concentrated on the diagnostic and therapeutic properties of bronchoscopy. Autofluorescence and fluorescence bronchoscopy significantly enhance the detection rate of premalignant and early neoplastic endobronchial lesions. Unfortunately, this technique is hampered by a low specificity. Endobronchial ultrasound examination is the first tool that has enabled the bronchoscopist to get an impression of the tracheal wall beyond its epithelial surface including the mediastinal and the hilar structures. Currently, the complexity of the procedure prevents its widespread application. Intervention bronchoscopy involves mechanical and laser removal of processes that may impede the central airways. Electrocauterization and laser dissection are regularly used to remove intrabronchial tumour depositions. Airway stenting is indicated if there are stenoses caused by compression from abnormalities located externally to the airways.

Bronchial Diseases↗

Identical chemotherapy schedules given on and off trial protocol in small cell lung cancer: response and survival results.

Patients who are treated within clinical trials may have a survival benefit dependent on being a trial participant. A number of factors may produce such beneficial outcome including more rigorous adherence to a peer reviewed trial protocol, management by an experienced treatment team, being treated in a specialist centre etc. The current investigation compared patients treated on and off trial with the same standard arm treatment regimen. The results could then be interpreted without the confounding factors of differing treatment regimens, treatment teams or treatment hospitals. The results demonstrated given these circumstances that survival was no different for patients participating in a randomised trial compared with a group of patients similarly treated who were not eligible for trial entry or who declined randomisation. These results were obtained by the rigorous adherence to a defined protocol with the invaluable assistance of designated lung cancer staff.

Adult↗

A model system for optimising the selection of membrane antigen-specific human antibodies on intact cells using phage antibody display technology.

The functional expression of human antibody fragments on the surface of filamentous bacteriophage, and selection of phage antibodies (PhAbs) with antigens, has provided a powerful tool for generating novel antibodies. Applications of phage antibody display technology have increased over the past decade. Successful isolation of phage antibodies has been reported mostly using purified antigens. Isolation has proven to be more complicated with complex mixtures of antigens, such as intact cells. A given cell type contains thousands of different epitopes, each capable in theory of binding phage antibodies. Often antigens are not known or cannot be purified without disrupting their conformational integrity. To overcome problems involving phage antibody selections on intact cells, we have developed an experimental model system that allows for optimisation and comparison of various selection strategies. The model system comprises labelling of intact cells with the fluorescently labelled phospholipid fluorescein-DHPE. Upon incubation, this phospholipid is readily incorporated in the membrane of any cell type. Labelling intensity is regulated by varying the phospholipid concentration. After optimisation of key steps in the selection procedure, we were able to isolate fluorescein-DHPE specific phage from a synthetic library using intact cells. This model system can be applied to any cell type and we demonstrate that it can be used to efficiently compare and optimise selection strategies.

Antibodies↗

Multicentre phase II study of gemcitabine and cisplatin in malignant pleural mesothelioma.

UNLABELLED: Malignant pleural mesothelioma is a notoriously chemoresistant tumour. However, a recent single institution study showed an impressive activity of gemcitabine and cisplatin. Our aim is to investigate the efficacy and toxicity of a gemcitabine and cisplatin combination in selected and chemo-naive patients with histologically proven malignant pleural mesothelioma. METHOD: Gemcitabine 1250 mg m(-2) was administered on day 1 and day 8 and cisplatin 80 mg m(-2) was administered on day 1 in a 3-week cycle with a maximum of six cycles. Response and toxicity evaluations were performed according to WHO and NCIC-CTC criteria. Pathology and radiology were centrally reviewed. Results show that in 25 evaluable patients, four PR were observed (ORR 16%, 95% CI 1-31%). Responses of seven patients were unevaluable. No unexpected toxicity occurred. Time to progression was 6 months (5-7 months) with a median survival from registration of 9.6 months (95% CI 8-12 months). In conclusion this trial excludes with 90% power a response rate of greater than 30% in patients with malignant pleural mesothelioma using a combination of gemcitabine and cisplatin at the proposed dose and schedule.

Aged↗

Endobronchial ultrasound.

Endobronchial ultrasound (EBUS) is a new diagnostic tool, which has expanded the view of the bronchoscopist beyond the confinements of the airways. It has great potential for diagnosis of mediastinal processes and staging of lung cancer. These will be discussed and illustrated. EBUS will become a superior tool for staging of lung cancer, and several comparative studies on EBUS as compared with standard techniques in order to assess its role in the staging procedure are just on their way or already completed.

Endosonography↗

Pseudoparasitic pneumonia after bone marrow transplantation.

We present a female patient from Somalia with an acute lymphoblastic leukemia, who received an allogeneic bone marrow transplantation (BMT) and developed several periods of moderate to severe pulmonary symptoms that were accompanied by pulmonary infiltrates and peripheral blood eosinophilia. After several recurrences an open lung biopsy was performed, which initially gave rise to the diagnosis parasitic infection. Later on this diagnosis was questioned and it was suggested that the structures were artifacts that might have been aspirated. Nevertheless, after the immediately given antihelminthic treatment no peripheral blood eosinophilia occurred anymore, but at that point of time pulmonary function was already severely hampered and eventually led to a lethal complication. With the worldwide increasing migration from Third World countries with a high prevalence of parasitic infections, more patients will receive immunosuppressive therapies in countries less familiar with parasites. This may complicate diagnostic procedures, prevent early recognition and delay adequate treatment. Specific screening for opportunistic parasitic infections of the population at risk before BMT and a great awareness for these infections is strongly recommended.

Adolescent↗

Central diabetes insipidus and Cushing's syndrome due to ectopic ACTH production by disseminated small cell lung cancer: a case report.

The present case report describes the rare clinical presentation of diabetes insipidus in a patient with an ectopic ACTH syndrome (morning plasma cortisol 1.10 mumol/l, morning plasma ACTH 322 ng/l) due to disseminated small cell lung cancer including a metastasis in the posterior pituitary. The patient was treated by combination chemotherapy and at the same time received octreotide to control hypercortisolism and desmopressin (DDAVP) to control polyuria. Partial tumour remission was achieved resulting in decreased cortisol production and disappearance of the diabetes insipidus. Medical treatment could be discontinued. Several months later tumour regrowth occurred, with recurrence of hypercortisolism (mean morning plasma cortisol 0.74 mumol/l, mean morning plasma ACTH 112 ng/l) but without diabetes insipidus. Early treatment of hypercortisolism in patients with an ectopic ACTH syndrome and disseminated small cell lung cancer may prolong survival and improve the quality of life.

ACTH Syndrome, Ectopic↗

Discontinuation of yellow jacket venom immunotherapy: follow-up of 75 patients by means of deliberate sting challenge.

BACKGROUND: Venom immunotherapy is effective in preventing systemic reactions in patients with a history of an anaphylactic reaction to Hymenoptera stings. It is uncertain how long venom immunotherapy should be continued. OBJECTIVE: We evaluated whether the duration of venom immunotherapy given to yellow jacket-sensitive patients related to the risk of an anaphylactic reaction to a later sting. METHODS: Seventy-five yellow jacket-sensitive patients (29 male and 46 female) received a median number of three in-hospital sting challenges from a live insect in 3 subsequent years after discontinuation of venom immunotherapy. An anaphylactic reaction to one or more of the sting challenges was considered a relapse. We analyzed whether patients with and patients without a relapse differed in terms of gender, age, preimmunotherapy skin test data, preimmunotherapy level of venom-specific IgE, severity of the field-sting reaction that preceded immunotherapy, severity of the reaction to the sting challenge that preceded immunotherapy, adverse reactions to immunotherapy, changes in IgE and IgG4 levels during immunotherapy, duration of immunotherapy, and presence of venom-specific IgE after cessation of therapy. RESULTS: Venom immunotherapy was given for a median duration of 40 months (range, 7 to 120 months). Relapses were observed in six patients. In two of them, a rather severe anaphylactic reaction was observed after the second sting challenge. No relation was found between duration of venom immunotherapy and relapse risk. The relapse rate was higher among patients with high levels of specific IgE before and after immunotherapy. During therapy, the mean level of specific IgE decreased. This decline persisted in the 3 following years. No relapses of sting reactions were observed among patients without detectable specific IgE. CONCLUSION: Discontinuation of venom immunotherapy appears safe for patients with pretreatment IgE antibodies if these antibodies can no longer be detected during immunotherapy. For the remaining patients, a treatment period of 3 years may suffice. After discontinuation of immunotherapy, a clinical sting challenge can be considered to estimate the patient's current grade of hypersensitivity.

Adolescent↗

Regulation of the receptor for platelet-activating factor on human platelets.

Human platelets possess about 300 receptors for platelet-activating factor (PAF) per cell with a Kd of about 0.2 nM. In the present study we investigated whether these receptors are subject to intracellular control mechanisms. Preincubation with the protein kinase C inhibitor staurosporine had no effect, and also agents that increase cyclic AMP failed to change the binding of [3H]PAF. The Ca(2+)-calmodulin inhibitors W-7 and sphingosine decreased PAF binding by 50-80%. Inhibition of energy metabolism induced a fall in adenylate energy charge [AEC = ([ATP] + 1/2[ADP])([ATP + ADP + AMP])] and an almost parallel decrease in specific [3H]PAF binding without changing the Kd. Restoration of the AEC restored the [3H]PAF binding. Abrupt arrest of energy metabolism during binding of [3H]PAF left the binding unchanged until the metabolic ATP level had decreased by about 90%. These data indicate that PAF receptors on human platelets are under close intracellular control, possibly via a Ca(2+)-calmodulin-dependent phosphorylation/dephosphorylation process.

Adenosine Diphosphate↗

Human platelets secrete chemotactic activity for eosinophils.

Thrombin-stimulated platelets liberate factors that induce chemotaxis of eosinophils and raise their cytosolic Ca2+ content ([Ca2+]i). The sources of this activity are the dense- and alpha-granules because inhibition of prostaglandin endoperoxide/thromboxane A2 formation and the platelet-activating factor receptor-antagonist WEB 2086 have no effect. Platelets from patients with Storage-Pool Deficiency show about 60% of the normal chemotactic activity with little effect on [Ca2+]i, whereas completely degranulated platelets fail to affect eosinophils. In concentrations secreted by the platelets, adenosine diphosphate (ADP), and platelet factor 4 have no effect, whereas adenosine triphosphate (ATP) induces a strong chemotactic response and increases [Ca2+]i. However, apart from ATP other modulating factors must be involved as platelet releasates induce more chemotaxis than ATP alone. Thus, platelets secrete factors that activate eosinophils and may contribute to inflammatory and allergic processes.

Adenosine Diphosphate↗

Occupancy of platelet receptors for platelet-activating factor in asthmatic patients during an allergen-induced bronchoconstrictive reaction.

The administration of platelet-activating factor (PAF) to human subjects triggers asthma-like responses. We investigated whether a bronchoconstrictive reaction was accompanied by the release of PAF in the circulation of allergic asthmatics. The appearance of PAF was assessed by measuring the number of freely accessible PAF-receptors on platelets in vitro, assuming that the contact between platelets and PAF in vivo would reduce the receptor binding of [3H]PAF in vitro. 16 asthmatics were challenged twice, first with buffer and the next day with allergen. A comparison between receptor binding after provocation with the data of the same patients after allergen challenge revealed a significant difference in PAF binding (P = 0.034), with an average decrease of 14% immediately after allergen challenge followed by a return to control values after about 4 h and a transient increase of 9% at 7 h after provocation. The decrease in accessible PAF receptors was accompanied by a slight decrease in platelet count in peripheral blood between 30 min and 4 h after allergen challenge. The platelet counts recovered to the original values afterwards. These data support the concept that in patients with allergic asthma PAF is secreted in the circulation. The contact between PAF and the platelets may trigger the transient sequestration of platelets, possibly in the lung. Thus, PAF and platelets may contribute to the pathogenesis of allergic asthma.

Adolescent↗