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Biomedical subjects

M Demedts

Publications and source records attributed to M Demedts.

At least 55 records · Page 3Linked to original sources

Determinants of the hypercapnic and hypoxic response in normal man.

The purpose of this study was: (1) to identify the determinants of the hypercapnic (HCR) and hypoxic response (HR) in normal man; (2) to find out if they are dependent on the HR model used; and (3) to investigate if the occlusion pressure (P0.1), in contrast to the VE HCR and HR, is independent of gender, anthropometrical and lung functional indices. A total of 26 men (42.4+/-12.4 years) and 25 women (40.1+/-13.7 years) were studied. We found that men and women have similar P0.1 respiratory drives, but VE differs and is higher in men because of their larger vital capacity. For comparisons of the HCR or HR either the P0.1, or the VE HCR and HR normalized for VC or FEV1 should be used. With advanced age the VE HCR decreases in women. Especially for the HR, the identification of determinants (including age) is dependent on the HR model used.

Adult↗

A mathematical and physiological evaluation of the different hypoxic response models in normal man.

The purpose was: (1) to investigate which hypoxic response (HR) model(s) might be most suitable to measure the HR taking into account 'goodness of fit' to the individual data, clinical applicability and information obtained from each model; and (2) to investigate if the models are mutually exchangeable. The ventilatory (VE) and occlusion pressure (P0.1) HR were measured in 33 healthy volunteers (37+/-12 years). We found that the exponential, linear on oxygen saturation (LINSAT), hyperbolic with either a fixed (HYPV) or a variable position of the vertical asymptote (HYPH) models were comparable with respect to 'goodness of fit' to the individual data, but the correlation between the HR models was poor, except for the correlation between LINSAT and HYPV. Comparing HR data is justified when they are either provided by the same HR model, or by LINSAT or HYPV. Within each model the VE HR can be replaced by the P0.1 HR. LINSAT has the advantage of an easy applicable linear relationship, HYPH provides additional information about the O2-CO2 interaction component of the HR, but the model is more complex because two variables have to be determined by computerized iteration.

Adult↗

Sequential treatment with vindesine-ifosfamide-platinum (VIP) chemotherapy followed by platinum sensitized radiotherapy in stage IIIB non-small cell lung cancer: a phase II trial.

PURPOSE: Daily administration of cisplatin concomitant with radiotherapy improved the overall survival in inoperable non-small cell lung cancer (NSCLC) in one EORTC study. In this study, we prospectively investigated the efficacy and toxicity of a sequential treatment with three cycles of vindesine-ifosfamide-platinum (VIP) induction chemotherapy, followed by daily cisplatin-sensitized radiotherapy. METHODS: Between June 1993 and June 1995, 23 previously untreated patients with stage IIIB NSCLC with World Health Organization performance status 0 or 1 were included. Chemotherapy consisted of platinum 30 mg/m2 and ifosfamide 1200 mg/m2 i.v. on days 1, 2 and 3, and vindesine 3 mg/m2 i.v. on days 1 and 8, every 4 weeks. After three cycles and at least stable disease, radiotherapy was started (30 Gy in 10 fractions, followed by a boost of 22 Gy in 10 fractions). Each fraction was preceded by Platinum 6 mg/m2 i.v. RESULTS: Nineteen patients completed the sequential therapy. One patient died from neutropenic sepsis during the first cycle of chemotherapy, and three patients had progressive disease after chemotherapy. The overall response rate after sequential therapy was 47% (95% confidence interval 24-80), median survival was 10.6 months, 1- and 2-year survival rates were 47 and 16%, respectively. Major toxicity consisted of neurotoxicity grade III-IV in 18% and of leukopenia grade III-IV in 22% of the patients. Acute radiation pneumonitis grade III occurred in 11% of the patients. CONCLUSION: Three-drug VIP induction chemotherapy followed by cisplatin-sensitized radiotherapy is feasible, with acceptable, albeit substantial, toxicity. In spite of the theoretically promising sequence of therapies, survival results remain disappointingly low.

Aged↗

Present status of induction treatment in stage IIIA-N2 non-small cell lung cancer: a review. The Leuven Lung Cancer Group.

BACKGROUND: Surgical exploration in mediastinoscopy proven N2 non-small cell lung cancer (NSCLC) is unrewarding. Theoretical concepts suggest a beneficial role for preoperative induction treatment. The solidity of the therapeutic results with this approach in the currently available data is examined. METHODS: Literature on induction therapy followed by surgical exploration, consisting of randomized reports and phase II reports meeting some essential criteria, are reviewed. RESULTS: Of the twenty-four analyzed phase II studies, thirteen lack adequate surgical staging. Stratification for various important prognostic factors in N2 disease is missing in many instances. Results with induction with a cisplatinum dose of less than 80 mg/m2 seem to be inferior. The use of mitomycin-C in patients scheduled for lung resection or irradiation deserves caution. No evident difference in efficacy between induction chemotherapy or chemo-radiotherapy is suggested, but toxicity and mortality appear to be somewhat higher with chemo-radiotherapy. Pathological complete response is mainly found after an at least partial clinical response. Effect on survival in non-controlled phase II studies and small randomized reports is encouraging. CONCLUSIONS: the role of chemotherapy induction in improving the long-term survival of N2 NSCLC is promising, but needs to be confirmed by large multi-center randomized data. Adequate surgical staging and attention to important prognostic factors in N2 disease should minimize the numerous institution based differences interfering in the currently available non-controlled studies.

Antineoplastic Combined Chemotherapy Protocols↗

Chronic lymphocytic alveolitis with migrating pulmonary infiltrates after localized chest wall irradiation.

In a number of patients, radiotherapy following surgery for breast carcinoma may induce radiation injury to the lungs. This has classically been divided into an early radiation pneumonitis and a late fibrosis, both confined to the irradiated lung volume. However we observed a female patient who similarly to other recent reports in the literature developed a recurring pneumonitis migrating from one lung to the other after radiotherapy for breast carcinoma. This migratory BOOP (bronchiolitis obliterans organizing pneumonia) was characterized by a lymphocytic alveolitis and responded well to corticosteroids. Clinicians should be aware of the possibility of a lymphocytic pneumonitis in both lungs after unilateral thoracic irradiation and recognize the distinctive features of fever, cough, dyspnoea and malaise in order to start an effective treatment with corticosteroids. They should also be aware of the high tendency for recurrence when tapering off.

Anti-Inflammatory Agents↗

Bronchiolitis obliterans organising pneumonia. A report of 11 cases and a review of the literature.

The clinical syndrome "Bronchiolitis Obliterans Organising Pneumonia" (BOOP) has to be considered in patients with a flu-like illness since some weeks, fine crackles, and on chest X-ray bilateral patchy infiltrates. There is no response to antibiotics. BOOP is essentially idiopathic, but associations to other conditions exist. Lung function is often restrictive; biochemistry is not pathognomonic. BAL shows a mixed cellular pattern. The gold standard for pathologic diagnosis is open or thoracoscopic lung biopsy. However, a BOOP pattern or reaction is often seen on histologic specimens without the clinical-radiologic features of the BOOP-entity. Therapy consists of corticosteroids, which have to be prescribed for a long time at a rather high dose. Recurrence is frequent, but prognosis is good. Evolution to respiratory insufficiency and death is rare and may occur in rapidly progressive BOOP. This study reports on 11 cases (6 males/5 females) of clinical-pathological BOOP-syndrome (mean age 58 yrs, range 17-73 yrs), with an unexpectedly high mortality rate of 36% (4 cases). The disease was idiopathic in 7, and was associated with intake of amiodarone (in 1), with past Mycoplasma pneumonia (in 1) and with connective tissue disease (in 2). There was a history of a flu-like syndrome, cough and dyspnea of a mean duration of 4 months (range 1 week to 8 months). Lung function was mostly restrictive or/and obstructive with a diffusing capacity ranging between 47 and 95% predicted; there was hypoxia in about half of the patients. Chest X-ray and computed tomography (CT) scan showed a patchy consolidation with linear opacities (unilateral in 4 patients, bilateral in 5) and/or a ground glass pattern (in 4 patients), and a focal pseudo-tumoral lesion (in 1). Bronchoalveolar lavage showed a variable pattern of mixed, or eosinophilic or neutrophilic alveolitis. Histologic diagnosis was based on open lung biopsy (in 3), on thoracoscopic biopsy (in 2), on transbronchial biopsy (in 2), on wedge resection of the nodular lesion (in 1) and on postmortem lung biopsy (in 3). One patient recovered spontaneously, 1 remained cured after resection of the focal lesion, 7 were treated with 16-125 mg methylprednisolone (of whom 3 had a temporary flare-up during tapering the corticosteroids and 2 died after 1 and 3 months due to infectious complications), 2 died due to rapidly progressive BOOP.

Adolescent↗

Pulmonary Langerhans' cell granulomatosis (histiocytosis X): clinical analysis of 8 cases.

A detailed retrospective analysis of 8 cases has been set up to obtain an update of the clinical, radiological, diagnostic and therapeutical aspects of pulmonary Langerhans' cell granulomatosis (PLCG), previously called Histiocytosis X. This disease represents 2.8% of interstitial lung diseases (ILD) in a registration by pneumologists in Flanders. Seventy five% of our patients were active smokers. Cough, dyspnoe and constitutional symptoms were the main presenting symptoms. There was a 37.5% frequency of pneumothorax during the whole disease evolution and all these patients had to be treated with chemical or surgical pleurodesis. Spirometric pattern was variable but CO-transferfactor (TLCO) was significantly impaired in all our patients. Radiologically nodules and/or cystic lesions were found with preserved volumes. Open lung biopsy led to the diagnosis in 6 of the 8 cases. Transbronchial biopsies (TBB) were found to be not sensitive. Systemic staging in our group showed 50% of the patients to have a second focus of organ involvement. Treatment with corticosteroids and possibly immunosuppressives was without clear effect. Since 25% of our patients ultimately became candidate for lung transplantation extrapulmonary staging is prerogative and the high frequency of pleurodesis procedures in the past medical history of our patients has important implications since bilateral pleurodesis is still a contraindication for lung transplantation in some but not all institutions.

Adrenal Cortex Hormones↗

Possible recurrence of desquamative interstitial pneumonitis in a single lung transplant recipient.

Idiopathic pulmonary fibrosis (cryptogenic fibrosing alveolitis) is a disorder with a very poor prognosis for patients who do not respond to therapy with corticosteroids alone or in combination with immunosuppressive drugs, e.g. cyclophosphamide or azathioprine. For patients with end-stage disease, lung transplantation remains the only possibility for long-term survival. We describe a patient who received a left single lung transplant for end-stage desquamative interstitial pneumonitis. One year later, the patient again began complaining of exertional dyspnoea and a gradual decline in the transfer factor of the lung for carbon monoxide (TL,CO) was apparent. A recurrence of the primary disease in the transplanted lung was suspected on transbronchial biopsies. During treatment with high doses of steroids, a Pneumocystis carinii pneumonia developed, which was treated with co-trimoxazole. The patient completely recovered and, after a period of over 2 yrs, remained in an excellent condition, after which time he was lost from follow-up.

Adult↗

Relationship between external resistances, lung function changes and maximal exercise capacity.

In upper airway obstruction (UAO) the relationship between the degree of obstruction, exercise limitation and lung function indices is not well established. Therefore, we investigated in nine healthy subjects (age 36+/-9 yrs) the effects of two added resistances at the mouth (R1 = added resistance with 7.8 mm diameter; R2 = 5.7 mm) on forced expiratory volume in one second (FEV1), peak expiratory flow (PEF), airway resistance (Raw) and maximal breathing capacity (measured during 15 s = measured maximum breathing capacity (MBCm); calculated as FEV1x37.5 = calculated maximum breathing capacity (MBCc)) on the one hand, and maximum exercise capacity (W'max), minute ventilation (V'E) and CO2 elimination (V'CO2) on the other. We found that R1 had almost no influence on FEV1 but decreased PEF by approximately 35% and increased Raw by almost 300%; it decreased W'max by merely approximately 10% while maximal exercise ventilation (V'Emax) was only 65% of control and only reached approximately 40% MBCc and approximately 70% MBCm; yet V'E and V'CO2 were significantly reduced at high exercise levels indicating hypoventilation. With R2, FEV1 was reduced by 25% and PEF by 55%, and Raw was increased by 600%; W'max was approximately 60% of control, V'Emax was only 35% of control and reached approximately 30% MBCc and approximately 60% MBCm, V'E was already reduced at moderate exercise levels. We conclude that: 1) an upper airway obstruction of 6 mm diameter (but not of 8 mm) had a marked influence on maximum exercise capacity due to hypoventilation; 2) calculated maximum breathing capacity markedly overestimated measured maximum breathing capacity because the forced expiratory volume in one second is an insensitive index of upper airway obstruction and because it does not take inspiratory flow limitation into account; and 3) a 10% decrease in maximum exercise capacity was linearly related with a 7% decrease in the forced expiratory volume in one second and a 150% increase in airway resistance. A 10% decrease in maximal exercise ventilation was related to a 8.5% decrease in peak expiratory flow and 9% decrease in measured maximum breathing capacity.

Adult↗

Interstitial lung disease more than 40 years after a 5 year occupational exposure to talc.

A 62 yr old woman was initially diagnosed with sarcoidosis until a thoracoscopic biopsy revealed the presence of numerous birefringent particles in fibrotic areas of the centrilobular lung zones. These particles were examined by electron microscopy and X-ray spectrometry and characterized as impure talc. Further inquiry into her occupational history revealed that she had worked from the age of 14-18 yrs in a factory making rubber hoses, where she had had an intense exposure to talc. There was no evidence of silicosis or asbestosis, and other significant causes of interstitial lung disease were excluded. This case emphasizes the importance of a thorough occupational history, which may reveal a remote and forgotten exposure to a significant cause of interstitial lung disease. Although this presentation of talcosis is unusual, this case suggests that even a relatively short, but presumably intense exposure to talc more than 40 yrs previously may be a cause of progressive lung fibrosis.

Female↗

High incidence of primary pulmonary hypertension associated with appetite suppressants in Belgium.

Primary pulmonary hypertension is a rare, progressive and incurable disease, which has been associated with the intake of appetite suppressant drugs. The importance of this association was evaluated in Belgium while this country still had no restriction on the prescription of appetite suppressants. Thirty-five patients with primary pulmonary hypertension and 85 matched controls were recruited over 32 months (1992-1994) in Belgium. Exposure to appetite-suppressants was assessed on the basis of hospital records and standardized interview. Twenty-three of the patients had previously taken appetite suppressants, mainly fenfluramines, as compared with only 5 of the controls (66 versus 6%, p<0.0001). Five patients died before the interview, all of them had taken appetite suppressants. In 8 patients the diagnosis of primary pulmonary hypertension was uncertain, 5 of them had taken appetite suppressants. The patients who had been exposed to appetite suppressants tended to be on average more severely ill, and to have a shorter median delay between onset of symptoms and diagnosis. A policy of unrestricted prescription of appetite suppressants may lead to a high incidence of associated primary pulmonary hypertension. Intake of appetite suppressants may accelerate the progression of the disease.

Adult↗

Bronchodilator response in 3-6.5 years old healthy and stable asthmatic children.

Few data are available on the bronchodilator response in preschool children. This study was set up to study baseline lung function and bronchodilator responses in healthy and asthmatic children younger than 7 yrs old. In 281 preschool children attending kindergarten (age range 2.7-6.6 yrs old) respiratory system resistance (Rrs) and reactance (Xrs) by impulse oscillation system at 5, 10, 15, 20, 25 and 35 Hz as well as resonance frequency (f0) were measured before and 20 min after 200 microg inhaled salbutamol by a metered-dose inhaler connected to a spacer device. Thirty-four of them were diagnosed as asthmatics based on a validated standardized questionnaire. The mean Rrs (+/-SD) at 5 Hz (Rrs,5) was 1.03 (+/-0.24) kPa x L(-1) x s for healthy children and 1.09 (+/-0.26) kPa x L(-1) x s for stable asthmatics. The mean change in Rrs,5 after salbutamol was -0.13 (+/-0.20) kPa x L(-1) x s for the healthy children and -0.09 (+/-0.25) kPa x L(-1) x s for the asthmatic group. The scatter for the measurements was striking. Neither baseline values of impulse oscillation nor its changes after bronchodilator administration was significantly different between healthy and stable asthmatic children. A change in respiratory system resistance at 5 Hz of 40% is to be considered the cut-off for a " positive" bronchodilator response.

Adrenergic beta-Agonists↗

No paradoxical bronchodilator response with forced oscillation technique in children with cystic fibrosis.

STUDY OBJECTIVES: The aim of the present study was to evaluate the forced oscillation technique (FOT) in cystic fibrosis (CF) children and to participate in the discussion about the usefulness of beta2-antagonists in CF. DESIGN: Pulmonary function was measured with spirometry, body plethysmography, and FOT before and after inhalation of 200 microg of albuterol (salbutamol). The following were collected: vital capacity (VC), FEV1, FEV1/VC, airway resistance (Raw), thoracic gas volume, respiratory system resistance (Rrs) and respiratory system reactance (Xrs) at 6 Hz (Rrs6 and Xrs6), and resonance frequency. SETTING: The study was set up at a university hospital with a CF population of 125 children and adolescents. PATIENTS: Data were collected on 20 patients in stable condition able to perform the three lung function tests. MEASUREMENTS AND RESULTS: Mean baseline values (+/-SD) were 0.36+/-0.15 kPa/L/s for Raw, 0.5+/-0.15 kPa/L/s for Rrs6, and 61+/-22% predicted for FEV1. The relationship between FEV1 and Raw or Rrs6 was poor. Xrs6 and FEV1/VC correlated weakly (r=0.56; p < 0.05). After bronchodilator administration, the mean changes +/-SD in percent of baseline were +3 +/- 11% for FEV1, -16 +/- 22% for Raw, and -16 +/- 9% for Rrs6. In six patients, a paradoxical decrease in FEV1 was measured but an increase in Rrs6 was never found; in two patients, an increase of Raw of < 10% was found. In 13 patients, the decrease of Rrs6 was > 12%. CONCLUSIONS: The results suggest that FOT measurements cannot replace baseline spirometric measurements in CF, but that the evaluation of the effect of beta2-agonists on the airway diameter in CF should include an FOT measurement.

Administration, Inhalation↗

Pulmonary tuberculosis in the adult in a low prevalence area: is the radiological presentation changing?

SETTING: Pulmonary division of a university hospital in Belgium, an area with a relatively low tuberculosis incidence (14.9 per 100 000 population in 1993). OBJECTIVE: To evaluate whether 'unusual' radiographic presentations of pulmonary tuberculosis (PTB) have increased in recent years, especially in elderly and non-indigenous patients. DESIGN: Retrospective study of chest X-rays of 219 patients aged over 18 years with bacteriologically proven PTB in the period 1981-1990, including 92 elderly (> or =65 years) and 17 non-indigenous patients. 'Unusual' presentations consisted of solitary pleural effusion, isolated hilar or mediastinal lymphadenopathies, normal chest X-ray, lower lung field TB, nodular lesions, diffuse infiltrations and atelectasis. RESULTS: There was an increase in 'unusual' presentations, from 24% in 1981-1985 to 35% in 1986-1990, yet this was not statistically significant (P = 0.08). This increase tended to be more pronounced in the elderly age group, i.e., from 24% to 42% compared to 23% to 31% in the younger age group. The proportion of elderly patients in the group with 'unusual' findings was 44% in 1981-1985 and 48% in 1986-1990. In the non-indigenous group, the percentage of 'unusual' findings did not change between the two periods (40% versus 41%). The proportion of non-indigenous patients in the group with 'unusual' findings increased from 7% in 1981-1985 to 13% in 1986-1990; however, this difference was not significant. CONCLUSIONS: In an area with low TB incidence, adult PTB still presents with the classical pattern of reactivation disease. Although not statistically significant, there is a trend towards a relative increase in the frequency of unusual presentations in recent years, which is most pronounced in the elderly and in non-indigenous adults.

Adolescent↗

Heparan sulfate proteoglycan expression in human lung-cancer cells.

Heparan sulfate (HS) functions as a co-factor in several signal-transduction systems that affect cellular growth, differentiation, adhesion and motility. HS, therefore, may also play a role in the malignant transformation of cells, tumor growth, cell invasiveness and the formation of tumor metastases. To explore this hypothesis, we analyzed the expression of HS and heparan sulfate proteoglycan (HSPG) in histological sections of human lung-cancer tissues and assayed for the presence of HSPGs in extracts of human lung-cancer cell lines, using a panel of native HS-, delta-HS- and HSPG (syndecan, glypican, CD44 and perlecan) core protein-specific monoclonal antibodies. Compared to normal epithelia, non-small-cell lung carcinomas, particularly poorly differentiated tumors, often expressed reduced amounts of the major cell surface-associated HSPGs (most consistently of syndecan-1). CD44 or CD44-variant proteins, in contrast, were found on all tumor cells, irrespective of their differentiation. Perlecan, a matrix-associated HSPG found in the basement membrane of normal bronchial epithelium, was consistently undetectable in invasive bronchogenic carcinomas. Staining reactions for native HS were consistently reduced in squamous-cell lung carcinomas, in the cells in contact with the stroma and in the less differentiated areas of these tumors. Reactions for delta-HS, however, were not reduced, suggesting a structural change in the HS of these tumor cells. Poorly differentiated adenocarcinomas, in contrast, yielded strong HS and delta-HS reactions. Marked differences in HSPG expression also were observed among various non-small-cell lung carcinoma cell lines. Our results suggest that poorly differentiated lung tumors have markedly altered patterns of HSPG expression, which may contribute to their invasive phenotype.

Adenocarcinoma↗

Assessment of the sensitization potential of five metal salts in the murine local lymph node assay.

The murine local lymph node assay (LLNA) has been proposed as a predictive test for the identification of sensitizing agents. We used this test to compare the sensitization potential of NiSO4, K2Cr2O7, CoCl2, Na2PtCl6 and BeSO4, salts of metals which have all been associated with allergic contact dermatitis and either bronchial asthma orinterstitial lung disease, by either humoral or cell-mediated allergic mechanisms. BALB/c mice (n = 3 per concentration studied, three concentrations studied per metal) received three daily applications of the metal salt (in DMSO) on the dorsum of both ears. On the fourth day the draining auricular lymph nodes were removed and the incorporation of [3H]-thymidine in the lymphocytes in culture was compared to that of concurrent vehicle-treated control mice, thus enabling to derive a stimulation index (SI), indicative of immunological sensitization potential. Each experiment was performed three times. Oxazolone and toluene diisocyanate, chosen as positive controls, yielded strongly positive SI values (> 20 and > 30 respectively). Na2PtCl6 (SI 2.6 +/- 1.0 at 2.5%), CoCl2 (SI 2.8 +/- 0.5 at 5%) and possibly also K2Cr2O7 (SI 2.1 +/- 1.2 at 0.5%) were positive in the LLNA, whereas NiSO4 (SI 0.9 +/- 0.2 at 5%) and BeSO4 (SI 1.3 +/- 0.6 at 4%) were negative. Although our results are still limited by the fact that only one mice strain was tested, they indicate that there is no strict relationship between the sensitization potential of metal salts, as evaluated in the murine LLNA, and their potential to cause either respiratory or dermal allergic disease. Consequently, caution should be exercised before proposing the murine LLNA as a valid test to predict the sensitization potential of low molecular weight chemicals.

Allergens↗