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Biomedical subjects

M Demedts

Publications and source records attributed to M Demedts.

At least 19 recordsLinked to original sources

In vitro cytotoxicity of various forms of cobalt for rat alveolar macrophages and type II pneumocytes.

It has been shown that cobalt (Co) and the mixture cobalt-tungsten carbide (CoWC) are cytotoxic for alveolar macrophages (AM) and alveolar type II cells (AT-II), but the exact mechanisms of toxicity are not entirely elucidated. In this study, we exposed primary cultures of AT-II and AM, in vitro, to different forms of Co (Co particles, CoWC particles, CoCl(2)) and assessed cell damage using the dimethylthiazol diphenyl tetrazolium bromide test. In some experiments, inserts were used to separate the particles from the cells. The results show that AT-II are twice as sensitive to the effects of 100 microg Co particles/well (1.88 cm(2)) than AM. For this latter cell type, the presence of WC almost doubled (at 25 microg Co/well) the toxic effects compared to pure Co, but this synergy between Co and WC only occurred if the particles were in close contact with the cells. Lactalbumin and, to a lesser degree, EDTA were able to reduce the toxicity of Co, CoWC, and CoCl(2) for AT-II and AM. CoCl(2) showed a similar toxicity for AT-II and AM. The use of Co-conditioned medium revealed that Co particles are "aged" after having been incubated for 24 h in an aqueous medium and are then no longer able to cause the same degree of cell damage as fresh Co particles (71 versus 15% viability for 100 microg Co/well). The time course of the toxicity of the different forms of Co for AT-II and AM showed different patterns in causing cell damage, suggesting different action mechanisms. Evaluation of cell damage by electron microscopy was consistent with biochemical indices. Overall, our results indicate that the Co ion does play a role in the toxicity of both Co particles and CoWC particles.

Animals

Cyclophosphamide rescue therapy for chronic rejection after lung transplantation.

BACKGROUND: Obliterative bronchiolitis remains the leading cause of late mortality after heart-lung and lung transplantation. Although several treatment options have been advocated, none has proven to be very successful. Cyclophosphamide is effective in the treatment of idiopathic pulmonary fibrosis, and chronic rejection after lung transplantation is also a fibroproliferative process. We therefore conducted an open, uncontrolled study to look at the effect of cyclophosphamide rescue therapy in the treatment of chronic rejection in lung transplant recipients. METHODS: Between October 1996 and March 1998 cyclophosphamide was prescribed to 7 patients with chronic and persistent rejection who failed to respond to conventional therapy (pulse steroids or antilymphocyte products or both). RESULTS: Cyclophosphamide therapy was initiated on postoperative day 478+/-366. At that time 2 patients were in bronchiolitis obliterans syndrome stage 0, 3 patients in stage 1, and 2 patients in stage 2. Their best postoperative forced expiratory volume in one second (FEV1) was 2.19+/-0.75 L. Three months before the start of cyclophosphamide the FEV1 had declined to 1.90+/-0.83 L, with a further decline to 1.63+/-0.64 L at the time of initiating cyclophosphamide. In 6 of the 7 patients the FEV1 stabilized or increased after cyclophosphamide had been started (mean FEV1 3 and 6 months after cyclophosphamide of 1.77+/-0.58 L and 1.79+/-0.48 L, respectively). One patient died 18 months after the introduction of cyclophosphamide due to progressive obliterative bronchiolitis. In one patient cyclophosphamide had to be stopped because of persistent leucopenia. CONCLUSIONS: Cyclophosphamide might be a promising therapeutic alternative for the treatment of chronic persistent rejection after lung transplantation.

Adult

Asthma symptoms: influence of personality versus clinical status.

The hypothesis that symptom-reporting in asthmatics does not necessarily correspond with clinical status, but is related to negative affectivity was investigated. One hundred and sixteen asthmatic patients filled out the Asthma Symptom Checklist (ASC), the Negative Emotionality Scale (NEM), and the McMaster-Asthma Quality-of-Life Questionnaire (AQLQ). The patients were grouped as either hospitalized, outpatient previously hospitalized or outpatient not previously hospitalized for asthma. Lung function data and Asthma Severity Scores (ASS) were also collected. The hospitalized group was retested after 3 months. The hospitalized group had lower AQLQ scores, higher ASS scores and worse lung function than both outpatient groups. However, the hospitalized group and the outpatients previously hospitalized group had higher ASC scores and NEM scores than the outpatients not previously hospitalized group. After discharge, when the hospitalized group had become clinically stable, their ASC and NEM scores remained comparable to those of the outpatient previously hospitalized group. Symptom-reporting in asthmatics is not necessarily in accordance with clinical status, but may be directly or indirectly mediated by personality, such as negative affectivity.

Adult

Systemic lupus erythematosus, eosinophilia and Löffler's endocarditis. An unusual association.

A 24-yr-old male, known since the age of 11 to have a nonerosive arthritis and later diagnosed as having systemic lupus erythematosus (SLE), developed subacute heart failure with diffuse lung infiltrates and died suddenly after having presented a moderate hypereosinophilia for 6 months for which no other causes besides the SLE were found. A post mortem examination revealed Löffler's endocarditis (endocarditis parietalis fibroplastica) with acute pulmonary capillaritis. This represents Löffler's endocarditis in the setting of SLE. To the best of the authors' knowledge, this association has not been reported before.

Adult

Medical thoracoscopic lung biopsy in interstitial lung disease: a prospective study of biopsy quality.

The aim of this study was to analyse the quality and diagnostic value of lung biopsies for the diagnosis of interstitial lung disease (ILD), taken with diathermy coagulation cup forceps during medical thoracoscopy. Patients with ILD, not specified after thorough clinical assessment, high-resolution CT (HRCT), bronchoalveolar lavage and transbronchial biopsy, were studied. Medical thoracoscopy was performed in an endoscopy suite under neuroleptic anaesthesia with spontaneous ventilation. Biopsy specimens were analysed prospectively by one lung pathologist blinded to the clinical findings. Over 2 yrs, 118 samples were analysed from 24 consecutive patients. A good quality biopsy was obtained in 23 patients, and 78% of the samples were of good quality. Biopsy findings plus clinical and HRCT data revealed a relevant diagnosis in 18 patients and some diagnostic clues in four patients, for whom further examinations were needed. No major complications occurred. Chest tube drainage averaged 5.3+/-4.7 days, and was related to the total lung capacity (p=0.008), which mirrors the severity of ILD. Separate sampling of biopsies from different lobes proved to be useful in one third of the cases. In conclusion, lung biopsy sampling can be performed safely by interventional pulmonary endoscopists and has a good diagnostic yield in interstitial lung disease of unknown origin.

Adult

Investigation of the transport of intact glutathione in human and rat type II pneumocytes.

The aim of the study was to investigate whether there is transmembrane transport of intact glutathione ([3H]-GSH, 0.1 microCi) in rat and human type II pneumocytes (T2P), and if this transport might be dependent on the redox state of the extracellular fluid. The T2P were pretreated with acivicin (250 microM) to inhibit gamma-glutamyltransferase activity and with L-buthionine-[SR]-sulfoximine (1 mM) to inhibit intracellular GSH synthesis. After 48 h in culture, initial GSH influx rate was 0.70 +/- 0.20 nmol/min/mg protein (37 degrees C) and 0.35 +/- 0.04 nmol/min/mg protein (4 degrees C) during the first 5 min in rat T2P. In human T2P, the initial GSH influx rate was 0.36 +/- 0.30 nmol/min/mg protein (37 degrees C) and 0.32 +/- 0.06 nmol/min/mg protein (4 degrees C) during the first 10 min. Thereafter no further influx was found. The influx of 1 mM GSH in freshly isolated rat and human T2P in suspension was 2.3 +/- 0.3 and 1.2 +/- 0.3 nmol/mg protein after 15 min at 37 degrees C, and 2.8 +/- 0.2 and 1.0 +/- 0.3 nmol/mg protein at 4 degrees C, respectively. When GSH influx was studied at different concentrations between 0 and 40 mM, a linear increase without saturation or difference between 37 degrees C and 4 degrees C was found. Pre-exposure to ouabain had no effect on GSH influx. Efflux of GSH was stimulated and influx inhibited by pre-exposure of the cells to reduced thiols, while disulphides inhibited efflux and favoured inward uptake. Thus, in human and rat T2P a GSH-carrier exists which operates as an effluxer. At GSH concentrations in the physiological range no uptake is seen, but some uptake can be observed at GSH concentrations above normal physiological levels. The uptake appears to be energy-independent and non-saturable. Efflux of GSH is stimulated and influx inhibited by reduced thiols, while disulphides inhibit the efflux and favour inward uptake. GSH uptake in T2P thus may depend on concentration gradients and driving forces, such as the redox state of the extracellular fluid.

Animals

Micturitional disturbances are associated with impaired breathing control in multiple sclerosis.

STUDY OBJECTIVES: To investigate whether the localization of multiple sclerosis (MS), the duration of the disease, and the level of neurologic functioning in patients with MS predispose them to disturbed breathing control. DESIGN: Case-control study. SETTING: Outpatient pneumology department of a university hospital. PATIENTS: Twenty-three MS patients and 51 healthy control subjects. MEASUREMENTS AND RESULTS: Resting mouth occlusion pressure at 0.1 s after onset of inspiratory effort (P0.1) was measured during the hypercapnic response (HCR) and the hypoxic response (HR) in all subjects. The Kurtzke expanded disability status scale and the functional system score were used to describe the level of neurologic functioning of the MS patients. Predictors of HCR and HR were assessed by multiple regression analysis. Low maximal inspiratory pressure (MIP) values correlated with low resting P0.1 values (r = 0.44; p = 0.05), although in neuromuscular diseases, high resting P0.1 values are usually found to compensate for low MIPs. Detrusor-sphincter dyssynergia (DSD) was the only predictor for lower ventilatory HCR (p = 0.006; r2 = 0.52), lower P0.1 HCR (p = 0.004; r2 = 0.47), lower ventilatory HR (p = 0.04; r2 = 0.28), and lower P0.1 HR (p = 0.04; r2 = 0.10); low MIPs and pyramidal tract involvement had no role. CONCLUSIONS: (1) Impaired control of breathing in some MS patients is related mainly to central defects. (2) DSD is the most important predictor of disturbed ventilatory control, presumably because the micturition and pneumotaxic center are closely related and located in the rostral pons. (3) No relationship with the duration of the MS disease could be demonstrated, which can be explained by the variable course of MS itself.

Adult

Preoperative work-up of a solitary diaphragmatic mass in a patient with right shoulder pain: a case for diagnosis.

A patient presented with right shoulder pain. Imaging studies revealed an apparently solitary soft tissue pleural lesion, accompanied by a very small pleural effusion. On medical thoracoscopy, a diffuse malignant pleural mesothelioma was found. Thoracoscopy proved to play an essential part in the diagnostic work-up, avoiding a futile thoracotomy for a presumed solitary soft tissue tumour.

Asbestos

[Asthma: general introduction, definition, incidence].

Our knowledge of asthma as well as the methods for investigation and the basic concepts of the treatment have been enormously expanded in recent years. The uniform application of the consensus reports are essential for a harmonic treatment policy. Molecular biologic strategies are expected in the near future.

Asthma

Dermal and respiratory sensitization to chromate in a cement floorer.

BACKGROUND: To report a well-documented case of both allergic contact dermatitis and occupational asthma due to chromate exposure in a 48-year-old floorer. METHODS AND RESULTS: A 48-year-old floorer, occupationally exposed to cement and with a documented chromate contact dermatitis, reported dyspnea and wheezing after work. These conditions were demonstrated by self-measured sequential peak expiratory flows. A first bronchial provocation (BPT) with potassium dichromate (K2Cr2O7) (0.3% nebulized for a total of 60 minutes) led to pronounced and sustained decreases in forced expiratory volume in 1 second (FEV1) and forced vital capacity, accompanied by pruritus, a decrease in arterial PO2, a slight rise in temperature, and peripheral blood leukocytosis. (This concentration of K2Cr2O7 is not recommended for BPT). Bronchoalveolar lavage performed 2 days later showed 18% eosinophils. Tow years later, a BPT with a lower dose of K2Cr2O7 (0.01% for the total of 31 min) led to an "earl late" reaction (FEV1 dropped by 195 compared with the initial FEV1 value), accompanied by pruritus. A BPT with dry cement, containing 12 ppm hexavalent chromium, was borderline (FEV1 dropped by 13%), and a similar result (FEV1 dropped by 14%) was obtained after smoking five cigarettes, laced with 10 mg of cement per cigarette. CONCLUSIONS: This report illustrates that a subject, with allergic contact dermatitis to chromates, may develop a respiratory allergic reaction to an airborne source of this metal. The main novelty of our report is that the smoking of cigarettes contaminated with cement may have been significant factor in the causation or elicitation of these reactions.

Asthma

Protective effects of the lazaroid U-74389G against hyperoxia in rat type II pneumocytes.

The aims of this study were to investigate the effect of hyperoxia on O2(-.), H2O2 and .NO generation and iNOS mRNA levels in rat type II pneumocytes in vitro and the possible protective effect of the lazaroid U-74389G. Rat type II pneumocytes were exposed, 36 h after isolation, to air, 60% or 85% O2 for 48 h. At the beginning of the experiment and 24 h later, the cells were exposed for 30 min to either 30 microM U-74389G or only the vehicle for the lazaroid (control). Exposure to 60% and 85% O2 decreased nitrite production 2.9-fold and 3.9-fold, and increased O2(-.) and H2O2 generation 4.6-fold and 6.7-fold, respectively. In the 85% O2-exposed cells, hyperoxia increased lipid peroxidation (thiobarbituric acid reactive substances, TBARS production) 2-fold and iNOS mRNA production 5.4-fold. U-74389G prevented the decrease in nitrite and the rise in O2(-.) and H2O2 production, the increase in TBARS and the rise in iNOS mRNA after hyperoxia. We conclude that exposure of type II pneumocytes in vitro to subtoxic oxygen levels leads to a disturbance in the .NO-O2(-.) balance despite increased iNOS mRNA levels. The lazaroid U-74389G appears to be a useful compound in the protection of hyperoxic lung injury by restoration of this .NO-O2(-.) balance and prevention of TBARS formation.

Animals

Expiratory CT in cigarette smokers: correlation between areas of decreased lung attenuation, pulmonary function tests and smoking history.

The aim of this study was to determine the correlation between cigarette-smoke-related bronchial disease and air trapping as assessed by expiratory high-resolution CT (HRCT) scans. Thirty healthy subjects (11 non-smokers, 7 ex-smokers for > 2 years, 12 current smokers; age range 35-55 years) with a smoking history between 0 and 28.5 pack-years underwent pulmonary function tests (PFT) and HRCT in inspiration and expiration in supine and prone position. The extent of air trapping was scored in ventral and dorsal aspects of the upper, middle and lower lung portions. In 24 subjects (7 non-smokers, 7 ex-smokers, 10 current smokers) areas of focal air trapping were found, and were present significantly more often in dependent lung portions (p < 0.05) compared with non-dependent portions. No significant differences were found between apical and basal lung zones. Scores of focal air trapping were not significantly different between smokers and ex-smokers, but were significantly lower (p < 0.05) in non-smokers and showed a significant (p < 0.0005) correlation with pack-years. The degree of air trapping was also associated with several lung function tests, especially RV, DLCO, FRC, FEV1 and FEV1/VC. Air trapping is seen in smokers with normal PFT and correlates with the severity of the smoking history, independently of current smoking status.

Adult

Primary ciliary dyskinesia: evolution of pulmonary function.

UNLABELLED: Pulmonary function tests were obtained in 11 patients with primary ciliary dyskinesia. Their mean age was 15 years (range 6-32). Their pulmonary function was obstructive, with a vital capacity (mean+/-SD) of 75%+/-20% predicted, a forced expiratory volume in 1s (FEV1) of 63%+/-20% predicted and a raised residual volume of 169%+/-50% predicted. After inhalation of 200 microg of salbutamol the mean change in FEV1 was + 13.2%+/-9.6% of the baseline value. In the 10 oldest patients, lung function had been measured at regular intervals during 3 20 years. Interestingly, during childhood and adolescence the evolution was not unfavourable: vital capacity increased by 8%+/-20% and FEV1 remained stable (mean change 0.3%+/-12%). Only 2 patients had an unfavourable evolution. CONCLUSION: At time of diagnosis, patients with primary ciliary dyskinesia have partially reversible obstructive airway disease. During regular follow up and therapy, there is no evidence of a further decline in lung function. Patients with associated immunodeficiency or important damage at the start of therapy may have a worse prognosis.

Adolescent

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