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M G Demedts

Publications and source records attributed to M G Demedts.

30 records · Page 2Linked to original sources
PubMed1998

Lymph node staging in non-small-cell lung cancer with FDG-PET scan: a prospective study on 690 lymph node stations from 68 patients.

PURPOSE: To compare the accuracy of computed tomography-(CT) scan and the radiolabeled glucose analog 18F-fluoro-2-deoxy-D-glucose (FDG) positron emission tomography (PET) visually correlated with CT (PET + CT) in the locoregional lymph node (LN) staging of non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: Sixty-eight patients with potentially operable NSCLC underwent thoracic CT, PET, and invasive surgical staging (ISS). Imaging studies were read prospectively and blinded to the surgical and pathologic data. A five-point visual scale was used for the interpretation of LNs on PET. Afterwards, with knowledge of the pathology, the relationship between standardized uptake values (SUVs) and the presence of metastasis in LNs was explored in a receiver operating characteristic (ROC) analysis, and the likelihood ratios (LRs) for SUVs of LNs were determined. RESULTS: ISS was available for 690 LN stations. CT correctly identified the nodal stage in 40 of 68 patients (59%), with understaging in 12 patients and overstaging in 16 patients. PET + CT was accurate in 59 patients (87%), with understaging in five patients and overstaging in four patients. In the detection of locally advanced disease (N2/N3), the sensitivity, specificity, and accuracy of CT were 75%, 63%, and 68%, respectively. For PET + CT, this was 93%, 95%, and 94% (P = .0004). In the ROC curve, the best SUV threshold to distinguish benign from malignant LNs was 4.40. The analysis with this SUV threshold was not superior to the use of a five-point visual scale. The LR of a SUV less than 3.5 in an LN was 0.152; for a SUV between 3.5 and 4.5, it was 3.157; and for a SUV greater than 4.5, it was 253.096. CONCLUSION: PET + CT is significantly more accurate than CT alone in LN staging of NSCLC. A five-point visual scale is as accurate as the use of an SUV threshold for LNs in the distinction between benign and malignant nodes. The very high negative predictive value of mediastinal PET could reduce the need for mediastinal ISS in NSCLC substantially.

Adult↗
PubMed1997

Survival and prognostic factors in resected N2 non-small cell lung cancer: a study of 140 cases. Leuven Lung Cancer Group.

BACKGROUND: The selection of stage IIIA N2 non-small cell lung cancer patients for primary surgical treatment remains controversial. METHODS: One hundred forty patients with resected non-small cell lung cancer who eventually proved to have pathologic N2 disease were studied with a univariate and multivariate analysis of prognostic factors. RESULTS: Nineteen patients had a positive mediastinoscopy; the others had a preoperative N0 or N1 stage. Complete resection rate was 80.7%. Five-year survival was 20.8% (95% confidence interval, 17.2% to 24.4%), 32.2% in mediastinoscopy-negative patients. In the univariate analysis, clinical N stage at mediastinoscopy, complete resection, performance status, T stage, number of metastatic levels in adenocarcinoma, and nodal capsule rupture were important factors. In a multivariate model, survival was worse in case of higher T stage (relative risk = 1.43), lower performance status (relative risk = 1.37), involvement of more than one node level (relative risk = 1.68), nonsquamous histology (relative risk = 1.29) and clinical N2 stage (relative risk = 1.43). Long-term survival was unlikely when lactic dehydrogenase or carcinoembryonic antigen levels were elevated. CONCLUSIONS: In clinical N0 or N1 cancer, complete resection resulted in reasonable survival prospects. In patients with N2 disease discovered at mediastinoscopy, surgical treatment was only worthwhile in case of minimal N2. Several unfavorable prognostic factors could be identified in the univariate analysis and confirmed in a multivariate Cox model.

Adenocarcinoma↗
PubMed1996

Epinastine (WAL 801CL) modulates the noncholinergic contraction in guinea-pig airways in vitro by a prejunctional 5-HT1-like receptor.

Electrical field stimulation (EFS) of guinea-pig airways, in vitro, evokes an excitatory nonadrenergic noncholinergic (eNANC) contraction mediated by release of tachykinins from sensory nerve endings. Epinastine (WAL 801CL) is an antihistaminic drug with binding affinity at certain other receptors, including alpha-adrenergic receptors and various serotonin (5-HT) receptor subtypes. It is used in asthma treatment; however, its mechanism of action remains to be fully defined. We have investigated whether epinastine could modulate the eNANC contraction in guinea-pig airways in vitro, and have tried to elucidate its receptor mechanism. Epinastine (0.1-100 microM) produced a concentration-dependent inhibition of the noncholinergic contraction, with a maximum inhibition of 91 +/- 7% at 100 microM. Pretreatment of the tissues with combined 5-HT1/5-HT2 antagonists, methysergide (1 microM) or methiothepin (0.1 microM), significantly attenuated the inhibitory effect of epinastine on the noncholinergic contraction. Pretreatment with tropisetron (1 microM), a 5-HT3 antagonist, ketanserin (10 microM), a 5-HT2 antagonist, thioperamide (10 microM), a histamine H3 antagonist, or phentolamine (10 microM), an alpha-adrenergic antagonist, however, had no effect. Chlorpheniramine (10 microM), another histamine H1 receptor antagonist without significant 5-HT receptor binding affinity, did not produce any inhibition of the eNANC contraction. Epinastine (100 microM) did not displace the dose-response curve to exogenously applied substance P (0.01-10 microM). These results suggest that epinastine, although identified as a 5-HT antagonist, acts as a 5-HT1 agonist and that it inhibits the noncholinergic contraction in guinea-pig airways through stimulation of a prejunctional 5-HT1-like receptor, located to sensory nerves.

Animals↗
PubMed1996

Hormonal treatment in advanced non-small cell lung cancer: fact or fiction?

In patients with advanced non-small cell lung cancer, cachexia is an important cause of morbidity and mortality. The pathogenic mechanism of this finding, usually referred to as "cancer anorexia and cachexia syndrome" (CACS), is complex and far from completely understood, but a disturbed equilibrium between possible food intake and metabolic needs seems to be fundamental. The literature data on the treatment options in advanced non-small cell lung cancer (NSCLC) with cachexia are reviewed. Based on the clinical studies on cancer cachexia, some recommendations for the therapeutic approach of this disorder in patients with advanced NSCLC can be given. Metoclopramide is easily administered, can alleviate gastric disturbances, but probably does not correct the catabolic spiral of CACS. There are not enough data to advise the use of parenteral nutritional support, hydrazine, cyproheptadine, tetrahydrocannabinol or nandrolone decanoate. Corticosteroids are useful in additional analgesia and fast palliation of very weak and debilitated patients in the final episode of their disease. Recent data in non-small cell lung cancer patients are in favour of the use of high-dose progestagens to improve both appetite and weight.

Cachexia↗
PubMed1996

Opioids modulate the cholinergic contraction but not the nonadrenergic relaxation in guinea-pig airways in vitro.

(D-ALa2, NMePhe4, Gly-ol5) encephalin (DAMGO), a selective mu-opioid receptor agonist, has previously been demonstrated to inhibit the cholinergic and the noncholinergic contraction in guinea-pig airways. In contrast, opioids had no inhibitory effect on cholinergic neurotransmission in the upper trachea when stimulated at 8 Hz. We investigated whether DAMGO, a selective mu-opioid receptor agonist, [D-Pen 2,5] encephalin (DPDPE), a selective delta-opioid receptor agonist, and U-69593, a selective kappa-opioid receptor agonist could modulate the cholinergic contraction in the upper trachea at different frequencies of stimulation. Moreover, we have investigated whether DAMGO, DPDPE and U-69593 could also modulate the iNANC relaxation. DAMGO (1-100 microM) inhibited the cholinergic contraction in the upper trachea with a maximum inhibition of 57+/-15% at 1 Hz (n=4; p<0.05). On the other hand, DPDPE (10 microM) and U69593 (10 microM) did not produce any significant inhibition of the cholinergic contraction. Naloxone, an opioid receptor antagonist (100 microM), was able to antagonize the inhibitory effect of DAMGO (n=5; p<0.01) on the cholinergic contraction at a frequency of 2 Hz. DAMGO (10 microM) did not displace the cumulative concentration-response relationship to acetylcholine (10 nM-10 mM), (n=4; NS). This provides evidence that prejunctional mu-opioid receptors (and not delta-opioid or kappa-opioid receptors) modulate cholinergic contraction in the upper trachea. In contrast, DAMGO (10 microM) had no significant inhibitory effect on the nonadrenergic relaxation (n=4; NS) in the upper trachea. Neither DPDPE nor U-69593 had any effect on the nonadrenergic relaxation. These findings suggest that DAMGO directly inhibits the cholinergic contraction and that the opioid receptor involved in the inhibition of the cholinergic contraction in the upper trachea is of the mu-opioid type. The finding that opioids inhibit cholinergic contraction without altering NANC relaxations suggests that distinct populations of nerves mediate these two effects.

Animals↗
PubMed1995

Normal thoracoabdominal motions. Influence of sex, age, posture, and breath size.

The purpose of this study was to assess normal values of thoracoabdominal motions (TAM) during spontaneous breathing and vital capacity (VC) maneuvers in relation to sex, age, and body position. For this, 120 healthy subjects from 10 to > 60 yr old were studied using the respiratory inductive plethysmograph (Respitrace). The volume-motion coefficients obtained during quiet breathing for the rib cage (RC) were almost twice those for the abdomen (ABD) and were not influenced by sex or age and also not by posture, except for the increased ABD coefficients in the supine posture (p < 0.05). Under most conditions RC motion predominated over ABD motion, except quiet breathing in the supine position. Sex-related differences in TAM were not found during quiet breathing, yet during VC maneuvers the women were slightly more RC breathing (p < 0.01). Age-related differences were also only significant during VC maneuvers: men of more than 50 yr old especially became less RC breathing. Posture had a very significant effect (p < 0.001) during quiet breathing as well as during VC maneuvers: the RC predominance was greatest in the standing posture and least in the supine posture. During VC maneuvers the subjects became more RC breathers than during quiet breathing (p < 0.001). The X-Y coordinates of RC motion (on the Y axis) versus ABD motion (on the X axis) showed under all conditions a counterclockwise looping during the breathing cycle: the looping was elliptic during quiet breathing but was more irregular and variable during VC maneuvers, and this also depended on body position.(ABSTRACT TRUNCATED AT 250 WORDS)

Abdomen↗
PubMed1994

Effect of loop diuretics on cholinergic neurotransmission in human airways in vitro.

BACKGROUND: Frusemide can inhibit various indirectly acting bronchoconstrictor stimuli in asthmatic patients. Both frusemide and bumetanide also modulate airway neurotransmission in some species but there are no data on the effect of loop diuretics on neurotransmission in man. An in vitro study was performed in human airways to investigate the possible neuromodulatory action of two loop diuretics, frusemide and bumetanide, and to elucidate whether a cyclooxygenase inhibitor such as indomethacin could modulate the effect of frusemide. The effect of acetazolamide, a carbonic anhydrase inhibitor, was also investigated. METHODS: Electrical field stimulation (EFS; 40 V, 0.5 ms, 0.5-32 Hz for 15 seconds) in human airways with or without epithelium was used to induce a cholinergic contraction (n = 5 in all experiments). Indomethacin was present throughout. After obtaining a control frequency-response curve, different concentrations of diuretic were added to the organ bath and another frequency-response curve was constructed. To determine whether the effect of the diuretic was prejunctional or postjunctional a cumulative concentration-response curve to exogenous acetylcholine (Ach, 0.3 mumol/l to 10 mmol/l) was constructed in the presence of a diuretic (frusemide 1 mmol/l or bumetanide 0.1 mmol/l) or its vehicle. In some experiments indomethacin was omitted from the organ bath to investigate the possible involvement of cyclooxygenase products. RESULTS: Both frusemide (10 mumol/l to 1 mmol/l) and bumetanide (1 mumol/l to 0.1 mmol/l) produced a concentration-dependent inhibition of the EFS-induced cholinergic contraction in human airways in vitro but only in epithelium denuded tissues. Frusemide (1 mmol/l) produced a maximum inhibition of 46.3% (SE 9.9%) at 0.5 Hz and bumetanide (0.1 mmol/l 39.6 (6.2)% at 0.5 Hz. Without indomethacin in the organ bath the frusemide-induced inhibition was enhanced at 4, 8, and 16 Hz, but bumetanide-induced inhibition was not enhanced at any frequency when indomethacin was omitted. Frusemide (1 mmol/l) and bumetanide (0.1 mmol/l) had no effect on the cumulative concentration-response curve to exogenous Ach (0.3 mumol/l to 10 mmol/l). Acetazolamide (100 mumol/l) had no effect on the EFS-induced cholinergic contraction in tissues with or without epithelium. CONCLUSIONS: In human airways in vitro both frusemide and bumetanide produced a concentration-dependent inhibition of the EFS-induced cholinergic contraction. This inhibition is mediated through a prejunctional mechanism. Epithelium removal was necessary to achieve this effect. The mechanism of action of frusemide and bumetanide on airway nerves remains unclear: inhibition of the Na-K-Cl cotransporter is a possibility and, for frusemide, release of endogenous cyclooxygenase products may be involved. Carbonic anhydrase inhibition, on the other hand, is unlikely to be a factor.

Acetazolamide↗
PubMed1994

5-HT modulates noncholinergic contraction in guinea pig airways in vitro by prejunctional 5-HT1-like receptor.

5-Hydroxytryptamine (5-HT) has been demonstrated to cause both constriction and relaxation of guinea pig airways, partly through direct action on airway smooth muscle and partly through postganglionic facilitation of cholinergic neurotransmission. We performed an in vitro study to investigate whether 5-HT can modulate the noncholinergic contraction in guinea pig airways due to release of neuropeptides from airway sensory nerves. In the presence of atropine (1 microM), ketanserin (10 microM), and indomethacin (10 microM), 5-HT (0.1-100 microM) produced concentration-dependent inhibition of electrical field stimulation-induced noncholinergic contraction with maximal inhibition of approximately 72 +/- 4%. Tropisetron (ICS-205-930, 1 microM), a 5-HT3 and 5-HT4 receptor antagonist, was unable to prevent the inhibition produced by 5-HT. Methiothepin (1-100 nM), a 5-HT1 and 5-HT2 receptor antagonist, produced a concentration-dependent inhibition of the effect of 5-HT (1 microM) with a 50% inhibition concentration value of 66 nM. 5-HT (100 microM) had no effect on the cumulative concentration-response relationship to exogenous substance P (10 nM-10 microM). The concentration of agonist causing 35% inhibition of the noncholinergic contraction (EC35) was calculated, and a rank order of potency was established: 5-carboxamidotryptamine (EC35 = 0.24 microM) > 5-HT (EC35 = 0.77 microM) > 8-hydroxy-2-(dipropylamino)tetralin (EC35 = 8.1 microM) > sumatriptan (EC35 = 18 microM). We conclude that 5-HT concentration dependently modulates noncholinergic contraction in guinea pig airways in vitro by a prejunctional mechanism. This effect is probably mediated through a 5-HT1-like receptor; however, the exact subtype remains to be elucidated.

Animals↗
PubMed1994

Furosemide and bumetanide, but not nedocromil sodium, modulate nonadrenergic relaxation in guinea pig trachea in vitro.

Furosemide has recently been shown to be effective in inhibiting various indirect challenges in asthmatic patients, but its mode of action is not yet clear. There is some evidence that furosemide has an inhibitory effect on sensory and cholinergic nerves in the airways. We have investigated the effects of furosemide, bumetanide, and nedocromil sodium on inhibitory nonadrenergic, noncholinergic (iNANC) responses in guinea pig trachea in vitro using electrical field stimulation (50 V, 0.5 ms, 2 to 32 Hz for 30 s) and exogenously applied vasoactive intestinal peptide (VIP) or nitroprusside. In the presence of atropine (1 microM), indomethacin (10 microM), and propranolol (1 microM), both furosemide and bumetanide but not nedocromil sodium produced a concentration-dependent inhibition of the iNANC response (maximum inhibition, 31.2 +/- 5.6% with 100 microM furosemide at 16 Hz and 44.2 +/- 4.1% with 10 microM bumetanide at 4 Hz). Furthermore, after pretreatment of the tissues with L-NG-monomethyl arginine (90 microM), alpha-chymotrypsin (2 U/ml), or both, furosemide and bumetanide produced a further inhibition of the iNANC relaxation. Neither loop diuretic had any effect on the concentration-response curves to exogenous VIP (10(-9) to 10(-7) M) or nitroprusside (10(-8) to 10(-6) M). These results indicate that loop diuretics may inhibit nonadrenergic relaxation in guinea pig trachea in vitro by a prejunctional mechanism, probably through inhibition of nerve activation, the exact mechanism of which is still undefined.

Animals↗
PubMed1994

Amiodarone and the development of ARDS after lung surgery.

An evaluation of amiodarone as prophylactic treatment for supraventricular tachyarrhythmias after pulmonary surgery was stopped because of a high incidence of the adult respiratory distress syndrome (ARDS) after a pneumonectomy. Retrospective analysis of all cases of resection for pulmonary neoplasm in our hospital between 1987 and 1991 indicates that amiodarone may be implicated in the development of ARDS after lung surgery.

Adult↗