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Biomedical subjects

C De Vos

Publications and source records attributed to C De Vos.

At least 19 recordsLinked to original sources
PubMed2005

Metastatic renal cell carcinoma to the temporal bone: case report.

We report an extremely rare case of metastasic renal cell carcinoma to the temporal bone which presented initially as a jugulotympanic paraganglioma. The clinical and radiological appearances were misleading.Investigations of concomitant high blood pressure revealed a tumour of the right kidney. Biopsy of the mastoid mass was histologically compatible with a metastasis from a clear cell renal carcinoma. The patient underwent a radical nephrectomy and local external radiotherapy to the head. He also received adjuvant treatment with interferon-_ and interleukin 2. The clinical presentation, the radiological and histological features, the patterns of spread, the treatment options and the prognosis of these tumours are discussed. A review of the literature confirms the extremely unusual occurrence of this localisation.

Adult↗
PubMed2001

A randomized, double-blind, crossover comparison among cetirizine, levocetirizine, and ucb 28557 on histamine-induced cutaneous responses in healthy adult volunteers.

BACKGROUND: Cetirizine is a highly efficacious and long-acting second-generation H1-receptor antagonist for the treatment of allergic diseases, such as allergic rhinitis and chronic idiopathic urticaria, in adults and children. Pharmacologic studies have demonstrated that cetirizine, a racemate mixture composed of equal amounts of two enantiomers, does not undergo hepatic metabolism to any significant level. The enantiomers are excreted mainly unchanged, predominantly in the urine and to a lesser extent in the faeces. METHODS: The pharmacologic activity and potency of the two enantiomers of cetirizine in the management of allergic skin conditions were investigated by studying the effect of treatment with 5.0 mg cetirizine; 2.5 mg levocetirizine, the (R)-enantiomer; and 2.5 mg ucb 28557, the (S)-enantiomer, on histamine-induced wheal and flare response in 18 healthy volunteers. Each treatment was administered as a single oral dose in randomized, double-blind, and crossover manner, and the efficacy of treatment was assessed over a period of 32 h, as per cent inhibition of the histamine-induced wheal and flare areas before treatment. Blood and urine samples were collected in a time-dependent manner and analyzed for the total amounts of each study drug, to elucidate their pharmacokinetic profiles. RESULTS: Both cetirizine and levocetirizine caused a marked inhibition of histamine-induced wheal and flare, whereas ucb 28557 was inactive in this model. Inhibition of the wheal response observed for cetirizine and levocetirizine was apparent by 1 h after dosage and lasted for mean durations of 24.4 and 28.4 h, respectively. In addition, the response for cetirizine and levocetirizine became maximal by 6 h after treatment, rising to 79.5% and 83.8%. Similarly, cetirizine and levocetirizine also markedly inhibited the histamine-induced flare response. This effect was evident for both drugs by 1 h after dosage and lasted over a mean period of 28.4 and 26.0 h, respectively, for cetirizine and levocetirizine. The inhibitory effect of these compounds on histamine-induced flare response was also maximal by approximately 6 h after dosage, peaking at 88.5%) and 83.6%, respectively. Statistical evaluation showed that cetirizine and levocetirizine were equivalent for maximum inhibition of histamine-induced wheal and flare. However, levocetirizine was found to be superior to cetirizine when area under the curve was compared. In contrast, ucb 28557 was not found to inhibit histamine-induced wheal and flare responses at any time during the study period. Plasma concentrations of levocetirizine were found to be approximately double those of ucb 28557 at 4 and 8 h after dosing, and 50-60% of the drugs were excreted unchanged in urine over a period of 32 h. CONCLUSIONS: The finding that, in this model, levocetirizine 2.5 mg has comparable antihistaminic activity to cetirizine 5 mg, whereas its other enantiomer ucb 28557 has no pharmacodynamic effect, suggests that the antihistaminic properties of cetirizine observed in the management of allergic skin conditions are likely to be attributable to levocetirizine.

Adolescent↗
PubMed2001

Effect of cetirizine, levocetirizine, and dextrocetirizine on histamine-induced nasal response in healthy adult volunteers.

BACKGROUND: Cetirizine, an effective H1-receptor antagonist, is a racemate mixture of two enantiomers: levocetirizine (R enantiomer) and dextrocetirizine (S enantiomer). METHODS: To investigate the pharmacologic activity of the two enantiomers of cetirizine, we conducted a randomized, double-blind, four-way, crossover study to assess the effect of treatment with 5 mg levocetirizine, 5 mg dextrocetirizine, and 10 mg cetirizine and matched placebo, on histamine-induced changes in the nasal airways of 24 healthy volunteers. Four hours after a single oral intake, all subjects were challenged by nasal aerosol application with increasing doubling concentrations (from 0.25 to 32 mg/ml) of histamine in both nostrils. Nasal resistance was measured by passive anterior rhinomanometry (PAR), and changes in histamine threshold were calculated together with the absolute number of sneezes after each challenge. RESULTS: Both levocetirizine and cetirizine significantly attenuated the histamine-induced increase in nasal airway resistance by nearly 50% (from a median resistance of 2.51 Pa per cm3/s to 1.29 and 1.31 Pa per cm3/s, respectively) at the maximal concentration, and they concomitantly increased the histamine threshold by fourfold (from 8 to 32 mg/ml), compared with placebo. Sneezing was also attenuated by both levocetirizine and cetirizine. However, these antihistaminic effects were not seen with dextrocetirizine. CONCLUSIONS: This study shows a similar activity of levocetirizine and cetirizine on the inhibition of histamine-induced increase in nasal resistance, indicating that the antihistaminic properties of cetirizine are probably attributable to levocetirizine.

Adult↗
PubMed2001

Controlled comparison of the efficacy and safety of cetirizine 10 mg o.d. and fexofenadine 120 mg o.d. in reducing symptoms of seasonal allergic rhinitis.

BACKGROUND: The efficacy, onset and duration of action and safety of cetirizine 10 mg o.d., fexofenadine 120 mg o.d., and placebo were compared in this investigator-blinded, crossover study involving the use of the Vienna Challenge Chamber. METHODS: 40 volunteers with seasonal allergic rhinitis were exposed to a controlled grass pollen concentration for 6 h on 2 consecutive days. Subjective symptoms and objective measurements were recorded during the allergen exposure periods. RESULTS: Both active medications were significantly more effective than placebo and had a comparable onset of action in alleviating the symptoms of seasonal allergic rhinitis. The efficacy of both active drugs was comparable for the first 4 h after administration of the drugs on day 1 and day 2. However from 22 to 24 h after the first dose cetirizine was significantly superior to fexofenadine for the major symptom complex score and for sneezing. Concerning the total symptom complex score at day 2 fexofenadine could not reach superiority to placebo. No serious adverse events were reported. CONCLUSIONS: Cetirizine and fexofenadine were significantly better than placebo, also in reducing the symptom of nasal congestion. However cetirizine appears to have a longer duration of action than fexofenadine.

Adult↗
PubMed1999

H1-receptor antagonists: effects on leukocytes, myth or reality?

H1-receptor antagonists of the first and second generation have been used for many years to relieve symptoms arising from the action of histamine on the H1 receptor. However, allergic inflammation is more than histamine release and action. Leukocyte infiltration during late allergic manifestations was demonstrated as being a hallmark of allergic inflammation. Second-generation H1-receptor antagonists were studied in models of mast cell degranulation in vitro and of leukocyte infiltration in vivo. Analysis of the literature showed that a drug which is no more metabolized than cetirizine and fexofenadine allows a better relevance of in vitro models. Up to now, cetirizine was the only product in vivo able to reduce eosinphil infiltration in skin, nose, eyes and lungs during experimental allergenic challenges and late allergic inflammatory manifestations. Today, relevance of these properties can be seen in the recently published clinical results showing that cetirizine prevents the development of asthma in specifically sensitized infants with atopic dermatitis.

Animals↗
PubMed1998

A controlled trial of two bicarbonate-containing dialysis fluids for CAPD--final report.

BACKGROUND: The combination of a low pH and a high concentration of lactate which is present in most dialysis fluids is found to be cytotoxic in vitro. For these reasons it would seem logical to use a bicarbonate-containing solution and thus automatically provide a solution with a neutral pH. METHODS: A parallel, randomized, open-label, prospective 2-month trial with an optional 4 month extension was undertaken to compare two novel bicarbonate-based solutions; one containing 38 mmol/l of bicarbonate (B), and one containing a mixture of 25 mmol/l bicarbonate and 15 mmol/l of lactate (B/L), with a control solution (C) containing 40 mmol/l lactate. RESULTS: Three groups of 19 (C), 20 (B), and 20 (B/L) patients were recruited and data from approximately 55 patient months were accumulated in each group. The data show that both bicarbonate-based solutions maintain acid-base levels within the normal range, that there were no changes in any of the other blood biochemistry parameters measured in the peritoneal equilibration test or with regard to adequacy of dialysis, and that furthermore, both solutions were well tolerated. CONCLUSIONS: This study showed that either the bicarbonate or bicarbonate/lactate solutions could be utilized efficaciously in patients undergoing CAPD.

Acid-Base Equilibrium↗
PubMed1996

A comparison of the effects of oral cetirizine and inhaled beclomethasone on early and late asthmatic responses to allergen and the associated increase in airways hyperresponsiveness.

BACKGROUND: Cetirizine is a non-sedating H1 antihistamine which is effective in the treatment of allergic rhinitis and urticaria. It inhibits eosinophil and basophil chemotaxis in late cutaneous allergic reactions in skin windows. Its effect on early (EAR) and late asthmatic reactions (LAR) is less certain. METHODS: We examined the effect on EAR and LAR of 3 days treatment with oral cetirizine (15 mg twice daily) compared with a single dose of inhaled beclomethasone 10 min prior to allergen challenge in a placebo-controlled (oral and inhaled) double-blind cross-over design with three treatment arms separated by 14 days. RESULTS: Cetirizine did not significantly inhibit either the EAR or LAR documented by maximum percentage fall in FEV1 (0-3 and 6-9 h) or as area under the curve (AUC between 0 and 3 and 6-9 h). Beclomethasone inhibited the LAR compared with placebo (P = 0.02) when expressed as AUC (6-9 h). This did not quite reach statistical significance (P = 0.06) when expressed as maximal percentage late fall in FEV1 between 6 and 9 h. A greater than twofold increase in airways responsiveness to methacholine was observed 3 h after challenge which was significantly reduced by beclomethasone compared with placebo (P < 0.02) and cetirizine (P < 0.05). The data suggest that oral cetirizine does not significantly inhibit either the EAR or LAR. Beclomethasone inhibited both the early increase in airways responsiveness and the subsequent LAR. Our study also confirms the view that early increases in airway responsiveness precede the late response and suggests that these associated events are not dissociable by the pharmacological treatments employed in this study.

Administration, Inhalation↗
PubMed1995

Clinical evaluation of an optimized 1.1% amino-acid solution for peritoneal dialysis.

A significant percentage of dialysed patients have inadequate protein intake. One strategy for treating the protein malnutrition in peritoneal dialysis patients is to replace glucose in the dialysis solution by amino acids. A new peritoneal dialysis solution containing 1.1% amino acids in a formulation optimized for renal patients and with a lactate concentration of 40 mmol/l has been evaluated. Fifteen CAPD patients completed a non-randomized prospective 3-month study. Each patient received 2 litres of the optimised 1.1% amino acid solution for the second exchange of the day with a dwell time of 5-6 h. Indicators of efficacy were serum albumin and transferrin. After 3 months of intraperitoneal amino acids, serum albumin levels significantly increased from 32.7 +/- 2.3 to 35.1 +/- 2.2 g/l (mean +/- SD; P < 0.01). This occurred in parallel with a significant increase in transferrin levels from 2.21 +/- 0.26 to 2.39 +/- 0.27 g/l (P < 0.05). As expected, urea rose from 23.7 +/- 6.8 to 29.9 +/- 9.4 mmol/l. Interestingly bicarbonate did not change (25.5 +/- 4.2 versus 25.2 +/- 3.3 mmol/l). These results suggest that the optimized formulation is effective in improving nutritional parameters in CAPD patients while avoiding unwanted side-effects such as acidosis.

Adult↗
PubMed1993

Effect of cetirizine, a potent H1 antagonist, on platelet activating factor induced bronchoconstriction in asthma.

Effect of cetirizine, a potent and specific H1 receptor antagonist, was examined on platelet activating factor-induced bronchoconstriction in 10 patients (5 male, mean [s.e.m.] aged 37.4 [3.6] years) with mild asthma in a placebo controlled, double-blind cross-over study. Airway responses were assessed by measuring specific airway conductance (SGaw). Patients were challenged with a single dose (12-96 micrograms) of PAF that had previously produced a 35% fall in SGaw. PAF challenges were performed after single dose (15 mg) and 1 week's treatment (15 mg twice daily) of cetirizine. There was no significant difference in pre- and post-treatment baseline values of SGaw on different study days and the percentage changes after cetirizine were 38.7 (7.01) and 45.6 (5.52) compared to 50.2 (2.89) and 43.9 (7.26) with placebo respectively. Similarly mean (s.e.m.) area under curve (AUC-SGaw/time course response) was 391 (143) and 514 (85) with cetirizine compared to 565 (37) and 461 (94) with placebo respectively. The difference was not statistically significant. There was no difference in facial flushing and feeling of warmth between cetirizine and placebo. We conclude that PAF induced bronchoconstriction in humans is not mediated by histamine release and that H1 receptor antagonists do not modify PAF induced bronchoconstriction.

Adult↗
PubMed1992

Inhibitory effect of cetirizine on the bronchial eosinophil recruitment induced by allergen inhalation challenge in allergic patients with asthma.

In patients with asthma there is a recruitment of eosinophils in bronchoalveolar lavage fluid (BALF) after the late asthmatic reaction (LAR). Cetirizine is a selective H1 antagonist that inhibits the eosinophil recruitment induced by allergen in the skin. The aim of this study was to evaluate whether cetirizine was able to inhibit the LAR-induced inflammatory reaction. Twelve allergic asymptomatic subjects with asthma (aged 18 to 58 years) without any treatment were enrolled in the study; FEV1 was greater than 83% predicted in each case. An allergen inhalation-challenge test was performed to assess the presence of an LAR. In a double-blind, randomized, placebo-controlled study, the patients were treated for 8 days with either cetirizine, 15 mg twice a day (six patients, group 1), or placebo (six patients, group 2). On day 8, a second allergen inhalation-challenge test with the same allergen was performed, and BAL was realized 24 hours later; as usual 250 ml of saline was instilled by 50 ml aliquots, and the first recovery was analyzed separately. In each case, the LAR observed after treatment was similar to the first one. In placebo-treated patients, an increased number of cells, mainly eosinophils, was observed in the first recovery of BALF compared with the number in subsequent recoveries. These numbers were significantly higher than numbers observed in cetirizine-treated patients. Cetirizine did not modify significantly the allergen inhalation-challenge test, but it inhibited the recruitment of inflammatory cells, mainly eosinophils.

Administration, Inhalation↗
PubMed1992

The effect of a single oral dose of prednisolone or cetirizine on inflammatory cells infiltrating allergen-induced cutaneous late-phase reactions in atopic subjects.

The effect of a single dose of prednisolone (20 mg) or cetirizine (10 mg) on the immunohistology of the cutaneous late-phase reaction was determined in a double-blind, placebo-controlled, cross-over study in 12 atopic allergic individuals. The subjects were challenged with intradermal allergen (30 BU) 2 hr after ingestion of the drugs or placebo. The magnitude of the cutaneous reactions were determined at 15 min, 6 and 24 hr, and skin biopsies performed at 24 hr. Cetirizine produced a 50% average inhibition of the immediate weal and flare response (P = 0.001) and a 27% average inhibition of the 6 hr late-phase induration (NS). Prednisolone reduced the immediate (27%, P = 0.03) and significantly inhibited the late-phase reaction (53%, P = 0.02). Prednisolone significantly inhibited infiltration of CD45+ (total leucocytes), neutrophil elastase+, EG2+ (activated eosinophils) and CD25+ (IL-2R) cells (P = 0.017, 0.005, 0.005 and 0.032 respectively). CD3, CD4, CD8 and HLA-DR expression was also inhibited but this was not significant. Cetirizine also reduced the numbers of EG2+ cells, particularly those with high counts before treatment but the overall results were not significant. No other changes in the cellular infiltrate were demonstrated when cetirizine was compared with placebo. These findings indicate a single dose of prednisolone significantly reduces leucocyte infiltration and activation as well as the magnitude of the cutaneous late-phase reaction.

Administration, Oral↗
PubMed1992

Pharmacological treatment of allergies.

According to recent literature, the "anti-allergy" properties of antihistamines are linked to their antagonistic ability on receptor H1. In the majority of experimental models the immediate allergic responses is followed by a late phase. Especially at the pulmonary level, the presence of a late response after an allergic provocation is considered to correlate with the severity of asthma. The reference anti-allergy drugs, such as the inhaled corticosteroids or the cromones, without anti H1 activity, inhibit this late pulmonary response. Azelastine, ketotifen and cetirizine, three substances that are antagonistic to the anti-H1 receptor reduce the late pulmonary response. In addition, these three substances have other "anti-allergy" characteristics. Azelastine inhibits production of superoxide by the pulmonary neutrophils and eosinophils after PAF provocation in animals. Cetirizine significantly inhibits eosinophil infiltration in the bronchoalveolar lavage liquid in asthmatics with a late allergic bronchospasm. The presence of anti-histaminic and anti-allergy characteristics on the same molecule may perhaps convey a supplementary therapeutic benefit in the treatment of allergic symptoms.

Animals↗
PubMed1991

The effect of cetirizine on the human isolated bronchus: interaction with salbutamol.

The effects of cetirizine (C), a new generation, nonsedative, H1-antihistamine drug, were studied on human isolated bronchi. C is a potent antagonist of the bronchial muscle contraction induced by histamine, irrespective of whether C is administered by cumulative addition or prophylactically. In the former case, this effect of C was significant at a concentration of 3 X 10(-8) mol/L and was maximal at a concentration of 10(-5) mol/L. The -log of concentration of C causing 50% of the maximal effect induced was 7.30 +/- 0.05 (n = 6), and the effect produced was not significantly modified by bronchial epithelium removal. When C was administered prophylactically, the concentration-response curves to histamine were displaced to the right, but the reduction of maximum histamine response suggests a noncompetitive type of antagonism. C is devoid of notable anticholinergic effects. At concentrations of 10(-8) to 10(-7) mol/L, C proved capable of enhancing the relaxant effect produced by salbutamol (10(-7) to 3 X 10(-7) mol/L) on human isolated bronchi that had been contracted by either histamine or acetylcholine (ACh). The synergy appeared to be additive or potentiating, depending on salbutamol (SAL) concentrations. Under similar conditions, mepyramine does not potentiate the effects of SAL against histamine. Finally, at concentrations of 10(-8) to 10(-6) mol/L, C reduced the functional antagonism observed between SAL and ACh, as can be observed by the increase, in the presence of C, of the maximal relaxant effect of SAL on contractions produced by 10(-3) mol/L of ACh. We may, therefore, conclude that C appears to be a specific antihistamine on human isolated bronchi and that it appears to potentiate the bronchodilator effect of SAL on this preparation.

Acetylcholine↗
PubMed1991

Effect of cetirizine on histamine- and leukotriene D4-induced bronchoconstriction in patients with atopic asthma.

Cetirizine, a derivative of hydroxyzine, is a new compound with potent antihistaminic property without antiserotonin and anticholinergic activities. The effect of both a single dose (15 mg) and 7 days of treatment (15 mg twice daily) with cetirizine, a potent H1 antagonist on bronchoconstriction induced by histamine and leukotriene D4 (LTD4) has been examined in 10 patients with mild atopic asthma in a placebo-controlled, double-blind, crossover study. Cetirizine, after a single dose and 7 days of treatment with placebo, the geometric mean values of the provocative concentration of histamine causing a 20% fall in FEV1 (millimolars) were 1.60 (95% confidence interval, 0.82 to 3.11) and 1.67 (0.77 to 3.65), compared with 118.07 (77.22 to 180.54) (p less than 0.0001) and 53.16 (20.50 to 137.84) after cetirizine administration (p less than 0.0002). The mean inhibition after a single dose was twofold higher than after 1 week of treatment (p less than 0.05). After a single dose and 7 days of treatment with placebo, the geometric mean values of the provocative concentration of LTD4 causing a 20% fall in FEV1 (micromolars) were 2.26 (1.74 to 2.94) and 2.37 (1.77 to 3.17), compared with 3.90 (2.60 to 5.86) (p less than 0.05) and 3.21 (2.28 to 4.52) after cetirizine administration. This result suggests that cetirizine is a potent H1 antagonist in the human airways. Diminished activity after 1 week of treatment suggests subsensitivity of H1 receptors developing in human airways. The small protective effect after a single dose against LTD4-induced bronchoconstriction indicates a nonspecific rather than a specific receptor antagonism.

Adult↗
PubMed1991

Effect of cetirizine on exercise induced asthma.

The effect of oral and inhaled cetirizine, a potent and specific H1 receptor antagonist, was studied in patients with exercise induced asthma. Twelve patients (five male; mean age 35.2 years) were given oral placebo or cetirizine 10 mg twice daily for one week, double blind and in randomised order, and exercised on a treadmill for six to eight minutes at a submaximal work load two hours after the final dose. There was no significant change in baseline FEV1 after treatment and cetirizine failed to inhibit exercise induced bronchoconstriction (maximum falls in FEV1 28% and 27% of baseline). In a further eight patients (four male; mean age 40.8 years) the effect of 1 ml cetirizine (5 and 10 mg/ml) given through a Wright nebuliser was compared with that of placebo in a double blind trial. The fall in FEV1 after exercise was reduced after both concentrations of cetirizine by 15.2% of baseline after 5 mg/ml and by 10.2% after 10 mg/ml, compared with 23.7% after placebo. In two patients cetirizine had no effect. In a further study cetirizine (10 mg/ml) given by inhalation displaced the geometric mean PC20 histamine 13.1 fold to the right by comparison with placebo. The reason for the difference between the effects of oral and of inhaled cetirizine on exercise asthma is not clear but may be related to differences in local concentration in the airway.

Administration, Inhalation↗