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G Garcia

Publications and source records attributed to G Garcia.

At least 19 recordsLinked to original sources
PubMed2003

[Pulmonary artery hypertension associated with connective tissue diseases].

MOST IMPORTANT: Pulmonary hypertension (PH) is a severe, potentially life-threatening complication of connective tissue diseases, among which scleroderma is first line. The aim of this paper was to review the literature and report our experience with this particular complication of connective tissue diseases. In our centre of pulmonary vascular diseases, connective tissue diseases represent the third cause of PH. RESULTS: Scleroderma and particularly its limited cutaneous variant, the CREST syndrome, is the most common connective tissue disease affected by pulmonary hypertension. It can be related to a specific lung parenchymal involvement (hypoxic PH), to an isolated pulmonary vascular involvement or to a cardiac dysfunction secondary to specific myocardial lesions. DIAGNOSIS: Echocardiography is an excellent examination to detect pulmonary hypertension. However, right heart catheterisation is necessary to confirm the diagnosis of pulmonary hypertension and to test vasoreactivity with a potent vasodilator such as nitric oxide (NO). REGARDING TREATMENTS: Oral calcium channel blockers are indicated in patients who are responders to acute NO tests. Treatment with continuous intravenous prostacylin is obviously an improvement, at least functionally, although it appears less effective than in primary PH. With the new subcutaneous, oral and inhaled vasodilatators (prostaglandin and endothelin receptor antagonists), a few cases of improvement of PH with intensive immunosuppressive therapy were observed, essentially during systemic lupus erythematosus and Sharp syndrome. IN PRACTICE: PH is a severe complication of connective tissue diseases. Early detection of this complication should allow an earlier and more aggressive therapeutic approach in these patients, before irreversible vascular lesions occur.

Adult↗
PubMed2003

[Pulmonary hypertension complicating systemic diseases other than connective tissue diseases].

A COMPLICATION OF CERTAIN SYSTEMIC DISEASES: Pulmonary hypertension (PH) can complicate the progression of certain systemic diseases such as sarcoidosis, histiocytosis X and some vasculites. The mechanisms at the origin of PH are varied and always require rigorous analysis in order to optimise treatment. DEPENDING ON THE DISEASE: PH associated with sarcoidosis is essentially related to specific lung parenchymal fibrosis and is poorly responder to corticosteroids. Other mechanisms may be more rarely incriminated (compressive andenopathies, mediastinal fibrosis, florid sarcoidosis concomitant to a pulmonary occlusive vascular disease...). During histiocytosis X, the ventilatory limitation of these patients does not always correlate with the severity of the respiratory failure, suggesting the existence of a pulmonary vascular disease progressing independently of the pulmonary parenchymal lesions. The pulmonary artery damage during Takayasu's arteritis and other auto-immune pulmonary arteritis may lead to potentially life-threatening complications, notably through stenosis and/or obstruction of the pulmonary arteries. Pulmonary hypertension is exceptional during Wegener's disease or periateritis nodosa. CONCLUSION: PH can complicate the progression of certain systemic diseases. The physiopathological mechanisms responsible are unclear (specific parenchymal fibrosis, isolated vascular involvement...). Globally, available treatments are disappointing.

Cardiac Catheterization↗
PubMed2003

Difficult asthma.

Explore the source record for details and available documents.

Anti-Asthmatic Agents↗
PubMed2003

Evaluation of CD4+ T cells proliferating to grass pollen in seasonal allergic subjects by flow cytometry.

Our objective was to characterize T-cell responses to Phleum pratense in grass pollen allergic individuals and healthy controls using the fluorescent dye PKH26. Peripheral blood mononuclear cells were stimulated with P. pratense, or with recall antigens, and CD3+/CD4+ and CD3+/CD8+ T-cells that had proliferated were analysed by flow cytometry. In the presence of P. pratense CD4+/CD3+ T-cells proliferated more in grass pollen sensitive atopic patients than in nonallergic controls or in nongrass pollen sensitive atopic subjects. PPD and TT recall antigens elicited uniformly high proliferation in all T-cell subsets. Only half of pollen sensitive patients also had an increased proliferation of CD3+/CD8+ T-cells in response to P. pratense. We determined precursor frequency of CD4+ T cells in the original population that responded to P. pratense and found values ranging from 1 x 10-3 to 0.6 x 10-1, in the same range as those measured for PPD and TT. In conclusion, grass pollen sensitive atopic patients show enhanced CD4+ T-cell reactivity to P. pratense, and this could be related to the presence of elevated numbers of circulating allergen-specific CD4+ T cells. This flow cytometric method should allow the identification of other phenotypic markers such as intracellular cytokines in allergen specific responding CD4+ T cells.

Allergens↗
PubMed2003

Hypogalactosylation of serum IgG in patients with coeliac disease.

Coeliac disease (CD) is described as an autoimmune enteropathy associated with the presence of IgG and IgA antigliadin and antitransglutaminase autoantibodies. While of diagnostic significance, the role of these autoantibodies in the immunopathogenesis of CD is elucidated. An inappropriate T cell immune response to gluten is also involved in the pathogenesis of CD, as evidenced by autoantibody switching. The N-glycans released from serum IgG of CD patients and three groups of healthy controls, of differing age ranges, were analysed by NH2-high performance liquid chromatography (HPLC). The fucosylated biantennary N- glycans were the most abundant neutral oligosaccharides; in particular, the agalacto form (G0F) showed a mean value of 42% (s.d. +/- 7.4), 30% (s.d. +/- 5.9), 26% (s.d. +/- 4.2) and 35% (s.d. +/- 6.8) for CD patients, healthy children, healthy adults under 40 and healthy adults over 40 years old, respectively. The ratio of asialo agalacto fucosylated biantenna to asialo monogalacto fucosylated biantenna (G0F)/(G1F) for CD patients showed a significant increase compared to healthy children (P < 0.0002), healthy adults under 40 (P < 0.0002) and healthy adults over 40 years old (P < 0.01). Hypogalactosylation was more pronounced for CD patients than for the patients with other autoimmune diseases such as rheumatoid arthritis or psoriatic arthritis.

Adult↗
PubMed2002

Nonpeptide vasopressin receptor antagonists: development of selective and orally active V1a, V2 and V1b receptor ligands.

The involvement of vasopressin (AVP) in several pathological states has been reported recently and the selective blockade of the different AVP receptors could offer new clinical perspectives. During the past few years, various selective, orally active AVP V1a (OPC-21268, SR49059 (Relcovaptan)), V2 (OPC-31260, OPC-41061 (Tolvaptan), VPA-985 (Lixivaptan), SR121463, VP-343, FR-161282) and mixed V1a/V2 (YM-087 (Conivaptan), JTV-605, CL-385004) receptor antagonists have been intensively studied in various animal models and have reached, Phase IIb clinical trials for some of them. For many years now, our laboratory has focused on the identification of nonpeptide vasopressin antagonists with suitable oral bioavailability. Using random screening on small molecule libraries, followed by rational SAR and modelization, we identified a chemical series of 1-phenylsulfonylindolines which first yielded SR49059, a V1a receptor antagonist prototype. This compound displayed high affinity for animal and human V1a receptors and antagonized various V1a AVP-induced effects in vitro and in vivo (intracellular [Ca2+] increase, platelet aggregation, vascular smooth muscle cell proliferation, hypertension and coronary vasospasm). We and others have used this compound to study the role of AVP in various animal models. Recent findings from clinical trials show a potential interest for SR49059 in the treatment of dysmenorrhea and in Raynaud's disease. Structural modifications and simplifications performed in the SR49059 chemical series yielded highly specific V2 receptor antagonists (N-arylsulfonyl-oxindoles), amongst them SR121463 which possesses powerful oral aquaretic properties in various animal species and in man. SR121463 is well-tolerated and dose-dependently increases urine output and decreases urine osmolality. It induces free water-excretion without affecting electrolyte balance in contrast to classical diuretics (e.g. furosemide and hydrochlorothiazide). Notably, in cirrhotic rats with ascites and impaired renal function, a 10-day oral treatment with SR121463 (0.5 mg/kg) totally corrected hyponatremia and restored normal urine excretion. This compound also displayed interesting new properties in a rabbit model of ocular hypertension, decreasing intraocular pressure after single or repeated instillation. Thus, V2 receptor blockade could be of interest in several water-retaining diseases such as the syndrome of inappropriate antidiuretic hormone secretion (SIADH), liver cirrhosis and congestive heart failure and deserves to be widely explored. Finally, further chemical developments in the oxindole family have led to the first specific and orally active V1b receptor antagonists (with SSR149415 as a representative), an awaited class of drugs with expected therapeutic interest mainly in ACTH-secreting tumors and various emotional diseases such as stress-related disorders, anxiety and depression. However, from the recently described tissue localization for this receptor, we could also speculate on other unexpected uses. In conclusion, the development of AVP receptor antagonists is a field of intensive pharmacological and clinical investigation. Selective and orally active compounds are now available to give new insight into the pathophysiological role of AVP and to provide promising drugs.

Animals↗
PubMed2002

[Pulmonary hypertension associated with connective tissue diseases].

PURPOSE: Pulmonary hypertension is a rare but well-known life-threatening complication of connective tissue diseases. The aim of this article is to analyse the available literature and to report the experience of a pulmonary vascular diseases centre about this complication. CURRENT KNOWLEDGE AND KEY POINTS: Scleroderma and its limited variant, the CREST syndrome (calcification, Raynaud phenomenon, esophageal dysmotility, sclerodactily, telangiectasia), is the most common connective tissue disease affected by pulmonary hypertension. Dyspnea is the main symptom and is frequently severe. Echocardiography is an excellent exam to detect pulmonary hypertension. However, right heart catheterization is necessary to confirm the diagnosis of pulmonary hypertension and to test vasoreactivity with a potent vasodilator such as nitric oxide. Pulmonary hypertension is less severe in patients with connective tissue diseases perhaps because of an earlier diagnosis. A significantly lower proportion of patients presents an acute vasodilator response, suggesting an early constitution of irreversible pulmonary vascular lesions. Continuous intravenous epoprostenol therapy seems to be less effective as compared with patients with primitive pulmonary hypertension and does not improve survival. So, we observed dramatic improvement in rare cases after immunosuppressive therapy. FUTURE PROSPECTS AND PROJECTS: New treatments with oral, subcutaneous or inhaled stable prostacyclin analogs or with an endothelin receptor antagonist are currently being evaluated. The role of immunosuppressive therapy has to be defined.

Antihypertensive Agents↗
PubMed2002

Airway neutrophil inflammation in nonasthmatic patients with food allergy.

BACKGROUND: Patients with food allergy (FA) have been recently shown to develop bronchial hyperresponsiveness (BHR), despite the absence of any concomitant asthmatic manifestation. In order to explain this observation, we sought to examine the presence of a bronchial inflammation in induced sputum of nonasthmatic patients with FA. METHODS: Twelve nonasthmatic patients with FA (urticaria, digestive symptoms, anaphylaxis) were included in the study. Results were compared to these obtained from eight asthmatic patients without food allergy and eight healthy controls. Diagnosis of FA was based on double-blind placebo-controlled challenge. Sputum cells and fluid-phase eosinophil cationic protein (ECP), myeloperoxidase (MPO) and interleukin-8 (IL-8) were measured in induced sputum. BHR was evaluated using methacholine inhalation. RESULTS: Sputum from asthmatics, in comparison with the sputum of healthy subjects and patients with FA contained a higher proportion of eosinophils and higher levels of ECP (< 0.001). In marked contrast, patients with FA exhibited an increased proportion of neutrophils and IL-8 in comparison with asthmatics and controls (P < 0.05 for neutrophils and P < 0.001 for IL-8). There was a significant correlation between sputum neutrophils and IL-8 (r = 0.68, P < 0.001). MPO levels were not different between the groups. There was a trend toward higher levels of IL-8 and ECP in food allergic patients with BHR in comparison with patients with FA without BHR. CONCLUSION: Our results demonstrate that a subclinical neutrophil airway inflammation is present in patients with food allergy free of clinical respiratory symptoms and that IL-8 may be an important mediator of this neutrophilia.

Adult↗
PubMed2001

Synthetic peptide vaccine against Taenia solium pig cysticercosis: successful vaccination in a controlled field trial in rural Mexico.

Taenia solium cysticercosis seriously affects human health when localised in the central nervous system (CNS) and causes great economic loss in pig husbandry in rural areas of endemic countries. Increasing the resistance to the parasite in the obligatory host pig may help in curbing transmission. Three synthetic peptides based on protein sequences of the murine parasite Taenia crassiceps, which had previously been shown to induce protection in mice against homologous challenge, were tested as a vaccine against T. solium cysticercosis in pigs. Vaccinated and unvaccinated piglets (240 in all) were distributed in pairs among the peasants' households of two rural villages in Mexico in which 14% of the native pigs were cysticercotic. Ten to twelve months later, the effect of vaccination was evaluated at necropsy. Vaccination decreased the total number of T. solium cysticerci (98.7%) and reduced the prevalence (52.6%). The natural challenge conditions used in this field trial strengthen the likelihood of successful transmission control to both pig and human through a large-scale pig vaccination program. We believe this is a major contribution in anticysticercosis vaccine development as these rather simple yet protective peptides are potentially more cost-effective to produce and less variable in results than antigens that are more complex.

Amino Acid Sequence↗
PubMed2001

[Etiology of asthma].

Asthma is a chronic inflammatory disease of the airways which occurs in genetically predisposed individuals. This common disease has an epidemic progression in western countries. Despite the identification of several candidate genes, genetic modifications cannot explain the recent increase in asthma prevalence and severity in the last forty years. Environmental factors are likely to be the cause of the progression of this epidemic inflammatory disease.

Asthma↗
PubMed2001

Morphological study of 5-HT neurons and astroglial cells on brain of adult rats perinatal or chronically exposed to 2,4-dichlorophenoxyacetic acid.

2,4-D is a chlorophenoxyherbicide used worldwide. We have studied the morphological alterations of 5-HT neurons and glial cells in the mesencephalic nuclei of adult rats exposed to 2,4-D both perinatally (during pregnancy and lactation) and chronically (during pregnancy, lactation and after weaning) with quantitative methods. Pregnant rats were daily exposed to 70 mg/kg of 2,4-D from gestation day (GD) 16 to post-natal day (PND) 23 through diet. After weaning, pups were assigned to one of two sub-groups: T1 (fed with untreated diet until PND 90) and T2 (maintained with 2,4-D diet until PND 90). Brain sections were immunocytochemically stained using polyclonal anti-5-HT, anti-GFAP and anti-S-100 protein antibodies as cells markers. 2,4-D exposure during pregnancy and lactancy (T1 group) produced an increase in 5-HT neuronal area and immunoreactivity (IR) in the mesencephalic nuclei studied. However, with the chronical 2,4-D exposure (T2 group) only the 5-HT neuronal area from the dorsal raphe nucleus (DRN) was increased, suggesting an adaptable response of 5-HT neurons in median raphe nucleus (MRN). The presence of reactive astrocytes in mesencephalic nuclei and in hippocampus were also different for the two 2,4-D exposure designs, showing the existence of a correspondence between neuronal changes and astrogliosis. Results support evidences that 2,4-D alters the serotoninergic system and that 5-HT neurons of each mesencephalic nuclei show different responses to the 2,4-D exposure designs which are parallel to astrogliosis.

2,4-Dichlorophenoxyacetic Acid↗
PubMed2001

Pathobiology of pulmonary hypertension. The role of platelets and thrombosis.

With the rare exceptions of PAH associated with antiphospholipid antibodies, genetic platelet dysfunction, or inherited deficiencies of antithrombotic pathways, the thrombotic lesions are secondary, but frequently occurring, in most cases of primary or secondary PAH. Pulmonary arterial hypertension is associated with thrombotic lesions and persistent vasoconstriction and structural remodeling of PA. Activated platelets interact with the PA wall and may contribute to the functional and structural alterations of pulmonary vessels by releasing vasoactive factors and mitogenic mediators.

Animals↗
PubMed2001

Effect of a hydrolytic/acidogenic pre-stage on the organic matter content of wastewater treated in a sequencing batch reactor for biological phosphorous removal.

An increase of 52.7% in acetate concentration was observed when urban wastewater was used to feed a pilot-scale upflow-type, fixed-bed fermentor under a hydraulic retention time of 0.78 h. The fermentor influent and effluent were successively used to feed a laboratory-scale sequencing batch reactor (SBR) using similar operational variables of wastewater volume, sludge purging volume and retention times during the anaerobic and aerobic phase, giving a nominal 4 h hydraulic retention time. The fermentor effluent contained an organic substrate, with a volatile fatty acid content higher than 50mg L(-1), which was appropriate for the growth of the type of microorganisms characteristically found in biological phosphorous removal (BPR) systems, and showed the behaviour of an easily and rapidly biodegradable wastewater. The specific rate of phosphorous release at the anaerobic stage was found to be higher than 0.04mg Pr g VSS(-1) min(-1), when the fermentor effluent is used as feed of the SBR, which demonstrated its favourable conditions for an efficient processing in this type of systems.

Acids↗
PubMed2001

[Prospective study comparing ultrasonography guided trans-rectal biopsy and finger guided trans-perineal biopsy in the diagnosis of prostatic cancer].

OBJECTIVE: To compare ambulatory ultrasound-guided transrectal biopsy and finger-guided transperineal biopsy. MATERIAL AND METHODS: From June 1997 to October 1999, 51 patients were simultaneously biopsied by the two techniques and by the same operator, 30 min after antibiotic prophylaxis with 200 mg of Ciprofloxacin by intravenous injection. Transperineal biopsies were performed first, followed by ultrasound-guided transrectal biopsies. Six cores were obtained with each technique, from the apex, the middle and the base of each lobe. RESULTS: For a PSA level between 4 and 10 ng/ml, 6 cancers were detected in 23 patients (26%) and one cancer was only detected via the transrectal route. For a PSA level greater than 10 ng/ml, 17 cancers were detected in 28 patients (60%), 15 (53%) by transperineal biopsy and 11 (39%) by transrectal biopsy. Six cancers were only detected by transperineal biopsy and two were only detected by transrectal biopsy. No statistically significant difference was observed between the numbers of positive biopsies obtained with the two techniques. CONCLUSION: The use of ultrasonography is not essential to perform systematic biopsies. Rather than the technique used, the detection of prostate cancer is improved by performing 12 cores instead of 6.

Aged↗
PubMed2000

Inhaled corticosteroids and Churg-Strauss syndrome: a report of five cases.

Churg-Strauss syndrome is an eosinophil-associated, small vessel granulomatous vasculitis, characterized by late onset asthma, upper airways disease, eosinophilia, and clinical manifestations of systemic vasculitis. Several cases of Churg-Strauss syndrome have been recognized in patients treated with cysteinyl leukotriene-receptor antagonists and weaned off systemic corticosteroids. These cases have led to a general warning on the possible development of Churg-Strauss syndrome after taking cysteinyl leukotriene-receptor antagonists. The authors report five cases of Churg-Strauss syndrome in severe steroid dependent asthmatics in whom inhaled corticosteroids allowed systemic corticosteroid withdrawal. It is concluded that physicians should monitor patients carefully when severe asthma is controlled with any substance allowing withdrawal from (or even avoidance) of systemic corticosteroids. Case-control studies should identify more precisely the risk factors of Churg-Strauss syndrome.

Administration, Inhalation↗
PubMed2000

A multicenter, randomized trial of daily high-dose interferon-alfa 2b for the treatment of chronic hepatitis c: pretreatment stratification by viral burden and genotype.

OBJECTIVES: The aim of this study was to determine prospectively whether an intensive regimen of daily, high-dose interferon would improve the response rate for the treatment of chronic hepatitis C in patients with unfavorable virological characteristics. METHODS: A total of 104 patients with chronic hepatitis C were randomized at eight centers to receive interferon alfa-2b at a dose of 5 million units (MU) daily or 3 MU t.i.w. for a period of 24 wk. Patients were prospectively randomized by low or high viral burden and stratified by genotype. HCV RNA was measured by quantitative polymerase chain reaction, and response rates were compared between the dosage regimens. RESULTS: HCV RNA levels dropped more rapidly to lower levels in the group treated with 5 MU daily. In this group, the initial virological response (IR) at wk 12 and the end-of-treatment response (ETR) at wk 24 were double that of patients treated with standard interferon (66% vs 33% and 48% vs 24%, p < 0.01). Sustained response rates were low for both dose groups (14% vs 4%, p = 0.08). Genotype-related differences in initial response rates were present in the standard dose group (63% non-1 genotype vs 24% genotype 1; p = 0.005) but not in those treated with 5 MU daily (66% vs 67%, p = NS). Using multivariate analysis, only the interferon dose was associated with IR and ETR (p = 0.002). CONCLUSIONS: Daily, high dose interferon rapidly dropped HCV RNA and increased initial and end-of-treatment response rates when compared to t.i.w. regimens. This effect, independent of viral burden and genotype, suggests that patients with unfavorable viral characteristics might benefit from an intensive regimen that promotes rapid viral clearance. These data support further study of the use of high-dose induction regimens. However, improvements in sustained response rates will require additional therapeutic maneuvers such as prolonged therapy or the adjunctive use of ribavirin.

Adult↗