Biomedical subjects

Y Cormier

Publications and source records attributed to Y Cormier.

At least 55 records · Page 3Linked to original sources

PubMed1996

Viral infection enhances the response to Saccharopolyspora rectivirgula in mice prechallenged with this farmer's lung antigen.

Sendai viral infection enhances mice lung response to Saccharopolyspora rectivirgula (SR). The mechanisms of this viral enhancement remain unclear. The present study was done to verify if the viral infection was required and if the presence of the viral infection needed to be given simultaneously with the SR antigen for the enhanced response to occur. In a first experiment groups of C57BL/6 mice were instilled concomitantly with SR and live or inactivated Sendai virus. In a second experiment the viral infection in the appropriate group preceded the SR challenges by 4 weeks. As reported previously SR induced a cellular inflammatory response. This effect of SR was enhanced by the viral infection but not by inactivated virus particles. Total lavage cells 3 weeks after the virus inoculation in the appropriate groups were: saline = 69 +/- 15 x 10(3); SR = 678 +/- 104 x 10(3); Sendai = 277 +/- 61 x 10(3); inactivated Sendai = 73 +/- 23 x 10(3); SR + Sendai = 1232 +/- 232 x 10(3); SR + inactivated Sendai = 515 +/- 54 x 10(3). In the second experiment, where the infection preceded the SR challenge, no enhancement was observed. We conclude that Sendai virus enhances mice lung response to SR by an infectious process when both SR and the virus are present simultaneously.

Animals↗

PubMed1996

Phase II study of docetaxel (taxotere) in patients with previously untreated extensive small cell lung cancer.

The objective of this multicenter phase II study was to evaluate the activity of docetaxel in previously untreated small cell lung cancer. Fourteen patients were treated at a dose of 75 mg/m2 intravenously every three weeks. Of the 12 patients evaluable for response, one had a partial response for a duration of 12 weeks for a response rate of 8.3%. Toxicity was mild. We conclude that docetaxel has, at the dose given in this study, little activity in previously untreated small cell lung cancer.

Aged↗

PubMed1996

Phase I trial of gemcitabine and cisplatin in advanced non-small cell lung cancer: a preliminary report.

A phase I trial was performed to investigate the tolerability and efficacy of the novel nucleoside analogue gemcitabine in combination with cisplatin in the treatment of advanced non-small cell lung cancer. Both cisplatin and gemcitabine were administered as 30 min infusions weekly x 3 with a week of rest. There was one dose escalation of cisplatin from 25 mg/m2 (dose level 1) to 30 mg/m2 (in subsequent dose levels 2-5), such that the mean dose intensity for the weekly x 3 q 4 week cycle was 22.5 mg/m2/week which is close to that achieved with 100 mg/m2 bolus monthly. Gemcitabine was initiated at 1000 mg/m2 (dose levels 1 and 2) then escalated by 250 mg/m2/week to 1750 mg/m2 (dose level 5). Of 32 chemotherapy-naive patients entered (22 males, 10 females; median age 61 years, range 29-74 years), 11 had localized tumours (2 stage IIIa, 9 IIIb) and 21 had stage IV tumours with haematogenous metastases and a poor prognosis. Twenty-one patients had adenocarcinoma, 4 squamous cell carcinoma, 6 large cell undifferentiated tumors, and one had mixed squamous and adenocarcinoma. Dose-limiting toxicity was not seen in more than one patient in cycle 1 at any dose level. Grade 4 granulocytopenia and thrombocytopenia occurred more frequently with repeated dosing, necessitating dose reductions except at the lowest dose level (cisplatin 25 mg/m2, gemcitabine 1000 mg/m2). Non-haematological toxicity was mild and rapidly reversible. Cisplatin administration led to a higher frequency of nausea and vomiting than that seen with gemcitabine alone, but this was easily controlled with antiemetics. In the 28 patients evaluable, to date responses have been seen at most dose levels, with an overall response rate 35.7%. This phase I trial is ongoing and further dose escalation is intended to determine the MTD of gemcitabine.

Adult↗

PubMed1996

Tallimustine is inactive in patients with previously treated small cell lung cancer. A phase II trial of the National Cancer Institute of Canada Clinical Trials Group.

Tallimustine binds to the minor groove of DNA where it alkylates the N3 position of adenine and may interfere with gene transcription. We conducted a phase II trial of Tallimustine given at a dose of 750 micrograms/m2 intravenously every 4 weeks in patients with small cell lung cancer progressing or relapsing following cisplatin or carboplatin-based chemotherapy. We treated 14 eligible patients with a performance status 0, 1 or 2, bi-dimensionally measurable disease and adequate end-organ function. The main toxicity was neutropenia with a median granulocyte count of 0.1 x 10(9) per liter (range 0-3.9) and four patients (27%) developing febrile neutropenia. In addition, most patients (93%) experienced lethargy. No objective responses were seen. A mixed response was seen in one patient and three others had stable disease for a median of 3.7 months. We conclude that Tallimustine is an ineffective agent in previously treated small cell lung cancer.

Aged↗

PubMed1996

Effect of contact avoidance or treatment with oral prednisolone on bronchoalveolar lavage surfactant protein A levels in subjects with farmer's lung.

BACKGROUND: Surfactant protein A (SP-A) acts as an immune system modulator in the lungs and may therefore be involved in the pathogenesis of hypersensitivity pneumonitis. METHODS: The levels of SP-A in bronchoalveolar lavage (BAL) fluid were measured in 20 subjects with acute farmer's lung, 16 asymptomatic dairy farmers, and 14 normal controls. Eight patients had a second evaluation after one month of treatment by either contact avoidance (n = 3) or oral prednisolone (20 or 25 mg/day, n = 5). Chest radiographs and lung function measurements were also obtained in all farmers, twice in those re-evaluated after treatment. RESULTS: Patients with acute farmer's lung had significantly higher levels of SP-A than asymptomatic farmers and normal controls (p = 0.005) with mean (SE) values of 1.43 (0.29) micrograms/ml, 0.62 (0.09) microgram/ml, and 0.68 (0.11) microgram/ml, respectively. In eight subjects tested after one month of treatment the level of SP-A was unchanged although all were clinically improved. No correlations were seen between levels of SP-A in BAL fluid and numbers of BAL cells, lung function measurements, or chest radiographic scores. CONCLUSION: Although the level of SP-A is increased in the BAL fluid of patients with acute farmer's lung, it is not correlated with clinical abnormalities of this disease.

Adult↗

PubMed1996

Elafin/elastase-specific inhibitor in bronchoalveolar lavage of normal subjects and farmer's lung.

Secretory leukocyte proteinase inhibitor (SLPI) and alpha1-proteinase inhibitor (alpha1(PI)) cannot fully explain the total neutrophil elastase (NE) inhibitory capacity detected in bronchoalveolar lavage (BAL) fluid, suggesting the existence of other NE inhibitor(s). In the present study, we measured the concentrations of elafin, a newly described, low-molecular-weight serine proteinase inhibitor, SLPI, and alpha1(PI) in BAL fluids from eight healthy subjects, 13 asymptomatic farmers, seven farmers with active farmer's lung (FL), and seven farmers with previous (Ex) FL. In addition to SLPI and alpha1(PI), elafin was present in BAL fluids from control subjects and asymptomatic farmers, 13 (7-31) and 12 (7-67) mmol/mol of albumin (median and range) respectively. Elafin concentration increased significantly to 105 (38-207) mmol/mol of albumin in farmers with active FL and was also elevated in farmers with Ex FL. Elafin levels were highly correlated with lung inflammatory cell numbers, especially lymphocytes, and the decrease in single-breath diffusion capacity (DLCO). Elafin and SLPI were linked to yet uncharacterized proteins in BAL fluids. In conclusion, elafin is a constituent of BAL fluid from normal subjects and is found in enhanced concentrations in FL and in farmers with lymphocytic alveolitis. This suggests that elafin may play a role in lung homeostasis and inflammation.

Adult↗

PubMed1996

Reactive airways dysfunction syndrome (RADS) following exposure to toxic gases of a swine confinement building.

We describe the case of a 58 year old male, who developed a reactive airways dysfunction syndrome (RADS) after exposure to a high level of toxic gases in a swine confinement building. This previously healthy, nonatopic man developed moderate, partially reversible, airway obstruction and increased responsiveness within a month after the toxic exposure. The circumstances of the incident and the concomitant death of two sows make it likely that hydrogen sulphide was the causative agent. To our knowledge, this is the first case of reactive airways dysfunction syndrome reported from swine confinement buildings and, therefore, should raise awareness of this potential risk in that work environment.

Administration, Inhalation↗

PubMed1996

Altered immunosuppressive activity of alveolar macrophages in farmer's lung disease.

Since normal alveolar macrophages (AMs) can suppress T-cell proliferation to mitogenic and antigenic stimuli both in vitro and in vivo, we questioned whether an altered AM immunosuppressive activity could account for the alveolar lymphocytosis observed in farmer's lung (FL) and whether granulocyte/macrophage colony-stimulating factor (GM-CSF), a cytokine able to abrogate AM-induced immunosuppression, is involved in the process. The ability of different concentrations of AMs to inhibit lymphocyte proliferation in response to the T-cell-specific mitogen phytohaemagglutin (PHA) after in vitro culture was tested in three groups of subjects: 12 patients with FL; four asymptomatic farmers (AS); and six normal volunteers (N). Release of GM-CSF by AMs was also measured. At all ratios tested, AMs from patients with FL did not suppress the lymphoproliferation but instead had an enhancing effect. In AS, AMs enhanced the proliferation at a lower ratio but inhibited it at high ratios. In N subjects, as described previously, AMs increasingly inhibited the blastogenesis of lymphocytes (L) at increasing ratios of AM:L. In some patients with FL, AMs spontaneously released more GM-CSF than in normal volunteers (206 +/- 84 versus 29 +/- 14 pg.mL-1, respectively). In AS, GM-CSF release was intermediate (74 +/- 36 pg.mL-1). In conclusion, a defect in the ability of alveolar macrophages to suppress the proliferation of lymphocytes in the lung of patients with farmer's lung is a major factor accounting for the development of the observed lymphocytic alveolitis. Granulocyte/macrophage colony-stimulating factor could be one factor which may contribute to this alteration.

Bronchoalveolar Lavage Fluid↗

PubMed1996

Proinflammatory effect of Pediococcus pentosaceus, a bacterium used as hay preservative.

Bacterial cultures, such as Pediococcus pentosaceus, are used to treat hay with the objective of preventing hay heating and moulding, and thus, the development of the microbial growth which causes farmer's lung. The aim of this study was to investigate whether such bacterial cultures have the potential to induce a pulmonary inflammatory response. Mice were instilled 3 days week-1 for 3 weeks with either saline or nonviable preparations of P. pentosaceus, Saccharopolyspora rectivirgula, Lactococcus lactis (control bacteria) or with the combinations of S. rectivirgula and P. pentosaceus. P. pentosaceus induced a significant inflammatory response in the lung which was similar to that produced by S. rectivirgula. L. lactis produced a response of a lower intensity. The total number of cells in bronchoalveolar lavage were: S. rectivirgula: 6.4 x 10(5) cells.mL-1; P. pentosaceus: 4.3 x 10(5) cells.mL-1; S. rectivirgula + P. pentosaceus: 5.4 x 10(5) cells.mL-1, L. lactis: 6.8 x 10(5) cells.mL-1 and saline group 3.7 x 10(4) cells.mL-1. The lung index was higher in S. rectivirgula+P. pentosaceus and P. pentosaceus groups than in S. rectivirgula, L. lactis and saline groups. The quantity of specific immunoglobulin G and A (IgG and IgA) to P. pentosaceus and L. lactis levels (in the blood and/or lavage fluid) were similar to those against S. rectivirgula. In mice, P. pentosaceus has the potential to induce a similar inflammatory response in the lung as S. rectivirgula, which is the most common antigen responsible for farmer's lung disease in Quebec. Further studies are needed to verify whether farmers can develop farmer's lung or other lung responses to this new potential antigen.

Animals↗

PubMed1996

Phase I dose-escalation trial of gemcitabine and cisplatin for advanced non-small-cell lung cancer: usefulness of mathematic modeling to determine maximum-tolerable dose.

PURPOSE: This study was undertaken to determine the maximum-tolerated doses of gemcitabine and cisplatin, each given weekly for 3 weeks with a 1-week rest. PATIENTS AND METHODS: Patients less than 75 years of age were eligible if they had stage III/IV non-small-cell lung cancer (NSCLC), life expectancy > or = 12 weeks, hemoglobin level > or = 10 g/dL, granulocyte count > or = 2 x 10(9)/L, platelet count > or = 100 x 10(9)/L, hepatic enzymes < or = three times the upper limit of normal, and creatinine concentration < or = 130 mumoles/L. The starting doses for gemcitabine and cisplatin were 1,000 mg/m2 and 25 mg/m2 per week for 3 weeks. At dose level 2, cisplatin was increased to 30 mg/m2/wk for 3 weeks, and thereafter only gemcitabine was increased by 250 mg/m2/wk at each dose level to a maximum of 2,250 mg/m2/wk. RESULTS: There were 33 men and 17 women, with a median age of 62 years. Pathology included adenocarcinoma in 35 patients, squamous in eight, large cell in six, and mixed histology in one. Sixteen patients had stage III and 34 had stage IV tumors. The median nadir granulocyte and platelet counts decreased with each dose level, but cycle 1 dose-limiting toxicity (DLT) in > or = two patients was not encountered in cycle 1, even at the highest dose level. Cumulative marrow toxicity was seen at all levels, which resulted in frequent dose reductions or omissions. A mathematic model of all toxicities over time suggested that dose level 4 (cisplatin 30 mg/m2/wk and gemcitabine 1,500 mg/m2/wk) would be the maximum dose at which grade 4 toxicity would be expected in < or = 33% of patients over four cycles. Of 47 assessable patients, 14 achieved a partial response (30%; confidence interval, 17% to 43%). The median duration was 16 weeks and the median survival time was 24 weeks (range, 3.5-64+). CONCLUSION: Weekly gemcitabine and cisplatin are active against NSCLC, and the recommended phase II doses are 30 and 1,500 mg/m2/wk for 3 weeks, respectively.

Adenocarcinoma↗

PubMed1996

Final results of the Canadian phase I dose escalation trial of gemcitabine and cisplatin for advanced non-small cell lung cancer.

When given at doses of > or = 1,250 mg2 weekly x 3 with a 1-week break, single-agent gemcitabine induces responses in more than 20% of previously untreated patients with non-small cell lung cancer (NSCLC). This study was undertaken to determine the maximum tolerated doses for a 4-week cycle of gemcitabine and cisplatin given in combination weekly x 3 with a 1-week rest. Patients younger than 75 years were eligible if they had stage III/IV NSCLC, life expectancy > or = 12 weeks, hemoglobin > or = 10 g/dL, absolute granulocyte count > or = 2 x 10(9)/L, platelets > or = 100 x 10(9)/L, hepatic enzymes < or = 3 times the upper limit of normal, and serum creatinine < or = 130 mumol/L. The starting doses for gemcitabine and cisplatin were 1,000 mg/m2 and 25 mg/m2 per week x 3, respectively. At dose level 2 cisplatin was increased to 30 mg/m2/week x 3. Thereafter only the gemcitabine was increased, by 250 mg/m2/wk at each dose level, to a maximum of 2,250 mg/m2/wk at dose level 7. The median nadir granulocyte and platelet counts decreased with each dose level, but dose-limiting toxicity in two or more patients was not encountered in the first treatment cycle, even at dose level 7. Cumulative bone marrow toxicity was seen at all dose levels, and this resulted in frequent dose reductions or omissions. Dose delivery was well maintained over time only at dose level 1. Grade 3-4 nonhematologic toxicity was infrequent and rarely dose limiting. An assessment of all toxicities seen during the treatment cycles was undertaken using continual reassessment methodology. This model suggested that dose level 4 (cisplatin 30 mg/m2/wk and gemcitabine 1,500 mg/m2/wk) would be the maximum dose at which grade 4 toxicity would be expected in up to 33% of patients at any time over four treatment cycles. Of 47 patients evaluable for response, partial remission was seen in 14, with an overall response rate of 30% (confidence interval, 17% to 43%). The median duration of response was 16 weeks and the median survival time was 24 weeks (range, 3.5 to 64+ weeks). A phase II trial is planned in which dose level 4 will be evaluated in a larger cohort of patients with NSCLC.

Adult↗

PubMed1995

PC:PS liposomes induce a recruitment of neutrophils and the release of TNF alpha in the lungs of mice sensitized with Saccharopolyspora rectivirgula.

The aim of this study was to verify the effect of nasally instilled liposomes (L) or dexamethasone-containing L (Ldexa) on normal or inflamed lung tissue. Three groups of mice were studied. Group I was given saline instillations for 3 weeks prior to the instillation with liposomes. In groups II and III lung inflammation was induced by repeated instillations of Saccharopolyspora rectivirgula before the instillation of liposomes (group II) or liposomes containing dexamethasone (group III). Animals from all groups were killed at regular time intervals for up to 48 h after the instillation of liposomes. The total cell count in bronchoalveolar lavage fluid did not differ significantly between groups I and II. However, in group III it decreased rapidly from 6.2 to 2.8 x 10(5) cells mL-1 within 2 h. Differential counts did not change in group I, but in group II a transient neutrophilia was observed 180 min after the instillation of liposomes. In group III, the instillation of dexamethasone-containing liposomes depleted all neutrophils and lymphocytes after 4 h. No TNF alpha was found in samples of lavage fluid from any of the groups at time 0. In group I, liposomes induced the production of 0.03 ng mL-1 of TNF alpha in the 1 h sample only. In group II, TNF alpha peaked to 1 ng mL-1 at 1 h and had decreased to 0.35 ng mL-1 by 3 h. In group III, TNF alpha peaked at 1 h, but only reached a level of 0.1 ng mL-1.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Intranasal↗

PubMed1995

Effects of a Bacterial Hay Preservative (Pediococcus pentosaceus) on Hay under Experimental Storage Conditions.

The abundant growth of molds and thermophilic actinomycetes in stored hay decreases its quality and can be hazardous for the producer who inhales these contaminants when the moldy hay is fed in closed barns. These microbes are responsible for a respiratory disease called farmer's lung. Products, including bacterial cultures that can be inoculated in hay, are available to prevent hay deterioration by molds and bacteria. The aim of this study was to verify the effectiveness of Pediococcus pentosaceus (a bacterial inoculant) in preventing hay deterioration at different humidity levels in a laboratory experiment. Mixtures of grasses (mostly alfalfa, timothy, and clover) placed in plastic bags were treated with the commercially available product (live culture of P. pentosaceus) at 500,000 and 5,000,000 CFU/g of hay and humidified at different levels (20, 25, 30, and 35%). Control batches of hay (untreated) were prepared at the same humidity levels. The growth of inoculated bacteria in hay, pH level, and hay deterioration were evaluated. Under these experimental conditions, the growth of P. pentosaceus was abundant only when it was inoculated in very moist hay (35% moisture), resulting in bacterium levels of 6.3 x 10(sup8) CFU/g after 30 days. This abundant growth did not prevent the pH from increasing (final pH of about 9.0), nor did it prevent molding. At lower humidity levels (20, 25, and 30%), the bacterial inoculant used did not grow and did not prevent hay deterioration.

Journal Article↗

PubMed1995

Farmer's lung and variables related to the decision to quit farming.

An exploratory strategy was used to investigate why 55% of patients with farmer's lung (FL) disease quit farming. Three groups were recruited: 47 patients with FL disease who quit farming because of the disease (FLq), 76 patients with FL disease who continued farming (FLc), and 123 control farmers without a history of FL disease. The severity of FL disease at diagnosis was similar in both groups of patients. For example, single-breath carbon monoxide diffusion capacity predicted for FLq and FLc was 64.4 +/- 28.2 and 63.9 +/- 22.0, respectively. Relying on a cognitive-behavior theory, numerous physiological, behavioral, cognitive, affective, and social variables were assessed. Results showed that the decision to quit farming was based on cognitive and behavioral motives rather than physiological factors. Subjects in the FLq group showed more negative beliefs toward FL and had more fears of FL disease. FLq subjects also reported that family members, friends, and family doctors were more inclined to consider that FL disease could stop them from farming. However, self-efficacy to continue farming despite having FL disease and perceived hindrance caused by FL disease played the most important roles in the decision to quit farming.

Agriculture↗

PubMed1995

[The effect of drugs taken by patients with respiratory pathology on the nature of sleep and on respiratory characteristics].

The influence of medications and the usual taken by patients with respiratory disease on the characteristics of sleep and nocturnal respiration is complex, due to the fact of the inter-dependence which exists between these two physiological domains. Numerous medications have been evaluated for the treatment of nocturnal respiratory anomalies observed in patients suffering from chronic airflow obstruction or from a sleep apnoea or hypopnoea syndrome. For the greater part, the efficacy of these drugs remains limited and in the case of nocturnal sleep apnoea no pharmacological approach has an efficacy comparable either to mechanical or surgical treatments. It is thus important in these patients to appreciate the limits of medications prescribed for a specific purpose and the deleterious effect which may occur with certain medications employed for a symptomatic goal.

Humans↗

PubMed1994

Viral infection enhances lung response to Micropolyspora faeni.

Farmer's lung is an important form of hypersensitivity pneumonitis. It is believed to represent a delayed type allergic reaction to microorganisms found in moldy hay dust. The disease is prevalent in farmers from countries where, because of high humidity in the summer, molding of stored hay is unavoidable.

Animals↗

PubMed1994

Animal models.

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Animals↗

PubMed1994

Gemcitabine is an active new agent in previously untreated extensive small cell lung cancer (SCLC). A study of the National Cancer Institute of Canada Clinical Trials Group.

BACKGROUND: The new pyrimidine antimetabolite Gemcitabine has shown preclinical efficacy in a number of solid tumour lines and acceptable toxicity in phase I trials. As part of an ongoing effort to identify active new agents in small cell lung cancer, the NCIC Clinical Trials Group studied Gemcitabine in previously untreated patients with extensive disease. PATIENTS AND METHODS: Twenty-nine newly diagnosed patients with untreated extensive small cell lung cancer and at least one bidimensionally measurable site received Gemcitabine as a 30 minute intravenous infusion weekly x 3 every 4 weeks. The starting dose was 1000 mg/m2/week in the first 17 patients and 1250 mg/m2/week in the remainder. Patients were reevaluated for response every 4 weeks. Those failing to respond after 2 cycles of therapy were to be offered standard chemotherapy. RESULTS: Of the 29 patients entered, all were evaluable for toxicity and 26 for response. One complete and 6 partial responses were seen giving a response rate of 27% (95% CI: 11%-47%). Median response duration was 12.5 weeks and the median survival of the entire population was 12 months. Toxic effects were mild to moderate: in particular serious myelosuppression was uncommon. CONCLUSIONS: Gemcitabine is active in previously untreated small cell lung cancer in doses which produce little toxicity. Combination studies of Gemcitabine with other agents active in this disease are warranted.

Aged↗