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Causes and Symptoms of Erectile Dysfunction

The erectile dysfunction has a variety of causes. Recreational drug abuse, alcohol abuse, smoking, hypertension, diseased condition or damage of nerves, atherosclerosis, prostate gland disorders and subsequent corrective surgeries, hormonal imbalance, mental disorders and old age are some of the known causes.

Early warning signs include infirm erections on most occasions, waning desire for sexual activities, emotional imbalances and psychological and social withdrawal.

Causes and Symptoms of Erectile Dysfunction

Treatment for Erectile Dysfunction

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How does Viagra work?

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Viagra

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Bronchoalveolar lavageBronchoalveolar lavage (BAL) was used in these studies to examine the local effects of inhalational antigen challenge on lung lavage cell populations and to determine the safety of BAL in this setting in mild asthmatic patients. For safety reasons, the timing of BAL in these studies was designed to purposefully avoid the peak airway responses to antigen challenge. We found, using strict selection criteria for subjects with bronchial asthma, that BAL performed after allergen BPC is feasible and can be a safe technique to evaluate local airway responses to antigen challenge. The BAL combined with BPC did not affect the occurrence of an early or late asthmatic response, and no fall in FEVi was induced by the lavage procedure itself.

Rankin and co-workers also found no significant decrease in FEV1 in mild asthmatic subjects undergoing BAL; however, the patients in this study were not exposed to an aerosol challenge with allergen. De-Monchy and co-workers also lavaged mild asthmatic subjects after exposure to aerosolized allergen. Although there did not appear to be any complications in this study, pulmonary function tests were not performed after the lavage to document the safety of this procedure after experimental exposure to antigen. The present studies also support the recent guidelines that were established for these types of studies by the American College of Chest Physicians, the American Academy of Allergy and Immunology, the American Thoracic Society, the National Heart, Lung and Blood Institute, and the National Institutes of Allergy and Infectious Diseases.

Prior studies by DeMonchy et alu showed that there were increased eosinophils but no neutrophils in lavage fluid of asthmatic patients after an aerosol challenge; however, no baseline studies were performed on these patients. In this regard, Godard et al showed that eosinophils were increased, at baseline, in asthmatic subjects. The present study shows that eosinophils are increased at baseline in lavage fluid of asthmatic patients and increased further with aerosol exposure to allergen. The increased numbers of neutrophils at four but not 24 hours in the present study may be explained by the fact that lavage was performed at earlier time points in the present study compared to the study by DeMonchy et al. These observations suggest that both neutrophils and eosinophils migrate into the airways within four hours of allergen challenge and are consistent with prior studies which showed an influx of neutrophils, especially at six hours, in late phase responses in the skin. In addition, both neutrophil chemotactic activity (NCA) and eosinophil chemotactic activity (ECA) have been demonstrated in peripheral blood during early and late phase responses which suggest that these cells may migrate into the airways in response to these inflammatory mediators. The present studies in asthmatic patients are also consistent with the studies of Marsh et al who showed an increase of neutrophils and eosinophils after antigen challenge in an animal model of asthma.

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asthmaPatient Population

The characteristics of the patients with asthma are shown in Table 1. All but one of the asthmatic subjects who were experimentally challenged and lavaged responded to BPC with both an early and late phase airway response; one had a late response only. Four of 12 asthmatic patients had dual skin responses. The five normal subjects were challenged with five breaths of 10,000 PNU/ml concentration of Altemaria without response. ‘In season” asthmatic subjects were experiencing mildly symptomatic asthma but were receiving no medication at the time of BAL.

Complications

We observed no complications during the bronchoalveolar lavages. There was an increased tendency for asthmatics to cough; however, coughing was never severe enough to prevent wedging of the bronchoscope. Ear oximetry measurements of arterial oxygen saturation during lavage were always above 94 percent. There were no ECG abnormalities.

Pulmonary Function Measurements

Pulmonary function measurements performed just prior to bronchoalveolar lavage were near the predicted normal baseline for all subjects except two (patients 3 and 9) who were occasionally mildly symptomatic during seasonal exposure. At the time of BAL, their FEVX was 60 and 65 percent of predicted, but their chests were clear of wheezes before BAL. An average decrease in FEVi of 13 percent below baseline values was measured just before BAL and following BPC for the entire group. There was no significant decrease in the FEVj of patients with asthma after lavage compared to their prelavage FEVi (Fig 1). One patient, however, (No. 9) had a 32 percent decrease in FEVj after BPC and lavage. Wheezes were heard in the area of lavage, but cleared with local epinephrine (1:10,000) to the carina. The other patient (No. 3) inadvertently did not have a postlavage FEVj measured but was asymptomatic without wheezing after lavage.

In the asthmatic subjects who were lavaged <4 hours after BPC, there was a similar maximal decrease in FEV1 during the early and late asthmatic response regardless of whether BAL was being performed (Fig 1). Four of five asthmatic subjects who were lavaged 24 hours after BPC had dual responses, but these responses were unaffected by BAL.

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inhalationInhalation of specific allergens usually results in increased airways resistance in asthmatic subjects. This reversible airway obstruction is associated with release of mast cell mediators and an inflammatory response in the airways. In the present studies, we used bronchoalveolar lavage (BAL) to directly assess local inflammatory changes occurring within the airways of atopic asthmatic subjects undergoing experimental bronchoprovocation (BPC), or during environmental, ie, “spontaneous” seasonal exposure. We also examined changes in local cell populations and evaluated lung eosinophils and mast cells morphologically for evidence of degranulation.

Methods

Subject Selection

Seventeen subjects volunteered for these studies. Twelve had mild allergic asthma and five were asymptomatic normal individuals. All subjects gave informed consent to undergo BAL and aeroallergen BPC before entering this study which had been approved by the Human Subjects Use Committee of the University of Iowa. These studies also strictly conform to the guidelines set forth by the American College of Chest Physicians, American Academy of Allergy and Immunology – https://www.aaaai.org/home.aspx, American Thoracic Society, the National Heart, Lung and Blood Institute, and the National Institutes of Allergy and Infectious Diseases. In order to evaluate each individuals atopic status, a complete medical history and physical examination were performed, and a routine battery of allergen skin tests was applied intradermally to the triceps area of the upper arm. A wheal 5×5 mm or greater than diluent control was considered positive. Specific allergens used for BPC were titered on the forearm and observed at 30 minutes and six hours. Histamine and codeine positive control substances were also applied. The atopic asthmatic individuals gave a history of mild seasonal asthma, were skin reactive to the appropriate allergen, developed bronchoconstriction in response to inhaled specific allergen, and demonstrated a positive methacholine aerosol challenge (Table 1). Normal control subjects had no symptoms of respiratory allergy treated by Canadian Health&Care Mall, negative skin tests, a negative methacholine challenge, and no immediate family history for allergic disease.

Criteria for Asthmatic Subjects Undergoing BAL

In order to reduce the risk of triggering already hyperresponsive airways and to maintain rigorous control of those who would be challenged and lavaged, we established specific criteria for all asthmatic subjects (Table 2). Subjects were between the ages of 18 and 45, nonsmokers, and had BALonly mildly symptomatic seasonal asthma. Immediately prior to BAL, they were required to have an FEV1.

Aerosol Challenges

A methacholine (Meth) aerosol challenge was employed to document hyperresponsive or normally responsive airways. Using established procedures, we employed the Johns Hopkins Dosimeter and concentrations of Meth from 0.075 to 25 mg/ml. Subjects were given five breaths of each concentration of Meth by taking slow deep breaths from functional residual capacity to total lung capacity, without breath-holding. A drop in FEVt by 20 percent (below diluent baseline) which persisted for at least five minutes was considered a positive response. The provocative dose producing a 20 percent decrease in FEVj (PDM [FEVJ) was calculated, and expressed as breath units (BU).

Allergen inhalation was performed in a similar manner, using increasing five-fold concentrations of allergens from 1 protein nitrogen unit (PNU)/ml to 10,000 PNU/ml. A 20 percent or greater drop in FEV1 which persisted ^5 minutes was considered positive, and the challenge was stopped. Those subjects who responded to allergen challenge were closely observed in the Clinical Research Center (CRC) of the University of Iowa for 24 hours. Pulmonary function tests were obtained (every 15 minutes for 60 minutes and then every hour from a total of 24 hours) using a forced expiratory maneuver with the Jones Pulmonor II (FVC, FEV^ and MEFR^ts). Normal individuals as control subjects were also challenged with allergen, observed in the CRC overnight, and pulmonary functions were similarly obtained.

Atopic symptomatic (in season) asthmatic subjects who were not taking any medications were challenged out of the appropriate historical season with an allergen to which they were clinically sensitive. Altemaria was used primarily, but cat dander extract was inhaled by one subject, short ragweed extract by another, and house dust by a third. Normal subject control subjects were challenged with 10,000 PNU/ml Altemaria. The PD* for the airway response following allergen challenge was calculated using previously described methods.

BAL Following BPC

For safety reasons, in most instances, we wished to lavage patients when the FEVt was near baseline value. For this reason, we chose time periods two to four hours or 24 hours after BPC for BAL (all asthmatic patients had late phase responses which occurred at 4 to 24 hours after inhalation of allergen). Each subject was prepared for BAL in a manner which is routine for all bronchoscopies, including bronchoalveolar lavage, at the University of Iowa. Atropine sulphate, 0.6 mg IM, and morphine sulphate, 8 mg IM, were given one half hour before the procedure. Xylocaine (4 percent) was aerosolized into the upper airways and applied topically to the pryriform sinuses to prevent coughing and to effect local anesthesia. Each individual also inhaled two puffs (0.65 mg/puff) of bronchoscopemetaproterenol 15 minutes prior to bronchoscopy. All patients and control subjects were medicated identically. Bronchoscopy was performed using a fiberoptic bronchoscope; the tip of the bronchoscope was wedged into three different subsegmental bronchi in the left upper lobe, left lower lobe, and right lower lobe for lavage. Lavage in each site was performed by injecting five 20-ml aliquots of warmed (37°C) normal saline solution (total = 100 ml). Immediately after the injection of each aliquot, suction was applied and the fluid recovered in a sterile trap. The volume of each lavage specimen was measured and then immediately transported to the laboratory.

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