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Biomedical subjects

J L Pinnas

Publications and source records attributed to J L Pinnas.

At least 37 records · Page 2Linked to original sources

Acetaldehyde-albumin adduct formation: possible relevance to an immunologic mechanism in alcoholism.

Acetaldehyde (A), an ethanol metabolite, was incubated with rabbit serum albumin (RSA) and human serum albumin (HSA) to form the corresponding soluble haptenized proteins, A-RSA and A-HSA respectively. Both protein adducts showed conjugation with acetaldehyde evidenced by more rapid anodal migration compared to RSA and HSA. A-RSA immunized rabbits produced titers greater than 1:100,000 by enzyme-linked immunosorbent assay (ELISA). Rabbit serum antibodies to A-RSA diluted 1:10,000 showed high specificity for the hapten when reacted with acetaldehyde conjugates of RSA, HSA, bovine serum albumin, bovine gamma globulin and human gamma globulin. Our findings support the possibility that acetaldehyde may serve as a hapten to form neoantigens relevant to an immunologic mechanism which might be associated with alcoholic liver disease.

Acetaldehyde↗

Multicenter study of bitolterol and isoproterenol nebulizer solutions in nonsteroid-using patients.

Bitolterol mesylate, 1.0 mg, or isoproterenol hydrochloride, 1.5 mg, was administered three times daily for 3 months in a double-blind, multicenter study via closed-port, intermittent-flow, compressor-driven nebulizer system (CPIF) to 182 nonsteroid-using patients with asthma. Mean baseline FEV1 was approximately 60% of predicted normal for both groups. Pulmonary function tests and vital signs were measured before and for up to 8 hours after treatments on test days 1, 30, 60, and 90. Mean maximum increases in FEV1 were 51%, 54%, 52%, and 55% for bitolterol versus 48%, 46%, 50%, and 43% for isoproterenol on these monthly test days. The mean FEV1 response remained greater than 15% over zero time (baseline) for greater than or equal to 8 hours after medication with bitolterol on each of four monthly pulmonary function test days and 2 1/2 to 5 hours for isoproterenol. Median durations of bronchodilator activity for bitolterol were 7.3, 6.5, 6.5, and 6.0 hours versus 4.0, 1.7, 3.7, and 1.9 hours for isoproterenol on the monthly test days. On these test days, 37% to 49% of the patients treated with bitolterol had a duration of action of at least 8 hours compared with 16% to 29% after isoproterenol treatment. The onset of activity was within 5 minutes for both drugs. Bitolterol provided superior bronchodilator activity with fewer adverse effects compared with isoproterenol, and there was no evidence for drug tolerance during this 3-month study.

Adult↗

Comparison of the bronchodilator effects of nebulized bitolterol mesylate and isoproterenol hydrochloride in steroid-dependent asthma.

This study of 183 ambulatory patients with steroid-dependent asthma was conducted to evaluate the efficacy and safety of nebulized bitolterol mesylate solution (0.2%) compared to isoproterenol hydrochloride solution (0.3%). A double-blind, randomized, parallel-group, repetitive-dose design was followed at nine centers for 3 months. Patients received either 1.0 mg of bitolterol or 1.5 mg of isoproterenol three times a day with a closed, intermittent-flow nebulization system. Pulmonary function was evaluated on four 8-hour office visits at approximately 30-day intervals. Efficacy was based on a 15% increase in FEV1 over baseline. Both medications resulted in bronchodilatation within 5 minutes, whereas nebulized bitolterol was statistically superior (p less than 0.05) to nebulized isoproterenol in terms of duration of action and area under the curve. The mean FEV1 response to bitolterol therapy remained greater than 15% over baseline for 5 to 8 hours on the four test days compared to 2 to 4.75 hours for isoproterenol therapy. Both medications were well tolerated. Adverse reactions were transient, and most were mild to moderate. Tremor was the most frequent side effect occurring in approximately 30% of the patients in both groups. There were no clinically significant laboratory changes or electrocardiographic findings. Nebulized bitolterol mesylate was found to be a safe and effective bronchodilator in steroid-dependent patients with asthma.

Adult↗

Dose-response study of nebulized bitolterol mesylate solution in asthmatic patients.

Bitolterol mesylate, a new beta 2 adrenergic bronchodilator, is a "pro-drug" which is activated by esterases in the lung. In order to determine the optimal bronchodilator dose of bitolterol, six doses, (0.5 mg, 1.0 mg, 1.5 mg, 2.0 mg, 2.5 mg and 3.0 mg), were administered by closed-port, intermittent-flow nebulization (CPIF) to asthmatic patients on different days. For most patients, the onset of bronchodilator activity (FEV1 increase of at least 15 percent above baseline) occurred within 5 minutes and lasted at least 8 hours. Maximum mean increases in FEV1 were 46-50 percent at the 1.0 mg to 3.0 mg doses. Beyond the 1.0 mg dose, there was no significant improvement in bronchodilator effect, but adverse effects, particularly tremor, increased at higher doses. The optimal dose of bitolterol administered by CPIF was determined to be 1.0 mg which is similar to the dose of bitolterol recommended for use by metered-dose inhaler (MDI) which is 0.7 mg to 1.1 mg. If continuous-flow nebulization is used, two-three times more drug may be needed for a comparable effect. Bitolterol appears to be a safe, effective and long-lasting bronchodilator when administered by jet nebulization.

Adolescent↗

A comparison of albuterol and metaproterenol nebulizer solutions.

Metaproterenol (15 mg) and albuterol (5 mg) solutions were each nebulized and delivered to 20 patients with reversible airway obstruction utilizing intermittent positive pressure ventilation in a double-blind comparison. Ten subjects were randomly assigned to each group and they were examined at the start (day 0) and at the end of the study (day 7). There were no significant differences observed between the spirometric responses or the untoward effects of the two groups to either agent. Albuterol and metaproterenol, when administered by intermittent positive pressure ventilation, are essentially equivalent in terms of the magnitude and duration of the response.

Adult↗

Comparison of airborne fungi in evaporative cooled and air conditioned homes.

The evaporative cooler (EC) is commonly used during the warmer months in millions of homes in the desert regions of the Southwestern United States. In this investigation fungi isolated from EC homes were compared with recoveries from air conditioned (AC) homes. Aspergillus tamarii was more abundant in EC homes (P less than .05) whereas Penicillium spp. were more prevalent in AC homes (P less than .05). Fusarium was recovered only from EC homes. Overall, more fungi were isolated from EC homes than AC homes both in terms of total numbers of isolates and numbers of species recovered. The EC appears to provide a niche for allergenic fungi that may be transmitted into the home or business.

Air Conditioning↗

Comparison of bronchodilator responses with bitolterol mesylate solution with the use of two different nebulizer systems in asthma.

Bitolterol mesylate is a beta 2-adrenergic bronchodilator that has been studied in a metered-dose inhaler formulation and as an aerosol in a closed, intermittent-flow nebulizer system. The optimum dose was found to be 1.0 mg in the closed system. In this dose-response study, 1.0 mg by closed-system nebulizer was compared with different doses delivered by an open, continuous-flow nebulizer system. Treatment with 2.5 mg of bitolterol mesylate in the open system is comparable to 1.0 mg in a closed system. Onset of bronchodilator activity occurred within 5 minutes for most patients, and median duration of action with different doses was 8 hours or longer. Mean maximum percent increases in FEV1 with 2.5, 3.5, and 4.5 mg of bitolterol mesylate with the open system were approximately 50% and comparable with that obtained with 1.0 mg with the closed system. Treatments with doses up to 3.5 mg in the open system were well tolerated with few side effects. We conclude that bitolterol mesylate is an effective, long-lasting bronchodilator when it is used as a nebulized aerosol by both open and closed delivery systems; a larger dose is optimal for the former system than for the latter. We believe that manufacturers' recommended doses should take into account the different efficiencies of open and closed nebulizer systems.

Adolescent↗

Studies of kissing bug-sensitive patients: evidence for the lack of cross-reactivity between Triatoma protracta and Triatoma rubida salivary gland extracts.

In the southern and western sections of the United States, bites from the reduviid bug, commonly known as the kissing bug, genus Triatoma, may induce serious life-threatening allergic reactions. This study was undertaken to identify the allergens responsible for patient sensitization and to determine the extent of cross-reactivity of these allergens. The Triatoma spp. most commonly encountered in California and Arizona, T. protracta and T. rubida, were obtained, maintained in the laboratory, and dissected to prepare extracts for testing. Extracts were prepared from T. protracta and T. rubida for study by RAST, lymphocyte transformation, leukocyte histamine release, and RAST inhibition. Sera and cells were collected from patients who had generalized reactions to Triatoma bites. Our results indicate that T. protracta and T. rubida antigens to which patients are sensitized are present in extracts that contain saliva and that human responses are specific for T. protracta or T. rubida, i.e., allergic cross-reactivity could not be demonstrated.

Adolescent↗

Pneumococcus-specific immunoglobulin E in cigarette smokers.

A relationship between elevated serum immunoglobulin E levels and smoking has been demonstrated in epidemiological studies. Allergy skin test data suggest that the excess immunoglobulin E of smokers is not specific for aeroallergens. It is possible that the excess immunoglobulin E is specific for microorganisms that often infect the lower respiratory tract of smokers. To investigate this possibility we utilized a radioallergosorbent test assay for detecting serum immunoglobulin E specific for Streptococcus pneumoniae, an organism commonly isolated from the respiratory tract of smokers with chronic bronchitis. We assayed sera of thirty smokers and thirty nonsmokers for immunoglobulin E specific for Streptococcus pneumoniae. Individual sera were considered positive for pneumococcus-specific immunoglobulin E if the binding was at least twice the non-specific binding at the total immunoglobulin E concentration of the particular serum. Eleven of the thirty sera of smokers and two of the thirty nonsmokers were positive for pneumococcus-specific immunoglobulin E. By chi-square analysis of these data, the prevalence of pneumococcus-specific immunoglobulin E was significantly greater in the smoking group compared with the non-smoking group (P less than 0.02). These results suggest that the excess immunoglobulin E of smokers is, at least in part, specific for microorganisms that infect the airways.

Adult↗

Deficiency of UV-induced excision repair in human thymocytes.

The capacity of human thymocytes and of differentiated lymphocytes circulating in peripheral blood to perform unscheduled DNA synthesis (a measure of nucleotide excision repair) after UV irradiation was measured by radioautographic analysis. Only 4% of immature T lymphocytes, but 68% of circulating lymphocytes exhibited unscheduled DNA synthesis. When UV sensitivity of peripheral blood lymphocytes and thymocytes from the same donor were compared, the thymocytes, in each case, were significantly more UV sensitive than were the circulating lymphocytes. Peripheral blood lymphocytes from subjects undergoing halothane and morphine anesthesia during surgery showed 56% less excision repair capacity than those from unanesthetized donors. The difference occurred in the number of cells capable of repair rather than in the extent of repair synthesis per cell. Ultraviolet-induced unscheduled DNA synthesis occurred in only 3% of the thymocytes removed from rats killed by cervical dislocation. Therefore, the deficiency of excision repair was observed in rat thymocytes which had not been affected by anesthesia or surgical trauma. Since the thymus contains more than 90% immature T-cells, our results indicate that immature T-cells are deficient in nucleotide excision repair whereas the majority of mature peripheral blood lymphocytes exhibit such repair.

Animals↗

Aerosol formulations of terbutaline and isoproterenol in theophylline-stabilized asthmatic patients.

A metered-dose aerosol formulation of terbutaline sulfate (Brethaire), 0.400 mg four times daily, was compared with an identical formulation of isoproterenol sulfate, 0.150 mg four times daily, in a parallel, double-blind, clinical study completed by 40 adult patients with asthma. All patients had been stabilized on theophylline (serum levels of 10 to 20 micrograms/ml). The effectiveness of isoproterenol peaked between 5 and 15 minutes after administration. The effectiveness of terbutaline peaked between 5 and 120 minutes after administration. In each of five visits spaced over a three-month period, patients receiving terbutaline showed a longer duration of bronchodilatory effect than those receiving isoproterenol, with the greatest difference occurring at 60 and 120 minutes after drug administration.

Adolescent↗

Pollen-induced chemiluminescence: inhibition by serum from allergic individuals.

The interaction between pollen grains, polymorphonuclear leukocytes (PMNs) and serum results in the formation of "pollen rosettes" and the production of chemiluminescence (CL). Significantly more CL is produced by cells exposed ot pollen and sera from nonallergic individuals compared with sera from allergic individuals. The source of the PMNs, however, has no effect on the CL produced, When IgG is isolated from the sera of allergic individuals and added to the test system, a large CL response is seen that is inhibited by the IgG-depleted fraction. No similar inhibition is produced by the IgG-depleted fraction of sera from nonallergic individuals. The inhibitor of CL in sera from allergic individuals appears to be IgE, since its removal leads to an enhanced CL response. These results suggest that competition for a limited number of binding sites on pollen grains exists between pollen specific IgG and IgE antibodies in serum from allergic patients.

Granulocytes↗

Frequency of airborne Alternaria spores in Tucson, Arizona over a 20-year period.

Once recommended by clinicians to the allergy sufferer as a refuge due to its healthful arid climate, Tucson is now noted for its incidence of asthma which if two to three times higher than the nation as a whole. This increase in asthma incidence has been attributed in part to a 10-fold increase in atmospheric pollen over the years due to the widespread use of high pollen-producing shade and ornamental trees. Data obtained by Durham slide sampler also reveal a five-to-tenfold increase in numbers of Alternaria (Alt) spores in Tucson over the last 20 years. This may be linked to the increasing numbers of certain pollen producing plants which may serve as the substrate for the mold. Relationships appear to exist between Alternaria frequency and numerous climatic conditions such as precipitation, average monthly relative humidity, average monthly temperature and incident radiation. Because of these relationships the frequency of Alternaria may be predictable on a daily, seasonal and yearly basis.

Alternaria↗