Search PubMed⌕ Search

Biomedical subjects

L Diamond

Publications and source records attributed to L Diamond.

At least 37 records · Page 2Linked to original sources
PubMed1992

Intranasal administration of a beta adrenergic amine: an alternative to metered-dose inhalers.

In anesthetized, artificially ventilated guinea pigs, intranasal and intravenous administration of albuterol produced the same maximum degree of protection against bronchoconstriction induced by bilateral electrical stimulation of the cervical vagal nerves. Intranasal albuterol showed a slower onset of action than intravenous albuterol and exhibited equivalent cardiovascular side effects for the same level of bronchoprotection. Accordingly, intranasal albuterol may represent an alternative to metered-dose inhalation for prophylaxis and treatment of bronchoconstriction in humans.

Administration, Inhalation↗
PubMed1991

A pilot study of state surveying methods for ESRD facilities.

End Stage Renal Disease (ESRD) facilities must meet certification requirements to receive Medicare reimbursement from the Health Care Financing Administration, Department of Health and Human Services (DHHS). State survey agencies, operating under contract with DHHS, assess compliance with conditions and standards for all Medicare facilities. The survey process has been criticized by renal professionals and organizations for its lack of objective criteria, because thresholds have not been established, and for the lack of a severity index. The current process promotes subjective decision making in determining facility deficiencies. Efforts to reorganize the survey process to make it more outcome-oriented are being initiated and, while this is laudable, there is no assurance that the process will be effective. Network #5 conducted a pilot study of state survey results to profile data for Medical Review Board (MRB) analysis and to identify potential areas where educational activities could be focused. Network #5 consists of dialysis and transplant providers in the District of Columbia (D.C.), Maryland, Virginia, and West Virginia. There are 139 dialysis facilities and 13 transplant centers serving over 7,000 dialysis patients. This pilot study was a retrospective analysis of surveys conducted in dialysis units that were operational as of August, 1988. This study did not include transplant providers.

Centers for Medicare and Medicaid Services, U.S.↗
PubMed1990

Adenosine-induced bronchoconstriction in human asthmatics: effects of pretreatment with indomethacin or atropine sulfate.

The present investigation was designed to evaluate the effects of pre-treatment with the cholinergic muscarinic receptor antagonist, atropine sulfate, or with the cyclooxygenase inhibitor, indomethacin, on adenosine-induced bronchoconstriction in human asthmatics. Eight male subjects with a FEV1 of greater than 70% of the predicted normal value underwent bronchial provocation challenges with adenosine and with the cholinergic agonist, methacholine, in a double-blind, randomized, cross-over fashion. The log10 of the agonist dose provoking a 20% decrease in FEV1 (log PD20FEV1) was used to assess airways responsiveness. Challenges were performed in the untreated state and 30 min after inhalation of atropine sulfate (0.05 mg/kg). Pre-challenge FEV1 values after atropine inhalation were higher than in the untreated state (p less than 0.01). Without atropine, the log PD20FEV1 values for adenosine were higher than those for methacholine (p less than 0.01). Atropine prevented a decrease in the FEV1 of 20% or more in seven of the eight subjects following inhalation of methacholine up to a concentration of 25 mg/ml, but did not significantly change the log PD20FEV1 for adenosine. The effects of a 75 mg oral dose of indomethacin or placebo, administered in a double-blind, randomized, cross-over fashion two hours before adenosine or methacholine challenge, were assessed in 12 asthmatics. In four subjects (two after placebo and two after indomethacin pretreatment), aerosols of the highest adenosine concentration (10 mg/ml) failed to decrease the FEV1 by 20% or more. In the remaining eight subjects, log PD20FEV1 values for adenosine or methacholine after indomethacin were not significantly different from those after placebo.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine↗
PubMed1990

Nicotinic agonist modulation of feline bronchomotor tone.

1. The bronchomotor actions of three nicotinic cholinoceptor agonists were investigated in anaesthetized, mechanically ventilated cats. The agonists were administered intravenously after increasing baseline airways smooth muscle tone with an infusion of 5-hydroxytryptamine. 2. Acetylcholine induced a biphasic change in lung resistance, characterized by initial bronchoconstriction followed by bronchodilation. The specific nicotinic cholinoceptor agonists, nicotine and dimethylphenylpiperazinium (DMPP), principally induced bronchodilator responses, although initial bronchoconstrictor phases were observed occasionally. 3. All bronchoconstrictor phases were sensitive to muscarinic cholinoceptor blockage with atropine. DMPP-induced bronchodilator responses were adrenergic in nature, whereas those induced by either nicotine or acetylcholine resulted from a combination of adrenergic and non-adrenergic influences. 4. It is concluded that intravenously administered nicotinic cholinoceptor agonists exert varying actions on feline bronchomotor tone and that these actions result from activation of different autonomic inputs.

Acetylcholine↗
PubMed1990

Nonadrenergic bronchodilation induced by high concentrations of sulfur dioxide.

SO2 is an environmental pollutant known to elicit bronchospasm in susceptible subjects. We observed that brief exposure of artificially bronchoconstricted cats to high concentrations of SO2 induces a bronchodilator response. This study assessed the characteristics of this response and examined various mechanisms that might underlie it. Cats were anesthetized with diallylbarbital-urethan, and airway smooth muscle tone, measured by lung resistance and dynamic lung compliance, was elevated with a continuous infusion of 5-hydroxytryptamine. Administration of 10 breaths of SO2 via a tracheostomy induced concentration-dependent bronchodilation in the range 100-1,000 parts/million. Only infrequently was bronchoconstriction observed before bronchodilation. SO2-induced bronchodilator responses were unaffected by pretreatment with intravenous atropine or propranolol, establishing them as nonadrenergic noncholinergic (NANC) in origin. Neither the ganglionic blocking agent hexamethonium nor the nerve toxin tetrodotoxin influenced the SO2-induced bronchodilation, thus excluding a role for central or local autonomic reflexes in the response. Efforts to modulate the response by pretreatment with the cyclooxygenase inhibitor indomethacin or the mediator release inhibitor cromolyn sodium also were unsuccessful. Administration of acidic aerosols failed to mimic the SO2-induced bronchodilator response. Although the mechanism whereby SO2 induces bronchodilation under these experimental conditions remains unclear, release of a NANC inhibitory transmitter from a neural, epithelial, or other cellular source via a mechanism insensitive to both tetrodotoxin and cromolyn is a distinct possibility. An intrinsic NANC inhibitory system may exist in feline airways functioning as a local regulator of bronchomotor tone and possibly serving to override responses to strong, potentially asphyxial bronchoconstrictive stimuli.

Animals↗
PubMed1990

Enzymatic modulation of vasoactive intestinal peptide and nonadrenergic noncholinergic inhibitory responses in guinea pig tracheae.

The airways of the guinea pig are innervated by four types of autonomic nerves: cholinergic excitatory, adrenergic inhibitory, nonadrenergic noncholinergic (NANC) excitatory, and NANC inhibitory. Tachykinins (neurokinins A and B and substance P) are believed to mediate NANC excitatory responses, and vasoactive intestinal peptide (VIP) has been proposed as the chemical mediator of the NANC inhibitory system. Enzymatic degradation represents an important means by which the biologic actions of neurotransmitters are terminated. In the present study, relaxation responses of guinea pig tracheae to NANC nerve stimulation and to exogenous VIP administration were compared in the absence and presence of various peptidase inhibitors. NANC inhibitory responses elicited by electrical field stimulation were unaffected by aprotinin or soybean trypsin inhibitor but were depressed by thiorphan or leupeptin. Concentration-response curves to exogenous VIP were shifted to the left by soybean trypsin inhibitor but were not affected by aprotinin, leupeptin, or thiorphan. After tachykinin depletion with capsaicin, thiorphan also induced a leftward shift in the VIP concentration-response curve. Under the same conditions, thiorphan failed to influence NANC inhibitory responses. These results indicate that the NANC inhibitory neurotransmitter is not metabolized by enzymes susceptible to inhibition by aprotinin, leupeptin, soybean trypsin inhibitor, or thiorphan and, accordingly, distinguish NANC nervous responses from those induced by VIP. The results also suggest that the NANC excitatory system can interact functionally with the NANC inhibitory system, as evidenced by the blunting of NANC relaxation responses following inhibition of tachykinin metabolism and elimination of this effect by capsaicin.

Animals↗
PubMed1990

Presynaptic alpha adrenoceptor modulation of neurally mediated cholinergic excitatory and nonadrenergic noncholinergic inhibitory responses in guinea pig trachea.

Cholinergic and nonadrenergic noncholinergic (NANC) excitatory nerves in guinea pig trachea are subject to presynaptic alpha-2 adrenoceptor inhibitory control. Although the trachea is also innervated by NANC inhibitory nerves, little is known about their presynaptic regulation. The present study assessed the capacity of alpha-1 and alpha-2 adrenoceptor agonists to modulate NANC inhibitory nerves and for comparison, cholinergic excitatory nerves in guinea pig trachea. To eliminate effects of intrinsic sympathetic nerve stimulation and prostanoid production, tissues were pretreated with guanethidine, propranolol and indomethacin. The alpha-2 adrenoceptor agonist, clonidine (1 microM), induced a 12-fold rightward shift of the frequency-response curve for neurally mediated cholinergic contractions but had no effect on the concentration-response curve for exogenously administered acetylcholine. This action of clonidine was inhibited in a concentration-dependent manner by the alpha-2 adrenoceptor antagonist, yohimbine, and by the alpha-1 adrenoceptor antagonist, prazosin, NANC inhibitory responses were unaffected by clonidine (1 microM). The alpha-1 adrenoceptor agonist, phenylephrine (1 microM), failed to influence responses induced by cholinergic or NANC inhibitory nerve stimulation, acetylcholine or vasoactive intestinal peptide. Furthermore, in tissues treated with propranolol but not subjected to adrenergic neuronal blockade with guanethidine, neurally mediated cholinergic responses were not altered by yohimbine (0.3 microM) treatment. These results indicate that in guinea pig trachea: 1) cholinergic nerves are modulated by presynaptic, prazosin-sensitive inhibitory presynaptic alpha-2 adrenoceptors and 2) NANC inhibitory nerves do not possess presynaptic, modulatory alpha adrenoceptors.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

High expression of ras p21 correlates with increased rate of abnormal mitosis in NIH3T3 cells.

The modulation of responsive genes by hormonal stimulation is an attractive in vitro model system for the study of a wide variety of biological processes. Using this methodology we have investigated the effect of the human oncogene protein p21ras on mitosis using mouse mammary tumor virus long terminal repeat (MMTV-LTR)-directed gene expression. Following the induction of p21 protein, abnormal mitotic figures were scored in metaphase and anaphase. Elevated expression of p21 was associated with marked increase in the proportion of abnormal mitoses most significantly during the metaphase. Concomitant with a three fold increase in p21 levels, abnormal mitosis rose from 14.0% to 27.25%. The increase in abnormal mitosis corresponded to a 225% increase in abnormal metaphase. The p21-induced mitotic abnormalities were exhibited as lagging chromosomes in prometaphase, 3 group metaphase and C-metaphase. In addition, high expression of p21 was accompanied by significant changes in the cell morphology and fine ultrastructure, e.g. disorganization of actin, the extensive formation of microvilli on the plasma membrane and marked dilatation of the rough endoplasmic reticulum. The mitotic and structural changes were reversible upon removal of dexamethasone and decline of p21 production to its basal levels. Our results identify an important biological effect of ras p21 during mitosis and the early stages of neoplastic transformation.

Animals↗
PubMed1989

SV40-transfected human melanocyte sensitivity to growth inhibition by the phorbol ester 12-O-tetradecanoylphorbol-13-acetate.

Normal human melanocytes, which require the phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA) for growth in culture, were transfected with a SV40 T-antigen-containing plasmid by using the technique of electroporation, and were scored for colonies of morphologically altered cells. The frequency of transformed colonies was higher when selection was done in the absence rather than the presence of TPA in the medium. Three cell lines derived from transformed colonies were characterized. All show an enhanced growth rate compared to parental cells, anchorage independence, loss of dependence on medium supplements for growth, chromosomal abnormalities, an extended life span, and growth inhibition by TPA. They express nerve growth factor receptor and Mr 97,000 protein, melanotransferrin, two antigens usually associated with melanocytic cells, but the transformed cells are not pigmented. The three cell lines underwent crisis at about passage 10 posttransfection; one cell line recovered and appears to have unlimited growth potential. None of the cell lines is tumorigenic. They should be interesting models for studying multistage carcinogenesis in human cells and transcriptional activation by TPA.

Antigens, Polyomavirus Transforming↗
PubMed1988

The effect of epithelium removal on non-adrenergic, non-cholinergic inhibitory responses in the isolated central airways of the cat and guinea pig.

Epithelium removal from the feline or the indomethacin-treated guinea pig trachea had no effect on tissue sensitivity or responsiveness to the contractile actions of pharmacological agonists or electrical field stimulation. In the feline hilar bronchus, epithelium removal had no effect on tissue sensitivity or responsiveness to acetylcholine or electrical field stimulation but increased bronchial sensitivity to serotonin without affecting responsiveness. Non-adrenergic non-cholinergic (NANC) relaxation responses elicited by electrical field stimulation in airway preparations from either species were unaffected by epithelium removal. These results suggest that the epithelium does not modulate contractile responses in the feline trachea but may modulate the actions of specific contractile agonists in the feline hilar bronchus. Further, NANC relaxation responses appear to occur independently of the airway epithelium.

Acetylcholine↗
PubMed1988

Multicenter, double-blind, multiple-dose, parallel-groups efficacy and safety trial of azelastine, chlorpheniramine, and placebo in the treatment of spring allergic rhinitis.

Azelastine, a novel antiallergic medication, was compared with chlorpheniramine maleate and placebo for efficacy and safety in the treatment of spring allergic rhinitis in a multicenter, double-blind, multiple-dose, parallel-groups study. One hundred fifty-five subjects participated. Subjects ranged in age from 18 to 60 years of age and had at least a 2-year history of spring allergic rhinitis, confirmed by positive skin test to spring aeroallergens. Medications were given four times daily; the azelastine groups received 0.5, 1.0, or 2.0 mg in the morning and evening with placebo in the early and late afternoon; the chlorpheniramine group received 4.0 mg four times daily. Daily subject symptom cards were completed during a screening period to assess pretreatment symptoms and during a 4-week treatment period while subjects received study medications. Individual symptoms, total symptoms, and major symptoms were compared to determine efficacy of medication. Elicited, volunteered, and observed adverse experiences were recorded for each subject and compared among groups. Vital signs, body weights, serum chemistry values, complete blood cell counts, urine studies, and electrocardiograms were obtained for each subject and compared among groups. Symptoms relief in the group receiving the highest concentration of azelastine (2.0 mg twice daily) was statistically greater than in the placebo group during all weeks of the study. Lower doses of azelastine were statistically more effective than placebo only during portions of the first 3 weeks of the study. In contrast, although the chlorpheniramine group did have fewer symptoms than the placebo group during the study, the difference never reached statistical significance during any week of the study. There were no serious side effects in any of the treatment groups. Drowsiness and altered taste perception were increased significantly over placebo only in the high-dose azelastine group. Azelastine appears to be a safe, efficacious medication for seasonal allergic rhinitis.

Adolescent↗
PubMed1988

Growth and phenotypic characteristics of human nevus cells in culture.

Nevus cells were isolated from the three cutaneous components, epidermis, basal layer, and dermis, of nonmalignant pigmented lesions and were cultured separately in the presence or absence of the phorbol ester 12-0-tetradecanoyl phorbol-13-acetate in medium that supports the rapid proliferation of melanocytic cells. The separation procedure used provided cultures that were essentially free from normal melanocytes (dermis) or fibroblasts (epidermis). In short term culture, nevus cells of all skin compartments expressed markers associated with differentiated melanocytes, such as presence of premelanosomes and melanosomes and elevated tyrosinase levels. Nevus cells also expressed melanoma-associated antigens, such as NGF-receptor, transferrin-related p97, proteoglycan, and HLA-DR as detected with monoclonal antibodies. After several subpassages, cells showed a decreased expression of melanoma-associated antigens, decreased tyrrosinase levels, and melanosomes could no longer be detected. Morphologically, these cells were similar to fibroblasts. The disappearance of melanoma-associated cell surface antigens was concomitant with the appearance of a melanocyte-associated 145 kd protein that might serve as a marker of fibroblast-like differentiation in nevus cells and normal melanocytes. Nevus cell cultures grown in the presence of 12-0-tetradecanoyl phorbol-13-acetate maintained a stable differentiated phenotype throughout their lifespan. As reported earlier, nevus cells in culture, irrespective of the presence or absence of 12-0-tetradecanoyl phorbol-13-acetate, have a finite lifespan in vitro, grow anchorage-independent in soft agar, but do not form tumors when xenografted to nude mice. These studies demonstrate that nevus cells isolated from the epidermal, basal layer, and dermal components of lesional skin can serve as models to characterize the initial steps of tumor progression in a human cell system.

Adolescent↗
PubMed1988

Augmentation of elastase-induced emphysema by cigarette smoke. Effects of reduced nicotine content.

To examine the role of nicotine in the augmentation of elastase-induced emphysema by cigarette smoke, animals that had been pretreated with porcine pancreatic elastase (PPE) were exposed to cigarette smokes that had a five-fold difference in their nicotine concentrations. Young adult female Long-Evans rats were divided into seven groups: (1) untreated controls; (2) low nicotine cigarette smoke exposure (Kentucky 2A1 reference cigarettes; 35.0 mg total particulate matter, 0.42 mg nicotine, and 0.38 mg nitrogen oxides per cigarette); (3) high nicotine cigarette smoke exposure (Kentucky 2R1 reference cigarettes; 38.8 mg total particulate matter, 2.2 mg nicotine, and 0.34 mg nitrogen oxides per cigarette; (4) PPE alone; (5) PPE + sham smoke exposure; (6) PPE + 2A1 smoke exposure; and (7) PPE + 2R1 smoke exposure. Three days after intratracheal administration of PPE (400 IU/kg), animals in the smoke-treated groups were exposed to 10 puffs of cigarette smoke daily, 7 days/wk for 14 wk. Sham-treated animals received room air in place of cigarette smoke. After the exposures, pulmonary function tests were performed under general anesthesia. Whole lungs were examined for gross pathologic changes, and samples of lung tissue were harvested for quantitative morphometry. Cigarette smoke exposure alone did not produce significant changes in pulmonary function or structure. On the other hand, treatment with elastase alone produced a constellation of pulmonary functional and structural changes that were pathognomonic of emphysema. Exposure to 2R1 but not 2A1 cigarette smoke significantly augmented the emphysematous changes produced by PPE.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗