Requirements for an enterprise digital image archive.

This report describes several image archival problems facing the authors' department and the results of their attempt to define the requirements for an enterprise digital image archive. The problems identified include the costs of supporting multiple distinct archives, the increased complexity of supporting multiple archive interfaces, the differences in data handling policies and resulting variations in data integrity, and variability in support for nonimage data. The authors also describe the data collected including image volumes and trends and imaging device trends. Finally, the resulting specification for an enterprise digital image archive, including storage and retrieval performance and interface requirements are presented.

Autosomal dominant syndrome of lipid neuromyopathy with normal carnitine: successful treatment with long-chain fatty-acid-free diet.

A family (mother and two sons) have had lifelong muscle weakness and intolerance to fatty food. Histochemistry of muscle biopsies of all three patients demonstrated increased lipids in type I muscle fibers and type II muscle fiber atrophy and paucity. Electronmicroscopy of muscle revealed increased lipids, abnormal mitochondria, and increased lipofuscin granules. Electronmicroscopy of sural nerve showed inclusions in most of the Schwann cell cytoplasm, with lipid droplets, zebra bodies, lipofuscin granules, and abnormal mitochondria. Carnitine and CPT I and II levels were normal in serum and muscle. Treatment with long-chain fatty-acid-free diet resulted in remarkable clinical improvement and in decrease of lipid droplets in the muscle. This dietary program may be useful in other forms of lipid myopathy.

Comparative actions of biologic and synthetic leukotrienes on isolated human bronchus and rat mast cells.

The effects of biologically prepared leukotriene C4 (LTCb) and leukotriene D4 (LTDb), obtained from rat monocytes stimulated with the calcium ionophore A23187, were compared with those of chemically synthetized leukotrienes (LTCs and LTDs) using two in vitro systems. All four leukotriene preparations (10(-10) to 6 X 10(-6) M) showed equal activity upon human bronchi, inducing slow, sustained contractions. LTCb alone (10(-7) to 6.9 X 10(-7) M) elicited histamine release and enhanced compound 48/80-induced release in a dose-dependent manner from rat mast cells. In contrast, LTDb alone was without effect but inhibited release caused by 48/80. FPL 55712 failed to block the LTCb and LTDb effects on the release process. The synthetic leukotrienes neither caused histamine release nor modulated 48/80-induced release from rat mast cells. We conclude that biologic and synthetic leukotrienes exhibit comparable contractile activity on isolated human bronchi but only biologic preparations modulate histamine release by previously unappreciated substances that isolate with the biologic leukotrienes.

Physiological and immunological effects of chronic antigen exposure in immunized guinea pigs.

Antigenic tolerance was induced in previously sensitized guinea pigs by challenging with ovalbumin (OA) aerosol 1 h/day, 5 days/week for 6 weeks. Reactivity was assessed visually and by lung mechanics. Sera from tolerant and sensitized animals showed comparable titers of antigen-specific antibody by passive cutaneous anaphylaxis with 6-hour, 4-day (heated serum) and 7-day sensitizations. In vitro contractile responses of airway smooth muscle revealed comparable histamine responses in sensitized and tolerant guinea pigs but decreased OA sensitivity in smooth muscle from tolerant animals. Although lung histamine content was equivalent in the two groups, antigen-induced histamine release from chopped lung preparations was significantly less in tolerant animals at a low antigen concentration. We conclude that antigen-induced histamine release is impaired in tolerant animals.

Equine immunology 4: vaccines and antisera.

This paper attempts to relate the practicalities of vaccine development to the ideals which should be aimed for in a new vaccine. The type of immune response induced is dependent upon the nature of the antigen in the vaccine and the site and timing of its presentation to the immune system. In this respect the influence of age, maternal immunity and antigenic competition are discussed. The possible side effects associated with vaccination are defined and vaccines which are currently available for horses are reviewed. These vaccines are mostly for the prevention of respiratory disease. Finally, the possible uses for antisera are considered.

Equine immunology 3: immunopharmacology--anti-inflammatory and antihypersensitivity drugs.

This article reviews anti-inflammatory and antihypersensitivity drugs under these 4 headings: Functional or physiological antagonists; Selective pharmacological inhibitors; Broad spectrum anti-inflammatory drugs; Miscellaneous inhibitors. The compounds considered include sympathomimetic amines, anticholinergic drugs, antihistamine drugs, tryptamine antagonists and dopamine antagonists, glucocorticosteroids and non-steroidal anti-inflammatory drugs, disodium cromoglycate and diethylcarbamazine citrate. The relationship of the pharmacological actions of these compounds is considered in the context of clinical conditions. The potential for immunomodulatory pharmacology is discussed using levamisole as an example.

Equine immunology 2: immunopharmacology--biochemical basis of hypersensitivity.

In general, 4 types of hypersensitivity reactions can be defined according to their immunological basis and clinical appearance. The differing mechanisms of these responses are described with particular reference to chemical mediators which through their pharmacological actions contribute to the clinical manifestations of hypersensitivity. Chemical mediators may exert their influence locally or systemically through their action on effector, tissues or organs and in addition, may be involved in the recruitment of cells of specific type to the site of the reaction. The possible role of these mediators in hypersensitivity in the equine species is discussed to provide a background for a subsequent paper which will be concerned with the therapy of hypersensitivity conditions.

Equine immunology: an introductory review.

This article attempts to relate some of the more recently accepted concepts of immunology to an understanding of the mechanisms of immunity in the horse. The cellular mechanisms involved in the immune response are outlined, with an indication of their likely role in humoral and cell-mediated immunity. In describing the humoral immune response, the structure and function of the different equine immunoglobulins are reviewed. The significance of humoral and cell-mediated immune responses are considered in relation to actively and passively acquired immunity.

Evaluation of the action of cholinergic agonists and cyclic guanosine monophosphate (c'GMP) on histamine release from purified rat mast cells.

Results from previous studies providing conflicting data regarding the effects of cholinomimetic drugs and cyclic 3',5'-guanosine monophosphate salts (cyclic GMP) upon the release of histamine from various tissues. In the present investigations, highly purified rat peritoneal mast cells were incubated with a wide range of concentrations of carbachol, acetylcholine, and cyclic GMP in the absence and presence of the histamine releasing agents compound 48/80 and concanavalin A (Con A). Neither carbachol nor acetylcholine (10(-13) to 10(-4) M) alone caused rat mast cells to secrete histamine. Furthermore, when these drugs were combined with Con A (Con A 1 and 10 microgram/ml, carbachol 10(-13) to 10(-4) M) and compound 48/80 (compound 48/80 0.2 microgram/ml) acetylcholine 10(-13) to 10(-4) M), no enhancement of histamine release was observed. Cyclic GMP (8-bromo and dibutyryl salts) failed to elicit histamine release from rat mast cells over the concentration range 10(-7) to 10(-3) M. As well, cyclic GMP did not enhance Con A (10 microgram/ml)-induced histamine release. In fact this substance inhibited the release by as much as 15% at 10(-3) M concentrations. The present data suggest that neither cholinomimetic drugs nor cyclic GMP evoked direct release or enhance the release of histamine from purified rat peritoneal mast cells.

Slow-reacting substances (leukotrienes) contract human airway and pulmonary vascular smooth muscle in vitro.

During a type I allergic reaction histamine, slow-reacting substance of anaphylaxis (SRS-A) and other mediator substances are elaborated from specific tissue sites. In allergic asthma these sites are in the lung and the mediator substances cause airway obstruction by contracting smooth muscle and altering mucociliary function. Unlike histamine, slow-reacting substances (SRSs) have been assessed very little for their roles in obstructive airways disease. This has been partly due to the fact that their chemical nature was unknown until recently and thus pure samples were not available for pharmacological studies. However, SRSs isolated from both immunological and non-immunological reactions have been identified as a combination of two related lipid substances--leukotriene C4 (LTC) and leukotriene D4 (LTD); thus it is now possible to use pure SRSs (leukotrienes) in pharmacological studies of airway smooth muscle. LTC and LTD have been shown to contract guinea pig tracheal and lung parenchymal strips but there is no evidence that these substances produce similar effects on human lung tissue. To clarify this, in vivo pharmacological studies were done to determine the actions of LTC and LTD on smooth muscle strips of human bronchus, pulmonary vein and artery, and lung parenchymal tissue containing smooth muscle components and pleura. As indicated in a preliminary report, all four types of tissues contracted in a dose-dependent fashion to the leukotrienes, although these substances only function as partial agonists.

Actions of the novel bronchodilator, trimetaquinol, on bovine pulmonary vein.

The actions of the beta-sympathomimetic bronchodilator trimetaquinol (TMQ) were examined on bovine pulmonary vein smooth muscle in vitro. TMQ partially and reversibly inhibited 5-hydroxytryptamine (5HT) induced contractions of the vein strips. The relaxant activity was neither blocked by propranolol (10(-7) M) nor enhanced by phentolamine (10(-7) M). Isoproterenol, alone or in the presence of phentolamine (10(-7) M), was much less effective than TMQ in relaxing 5HT-induced contractions. From these results it is suggested that TMQ functions via a "non-beta-adrenergic" mechanism to relax bovine pulmonary vein smooth muscle.

Combination bronchodilators: antagonism of airway smooth muscle contractions in vitro.

The component drugs of fixed-dose combination bronchodilators may interact in a synergistic manner to antagonize airway contractions. To examine this hypothesis, combinations of ephedrine (E) and theophylline (Th) or salbutamol (S) and theophylline were tested for their ability to relax contracted guinea-pig airway smooth muscle in vitro. The combination bronchodilator effect was compared to the summed effects of the component drugs given individually (i.e. a theoretical additive response, Ta). Relaxation responses to combination bronchodilators were considered less-than-additive if significantly less than Ta, additive if non-significant and greater-than-additive or synergistic if the values were significantly greater than Ta. It was found that the E-Th combinations interacted primarily in an additive fashion to relax contractions induced by histamine, acetylcholine and 5-hydroxytryptamine at concentrations that produced one-half maximal contractile response (ED50). Similarly S-Th combinations interacted in an additive manner to reverse histamine and acetylcholine contractions. In the case of both E-Th and S-Th combinations, the drugs were more effective in reducing the smooth muscle contractions when given during rather than prior to the response. It may be concluded that beta-sympathomimetics and methylxanthines when combined do not interact in a synergistic fashion to produce relaxation of contracted airway smooth muscle.

The guinea pig tracheobronchial spiral strip: responses to selected agonists.

The guinea pig tracheal spiral strip is a useful preparation for studying bronchoconstrictor and bronchodilator compounds. Employing a simple and rapid modification of this technique, experiments were performed in vitro to quantitate the effects of selected bronchospastic agents on guinea pig tracheobronchial smooth muscle. Three sections of the main airways were prepared from each animal: an upper tracheal, a lower tracheal, and a bronchial segment. The dose-dependent contractile responses of the three tissue segments were determined for carbachol, acetylcholine, histamine, 5-hydroxytryptamine, and bradykinin. Differences were observed amongst the agonists in magnitudes of contraction, effective concentration ranges, and slopes of dose-response curves. ED25, ED50, and ED75 values were calculated from regression analysis of dose-response data. The relative order for these agents to produce maximum contractions was found to be carbachol congruent to acetylcholine greater than histamine greater than 5-hydroxytryptamine greater than bradykinin. Furthermore, it was found that there was no significant difference between the three tissue segments in their responses to the various agonists.

Pharmacological studies on the pulmonary vein of the horse. I. Effects of selected spasmogens.

Horses suffer from a respiratory condition, similar to human allergic asthma, that is characterized by severe dyspnea, wheezing, coughing, and mucus production. Mediator substances released during the allergic reaction may contract airways and pulmonary vasculature. Nothing is known of the effects of autacoids and other vasoactive substances on equine pulmonary vessels. Therefore, spiral strips of equine pulmonary vein were prepared in vitro and the effects of histamine (H), 5-hydroxytryptamine (5HT), bradykinin (BK), carbachol (Carb), and phenylephrine (phen) were studied. The order of contractile effectiveness for the agonists on the vein was found to be 5HT greater than H greater than Bk greater than Phen greater than Carb, although H consistently produced the greatest maximal effects. H1-receptors appeared to mediate H contractions while H2-receptors had no measurable effect. 5HT responses were mediated directly by 'D-type' smooth muscle receptors. Bk produced contractions but of a lesser magnitude than either H or 5HT. Varying degrees of tachyphylaxis were observed for each agent. alpha-Adrenergic receptor stimulation by Phen initiated low-magnitude contractions whereas Carb exhibited virtually no activity on the pulmonary vein. Contractile responses of pulmonary veins to various spasmogens may contribute to the equine asthmatic response by raising vascular hydrostatic pressure, thereby enhancing edema formation.