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Biomedical subjects

J A Mitchell

Publications and source records attributed to J A Mitchell.

268 records · Page 15Linked to original sources
PubMedDate not supplied

Vasodilatory effect of aerosol histamine during pulmonary vasoconstriction in unanesthetized sheep.

The effects of aerosol histamine on pulmonary vascular resistance during pulmonary vasoconstriction were studied in 12 unanesthetized sheep. Sheep were chronically instrumental with Silastic catheters in the pulmonary artery and left atrium, thermodilution Swan-Ganz catheter in the main pulmonary artery for measurement of cardiac output, and tracheostomy for delivery of hypoxic gas and/or aerosol histamine. Seven minutes of isocapnic hypoxia (FIO2 = 0.12) caused pulmonary artery pressure (PPA) to increase from 17.2 +/- 0.4 to 27.0 +/- 1.0 cm H2O (mean +/- SEM, P less than 0.05) and pulmonary vascular resistance (PVR) to increase from 3.94 +/- 0.33 to 4.71 +/- 0.38 cm H2O x L-1 x min (P less than 0.05). When sheep breathed a combination of aerosol histamine (5 mg/ml) and 12% O2, PPA rose only 21.3 +/- 1.11 cm H2O and PVR decreased to 3.51 +/- 0.31 cm H2O x L-1 x min. This was a significantly (P less than 0.05) smaller response compared to hypoxia alone. Aerosol histamine alone had to significant effect on PPA or PVR. Meclofenamate did not restore the histamine-induced loss of hypoxic vasoconstriction. Aerosol histamine significantly blunted the pulmonary vasoconstriction caused by intravenous serotonin (8 micrograms/kg/min) and intravenous prostaglandin H2-analog (0.74 microgram/kg/min). It was concluded that in the awake sheep aerosol histamine acted as a pulmonary vasodilator only in the presence of pulmonary vasoconstriction.

Aerosols↗
PubMedDate not supplied

Temporal correlations between plasma ovarian steroid hormone levels and intrauterine oxygen tension in the guinea pig.

In summary, while arterial and venous pO2 remain constant throughout the estrous cycle, dramatic fluctuations in intrauterine oxygen tension occur, reaching maximal levels on Days 0 and 6 when plasma estrogen levels are elevated. This correlation suggests that ovarian steroids regulate intrauterine pO2 via their actions upon a number of uterine and vascular parameters, the temporal relationships existing between the mid-luteal rise in plasma estrogen, intrauterine pO2 and implantation suggesting that the steroid induced increase in oxygen availability to the blastocyst may participate in the process of implantation in the guinea pig.

Animals↗
PubMedDate not supplied

Behavioral effects of pydrin and ambush in male mice.

Male Swiss mice, 20-25 g, were utilized to assess the effects of dermal and oral administration of the pyrethroid insecticide formulations Pydrin (30% fenvalerate) and Ambush (25.6% permethrin). Animals were subjected to a conditioned taste aversion procedure using a normally preferred 0.3% saccharin solution. Subjects were allowed 30 min access to a drinking syringe containing the saccharin solution, followed immediately by the administration of the pyrethroid or control solution. Pydrin (0.3, 3.0, or 30 mg/kg orally; 60, 600, or 1800 mg/kg dermally) and Ambush (0.5, 5.0, or 50 mg/kg orally; 30, or 300 mg/kg dermally) produced significant (p less than 0.05) reductions in the percent saccharin consumed. Total fluid intake, however, was not significantly altered by any of the treatments. The effect of the insecticides on both grouped and individual activity was also assessed in 20-25 g male Swiss mice. Activity measurements were taken over the 4-hr time period immediately following the administration of the pyrethroid or control solution. Pydrin (30 mg/kg orally; 600 and 1800 mg/kg dermally) and Ambush (50 mg/kg orally; 300 mg/kg dermally) significantly (p less than 0.05) increased activity in both grouped and individually tested mice. When subjects were individually tested, significant increases were seen in non-ambulatory, but not in ambulatory activity. The results of this work indicate that administration of the commercially available preparations of Pydrin and Ambush in mice at doses that do not induce the tremor and choreoathetosis-salivation syndromes usually associated with pyrethroid insecticides may result in behavioral changes.

Administration, Cutaneous↗
PubMedDate not supplied

The behavioral effects of pesticides in male mice.

Male Swiss mice, 25-30 g, were utilized to define some of the behavioral effects of the herbicides Lasso [alachlor 43%; (A)], Basalin [fluchloralin 45%; (F)], Premerge 3 [dinoseb 51%; (D)], and the fungicide Maneb-80 [maneb 80%; (M)]. These compounds were tested for their effects on locomotor activity and for their ability to establish a conditioned taste aversion following oral or dermal exposure. Individual and grouped (N = 5) activity measures were assessed immediately following the dermal administration of the commercially available pesticide formulations. Grouped activity measures were also assessed following the oral administration of the compounds. Total activity was significantly (p less than 0.05) increased over vehicle controls in both grouped and individual subjects by A, F, and D following dermal administration. Grouped activity measures were also increased by A, F, D, and M following the oral administration of the compounds. Similar subjects were tested in a conditioned taste aversion paradigm using a normally preferred 0.3% saccharin solution. Animals were given 30 min access to the saccharin solution followed immediately by the administration of the pesticide or control solution. Twenty-four hours later, animals were given the choice of 2 solutions, one containing water and the other the 0.3% saccharin solution. The percent saccharin consumed and the total fluid intake were calculated for each group (N = 8/group). A, F, and D produced a significant aversion to (N = 8/group) the saccharin following both oral and dermal administration. Oral administration of M, but not dermal exposure, also resulted in a flavor aversion. Total fluid intake, however, was not altered by any of the treatments.(ABSTRACT TRUNCATED AT 250 WORDS)

2,4-Dinitrophenol↗
PubMedDate not supplied

Virtual shelves in a digital library: a framework for access to networked information sources.

OBJECTIVE: Develop a framework for collections-based access to networked information sources that addresses the problem of location-dependent access to information sources. DESIGN: This framework uses a metaphor of a virtual shelf. A virtual shelf is a general-purpose server that is dedicated to a particular information subject class. The identifier of one of these servers identifies its subject class. Location-independent call numbers are assigned to information sources. Call numbers are based on standard vocabulary codes. The call numbers are first mapped to the location-independent identifiers of virtual shelves. When access to an information resource is required, a location directory provides a second mapping of these location-independent server identifiers to actual network locations. RESULTS: The framework has been implemented in two different systems. One system is based on the Open System Foundation/Distributed Computing Environment and the other is based on the World Wide Web. CONCLUSIONS: This framework applies in new ways traditional methods of library classification and cataloging. It is compatible with two traditional styles of selecting information searching and browsing. Traditional methods may be combined with new paradigms of information searching that will be able to take advantage of the special properties of digital information. Cooperation between the library-informational science community and the informatics community can provide a means for a continuing application of the knowledge and techniques of library science to the new problems of networked information sources.

Catalogs, Library↗
PubMedDate not supplied

An expert system for performance-based direct delivery of published clinical evidence.

OBJECTIVE: To develop a system for clinical performance improvement through rule-based analysis of medical practice patterns and individualized distribution of published scientific evidence. METHODS: The Quality Feedback Expert System (QFES) was developed by applying a Level-5 expert system shell to generate clinical direct reports for performance improvement. The system comprises three data and knowledge bases: 1) a knowledge base of measurable clinical practice parameters; 2) a practice pattern database of provider-specific numbers of patients and clinical activities; and 3) a management rule base comprising "redline rules" that identify providers whose practice styles vary significantly. Clinical direct reports consist of a table of practice data highlighting individual utilization vs recommendation and selected pertinent statements from medical literature. RESULTS: The QFES supports integration of recommendations from several guidelines into a comprehensive and measurable quality improvement plan, analysis of actual practice patterns and comparison with accepted recommendations, and generation of a confidential individualized direct report to those who significantly deviate from clinical recommendations. The feasibility of the practice pattern analysis by the QFES was demonstrated in a sample of 182 urinary tract infection cases from a primary care clinic. In a set of clinical activities, four questions/procedures were associated with significant (p < 0.001) and unexplained variation. CONCLUSION: The QFES provides a flexible tool for the implementation of clinical practice guidelines in diverse and changing clinical areas without the need for special program development. Preliminary studies indicate utility in the analysis of clinical practice variation and deviations. Using data obtained through a retrospective chart audit, the QFES was able to detect overutilization, and to identify nonrandom differences in practice patterns.

Databases, Factual↗
PubMedDate not supplied

Immunotoxic side-effects of drug therapy.

Adverse reactions to drugs in which an immune mechanism is responsible for toxicity have been described as idiosyncratic. Understanding these toxic effects is important to enable the identification of patients at risk. The specific toxic side effects considered are heparin-induced thrombocytopenia, penicillin-induced haemolytic anaemia, hepatitis as a result of halothane and tienilic acid therapy, quinine- and quinidine-dependent thrombocytopenia, methyldopa-induced haemolytic anaemia and immune-complex disease following administration of hydralazine, procainamide and penicillamine. The molecular mechanisms of immunotoxicity are presented where such information is available although more than one effect may contribute to the observed pattern of toxicity. The initial events leading to antibody production in certain individuals in response to drug therapy are not understood and, in many of the examples described, antibody production occurs in some patients who do not subsequently experience clinical problems. Clinically serious adverse effects involving immune reactions are infrequent, and a range of genetic and environmental circumstances need to be present simultaneously in an individual before toxicity develops. The ability to metabolise a particular drug has been shown to be one major predisposing factor in toxicity; the immunocompetence of the patient is likely to be another. Both of these considerations are subject to genetic and environmental controls, including infection and disease.

Drug-Related Side Effects and Adverse Reactions↗
PubMedDate not supplied

An investigation of an autonomic innervation of the vertebral artery using monoamine histofluorescence.

Blood flow to the hindbrain, via the paired vertebral arteries, must be uncompromised for adequate neurological functioning of its vital centres. Therefore, it would seem unlikely that the intracranial vertebral artery would need to vasoconstrict, thus reducing its blood flow. In order to investigate the existence and location of a noradrenaline-mediated constrictor mechanism in the wall of the intracranial vertebral artery, transverse sections of ten baboon and ten monkey vessels were stained with sucrose-potassium phosphate-glyoxylic acid (counterstained with malachite-green). This method allows the visualisation of catecholaminergic nerves when the sections are exposed to ultraviolet light. In this study of primate vascular tissue, however, none of the monkey or baboon vertebral artery sections showed the presence of noradrenergic nerves in the tunica media - tunica adventitia junction or penetrating the tunica media of the arteries. These findings indicate that the intracranial vertebral artery does not have a neurogenic vasomotor function in primates.

Adrenal Medulla↗
PubMedDate not supplied

An investigation of a sympathetic innervation of the vertebral artery in primates: is there a neurogenic substrate for vasoconstriction?

Vasoconstriction of the vertebral artery may be neurogenic in origin. Although the existence of a perivascular sympathetic plexus of the vertebral artery is not in doubt, no method used to date has conclusively demonstrated a direct sympathetic innervation of the vascular smooth muscle cells and, hence, vasomotor function. It was the aim of this study, therefore, to visualise and localise noradrenergic fibres in the wall of the vertebral artery. Intracranial vertebral artery specimens (10 vervet monkeys and 10 baboon vessels) were sectioned (40 mm serial sections) and treated with anti-tyrosine hydroxylase, anti-dopamine b-hydroxylase, and anti-chromogranin-A antibodies. Some evidence of catecholaminergic fibres in the tunica adventitia but not penetrating the external elastic lamina or tunica media of the vertebral artery wall was seen. These findings were confirmed by electron microscopy. It was concluded that although a perivascular sympathetic plexus exists, the vertebral artery of primates was not shown to have a direct sympathetic innervation and a neurogenic vasoconstrictor function is unlikely.

Adrenergic Fibers↗
PubMedDate not supplied

Relationship between different isoforms of nitric oxide synthase and cyclooxygenase in various cell types.

Nitric oxide (NO) and prostacyclin (PGI2), formed by NO synthase (NOS) and cyclooxygenase (COX), respectively, are two potent anti-aggregatory vasodilators released from endothelial cells. Both NOS and COX exist as constitutive and inducible isoforms. We have shown that NOS and COX are co-induced in vitro and in vivo by bacterial endotoxin and that low amounts of NO increase whereas high amounts inhibit the activity and expression of inducible COX in vitro.

6-Ketoprostaglandin F1 alpha↗
PubMedDate not supplied

Nitric oxide as a neurotransmitter in human airways.

Human airway smooth muscle possesses a prominent nonadrenergic noncholinergic (i-NANC) bronchodilator response. Nitric oxide (NO) appears to account for all the i-NANC response in human central and peripheral airways in vitro. Furthermore, it appears that i-NANC relaxations in human trachea are associated with a concomitant selective elevation of cGMP, but not cAMP levels, which are inhibited by an NO synthase (NOS) inhibitor. This confirms the hypothesis that the L-arginine/NO/cGMP pathway is responsible for mediating the i-NANC response in this tissue. It is not certain from where the NO is formed or the location of the NOS enzyme. However, in human trachea, NOS immunoreactivity (NOS-IR) has been described in nerve fibres originating from intrinsic neurons. In addition, the density of NOS-IR is reduced from proximal to distal airways and this correlates with functional data describing a reduced i-NANC relaxation response from central to peripheral airways. The i-NANC bronchodilator nerves are the only neural relaxant pathway in human airways and, therefore, it is important to determine whether there is any defect in the ability of these nerves to function in diseased airways. In fact, functional and immunohistochemical data suggest that there may be a deficiency in NOS-IR nerves leading to a decreased i-NANC response in tissue from patients with cystic fibrosis. NOS inhibitors appear to enhance the cholinergic bronchoconstriction in human airways in vitro. Therefore, if the nitrergic innervation is dysfunctional in inflammatory conditions, its absence may lead to exaggerated bronchoconstriction.

Arginine↗
PubMedDate not supplied

Basic principles of information technology organization in health care institutions.

This paper focuses on the basic principles of information technology (IT) organization within health sciences centers. The paper considers the placement of the leader of the IT effort within the health sciences administrative structure and the organization of the IT unit. A case study of the University of Missouri-Columbia Health Sciences Center demonstrates how a role-based organizational model for IT support can be effective for determining the boundary between centralized and decentralized organizations. The conclusions are that the IT leader needs to be positioned with other institutional leaders who are making strategic decisions, and that the internal IT structure needs to be a role-based hybrid of centralized and decentralized units. The IT leader needs to understand the mission of the organization and actively use change-management techniques.

Health Facility Administration↗