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Biomedical subjects

C Mason

Publications and source records attributed to C Mason.

At least 91 records · Page 5Linked to original sources

Ethanol suppresses Mycobacteria tuberculosis-induced mRNA for nitric oxide synthase in alveolar macrophages, in vivo.

Acute ingestion of alcohol [ethanol (ETOH)] adversely affects the immunocompetence of both naive individuals as well as chronic alcohol abusers. An increased incidence and severity of tuberculosis is found in chronic alcohol abusers. Nitric oxide (NO) produced by alveolar macrophages (AMs) may play a role in the in vitro killing of Mycobacterium avium and Mycobacterium tuberculosis (MTB). Moreover, tumor necrosis factor-alpha (TNF-alpha) is believed to be a primary cytokine mediator of NO production by AMs. Recent studies from our laboratory demonstrated that ETOH suppressed endotoxin-induced increases in both TNF-alpha and NO in AMs, in vivo. We tested the postulate that acute ingestion of ETOH can interfere with mycobacteria-induced upregulation of the NO system in AMs, in vivo. We show that heat-killed M. avium complex (MAC) and human virulent MTB instilled into rat lungs rapidly increased mRNA for inducible NO synthase II (iNOS) of AMs in fluid obtained by bronchoalveolar lavage (BAL fluid). This was associated with production of reactive nitrogen intermediates [(RNIs); NO2- and NO3-] in BAL fluid, lung homogenate, and AMs in the absence of a significant increase in BAL fluid TNF-alpha. A single dose of ETOH (5.5 g/kg, ip) administered 30 min before intratracheal administration of MAC or MTB attenuated both MAC and MTB-induced increases in RNI in BAL fluid, lung, and AMs, and the increase in mRNA for iNOS. Thus, mycobacteria upregulate iNOS mRNA and enhance RNI production by AMs without any increase in the production of TNF-alpha. Moreover, ETOH attenuates mycobacteria-induced upregulation of mRNA for iNOS and RNI production in the absence of ETOH-mediated suppression of TNF. Speculatively, ETOH-mediated inhibition of the AM NO system may offer an explanation for the increased severity of mycobacterial infections in alcoholics.

Alcoholic Intoxication↗

In vitro activity of D0870 compared with those of other azoles against fluconazole-resistant Candida spp.

We compared the in vitro activity of a new triazole, D0870, with those of fluconazole, itraconazole, and ketoconazole against 41 clinical isolates of fluconazole-resistant Candida belonging to nine different species. The 50% inhibitory concentrations (IC50s) were determined by a microdilution method with morpholinopropanesulfonic acid (MOPS)-buffered RPMI medium and an inoculum of approximately 10(4) yeasts per ml. After incubation for 48 h at 37 degrees C the optical density at 550 nm was measured. The IC50 was the lowest drug concentration which reduced the optical density at 550 nm by > or = 50% compared with that for a drug-free control. D0870 had significant activity against many of the isolates. Its activity was comparable to that of ketoconazole, slightly superior to that of itraconazole, and markedly superior to that of fluconazole against Candida albicans. Against Candida glabrata, Candida krusei, and Candida inconspicua, it had activity similar to those of itraconazole and ketoconazole but had activity superior to that of fluconazole. D0870 IC50s for some isolates were increased. This may be due to cross-resistance mechanisms because the IC50s of both itraconazole and ketoconazole for these isolates were often high. When IC50s and IC80s were compared there was a marked organism and drug variation. With C. glabrata much higher endpoints for itraconazole were observed when an IC80 endpoint was used. For C. albicans there was also a significant shift upward in endpoints for itraconazole and ketoconazole. Values were changed little when IC50 and IC80 endpoints of D0870 were compared. For 35 of 41 isolates tested the D0870 IC50 was less than the 2.5-mg/liter breakpoint threshold proposed previously. Therefore, D0870 may be a useful agent for the therapy of infections caused by fluconazole-resistant Candida spp.

Antifungal Agents↗

Rapid induction of mRNA for nitric oxide synthase II in rat alveolar macrophages by intratracheal administration of Mycobacterium tuberculosis and Mycobacterium avium.

Mycobacterium avium complex (MAC) organisms are among the most common bacterial cause of disseminated infection in patients with acquired immune deficiency syndrome (AIDS). An increase in the incidence of virulent Mycobacterium tuberculosis (MTB) is also occurring throughout the world. In vitro data suggest that nitric oxide (NO) may be important in restricting the growth of MAC. However, the ability of MTB to stimulate NO production and the susceptibility of MTB to the bactericidal activity of NO produced by murine alveolar macrophages (AM) is controversial. This study tested the hypothesis that in vivo administration of heat-killed MAC (strain 100 and 101) and human virulent MTB (strain F1) to rats stimulated NO production by rat AM, ex vivo. We show that heat-killed MTB instilled into rat lungs rapidly induced mRNA for NO synthase (iNOS) II in AM obtained by bronchoalveolar lavage (BAL). In contrast, expression of AM iNOS mRNA was only found in 40% of the rats given MAC. Moreover, the change in iNOS mRNA in the AM obtained from rats given MTB and MAC correlated with the production of the reactive nitrogen intermediates (RNI) NO2- and NO3- in BAL fluid, lung homogenate, and the spontaneous generation of RNI by isolated AM ex vivo and occurred without measurable increases in BAL fluid tumor necrosis factor-alpha (TNF-alpha). L-NG-monomethylarginine (50 mg/kg, ip) given 30 min before MAC or MTB attenuated the increase in RNI in lung homogenates and BAL fluid. This is the first demonstration that in vivo exposure to MTB results in rapid upregulation of gene expression for iNOS which is associated with functional RNI production by rat AM. These results show that MTB human virulent strain 1 has the ability to rapidly upregulate iNOS mRNA in AM. If human AM generate NO from L-arginine by either iNOS or other NADPH oxidases then NO may play a role in the overall host-defense response of the lung to MAC and MTB.

Amino Acid Oxidoreductases↗

Enroute toward a computer based patient record: the ACIS project.

The clinical arm of the University of Utah operates a 400 bed general hospital and 30 specialty and subspecialty clinics and with the advent of managed care will soon be linked to a much wider network of health care facilities throughout the state. Each of these patient care facilities maintains its own patient record. To provide common access to data on any patient needed to provide continuity to the care process where ever it occurs, the institution has embarked on the development of a completely electronic patient record. In this paper we will describe the route we have taken to achieve this goal in hopes of providing some sign posts along the way for others seeking the same destination.

Computer Communication Networks↗

Cimetidine does not impair pulmonary clearance of Pseudomonas aeruginosa in normal rats.

Histamine (H2)-receptor blockers are commonly used in critically ill patients to prevent gastric bleeding and have been implicated in the pathogenesis of gram-negative bacterial (GNB) nosocomial pneumonia. These experiments were undertaken to determine if cimetidine affects pulmonary GNB clearance. Groups of normal Sprague-Dawley rats were given cimetidine (75 mg/kg) or an equal volume of sterile buffer intraperitoneally every 6 hr for 24 hr prior to intratracheal challenge with 1.0 x 10(8) Pseudomonas aeruginosa. At 6 and 24 hr after challenge, animals were sacrificed and gastric pH, quantitative lung cultures, and total and differential [alveolar macrophages (AM) and polymorphonuclear leukocytes (PMN)] cell counts in bronchoalveolar lavage fluid were performed. Results showed that cimetidine therapy resulting in gastric pH greater than 4.0 has no effect on the pulmonary clearance of P. aeruginosa.

Animals↗

An evaluation of the adequacy of health visitor education for neonatal hip screening.

Congenital dislocation of the hip (CDH) affects two children per 1000, with potentially serious consequences. Student health visitors in Northern Ireland learn screening techniques for CDH at a half-day workshop at a regional hospital. In order to evaluate the adequacy of this preparation, 71 qualified health visitors were surveyed to assess their knowledge relating to CDH, their views on the adequacy of the training, and their opinions about referral of positive cases. Knowledge in some areas was poor and preparation was considered too short. Direct referrals of positive cases to orthopaedic clinics, without a general practitioner acting as an intermediary, was a frequently cited desire. Recommendations include extending the training for those involved in CDH screening while ensuring that experienced health visitors, from whom novices learn, are themselves using correct procedures.

Attitude of Health Personnel↗

The use of CO2 laser in the treatment of gingival fibromatosis: a case report.

A case is described of gingival fibromatosis in a 10-year-old boy, in which gingival tissue was removed using a CO2 laser. The advantages of this method over conventional surgery were minimal bleeding and pain, allowing treatment of all quadrants in one visit. The disadvantages were the potential risks to the teeth and to the endotracheal tube. In this case laser treatment achieved a good result with minimal post-operative discomfort, which is an important consideration for children.

Carbon Dioxide↗

Dental complications associated with repeated orotracheal intubation in infancy: a case report.

Various oral and dental problems have been attributed to orotracheal intubation in the neonatal period. A case is described of a child whose dental anomalies are ascribed to multiple orotracheal intubations for the management of a complex cardiac abnormality. Six intubations were required between the ages of 9 days and 4 years for investigation and surgery. His maxillary right primary central incisor did not erupt until 3 years of age and the maxillary left was still unerupted at 6 years and 10 months and was rotated in its crypt. At this time, the mandibular primary incisors were physiologically mobile but the maxillary right primary central incisor remained firm. Both maxillary primary central incisors were extracted and examined histologically and showed abnormal morphology, enamel hypoplasia, and disordered dentine formation and root resorption. Subsequent eruption of the left permanent central incisor revealed hypoplasia of its incisal edge. It is suggested that the delayed eruption and abnormal morphology of the primary incisors were due to pressure effects on the overlying mucosa, follicular displacement and localized trauma caused by intubation. This case highlights the importance of monitoring the developing dentition of patients with a history of orotracheal intubation, so that interceptive treatment may be instituted when appropriate.

Dental Enamel Hypoplasia↗

Trigeminal neurapraxia following a blow to the face: a case report.

Examination of the cranial nerves is a simple and valuable procedure following trauma to the head and neck. By understanding their courses, branches and distributions, the site of any damage may be localized. Once the site and nature of injury has been determined, correct management may be instigated. A case is presented in which there was some degree of trigeminal nerve damage following trauma. The site of damage was determined to be extracranial and therefore a conservative regimen adopted. The mechanism of injury is postulated.

Child↗

A cardiovascular health education program for rural schools.

Public understanding of cardiovascular disease (CVD) risk factors and primary prevention has increased, due in part to community prevention efforts. However, many segments of society are difficult to reach. Such groups still need public education to acquire the knowledge that can lead to behavior change. Community intervention programs in rural areas face the challenge of disseminating health information to widely scattered populations isolated by difficult terrain and weather, and restricted by the sparsity of channels for mass communication. School health promotion programs, because of the special role schools play in rural communities, can help reach rural populations. During a five-year period, the Otsego-Schoharie Healthy Heart Program, a state-funded community intervention program, provided presentations to 18% of the combined total population of two rural counties through its school-based component. It also helped promote other program initiatives by establishing linkages in the community. Schools provide an effective channel for health promotion efforts to reach rural populations.

Adolescent↗

Naturally acquired CD8+ cytotoxic T lymphocytes against the Plasmodium falciparum circumsporozoite protein.

In rodent malaria model systems, protective immunity induced by immunization with irradiated sporozoites is eliminated by in vivo depletion of CD8+ T cells, and adoptive transfer of CTL clones against the circumsporozoite protein protects against malaria. We recently demonstrated that volunteers immunized with irradiated Plasmodium falciparum sporozoites produce CTL against peptide 368-390 of the P. falciparum circumsporozoite protein. To determine whether natural exposure to malaria induced similar CTL, we studied 11 adult, male, life-long residents of a highly malarious area of Kenya, who were selected because their lymphocytes had been shown to proliferate after stimulation with peptides 361-380, 371-390, or 368-390 and because nine had been resistant to malaria in previous studies. In four of the 11 individuals there was peptide-specific, genetically restricted, CTL activity. In all four individuals, this activity was unaffected by depletion of CD4+ T cells. In three volunteers the activity was eliminated or reduced by depletion of CD8+ T cells; in the fourth volunteer the CD8+ T cell depletion was uninterpretable. This first demonstration of CD8+ T cell, genetically restricted, Ag-specific CTL against a malaria protein among individuals exposed to endemic malaria provides a foundation for studying the relationship between circulating CTL and resistance to malaria infection.

Amino Acid Sequence↗

Non-attendance at out-patient clinics: a case study.

Non-attendance at out-patient clinics is a persistent, worldwide problem. In contrast with previous research, a qualitative approach was used in this study to examine reasons for non-attendance at out-patient clinics in one Belfast hospital, by exploring perspectives of general practitioners (GPs), hospital staff and defaulters. Findings revealed conflicts of opinion between GPs and hospital staff on appropriate management of certain medical and postnatal patients. Patients' reasons for defaulting were wide-ranging; however, 32% of those interviewed did not attend, or were recorded as non-attenders, for reasons relating to inefficient hospital administration. It is concluded that the causes of non-attendance were multifactorial, and non-attenders could not be stereotyped as irresponsible. Suggested measures to alleviate the problem include discussion between groups of professionals on responsibility for care of medical and postnatal patients, increased negotiation between patients and physicians in order to develop agreed programmes of care, and, where possible, a shifting of the onus of responsibility for making and cancelling appointments onto patients.

Conflict, Psychological↗

Carbon monoxide exposure in blast furnace workers.

This study investigated the occupational exposure to carbon monoxide (CO) of a group of blast furnace workers from an integrated steelworks, compared to a control group having no significant occupational CO exposure from other areas in the same works. The study was undertaken in 1984 at Port Kembla, New South Wales. Carboxyhaemoglobin (COHb) levels before and after an eight-hour work shift were measured in 98 male steelworkers: 52 from two CO-exposed iron blast furnaces and 46 controls from production areas in the same steelworks. The sample was stratified by smoking habits. Environmental air CO levels had been found to be consistently higher on one furnace than on the other. Absorption of CO from the working environment occurred in workers on the blast furnace with higher CO levels, regardless of smoking habits. On this blast furnace, some readings of COHb levels after a workshift in nonsmokers approached the proposed Australian occupational limit of 5 per cent COHb saturation. Overall, workers with the highest occupational exposure who smoked most heavily had the highest absorption of CO over a work shift. Biological monitoring gives an accurate measure of individual worker 'dose' of CO from all sources. Both environmental monitoring and biological monitoring need to be included as part of a program for controlling occupational CO exposure.

Breath Tests↗

Triazolobenzo- and triazolothienodiazepines as potent antagonists of platelet activating factor.

A series of [1,2,4]triazolo[4,3-alpha][1,4]benzodiazepines bearing an ethynyl functionality at the 8-position and the isosteric thieno[3,2-f][1,2,4]triazolo[4,3-alpha][1,4]diazepines were prepared and evaluated as antagonists of platelet activating factor. The effects of substitution were explored in in vitro and in vivo test systems designed to measured PAF-antagonistic activity. Results are discussed and compared with previously published data. Many of the compounds had activity superior to WEB 2086, compound 1. In general, the thieno analogues exhibited better oral activity than the corresponding benzodiazepines. The duration of activity upon oral administration was modulated by the substitution on the acetylenic side chain. Compounds 71 and 81 were selected for further pharmacological evaluation as a result of their good oral potency and exceptionally long duration of action.

Animals↗

Thienotriazolodiazepines as platelet-activating factor antagonists. Steric limitations for the substituent in position 2.

The preparations of thienotriazolodiazepines bearing a substituted ethynyl group at the 2-position, and the corresponding cis-olefins and fully saturated analogues are described. The compounds were evaluated as potential antagonists of platelet-activating factor (PAF) in in vitro and in vitro test models. The new thienotriazolodiazepines are compared with known related compounds such as WEB 2086 (compound 6) and the phenylethyl derivatives 27 and 28.

Animals↗