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Biomedical subjects

M Foster

Publications and source records attributed to M Foster.

At least 37 records · Page 2Linked to original sources

Anti-inflammatory properties of ebselen in a model of sephadex-induced lung inflammation.

Ebselen (2-phenyl-1,2-benzisoselenazol-3(2H)-one), is a seleno-organic compound which protects tissues against oxidative stress. Furthermore, recent data has suggested that this compound possesses a range of anti-inflammatory properties. In this study the authors have investigated the effects of ebselen on Sephadex-induced lung oedema and bronchoalveolar lavage (BAL) tumour necrosis factor (TNF)-alpha and endothelin(ET)-1 levels in rats. Sephadex administration induced lung oedema which was accompanied by an increase in BAL TNF-alpha and ET-1 levels. Ebselen administration (1-30 mg x kg(-1), i.p. at 0, 4 and 12 h post Sephadex) significantly inhibited lung oedema (dose that produced 50% of the maximum inhibition of lung oedema 4.6 mg x kg(-1)) and BAL TNF-alpha levels in a dose-related manner with no effect on ET-1 levels. These data suggest that ebselen may be a useful therapy in lung pathologies in which bronchiolar inflammation is a feature.

Animals↗

Laparoscopic repair of chronic intrathoracic gastric volvulus.

BACKGROUND: Totally intrathoracic gastric volvulus is an uncommon presentation of hiatal hernia, in which the stomach undergoes organoaxial torsion predisposing the herniated stomach to strangulation and necrosis. This may occur as a surgical emergency, but some patients present with only chronic, non-specific symptoms and can be treated electively. The aim of this study is to describe a comprehensive approach to laparoscopic repair of chronic intrathoracic gastric volvulus and to critically assess the pre-operative work-up. METHODS: Eight patients (median age, 71 years) underwent complete laparoscopic repair of chronic intrathoracic gastric volvulus. Symptoms of epigastric pain and early satiety were universally present. Five patients had reflux symptoms. The diagnostic evaluation included a video esophagogram, upper endoscopy, 24-hour pH measurement, and esophageal manometry in all patients. Operative results and postoperative outcome were recorded and follow-up at 1 year included a barium swallow in all patients. RESULTS: All patients had documented intrathoracic stomach. Five of 8 patients had a structurally normal lower esophageal sphincter. All 4 patients with reflux esophagitis on upper endoscopy had a positive 24-hour pH study, and 2 of these patients had a structurally defective lower esophageal sphincter on manometry. None of the patients had preoperative evidence of esophageal shortening. All procedures were completed laparoscopically. The procedure included reduction of the stomach into the abdomen, primary closure of the diaphragmatic defect, and the construction of a short, floppy Nissen fundoplication. There were no major complications. One patient required repair of a trocar site hernia 6 months postoperatively. At 1-year follow-up, there were no radiologic recurrences of the volvulus. One patient complained of temporary swallowing discomfort and another had recurrent gastroesophageal reflux disease (GERD) symptoms caused by a breakdown of the wrap. All other patients remained asymptomatic during follow-up. CONCLUSIONS: The repair of chronic gastric volvulus can be accomplished successfully with a laparoscopic approach. A preoperative endoscopy and esophagogram are crucial to detect esophageal stricture or shortening, and manometry is needed to access esophageal motility; pH measurements do not affect operative strategy. The procedure should include a Nissen fundoplication to treat preoperative GERD, to prevent possible postoperative GERD, and to secure the stomach in the abdomen. The procedure is safe but technically challenging, requiring previous laparoscopic foregut surgical expertise.

Aged↗

Referral to post-acute care following traumatic brain injury (TBI) in the Australian context.

The study aimed to describe the types of care allocated at the end of acute care to people diagnosed with TBI and to identify the factors associated with variations in referral to care. A retrospective analysis of medical records of 61 patients was conducted based on a sample from two hospitals. While 60.7% of the study sample were referred to formal rehabilitation care, this was primarily non-inpatient rehabilitation care (32.8%). Discriminant analysis was used to determine medical and non-medical predictors of referral. Results indicated that place of treatment and age contribute to group differences and were significant in separating the inpatient rehabilitation group from the non-inpatient and no rehabilitation groups. Review by a rehabilitation physician was associated with referral to inpatient rehabilitation but was not adequate to explain referral to non-inpatient rehabilitation. An in-depth exploration of post-acute referral is warranted to improve policy and practice in relation to continuity of care following TBI.

Adolescent↗

Inhibition of interferon, cytokine, and lymphocyte proliferative responses in elite swimmers with altitude exposure.

To determine the immunologic consequences of athletic training at altitude, blood samples were taken at rest from 10 swimmers and 8 control nontraining but altitude-exposed members of the 1996 Australian Olympic Swimming Team, near the start and completion of a 21-day training camp at 2102 m. Blood leukocyte numbers dropped in both groups (p < 0.05), with the decrease greater in the swimmers (-38% swimmers, -3% controls). Concanavalin A (ConA)-induced blastogenesis decreased in both groups (p < 0.01), but the drop was greater in the control group (-32% swimmers, -56% controls, p < 0.05). Lipopolysaccharide (LPS)-induced blastogenesis more than doubled in both groups (281% swimmers, 249% controls, p < 0.01). Increases in mitogen-induced interleukin-1beta (IL-1beta), IL-4, and interferon-gamma (IFN-gamma) production and a decrease in IL-2 levels were observed in both groups after altitude exposure (all p < 0.05). The percentage of cells expressing HLA-DR fell (-33% swimmers, -20% controls, p < 0.01), whereas those expressing CD-4 expression increased (16% swimmers only, p < 0.01). Although training at medium-level altitude alters some immunologic parameters, the training-induced changes may be secondary to those induced by altitude alone.

Adaptation, Physiological↗

Effects of 2-deoxy-D-glucose administration on cytokine production in BDF1 mice.

Physical exercise and diet changes have been shown to affect immune parameters, and similar effects are also induced by the administration of a nonmetabolizable glucose analog, 2-deoxy-D-glucose (2-DG). The present study was designed to characterize the effects of glucoprivation induced by 2-DG administration on concentrations of tumor necrosis factor-alpha (TNF-alpha), interleukin-1beta (IL-1beta), and IL-6 in the blood and interferon-gamma (IFN-gamma), IL-2, and IL-4 in vitro production by partially purified T splenocytes in BDF1 mice. Mice (n = 8 per group) were injected intraperitoneally one or three times with 0, 500, 750, or 1000 mg/kg of 2-DG, and blood and spleens were collected 2 h after the last injection. Partially purified T splenocytes were cultured 24 h in the presence of concanavalin A (ConA). A significant increase in the corticosterone levels with the amount of 2-DG injected was observed after one or three injections (p<0.05). The amount of 2-DG injected was associated with an increase in TNF-alpha, IL-1beta, and IL-6 concentrations in the blood of mice after one or three injections of 2-DG (p<0.05). A significant decrease in in vitro proliferation of partially purified splenocytes in the presence of ConA was associated with a decrease in IFN-gamma production in the culture supernatants and an increase in IL-1 receptor expression on the cell surface (p<0.05).

Animals↗

Comparative prevalence of infection with Trichomonas vaginalis among men attending a sexually transmitted diseases clinic.

OBJECTIVE: Although established in women as a common cause of vaginal discharge, the prevalence of Trichomonas vaginalis (TV) in men compared with other classic urethral pathogens has not been well characterized. To assess this issue, the authors compared the prevalence of Neisseria gonorrhoeae (GC), Chlamydia trachomatis (CT), and TV in consecutive men attending a sexually transmitted diseases (STD) clinic. METHODS: From June 1, 1998 to July 27, 1998, 454 consecutive men presenting to the Denver Metro Health Clinic with a new problem were tested for GC by urethral swab culture, for CT by polymerase chain reaction of urine, and for TV by urine sediment culture. RESULTS: GC, CT, and TV were detected in 23 (5.1%), 34 (7.5%), and 13 (2.8%) of men, respectively. There were significant differences by age for both CT (11.3% in men younger than 30 years versus 3.3% in men 30 years and older, P < 0.05) and TV (0.8% in men younger than 30 years versus 5.1% in men 30 years and older, P < 0.05). In 50 men 30 years or older with symptoms of urethral discharge, TV prevalence (12.0%) rivalled that of GC (12.0%) and CT (14.0%). In 45 men 30 years and older with nongonococcal urethritis, the prevalence of TV and CT were each 13.3%. Multivariate logistical regression analysis showed the presence of discharge and nongonococcal urethritis in men 30 years and older to be an independent predictor of TV. CONCLUSIONS: TV is common in men attending sexually transmitted disease clinics, especially in those 30 years or older, in whom it may account for as much urethritis as GC or CT. These findings suggest that in older men with nongonococcal urethritis, diagnostic evaluation, empiric treatment, and partner management should include the possibility of TV infection.

Adult↗

Effect of the p38 kinase inhibitor, SB 203580, on sephadex induced airway inflammation in the rat.

SB 203580 is a pyridinyl imidazole compound which inhibits the release of pro-inflammatory cytokines, such as tumour necrosis factor-alpha (TNF-alpha) and interleukin-1beta (IL-1beta), in vitro and in vivo by inhibiting p38 mitogen-activated protein kinase (MAPK). The present study investigated the effects of SB 203580 in a model of airway inflammation induced by the topical administration of Sephadex into the rat airways. This inflammatory response is characterized by the development of lung oedema, airway tissue inflammatory cell recruitment and an increase in lung TNF-alpha and IL-1beta levels. Sephadex-induced lung oedema was accompanied by a significant increase in lung tissue TNF-alpha but not IL-1beta levels. There was also a significant increase in lung tissue macrophages and an increase in eosinophils which did not reach significance. SB 203580 administration significantly inhibited lung oedema (ED50=18 mg x kg(-1)) in a dose-related manner but was without significant effect on lung tissue cell recruitment or cytokine levels. These data suggest that the increase in tumour necrosis factor-alpha and lung oedema are separate processes which both contribute to Sephadex pathology. Furthermore, the inhibitory effect of SB 203580 on Sephadex-induced lung oedema suggests that p38 kinase inhibitors may be of use in pulmonary pathologies in which lung oedema is a feature.

Animals↗

Angiogenic and immune parameters during recombinant interferon-alpha2b adjuvant treatment in patients with melanoma.

As an adjuvant therapy for patients with high risk of recurrent melanoma, high-dose interferon (IFN)-alpha2b therapy has been shown to have some efficacy. We examined 22 patients with resected melanoma who were treated with repeated injections of recombinant IFN-alpha2b during the treatment. Both angiogenic and immune parameters were measured. White blood cells (WBCs) and lymphocyte numbers, lymphocyte subpopulations, serum concentrations of IFN-alpha and anti-IFN-alpha antibodies, and the serum vascular endothelial growth factor (VEGF), interleukin (IL)-8, and basis fibroblast growth factor (bFGF) concentrations were determined over time in resected, recurrence-free patients with American Joint Committee on Cancer (AJCC) stage III melanoma with one or less (LN+ < or = 1, n = 7) or more than one (LN+ > 1, n = 8) lymph nodes involved, and AJCC stage IV resected disease (n = 7). Follow-up and recurrence-free intervals were longer in stage III (LN+ < or = 1) patients compared with stage IV patients (P < 0.05). The number of WBCs and lymphocytes decreased during the treatment for all patient groups (P < 0.001). In addition, percentages of CD8 and CD20 were higher in stage IV patients than in stage III (LN+ > 1) and stage III (LN+ < or = 1) patients at the beginning of therapy (P < 0.05). A significant increase in the percentage of CD20+ cells, mostly B lymphocytes, was observed in the stage III (LN+ > 1) and stage III (LN+ < or = 1) patients over time but not in stage IV patients (P < 0.001). Low IL-8 and bFGF concentrations at the beginning of therapy were associated with significantly longer recurrence-free survival (P < 0.05). These results warrant a larger trial to determine if the differences observed in patients before treatment can provide prognostic markers in patients receiving IFN-alpha2b therapy.

Adjuvants, Immunologic↗

Recurrent acute life-threatening events and lactic acidosis caused by chronic carbon monoxide poisoning in an infant.

Acute severe carbon monoxide poisoning is usually easy to recognize and diagnose. However, chronic or less severe exposure may produce more subtle symptoms. We report on a 31/2-year-old girl who was admitted to the hospital several times with acute, life-threatening events, acidosis, and flu-like symptoms. The diagnosis was elusive, but after careful questioning of family members and a home visit, chronic carbon monoxide poisoning was diagnosed.

Acidosis, Lactic↗

Regulation of B and T cell development by anterior pituitary hormones.

Hormones produced by the anterior pituitary gland have been implicated in the regulation of primary lymphocyte development. In order to identify endocrine factors involved in that process, several strains of mice with genetic defects resulting in a selective impairment in the production of one or more anterior pituitary-derived hormones have been analysed. This study has resulted in the classification of endocrine hormones into the following four categories: (i) hormones such as prolactin with no apparent effects on primary lymphopoiesis; (ii) anabolic hormones such as growth hormone and insulin-like growth factor-I whose stimulatory effects on primary lymphopoiesis are non-lineage-specific and related to their actions as systemic mediators of growth and/or differentiation; (iii) hormones such as thyroid hormones that have an obligate role in primary B lymphopoiesis; and (iv) hormones such as oestrogens that act as negative regulators of lymphopoiesis.

Animals↗

Effects of 2-deoxy-D-glucose administration on immune parameters in mice.

Physical exercise and diet alterations have been shown to affect immune parameters. Similar effects are also induced by the administration of the non-metabolizable glucose analog, 2-deoxy-D-glucose (2-DG). The current study was designed to characterize the effects of glucoprivation induced by 2-DG administration on leukocyte subset distribution and function. BDF1 mice (n = 8 per group) were injected intraperitoneally one or three times with 0, 500, 750, 1000 or 1500 mg/kg of 2-DG. Two hours after the last injection of 2-DG, immunological parameters were analyzed. A dose-dependent increase in plasma glucose concentrations of mice injected once with up to 1500 mg/kg of 2-DG was observed (p < 0.001). After either one or three injections of up to 1500 mg/kg of 2-DG, corticosterone levels, leukocyte counts in the spleen, and CD3+ cells in the thymus increased. In vitro proliferation of partially purified lymphocytes from the spleen in the presence of both concanavalin-A and lipopolysaccharide decreased in a dose dependent manner (p < 0.05). In addition, after three injections, the proportion of both thymocytes and splenocytes bearing alphabeta-TCR increased as the concentration of 2-DG increased (p < 0.01). These results demonstrate that 2-DG administration induced dose-dependent changes in both thymus and spleen cell distribution and function.

Animals↗

Serological and cellular immune responses to non-structural proteins in animals infected with FMDV.

In order to provide a rational base for the evaluation of FMDV non structural proteins as diagnostic probes, we have performed systematic longitudinal studies of the humoral and cellular immune responses to these proteins in animals infected with different FMDV serotypes. Although primary antibody responses to all the non structural proteins were observed, antibody titres were highly variable, ranging from insignificant in some cases, to clearly positive in others. In general, even the obvious positive responses were of short duration. For this reasons, discrimination between infected and vaccinated cattle is only possible at a herd level, and in our experiments the most useful target was the non structural protein 3A, although addition of 2C and 3C would provide a more sensitive test. As an alternative, with the major advantage of use directly on living cattle in the field, recombinant non structural proteins were evaluated in Delayed Type Hypersensitivity (DTH) skin tests. With this test, which measures Th1 type cellular immune responses, the most T cell immunogenic non structural proteins were 2B, 2C and 3D. Thus, DTH skin test could be a very useful tool to differentiate infected from vaccinated cattle.

Animals↗

Spaceflight and development of immune responses.

The NIH.R1 Space Shuttle experiment was designed to study the effects of spaceflight on rodent development. Pregnant rats were flown on the Space Shuttle for 11 days, and pregnant control rats were maintained in animal enclosure modules in a ground-based chamber under conditions approximating those in flight. Additional controls were in standard housing. The effects of the flight on immunological parameters of dams, fetuses, and pups were determined. Blastogenesis of spleen cells in response to mitogen was inhibited in flown dams but was not inhibited in cells from their pups. Interferon-gamma production by spleen cells showed a trend toward inhibition in flown dams but not in their pups. The response of bone marrow cells to colony-stimulating factor showed a trend toward inhibition after spaceflight in dams, but the response of fetus and pup liver cells was not inhibited. Total serum IgG was not affected by spaceflight. None of the examined immune parameters that were altered in rat dams after spaceflight was found to be altered in their offspring.

Animals↗

A behavioral intervention for improving verbal behaviors of heroin addicts in a treatment clinic.

Positively reinforcing appropriate behaviors improved verbal behaviors of opioid-dependent patients in a buprenorphine treatment clinic. During B phases of an ABAB design, clients received stickers for engaging in appropriate verbal or nonverbal behaviors. Each sticker provided a chance of winning $25. No reinforcement was provided during the A phases. Appropriate verbal behaviors increased during reinforcement periods, and inappropriate verbal behaviors decreased.

Adult↗