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Biomedical subjects

R O'Brien

Publications and source records attributed to R O'Brien.

At least 91 records · Page 5Linked to original sources

Evidence that murine V gamma 5 and V gamma 6 gamma delta-TCR+ lymphocytes are derived from a common distinct lineage.

Murine V gamma 5 and V gamma 6+ T lymphocytes develop sequentially in the thymus during fetal and newborn life, giving rise to intraepithelial lymphocytes of the epidermis and female reproductive tract. In analyzing a panel of gamma delta T cell hybridomas derived from various tissues, we found that all V gamma 6+ cells tested (n = 25) expressed V gamma 5-C gamma 1 mRNA, whereas none of a panel of V gamma 6- cells analyzed (n = 33) expressed this mRNA. V gamma 6 mRNA was rare in V gamma 5+ cells (1 of 9), and absent in all other gamma delta T cells (n = 10). These findings suggest that most, if not all, V gamma 6-TCR+ lymphocytes arise from precursor cells that have previously rearranged the V gamma 5 gene, and indicate that V gamma 5 and V gamma 6+ lymphocytes belong to a common, distinct lineage that does not give rise to other gamma delta T cells.

Animals↗

Molecular chaperones and the immune response.

Molecular chaperones belonging to heat shock protein families have been identified as prominent antigens in the immune response to a wide variety of infections. Recognition of such highly conserved antigens may contribute to protective immunity but, in some circumstances, may also have pathological autoimmune consequences. Recognition of chaperones may be an inherent feature of the immune system. Peptide mapping experiments revealed an overlap between hsp 70-binding sites and immunodominant regions of three protein antigens, consistent with a possible functional activity for molecular chaperones in the processing and presentation of peptides during class II-restricted T lymphocyte responses. A functional role for molecular chaperones in antigen processing may be a factor which contributes to their immunogenicity.

Animals↗

Derangements in peripheral glucose and oxygen utilization induced by catabolic hormones.

OBJECTIVE: To assess if the derangements in peripheral glucose, lactate, and oxygen utilization that are observed in severely injured patients are due to the hormonal response to injury or are related to the extent of the wound. DESIGN: Comparison study. INTERVENTIONS: The catabolic hormones epinephrine, cortisol, and glucagon were infused simultaneously into the femoral artery of six healthy volunteers, thus simulating the hormonal milieu associated with severe trauma in an uninjured leg. SETTING: Clinical research center at a university-affiliated hospital. PATIENTS: Young, adult males deemed healthy by screening medical history, physical examination, and blood chemistries. MEASUREMENTS AND MAIN RESULTS: Substrate net balance and indirect calorimetry measurements were performed before and then at the completion of 2 hrs of catabolic hormone infusion. Catabolic hormones elicited significant increases in leg glucose uptake and oxidation, and an increased net efflux from the leg of lactate and alanine. While leg oxygen delivery also increased, catabolic hormones failed to alter peripheral oxygen consumption. CONCLUSIONS: Catabolic hormones can elicit a similar peripheral metabolic response in an uninjured leg as that reported previously by Wilmore et al. in severely burned extremities. This finding suggests that the hormonal milieu associated with severe injury is influential in regulating peripheral glucose and oxygen utilization and that wound inflammation is not an essential component of this response.

Adult↗

Effect of gallopamil on electrophysiologic abnormalities and ventricular arrhythmias associated with left ventricular hypertrophy in the feline heart.

Left ventricular hypertrophy increases vulnerability to ventricular fibrillation. To determine whether calcium channel blockade protects against ventricular arrhythmia in left ventricular hypertrophy, we studied the effects of gallopamil, a potent and specific calcium channel antagonist, in 37 cats undergoing aortic banding (group 1, n = 28) or a sham procedure (group 2, n = 9). Each cat underwent serial echocardiography and was studied after the development of left ventricular hypertrophy, defined as an increase of at least 30% in left ventricular posterior wall thickness. After baseline electrophysiologic testing, animals received gallopamil (70 micrograms/kg loading dose followed by 2.5 micrograms/kg/min infusion) (n = 19) or a control infusion of saline solution (n = 18), and testing was repeated. There was no significant difference between groups 1 and 2 in baseline excitability thresholds intraventricular conduction times, ventricular effective refractory periods, or monophasic action potential durations. Thresholds for induction of ventricular fibrillation were lower in group 1 than in group 2, and only in group 1 was ventricular fibrillation inducible during programmed stimulation. This altered vulnerability was associated with a significantly greater dispersion of excitability thresholds, ventricular effective refractory periods, and monophasic action potential durations. Gallopamil did not change baseline measurements except for prolonging sinus cycle length and atrioventricular conduction time.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

The effect of albumin or crystalloid resuscitation on bacterial translocation and endotoxin absorption following experimental burn injury.

Burn injury induces immune suppression and increases susceptibility to infection. Hypoalbuminemia is an early and consistent finding following thermal injury and is independently associated with gastrointestinal dysfunction and increased rates of infectious morbidity. This study assessed the effects of albumin resuscitation on burn-induced immunosuppression, bacterial translocation, and absorption of gut endotoxin. Male Sprague-Dawley rats, presensitized to keyhole limpet hemocyanin (KLH), underwent a 20% dorsal scald burn injury, followed by laparotomy and IVC catheterization for fluid resuscitation. Animals were randomized to one of three resuscitative regimens: Ringer's lactate 3 ml/kg/% burn, Ringer's lactate 9 ml/kg/% burn, or 5% human albumin 3 ml/kg/% burn. Delayed hypersensitivity (DTH) responses to KLH were depressed 24 hr following injury (preburn 8.9 +/- 0.2 mm, post-burn 3.1 +/- 0.3 mm, P less than 0.001) and were significantly lower in animals in whom gram-negative bacterial translocation had occurred (2.3 +/- 0.4 vs 3.6 +/- 0.2 mm, P less than 0.005). Serum albumin levels were lower and rates of gram-negative bacterial translocation higher for those animals receiving low volume crystalloid resuscitation; animals resuscitated with albumin or high volume crystalloid experienced similar degrees of postinjury hypoalbuminemia and bacterial translocation. Uptake of radiolabeled endotoxin was maximal in animals resuscitated with albumin. Bacterial translocation is believed to be responsible for a significant number of late nosocomial infections following trauma. These data suggest that the adequacy of early resuscitation rather than the type of resuscitative solution is the more important factor in minimizing translocation.

Animals↗

Evaluation of new anti-infective drugs for the treatment and prevention of tuberculosis. Infectious Diseases Society of America and the Food and Drug Administration.

This guideline addresses the evaluation of new antimycobacterial drugs in the treatment and prevention (secondary prophylaxis) of infection by M. tuberculosis. Patients may be enrolled in clinical trials on the basis of clinical and/or microbiological criteria. A therapeutic regimen will likely include a combination of drugs; a randomized, active-control, comparative clinical trial is recommended. If appropriate samples can be obtained for culture during follow-up without placing the patient at unwarranted risk, the assessment of microbiological outcome is paramount. Prophylaxis will probably require a single drug, and a similar study design is preferred.

Adult↗

Evaluation of new anti-infective drugs for the treatment and prevention of infections caused by the Mycobacterium avium complex. Infectious Diseases Society of America and the Food and Drug Administration.

The bacteria of the Mycobacterium avium complex are ubiquitous; thus it is often difficult to distinguish environmental contamination from colonization or infection. Patients with either pulmonary or disseminated infection may be enrolled in clinical trials. Disseminated disease occurs mostly in patients infected with the human immunodeficiency virus. In general, a randomized, active-control, double-blinded clinical trial is preferred; there should at least be a blinded evaluator. With regard to immunosuppressed populations, new antimycobacterial drugs need to be evaluated not only for the treatment but also for the prevention of disease. For trials of prophylaxis a placebo-controlled design is ethical until a drug is proven effective; then the use of an active-control regimen is appropriate. Since no regimen has been approved by the U.S. Food and Drug Administration for treatment or prevention of disease caused by the M. avium complex, demonstration of the superiority of the study regimen to the control regimen should be the objective of the clinical trial.

Anti-Bacterial Agents↗

Evaluation of new anti-infective drugs for the treatment of disease caused by Mycobacterium kansasii and other mycobacteria. Infectious Diseases Society of America and the Food and Drug Administration.

Mycobacterium kansasii is a photochromogenic nontuberculous mycobacterium that usually causes infections of the respiratory tract in humans. Although spontaneous resolution of infection has been reported, most patients require antimycobacterial therapy. A three- or four-drug combination--isoniazid, rifampin, and ethambutol and/or streptomycin--usually is prescribed. For evaluation of a new drug, a randomized, double-blind or evaluator-blinded, active-control comparative study design is recommended. Treatment should continue for 18-24 months, and follow-up evaluations should be conducted every 6 months for 3 years. Microbiological outcome is paramount.

Anti-Infective Agents↗

Tsukamurella paurometabolum: a novel pathogen causing catheter-related bacteremia in patients with cancer.

Tsukamurella paurometabolum is a weakly acid-fast, pleomorphic gram-positive bacterium found in soil. Human infection due to this organism has rarely been described, and there are no published accounts of bacteremia. Three cases of bacteremia due to T. paurometabolum and related to long-term use of a central venous catheter in patients with cancer who were receiving chemotherapy are described.

Actinomycetales↗

Use of formal community resources by spouse caregivers of chronically ill adults.

This descriptive correlational study examined the use of formal community resources of spouse caregivers of progressively chronically ill individuals. The convenience sample was 61 individuals with a definitive diagnosis of multiple sclerosis and their spouse caregivers. Results indicated that 34.4% of the sample used community resources. Relationships among caregiver demographics, extent of caregiving tasks, subjective burden, perceived uncertainty of the caregiver, functional incapacity of the chronically ill individual, level of social support, and the use of formal community resources were analyzed. Positively correlated (P less than 0.05) with the criterion variable of use of formal community resources were the variables of caregiver age (rpb = 0.342), number of caregiving tasks (rpb = 0.424), caregiver employment level (chi 2 = 8.25), and functional incapacity of the care receiver (rpb = 0.565). Results of discriminate function analysis indicated that three variables, functional incapacity, caregiver age, and number of caregiving tasks, correctly classified users versus nonusers of community resources 83.6% of the time.

Adult↗

Alpha beta T-lymphocyte depleted mice, a model for gamma delta T-lymphocyte functional studies.

Adult mice can be depleted of essentially all mature alpha beta T lymphocytes by chronic treatment with the framework-recognizing, pan-specific anti-TCR alpha beta mAb, H57-597. Similar findings have been reported in rats, gamma delta cell populations remain essentially unaltered in size and reactivity. Suppression of alpha beta T-cell development results in the loss of alloantigen reactivity and of B-cell help, suggesting that gamma delta and alpha beta populations differ in their functional capabilities. Indirect effects of the antibody treatment include quantitative changes in splenic B cells, as well as reduced sizes and weights of experimental animals. alpha beta-suppressed mice and rats may provide model systems for studies on gamma delta cell function in vivo.

Animals↗

Starting intravenous lines in children.

Starting an IV line in children can be difficult. As with most skills, practice improves performance. However, a lack of practice for the clinician with otherwise good IV skills need not be an impediment. The suggestions described in this article can assist you in adapting your good IV technique to the pediatric patient.

Catheterization, Peripheral↗