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Biomedical subjects

Michael Bell

Publications and source records attributed to Michael Bell.

11 recordsLinked to original sources
PubMed2006

Lymphocytic choriomeningitis virus: an emerging obstetric pathogen?

A report in May 2005 from the Centers for Disease Control and Prevention describing a cluster of lymphocytic choriomeningitis virus (LCMV) infections among 4 solid organ recipients has increased awareness of and clinical interest in this pathogen. Human infection with LCMV results from direct or indirect contact with rodents. LCMV has particular relevance to obstetrics, as it is likely an under-recognized abortifacient and fetal teratogen. There have been 54 cases of congenital LCMV reported since 1955, with 34 of the cases diagnosed since 1993. Chorioretinitis and hydrocephalus are the predominant characteristics among children diagnosed with congenital LCMV infection. Obstetricians should educate their pregnant patients about the risks of exposure to laboratory, pet, and wild rodents.

Abortion, Spontaneous↗
PubMed2006

Microglia and inflammation: impact on developmental brain injuries.

Inflammation during the perinatal period has become a recognized risk factor for developmental brain injuries over the past decade or more. To fully understand the relationship between inflammation and brain development, a comprehensive knowledge about the immune system within the brain is essential. Microglia are resident immune cells within the central nervous system and play a critical role in the development of an inflammatory response within the brain. Microglia are critically involved with both the innate and adaptive immune system, regulating inflammation and cell damage within the brain via activation of Toll-like receptors, production of cytokines, and a myriad of other intracellular and intercellular processes. In this article, microglial physiology is reviewed along with the role of microglia in developmental brain injuries in humans and animal models. Last, microglial functions within the innate and adaptive immune system will be summarized. Understanding the processes of inflammation and microglial activation is critical for formulating effective preventative and therapeutic strategies for developmental brain injuries.

Biomarkers↗
PubMed2005

F110I and R278C troponin T mutations that cause familial hypertrophic cardiomyopathy affect muscle contraction in transgenic mice and reconstituted human cardiac fibers.

We have studied the physiological effects of the troponin T (TnT) F110I and R278C mutations associated with familial hypertrophic cardiomyopathy (FHC) in humans. Three to four-month-old transgenic (Tg) mice expressing F110I-TnT and R278C-TnT did not develop significant hypertrophy or ventricular fibrosis even after chronic exercise challenge. The F110I mutation impaired acute exercise tolerance, whereas R278C did not. Skinned papillary muscle fibers from transgenic mice expressing F110I-TnT demonstrated increased Ca(2+) sensitivity of force and ATPase activity, and likewise an increased Ca(2+) sensitivity of force was observed in F110I-TnT-reconstituted human cardiac muscle preparations. In contrast, no changes in force or the ATPase-pCa dependencies were observed in transgenic R278C fibers or in human fibers reconstituted with the R278C-TnT mutant. The maximal level of force development was dramatically decreased in both transgenic mice. However, the maximal ATPase was not different (R278C-TnT) or only slightly less (F110I-TnT) than that of non-Tg and WT-Tg littermates. Consequently, their ratios of ATPase/force (energy cost) at all Ca(2+) concentrations were dramatically higher compared with non-Tg and WT-Tg fibers. This increase in energy cost most likely results from a decrease in force per myosin cross-bridge, because forcing all cross-bridges into the force generating state by substitution of MgADP for MgATP in maximum contracting solutions resulted in the same increase in maximal force (15%) in all transgenic and non-transgenic preparations. The combination of increased Ca(2+) sensitivity and energy cost in the F110I hearts may be responsible for the greater severity of this phenotype compared with the R278C mutation.

Adenosine Triphosphatases↗
PubMed2005

A multicenter prospective study of 3,110 consecutive cases of elective epinephrine use in the fingers and hand: the Dalhousie Project clinical phase.

PURPOSE: To examine prospectively the incidence of digital infarction and phentolamine rescue in a large series of patients in whom local anesthesia with adrenaline was injected electively into the hand and fingers. There continues to be a commonly held belief that epinephrine injection is contraindicated in the finger despite a lack of valid evidence to support this concept in the literature. METHODS: From 2002 to 2004 there were 9 hand surgeons in 6 cities who prospectively recorded each consecutive case of elective hand and finger epinephrine injection. They recorded each instance of skin or tissue loss and the number of times phentolamine reversal of adrenaline vasoconstriction was required. RESULTS: There were 3,110 consecutive cases of elective injection of low-dose epinephrine (1:100,000 or less) in the hand and fingers and none produced any instance of digital tissue loss. Phentolamine was not required to reverse the vasoconstriction in any patients. CONCLUSIONS: The true incidence of finger infarction in elective low-dose epinephrine injection into the hand and finger is likely to be remote, particularly with the possible rescue with phentolamine.

Canada↗
PubMed2004

A preliminary study of the role of modulated electron beams in intensity modulated radiotherapy, using automated beam orientation and modality selection.

PURPOSE: To develop an algorithm for optimal beam arrangement selection in intensity-modulated radiotherapy (IMRT) of mixed photon and electron beams. To apply this algorithm to study the utility of modulated electron beams in the context of IMRT planning. METHODS AND MATERIALS: The optimization algorithm selects, for a user-specified number of beams, the optimal IMRT arrangement (beam orientations, and photon/electron modality for each orientation) using a novel fast heuristic intensity modulation procedure. The algorithm was employed to select optimal beam arrangements for breast (two, four, and six axial beams) and head-and-neck (three, four, five, and seven nonaxial beams) cases. RESULTS: For the two cases, increasing the number of selected beams: (1) increased the number of electron beams for the breast case, but not more than one electron beam was selected for the head-and-neck case; (2) decreased critical structure doses for both cases; and (3) decreased target homogeneity for the breast case, but improved it for the head-and-neck case. CONCLUSIONS: In the two cases analyzed using the selection algorithm, the primary role of modulated electrons differs based on treatment site-normal tissue dose reduction in breast and target homogeneity improvement in head and neck. Although this preliminary study with two cases appears to suggest that the role of intensity-modulated electrons differs based on treatment site, further investigation of large numbers of cases and varied treatment sites are required to establish a definitive conclusion.

Algorithms↗
PubMed2003

Outbreak of invasive aspergillosis among renal transplant recipients.

Invasive aspergillosis (IA) is rare among renal transplant recipients (RTRs). We investigated a cluster of IA among RTRs at a California hospital from January to February 2001, when construction was ongoing. We conducted a cohort study among RTRs who were hospitalized between January 1 and February 5, 2001, to determine risk factors for IA. IA was defined using established guidelines. Four IA cases occurred among 40 RTRs hospitalized during the study period. Factors associated with an increased risk of IA included prolonged hemodialysis, lengthy corticosteroid treatment posttransplant, and use of sirolimus alone or with mycophenolate (P<0.05). After the study period, three additional RTRs developed IA; two Aspergillus isolates recovered from these patients had indistinguishable profiles by DNA fingerprinting, suggesting common-source exposure. This study suggests that immunosuppressed RTRs can be at an increased risk for IA. Measures to prevent IA in these patients should be taken during hospital construction.

Adult↗
PubMed2003

Prevalence of and risk factors for colonization with methicillin-resistant Staphylococcus aureus at the time of hospital admission.

OBJECTIVES: To determine the prevalence of methicillin-resistant Staphylococcus aureus (MRSA) colonization among patients presenting for hospital admission and to identify risk factors for MRSA colonization. DESIGN: Surveillance cultures were performed at the time of hospital admission to identify patients colonized with S. aureus. A case-control study was performed to identify risk factors for MRSA colonization. SETTING: A tertiary-care academic medical center. PATIENTS: Adults presenting for hospital admission (N = 974). RESULTS: S. aureus was isolated from 205 (21%) of the patients for whom cultures were performed. Methicillin-sensitive S. aureus was isolated from 179 (18.4%) of the patients, and MRSA was isolated from 26 (2.7%) of the patients. All 26 MRSA-colonized patients had been admitted to a healthcare facility in the preceding year, had at least one chronic illness, or both. In multivariate analyses comparing MRSA-colonized patients with control-patients, admission to a nursing home (odds ratio [OR], 16.5; 95% confidence interval [CI95], 1.4 to 192.1; P = .025) or a hospitalization of 5 days or longer during the preceding year (OR, 3.91; CI95, 1.1 to 13.9; P = .035) were independent predictors of MRSA colonization. CONCLUSIONS: Patients colonized with MRSA admitted to this hospital likely acquired the organism during previous encounters with healthcare facilities. There was no evidence that MRSA colonization occurs commonly among low-risk individuals in this community. These data suggest that evaluation of recent healthcare exposures is essential if true community acquisition of MRSA is to be confirmed.

Academic Medical Centers↗
PubMed2002

Flow cytometric ion detection with plasticized poly(vinyl chloride) microspheres containing selective lonophores.

The use of flow cytometry as a rapid, high-throughput diagnostic tool for the analysis of ions is described. Monodisperse, uniform microspheres, which obey bulk optode theory and are governed by bulk extraction processes rather than surface phenomena, were prepared under mild, nonreactive conditions using a sonic stream particle casting apparatus. As an initial example demonstrating the utility of this approach, microspheres that contained a H+-selective fluorescent chromoionophore (ETH 5294), a cation-exchanger (NaTFPB), and either a highly sodium-selective (sodium ionophore X) or a potassium-selective ionophore (BME-44) were prepared. Separate solution analysis of sodium- and potassium-selective microspheres resulted in the generation of functional response curves using peak channel fluorescence intensities. The selectivity observed for both types of particles is sufficient for the clinical determination of Na+ and K+. Furthermore, sodium- and potassium-selective microspheres were analyzed in parallel using sodium sample solutions, resulting in the successful determination of sodium ion concentrations and providing important information about the selectivity of the potassium-selective sensors over sodium. This work demonstrates the potential applicability of flow cytometry as a means for developing multiplexed, rapid, high-throughput analyses for clinically relevant ions.

Flow Cytometry↗
PubMed2002

Vitamin A levels and immunity in humans.

In animal studies, vitamin A deficiency induces a shift from type 2 (humoral) to type 1 (cellular) cytokines; there are no similar data for humans. Control of human immunodeficiency virus (HIV) and Mycobacterium tuberculosis infections requires type 1 cytokine (cellular) immunity. These infections and vitamin A deficiency are highly prevalent in Africa. We therefore examined the interactions among serum vitamin A levels, immune parameters, HIV infection status, Mycobacterium bovis BCG vaccine scarring (as an indicator of a type 1 cytokine profile), and clinical findings for 70 hospitalized children in Malawi, Africa. Directly conjugated monoclonal antibodies and flow cytometry were used to assess cell-specific cytokine production by peripheral blood monocytes and lymphocyte subpopulations. The statistical techniques employed included nonparametric statistics and logistic regression analyses. Thirty percent of the participants had severe vitamin A deficiency (<10 microg/dl), 34% had moderate deficiency (10 to <20 microg/dl), and 36% had normal levels (> or = 20 microg/dl). Vitamin A levels were lower for HIV-positive than for HIV-negative children (median, 10 and 17 microg/dl, respectively). Vitamin A-deficient children (<20 microg/dl) were more likely than non-vitamin A-deficient children to have higher proportions of natural killer (NK) cells (median, 8.3 and 5.2%, respectively) and lower ratios of interleukin-10-producing monocytes to tumor necrosis factor alpha-producing monocytes after induction (median, 1.0 and 2.3, respectively). Vitamin A-deficient children were also more likely than non-vitamin A-deficient children to exhibit respiratory symptoms (47% versus 12%) and visible BCG vaccine scars (83% versus 48%), which are indicative of a type 1 response to vaccination. Vitamin A status did not vary with gender, age, incidence of malaria parasitemia, blood culture positivity, or rates of mortality (6% of vitamin A-deficient children died versus 20% of non-vitamin A-deficient children). Lower vitamin A levels were associated with a relative type 1 cytokine dominance and proportionately more NK cells, both of which may be somewhat beneficial to persons who are exposed to HIV, M. tuberculosis, or other type 1 pathogens.

BCG Vaccine↗
PubMed2001

Biofilms: A Clinical Perspective.

Biofilms play an increasingly recognized role in many aspects of human disease. Most of our understanding of infections is based on research that has examined free-living organisms. The results do not necessarily apply to biofilm organisms, since metabolic and synthetic characteristics of free-living organisms can change when they assume the biofilm mode of growth. Biofilms reduce our ability to eradicate infections, causing relapses after seemingly appropriate therapy. Awareness of biofilms, prevention of contamination of implanted or invasive devices, and use of appropriate antimicrobial dosing and treatment durations can limit the negative impact of biofilms while we strive for new technological solutions.

Journal Article↗