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Biomedical subjects

M Hogan

Publications and source records attributed to M Hogan.

At least 19 recordsLinked to original sources

Atypical mycobacterial cervical lymphadenitis with extensive local spread: a surgical disease.

Atypical (nontuberculous) mycobacterium is an uncommon cause of cervical lymphadenitis in immunocompetent children. Rarely, this disease progresses to locoregional destruction of the deep structures of the neck including salivary glands. Recent reports suggest medical monotherapy as an effective treatment of this disease. We report three cases of children who experienced progression to locoregional disease while on appropriate antibiotics. We suggest that the patient population to benefit from medical monotherapy has yet to be adequately defined. In our experience, surgical therapy is the only effective treatment for locoregional disease.

Biopsy, Needle↗

Hyperperfusion on perfusion computed tomography following revascularization for acute stroke.

PURPOSE: To describe the findings of hyperperfusion on perfusion computed tomography (CT) in four patients following revascularization for acute stroke. MATERIAL AND METHODS: In 2002-2003, among a series of 6 patients presenting with an acute stroke and treated with intra-arterial thrombolysis, we observed the presence of hyperperfusion in 3 patients on the follow-up CT perfusion. We included an additional patient who was treated with intravenous thrombolysis and who had hyperperfusion on the follow-up CT perfusion. We retrospectively analyzed their CT perfusion maps. Cerebral blood volume (CBV) and cerebral blood flow (CBF) maps were compared between the affected territory and the normal contralateral hemisphere. RESULTS: In the four patients, the mean CBV and CBF were 3.6 +/- 2.0 ml/100 g and 39 +/- 25 ml/100 g/min in the affected territory compared to the normal side (mean CBV = 2.7 +/- 2.1 ml/100 g, mean CBF = 27 +/- 23 ml/100 g/min). There was no intracranial hemorrhage in the hyperperfused territories. At follow-up CT, some hyperperfused brain areas progressed to infarction, while others retained normal white to gray matter differentiation. CONCLUSION: CT perfusion can demonstrate hyperperfusion, which can be seen in an ischemic brain territory following recanalization.

Aged↗

Multiple deprivation and excess winter deaths in Scotland.

The recent publication of the Scottish Index of Multiple Deprivation (SIMD) has allowed some tentative statistical correlations to be undertaken to assess the impact poverty may have on mortality and morbidity. During the period 1989 to 2001, Scotland registered around 51,600 excess winter deaths (EWDs). An EWD is taken as the additional deaths during December to March than occurred in the preceding and subsequent four-month periods. Almost all of these EWDs were in the population aged over 65. This represents 50 more deaths per day in January than in July. The SIMD measured five criteria by region: income; employment; health and disability; education, skills and training; and geographical access to services. Glasgow was the most deprived region with an SIMD score of 46.88 and East Dunbartonshire, the least deprived region, with a score of 9.07. For the over 65s, the chance of becoming an EWD in Glasgow is one in 36, rising to one in 68 for North Ayrshire. The SIMD is positively correlated with EWD by region (0.35 at the 5% confidence level). This correlation appears to go against the influence of climatic variations, house type, energy efficiency and access to the gas network which favours urban areas. Although some of the additional winter deaths have been ascribed to outdoor cold exposure--exacerbated by inappropriate clothing or culturally determined behaviour--the majority of EWDs are premature and essentially preventable if the elderly can be kept warm in their homes during the winter months.

Aged↗

Synthesis and SAR of bicyclic heteroaryl hydroxamic acid MMP and TACE inhibitors.

Potent and selective bicyclic heteroaryl hydroxamic acid MMP and TACE inhibitors were synthesized by a novel convergent route. Selectivity and efficacy versus MMPs and TACE could be controlled by appropriate substitution on the scaffolds and by variation of the P1' group. Select compounds were found to be effective in in vivo models of arthritis.

ADAM Proteins↗

Oligonucleotides form a duplex with non-helical properties on a positively charged surface.

The double helix is known to form as a result of hybridization of complementary nucleic acid strands in aqueous solution. In the helix the negatively charged phosphate groups of each nucleic acid strand are distributed helically on the outside of the duplex and are available for interaction with cationic groups. Cation-coated glass surfaces are now widely used in biotechnology, especially for covalent attachment of cDNAs and oligonucleotides as surface-bound probes on microarrays. These cationic surfaces can bind the nucleic acid backbone electrostatically through the phosphate moiety. Here we describe a simple method to fabricate DNA microarrays based upon adsorptive rather than covalent attachment of oligonucleotides to a positively charged surface. We show that such adsorbed oligonucleotide probes form a densely packed monolayer, which retains capacity for base pair-specific hybridization with a solution state DNA target strand to form the duplex. However, both strand dissociation kinetics and the rate of DNase digestion suggest, on symmetry grounds, that the target DNA binds to such adsorbed oligonucleotides to form a highly asymmetrical and unwound duplex. Thus, it is suggested that, at least on a charged surface, a non-helical DNA duplex can be the preferred structural isomer under standard biochemical conditions.

Carbocyanines↗

DNA microarrays based on noncovalent oligonucleotide attachment and hybridization in two dimensions.

Short oligonucleotide probes have been linked to a solid support by simple electrostatic adsorption onto a positively charged surface film. Attachment was obtained by microfluidic application of unmodified oligonucleotides in distilled water onto amino-silanized glass. It has been demonstrated that an extremely stable monolayer of oligonucleotide is obtained by this method, at a density of about 10(11) molecules/mm(2), which approaches the limit expected for a two-dimensional closest-packed array. Application of oligonucleotide by adsorption is followed by capping with acetic anhydride in the vapor phase, and then capping with succinic anhydride in solution to form a surface with weak negative charge. The capping method has been successfully employed for microarray fabrication and for the analysis of single nucleotide polymorphisms in the k-ras gene. The data reveal that, subsequent to capping, the adsorptive association of oligonucleotide to the surface yields a probe layer which is capable of single nucleotide base mismatch discrimination and high apparent binding affinity.

Acetic Anhydrides↗

Nearly instantaneous, cation-independent, high selectivity nucleic acid hybridization to DNA microarrays.

Hybridization rate enhancement has been demonstrated for high molecular weight DNA target binding to a microarray. Microarrays were fabricated using biotin-modified oligonucleotides complexed with streptavidin (SA), which serves as an attachment to the underlying surface. It is shown that at low salt and pH 5, where SA develops a positive charge, duplex formation becomes at least 80-fold faster than seen under standard conditions, where SA is neutral or anionic. Duplex formation becomes independent of solution state cation concentration in the low pH state, under conditions where specificity remains high. The utility of such applied surface science is discussed.

Biotin↗

Diagnostic and interventional ultrasound of the pediatric spine.

Ultrasound is useful as a diagnostic tool in the evaluation of the pediatric spine, and can also help guide procedures in the interventional radiology suite or the operating room. This pictorial exhibit will display examples of diagnostic and interventional uses of ultrasound with respect to the pediatric spine.

Humans↗

Cross-tolerance to otherwise lethal N-methyl-D-aspartate and oxygen-glucose deprivation in preconditioned cortical cultures.

In vitro ischemic preconditioning induced by subjecting rat cortical cultures to nonlethal oxygen-glucose deprivation protects against a subsequent exposure to otherwise lethal oxygen-glucose deprivation. We provide evidence that attenuation of the postsynaptic N-methyl-D-aspartate (NMDA) receptor- and Ca(2+)-dependent neurotoxicity underlies oxygen-glucose deprivation tolerance. It is demonstrated that extended tolerance to otherwise lethal NMDA or oxygen-glucose deprivation can be induced by either of their sublethal forms of preconditioning. These four pathways are linked, since NMDA receptor blockade during preconditioning by oxygen-glucose deprivation eliminates tolerance. These results suggest that NMDA tolerance, induced by nonlethal activation of these receptors during oxygen-glucose deprivation preconditioning, underlies oxygen-glucose deprivation tolerance. Several neurotoxic downstream Ca(2+)-dependent signaling events specifically linked to NMDA receptor activation are attenuated during otherwise lethal oxygen-glucose deprivation in preconditioned cultures. Specifically, calpain activation, as well as degradation of microtubule-associated protein-2 and postsynaptic density-95, are attenuated 2 h following otherwise lethal NMDA treatment alone or oxygen-glucose deprivation in preconditioned cultures. Formation of microtubule-associated protein-2-labeled dendritic varicosities is also attenuated in preconditioned cultures within 1 h of lethal oxygen-glucose deprivation or NMDA application. Intracellular Ca(2+) levels, measured using the high- or low-affinity dyes Fluo-4 (K(d) approximately equal 345 nM) or Fluo-4FF (K(d) approximately equal 9.7 microM) respectively, are markedly attenuated during lethal oxygen-glucose deprivation in preconditioned cultures.Collectively, the results suggest the attenuation of the postsynaptic NMDA-mediated component of otherwise lethal oxygen-glucose deprivation through the suppression of Ca(2+)-dependent neurotoxic signaling, a mechanism that is initially induced by transient nonlethal activation of this receptor during ischemic preconditioning.

Aniline Compounds↗

Policy implications for implementing evidence-based practices.

The authors describe the policy and administrative-practice implications of implementing evidence-based services, particularly in public-sector settings. They review the observations of the contributors to the evidence-based practices series published throughout 2001 in Psychiatric Services. Quality and accountability have become the watchwords of health and mental health services; evidence-based practices are a means to both ends. If the objective of accountable, high-quality services is to be achieved by implementing evidence-based practices, the right incentives must be put in place, and systemic barriers must be overcome. The authors use the framework from the U.S. Surgeon General's 1999 report on mental health to describe eight courses of action for addressing the gap between science and practice: continue to build the science base; overcome stigma; improve public awareness of effective treatments; ensure the supply of mental health services and providers; ensure delivery of state-of-the-art treatments; tailor treatment to age, sex, race, and culture; facilitate entry into treatment; and reduce financial barriers to treatment.

Ethnicity↗

Relatives' views of health care in the last year of life.

This article reports the views of 155 relatives of patients who died during a 12-month period with varying degrees of palliative care service (hospital-based, home care and no palliative care). Although overall care was rated as excellent or good by the majority of interviewees, the Critical Incident Technique (Flanagan, 1954) was used to gather examples of good and poor care from relatives' perspectives. These incidents are recounted here under a framework describing the process of care from access to services through to care at the time of death and aftercare for relatives. The range of incidents reported suggest that relatives consider all aspects of care - technical and interpersonal - as important towards the end of life, but particular importance is placed on the attitudinal and dignity-preserving aspects of care. The movement to integrate principles of palliative care into all clinical practice is reinforced by the findings from this study.

Communication↗

Simultaneous multianalyte ELISA performed on a microarray platform.

BACKGROUND: A logical progression of the widely used microtiter plate ELISA is toward a protein array format that allows simultaneous detection of multiple analytes at multiple array addresses within a single well. Here we describe the construction and use of such a multiplex ELISA to measure prostate-specific antigen (PSA), alpha1-antichymotrypsin-bound PSA (PSA-ACT), and interleukin-6 (IL-6). METHODS: We silanized glass plates and printed the appropriate capture antibodies to allow for the construction of "sandwich" ELISA quantification assays. We examined specificity of the assay for appropriate antigen, assembled calibration curves, and obtained PSA concentrations for 14 human serum samples. We compared the serum PSA concentrations derived through the use of our array with values obtained independently using a standard ELISA method. RESULTS: R2 values generated by our microarray for the PSA and PSA-ACT calibration curves were 0.989 and 0.979, respectively. Analyte concentrations used for the construction of these curves were 0.31-20 microg of protein/L of diluent. IL-6 calibration curve concentrations were 4.9-300 ng of IL-6/L of diluent. The R2 value for the IL-6 calibration curve was 0.983. The 14 human serum samples screened by this micro-ELISA technique for PSA concentrations generated a regression equation (linear) with a slope of 0.83 +/- 0.10 and intercept of 0.74 +/- 0.70 (R2 = 0.88). CONCLUSIONS: Multiplexed ELISA arrays are a feasible option for analyte quantification in complex biologic samples.

Autoanalysis↗

Media matters for youth health.

We live in a media world and the mass media offer educational and entertainment opportunities for adults and children. However, pediatricians and parents are increasingly aware of the potential health risks that media exposure presents to children and adolescents. For many years, the American Academy of Pediatrics (AAP) has made media education a key goal for member pediatricians: Six policy statements about the impact of mass media have been published (and revised) over the past decade. In 1997, the AAP launched a 5-year, nationwide media education campaign called Media Matters. Although education about media is the cornerstone of Media Matters, pediatricians have other important roles. In offices and clinics, the AAP suggests that pediatricians take a media history from patients and discuss connections between a child's health and behavior and media use habits. Pediatricians can also provide anticipatory guidance to families about media in the home, including limiting media use, making wise media choices, encouraging co-viewing and critical thinking, and making the home a positive media environment. Many gaps in our knowledge about the effects of media images and messages on young people still exist; pediatricians call for ongoing, targeted research about media. In this way, we can all enjoy the benefits offered by media, while minimizing the risks.

Adolescent↗

Ventilator-associated pneumonia in very low-birth-weight infants at the time of nosocomial bloodstream infection and during airway colonization with Pseudomonas aeruginosa.

PURPOSE: To study retrospectively the incidence of ventilator-associated pneumonia (VAP) at the time of Pseudomonas aeruginosa nosocomial bloodstream infection (BSI) and at the time of P aeruginosa airway colonization. MATERIALS AND METHODS: Fifteen very low-birth-weight infants who had P aeruginosa BSI and 33 others who did not but who had P aeruginosa airway-colonization were studied. We correlated clinical data, blood cultures (BCs), and tracheal cultures (TCs) with radiologic findings from radio-graphs taken within 2 days before, the day of, and 1 day after BCs or TCs were first positive for P aeruginosa. Chest radiographs were graded by using semiquantitative scores for bronchopulmonary dysplasia and for pneumonia. RESULTS: Mean birth weight, gestational age, and age when BC or TC became positive were similar for patients with BSI and colonization. At the time of BSI, 2 infants had airway colonization with P aeruginosa; the TCs of the remaining 13 grew P aeruginosa as a new pathogen. Thirteen of 15 patients with BSI, but none of 33 infants with colonization, died within 2 days of positive BC. VAP was diagnosed in 13 of 15 patients with BSI and in 3 of 33 infants with colonization. CONCLUSION: Mechanically ventilated very low-birth-weight infants whose TCs yield P aeruginosa but whose BCs remain negative infrequently have VAP are presumed airway-colonized and are expected to survive. Conversely, VAP is likely to be found when BCs and TCs simultaneously grow P aeruginosa, and high mortality is anticipated.

Birth Weight↗

Evaluation of glutathione-sensitive fluorescent dyes in cortical culture.

The sensitivity of six fluorophores to glutathione (GSH) was evaluated in living rat cortical neuronal/glial mixed cultures during the first 23 days in vitro (DIV). Four of the dyes require glutathione-S-transferase (GST) to form a fluorescent conjugate, potentially conferring specificity for GSH: these included t-butoxycarbonyl-Leu-Met-7-amino-4-chloromethylcoumarin (CMAC), 7-amino-4-chloromethylcoumarin (CMAC-blue), monochlorobimane (MCB), and 5-chloromethylfluorescein diacetate (CMFDA). The final two dyes examined, 2,3-naphthalenedicarboxaldehyde (NDA) and o-phthaldehyde (OPD), do not require GST for adduct formation with GSH. To examine the specificity of the dyes for GSH, cultures grown less than 6 DIV were pretreated with diethyl maleate or DL-buthionine-(S, R)-sulfoximine to deplete endogenous GSH. This resulted in a substantial loss of staining by CMAC, CMAC-blue, and MCB and partial loss of staining by OPD, indicating specificity for GSH, while staining by CMFDA or NDA was not altered, indicating a lack of specificity for GSH. Neurons experienced a dramatic decline in GSH levels relative to astrocytes between 5-6 DIV, as shown by a loss of neuronal staining with CMAC, CMAC-blue and MCB. This decrease in staining was not due to a decrease in GST activity, as neurons stained with the GST-insensitive OPD also exhibited a decline in GSH-sensitive staining. Immunolabeling experiments demonstrated that CMAC staining co-localized with GFAP-positive astrocytes, but not with MAP-2-positive neurons, in 18 DIV cultures. Finally, CMAC was exploited as a specific morphological marker of astrocytes in cultures aged >5 DIV. CMAC staining was employed to monitor astrocyte proliferation and to resolve astrocytes in living mixed cultures co-loaded with the Ca(2+)-sensitive dye, calcium green 5N-AM. GLIA 30:329-341, 2000. Published 2000 Wiley-Liss, Inc.

Animals↗