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Biomedical subjects

William Brown

Publications and source records attributed to William Brown.

14 recordsLinked to original sources
PubMed2007

A national assessment of knowledge, attitudes, and confidence of prehospital providers in the assessment and management of child maltreatment.

OBJECTIVE: The goal was to assess the knowledge and confidence in recognition, management, documentation, and reporting of child maltreatment among a representative sample of emergency medical services personnel in the United States. METHODS: A questionnaire was developed and pilot-tested, with the input of experts in emergency medical services and child maltreatment, to assess knowledge, attitudes, confidence, and training needs regarding assessment and treatment of child maltreatment. The questionnaire was distributed nationally to a random sample of prehospital providers by using a previously validated sampling plan. RESULTS: Of 2863 surveys sent to prehospital providers, 1237 (43%) were returned. Most prehospital providers reported receiving < or = 1 hour of continuing medical education regarding child maltreatment. Most (78%) asked for additional educational opportunities, with only 3% stating that they required no additional training. Participants lacked knowledge regarding the developmental abilities of children, management of families in which child maltreatment is suspected, key elements of the history that should be noted, and the degree of suspicion necessary for reporting. CONCLUSIONS: Prehospital providers expressed confidence in their abilities to recognize and to manage cases of child abuse and neglect; however, significant deficiencies were reported in several critical knowledge areas, including identification of child maltreatment, interviewing techniques, and appropriate documentation.

Attitude of Health Personnel↗
PubMed2006

A novel mycoplasma detected in association with upper respiratory disease syndrome in free-ranging eastern box turtles (Terrapene carolina carolina) in Virginia.

Clinical signs of upper respiratory tract disease-like syndrome (URTD-LS) were observed in free-ranging eastern box turtles (Terrapene carolina carolina) from Virginia, USA (May 2001-August 2003), some of which also had aural abscesses. After a Mycoplasma sp. was detected by polymerase chain reaction (PCR), a study was undertaken to better define the range of clinical signs of disease and to distinguish mycoplasma-associated URTD-LS from other suspected causes of URTD-LS and aural abscessation in box turtles. Nasal and/or ocular swabs (from turtles possessing URTD-LS) or nasal washes (from asymptomatic turtles) were collected from turtles May 2001-August 2003; samples were assayed for Mycoplasma spp., chelonian herpesvirus, and iridoviruses by PCR testing. A partial DNA sequence (933 bases) of the small ribosomal subunit (16S rRNA) of the box turtle Mycoplasma sp. was analyzed to determine its phylogenetic relatedness to other Mycoplasma spp. of veterinary interest. Mycoplasma sp. was detected in seven (six with clinical signs of URTD-LS; one asymptomatic) of 23 fortuitously collected animals from six of 11 Virginia counties. Clinical signs in Mycoplasma sp.-infected animals included unilateral to bilateral serous to mucopurulent nasal discharge, epiphora, ocular edema, and conjunctival injection. Five Mycoplasma sp.-positive animals possessed aural abscesses; two did not. Analysis of the mycoplasma 16S rRNA gene sequence from one asymptomatic and three symptomatic animals representing four counties revealed a consensus Mycoplasma sp. sequence closely related to, but distinct from, M. agassizii. None of the samples collected contained viral DNA of chelonian herpesviruses or invertebrate and vertebrate (including FV3) iridoviruses. In conclusion, a new Mycoplasma sp. was associated with URTD-LS in native box turtles from Virginia that was not codetected with other suspected causes of chelonian upper respiratory disease; there was no proof of a direct relationship between aural abscessation and the Mycoplasma sp.

Animals↗
PubMed2005

Oral dosage form performance tests: new dissolution approaches.

The performance test is one of a series of tests that compose the specification in a United States Pharmacopeia (USP) dosage form monograph. For an orally administered, nonsolution dosage form, it is usually satisfied by either a dissolution or disintegration procedure. Dissolution acceptance criteria are usually set in private negotiations between an applicant and a regulatory agency. With information about this private agreement and other information provided in a sponsor's Request for Revision to USP, the USP's Council of Experts elaborates a public dosage form monograph. Based on the relationship between the regulatory decisions and the Request for Revision, the USP dissolution procedure links to a regulatory judgment about bioavailability and bioequivalence and, ultimately, to a judgment about safety and efficacy. The current dissolution procedure and acceptance criteria are perceived as having worked well over the years and are generally accepted. This article discusses new approaches that merit consideration. These approaches focus on a) explicit use of hypothesis testing, b) use of parametric tolerance intervals, c) improved ways to set dissolution acceptance criteria, and d) a more flexible protocol to assess conformity. Application of the proposed approaches may better assess, manage, and communicate both manufacturer and consumer risk for dissolution testing.

Administration, Oral↗
PubMed2005

Physician knowledge of the Glasgow Coma Scale.

Appropriate triage is critical to optimizing outcome from battle related injuries. The Glasgow Coma Scale (GCS) is the primary means by which combat casualties, who have suffered head injury, are triaged. For the GCS to be reliable in this critical role, it must be applied accurately. To determine the level of knowledge of the GCS among military physicians with exposure and/or training in the scale we administered a prospective, voluntary, and anonymous survey to physicians of all levels of training at military medical centers with significant patient referral base. The main outcome measures were correct identification of title and categories of the GCS along with appropriate scoring of each category. Overall performance on the survey was marginal. Many were able to identify what "GCS" stands for, but far fewer were able to identify the titles of the specific categories, let alone identify the specific scoring of each category. When evaluated based on medical specialties, those in surgical specialties outperformed those in the medical specialties. When comparing the different levels of training, residents and fellows performed better than attending staff or interns. Finally, those with Advanced Trauma Life Support (ATLS) certification performed significantly better than those without the training. Physician knowledge of the GCS, as demonstrated in this study, is poor, even in a population of individuals with specific training in the use of the scale. It is concluded that, to optimize outcome from combat related head injury, methods for improving accurate quantitation of neurologic state need to be explored.

Certification↗
PubMed2005

CENP-A is required for accurate chromosome segregation and sustained kinetochore association of BubR1.

CENP-A is an evolutionarily conserved, centromere-specific variant of histone H3 that is thought to play a central role in directing kinetochore assembly and in centromere function. Here, we have analyzed the consequences of disrupting the CENP-A gene in the chicken DT40 cell line. In CENP-A-depleted cells, kinetochore protein assembly is impaired, as indicated by mislocalization of the inner kinetochore proteins CENP-I, CENP-H, and CENP-C as well as the outer components Nuf2/Hec1, Mad2, and CENP-E. However, BubR1 and the inner centromere protein INCENP are efficiently recruited to kinetochores. Following CENP-A depletion, chromosomes are deficient in proper congression on the mitotic spindle and there is a transient delay in prometaphase. CENP-A-depleted cells further proceed through anaphase and cytokinesis with unequal chromosome segregation, suggesting that some kinetochore function remains following substantial depletion of CENP-A. We furthermore demonstrate that CENP-A-depleted cells exhibit a specific defect in maintaining kinetochore localization of the checkpoint protein BubR1 under conditions of checkpoint activation. Our data thus point to a specific role for CENP-A in assembly of kinetochores competent in the maintenance of mitotic checkpoint signaling.

Animals↗
PubMed2004

Sperm-specific protein kinase A catalytic subunit Calpha2 orchestrates cAMP signaling for male fertility.

An unusual cAMP signaling system mediates many of the events that prepare spermatozoa to meet the egg. Its components include the atypical, bicarbonate-stimulated, sperm adenylyl cyclase and a cAMP-dependent protein kinase (PKA) with the unique catalytic subunit termed Calpha(2) or C(s). We generated mice that lack Calpha(2) to determine its importance in the events downstream of cAMP production. Male Calpha(2) null mice produce normal numbers of sperm that swim spontaneously in vitro. Thus, Calpha(2) has no required role in formation of a functional flagellum or the initiation of motility. In contrast, we find that Calpha(2) is required for bicarbonate to speed the flagellar beat and facilitate Ca(2+) entry channels. In addition, Calpha(2) is needed for the protein tyrosine phosphorylation that occurs late in the sequence of sperm maturation and for a negative feedback control of cAMP production, revealed here. Consistent with these specific defects in several important sperm functions, Calpha(2) null males are infertile despite normal mating behavior. These results define several crucial roles of PKA in sperm cell biology, bringing together both known and unique PKA-mediated events that are necessary for male fertility.

Adenylyl Cyclases↗
PubMed2004

Clinical experience with Staphylococcus lugdunensis bacteremia: a retrospective analysis.

We report a retrospective review of all cases of Staphylococcus lugdunensis bacteremia identified during a period of more than 10 years (January 1990 to May 2002) in a large medical center. Twenty-one cases occurred over that period; 20 cases were available for review. In six instances, the organism appeared to be clinically significant and was most commonly related to a vascular line infection. No deaths, secondary suppurative complications, prolonged bacteremia, or prolonged fever appeared to be caused by S. lugdunensis in our experience. Twenty-five percent of our isolates were resistant to multiple antibiotics, including oxacillin.

Adult↗
PubMed2003

Characterization of chicken CENP-A and comparative sequence analysis of vertebrate centromere-specific histone H3-like proteins.

Centromere protein A (CENP-A) is a centromere-specific histone H3 variant conserved amongst all eukaryotes. We have isolated the chicken gene for CENP-A (GgCENP-A). It encodes a 131-amino-acid polypeptide that possesses an average identity of 54% with human CENP-A, reaching 69% in the histone-fold domain. The gene spans 1.7 kb of genomic DNA and contains four exons that range in size from 78 to 186 bp. The exon/intron organisation of the chicken gene is conserved with its mammalian counterparts in the carboxy-terminal histone-fold domain (exons 2 to 4), consistent with the strong conservation of this domain at the amino acid level. Sequence analysis of the chicken CENP-A locus revealed that the gene is located within the class III genes of the major histocompatibility complex (MHC), and extended the previously defined limit of the compact chicken MHC complex. We compared the sequences of CENP-A from mammals, chicken and fishes and thereby identified conserved motifs in the otherwise variable amino-terminal tail that may be important for functional reasons. We also identified evolutionarily variable regions within the conserved histone-fold domain. We found that loop 1 between the first and second alpha-helix is the region that diverged most widely. This finding is in agreement with evolutionary studies in Drosophila species, and suggests that this domain could play a role in species-specific centromere targeting of CENP-A. In addition, protein sequence comparison of several vertebrate species revealed that the RT-PCR strategy we have developed for isolating the chicken centromeric histone H3 variant gene should be applicable to the isolation of CENP-A from a wide range of vertebrates.

Amino Acid Sequence↗
PubMed2003

New scaffolds in the development of mu opioid-receptor ligands.

A new class of mu selective receptor antagonists has been developed using a combinatorial approach based on previously reported Dmt-Tic dipeptide ligands. Modified tetrahydroisoquinoline (Tiq) residues were reacted with different electrophiles in order to create novel molecules that would mimic the original dipeptide. A specific class of thioureas bearing basic pyrrolidine residues were shown to give good binding affinities. Further alkylation of the pyrrolidine ring with benzyl derivatives also proved to increase the mu binding affinity. In addition, it was demonstrated that mu binding was enhanced by the presence of polar groups around the benzyl ring having hydrogen-bonding character (donor/acceptor). This new class of ligands represents a novel scaffold in the development of opioid analogues.

Binding, Competitive↗
PubMed2002

Supplementation with omega-3 polyunsaturated fatty acids in the management of recurrent migraines in adolescents.

PURPOSE: To examine whether dietary supplementation with fish oil rich in very long-chain n-3 polyunsaturated fatty acids might reduce frequency and severity of migraines in adolescents. METHODS: Twenty-seven adolescents suffering from frequent migraines for at least 1 year (mean 4 +/- 1 years since migraine onset) participated in a randomized, double-blind, cross-over study consisting of 2 months of fish oil, 1-month washout period, and 2 months of placebo (olive oil). Participants self-assessed severity and duration of headache episodes (7-point faces and 10-point visual analog pain scales, 5-point frequency and severity rating scale) throughout the study. At the end of every 2-month treatment period, participants rated the effectiveness of treatment on a 7-point Likert scale (1,"not effective, not worthwhile"; 4,"moderately effective, moderately worthwhile"; 7, "totally effective, totally worthwhile"). A score of > or = 4 on the Likert scale was considered as improvement. RESULTS: Twenty-three adolescents (16 girls, 7 boys, 18 Whites, 3 Hispanics, 1 African-American, 1 Cape Verdean, mean age 15 +/- 1 years) completed the study. Compared with frequency of headaches before the study (31 +/- 4 episodes/2 months), there was a significant (p <.0001) reduction in headache frequency during fish oil treatment (4 +/- 1 episodes/2 months) and during placebo (olive oil) treatment (4 +/- 1 episodes/2 months) but no significant (NS) difference between treatments. Likewise, self-assessment on a 7-point faces pain scale revealed a significant reduction in headache severity during fish oil treatment (2.9 +/- 0.5, p =.01) and during placebo (olive oil) treatment (3.5 +/- 0.4, <p =.03), compared with headache severity before study (5.0 +/- 0.3) and no significant difference between treatments. Patients' ratings of treatments revealed that 87% experienced reduction in headache frequency, 74% experienced reduction in headache duration, and 83% experienced reduction in headache severity during treatment with fish oil, compared with 78% who experienced reduction in headache frequency, 70% who experienced reduction in headache duration, and 65% who experienced reduction in headache severity during treatment with placebo (olive oil, NS). About 91% stated that they would recommend fish oil to friends or relatives with headaches vs. 91% who would recommend placebo (olive oil, NS). CONCLUSIONS: Patients experienced a similar reduction in frequency, duration, and severity of headaches during treatment with fish oil and during treatment with olive oil. Although there was no significant difference between treatments, the marked improvement from baseline experienced by the patients suggests that the effect should not be dismissed as simply a placebo effect. In fact, results of this preliminary study suggest that both fish oil and olive oil may be beneficial in the treatment of recurrent migraines in adolescents. Further studies are warranted to compare each of these treatments with other interventions.

Adolescent↗
PubMed2002

Functional magnetic stimulation facilitates gastric emptying.

OBJECTIVE: To evaluate the effect of functional magnetic stimulation (FMS) on gastric emptying in able-bodied and spinal cord injury (SCI) subjects. DESIGN: A prospective, nonrandomized clinical experiment. SETTING: SCI and disorder center in a Veterans Affairs medical facility. PARTICIPANTS: Five healthy, able-bodied subjects and 4 subjects with SCI. INTERVENTION: A commercially available magnetic stimulator was used; a round magnetic coil was placed along the T9 spinous process. The intensity of the magnetic stimulation was 60%, with a frequency of 20 Hz, and a burst length of 2 seconds for the gastric emptying protocol. Man Outcome Measures: Rate of gastric emptying and time required to reach gastric emptying half-time (GE(t1/2)) with and without FMS. Data fit into linear regression curve. RESULTS: Accelerated gastric emptying was achieved in both able-bodied and SCI subjects. The mean +/- standard error of mean of the GE(t1/2) at baseline and with FMS was 36+/-2.9 minutes and 33+/-3.1 minutes, respectively, for able-bodied subjects, and 84+/-11.1 minutes and 59+/-12.7 minutes, respectively, for SCI subjects. CONCLUSION: Gastric emptying was enhanced by FMS in able-bodied subjects and was greatly enhanced in SCI subjects. FMS can be a useful noninvasive therapeutic tool to facilitate gastric emptying in humans.

Adult↗
PubMed2002

Mycoplasma hominis scalp abscess in the newborn.

Scalp abscess in the newborn is usually a complication of fetal scalp monitoring and is typically polymicrobial, reflecting maternal vaginal flora. We present a newborn with no apparent scalp trauma who developed scalp abscess that yielded pure growth of Mycoplasma hominis. The clue to diagnosis was the growth of pinpoint translucent colonies on blood agar that were Gram stain-negative. Abscess drainage and systemic clindamycin were curative.

Abscess↗
PubMedDate not supplied

Vaginal flora morphotypic profiles and assessment of bacterial vaginosis in women at risk for HIV infection.

Specific morphotypic profiles of normal and abnormal vaginal flora, including bacterial vaginosis (BV), were characterized. A prospective study of 350 women yielded concurrent Gram-stain data and clinical assessment (n = 3455 visits). Microbiological profiles were constructed by Gram stain. Eight profile definitions were based on dichotomizing the levels of Lactobacillus, Gardnerella, and curved, Gram-negative bacillus (Mobiluncus) morphotypes. Of these, two were rare, and the other six demonstrated a graded association with the clinical components of BV. The proposed profiles from the Gram stain reflect the morphotypic categories describing vaginal flora that may enable clearer elucidation of gynecologic and obstetric outcomes in various populations.

Adolescent↗