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Biomedical subjects

A F Brown

Publications and source records attributed to A F Brown.

At least 19 recordsLinked to original sources

Rheological characterization of bioadhesive, antimicrobial, semisolids designed for the treatment of periodontal diseases: transient and dynamic viscoelastic and continuous shear analysis.

This study examined the creep behavior and oscillatory and flow properties of tetracycline-containing, bioadhesive semisolid formulations, designed for localized treatment of periodontal disease. Formulations were prepared containing hydroxyethylcellulose (HEC, 1, 3, or 5% w/w), poly(vinylpyrrolidone) (PVP, 2 or 3% w/w), polycarbophil (PC, 1 or 3% w/w), and tetracycline (5% w/w, as the hydrochloride). In creep analysis, each formulation exhibited several distinct regions that were mathematically modelled using a multi-element Voigt model with a residual spring and dashpot. Increasing the concentrations of each polymeric component decreased the elastic compliance (J(0)) yet increased the residual viscosity. In oscillatory analysis, increased polymer concentrations increased the storage modulus (G'), the loss modulus (G") and the dynamic viscosity (eta'), yet decreased the loss tangent (tan delta). The relationships between G' or G" and frequency were observed to plateau at higher frequencies, which is indicative of polymer chain entanglement and network formation. With the exception of formulations containing 1% HEC, the formulations were elastic (tan delta < 1), with large G' and small J(0) values. All formulations exhibited pseudoplastic flow with thixotropy. Increasing concentrations of each polymeric component increased the zero-shear viscosity (determined using the Cross model) and was further evidence of polymer chain entanglement. Formulations containing 1% w/w HEC possessed excellent flow properties, however, their thixotropic behavior and essentially elastoviscous nature (large J(0) and tan delta) would be disadvantageous for use in the treatment of periodontal disease because of rapid removal from the pocket and relatively uncontrolled drug release. Despite their advantageous viscoelastic properties, the flow properties of formulations containing 5% w/w HEC were inappropriate, rendering administration through a periodontal syringe potentially difficult. Based on their rheological behavior, formulations containing HEC (3% w/w), PVP (2 or 3% w/w), and PC (1 or 3% w/w) would be suitable for clinical application. However, consideration of other physicochemical properties (e.g., bioadhesion, drug release kinetics) must be performed prior to selection of the most suitable formulation for clinical examination. This study has highlighted the successful complimentary application of creep analysis and oscillatory and flow rheometry for the characterization and development of bioadhesive semisolid formulations for the treatment of periodontal disease.

Adhesives↗

Analysis of the study design and manuscript deficiencies in research articles submitted to Emergency Medicine.

OBJECTIVE: To describe and analyse the study design and manuscript deficiencies in original research articles submitted to Emergency Medicine. METHODS: This was a retrospective, analytical study. Articles were enrolled if the reports of the Section Editor and two reviewers were available. Data were extracted from these reports only. Outcome measures were the mean number and nature of the deficiencies and the mean reviewers' assessment score. RESULTS: Fifty-seven articles were evaluated (28 accepted for publication, 19 rejected, 10 pending revision). The mean (+/- SD) number of deficiencies was 18.1 +/- 6.9, 16.4 +/- 6.5 and 18.4 +/- 6.7 for all articles, articles accepted for publication and articles rejected, respectively (P = 0.31 between accepted and rejected articles). The mean assessment scores (0-10) were 5.5 +/- 1.5, 5.9 +/- 1.5 and 4.7 +/- 1.4 for all articles, articles accepted for publication and articles rejected, respectively. Accepted articles had a significantly higher assessment score than rejected articles (P = 0.006). For each group, there was a negative correlation between the number of deficiencies and the mean assessment score (P > 0.05). Significantly more rejected articles ' em leader did not further our knowledge' (P = 0.0014) and ' em leader did not describe background information adequately' (P = 0.049). Many rejected articles had ' em leader findings that were not clinically or socially significant' (P = 0.07). Common deficiencies among all articles included ambiguity of the methods (77%) and results (68%), conclusions not warranted by the data (72%), poor referencing (56%), inadequate study design description (51%), unclear tables (49%), an overly long discussion (49%), limitations of the study not described (51%), inadequate definition of terms (49%) and subject selection bias (40%). CONCLUSIONS: Researchers should undertake studies that are likely to further our knowledge and be clinically or socially significant. Deficiencies in manuscript preparation are more frequent than mistakes in study design and execution. Specific training or assistance in manuscript preparation is indicated.

Australia↗

Abdominal injury and the seat-belt sign.

OBJECTIVE: To report on: 1. Prevalence of seat-belt sign in motor vehicle accident victims with abdominal injuries; 2. Prevalence of intestinal injuries in patients with seat-belt sign; and 3. Spectrum of abdominal injuries in a population with high usage of three-point restraints. METHODS: A retrospective chart review was conducted in an adult tertiary-referral hospital from January 1992 to August 1998. Patients were identified from International Classification of Disease-9 codes for abdominal wall and intra-abdominal injuries. RESULTS: The seat-belt sign was present in 60/99. The proportion of intestinal injuries in patients with and without seat-belt sign were 9/60 and 0/39, respectively (P = 0.01). In the 25 patients with intra-abdominal injuries, there were 10 hepatic, 8 splenic, 9 intestinal and 4 retroperitoneal injuries. CONCLUSION: The seat-belt sign is indicative of an increased risk of intestinal injury, which is difficult to detect with no single test providing reliable diagnosis. Other intra-abdominal and retroperitoneal injuries may also occur, which are more readily diagnosed on computed tomography scan or focused abdominal utlrasound when available, but are no more frequent in patients with the seat-belt sign than those without.

Abdominal Injuries↗

Emergency department anaphylaxis: A review of 142 patients in a single year.

BACKGROUND: There are few data on the incidence, clinical features, and management of patients with acute anaphylaxis presenting to the emergency department. We investigated all presentations to one department during the course of a year to improve current awareness of this medical emergency. OBJECTIVE: The purpose of the study was to describe the clinical features, management, and outcome of anaphylaxis presentations to a single Australian adult emergency department in a single year, 1998-1999. METHODS: This was a retrospective, case-based study of adult patients (>or=13 years of age) attending a single emergency department in Brisbane, Australia, during the year 1998-1999. The medical records of 304 patients satisfying the relevant discharge diagnostic codes were studied. We determined incidence, sex ratio, age, clinical features, management, disposal, asthma prevalence, and causes in patients presenting with acute allergic reactions and anaphylaxis. RESULTS: In all, 162 emergency department patients with acute allergic reactions and 142 emergency department patients with anaphylaxis, including 60 whose anaphylaxis was severe, were seen during the year, for an anaphylaxis presentation incidence of 1 in 439. One patient died; this gave a case fatality rate of 0.70%. Cutaneous features were present in 94% of the patients with anaphylaxis. Of those with severe anaphylaxis, 35% had dizziness/syncope before hospital presentation, 25% laryngeal edema, and 21.7% systolic hypotension on hospital presentation. A cause was recognized in 73% of the anaphylaxis cases; most commonly, the causative agent was a drug, insect venom, or food. Adrenaline was used in 57% of the severe cases before hospital presentation or in the hospital. The emergency department alone definitively cared for 94% of all patients, though only 43% severe anaphylaxis cases were referred for follow-up. CONCLUSION: The emergency department anaphylaxis presentation incidence of 1 in 439 cases is greater than previously recognized, though death remains rare. In three fourths of cases, a precipitant was identified, a fact that emphasizes the need for a detailed initial history. Definitive management in the emergency department alone is possible in most cases, provided that the appropriate use of adrenaline and the need for allergy clinic follow-up are appreciated.

Adolescent↗

Ciguatera poisoning: a global issue with common management problems.

Ciguatera poisoning, a toxinological syndrome comprising an enigmatic mixture of gastrointestinal, neurocutaneous and constitutional symptoms, is a common food-borne illness related to contaminated fish consumption. As many as 50000 cases worldwide are reported annually, and the condition is endemic in tropical and subtropical regions of the Pacific Basin, Indian Ocean and Caribbean. Isolated outbreaks occur sporadically but with increasing frequency in temperate areas such as Europe and North America. Increase in travel between temperate countries and endemic areas and importation of susceptible fish has led to its encroachment into regions of the world where ciguatera has previously been rarely encountered. In the developed world, ciguatera poses a public health threat due to delayed or missed diagnosis. Ciguatera is frequently encountered in Australia. Sporadic cases are often misdiagnosed or not medically attended to, leading to persistent or recurrent debilitating symptoms lasting months to years. Without treatment, distinctive neurologic symptoms persist, occasionally being mistaken for multiple sclerosis. Constitutional symptoms may be misdiagnosed as chronic fatigue syndrome. A common source outbreak is easier to recognize and therefore notify to public health organizations. We present a case series of four adult tourists who developed ciguatera poisoning after consuming contaminated fish in Vanuatu. All responded well to intravenous mannitol. This is in contrast to a fifth patient who developed symptoms suggestive of ciguatoxicity in the same week as the index cases but actually had staphylococcal endocarditis with bacteraemia. In addition to a lack of response to mannitol, clinical and laboratory indices of sepsis were present in this patient. Apart from ciguatera, acute gastroenteritis followed by neurological symptoms may be due to paralytic or neurotoxic shellfish poisoning, scombroid and pufferfish toxicity, botulism, enterovirus 71, toxidromes and bacteraemia. Clinical aspects of ciguatera toxicity, its pathophysiology, diagnostic difficulties and epidemiology are discussed.

Adult↗

Gene flow versus local adaptation in the northern acorn barnacle, Semibalanus balanoides: insights from mitochondrial DNA variation.

In reciprocal transplant experiments, Bertness and Gaines (1993) found that Semibalanus balanoides juveniles that had settled in an upper Narragansett Bay estuary survived better in that estuary that did juveniles from coastal localities. The observed pattern of survivorship led to the claim that local adaptation may result from a combination of limited gene flow between and strong selection within these habitats. Here we test the hypothesis that limited gene flow has led to habitat-specific population differentiation using sequence and restriction fragment length polymorphism analyses of the mitochondrial DNA D-loop region of S. balanoides. Samples were analyzed from replicated coastal and estuary localities in both Narragansett Bay, Rhode Island, and Damariscotta River, Maine. The patterns of F(ST) indicate that gene flow between coast and estuary is extensive (Nm > 100) and is not lower in the estuary with lower flushing rates (Narragansett Bay). Given the high estimate of genetic exchange, adaptations for unpredictable environments seem more likely than local adaptation in this species because loci that respond to selection in one generation are essentially homogenized by the next seasons' settlement. Nevertheless, these estimates of neutral gene flow can help identify the strength of selection necessary for local adaptation to accumulate in Semibalanus.

Animals↗

Design, characterisation and preliminary clinical evaluation of a novel mucoadhesive topical formulation containing tetracycline for the treatment of periodontal disease.

This study describes the formulation, characterisation and preliminary clinical evaluation of mucoadhesive, semi-solid formulations containing hydroxyethylcellulose (HEC, 1-5%, w/w), polyvinylpyrrolidine (PVP, 2 or 3%, w/w), polycarbophil (PC, 1 or 3%, w/w) and tetracycline (5%, w/w, as the hydrochloride). Each formulation was characterised in terms of drug release, hardness, compressibility, adhesiveness (using a texture analyser in texture profile analysis mode), syringeability (using a texture analyser in compression mode) and adhesion to a mucin disc (measured as a detachment force using the texture analyser in tensile mode). The release exponent for the formulations ranged from 0.78+/-0.02 to 1. 27+/-0.07, indicating that drug release was non-diffusion controlled. Increasing the concentrations of each polymeric component significantly increased the time required for 10 and 30% release of the original mass of tetracycline, due to both increased viscosity and, additionally, the unique swelling properties of the formulations. Increasing concentrations of each polymeric component also increased the hardness, compressibility, adhesiveness, syringeability and mucoadhesion of the formulations. The effects on product hardness, compressibility and syringeability may be due to increased product viscosity and, hence, increased resistance to compression. Similarly, the effects of these polymers on adhesiveness/mucoadhesion highlight their mucoadhesive nature and, importantly, the effects of polymer state (particularly PC) on these properties. Thus, in formulations where the neutralisation of PC was maximally suppressed, adhesiveness and mucoadhesion were also maximal. Interestingly, statistical interactions were primarily observed between the effects of HEC and PC on drug release, mechanical and mucoadhesive properties. These were explained by the effects of HEC on the physical state of PC, namely swollen or unswollen. In the preliminary clinical evaluation, a formulation was selected that offered an appropriate balance of the above physical properties and contained 3% HEC, 3% PVP and 1% PC, in addition to tetracycline 5% (as the hydrochloride). The clinical efficacy of this (test) formulation was compared to an identical tetracycline-devoid (control) formulation in nine periodontal pockets (>/=5 mm depth). One week following administration of the test formulation, there was a significant improvement in periodontal health as identified by reduced numbers of sub-gingival microbial pathogens. Therefore, it can be concluded that, when used in combination with mechanical plaque removal, the tetracycline-containing semi-solid systems described in this study would augment such therapy by enhancing the removal of pathogens, thus improving periodontal health.

Acrylic Resins↗

MuStaR and other software for locus-specific mutation databases.

As the human genome sequencing project nears completion, there has been a vast increase in the rate at which disease and nondisease associated variant sequences are being sought and detected. This has heightened the need for software with which to accumulate allelic variant (mutation) data, and with which to make the data accessible to the scientific community. Many ad hoc solutions have been developed by those interested in specific genes and diseases, and the creation of central databases which hold data for all genes has provided an alternative repository for some of the locus data. Despite this, few specialised software tools exist for researchers to create their own locus-specific allelic variant databases. This article describes methods available to potential curators, including software systems developed with the sole purpose of generating locus-specific mutation databases. In particular, the authors' own software, MuStaRtrade mark, is described. MuStaRtrade mark allows curators to maintain a database on a laptop computer if desired, while being able to export the data to an automatically generated Website which will run on any cgi compliant Web server. Searching the database and the submission of new mutations are made possible through fill-in Web forms. A number of other software tools which may be of use to curators are also described.

Chromosome Mapping↗

Examination of the physical state of chlorhexidine within viscoelastic, bioadhesive semisolids using raman spectroscopy.

This study examined the effects of polymeric components on the physical state of chlorhexidine within bioadhesive, semisolid formulations using Raman spectroscopy. Semisolid formulations were prepared in which chlorhexidine base (CHX, 5%w/w, particle size <63 microm) was dispersed in aqueous (phosphate-buffered saline, pH 6.8) polymer matrices consisting of one or more polymeric components, namely HEC (3%w/w), PVP (3%), and PC (PC, 3%). Raman spectra were recorded using 785-nm excitation and were typically accumulated for 360 s. The Raman spectra were dominated by the presence of CHX. The spectra of CHX in HEC and in HEC/PVP gels were indistinguishable from that for solid CHX as a result of the insolubility of CHX in these formulations. However, in systems containing PC and CHX, there was a shift in the strongest band from 1564 cm(-1) to 1608 cm(-1), which may be accredited to protonation of the basic CHX by the numerous carboxylic acidic groups on PC. Identical shifts in the band positions were observed when this protonation was modeled using ethanoic acid, supporting the view that there was a simple acid base reaction between PC and CHX. However, there were notable differences in the relative intensities of the peaks from these samples, with the spectrum of CHX in the PC matrix displaying properties intermediate between those of CHX dissolved in ethanoic acid and solid CHX diacetate. This may be accredited to the limited solubility of the CHX-PC ion pair. In matrices containing HEC and PC, no peak was observed at 1564 cm(-1), whereas the intensity of the peak at 1608 cm(-1) was increased. Therefore, in these formulations CHX was completely converted to the di-cation as a result of the synergistic effects of PC (which protonated CHX) and HEC (which solubilized the di-cation). In the absence of either HEC or PC, complete protonation was not achieved. It is suggested that this enhancement of solubility of H(2)CHX(2+) may be due to hydrogen bonding, given the hydroxylated nature of HEC. In conclusion, this study has shown the applicability of Raman spectroscopy for both the analysis of opaque, semisolid formulations and, additionally, for the examination of the state of therapeutic agents within such matrices. In particular, using Raman spectroscopy, it was uniquely possible to identify the roles of various polymeric components on both the ionization and solubilization of CHX within aqueous semisolid systems.

Chemistry, Pharmaceutical↗

Variation of glucosinolates in vegetable crops of Brassica oleracea.

Glucosinolates were evaluated in 5 groups and 65 accessions of Brassica oleracea (50 broccoli, 4 Brussels sprouts, 6 cabbage, 3 cauliflower, and 2 kale) grown under uniform cultural conditions. Glucosinolates and their concentrations varied among the different groups and within each group. The predominant glucosinolates in broccoli were 4-methylsulfinylbutyl glucosinolate (glucoraphanin), 3-butenyl glucosinolate (gluconapin), and 3-indolylmethyl glucosinoate (glucobrassicin). Glucoraphanin concentration in broccoli ranged from 0.8 micromol g(-1) DW in EV6-1 to 21.7 micromol g(-1) DW in Brigadier. Concentrations of the other glucosinolates in broccoli varied similarly over a wide range. In Brussels sprouts, cabbage, cauliflower, and kale, the predominant glucosinolates were sinigrin (8.9, 7.8, 9.3, and 10.4 micromol g(-1) DW, respectively) and glucobrassicin (3.2, 0.9, 1.3, and 1.2 micromol g(-1) DW, respectively). Brussels sprouts also had significant amounts of gluconapin (6.9 micromol g(-1) DW). Wide variations in glucosinolate content among genotypes suggest differences in their health-promoting properties and the opportunity for enhancement of their levels through genetic manipulation.

Brassica↗

Ethnic differences in hormone replacement prescribing patterns.

OBJECTIVE: To determine whether prescription patterns of hormone replacement therapy (HRT) differ in African-American, Asian, Latina, Soviet immigrant, and white women. DESIGN: Retrospective review of computerized medical records. SETTING: The general internal medicine, family medicine, and gynecology practices of an academic medical center. PATIENTS: Women aged 50 years or older with at least one outpatient visit from January 1, 1992, to November 30, 1995. MEASUREMENTS AND MAIN RESULTS: Use of HRT was defined as documentation of systemic estrogen use. The main predictor variable was self-identified ethnicity. Age, diagnosis (coronary heart disease, hypertension, diabetes, osteoporosis, or breast cancer), and median income were included in the analysis. Of the 8,968 women (mean age, 65.4 years) included, 50% were white, 20% Asian, 15% African American, 9% Latina, and 6% Soviet immigrants. Whites (33%) were significantly more likely to be prescribed HRT than Asians (21%), African Americans (25%), Latinas (23%), or Soviet immigrants (6.6%), p < 0.01 for each. Multivariate analysis, comparing ethnic groups and controlling for confounding variables, showed that Asians (odds ratio [OR] 0.56; 95% confidence interval [CI] 0.49, 0.64), African Americans (OR 0.70; 95% CI 0.60, 0.81), Latinas (OR 0.70; 95% CI 0.58, 0.84), and Soviet immigrants (OR 0.14; 95% CI 0.10, 0. 20) were each less likely to be prescribed HRT than were white women. Although women with osteoporosis were more likely to receive HRT (OR 2.28; 95% CI 1.71, 2.99), those with coronary heart disease were not (OR 0.88; 95% CI 0.68, 1.09). CONCLUSIONS: Physicians at this medical center were more likely to prescribe HRT for white women and women with osteoporosis. Further study is needed to address whether these differences in HRT prescribing result in different health outcomes.

Aged↗

Hormone replacement therapy for African American women: missed opportunities for effective intervention.

OBJECTIVES: Because of the potential benefits and risks of hormone replacement therapy (HRT), information about the efficacy of HRT in different groups of women is important to patients and providers. The objectives of this study were to review the evidence on the benefits and risks of HRT in African American women and to present a quantitative analysis of the potential reduction in mortality from osteoporotic fractures and coronary heart disease and the potential increase in risk of breast and endometrial cancer. METHODS: A MEDLINE search of English-language observational studies and clinical trials on the effects of HRT on osteoporotic fractures and coronary heart disease (CHD) was conducted for the time period from 1966 to September 1998. Using available CHD mortality data for African American women and white women, potential reductions in mortality with HRT were explored for African American and white women. RESULTS: In the 30 studies on CHD and HRT, African American women were known to comprise only 173 (0.1%) of 148,437 participants. In 11 studies of HRT and osteoporotic fractures, only 128 (0.4%) of 40,299 participants were known to be African American women. An analysis of CHD mortality by decade intervals indicated that African American women, aged 55 to 64, are more likely to die from CHD each year than white women. Despite a lower incidence of breast and endometrial cancer among African American women, the mortality rates of African American women with these cancers is higher compared with white women. CONCLUSIONS: With the higher underlying CHD mortality rate among African American women, HRT is an important potential preventive therapy. The absence of African American women and other non-white women from clinical studies of HRT makes it difficult to fully assess the risks and benefits of HRT in this group of women.

Black or African American↗

Viscoelastic properties of bioadhesive, chlorhexidine-containing semi-solids for topical application to the oropharynx.

PURPOSE: This study examined the viscoelastic properties of bioadhesive, chlorhexidine-containing semi-solid formulations, designed for topical application to the oropharynx. METHODS: Oscillatory rheometry was performed using a Carri-Med CSL2-100 rheometer at 20.0 +/- 0.1 degrees C in conjunction with parallel plate geometry (2 cm diameter, 0.5 mm sample thickness). Samples were subjected to a constant strain (6.5 x 10(-3) rad) and defined viscoelastic parameters, namely storage modulus (G'), loss modulus (G"), loss tangent (tan delta) and dynamic viscosity (eta'), measured over a defined frequency range (0.01-1.0 Hz). RESULTS: As the oscillatory frequency was increased, G' G" of all formulations increased, whereas both eta' and tan delta significantly decreased. The magnitude of increase of G' and G" as a function of frequency was relatively small, indicating that, in general, the formulations were non-cross-linked elastic systems. Increasing concentrations of HEC, PVP and PC significantly increased G', G", eta' yet decreased tan delta, observations that may be attributed to the physical state of each polymer in the formulations. Formulation elasticity increased (i.e. tan delta decreased) as a result of increased entanglement of polymeric chains of dissolved components (i.e. HEC and PVP) and the restrained extension of swollen, cross-linked chains of PC. Additionally, in formulations where the saturation solubility of PVP was exceeded and/or insufficient "free-water" was available for maximal swelling of PC, formulation elasticity increased as a result of the increasing mass of dispersed solid particles of PVP and/or PC. Formulation eta' increased due to the attendant effects of polymer chain entanglement and polymer state on overall formulation viscosity. CONCLUSIONS: Following application to the oropharynx, the formulations will behave as elastic systems. Thus, these formulations would be expected to offer advantageous clinical properties, e.g., prolonged drug release, increased bioadhesion. However, it is noteworthy that the final choice of formulation for clinical evaluation will involve a compromise between viscoelastic characteristics and acceptable textural properties, e.g. ease of product application. This study has shown the applicability of oscillatory rheometry for both the characterisation and selection of candidate, topical bioadhesive formulations for clinical evaluation.

Acrylic Resins↗

Ciguatera poisoning: an example of a public health challenge.

Ciguatera is a common form of fish poisoning, endemic in all nations of the Pacific region. Several thousand cases have been notified to Queensland authorities over a 10-year period. However, many cases remain undiagnosed and most go unreported. The public health implications include raising awareness of the condition, ensuring that ciguatera is considered in differential diagnosis and promoting better documentation and reporting.

Adult↗

Tick bite anaphylaxis in Australia.

Tick bite anaphylaxis has rarely been reported. It may follow the bite of any of the different tick life cycle forms, is related to the release of salivary juices, and may range from mild itch to severe wheeze or shock. Data obtained suggest that it is more common and potentially life threatening than tick paralysis, which is more widely reported. Emergency physicians should recognise this possibility following a tick bite and be prepared to give treatment such as adrenaline rapidly. Patients should be referred to an allergist after recovery.

Adolescent↗