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Biomedical subjects

A Allen

Publications and source records attributed to A Allen.

At least 19 recordsLinked to original sources
PubMed2006

Enhanced cyclooxygenase-2 expression in olfactory-limbic forebrain following kainate-induced seizures.

Cyclooxygenase-2 is expressed at low levels in a subset of neurons in CNS and is rapidly induced by a multiplicity of factors including seizure activity. A putative relationship exists between cyclooxygenase-2 induction and glutamatergic neurotransmission. Cyclooxygenase-1 is constitutively expressed in glial cells and has been specifically linked to microglia. In this study we evaluated cyclooxygenase-2 protein immunocytochemically and found markedly enhanced immunostaining primarily in olfactory-limbic regions at 2, 6 and 24 h following kainate-induced status epilepticus. Impressive enhanced cyclooxygenase-2 immunoreactivity was localized in anterior olfactory nucleus, tenia tecta, nucleus of the lateral olfactory tract, piriform cortex, lateral and basolateral amygdala, orbital frontal cortex, nucleus accumbens (shell) and associated areas of ventral striatum, entorhinal cortex, dentate gyrus granule cells and hilar neurons, hippocampal CA subfields and subiculum. Alternate sections were processed for dual immunocytochemical analysis utilizing c-Fos and cyclooxygenase-2 antiserum to examine the possibility that the neuronal induction of cyclooxygenase-2 was associated with seizure activity. Neurons that showed a timeline of cyclooxygenase-2 upregulation were found to possess c-Fos immunopositive nuclei. Additional results from all seizure groups showed cyclooxygenase-1 induction in microglia, which was confirmed by Western blot analysis of hippocampus. Western blot and real-time quantitative RT-PCR analysis showed significant upregulation of cyclooxygenase-2 expression, confirming its induction in neurons. These data indicate that cyclooxygenase-2 induction in a neuronal network can be a useful marker for pathways associated with seizure activity.

Animals↗
PubMed2005

Alginate as a source of dietary fiber.

Alginate, an algal polysaccharide, is widely used in the food industry as a stabilizer, or as a thickening or emulsifying agent. As an indigestible polysaccharide, alginate may also be viewed as a source of dietary fiber. Previous work has suggested that dietary fibres may protect against the onset and continuation of a number of cardiovascular and gastrointestinal diseases. This article aims to examine what is currently understood about the fiber-like activities of alginate, particularly its effects on intestinal absorption and the colon, and therefore aims to gauge the potential use of alginate as a dietary supplement for the maintenance of normal health, or the alleviation of certain cardiovascular or gastrointestinal diseases.

Alginates↗
PubMed2004

Factors associated with abnormal Pap results in systemic lupus erythematosus.

OBJECTIVE: Previous studies have suggested that women with systemic lupus erythematosus (SLE) are at greater risk for cervical dysplasia than are women in the general population. However, the factors associated with abnormal Pap test results in SLE have not been well studied. We therefore aimed to determine the factors associated with lifetime occurrence of an abnormal Pap test in women with SLE, and the influence of immunosuppressive exposure on the odds of abnormal Pap test results occurring after diagnosis of SLE. METHODS: Data were pooled from SLE cohorts from three centres. Self-report data were available on smoking, reproductive history, use of oral contraceptives (OC), history of sexually transmitted diseases (STDs) and whether the subjects had had cervical dysplasia on Pap testing. Logistic regression was used to examine the effect of these variables on the lifetime odds of cervical dysplasia. We then generated the adjusted odds ratio (OR) for the effect of immunosuppressive exposure on cervical dysplasia occurring after diagnosis of SLE. RESULTS: History of STDs and use of OCs were positively associated with reports of cervical dysplasia in adjusted analyses. The ORs for the effect of immunosuppressives on abnormal Pap test occurrence (adjusted for race, age, smoking, nulliparity, OC use and history of STDs) after diagnosis of SLE was 1.6 (95% CI 1.0, 2.7). CONCLUSIONS: A history of STDs and use of OCs were associated with abnormal Pap reports in this SLE sample. Immunosuppressive exposure may confer further risk to women with SLE.

Adult↗
PubMed2004

Hormonal exposures and breast cancer in a sample of women with systemic lupus erythematosus.

OBJECTIVES: To determine if breast cancer risk in women with SLE is modified by a history of exposure to hormone replacement therapy (HRT) or oral contraceptives (OC), after adjusting for other risk factors. METHODS: Data were pooled from SLE cohorts at three centres. For each female cohort member (n = 871), the probability of developing breast cancer was estimated from factors (age, parity, age at first live birth, age of menarche, personal history of benign breast disease, family history) in the Gail model, an established tool for predicting breast cancer risk. From these probabilities, the expected number of breast cancers for the cohort was estimated. Actual occurrence of cases was determined by linkage with regional cancer registries. Standardized incidence ratios (SIRs; ratio of cancers observed to expected) were calculated, with subgroup analyses according to HRT and OC exposure. RESULTS: In the cohort, 15 breast cancers occurred vs 7.2 predicted [SIR 2.1, 95% confidence interval (CI) 1.1, 3.5]. When controlling for Gail model risk factors, estimates were similar for women never exposed to HRT vs those exposed to HRT. Adjusted SIR estimates appeared similar also for women exposed or not exposed to OC. CONCLUSIONS: Although not definitive, the data suggest that the breast cancer experience in this sample is not completely explained by factors such as reproductive and family history, or by exogenous hormonal exposures. Other determinants, including medication exposures or genetic factors (possibly related to oestrogen receptors or metabolism) may be important. Variations in these factors might explain why an elevated risk of breast cancer has not been apparent in all SLE populations.

Adult↗
PubMed2004

The toll-like receptor 4 Asp299Gly variant: no influence on LPS responsiveness or susceptibility to pulmonary tuberculosis in The Gambia.

SETTING: Tuberculosis (TB) remains a major cause of morbidity and mortality worldwide. Studies in a murine model of pulmonary TB have identified a role for Toll-like receptor 4 (TLR4) in the development of chronic lung infection with Mycobacterium tuberculosis. The Asp299Gly polymorphism in the human TLR4 gene is associated with in vivo hyporesponsiveness to lipopolysaccharide (LPS) in Caucasians. OBJECTIVE: To determine whether TLR4 Asp299Gly influences LPS responses or susceptibility to pulmonary TB in humans in a Gambian population sample. DESIGN: We compared whole blood monokine responses to LPS in 245 healthy blood donors stratified by TLR4 Asp299Gly genotype to assess whether this polymorphism was functional in this population. A case-control study of 640 subjects was conducted to investigate whether TLR4 Asp299Gly was associated with TB. RESULTS: LPS-induced tumour necrosis factor, interleukin-1 beta and interleukin-10 production was not influenced by TLR4 Asp299Gly genotype. There was no association between TLR4 Asp299Gly and TB. CONCLUSION: Our data suggest that TLR4 Asp299Gly has no influence on monocyte LPS responses or susceptibility to TB in Gambians and could be an ancient neutral polymorphism.

Adolescent↗
PubMed2004

The diurnal profile of gastric pepsin activity is reduced with Helicobacter pylori infection.

Both Helicobacter pylori and pepsin are proven mucosal damaging agents and implicated in the aetiology of peptic ulcer disease. Historically studies of pepsin over time have proved methodologically difficult, and as a result little work has been done on the effect of H. pylori on luminal pepsin secretion. Our objectives were to determine pepsin activity over 24 hr in normal human subjects and to examine luminal pepsin activity in relation to H. pylori infection. Twenty-seven healthy volunteers had gastric juice samples aspirated every 2 hr for 24 hr. All subjects had H. pylori status determined by C13 urea breath test and serology. Meals were standardized throughout the study period. Gastric juice samples were measured for pH, diluted, and frozen in acetate buffer pH 4.1 for up to 1 month, conditions shown to cause no loss of activity. Individual samples were measured for pepsin activity by assaying for new N-terminal peptide formation. Mean pepsin activity (microg enzyme/ml) in 21 normal H. pylori-negative subjects ranged from 114 to 1030 microg/ml, with a characteristic diurnal profile of increasing activity to maximum after the evening meal. Mean pepsin activity in subjects with H. pylori was consistently below that for age-matched H. pylori-negative subjects at each time point. Overall mean pepsin activity was significantly lower in those with H. pylori compared to those without (P < 0.001). There is significant pepsin activity in the stomach throughout the 24-hr period, with a trend for the highest activity through the night. Subjects with H. pylori infection have lower luminal pepsin activity.

Adolescent↗
PubMed2004

Parental concern and distress about infant pain.

OBJECTIVE: To describe parent views on infant pain care and to explore relations between parents' experience of their infant's pain care and parental stress. DESIGN: Descriptive, cross sectional survey. SETTING: Nine neonatal units (196 parents) in the United Kingdom and two neonatal units in the United States (61 parents). PARTICIPANTS: Parents of preterm and full term infants admitted to hospital. INTERVENTIONS: Parents completed a three part questionnaire after the second day of the infant's admission and after they had made at least one previous visit to see their infant in the neonatal unit. MAIN OUTCOME MEASURES: Parent concerns about infant pain; parental stress; parent state and trait anxiety. RESULTS: Parents reported that their infants had experienced moderate to severe pain that was greater than they had expected (p < 0.001). Few parents (4%) received written information, although 58% reported that they received verbal information about infant pain or pain management. Only 18% of parents reported that they were shown signs of infant pain, but 55% were shown how to comfort their infant. Parents had numerous worries about pain and pain treatments. Parental stress was independently predicted by parents' estimation of their infant's worst pain, worries about pain and its treatment, and dissatisfaction with pain information received, after controlling for state anxiety and satisfaction with overall care (F = 29.56, df 6, p < 0.001, R(2) = 0.44). The findings were similar across sites, despite differences in infant characteristics. CONCLUSIONS: Parents have unmet information needs about infant pain and wish greater involvement in their infant's pain care. Parent concerns about infant pain may contribute to parental stress.

Anxiety↗
PubMed2003

Effect of calcium carbonate on bioavailability of orally administered gemifloxacin.

We investigated the effect of calcium carbonate on the oral bioavailability of gemifloxacin. Gemifloxacin was administered alone, 2 h before, simultaneously, or 2 h after calcium carbonate in 16 volunteers. Data for 320 mg of gemifloxacin alone were as follows: maximum concentration of drug in serum (C(max)),13 microg/ml; half-life, 7.33 h; and area under the concentration-time curve from 0 h to infinity (AUC( infinity )), 6.79 microg. h/ml. Only simultaneous coadministration of calcium carbonate reduced C(max) (-17%) and AUC( infinity ) (-21%) significantly.

Administration, Oral↗
PubMed2002

Attitudes towards and beliefs about schizophrenia in Xhosa families with affected probands.

OBJECTIVE: The development of effective psychoeducational programs for the management of schizophrenia requires an understanding of attitudes towards and beliefs about the disorder in families of affected probands. In order to establish the need for adaptation of Western psychoeducational programs, these variables were investigated in Xhosa speaking families in South Africa. DESIGN: Xhosa speaking family members of patients with DSM-IV schizophrenia were recruited on a voluntary basis, and interviewed with a structured belief and attitudes questionnaire adapted from previous studies in the West. SETTING: The study population was drawn from both urban and rural Xhosa communities in South Africa. SUBJECTS: 100 Xhosa speaking family members participated in the study. RESULTS: Family members most often recommended treatment with psychotropic medications (88%) and traditional healers (32%), and least often recommended psychotherapy (4%) and meditation (1%). Of the respondents who recommended traditional healing methods, 92% also recommended simultaneous use of allopathic treatment. CONCLUSION: Attitudes towards and beliefs about schizophrenia in family members of patients with schizophrenia may differ substantially from those described in previous work in the West. An understanding of local attitudes and beliefs is crucial for the successful development of local psychoeducational programs.

Adult↗
PubMed2001

Anomalous elastic response of silicon to uniaxial shock compression on nanosecond time scales.

We have used x-ray diffraction with subnanosecond temporal resolution to measure the lattice parameters of orthogonal planes in shock compressed single crystals of silicon (Si) and copper (Cu). Despite uniaxial compression along the (400) direction of Si reducing the lattice spacing by nearly 11%, no observable changes occur in planes with normals orthogonal to the shock propagation direction. In contrast, shocked Cu shows prompt hydrostaticlike compression. These results are consistent with simple estimates of plastic strain rates based on dislocation velocity data.

Journal Article↗
PubMed2001

The clinical pharmacokinetics of a new pharmacokinetically enhanced formulation of amoxicillin/clavulanate.

BACKGROUND: A new oral pharmacokinetically enhanced formulation of the broad-spectrum antibiotic amoxicillin/clavulanate has been developed to provide more effective therapy against resistant pathogens than is provided by currently available formulations by maintaining therapeutically useful plasma amoxicillin concentrations for a longer period after dosing. OBJECTIVE: This study explored the pharmacokinetics of the new oral formulation of amoxicillin/clavulanate in healthy male and female subjects. METHODS: A single oral dose of pharmacokinetically enhanced amoxicillin/clavulanate (2000/125 mg; 16:1 ratio) was administered to subjects at the start of a meal. After dosing, blood samples were collected at frequent intervals up to 12 hours, and plasma was assayed for amoxicillin and clavulanate concentrations using validated procedures. The new formulation consisted of 1 layer of immediate-release amoxicillin and clavulanate and another of sustained-release amoxicillin in a proportion such that for an amoxicillin minimum inhibitory concentration (MIC) of 4 microg/mL, the time above the MIC (T >MIC) would be approximately > or = 40% over a 12-hour dosing interval. RESULTS: The study enrolled 24 and 31 healthy male and female subjects, respectively. Their mean age was 35 years (range, 18-58 years) and mean body weight was 69 kg (range, 51-86 kg). After the expected sharp peak in plasma amoxicillin concentration, there appeared to be a slower decline with the pharmacokinetically enhanced formulation than is usually seen with conventional formulations, and there was evidence of a second amoxicillin absorption phase. The mean T >MIC for an amoxicillin MIC of 4 microg/mL was 49.4% of a 12-hour dosing interval, a value that cannot be achieved with existing approved doses and formulations of amoxicillin/clavulanate. By 12 hours, plasma amoxicillin concentrations were very low (approximately 0.05 microg/mL), suggesting no expectation of notable dose-to-dose accumulation on repeat dosing with a BID regimen. The terminal half-lives of amoxicillin (1.27 hours) and clavulanate (1.03 hours) with the new formulation were similar to those of existing formulations of amoxicillin/clavulanate. No deaths or serious adverse events were reported. CONCLUSIONS: The enhanced pharmacokinetic profile of amoxicillin/clavulanate seen in this study suggests that this formulation is likely to be highly effective for the oral treatment of infections caused by bacteria--including beta-lactamase-producing organisms--and strains with amoxicillin MICs < or = 4 microg/mL.

Adolescent↗
PubMed2001

MUC1 expression in primary breast cancer: the effect of tamoxifen treatment.

This was a non-randomised single institution retrospective study. Forty-six banked frozen tumour specimens were obtained from a group of patients who had undergone 3 weeks of neoadjuvant treatment with tamoxifen between biopsy and surgery. Fifty-one comparison specimens were randomly selected from a group of concomitantly treated primary breast cancer patients who did not receive neoadjuvant tamoxifen. Specimen selection was not based on prognostic factors: hormone receptor status, patient age, or menopausal status. MUC1 expression and cell cycle distribution were assessed by flow cytometry. S-phase fraction of MUC1 positive and MUC1 negative cells were compared. A lower percentage of cells expressed MUC1 following 3-week tamoxifen treatment 18.2% versus 28.5% (p = 0.03, Mann-Whitney) and lower levels of MUC1 expression were seen following tamoxifen treatment 31,519 molecules/cell versus 39,387 (p = 0.04, Mann-Whitney). MUC1 positive cells, irrespective of treatment group, had a greater proportion of cells in S-phase of the cell cycle 27.9% versus 16.8% (p = 0.0004, Mann-Whitney) and demonstrated more cases of aneuploidy 80.65% versus 42.6% (p < 0.0001). MUC1 levels in primary tumours treated neoadjunctively with 3 weeks of tamoxifen were lower than a comparison group which did not receive tamoxifen. MUC1 should be explored further as an intermediate biomarker for assessment of treatment and prognosis.

Aged↗
PubMed2001

Emergency preparation in schools: a snapshot of a rural state.

OBJECTIVE: To study emergency preparedness in public schools in a rural state. METHOD: Questionnaires were mailed to school nurses registered with the State Department of Education. Data collected included school nurse and staff training, school location, emergency equipment available, and Emergency Medical Service (EMS) access. RESULTS: Seventy-two percent of the surveys were returned after one or two mailings. They report little emergency training for both school nurses and school staff. Emergency equipment available varies widely: oxygen 20%, artificial airways 30%, cervical collars 22%, splints 69%. Equipment was more likely to be available in communities with populations of less than 200,000. Sixty-seven percent of schools activate EMS for a student and 37% for an adult annually. Eighty-four percent of schools have a less than 10-minute EMS response time. CONCLUSIONS: EMS activation to schools is a common occurrence. Schools are ill prepared to care for this acuity of student or staff as assessed by equipment and emergency training. Schools in smaller communities, however, are better prepared for emergencies.

Child↗
PubMed2001

The Detroit Community-Academic Urban Research Center: development, implementation, and evaluation.

There is increasing research evidence that stressors in the social and physical environment (e.g., poverty, inadequate housing, air pollution, and racism) are associated with poor health outcomes. Given the complex set of determinants of health status, the disproportionate burden of disease experienced within marginalized communities, and the limited effectiveness of traditional prevention research, particularly within communities of color, there have been growing calls for more comprehensive and participatory approaches to public health research and practice. The purpose of this article is to describe and analyze the process of establishing, implementing, and evaluating the Detroit Community-Academic Urban Research Center (URC), a community-based participatory research (CBPR) partnership involving community-based organizations, a local health department, academia, and an integrated health care system. Lessons learned and recommendations for creating effective CBPR partnerships are presented.

Community Participation↗
PubMed2001

Esophageal mucin: an adherent mucus gel barrier is absent in the normal esophagus but present in columnar-lined Barrett's esophagus.

OBJECTIVES: The presence of a protective adherent mucus gel barrier against gastric reflux in the healthy esophagus is uncertain. The aim was to characterize the surface mucin composition and determine the extent of any adherent mucus gel layer on the normal esophagus, and compare this with that in Barrett's esophagus. METHODS: Isolated surface mucins were characterized by density centrifugation, gel filtration chromatography, and chemical composition. Adherent surface mucus was visualized in situ on unfixed and cryostat sections of mucosa and biopsies using a method that preserves mucus layer thickness. RESULTS: There was a complete absence of adherent mucus gel layers on normal human, pig, and rat esophagi. This was in contrast to the thick adherent mucous layer (median thickness = 100-200 microm) seen on the corresponding gastric mucosa. Small quantities of glycoprotein with a composition characteristic of a secretory mucin were isolated from the pig esophagus surface. The mucin, density range between 1.44 and 1.48 g x ml(-1), contained 80% carbohydrate and was rich in serine, threonine, and proline. The mucin fragmented into smaller glycoprotein units on proteolysis and partially on reduction. Cryostat sections from columnar-lined esophageal biopsies had a substantial adherent surface mucous layer (median thickness = 90 microm, interquartile range = 84-94 microm) staining for neutral mucins (gastric-type epithelium) and acidic mucins (intestinal metaplasia). CONCLUSIONS: A secretory mucin, with an analysis distinct from that of gastric or salivary mucin, is present in very small quantities on the esophageal mucosa and in amounts insufficient to form an adherent gel layer. It is unlikely that mucus has a role in protecting the normal esophagus against reflux. However, an adherent mucous layer was observed over columnar-lined esophagus, and this may protect against reflux.

Animals↗
PubMed2001

Multiple-dose pharmacokinetics and tolerability of gemifloxacin administered orally to healthy volunteers.

Gemifloxacin mesylate (SB-265805-S, LB-20304a) is a potent, novel fluoroquinolone agent with a broad spectrum of antibacterial activity. The pharmacokinetics and tolerability of oral gemifloxacin were characterized in two parallel group studies in healthy male volunteers after doses of 160, 320, 480, and 640 mg once daily for 7 days. Multiple serum or plasma and urine samples were collected on days 1 and 7 and were analyzed for gemifloxacin by high-performance liquid chromatography (HPLC)-fluorescence (study 1) or HPLC-mass spectrometry (study 2). Safety assessments included vital signs, 12-lead electrocardiogram (ECG) readings, hematology, clinical chemistry, urinalysis, and adverse experience monitoring. Gemifloxacin was rapidly absorbed, with a time to maximum concentration of approximately 1 h after dosing followed by a biexponential decline in concentration. Generally, maximum concentration and area under the concentration-time curve (AUC) increased linearly with dose after either single or repeat doses. Mean +/- standard deviation values of AUC(0-tau) on day 7 were 4.92 +/- 1.08, 9.06 +/- 2.20, 12.2 +/- 3.69, and 20.1 +/- 3.67 microg x h/ml following 160-, 320-, 480-, and 640-mg doses, respectively. The terminal-phase half-life was approximately 7 to 8 h, independent of dose, and was similar following single and repeated administrations. There was minimal accumulation of gemifloxacin after multiple dosing. Approximately 20 to 30% of the administered dose was excreted unchanged in the urine. The renal clearance was 160 ml/min on average after single and multiple doses, which was slightly greater than the accepted glomerular filtration rate (approximately 120 ml/min). These data show that the pharmacokinetics of gemifloxacin are linear and independent of dose. Gemifloxacin was generally well tolerated, although one subject was withdrawn from the study after 6 days at 640 mg for mild, transient elevations of alanine aminotransferase and aspartate aminotransferase not associated with any clinical signs or symptoms. There were no other significant changes in clinical chemistry, hematology or urinalysis parameters, vital signs, or ECG readings. In conclusion, the results of these studies, combined with the antibacterial spectrum and potency, support the further investigation of once-daily administration of gemifloxacin for indications such as respiratory tract and urinary tract infections.

Adult↗
PubMed2001

The adherent gastrointestinal mucus gel layer: thickness and physical state in vivo.

Divergent results from in vitro studies on the thickness and appearance of the gastrointestinal mucus layer have previously been reported. With an in vivo model, we studied mucus gel thickness over time from stomach to colon. The gastrointestinal tissues of Inactin-anesthetized rats were mounted luminal side up for intravital microscopy. Mucus thickness was measured with a micropipette before and after mucus removal by suction. The mucus layer was translucent and continuous; it was thickest in the colon (approximately 830 microm) and thinnest in the jejunum (approximately 123 microm). On mucus removal, a continuous, firmly adherent mucus layer remained attached to the epithelial surface in the corpus (approximately 80 microm), antrum (approximately 154 microm), and colon (approximately 116 microm). In the small intestine, this layer was very thin (approximately 20 microm) or absent. After mucus removal, there was a continuous increase in mucus thickness with the highest rate in the colon and the lowest rate in the stomach. In conclusion, the adherent gastrointestinal mucus gel in vivo is continuous and can be divided into two layers: a loosely adherent layer removable by suction and a layer firmly attached to the mucosa.

Animals↗