Search PubMed⌕ Search

Biomedical subjects

K Hall

Publications and source records attributed to K Hall.

At least 19 recordsLinked to original sources

A novel method for assessing the role of air in the microbiological contamination of poultry carcasses.

This paper describes a novel method of measuring the contamination of raw foods with airborne bacteria during primary processing. To demonstrate the approach, this study aimed to quantify the role of airborne bacteria in the contamination of broiler chicken carcasses undergoing processing in an evisceration room. Settle plates and broiler carcasses were exposed to the evisceration room air or to ultra-clean air provided by a high efficiency particulate air (HEPA) unit located within the room. The use of ultra-clean air reduced the total aerobic counts on horizontal settle plates by 68-fold, and on vertical settle plates by 14-fold. The use of ultra-clean air had no significant effect on the total aerobic counts on carcasses as measured by sponging (3.5 log(10) CFU cm(-2)) or skin excision (4.0 log(10) CFU cm(-2)). The novel approach was able to show that the carcasses entering the room were so heavily contaminated that the airborne bacteria in the evisceration room contributed less than 1% of the total numbers of bacteria on the carcasses.

Air Microbiology↗

Local changes in the insulin-like growth factor system in human skeletal muscle assessed by microdialysis and arterio-venous differences technique.

IGF-I plays a direct role in whole body glucose homeostasis primarily by stimulating skeletal muscle glucose uptake. IGF-I is also involved in exercise induced muscle hypertrophy. Knowledge regarding local changes in muscle IGF-I bioavailability and its regulation by IGFBPs at rest and during exercise is limited. We have therefore explored changes in total IGF-I levels as well as circulating IGFBP levels and their post-translational modifications over an exercising leg. For the first time we have determined IGF-I levels in exercising skeletal muscle microdialysate in an attempt to assess local IGF-I bioavailability. Eighteen healthy young men performed one legged knee-extension exercise during 45min. Blood samples were taken from the femoral artery and vein of the exercising leg. No significant differences between arterial and venous concentrations of total IGF-I or IGFBP-1 were detected over the leg at any time. IGF-I concentrations increased significantly during exercise in the artery but not in the vein. Total IGFBP-1 increased after exercise in both artery and vein. The increase in non-plus less phosphorylated forms of IGFBP-1 was less pronounced and did not reach statistical significance. The proportion of fragmented IGFBP-3 (IGFBP-3 proteolysis) assessed by Western immunoblotting did not change significantly during or after exercise. Although optimization and validation of IGF-I determinations in muscle microdialysate (md) will be required, our first results using this technique demonstrate a significant 2-fold increase in mdIGF-I collected during and after exercise. We conclude that determination of A-V-differences appears to be of limited value in the assessments of local muscle change in the IGF-system. A substantial release of IGF-I during short time is required to detect significant change in the large circulating store of IGF-I. We suggest that an optimized and validated microdialysis technique for determination of local IGF-I may be advantageous in future studies.

Adult↗

Protein substitute dosage in PKU: how much do young patients need?

BACKGROUND: The optimal dose of protein substitute has not been determined in children with phenylketonuria (PKU). AIM: To determine if a lower dose of protein substitute could achieve the same or better degree of blood phenylalanine control when compared to the dosage recommended by the UK MRC.(1) METHODS: In a six week randomised, crossover study, two doses of protein substitute (Protocol A: 2 g/kg/day of protein equivalent; Protocol B: 1.2 g/kg/day protein equivalent) were compared in 25 children with well controlled PKU aged 2-10 years (median 6 years). Each dose of protein substitute was taken for 14 days, with a 14 day washout period in between. Twice daily blood samples (fasting pre-breakfast and evening, at standard times) for plasma phenylalanine were taken on day 8-14 of each protocol. The median usual dose of protein substitute was 2.2 g/kg/day (range 1.5-3.1 g/kg/day). RESULTS: When compared with control values, median plasma phenylalanine on the low dose of protein substitute increased at pre-breakfast by 301 mumol/l (95% CI 215 to 386) and in the evening by 337 micromol/l (95% CI 248 to 431). On the high dose of protein substitute, plasma phenylalanine concentrations remained unchanged when compared to control values. However, wide variability was seen between subjects. CONCLUSIONS: A higher dosage of protein substitute appeared to contribute to lower blood phenylalanine concentrations in PKU, but it did have a variable and individual impact and may have been influenced by the carbohydrate (+/- fat) content of the protein substitute.

Child↗

Cholesterol, APOE genotype, and Alzheimer disease: an epidemiologic study of Nigerian Yoruba.

OBJECTIVE: To examine the relationship between cholesterol and other lipids, APOE genotype, and risk of Alzheimer disease (AD) in a population-based study of elderly Yoruba living in Ibadan, Nigeria. METHODS: Blood samples and clinical data were collected from Yoruba study participants aged 70 years and older (N = 1,075) as part of the Indianapolis-Ibadan Dementia Project, a longitudinal epidemiologic study of AD. Cholesterol, low-density lipoprotein (LDL), high-density lipoprotein (HDL), and triglyceride levels were measured in fasting blood samples. DNA was extracted and APOE was genotyped. Diagnoses of AD were made by consensus using National Institute of Neurologic Disorders/Stroke-Alzheimer's Disease and Related Disorders Association criteria. RESULTS: Logistic regression models showed interaction after adjusting for age and gender between APOE-epsilon4 genotype and biomarkers in the risk of AD cholesterol*genotype (p = 0.022), LDL*genotype (p= 0.018), and triglyceride*genotype (p = 0.036). Increasing levels of cholesterol and LDL were associated with increased risk of AD in individuals without the APOE-epsilon4 allele, but not in those with APOE-epsilon4. There was no significant association between levels of triglycerides and AD risk in those without APOE-epsilon4. CONCLUSIONS: There was a significant interaction between cholesterol, APOE-epsilon4, and the risk of Alzheimer disease (AD) in the Yoruba, a population that has lower cholesterol levels and lower incidence rates of AD compared to African Americans. APOE status needs to be considered when assessing the relationship between lipid levels and AD risk in population studies.

Aged↗

A comparison of the efficacy and safety of olanzapine and risperidone in the treatment of elderly patients with schizophrenia: an open study of six months duration.

BACKGROUND: Following an earlier study in which elderly patients with schizophrenia had their typical antipsychotic medication changed to olanzapine or risperidone, the 61 patients were followed for up to a further six months to see if either treatment was superior in terms of efficacy or side effects. AIMS: To determine whether either olanzapine or risperidone was superior in terms of efficacy or side effects when treating schizophrenia in late life. METHODS: Psychiatric symptoms, side effects and quality of life were rated every six weeks for 24 weeks of open label comparative treatment using standard measures. Group differences were examined using analysis of covariance and within-group changes over time were assessed using paired t-tests. RESULTS: There were 34 olanzapine and 32 risperidone patients who entered the study, but intention to treat data was only available for 61 of the 66 patients. There were no clinical or demographic differences between the groups. Parkinsonism, positive and negative symptoms of schizophrenia improved in both groups both from baseline switch to olanzapine or risperidone and during the six month follow-up after completion of crossover. No significant differences were seen between groups on most measures. However, patients treated with olanzapine showed a significantly greater improvement in quality of life from baseline compared to risperidone patients. CONCLUSIONS: Both drugs were well tolerated and their use was associated with fewer symptoms of schizophrenia and less adverse effects than were seen when the patients were taking a typical antipsychotic at baseline. Olanzapine appears to have particular benefit with regard to quality of life.

Aged↗

Specific cleavage of insulin-like growth factor-binding protein-1 by a novel protease activity.

Insulin-like growth factor-binding protein-1 (IGFBP-1) is secreted in a highly phosphorylated form that binds IGF-I with high affinity and is resistant to proteolysis. We have purified IGFBP-1-specific protease activity from the urine of an individual with multiple myeloma. This protease efficiently cleaves both phosphorylated and non-phosphorylated IGFBP-1 at Ile130-Ser131, generating fragments that together have higher association and dissociation rates for IGFs compared with intact IGFBP-1. The proteolytic fraction contained azurocidin, a protease homologue hitherto considered inactive. After cleavage of IGFBP-1, there was a lower affinity, but higher capacity for IGF-I binding, suggesting both N- and C-terminal fragments may interact with ligand independently. There was decreased inhibition of IGF-II-stimulated cell growth and glucose uptake. Alone, proteolysed IGFBP-1 stimulated glucose uptake in muscle. We conclude that specific cleavage of IGFBP-1 at target tissues is important in cellular growth and metabolism and opens novel strategies for targeting IGFBP-1 in treatment of disease.

Antimicrobial Cationic Peptides↗

Isolation and characterization of polycyclic aromatic hydrocarbon-degrading Mycobacterium isolates from soil.

Bioremediation of soils contaminated with wood preservatives containing polycyclic aromatic hydrocarbons (PAHs) is desired because of their toxic, mutagenic, and carcinogenic properties. Creosote wood preservative-contaminated soils at the Champion International Superfund Site in Libby, Montana currently undergo bioremediation in a prepared-bed land treatment unit (LTU) process. Microbes isolated from these LTU soils rapidly mineralized the (14)C-labeled PAH pyrene in the LTU soil. Gram staining, electron microscopy, and 16S rDNA-sequencing revealed that three of these bacteria, JLS, KMS, and MCS, were Mycobacterium strains. The phylogeny of the 16S rDNA showed that they were distinct from other Mycobacterium isolates with PAH-degrading activities. Catalase and superoxide dismutase (SOD) isozyme profiles confirmed that each isolate was distinct from each other and from the PAH-degrading mycobacterium, Mycobacterium vanbaalenii sp. nov, isolated from a petroleum-contaminated soil. We find that dioxygenase genes nidA and nidB are present in each of the Libby Mycobacterium isolates and are adjacent to each other in the sequence nidB-nidA, an order that is unique to the PAH-degrading mycobacteria.

Base Sequence↗

Moraxella catarrhalis induces mast cell activation and nuclear factor kappa B-dependent cytokine synthesis.

Human mast cells are often found perivascularly and at mucosal sites and may play crucial roles in the inflammatory response. Recent studies have suggested a prominent role for mast cells in host defense. In this study, we analyzed the effects of a common airway pathogen, Moraxella catarrhalis and a commensal bacterium, Neiserria cinerea, on activation of human mast cells. Human mast cell leukemia cells (HMC-1) were activated with either phorbol myristate acetate (PMA) and calcium ionophore or with varying concentrations of heat-killed suspensions of bacteria. Supernatants were assayed for the cytokines interleukin-4 (IL-4), granulocyte macrophage colony stimulating factor (GM-CSF), IL-6, IL-8, IL-13 and monocyte chemotactic protein-1 (MCP-1). Nuclear proteins were isolated and assayed by electrophoretic mobility shift assay (EMSA) for nuclear factor kappaB (NF-kappaB) nuclear binding activity. In some experiments, NF-kappaB inhibitor, Bay-11 was added to determine functional significance. Both M. catarrhalis and N. cinerea induced mast cell activation and selective secretion of two key inflammatory cytokines, IL-6 and MCP-1. This was accompanied by NF-kappaB activation. Neither spun bacterial supernatants nor bacterial lipopolysaccharide induced cytokine secretion, suggesting need for direct bacterial contact with mast cells. Scanning electron microscopy revealed active aggregation of bacteria over mast cell surfaces. The NF-kappaB inhibitor, Bay-11, inhibited expression of MCP-1. These findings suggest the possibility of direct interactions between human mast cells and common bacteria and provide evidence for a novel role for human mast cells in innate immunity.

Cell Line, Tumor↗

The impact upon extra-pyramidal side effects, clinical symptoms and quality of life of a switch from conventional to atypical antipsychotics (risperidone or olanzapine) in elderly patients with schizophrenia.

BACKGROUND: Atypical antipsychotics are commonly used in the management of schizophrenia in late life with evidence suggesting they induce lower rates of motor disturbance, but have similar efficacy to conventional antipsychotics. Trials in the elderly have been either retrospective, small, of short duration or of a single-arm design. AIMS: To demonstrate the effects upon motor side-effects, efficacy, safety and quality of life (QOL) of switching elderly patients with schizophrenia from conventional antipsychotics to olanzapine or risperidone. METHODS: Elderly patients with schizophrenia were randomly allocated to olanzapine or risperidone and followed through an open-label crossover period. Between and within group intention to treat analyses were conducted. RESULTS: 66 patients were randomised (mean age 69.6 [SD +/- 6.2]). Four (11.8%) patients on olanzapine and 8 (26.7%) patients on risperidone failed to complete the crossover because of treatment failure [Odds Ratio (OR) = 2.73[0.73-10.2] p = 0.14]. The mean doses upon completion of switching in each arm were 9.9 mg (SD = 4.2) and 1.7 mg (SD = 1.2) for olanzapine and risperidone respectively. In both arms there was improvement in Parkinsonism, though only olanzapine was associated with a reduction in dyskinetic symptoms. The Brief Psychiatric Rating Scale, Scale for the assessment of Negative Symptoms and Montgomery and Asberg Depression Rating Scale scores all improved through the crossover period in both arms with no between group differences. Treatment with olanzapine was associated with a better response over risperidone on the psychological domain of the World Health Organisation-Quality Of Life [Brief] (WHO-QOL-BREF) scale ( p = 0.02). Patients in the olanzapine arm also demonstrated improvement from baseline in the WHO-QOL-BREF physical, psychological and health satisfaction domains, but risperidone had no effect on any Quality of Life (QOL) measure. CONCLUSIONS: After switching from a conventional antipsychotic, olanzapine and risperidone were associated with improvement in core symptoms of schizophrenia and motor side effects. Subjects switched to olanzapine were more likely to complete the switching process and show an improvement in psychological QOL.

Aged↗

Evaluation of magnetic resonance myelography in the investigation of cervical spondylotic radiculopathy.

The objective of this study was to prospectively evaluate the accuracy of MR myelography for the demonstration of foraminal nerve root impingement in cervical spondylotic radiculopathy. 40 patients with cervical spondylotic radiculopathy were imaged with conventional MRI and with MR myelography. The diagnostic accuracy of these imaging strategies for the demonstration of exit foraminal stenosis was calculated relative to a gold standard of the combination of conventional MRI and MR myelography. Conventional MRI had a sensitivity of 88.9%, specificity of 99.1%, and diagnostic accuracy of 94.5% for the demonstration of exit foraminal disease (p<0.001). MR myelography alone had a sensitivity of 84.4%, a specificity of 90.1%, and diagnostic accuracy of 88% (p<0.001). However, the addition of MR myelography increased the diagnostic yield of the MR examination for the detection of foraminal stenotic disease. MR myelography is a useful adjunct to conventional MRI in the investigation of cervical spondylotic radiculopathy.

Adult↗

Phase I study of docetaxel plus ifosfamide in patients with advanced cancer.

The aim of this study was to determine the maximum tolerated dose of a fixed dose of docetaxel when combined with continuous infusion ifosfamide, with and without G-CSF support, in the treatment of advanced cancer, and to evaluate anti-tumour activity of this combination. Thirty-one patients with advanced malignancies were treated with docetaxel 75 mg/m(2) intravenously on days 1, and ifosfamide at increasing dose levels from 1500 mg/m(2)/day to 2750 mg/m(2)/day as a continuous infusion from day 1-3, every 3 weeks. A total of 107 cycles of treatment were administered. Without G-CSF support dose-limiting toxicity of grade 4 neutropenia greater than 5 days duration occurred at dose level 1. With the addition of G-CSF the maximum tolerated dose was docetaxel 75 mg/m(2) on day 1 and ifosfamide 2750 mg/m(2)/day on days 1-3. Dose limiting toxicity (DLT) included ifosfamide-induced encephalopathy, febrile neutropenia and grade three mucositis. Three complete responses and 3 partial responses were seen. This combination of docetaxel and infusional ifosfamide is feasible and effective. The recommended dose for future phase II studies is docetaxel 75 mg/m(2) on day 1 and ifosfamide 2500 mg/m(2)/day continuous infusion on days 1-3.

Adenocarcinoma↗

Application of micro-scale sealed vessel thermal desorption-gas chromatography-mass spectrometry for the organic analysis of airborne particulate matter: linearity, reproducibility and quantification.

Micro-scale sealed vessel thermal desorption-gas chromatography-mass spectrometry (MSSV-TD-GC-MS) has been applied to the analysis of airborne particulate matter using the US NIST Standard Reference Material (SRM1649a) urban dust. We make qualitative comparisons with open system desorption and illustrate that caution should be used when using the technique without an open system comparison. We report linear responses over the same particulate mass range (1-5 mg) and good reproducibility [SD< or =0.62 mg kg(-1) (< or = 11%)]. We show linearity for a series of 10 n-alkanes and 10 polycyclic aromatic hydrocarbons (PAHs) in the SRM. The technique is also shown to be quantifiable (PAH concentrations typically 4-6 mg kg(-1)).

Gas Chromatography-Mass Spectrometry↗

Restricted feedback control of one-dimensional maps.

Dynamical control of biological systems is often restricted by the practical constraint of unidirectional parameter perturbations. We show that such a restriction introduces surprising complexity to the stability of one-dimensional map systems and can actually improve controllability. We present experimental cardiac control results that support these analyses. Finally, we develop new control algorithms that exploit the structure of the restricted-control stability zones to automatically adapt the control feedback parameter and thereby achieve improved robustness to noise and drifting system parameters.

Journal Article↗

A preliminary model for predicting heavy metal contaminant loading from an urban catchment.

The toxicity of heavy metals to biota in urban catchments has been regarded as a very important non-point source pollution issue. Numerous studies on heavy metal pollution in urban receiving waters have found that metal transport by surface runoff is closely correlated to the partitioning of the metal forms between dissolved and particulate phases, where sediment plays an important role in the transport process. Sediment cycling on urban streets, metal binding form, and rainfall character in the catchment area are considered to be the key factors for metal transport. A preliminary model is developed based on these considerations. Starting from classical build-up and wash-off processes for the suspended sediment (SS) on the urban impervious surface, the model links the transport of suspended sediment to the transport of metal species. Monitoring data from a small highway catchment were used in the model development. A total of 47 rain events over 1 year were monitored intensively at short time intervals (5-10 min) for hydrological data, rainfall intensity, and stormwater quality. In developing the model, lead was used for the metal load prediction, as it has been a common fuel additive for urban transportation. Agreement between model results and monitoring data indicates that the model can be used in predicting metal load from impervious urban areas, such as streets and roadways, on a long-term basis.

Animals↗

Expression levels of insulin-like growth factor binding proteins and insulin receptor isoforms in hepatoblastomas.

Hepatoblastoma, a rare pediatric liver tumour, is a poorly understood disease. While expression studies for some members of the Insulin-like growth factor axis have been studied in hepatoblastoma, a systematic analysis of the IGF-axis has not been carried out. We have examined a series of hepatoblastomas with matched normal liver tissue for gene expression differences with emphasis on members of the insulin-like growth factor binding proteins. The expression profiles obtained reveal that the expression of these genes are altered in these tumors. The results indicate that the IGF-axis is seriously disturbed in the tumors.

Adolescent↗

Antipsychotics and the risk of sudden cardiac death.

BACKGROUND: Case reports link antipsychotic drugs with sudden cardiac deaths, which is consistent with dose-related electrophysiologic effects. Because this association has not been confirmed in controlled studies, we conducted a retrospective cohort study in Tennessee Medicaid enrollees, which included many antipsychotic users; there were also computer files describing medication use and comorbidity. The study was conducted before the introduction of risperidone and, thus, did not include the newer atypical agents. METHODS: The cohort included 481,744 persons with 1,282,996 person-years of follow-up. This included 26,749 person-years for current moderate-dose antipsychotic use (>100-mg thioridazine equivalents), 31,864 person-years for current low-dose antipsychotic use, 37,881 person-years for use in the past year only, and 1 186,501 person-years for no use. The cohort had 1487 confirmed sudden cardiac deaths; from these, we calculated multivariate rate ratios adjusted for potential confounding factors. RESULTS: When current moderate-dose antipsychotic use was compared with nonuse, the multivariate rate ratio was 2.39 (95% confidence interval, 1.77-3.22; P<.001). This was greater than that for current low-dose (rate ratio, 1.30; 95% confidence interval, 0.98-1.72; P=.003) and former (rate ratio, 1.20; 95% confidence interval, 0.91-1.58; P<.001) use. Among cohort members with severe cardiovascular disease, current moderate-dose users had a 3.53-fold (95% confidence interval, 1.66-7.51) increased rate relative to comparable nonusers ( P<.001), resulting in 367 additional deaths per 10,000 person-years of follow-up. CONCLUSIONS: Patients prescribed moderate doses of antipsychotics had large relative and absolute increases in the risk of sudden cardiac death. Although the study data cannot demonstrate causality, they suggest that the potential adverse cardiac effects of antipsychotics should be considered in clinical practice, particularly for patients with cardiovascular disease.

Adolescent↗

Vastus medialis muscle oxygenation trends during a simulated 20-km cycle time trial.

In this study we examined the oxygenation trend of the vastus medialis muscle during sustained high-intensity exercise. Ten cyclists performed an incremental cycle ergometer test to voluntary exhaustion [mean (SD) maximum oxygen uptake 4.29 (0.63) l x min(-1); relative to body mass 60.8 (2.4) ml x kg(-1)min(-1)] and a simulated 20-km time trial (20TT) on a wind-loaded roller system using their own bicycle (group time = 23-31 min) in two separate sessions. Cardiorespiratory responses were monitored using an automated metabolic cart and a wireless heart rate monitor. Tissue absorbency, which was used as an index of muscle oxygenation, was recorded simultaneously from the vastus medialis using near-infrared spectroscopy. Group mean values for oxygen uptake, ventilation, heart rate, respiratory exchange ratio, power output, and rating of perceived exhaustion were significantly (P < or = 0.05) higher during the incremental test compared to the 20TT [4.29 (0.63) l x min(-1) vs 4.01 (0.55) l x min(-1), 120.4 (26) l x min(-1) vs 97.6 (16.1) l x min(-1), 195 (8) beats x min(-1) vs 177 (9) beats min(-1), 1.15 (0.06) vs 0.93 (0.06), 330.1 (31) W vs 307.2 (24.5) W, and 19 (1.5) vs 16 (1.7), respectively]. Oxygen uptake and heart rate during the 20TT corresponded to 93.5% and 90.7%, respectively, of the maximal values observed during the incremental test. Comparison of the muscle oxygenation trends between the two tests indicated a significantly greater degree of deoxygenation during the 20TT [-699 (250) mV vs 439 (273) mV; P < or = 0.05] and a significant delay in the recovery oxygenation from the 20TT. The mismatching of whole-body oxygen uptake and localised tissue oxygenation between the two tests could be due to differences in muscle temperature, pH, localised blood flow and motor unit recruitment patterns between the two tests.

Adult↗