Laryngeal tuberculosis: not the usual suspect.
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Adult↗
Biomedical subjects
A Sawyer
Publications and source records attributed to A Sawyer.
Pharmacokinetic and tolerability profile of twice-daily saquinavir hard gelatin capsules and saquinavir soft gelatin capsules boosted with ritonavir in healthy volunteers.
OBJECTIVE: To evaluate the pharmacokinetics and safety of a boosted saquinavir (SQV)/ritonavir (RTV) combination, administered as either the hard gelatin capsule (HGC) or soft gelatin capsule (SGC) formulation of SQV, in 24 healthy volunteers. METHODS: This was a single-centre, open-label, randomized, 2 x 2 crossover study. Twelve subjects were randomized to receive SQV/RTV 1000 mg/100 mg twice daily (BID) orally for 10 days, as either the HGC or SGC formulation. The pharmacokinetic profile of SQV was determined on day 10. Subjects then crossed over to the opposite SQV formulation, and the pharmacokinetic profile was determined again on day 20. The primary analysis was the assessment of bioequivalence based on logarithmically transformed values for AUC(0-24 h) and Cmax for the two formulations. RESULTS: There was a statistically significant increase in the geometric means of all the pharmacokinetic variables evaluated for SQV-HGC/RTV compared with SQV-SGC/RTV. A mean AUC0-24 h-value of 15.798 micro g/mL/h was reported for the HGC formulation compared with 11.655 micro g/mL/h for the SGC formulation (P = 0.0043). The SQV-HGC/RTV combination was better tolerated in terms of gastrointestinal system disorders. Furthermore, no elevations in triglycerides or total cholesterol were reported with SQV/RTV during the entire study period. CONCLUSION: In healthy volunteers, RTV boosting of SQV-HGC produces plasma exposures at least comparable to SQV-SGC, which is accompanied by an improvement in gastrointestinal system disorders.
Adult↗
Quantification of tartrate resistant acid phosphatase distribution in mouse tibiae using image analysis.
Tartrate resistant acid phosphatase (TRAP) activity of bone is a suitable biochemical marker for osteoclastic bone resorption. Qualitatively, the histochemical distribution of TRAP has been used to identify osteoclasts responsible for bone resorption; however, there have been few attempts to quantify TRAP localization. We describe a method for evaluating bone resorption by quantifying area percentages of positive TRAP localization using image analysis. Mouse tibiae were paraffin embedded following demineralization in disodium ethylenediamine tetraacetic acid. Longitudinal sections of tibia were cut from 15 levels in the left and the right limbs of six mice (180 sections total) and stained for TRAP distribution. Positive TRAP localization was quantified by pixel area count and reported as a percentage of the total tissue area specified. The 1.85 mm2 region of interest was placed at the midpoint of the epiphyseal growth plate containing the provisional calcification layer and the primary spongiosa, while excluding cortical bone of each mouse tibia. The percentage of TRAP localization ranged from 0.95 to 1.31% and was not significantly different from level to level or limb to limb in each mouse (p > 0.100). Within the same region of interest, an osteoclast count along the bone perimeter also was performed. We demonstrated a strong correlation (r2 = 0.903) between the conventional histomorphometric osteoclast index and positive TRAP localization, validating the latter as an alternative method to assess bone resorption. Quantitative analysis of TRAP is significant because it allows statistical comparisons between treatment groups, promotes precise pathological diagnoses and facilitates a reference data base that may aid the study of bone related diseases involving increased bone resorption.
Acid Phosphatase↗
Limited effect of food composition on the pharmacokinetics of nelfinavir administered twice daily.
UNLABELLED: The objective of the study was to investigate the effect of two different breakfasts on the pharmacokinetics of nelfinavir under steady state conditions. METHODS: Twenty-four healthy male volunteers were evaluated in a 17 days open labeled one sequence crossover study evaluating the effect of a 'light' breakfast (350 kcal) compared to a standard breakfast (800 kcal) on the pharmacokinetics of nelfinavir at steady state during 1250 mg twice daily (BID) administration. RESULTS: After administration with a standard breakfast higher concentrations of nelfinavir were observed during the terminal phase than after administration with a 'light' breakfast. The comparison of the log subset 10 transformed parameters C subset 1-hr-postdose, AUC subset 0-12h, C subset max, and C subset 12 hours, showed that the AUC subset 0-12h was decreased by 13% (P = 0.01) after administration with the 'light' breakfast. Nelfinavir 1250 mg BID was well tolerated. CONCLUSIONS: Although drug intake with a 'light' breakfast' showed a statistically significant decrease for nelfinavir AUC subset 0-12h, this marginal 13% reduction is not considered clinically relevant. No significant effects of the two different breakfasts were found for the remaining three parameters tested C subset 1-hr-postdose, C subset max, and C subset 12 hours.
Adult↗
Contribution of the left dorsomedial thalamus to recognition memory: a neuropsychological case study.
This study reports a patient with a unilateral left thalamic lesion which was centred on the dorsomedial thalamic nucleus. Cognitive neuropsychological assessment revealed a severe impairment in verbal memory and symptoms of executive dysfunction, in the presence of relatively intact visual and facial recognition, working memory, praxis, language and IQ. Verbal and visual recognition memory were investigated using the remember-know paradigm. The results indicated a profound impairment in recollection-driven verbal recognition memory. These results are discussed in the context of the role of the dorsomedial thalamic nucleus in recognition memory, and functional models of memory.
Brain Infarction↗
Does surface chemistry affect thrombogenicity of surface modified polymers?
With some exceptions, surface chemistry had little effect on platelet and leukocyte activation, and cell deposition, by scanning electron microscopy after blood exposure and clotting times among a group of 12 unmodified and plasma modified tubings. All materials activated platelets and leukocytes to detectable levels, although some materials increased the value of one activation parameter but not another. Unmodified materials [polyethylene (PE), Pellethane (PEU), latex, nylon, and Silastic] and modified materials (H(2)O plasma treated PE and PEU, CF(4) plasma treated PE, fluorinated PEU, NH(4) plasma treated PEU, polyethylene imine treated PEU, and heparin treated PEU) were characterised by XPS and contact angle. The objective of this project was to define a series of assays for the evaluation of hemocompatibility of cardiovascular devices with a view to clarify the specific requirements of ISO-10993-4, and to define an appropriate screening program for new blood contacting biomaterials. PE, PE--CF(4), PE--H(2)0, PEU--F, latex, and PEU-heparin were the exceptions to the general observations, although each behaved differently. PE proved to be least reactive, whereas PE-CF(4) was most reactive by several assays. Platelet microparticle formation (determined by flow cytometry), PTT, postblood exposure SEM, total SC5b-9, C3a, and platelet and leukocyte loss (cell counts) were able to distinguish differences among these materials, and often, but not always, showed expected correlations.
Biocompatible Materials↗
Environmentally sensitive plot-scale timber harvesting: impacts on suspended sediment, bedload and bank erosion dynamics.
The impact on sediment pollution of environmentally sensitive harvesting of a 15 ha plot (20% of the catchment area) of mature coniferous plantation forest in the 0.89 km2 Afon Tanllwyth catchment, Plynlimon, was investigated for 12 months before harvesting began and a further 18 months after. The results revealed: (a) a steepening of the suspended sediment concentration vs. discharge rating curve resulting in a 39% increase in suspended sediment yield (as compared to the adjacent forested Hafren catchment) during the year in which the harvesting operations took place; (b) a statistically significant increase in main channel bank erosion rates, as compared with the nearby Afon Cyff; main channel banks are estimated to have contributed around 80% of the total catchment suspended sediment yield during the two year period (1995-1996), and (c) no significant change in bedload yields over the duration of the study, though a longer post-harvesting time series of bedload data will be required to properly assess the impact of the harvesting operation upon bedload yields. Forest management implications of these findings are discussed in detail with respect to the existing Forest and Water guidelines.
Conservation of Natural Resources↗
Calcaneus ultrasound measurements in a convenience sample of healthy youth.
We examined age-related changes in quantitative ultrasound of the calcaneus in 311 healthy males and females ages 6.6-20 yr using the Lunar Achilles ultrasound device. This equipment has been adapted for pediatric use with the provision of shims designed to properly position smaller feet relative to the transducers. Broadband ultrasound attenuation (BUA) (decibels/megahertz), speed of sound (SOS) (meters/second), and stiffness index (SI) (percent) increased across the age range until a plateau was reached at 16-18 yr. BUA increased by 40%, SOS by 4%, and SI by 80% across this age range. There was no gender difference in age-related gains. Age, weight, height, and hours of weight-bearing physical activity were all significantly associated with BUA, SOS, and SI. After controlling for age and weight, hours of weight-bearing physical activity showed little to no additional effect on these parameters. Short-term in vivo precision using this device was similar in children to that observed in adults in our laboratory; coefficients of variation for between-day measurements were 1.8, 0.6, and 3.2% for BUA, SOS, and SI, respectively. These data support the feasibility of using the Lunar Achilles in evaluating pediatric bone mass. The ability of this technique to discriminate between osteopenic and normal children remains to be determined.
Adolescent↗
Results of a method of leg-length equalization for patients undergoing primary total hip replacement.
The postoperative leg-length discrepancy was determined radiographically for a consecutive series of 351 patients (408 hips) who underwent bilateral or unilateral primary total hip replacement using a single method of leg-length equalization by preoperative planning with overlay templates. The method of equalization was performed by a measurement of the femoral head and neck segment to be resected from a reference point at the superior aspect of the dislocated femoral head. The amount of femoral bone resected was determined preoperatively by determining the dimensions of the acetabular component thickness and the femoral component head and neck height that would be replacing this resected bone and adjusting this distance for any preexisting leg-length discrepancy. Using this leg-length equalization method, the length of the modular femoral head neck was chosen preoperatively, rather than using soft tissue tension across the prosthetic hip joint to determine whether the leg lengths were equal. Postoperative leg lengths were determined radiologically from a measurement from the acetabular teardrop to the lesser trochanter. Ninety-seven percent of the patients had a postoperative leg-length discrepancy that was less than 1 cm, and 86% had a leg-length difference that was 6 mm (1/4 inch) or less. The average postoperative discrepancy for these 351 patients was 1 mm.
Adult↗
Ikaros DNA-binding proteins direct formation of chromatin remodeling complexes in lymphocytes.
The Ikaros gene family encodes zinc finger DNA-binding proteins essential for lineage determination and control of proliferation in the lymphoid system. Here, we report that, in the nucleus of a T cell, a major fraction of Ikaros and Aiolos proteins associate with the DNA-dependent ATPase Mi-2 and histone deacetylases, in a 2 MD complex. This Ikaros-NURD complex is active in chromatin remodeling and histone deacetylation. Upon T cell activation, Ikaros recruits Mi-2/HDAC to regions of heterochromatin. These studies reveal that Ikaros proteins are capable of targeting chromatin remodeling and deacetylation complexes in vivo. We propose that the restructuring of chromatin is a key aspect of Ikaros function in lymphocyte differentiation.
Adenosine Triphosphatases↗
Restructuring asthma care in a hospital setting to improve outcomes.
STUDY OBJECTIVES: To restructure asthma care as the pilot program in hospital-wide redesign aimed at providing better and more standardized care. We chose asthma care to begin our reorganization because it is the highest-volume diagnosis at our hospital and it involves a broad spectrum of services. DESIGN: Key elements of our restructuring included the following: (1) establishing a pulmonary unit with expanded bed capacity from 8 to 22 beds for asthma patients; (2) standardized treatment protocols; (3) availability of direct admission by primary care physicians who maintained management of their patients with the option of consultation with a specialist; and (4) use of case managers who helped patients and their families overcome obstacles to optimum care. SETTING: A hospital serving a high proportion of Medicaid patients. PATIENTS/PARTICIPANTS: Children with asthma and their families. INTERVENTIONS: Standardized care for asthma; use of case managers to facilitate adherence to treatment. RESULTS: With the restructured asthma care program, parent satisfaction with treatment was sustained; the average length of stay and use of the emergency department (ED) were reduced; observation unit use increased; and there were fewer readmissions to both the inpatient unit and the ED. CONCLUSIONS: We conclude that an inner-city hospital can provide optimum care for asthma patients by standardizing treatment, aggregating asthma patients in one location, and providing education and follow-up through the use of case managers. The protocol shifts some costs from expensive services such as the pediatric ICU and the ED to less costly case management and outreach personnel. In the long run, this allocation of resources should help to lower costs as well as improve quality of care.
Asthma↗
A computational study on the relative reactivity of reductively activated 1,4-benzoquinone and its isoelectronic analogs.
The redox capacities of p-benzoquinone (I) and its analogs p-benzoquinone imine (VI) and p-benzoquinone diimine (XI) as the simplest model systems for the biochemically important quinone site of the pharmacophores of the anthracyclines has been investigated by AM1 semi-empirical and ab initio methods. The reductive activation of the parent (Q) model systems to their various redox states (quinone radical anion (Q.-), semiquinone (QH.), semiquinone anion (QH-) and hydroquinone (QH2)), the internal geometrical reorganization and the redox capacities of the redox states have been examined by using energy-partitioning analysis, reaction enthalpies/energies for electron and proton attachments, adiabatic ionization potentials (IPad) and electron affinities (EAad), adiabatic electronegativities (Xad), dipole moments, electrostatic potentials and spin-density surfaces. EAad data and results of energy-partitioning analysis suggest that the one-electron Q to Q.- reducibility of VI is diminished when compared to that of I. The data also predict that reduction to QH., QH- and QH2 is more favorable in VI (cf. I). Deprotonation enthalpy/energy calculations predict that the oxidizability of the reduced forms of VI is diminished when compared to I. Overall, the calculations suggest that the redox cycling of VI should be diminished if deprotonation is the first step of the autoxidation of the reduced forms. The results suggest that the electron affinity of Q and deprotonation of the reduced forms (e.g., QH.) may play important roles in the redox cycling of the anthracyclines. It is further suggested that these same factors are probably responsible for the reduced toxicity of 5-iminodaunomycin, which consists of VI as part of its pharmacophore. A comparison of the AM1 results with ab initio results suggests that the AM1 method is capable of predicting trends in redox capacity, nucleophilicity, electrophilicity and electron affinity in the systems investigated.
Antibiotics, Antineoplastic↗
The core of the mammalian centriole contains gamma-tubulin.
BACKGROUND: The microtubule network, upon which transport occurs in higher cells, is formed by the polymerization of alpha and beta tubulin. The third major tubulin isoform, gamma tubulin, is believed to serve a role in organizing this network by nucleating microtubule growth on microtubule-organizing centers, such as the centrosome. Research in vitro has shown that gamma tubulin must be restored to stripped centrioles to regenerate the centrosomal functions of duplication and microtubule nucleation. RESULTS: We have re-examined the localization of gamma tubulin in isolated and in situ mammalian centrosomes using a novel immunocytochemical technique that preserves antigenicity and morphology while allowing increased accessibility. As expected, alpha tubulin was localized in cytoplasmic and centriolar barrel microtubules and in the associated pericentriolar material. Foci of gamma tubulin were observed at the periphery of the organized pericentriolar material, as reported previously, often near the termini of microtubules. A further and major location of gamma tubulin was a structure within the proximal end of the centriolar barrel. The distributions were complementary, in that alpha tubulin was excluded from the core of the centriole, and gamma tubulin was excluded from the microtubule barrel. CONCLUSIONS: We have shown that gamma tubulin is localized both in the pericentriolar material and in the core of the mammalian centriole. This result suggests that gamma tubulin has a role in the centriolar duplication process, perhaps as a template for growth of the centriolar microtubules, in addition to its established role in the nucleation of astral microtubules.
Amino Acid Sequence↗
FT-IR spectroscopic studies of polyurethanes: IV. Studies of the effect of the presence of processing aids on the hemocompatibility of polyurethanes.
Many types of proprietary processing aids are used by the manufacturers of polymer medical devices, which are difficult to completely eliminate from the end product. In such cases, it is important to investigate how such processing aids affect the properties of the materials. One such material is Pellethane and a most commonly found processing aid is wax. We investigated the effect of the presence of such wax on hecompatibility properties, particularly on the adhesion and activation of human platelets, on a group of Pellethane samples with varying amounts of wax. The effectiveness of cleaning agents, like Freon, was examined for wax removal. The type and quantity of wax present within the near-surface regions of the Pellethane tubings was estimated by using the FT-IR-ATR technique. The presence of bis amide processing wax was found to affect the hemocompatibility properties of the Pellethane samples. Correlation between hemocompatibility and the amount of wax was made; platelet activation, as well as amount and density of fibrin formation, showed a linear correlation.
Biocompatible Materials↗
Prospective study of verocytotoxin-producing, enteroaggregative and diffusely adherent Escherichia coli in different diarrhoeal states.
One hundred and eighty-one stool specimens from patients with various types of diarrhoea (135 patients) or from non-diarrhoeal controls (23 acute medical patients, 23 inflammatory bowel disease in remission) were investigated using a colony-blot DNA hybridization assay for the presence of Verocytotoxin-producing (VTEC), enteroaggregative (EAggEC) and diffusely adherent (DAEC) Escherichia coli. Twelve patients had probe-positive EAggEC in the stool and 8 of these had diarrhoea, 6 following recent travel. Eight patients had DAEC, 7 of whom had travellers' diarrhoea. Six of 10 (60%) travellers with gastroenteritis, but without a recognized enteric pathogen, were positive for EAggEC (4) or DAEC (2). Five of 10 (50%) travellers with gastroenteritis related to a recognized enteric pathogen also had DAEC identified in their stool. Of the 23 acute medical control patients 11 had been abroad, 4 of these were immigrants and had EAggEC. VTEC were not found and, with one exception, immunoassays for antibodies to E. coli O 157 and O 2 lipopolysaccharides were negative.
Adult↗
Effect on microtubule dynamics of XMAP230, a microtubule-associated protein present in Xenopus laevis eggs and dividing cells.
The reorganization from a radial [corrected] interphase microtubule (MT) network into a bipolar spindle at the onset of mitosis involves a dramatic change in MT dynamics. Microtubule-associated proteins (MAPs) and other factors are thought to regulate MT dynamics both in interphase and in mitosis. In this study we report the purification and functional in vitro characterization of a 230-KD MAP from Xenopus egg extract (XMAP230). This protein is present in eggs, oocytes, testis and a Xenopus tissue culture cell line. It is apparently absent from non-dividing cells in which an immunologically related 200-kD protein is found. XMAP230 is composed of two isoforms with slightly different molecular masses and pIs. It is localized to interphase MTs, dissociates from MTs at the onset of prophase and specifically binds to spindle MTs during metaphase and anaphase. The dissociation constant of XMAP230 is 500 nM, the stoichiometry of binding to MTs is between 1:8 and 1:4, and the in vivo concentration is approximately 200 nM. Both isoforms are phosphorylated and have reduced affinity for microtubules in mitotic extracts. Analysis of the effect of XMAP230 on MT dynamics by video microscopy shows that it increases the growth rate, decreases the shrinking rate of MTs and strongly suppresses catastrophes. These results suggest that in vivo, XMAP230 participates in the control of the MT elongation rate, stabilizes MTs and locally modulates MT dynamics during mitosis.
Animals↗
Influence of surface morphology on in vitro bacterial adherence to central venous catheters.
The detailed surface topography of five polyurethane central venous catheters (CVC) (Hydrocath, Deltacath, Certofix trio, Arrow-Howes and Multicath three) was examined by scanning electron microscopy and laser profilometry. The results were correlated with the ability of Staphylococcus epidermidis to adhere to each CVC. Hydrocath CVC had the smoothest surface, as determined by profile peak values of 0.17 microns (Ra) and 0.94 microns (Rz). These CVC also had the lowest number of staphylococci adhering to the surface. In contrast, Certofix trio CVC had an irregular surface (Ra 1.29 microns and Rz 6.35 microns) which was confirmed by scanning electron microscopy. These latter CVC had significantly more bacteria colonizing their surface compared with Hydrocath and Arrow-Howes CVC (P < 0.01). The results suggest that a CVC with a smooth surface, absent of surface defects, may reduce the risk of colonization with bacteria and therefore subsequent sepsis.
Bacterial Adhesion↗