Search PubMed⌕ Search

Biomedical subjects

D O'Connor

Publications and source records attributed to D O'Connor.

At least 37 records · Page 2Linked to original sources

Larger diameter femoral heads used in conjunction with a highly cross-linked ultra-high molecular weight polyethylene: a new concept.

The design of femoral and acetabular components of metal-on-polyethylene total hip arthroplasty implants has been dominated by the limitations of the wear properties of ultra-high molecular weight polyethylene (UHMWPE). As a result, the commonest femoral head diameters used range from 22 to 32 mm, the latter producing maximal volumetric wear. Cross-linking has been shown to improve significantly the wear resistance of acetabular components when tested in vitro against conventional femoral head sizes (22-32 mm). We expanded the study of the wear behavior of 1 type of electron-beam cross-linked UHMWPE with femoral head diameters ranging from 22 to 46 mm. The simulated gait studies showed that wear was independent of head size for the range of femoral head sizes studied. Even for the 46-mm femoral head, wear was reduced significantly using criteria of gravimetric and geometric measurements and morphologic appearance of the machining marks out to 11 million cycles of simulated gait.

Acetabulum↗

Primary care of patients without insurance by community health centers.

Community health centers (CHCs) are in a strong position to meaningfully contribute to health promotion, early detection, and improvement in health care outcomes for some of the most vulnerable person in the nation, since almost one in three users of federally funded CHCs was uninsured in 1994. The purpose of this article is to compare uninsured CHC users with uninsured people nationwide. Data for the analysis came primarily from two population-based surveys: the 1994 National Health Interview Survey (NHIS) and the 1995 Community Health Center (CHC) User Survey.

Adolescent↗

Evaluation of methods for detection of toxins in specimens of feces submitted for diagnosis of Clostridium difficile-associated diarrhea.

Clostridium difficile is the principal pathogen associated with hospital-acquired acute diarrheal disease. We have evaluated the performances of six approaches for diagnosis of C. difficile-associated diarrhea (CDAD). Consecutive stool specimens (n = 200) from 133 patients were examined by cytotoxin assay, by culture of C. difficile on cycloserine-cefoxitin-fructose agar, and by toxin detection using four rapid immunoassay systems (Oxoid Toxin A test, ImmunoCard Toxin A test, TechLab Tox A/B II test, and Premier Toxins A&B test). A diagnosis of CDAD was established for 35 (27%) patients (representing 29% of specimens). The adjusted sensitivity and specificity of the methods were, respectively, 98 and 99% for the cytotoxin assay, 54 and 99% for ImmunoCard, 50 and 98% for Oxoid, 79 and 98% for TechLab, 80 and 98% for Premier, and 57 and 100% for culture. The TechLab and Premier assays are acceptable tests for diagnosis of CDAD but are not equivalent to the cytotoxin assay.

Adult↗

Leptin levels in preterm human breast milk and infant formula.

OBJECTIVE: Leptin, a hormone present in breast milk, is involved in energy regulation and metabolism. The purpose of this investigation was to determine whether leptin is present in either preterm breast milk (PBM) or preterm formula (PF). The effects of delivery methods and pasteurization on leptin levels also were evaluated. METHODS: PBM samples were obtained from 29 mothers who delivered infants at between 23 and 34 weeks' gestation. Leptin levels were measured in PBM and PF with the use of a radioimmunoassay specific for human and bovine leptin, respectively. Milk samples were pasteurized by fast- and slow-heating methods. PBM and PF spiked with human leptin were delivered through catheters by bolus and continuous administration to determine the effects of delivery method on recoverable leptin levels. RESULTS: Median PBM leptin concentration was 5.28 ng/mL (intraquartile range: 24.79). Birth gestational age, birth weight, and gender of the infant did not significantly influence PBM leptin levels. Neither bolus nor continuous feeding practices affected leptin levels in PBM or spiked PF. However, pasteurization significantly reduced the amount of detectable leptin in PBM. CONCLUSIONS: PBM leptin levels were highly variable and similar to levels reported for term breast milk. There was no effect of postnatal age on PBM leptin concentrations. Sterilization decreased detectable leptin levels, whereas feeding practices had no adverse effect on the quantity of leptin delivered. Although no infant formula contained leptin, leptin could be added to formula and delivered through various feeding methods without loss.

Blotting, Western↗

Eye colour and reaction time to visual stimuli in rugby league players.

Subjects with dark eye colour are thought to perform better on reactive tasks in comparison to light-eyed subjects, whereas light-eyed subjects show enhanced performance over dark-eyed subjects on self-paced activities. This study examined reaction time using unrestricted and peripheral vision and success at the self-paced activity of goal kicking in 59 elite male Rugby League players. Subjects with dark eye colour did not react significantly faster than the light-eyed subjects when tested using unrestricted vision or peripheral vision. Examination of the self-paced activity of goal kicking showed that the percentage success rate was not significantly higher in the light-eyed group than the dark-eyed group. In conclusion, there was no significant difference in reaction time to a visual stimulus or success in goal kicking between dark- and light-eyed Rugby League players.

Adolescent↗

Alterations in the adhesion behavior of osteoblasts by titanium particle loading: inhibition of cell function and gene expression.

Total joint replacement prostheses are required to withstand corrosive environments and sustain millions of loading and articulation cycles during their term of implantation. Wear debris generation has been implicated as one of the primary causes of periprosthetic osteolysis and subsequent implant loosening in total joint replacements. Particulate debris consisting of metals, polyethylene, ceramics, and bone cement have each been shown to provoke a biological response in joint tissues. The major cell types within the interfacial granulomatous fibrous tissues consist of fibroblasts, macrophages, lymphocytes, and foreign-body giant cells. Osteoblasts are one of the principal cell types in the bone tissue adjacent to prostheses, maintaining physiologic bone remodeling through the balanced coordination of bone formation and resorption in concert with osteoclasts. To date the phenomenon of osteoblast phagocytosis of titanium particles has been suggested, but has not been sufficiently studied or confirmed. This study seeks to clarify the influence of titanium particles on osteoblast adhesion, deformability, proliferation, and gene expression profile. These studies were accomplished by performing biorheological testing, Northern blot analysis and RNase protection assay. The uptake of metallic particles by the osteoblast resulted in a particle-filament complex formation, which induced a series of variations in cell function. Understanding these variations is critical to expanding our knowledge of implant loosening and elucidating the nature of prosthetic joint failure. This study suggests that the impact of titanium particles on osteoblast function and subsequent implant loosening may have been previously underestimated.

Actin Cytoskeleton↗

Impact of practice guidelines on support surface selection, incidence of pressure ulcers, and fiscal dollars.

Predicated on a need to control overall hospital costs and to integrate a Level 1 trauma center (Campus A) with a family practice based tertiary care hospital system (Campus B), expenditures associated with rental support surfaces were evaluated. Consistency and appropriateness of support surface selection is necessary to promote positive clinical outcomes, patient comfort, and a healthier bottom line, despite increasing costs. Clinical practice guidelines for therapeutic support surfaces were developed to decrease support surface expenditures and maintain prevalence rates below national averages. Utilizing the Agency for Health Care Policy and Research algorithm for managing tissue loads, along with other guidelines, criteria for prevention, comfort, and treatment were developed to assist nurses and physicians in support surface selections. A prevalence study was conducted before these criteria were implemented and repeated 1 year later. Expenditures for all rental support surfaces were assessed quarterly. Campus A, with a history of higher financial expenditures, was monitored weekly to assess whether support surfaces selections met guideline recommendations. Nursing staff reviewed hospital protocol regarding guidelines before implementation, and a self-administered review test was required during the first year post-implementation. One year later, a modest decrease in annual expenditures for rental support surfaces was noted. Campus A had a decrease in nosocomial pressure ulcers, while Campus B had an increased prevalence rate. Staff selection of support surfaces, within guideline recommendations, improved to 75% on medical/surgical units, and 98.8% in ICUs on Campus A. Although implementing support surface selection guidelines did not result in a significant reduction in cost, it created a framework for monitoring future related decisions.

Beds↗

3-(4-Piperidinyl)- and 3-(8-aza-bicyclo[3.2.1]oct-3-yl)-2-phenyl-1H-indoles as bioavailable h5-HT2A antagonists.

A series of 3-(4-piperidinyl)- and 3-(8-aza-bicyclo[3.2.1]oct-3-yl)-2-phenyl-1H-indoles have been prepared and evaluated as ligands for the h5-HT2A receptor. 3-(8-Phenethyl-8-aza-bicyclo[3.2.1]oct-3-yl)-2-phenyl-1H-indole is a high-affinity (1.2nM), selective (>800 fold over h5-HT2C and hD2 receptors) antagonist at the h5-HT2A receptor with oral bioavailability in rats.

Administration, Oral↗

A mucosal vaccine against diphtheria: formulation of cross reacting material (CRM(197)) of diphtheria toxin with chitosan enhances local and systemic antibody and Th2 responses following nasal delivery.

The development of new generation vaccines against diphtheria is dependent on the identification of antigens and routes of immunization that are capable of stimulating immune responses similar to, or greater than, those obtained with the parenterally-delivered toxoid vaccine, while reducing the adverse effects that have been associated with the traditional vaccine. In this study, we examined the cellular and humoral immune responses in mice generated after both parenteral and mucosal immunizations with cross-reacting material (CRM(197)) of diphtheria toxin. We found that both native and mildly formaldehyde-treated CRM(197) and conventional diphtheria toxoid (DT) induced mixed Th1/Th2 responses and similar levels of anti-DT serum IgG following parenteral immunization. In contrast, CRM(197) preparations were poorly immunogenic when administered intranasally in solution. However, formulation of the antigens with chitosan significantly enhanced their immunogenicity, inducing high levels of antigen-specific IgG, secretory IgA, toxin-neutralizing antibodies and T cell responses, predominately of Th2 subtype. Furthermore, intranasal immunization with CRM(197) and chitosan induced protective antibodies against the toxin in a guinea pig passive challenge model. We also found that priming parenterally with DT in alum and boosting intranasally with CRM(197) was a very effective method of immunization in mice, capable of inducing high levels of anti-DT IgG and neutralizing antibodies in the serum and secretory IgA in the respiratory tract. Our findings suggest that boosting intranasally with CRM(197) antigen may be very effective in adolescents or adults who have previously been parenterally immunized with a conventional diphtheria toxoid vaccine.

Administration, Intranasal↗

Time- and space-resolved dynamic studies on ceramic and cementitious materials.

A review is given of the results and lessons arising from a sustained in situ diffraction study of the structure and performance of functional ceramic/cementitious materials in which synchrotron-based energy-dispersive diffraction has been the central under-pinning technique. Five particular points of discussion emerge: the demands on time resolution; the use of penetrating radiation for the in situ mode; the need for complementary techniques; re-analysing of data; spatially resolved diffraction: a new tomography. These aspects are discussed in turn using illustrative examples taken from the fields of cement hydration, clay intercalation, cation-exchanged zeolites, and particulate/fluid invasion into building and archaeological objects.

Journal Article↗

Evidence for accelerated desensitisation of 5-HT(2C) receptors following combined treatment with fluoxetine and the 5-HT(1A) receptor antagonist, WAY 100,635, in the rat.

Both pre-clinical and clinical studies suggest that additional treatment with 5-HT(1A) receptor antagonists may accelerate the antidepressant efficacy/onset of selective serotonin re-uptake inhibitors (SSRIs). Given that chronic SSRI treatment has been shown to desensitise 5-HT(2C) receptor mediated responses, we have used the rat social interaction test to determine if combined treatment with WAY 100,635, a selective 5-HT(1A) receptor antagonist, will accelerate this effect. In pairs of unfamiliar rats, acute administration of the 5-HT(2C) receptor agonist m-chlorophenylpiperazine (mCPP) or fluoxetine decreased the time spent in social interaction, responses which were reversed by the 5-HT(2C/2B) receptor antagonists SB 200646A and SB 221284. Similar reductions in social interaction were observed in rats treated with fluoxetine (10 mg/kg, i.p. daily) for 4, 7 and 14 days but was no longer apparent after 28 days of treatment. In contrast, only 7 days of combined treatment with WAY 100,635 (1 mg/kg/s.c./day) and fluoxetine were needed to reverse this response. The decrease in social interaction induced by an acute challenge of mCPP (1 mg/kg, i. p.) was also reduced after 6 days co-treatment with WAY 100,635 and fluoxetine. Thus, WAY 100,635 accelerates SSRI-induced desensitisation of 5-HT(2C) receptors, suggesting that this response might contribute towards the therapeutic effects of SSRIs in man.

Animals↗

Evaluation of the safety and efficacy of enoxaparin and warfarin for prevention of deep vein thrombosis after total knee arthroplasty.

Of 263 patients who underwent total knee arthroplasty, 122 received adjusted low-dose warfarin and 141 received enoxaparin as deep vein thrombosis (DVT) prophylaxis. Three patients in the warfarin group and 3 in the enoxaparin group developed ultrasound-detectable DVT (P > .05). Although the amount of perioperative blood transfused was equivalent in both groups, the overall hemoglobin drop was greater (P < .005) in the enoxaparin group (2.9 g/dL) as compared with the warfarin group (2.3 g/dL). Five patients (4.6%) in the warfarin group and 16 (11.3%) in the enoxaparin group had bleeding complications (P < .05). Our data support earlier published reports suggesting that reductions, if any, in the incidence of DVT associated with enoxaparin are offset by a significant increase in bleeding complications as compared with adjusted-dose warfarin. We continue to use adjusted-dose warfarin as primary thromboembolic prophylaxis after total knee arthroplasty.

Aged↗

Neuropathological findings in the very old. Results from the first 101 brains of a population-based longitudinal study of dementing disorders.

We report a unique longitudinal epidemiological study of cognitive decline in the elderly population of the city of Cambridge, UK. A population sample of people aged 75 and over was surveyed between 1984-1996 (n = 2,616) and followed 2.4, 6, and 9 years later. CAMDEX diagnostic criteria were used for clinical assessment, and the neuropathological protocol (in 101 cases) was based on the CERAD method, with additional features to allow Braak staging of neurofibrillary pathology. The main findings are of the heterogeneity of lesions to be found in very old populations, and the existence of considerable overlap in the pathologies found in the demented and nondemented. It seems that white matter (ischemic) pallor an amyloid angiopathy, as well as neuritic plaques, neurofibrillary tangles and Lewy body formation are all lesions that increase the likelihood of dementia.

Age Factors↗

Enhanced growth of preterm infants fed a new powdered human milk fortifier: A randomized, controlled trial.

OBJECTIVE: A prospective, double-blind, randomized, controlled trial was conducted to evaluate the growth and nutritional status of preterm infants receiving preterm human milk supplemented with a newly formulated powdered human milk fortifier (HMF), study fortifier (SF), or a powdered commercial HMF (CF). METHODS: Infants (n = 144) with a birth weight </=1600 g and gestational age at birth of </=33 weeks were enrolled and randomized before 21 days of life. Study day (SDAY) 1 was defined as the day full-strength fortification (4 packets/100 mL) began and the infant reached an intake of at least 100 mL/kg/day. Growth, biochemical indices of nutritional status, enteral intake, feeding tolerance, clinical histories, and morbidity were assessed serially. The primary outcome variable was weight gain (g/kg/day) from SDAYs 1 to 29 or hospital discharge, whichever came first. RESULTS: Infants fed human milk supplemented with SF consistently grew more rapidly from SDAYs 1 to 29 (or hospital discharge), regardless of whether the statistical analyses were performed on all subjects who were randomized into the study and reached SDAY 1 (intent-to-treat) or were limited to those able to adhere strictly to the feeding protocol of the study (subgroup). Using mean values adjusted for study site (least square [LS] means), the weight gain differences were 2.6 and 3.8 g/kg/day for the intent-to-treat and subgroup analyses, respectively. Likewise, the length-gain differences were.14 and.18 cm/week for the intent-to-treat and subgroup analyses, respectively. Infants in the SF group reached a weight of 1800 g at SDAY 18, and those in the CF group at SDAY 25. Mean alkaline phosphatase values among infants in the SF group were higher than for the CF infants (eg, LS means: 327 U/L vs 272 U/L, intent-to-treat analysis), likely reflecting the more rapid linear growth of the SF infants. Mean serum calcium values tended to be lower in the SF group in the intent-to-treat analysis and were significantly lower in the subgroup analysis (LS means: 10.3 mg/dL vs 11.2 mg/dL). Both fortifiers were generally well-tolerated, although an increased number of infants in the CF group exited the feeding protocol because of gastric residuals and abdominal distention. CONCLUSION: A new powdered HMF was shown to enhance the growth of preterm infants, compared with a commercially available powdered HMF in the United States.

Anthropometry↗

Fluorination of 3-(3-(piperidin-1-yl)propyl)indoles and 3-(3-(piperazin-1-yl)propyl)indoles gives selective human 5-HT1D receptor ligands with improved pharmacokinetic profiles.

It has previously been reported that a 3-(3-(piperazin-1-yl)propyl)indole series of 5-HT1D receptor ligands have pharmacokinetic advantages over the corresponding 3-(3-(piperidin-1-yl)propyl)indole series and that the reduced pKa of the piperazines compared to the piperidines may be one possible explanation for these differences. To investigate this proposal we have developed versatile synthetic strategies for the incorporation of fluorine into these ligands, producing novel series of 4-fluoropiperidines, 3-fluoro-4-aminopiperidines, and both piperazine and piperidine derivatives with one or two fluorines in the propyl linker. Ligands were identified which maintained high affinity and selectivity for the 5-HT1D receptor and showed agonist efficacy in vitro. The incorporation of fluorine was found to significantly reduce the pKa of the compounds, and this reduction of basicity was shown to have a dramatic, beneficial influence on oral absorption, although the effect on oral bioavailability could not always be accurately predicted.

Administration, Oral↗