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Biomedical subjects

K Gallagher

Publications and source records attributed to K Gallagher.

At least 19 recordsLinked to original sources
PubMed2006

Lower limb cellulitis: features associated with length of hospital stay.

AIMS: This study aimed to identify features associated with length of hospital stay (LOHS), length of intravenous antibiotic therapy (LIVAT) and six-week outcomes for patients with lower limb cellulitis, and to test the Eron/Passos classification of cellulitis in the New Zealand system. METHODS: Eighty-five variables were collected prospectively from a cohort of 51 inpatients admitted to Christchurch hospital. The primary end-point for analysis was LOHS. LIVAT and six-week outcomes were secondary end-points. RESULTS: On univariate analysis use of diuretics, living alone, cellulitis acuity, a creatinine concentration of >0.1 mmol/l, poor mobility, pulse >90 bpm, age >70 years, oedema extent, chronic oedema, ulceration, neutrophil count >10x10(9)/l, erythema area >1000 cm2 and haemoglobin concentration less than normal were significantly (P= or <0.05) associated with LOHS. A stay of < or =3 days was associated with less oedema, absence of diuretic use and less acute cellulitis. A stay of >7 days was associated with use of diuretics, living alone, age >70 years, more oedema, erythema area >1000 cm2, haemoglobin less than normal, ulceration, creatinine >0.1 mmol/l and poor mobility. The presence of a discharge was associated with LIVAT. Multivariate analysis accounted for 48% of the variance in LOHS and 16% for LIVAT. Use of diuretics, neutrophil count >10x10(9)/l and oedema score were independently associated with LOHS, with oedema score associated with short stay and diuretic use with long stay. The Eron/Passos system was not helpful so a new scoring system was devised which successfully classified patients into length of stay groups. CONCLUSIONS: The clinical features analysed accounted for half of the variance in LOHS. An important reason may be physician discretion. If so, our scoring system based on these results could be used in a clinical pathway to improve patient care. This tool would need to be evaluated prospectively.

Adolescent↗
PubMed2002

Immunofluorescent patterns produced by antineutrophil cytoplasmic antibodies (ANCA) vary depending on neutrophil substrate and conjugate.

BACKGROUND: The "International consensus statement on testing and reporting antineutrophil cytoplasmic antibodies (ANCA)" advocates screening by indirect immunofluorescence (IIF), but external quality assessment programmes often demonstrate different IIF patterns for a single serum. AIM: To determine whether the variation in IIF patterns can be attributed solely to errors in interpretation. METHODS: This study compared the IIF patterns produced by four sera (two with cytoplasmic or C-ANCA; one with perinuclear or P-ANCA with myeloperoxidase (MPO) specificity; and one P-ANCA without MPO specificity) that were tested in 11 different laboratories. The sera were examined according to individual laboratory protocols at dilutions of 1/10 to 1/40 using P1 (n = 4), P2 (n = 2), P3 (n = 2), or in house (n=3) neutrophil preparations and conjugates from manufacturers C1 (n = 3), C2 (n = 1), C3 (n = 2), C4 (n = 1), C5 (n = 2), and C6 (n = 2). The IIF patterns were noted in each laboratory, the testing repeated, and the fluorescent patterns photographed and subsequently discussed at a meeting of the Australian ANCA study group. RESULTS: All IIF patterns described in individual laboratories were confirmed on retesting and by the ANCA study group. Neutrophil substrates produced commercially or in house varied in their ability to demonstrate cytoplasmic granularity and interlobular accentuation, which distinguish between "C-ANCA" and "C-ANCA (atypical)". All commercial and in house neutrophil substrates demonstrated neutrophil nuclear extension of P-ANCA fluorescence, which correlates with MPO specificity. However, eight assays (eight of 43) from eight laboratories resulted in IIF patterns different from those usually seen. One of these produced a C-ANCA (atypical) rather than a C-ANCA pattern. The other seven resulted in at least some cytoplasmic fluorescence when the consensus pattern was P-ANCA with (n = 4) or without (n = 3) MPO specificity. These assays used three different commercial and one in house neutrophil substrate, and six different conjugates, with anti-IgG, anti-(Fab)'(2), anti-Ig (heavy and light chain), and anti-G, A, and M activity. Four of the seven assays tested on commercial substrates had used the manufacturer's conjugates. CONCLUSIONS: This study indicates that the variation in IIF patterns seen with ANCA positive sera tested in different laboratories does not necessarily result from errors in the interpretation of patterns and cannot be attributed solely to the use of a particular neutrophil substrate or conjugate, or to the use of substrate from one manufacturer and conjugate from another.

Antibodies, Antineutrophil Cytoplasmic↗
PubMed2001

Volunteer-based universal newborn hearing screening program.

OBJECTIVE: To evaluate efficacy and costs of a volunteer-based universal newborn hearing screening program. METHODS: The Lucile Packard Children's Hospital at Stanford newborn hearing screening program database was reviewed. Results and costs of the hearing screens were analyzed. RESULTS: Hearing screens were performed on 5771 newborns treated in the well-baby nursery and nine infants from this population were identified with hearing loss, seven of whom had no risks factors for hearing loss. Using volunteers to perform the first-line screen with the automated auditory brainstem response (AABR) technology, 91% of infants registered for screening were evaluated prior to discharge. An additional 4% of infants were screened as outpatients. If an infant failed the AABR on two occasions, he or she was rescreened with the AABR or transient evoked otoacoustic emissions by a licensed audiologist, often while the infant was still in the hospital. Using this algorithm, 5% of infants tested in the well-baby nursery needed additional follow-up as an outpatient. Cost analysis of this volunteer-based program reveals a per/baby screening cost of $27.41. CONCLUSIONS: A volunteer-based hearing screening program is a viable option for hearing screening in well-baby nurseries but does not result in significant cost savings during the first 2 years of the program.

Audiometry↗
PubMed2001

Etanercept therapy in children with treatment-resistant uveitis.

OBJECTIVE: To evaluate the safety and efficacy of the tumor necrosis factor fusion protein etanercept in children with treatment-resistant uveitis. METHODS: Ten children with chronic active uveitis (7 girls and 3 boys, mean age 7.5 years [range 3-12 years]) were enrolled in this prospective study. In 7 children, uveitis was associated with pauciarticular juvenile rheumatoid arthritis. Five children were antinuclear antibody positive. All patients had failed previous therapy with topical steroids and methotrexate and/or cyclosporine. All were treated with etanercept at a dosage of 0.4 mg/kg twice weekly for the first 3 months, and then, if eyes did not improve, with 25 mg twice weekly (mean 1.1 mg/kg) for at least 3 additional months. RESULTS: At the beginning of the trial, uveitis affected 18 eyes in the 10 children. Within 3 months, 10 of 16 affected eyes (63%; P = 0.017) showed a rapid decrease in anterior chamber cell density, including remission of uveitis in 4 eyes. In children with visual acuity of less than 20/25, 4 of 10 eyes (40%) improved. An exacerbation of uveitis during etanercept therapy occurred in only 1 child (1 of 14 eyes [7%]). Other ocular outcome parameters, such as intraocular pressure, synechia formation, and lens clarity, remained unchanged. Following a dosage increase to an average of 1.1 mg/kg after 3 months in 7 children, no further improvement was noted. CONCLUSION: Our data suggest that etanercept injected subcutaneously twice a week has a beneficial effect on treatment-resistant chronic uveitis in children. Further controlled studies with etanercept in systemic or topical form are necessary to confirm its efficacy and optimal mode of administration.

Administration, Topical↗
PubMed2001

Hand-assisted laparoscopic donor nephrectomy minimizes warm ischemia.

OBJECTIVES: Traditional open donor nephrectomy is associated with good donor outcomes and excellent allograft function. Laparoscopic donor nephrectomy may accomplish these same goals with less morbidity. We report our initial experience with hand-assisted laparoscopic living donor nephrectomy using a commercially available hand-assist device. METHODS: Donor and allograft outcomes for the first 30 patients undergoing hand-assisted laparoscopic live donor nephrectomy in our institution were prospectively analyzed. RESULTS: Hand-assisted laparoscopic donor nephrectomy was successfully completed in 29 (97%) of 30 donors. Organ dissection was carried out purely laparoscopically. Vessel division and allograft extraction were performed using a hand-assisted technique. The average operative time was 275 minutes (range 193 to 360), with an estimated blood loss of 99 mL (range 50 to 300). Pneumoperitoneum was consistently maintained during the hand-assisted portion of the procedure. The mean warm ischemic time was 72.5 seconds (range 30 to 165). On average, the regular diet was resumed after 2.2 days (range 1 to 3), and patients were discharged home 3.4 days (range 2 to 5) after surgery. Eight minor complications occurred in the donor group. Immediate graft function occurred in all 30 cases. No ureteral complications occurred. The recipient creatinine levels ranged from 0.6 to 2.4 mg/dL at an average follow-up of 11.5 months (range 1 to 23). CONCLUSIONS: Laparoscopic donor nephrectomy is technically feasible and can be performed with minimal morbidity. Hand-assisted kidney extraction may help to facilitate immediate allograft function by minimizing the warm ischemic time.

Adult↗
PubMed2001

The completeness, validity, and timeliness of AIDS surveillance data.

PURPOSE: To assess the completeness, validity, and timeliness of the AIDS surveillance system after the 1993 change in the surveillance case definition. METHODS: To assess completeness of AIDS case reporting, three study sites conducted a comparison of their AIDS surveillance registries with an independent source of information. To evaluate validity, the same sites conducted record reviews on a sample of reported AIDS cases, we then compared agreement between the original report and the record review for sex, race, and mode of transmission. To evaluate timeliness, we calculated the median delay from time of diagnosis to case report, before and after the change in case definition, in each of the three study sites. RESULTS: After expansion of the case definition, completeness of AIDS case reporting in hospitals (> or = 93%) and outpatient settings (> or = 90%) was high. Agreement between the information provided on the original case report and the medical record was > 98% for sex, > 83% for each race/ethnicity group; and > 67% for each risk group. The median reporting delay after the change was four months, but varied by site from three to six months. CONCLUSIONS: The completeness, validity, and timeliness of the AIDS surveillance system remains high after the 1993 change in the surveillance case definition. These findings might be useful for programs implementing integrated HIV and AIDS surveillance systems.

Acquired Immunodeficiency Syndrome↗
PubMed2001

High-quality, cost-effective strategy for detection of autoantibodies to extractable nuclear antigens.

We evaluated methods for the detection of autoantibodies to extractable nuclear antigens (ENAs) to determine the strategy that yielded the most cost effective and clinically meaningful result. We prospectively compared counterimmunoelectrophoresis (CIEP) with and without serum prediffusion (SPD) and found that SPD significantly improved the quality of precipitation lines. This resulted in a decreased requirement for repeat testing and, consequently, was associated with a significant decrease in reagent costs and specimen turnaround time. We also retrospectively compared reactivity by CIEP, CIEP plus SPD, enzyme-linked immunosorbent assay (ELISA), and line immunoassay (LIA) of 52 serum samples that were previously determined to be positive for ENAs, and we correlated the results with clinical diagnoses. There was significant agreement among CIEP, CIEP plus SPD, ELISA, and LIA for the detection of anti-SS-A, anti-SS-B and anti-RNP. In general, CIEP, CIEP plus SPD, and LIA correlated better with the clinical diagnoses than ELISA, even though ELISA detected anti-ENAs more often than the other methods. CIEP plus SPD is therefore the most cost effective method for the identification of clinically meaningful ENAs. Based on our experience, we now screen for ENAs by CIEP, and positive samples are then typed by CIEP plus SPD. Samples that are difficult to interpret are then further assessed by an alternative method.

Antigens, Nuclear↗
PubMed2001

Genotypic correlates of phenotypic resistance to efavirenz in virus isolates from patients failing nonnucleoside reverse transcriptase inhibitor therapy.

Efavirenz (also known as DMP 266 or SUSTIVA) is a potent nonnucleoside inhibitor of human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT) activity and of HIV-1 replication in vitro and in vivo. Most patients on efavirenz-containing regimens have sustained antiviral responses; however, rebounds in plasma viral load have been observed in some patients in association with the emergence of mutant strains of HIV-1. Virus isolates from the peripheral blood mononuclear cells (PBMCs) of patients with such treatment failures, as well as recombinant viruses incorporating viral sequences derived from patient plasma, show reduced in vitro susceptibility to efavirenz in association with mutations in the RT gene encoding K103N, Y188L, or G190S/E substitutions. Patterns of RT gene mutations and in vitro susceptibility were similar in plasma virus and in viruses isolated from PBMCs. Variant strains of HIV-1 constructed by site-directed mutagenesis confirmed the role of K103N, G190S, and Y188L substitutions in reduced susceptibility to efavirenz. Further, certain secondary mutations (V106I, V108I, Y181C, Y188H, P225H, and F227L) conferred little resistance to efavirenz as single mutations but enhanced the level of resistance of viruses carrying these mutations in combination with K103N or Y188L. Viruses with K103N or Y188L mutations, regardless of the initial selecting nonnucleoside RT inhibitor (NNRTI), exhibited cross-resistance to all of the presently available NNRTIs (efavirenz, nevirapine, and delavirdine). Some virus isolates from nevirapine or delavirdine treatment failures that lacked K103N or Y188L mutations remained susceptible to efavirenz in vitro, although the clinical significance of this finding is presently unclear.

Alkynes↗
PubMed2001

Safety and efficacy of high dose etanercept in treatment of juvenile rheumatoid arthritis.

OBJECTIVE: To evaluate safety and efficacy of high dose etanercept (> 0.8 mg/kg, maximum 25 mg subcutaneously twice weekly) (Enbrel) in children with juvenile rheumatoid arthritis (JRA) and inadequate prior response to standard dose etanercept. METHODS: Retrospective chart review of 8 children (6 girls, 2 boys, mean age 8.4 yrs, range 5-16 yrs). Five children had systemic onset, polyarticular course JRA; 2 had polyarticular onset; and one had pauciarticular onset, polyarticular course JRA. All children had failed at least 3 mo (mean 9 mo) treatment with standard dose etanercept (0.4 mg/kg SC twice a week). All 8 children had increase in the etanercept dose to at least 0.8 mg/kg (mean 1.1 mg/kg, maximum 25 mg SC twice weekly) for a mean of 7 mo (range 3-10 mo). Efficacy of high dose etanercept was evaluated by changes in joint count, laboratory data, and ability to decrease concomitant medication. RESULTS: Improvements in the joint count and laboratory findings (erythrocyte sedimentation rate, hemoglobin and platelet count) were observed in 2 of 8 (25%) children. In these 2, concomitant prednisone was reduced or discontinued. In contrast, no changes in disease activity or laboratory findings were observed in the other 6 children. Overall, high dose etanercept was well tolerated. No laboratory abnormalities were detected and no child withdrew because of adverse events. CONCLUSION: High dose etanercept is safe and well tolerated in children, but efficacy seems limited. In children with unsatisfactory response to standard dose etanercept, an increased dose or treatment prolongation may not offer any additional benefit.

Adolescent↗
PubMed2000

Roles for polarity and nuclear determinants in specifying daughter cell fates after an asymmetric cell division in the maize leaf.

Asymmetric cell divisions occur repeatedly during plant development, but the mechanisms by which daughter cells are directed to adopt different fates are not well understood [1,2]. Previous studies have demonstrated roles for positional information in specification of daughter cell fates following asymmetric divisions in the embryo [3] and root [4]. Unequally inherited cytoplasmic determinants have also been proposed to specify daughter cell fates after some asymmetric cell divisions in plants [1,2,5], but direct evidence is lacking. Here we investigate the requirements for specification of stomatal subsidiary cell fate in the maize leaf by analyzing four mutants disrupting the asymmetric divisions of subsidiary mother cells (SMCs). We show that subsidiary cell fate does not depend on proper localization of the new cell wall during the SMC division, and is not specified by positional information acting on daughter cells after completion of the division. Instead, our data suggest that specification of subsidiary cell fate depends on polarization of SMCs and on inheritance of the appropriate daughter nucleus. We thus provide evidence of a role for unequal inheritance of an intracellular determinant in specification of cell fate after an asymmetric plant cell division.

Cell Division↗
PubMed2000

Patient compliance and blood pressure control on a nuclear-powered aircraft carrier: impact of a pharmacy officer.

The impact of a pharmacy officer on patient compliance and blood pressure control on a deployed nuclear-powered aircraft carrier for a 2-week at-sea period was evaluated. Before any counseling by a pharmacy officer, 43 crewmembers on chronic medications anonymously completed a compliance questionnaire. The pharmacy officer then counseled these crewmembers. A follow-up compliance questionnaire was completed 2 weeks later. After counseling, compliance had increased 58% (p < 0.0001) from compliance measured before counseling. The pharmacy officer also initiated therapeutic interventions. Among 26 crewmembers diagnosed as hypertensive, preintervention blood pressure (BP) measurements were obtained. Ten to 14 days after the initial BP measurement, BP was remeasured. After intervention, 31% (p < 0.02) more crewmembers were at BP goal compared with before intervention. A pharmacy officer, working closely with a medical officer, improved patient compliance and blood pressure control. One problem identified was that these warships require computer software that can prospectively identify drug-drug interactions.

Blood Pressure↗
PubMed1999

discordia mutations specifically misorient asymmetric cell divisions during development of the maize leaf epidermis.

In plant cells, cytokinesis depends on a cytoskeletal structure called a phragmoplast, which directs the formation of a new cell wall between daughter nuclei after mitosis. The orientation of cell division depends on guidance of the phragmoplast during cytokinesis to a cortical site marked throughout prophase by another cytoskeletal structure called a preprophase band. Asymmetrically dividing cells become polarized and form asymmetric preprophase bands prior to mitosis; phragmoplasts are subsequently guided to these asymmetric cortical sites to form daughter cells of different shapes and/or sizes. Here we describe two new recessive mutations, discordia1 (dcd1) and discordia2 (dcd2), which disrupt the spatial regulation of cytokinesis during asymmetric cell divisions. Both mutations disrupt four classes of asymmetric cell divisions during the development of the maize leaf epidermis, without affecting the symmetric divisions through which most epidermal cells arise. The effects of dcd mutations on asymmetric cell division can be mimicked by cytochalasin D treatment, and divisions affected by dcd1 are hypersensitive to the effects of cytochalasin D. Analysis of actin and microtubule organization in these mutants showed no effect of either mutation on cell polarity, or on formation and localization of preprophase bands and spindles. In mutant cells, phragmoplasts in asymmetrically dividing cells are structurally normal and are initiated in the correct location, but often fail to move to the position formerly occupied by the preprophase band. We propose that dcd mutations disrupt an actin-dependent process necessary for the guidance of phragmoplasts during cytokinesis in asymmetrically dividing cells.

Actins↗
PubMed1998

Electrostatic contributions to heat capacity changes of DNA-ligand binding.

Significant heat capacity changes (DeltaCp) often accompany protein unfolding, protein binding, and specific DNA-ligand binding reactions. Such changes are widely used to analyze contributions arising from hydrophobic and polar hydration. Current models relate the magnitude of DeltaCp to the solvent accessible surface area (ASA) of the molecule. However, for many binding systems-particularly those involving non-peptide ligands-these models predict a DeltaCp that is significantly different from the experimentally measured value. Electrostatic interactions provide a potential source of heat capacity changes and do not scale with ASA. Using finite-difference Poisson-Boltzmann methods (FDPB), we have determined the contribution of electrostatics to the DeltaCp associated with binding for DNA binding reactions involving the ligands DAPI, netropsin, lexitropsin, and the lambda repressor binding domain.

Antineoplastic Agents↗
PubMed1998

Induction of mortality and malformation in Xenopus laevis embryos by water sources associated with field frog deformities.

Water samples from several ponds in Minnesota were evaluated for their capacity to induce malformations in embryos of Xenopus laevis. The FETAX assay was used to assess the occurrence of malformations following a 96-hr period of exposure to water samples. These studies were conducted following reports of high incidences of malformation in natural populations of frogs in Minnesota wetlands. The purpose of these studies was to determine if a biologically active agent(s) was present in the waters and could be detected using the FETAX assay. Water samples from ponds with high incidences of frog malformations (affected sites), along with water samples from ponds with unaffected frog populations (reference sites), were studied. Initial experiments clearly showed that water from affected sites induced mortality and malformation in Xenopus embryos, while water from reference sites had little or no effect. Induction of malformation was dose dependent and highly reproducible, both with stored samples and with samples taken at different times throughout the summer. The biological activity of the samples was reduced or eliminated when samples were passed through activated carbon. Limited evidence from these samples indicates that the causal factor(s) is not an infectious organism nor are ion concentrations or metals responsible for the effects observed. Results do indicate that the water matrix has a significant effect on the severity of toxicity. Based on the FETAX results and the occurrence of frog malformations observed in the field, these studies suggest that water in the affected sites contains one or more unknown agents that induce developmental abnormalities in Xenopus. These same factors may contribute to the increased incidence of malformation in native species.

Animals↗