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Biomedical subjects

M Kelly

Publications and source records attributed to M Kelly.

At least 109 records · Page 6Linked to original sources
PubMed1999

Normal urodynamics in patients with bladder exstrophy: are they achievable?

PURPOSE: Urodynamic study was performed in patients with exstrophy to determine the effect of bladder neck reconstruction and the ability to achieve normal urodynamics following surgery. MATERIALS AND METHODS: A total of 30 exstrophy cases at different stages of reconstruction were retrospectively reviewed in terms of bladder capacity, compliance, stability and presence of detrusor contractions following urodynamic study. RESULTS: Bladder capacity increased from a third predicted volume for age to half after reconstruction. Approximately 80% of patients had compliant and stable bladders before bladder neck reconstruction. Following bladder neck reconstruction approximately half of the patients maintained normal compliance with a smaller number maintaining normal stability. A quarter of patients maintained normal filling dynamics following bladder neck reconstruction, and 19% maintained normal filling and voiding dynamics after reconstruction. CONCLUSIONS: The majority of closed exstrophy bladders have normal filling dynamics before bladder neck reconstruction. Compliance and stability are impaired following bladder neck reconstruction. Approximately 25% of patients with exstrophy may maintain normal detrusor function following reconstruction. However, less invasive alternatives to the Young-Dees-Leadbetter bladder neck reconstruction should be sought.

Adolescent↗
PubMed1999

Solution structure of the receptor tyrosine kinase EphB2 SAM domain and identification of two distinct homotypic interaction sites.

The sterile alpha motif (SAM) is a protein interaction domain of around 70 amino acids present predominantly in the N- and C-termini of more than 60 diverse proteins that participate in signal transduction and transcriptional repression. SAM domains have been shown to homo- and hetero-oligomerize and to mediate specific protein-protein interactions. A highly conserved subclass of SAM domains is present at the intracellular C-terminus of more than 40 Eph receptor tyrosine kinases that are involved in the control of axonal pathfinding upon ephrin-induced oligomerization and activation in the event of cell-cell contacts. These SAM domains appear to participate in downstream signaling events via interactions with cytosolic proteins. We determined the solution structure of the EphB2 receptor SAM domain and studied its association behavior. The structure consists of five helices forming a compact structure without binding pockets or exposed conserved aromatic residues. Concentration-dependent chemical shift changes of NMR signals reveal two distinct well-separated areas on the domains' surface sensitive to the formation of homotypic oligomers in solution. These findings are supported by analytical ultracentrifugation studies. The conserved Tyr932, which was reported to be essential for the interaction with SH2 domains after phosphorylation, is buried in the hydrophobic core of the structure. The weak capability of the isolated EphB2 receptor SAM domain to form oligomers is supposed to be relevant in vivo when the driving force of ligand binding induces receptor oligomerization. A formation of SAM tetramers is thought to provide an appropriate contact area for the binding of a low-molecular-weight phosphotyrosine phosphatase and to initiate further downstream responses.

Amino Acid Motifs↗
PubMed1999

Deep brain stimulation of the ventral intermediate nucleus of the thalamus for control of tremors in Parkinson's disease and essential tremor.

The beneficial effects of ventral intermediate nucleus (VIM) stimulation were evaluated in 20 patients with tremor refractory to medical therapy. Thalamic stimulation is a non-ablative procedure which has the advantage of a reversible, non-destructive lesion. Eleven patients [7 with Parkinson's disease (PD) and 4 with essential tremor (ET)] received unilateral VIM implantation, while 9 patients had staged bilateral VIM implantation (4 with PD, 5 with ET). PD patients showed a significant improvement in contralateral arm and leg rest tremor and ipsilateral leg rest tremor (p < 0.02) at a mean follow-up period of 16.2 +/- 7.0 months. Patients with PD did not demonstrate any significant decrease in medication use at follow-up. ET patients demonstrated significant improvement in postural and action tremor in the contralateral arm (p < 0.001), but no significant improvement in the contralateral leg tremor at follow-up. Significant improvements were also seen in ET patients in the Clinical Rating Scale for Tremor (p < 0.001) with respect to several activities of daily living at a mean follow-up of 14.9 +/- 8. 1 months. Deep brain stimulation is a safe and effective treatment for severe tremor refractory to medications. It is a highly effective, reversible, adaptable, and predictable procedure which avoids the complication of cognitive deficit seen in patients with bilateral thalamotomies.

Aged↗
PubMed1999

Construction of gene targeting vectors from lambda KOS genomic libraries.

We describe a highly redundant murine genomic library in a new lambda phage, lambda knockout shuttle (lambda KOS) that facilitates the very rapid construction of replacement-type gene targeting vectors. The library consists of 94 individually amplified subpools, each containing an average of 40,000 independent genomic clones. The subpools are arrayed into a 96-well format that allows a PCR-based efficient recovery of independent genomic clones. The lambda KOS vector backbone permits the CRE-mediated conversion into high-copy number pKOS plasmids, wherein the genomic inserts are automatically flanked by negative-selection cassettes. The lambda KOS vector system exploits the yeast homologous recombination machinery to simplify the construction of replacement-type gene targeting vectors independent of restriction sites within the genomic insert. We outline procedures that allow the generation of simple and more sophisticated conditional gene targeting vectors within 3-4 weeks, beginning with the screening of the lambda KOS genomic library.

Animals↗
PubMed1999

Prat falls, missteps, & solutions in implementing change.

Agencies across the country are preparing for OASIS, PPS, and other changes. The Visiting Nurse Association of Northern California shares its story of preparing for changes while simultaneously shifting gears to achieve compliance with regulations amid competing priorities and financial pressures.

California↗
PubMed1999

Comparison of costing tools in paediatric intensive care.

The cost of service provision is an issue of concern to all professionals working in health care. Department of Health reports have highlighted the need for more effective costing mechanisms for provision of paediatric intensive care (PIC). This study aimed to determine whether nurse-patient dependency scoring would be as effective as the Therapeutic Intervention Scoring System (TISS) at providing a differential costing tool for PIC. Data were collected on 251 patient admissions over 1,741 nursing shifts and analysis of variance undertaken. Findings suggest that a modified nurse-patient dependency score would be as good as TISS as a potential costing tool in PICU.

Activities of Daily Living↗
PubMed1998

A genome-wide search for schizophrenia susceptibility genes.

We completed a systematic genome-wide search for evidence of loci linked to schizophrenia using a collection of 70 pedigrees containing multiple affected individuals according to three phenotype classifications: schizophrenia only (48 pedigrees; 70 sib-pairs); schizophrenia plus schizoaffective disorder (70 pedigrees; 101 sib-pairs); and a broad category consisting of schizophrenia, schizoaffective disorder, paranoid or schizotypal personality disorder, psychosis not otherwise specified (NOS), delusional disorder, and brief reactive psychosis (70 pedigrees; 111 sib-pairs). All 70 families contained at least one individual affected with chronic schizophrenia according to DSM-III-R criteria. Three hundred and thirty-eight markers spanning the genome were typed in all pedigrees for an average resolution of 10.5 cM (range, 0-31 cM) and an average heterozygosity of 74.3% per marker. The data were analyzed using multipoint nonparametric allele-sharing and traditional two-point lod score analyses using dominant and recessive, affecteds-only models. Twelve chromosomes (1, 2, 4, 5, 8, 10, 11, 12, 13, 14, 16, and 22) had at least one region with a nominal P value <0.05, and two of these chromosomes had a nominal P value <0.01 (chromosomes 13 and 16), using allele-sharing tests in GENEHUNTER. Five chromosomes (1, 2, 4, 11, and 13) had at least one marker with a lod score >2.0, allowing for heterogeneity. These regions will be saturated with additional markers and investigated in a new, larger set of families to test for replication.

Chromosome Mapping↗
PubMed1998

Improved method for the on-line metal chelate affinity chromatography-high-performance liquid chromatographic determination of tetracycline antibiotics in animal products.

An improved on-line metal chelate affinity chromatography-high-performance liquid chromatography (MCAC-HPLC) method for the determination of tetracycline antibiotics in animal tissues and egg has been developed. Extraction was carried out with ethyl acetate. The extract was then evaporated to dryness and reconstituted in methanol prior to on-line MCAC clean-up and HPLC-UV determination. Recoveries of tetracycline, oxytetracycline, demeclocycline and chlortetracycline in the range 42% to 101% were obtained from egg, poultry, fish and venison tissues spiked at 25 micrograms kg-1. Limits of detection less than 10 microgram kg-1 were estimated for all four analytes. This method has higher throughput, higher recovery and lower limits of detection than a previously reported on-line MCAC-HPLC method which involved aqueous extraction and solid-phase extraction clean-up.

Animals↗
PubMed1998

The effects of iron and vitamin C co-supplementation on oxidative damage to DNA in healthy volunteers.

The effects of co-supplementing healthy volunteers with iron (14 mg/day ferrous sulphate) and vitamin C (either 60 mg/day or 260 mg/day as ascorbic acid) on levels of oxidative DNA damage in white blood cells were studied. The subjects were divided into two groups: one group of 20 volunteers with a higher mean initial level of plasma vitamin C (71.9 +/- 14.0 mumol/l) and a second group of 18 volunteers with a lower mean level (50.4 +/- 25.8 mumol/l). In the first group there was a significant rise in several oxidative DNA base damage products and in total oxidative DNA damage in DNA extracted from white blood cells, but not in 8-hydroxyguanine, after 6 weeks of supplementation. However, after 12 weeks levels returned approximately to normal. In the group with the lower initial level of plasma ascorbate, presupplemental levels of oxidative DNA damage were higher and decreased on supplementation with iron and ascorbate. Since oxidative DNA damage has been suggested as a risk factor for the development of cancer, the implications of increased levels in well-nourished subjects after iron/ascorbate supplementation are disturbing in view of the frequent use of dietary supplements containing both iron salts and ascorbate.

Adult↗
PubMed1998

A preliminary study to determine the effect of an infusion of cryopreserved autologous lymphocytes on immunocompetence and viral load in HIV-infected patients.

Therapeutic measures aimed at boosting the immunity of HIV-infected patients are a critical component of strategies for effective therapy of HIV and AIDS. To improve immunocompetence in patients with progressive disease, autologous lymphocytes that were collected and cryopreserved earlier in the course of HIV-infection were reinfused. None of the 12 patients receiving cell infusions experienced any adverse effects. Improvements in immunologic parameters (CD4+ counts, CD8+ counts, or both; HIV-specific cytotoxic T-lymphocyte (CTL) activity; or viral load) were seen in seven patients. Restoration of the CD4+ count to the level recorded at the time of cell harvest was achieved in two patients with less advanced disease. Plasma HIV RNA was reduced by >0.5 logs in two of the four patients tested. These preliminary results suggest that cellular immunotherapy using cryopreserved autologous lymphocytes has the potential to improve some measures of immunity in patients with HIV/AIDS and warrants further investigation.

Adult↗
PubMed1998

Comparison of responses of tattoos to picosecond and nanosecond Q-switched neodymium: YAG lasers.

OBJECTIVE: To test the hypothesis that picosecond laser pulses are more effective than nanosecond domain pulses in clearing of tattoos. DESIGN: Intratattoo comparison trial of 2 laser treatment modalities. SETTING: A large interdisciplinary biomedical laser laboratory on the campus of a tertiary medical center. PATIENTS: Consecutive patients with black tattoos were enrolled; all 16 patients completed the study. INTERVENTION: We treated designated parts of the same tattoo with 35-picosecond and 10-nanosecond pulses from 2 neodymium:YAG lasers. Patients received a total of 4 treatments at 4-week intervals. All laser pulse parameters were held constant except pulse duration. Radiation exposure was 0.65 J/cm2 at the skin surface. Biopsies were performed for routine microscopic and electron microscopic analysis at the initial treatment session and 4 weeks after the final treatment in 8 consenting patients. Also, ink samples were irradiated in vitro. MAIN OUTCOME MEASURES: In vivo, on the completion of treatment, a panel of dermatologists not associated with the study (and blinded to the treatment type) evaluated photographs to assess tattoo lightening. Formalin-fixed specimens were examined for qualitative epidermal and dermal changes as well as depth of pigment alteration. Electron micrographs were examined for particle electron density and size changes (in vivo and in vitro). The gross in vitro optical density changes were measured. RESULTS: In 12 of 16 tattoos, there was significant lightening in the picosecond-treated areas compared with those treated with nanosecond pulses. Mean depth of pigment alteration was greater for picosecond pulses, but the difference was not significant. In vivo biopsy specimens showed similar electron-lucent changes for both pulse durations. In vitro results were similar for both pulse durations, showing increases in particle sizes and decreased electron density as well as gross ink lightening. CONCLUSIONS: Picosecond pulses are more efficient than nanosecond pulses in clearing black tattoos. Black tattoos clear principally by laser-induced changes in the intrinsic optical properties of the ink.

Aluminum Silicates↗
PubMed1998

Multiplicity-Selective Coherence Transfer Steps for the Design of Amino Acid-Selective Experiments-A Triple-Resonance Experiment Selective for Asn and Gln

A multiplicity-selective coherence transfer step is discussed, that can replace the normal INEPT transfer in triple-resonance experiments. Depending on the pulse sequence in which they are implemented, amino acid-selective experiments will be created. Two experiments selective for Asn and Gln are proposed. Copyright 1998 Academic Press.

Journal Article↗
PubMed1998

Gestational carrier pregnancy.

OBJECTIVE: To evaluate the results of a gestational carrier program in terms of pregnancy rates in fresh and cryopreserved cycles. DESIGN: Retrospective analysis. SETTING: Private IVF program. PATIENT(S): Women with uterine or medical reasons for unsuccessful gestation. INTERVENTION(S): In vitro fertilization of oocytes with fresh or cryopreserved ET to gestational carriers. MAIN OUTCOME MEASURE(S): Pregnancy rates and deliveries. RESULT(S): A PR of 56.3% and a cycle rate of 30.8% was achieved in each patient <40 years of age in 117 cycles of fresh or cryopreserved ET. There were no pregnancies for nine patients >40 years of age in 27 cycles. CONCLUSION(S): Carrier gestation offers a satisfactory solution to childlessness caused by uterine or major medical factors.

Adult↗
PubMed1998

Pelvic fractures: the golden hour.

Major accident units should be able to apply standard treatment methods to control life threatening haemorrhage within the 'Golden Hour', as recommended by the ATLS guidelines. In this study all 31 major accident units in Scotland were examined to determine their ability to stabilize a pelvic fracture within this period. We found that only eight units could potentially stabilize a pelvis within 1 h. In eight other units no appropriate emergency treatment was available. We recommend that all units designated to receive multiple injuries should have a pelvic stabilization device as well as the training and expertise to use it.

Acute Disease↗
PubMed1998

Differential regulation of ventricular adrenomedullin and atrial natriuretic peptide gene expression in pressure and volume overload in the rat.

1. Adrenomedullin is a recently discovered vasodilating and natriuretic peptide whose physiological and pathophysiological roles remain to be established. Like atrial natiuretic peptide adrenomedullin is expressed in the left ventricle. Ventricular expression of atrial natriuretic peptide is known to be markedly increased by volume or pressure overload. In this study we investigated whether ventricular expression of adrenomedullin is similarly stimulated under such conditions. 2. Ventricular adrenomedullin and atrial natriuretic peptide mRNA levels as well as those of a loading control mRNA (glyceraldehyde-3-phosphate dehydrogenase) were quantified by Northern blot analysis in (a) rats with severe post-infarction heart failure induced by left coronary ligation at 30 days post-surgery and (b) in rats with pressure-related cardiac hypertrophy induced by aortic banding at several time points (0.5, 1 and 4 h, and 1, 4, 7 and 28 days) after surgery. Levels were compared with those in matched sham-operated controls. 3. The mRNA level of atrial natriuretic peptide was markedly increased (8-10-fold) in the left ventricle of animals with post-infarction heart failure. In contrast, there was only a modest (40%) increase in the level of adrenomedullin mRNA. In rats with pressure-induced cardiac hypertrophy the ventricular level of atrial natriuretic peptide mRNA was again markedly increased (maximum 10-fold). The increase was first noticeable at 24 h post-banding and persisted until 28 days. In contrast, there was no change in adrenomedullin mRNA level compared with sham-operated rats at any time point. 4. Despite having similar systemic effects, the expression of adrenomedullin and atrial natriuretic peptide in the left ventricle is differently regulated. The findings imply distinct roles for the two peptides. The results do not support an important role for ventricular adrenomedullin expression in the remodelling process that occurs during the development of cardiac hypertrophy but suggest that ventricular adrenomedullin participates in the local and/or systemic response to heart failure.

Adrenomedullin↗