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Biomedical subjects

R Marshall

Publications and source records attributed to R Marshall.

At least 37 records · Page 2Linked to original sources
PubMed2000

Is the apparent cardioprotective effect of recent alcohol consumption due to confounding by prodromal symptoms?

Previous research has reported a protective association between alcohol drinking and acute coronary heart disease in the 24-hour period after drinking. This study investigated whether this apparent protective association resulted from confounding due to the effect of prodromal symptoms on drinking behavior. In 1992, the authors conducted a case-control study that measured recent alcohol consumption and reasons for recent abstention from alcohol among patients with acute coronary heart disease identified from a community-based disease register and a representative control sample from the same community (Auckland, New Zealand). Cases were significantly more likely than controls to report recent abstention from drinking because they felt unwell. In unadjusted analyses, a protective association was observed between recent alcohol consumption and acute coronary heart disease; however, this association was weakened considerably after adjustment for the effect of prodromal symptoms on drinking behavior. The previously reported protective association between recent alcohol consumption and acute coronary heart disease appears to be largely due to the confounding effect of prodromal symptoms on drinking.

Alcohol Drinking↗
PubMed2000

Mutagenesis of E477 or K505 in the B' domain of human topoisomerase II beta increases the requirement for magnesium ions during strand passage.

A type II topoisomerase is essential for decatenating DNA replication products, and it accomplishes this task by passing one DNA duplex through a transient break in a second duplex. The B' domain of topoisomerase II contains three highly conserved motifs, EGDSA, PL(R/K)GK(I/L/M)LNVR, and IMTD(Q/A)DXD. We have investigated these motifs in topoisomerase II beta by mutagenesis, and report that they play a critical role in establishing the DNA cleavage-religation equilibrium. In addition, the mutations E477Q (EGDSA) and K505E (PLRGKILNVR) increase the optimal magnesium ion concentration for strand passage, without affecting the Mg(2+) dependence of ATP hydrolysis. It is likely that the binding affinity of the magnesium ion(s) specifically required for DNA cleavage has been reduced by these mutations. The crystal structure of yeast topo II indicates that residues E477 and K505 may help to position the three aspartate residues of the IMTD(Q/A)DXD motif for magnesium ion coordination, and we propose two possible locations for the magnesium ion binding site(s). These observations are consistent with a previous model in which the B' domain is positioned such that these acidic residues lie next to the active site tyrosine residue. A magnesium ion bound by these aspartate residues could therefore mediate the DNA cleavage-religation reaction.

Adenosine Triphosphate↗
PubMed2000

Evaluation of thresholds for benomyl- and carbendazim-induced aneuploidy in cultured human lymphocytes using fluorescence in situ hybridization.

Threshold mechanisms of activity for mutagenic agents have been debated for some time, especially for those substances which induce aneuploidy by inhibiting mitotic spindle function. No observed effect levels (NOELs) or "practical thresholds" have been demonstrated for several aneugens both in vitro and in vivo generally by either counting chromosomes in metaphase preparations or by observing micronuclei. Recently, fluorescence in situ hybridization (FISH) has proven to be a sensitive and useful technique for the assessment of aneuploidy at low concentrations. Using binucleate human lymphocytes coupled with FISH, we have been able to characterize a threshold mechanism of action for two spindle inhibitors, benomyl and its active metabolite, carbendazim. Test chemicals were added 24 h following culture initiation. After a further 20 h, cytochalasin B was added, and cells were harvested 28 h later (72 h post initiation). The distribution of chromosomes between the nuclei of binucleate cells was evaluated by fluorescence microscopy for the simultaneous detection of centromeres labeled with FITC (green) or Cy-3 (red). Six human chromosomes were investigated in pairs (1 and 8, 11 and 18, and X and 17). Abnormalities were classified as chromosome loss (including centromeric positive micronuclei), chromosome gain, non-disjunction, or polyploidy. Dose-response data were generated over a range of closely spaced concentrations at 100 ng/ml intervals. The threshold, defined as the lowest "effect" concentration using statistical methods, was determined for each chromosome. Non-disjunction proved to be the most sensitive endpoint for the detection of aneuploidy occurring at higher frequencies and lower concentrations. Results for the six chromosomes demonstrated similar dose-response data which included a series of concentrations with no statistically significant increase above background, followed by a second range of higher concentrations with a statistically significant, concentration-dependent increase. Nearly equimolar threshold concentrations were determined for benomyl- and carbendazim-induced non-disjunction.

Adult↗
PubMed2000

One foot in-one foot out: weathering the storm of pregnancy after perinatal loss.

Pregnancies after perinatal loss are oftentimes anxiety-laden and lacking in joy. This may lead to potential negative obstetrical and parenting outcomes. The purpose of this qualitative inquiry was to gain insights into women's pregnancy after perinatal loss experiences, including major features and helpful provider responses. Thirteen women, at varying points surrounding pregnancy after perinatal loss, participated in either a focus group or interview. An overall metaphor of "One Foot In-One Foot Out" and seven themes within four contexts emerged from the data. Women found themselves living within the contexts of (a) reliving the past, (b) trying to find a balance in the present, (c) recognizing their changed reality, and (d) living with wavering expectations. Seven themes characterized their navigation of the pregnancy: (1) setting the stage, (2) weathering the storm, (3) gauging where I am, (4) honoring each baby, (5) expecting the worst, (6) supporting me where I am, and (7) realizing how I've changed. Trying to stay balanced is the major challenge in pregnancy after perinatal loss.

Adaptation, Psychological↗
PubMed2000

Ataque de nervios and history of childhood trauma.

OBJECTIVE: Ataque de nervios is a common, self-labeled Hispanic folk diagnosis. It typically describes episodic, dramatic outbursts of negative emotion in response to a stressor, sometimes involving destructive behavior. Dissociation and affective dysregulation during such episodes suggested a link to childhood trauma. We therefore assessed psychiatric diagnoses, history of ataque, and childhood trauma in treatment-seeking Hispanic outpatients (N = 70). Significantly more subjects with an anxiety or affective disorder plus ataque reported a history of physical abuse, sexual abuse, and/or or a substance-abusing caretaker than those with psychiatric disorder but no ataque. In some Hispanic individuals, ataque may represent a culturally sanctioned expression of extreme affect dysregulation associated with childhood trauma. Patients with ataque de nervios should receive a thorough traumatic history assessment.

Adult↗
PubMed2000

Walking index for spinal cord injury (WISCI): an international multicenter validity and reliability study.

STUDY DESIGN: Construction of an international walking scale by a modified Delphi technique. OBJECTIVE: The purpose of the study was to develop a more precise walking scale for use in clinical trials of subjects with spinal cord injury (SCI) and to determine its validity and reliability. SETTING: Eight SCI centers in Australia, Brazil, Canada (2), Korea, Italy, the UK and the US. METHODS: Original items were constructed by experts at two SCI centers (Italy and the US) and blindly ranked in an hierarchical order (pilot data). These items were compared to the Functional Independence Measure (FIM) for concurrent validity. Subsequent independent blind rank ordering of items was completed at all eight centers (24 individuals and eight teams). Final consensus on rank ordering was reached during an international meeting (face validation). A videotape comprised of 40 clips of patients walking was forwarded to all eight centers and inter-rater reliability data collected. RESULTS: Kendall coefficient of concordance for the pilot data was significant (W=0. 843, P<0.001) indicating agreement among the experts in rank ordering of original items. FIM comparison (Spearman's rank correlation coefficient=0.765, P<0.001) showed a theoretical relationship, however a practical difference in what is measured by each scale. Kendall coefficient of concordance for the international blind hierarchical ranking showed significance (W=0.860, P<0.001) indicating agreement in rank ordering across all eight centers. Group consensus meeting resulted in a 19 item hierarchical rank ordered 'Walking Index for Spinal Cord Injury (WISCI)'. Inter-rater reliability scoring of the 40 video clips showed 100% agreement. CONCLUSIONS: This is the first time a walking scale for SCI of this complexity has been developed and judged by an international group of experts. The WISCI showed good validity and reliability, but needs to be assessed in clinical settings for responsiveness.

Australia↗
PubMed2000

Activation of cutaneous sarcoidosis following Mycobacterium marinum infection of skin.

Sarcoidosis has long been associated with mycobacterial infection, especially with Mycobacterium tuberculosis, although a causal association has not been proven. Atypical mycobacteria have also been implicated in causing sarcoidosis, but there is as yet no conclusive evidence. We report the activation of cutaneous sarcoidosis following infection with M. marinum, raising further questions about the role of these bacteria in causing this chronic granulomatous disorder.

Humans↗
PubMed2000

Identification of cathepsin C mutations in ethnically diverse papillon-Lefèvre syndrome patients.

INTRODUCTION: Papillon-Lefèvre syndrome (PLS) is an autosomal recessive disorder characterised by palmoplantar keratoderma and severe, early onset periodontitis, which results from deficiency of cathepsin C activity secondary to mutations in the cathepsin C gene. To date, 13 different cathepsin C mutations have been reported in PLS patients, all of which are homozygous for a given mutation, reflecting consanguinity. AIM: To evaluate the generality of cathepsin C mutations in PLS, we studied an ethnically diverse group of 20 unrelated families. METHODS: Mutations were identified by direct automated sequencing of genomic DNA amplified for exonic regions and associated splice site junctions of the cathepsin C gene. Long range PCR was performed to determine the genomic structure of the cathepsin C gene. RESULTS: The cathepsin C gene spans over 46 kb, with six introns ranging in size from 1.6 to 22.4 kb. Eleven novel mutations and four previously reported mutations were identified in affected subjects from 14 families. Missense mutations were most common (9/15), followed by nonsense mutations (3/15), insertions (2/15), and deletions (1/15). Among these 14 probands, two were compound heterozygotes. Affected subjects with transgressions of the dermal lesions onto the knees or elbows or both had mutations in both the pro- and mature regions of the enzyme, although most were in the mature region. CONCLUSION: Mutations in the mature region of cathepsin C were more likely to be associated with the transgressions of the dermatological lesions, although the results were not statistically significant. A comprehensive list of all cathepsin C mutations described to date, representing 25 mutations from 32 families with PLS and related conditions, is also presented.

Cathepsin C↗
PubMed2000

Glycosaminoglycans in gingival crevicular fluid of patients with periodontal class II furcation involvement before and after guided tissue regeneration. A pilot study.

BACKGROUND: The levels of glycosaminoglycans in gingival crevicular fluid (GCF) are good indicators of underlying tissue turnover. We hypothesize that connective tissue elements in GCF may be used as indicators of tissue maturation underneath barrier membranes. Therefore, we investigated the levels of sulfated glycosaminoglycans in GCF at sites before and after guided tissue regeneration (GTR). METHODS: Six patients were selected on the basis of having at least one Class II buccal furcation involvement on a molar tooth. Each molar furcation was treated with the standard GTR surgical protocol using a non-resorbable expanded polytetrafluoroethylene membrane. Gingival crevicular fluid samples were taken at baseline (immediately prior to insertion of the membrane) and at 1, 2, 3, 4, 5, and 6 weeks (immediately prior to removal of the membrane). Glycosaminoglycan levels were determined using an Alcian blue dye detection system. RESULTS: The mean levels of chondroitin sulfate and total sulfated glycosaminoglycans in GCF significantly decreased during the first 4 weeks after GTR surgery. By week 5, the levels began to rise, and by week 6 the levels had returned to baseline levels. CONCLUSIONS: Sulfated glycosaminoglycans can be monitored in GCF at healing GTR sites. It is proposed that this is a useful means of monitoring the status of the regenerating tissues. However, further longitudinal studies are required to assess if the sulfated glycosaminoglycans can be used as indicators of tissue maturation under guided tissue membranes used to treat periodontal defects.

Adult↗
PubMed2000

Use of a clinical event monitor to prevent and detect medication errors.

Errors in health care facilities are common and often unrecognized. We have used our clinical event monitor to prevent and detect medication errors by scrutinizing electronic messages sent to it when any medication order is written in our facility. A growing collection of medication safety rules covering dose limit errors, laboratory monitoring, and other topics may be applied to each medication order message to provide an additional layer of protection beyond existing order checks, reminders, and alerts available within our computer-based record system. During a typical day the event monitor receives 4802 messages, of which 4719 pertain to medication orders. We have found the clinical event monitor to be a valuable tool for clinicians and quality management groups charged with improving medication safety.

Decision Support Systems, Clinical↗
PubMed1999

Angiotensin-converting-enzyme gene insertion/deletion polymorphism and response to physical training.

BACKGROUND: The function of local renin-angiotensin systems in skeletal muscle and adipose tissue remains largely unknown. A polymorphism of the human angiotensin converting enzyme (ACE) gene has been identified in which the insertion (I) rather than deletion (D) allele is associated with lower ACE activity in body tissues and increased response to some aspects of physical training. We studied the association between the ACE gene insertion or deletion polymorphism and changes in body composition related to an intensive exercise programme, to investigate the metabolic effects of local human renin-angiotensin systems. METHODS: We used three independent methods (bioimpedance, multiple skinfold-thickness assessment of whole-body composition, magnetic resonance imaging of the mid-thigh) to study changes in body composition in young male army recruits over 10 weeks of intensive physical training. FINDINGS: Participants with the II genotype had a greater anabolic response than those with one or more D alleles for fat mass (0.55 vs -0.20 kg, p=0.04 by bioimpedance) and non-fat mass (1.31 vs -0.15 kg, p=0.01 by bioimpedance). Changes in body morphology with training measured by the other methods were also dependent on genotype. INTERPRETATION: II genotype, as a marker of low ACE activity in body tissues, may conserve a positive energy balance during rigorous training, which suggests enhanced metabolic efficiency. This finding may explain some of the survival and functional benefits of therapy with ACE inhibitors.

Adipose Tissue↗