PubMed Health⌕ Search

Biomedical subjects

M Clark

Publications and source records attributed to M Clark.

At least 73 records · Page 4Linked to original sources
PubMed2000

Home or hospital for stroke Rehabilitation? Results of a randomized controlled trial : II: cost minimization analysis at 6 months.

BACKGROUND AND PURPOSE: The goal of the present study was to examine the resource and economic implications of an early hospital discharge and home-based rehabilitation scheme for patients with acute stroke. METHODS: A cost minimization analysis in conjunction with a randomized controlled trial was carried out at 2 affiliated teaching hospitals in the southern metropolitan region of Adelaide, South Australia, between 1997 and 1998. Eighty-six hospitalized patients with acute stroke who required rehabilitation were randomized to receive both early hospital discharge and home-based rehabilitation, or conventional in-hospital rehabilitation and community care. Direct and indirect costs related to stroke rehabilitation were calculated, including hospital bed days, home-based intervention program, community services, and personal expenses during the 6 months after randomization. RESULTS: The mean cost per patient was lower for patients randomized to the early hospital discharge and home-based rehabilitation ($8040) compared with those who received conventional care ($10 054). This cost saving was not statistically significant (P=0.14). However, sensitivity analyses indicated that the cost of home-based rehabilitation was consistently lower than that of conventional care except when hospital costs were assumed to be 50% less than those used in the main analysis. Multiple regression analysis demonstrated that the cost of the home-based program was significantly related to a patient's level of disability after adjustment for age, comorbidity, and the presence or absence of a caregiver. CONCLUSIONS: The early hospital discharge and home-based rehabilitation scheme was less costly than conventional hospital care for patients with stroke. Limitation of the provision of such services to patients with mild disability is likely to be most cost effective.

Cost Savings↗
PubMed2000

An optimization of the Waterlow score using regression and artificial neural networks.

OBJECTIVES: To optimize the ability of the Waterlow Scale to predict individuals vulnerable to developing pressure ulcers. DESIGN: Prospective cohort study. SETTING: Two acute care UK National Health Service (NHS) providers. SUBJECTS: Four hundred and twenty-two inpatients across five specialities (general medicine, general surgery, orthopaedics, oncology and rehabilitation). INTERVENTIONS: Waterlow scores recorded weekly for 14 days post admission to hospital. MAIN OUTCOME MEASURE: Development of a pressure ulcer. RESULTS: Nonlinear analysis using neural networks did not outperform linear methods. Only five items out of 11 in the Waterlow Scale appeared to have any classification ability in this patient population. CONCLUSIONS: The Waterlow score when modelled as a linear equation appears as effective as more complicated nonlinear mappings using neural networks. Only a subset of the variables of the Waterlow Scale have predictive value in this patient population, but this is a different subset to those found in a previous study of a different client group (wheelchair users).

Disease Susceptibility↗
PubMed2000

The physics of sub-bandage pressure measurement.

Compression therapy is the principal treatment for leg ulcers associated with venous disease. The extent of compression generally can be estimated from the general Laplace equation relating pressure, bandage tension and leg radius. This study aimed to investigate the physical forces under long stretch bandages applied under constant tensions to cylinders of three defined radii ('model limbs'). Force expressed as pressure was measured under one, two and three layers of eight long stretch bandages and a plastic film (control) using temperature-compensated, strain-gauge pressure transducers. The bandages were applied at the manufactures' recommended extensions/tensions and at constant tensions (2-10N) to three rigid plastic tubes of increasing size, covered with a layer of soft foam. Foams of different hardnesses ranging from 20 to 230N were assessed. The median applied pressure and observed bandage characteristics changed with bandage type. The median applied pressure also changed with tension, number of layers, tube radius and foam hardness. The inter-layer shear component also tended to increase with the number of layers. An increase in sub-bandage pressure was observed relative to the radius, tension, foam hardness and number of layers but the relationship was not directly proportional. The shear force tended to be associated with increased bandage layers.

Bandages↗
PubMed2000

Stereotactic breast biopsy: recumbent biopsy using add-on upright equipment.

OBJECTIVE: The purpose of the study was to show that stereotactic breast biopsy can be performed effectively and accurately using add-on stereotactic equipment when it is performed with the patient in a decubitus or recumbent position. MATERIALS AND METHODS: We retrospectively reviewed the results of 225 stereotactic core breast biopsies performed during a 42-month period. The biopsies were performed using a reclining mammography chair and add-on stereotactic equipment. Procedures were performed with the patient in the right or left lateral decubitus position or upright. Patients with benign biopsy results were followed up mammographically at 6 months initially, then yearly. RESULTS: Of the 225 lesions biopsied stereotactically, 205 lesions (91%) were biopsied with the patient in the decubitus (right or left) position and 20 (9%) biopsied with the patient upright. Pathology results were classified as abnormal in 45 lesions (20%) and normal in 180 lesions (80%). All but one of the abnormal lesions were followed up with surgical excision. One hundred thirty-four of the 180 benign lesions have been followed up with at least one 6-month mammogram (follow-up range, 6-40 months), and none of the lesions has been subsequently proven malignant. CONCLUSION: Stereotactic core biopsy can be performed effectively and accurately using standard add-on equipment when it is performed with the patient in the decubitus position. This approach obviates the use of dedicated prone stereotactic equipment.

Biopsy, Needle↗
PubMed2000

Induction of apoptosis by idarubicin: how important is the plasma peak?

OBJECTIVES: It is still not clear whether a high plasma peak or a prolonged plasma presence of the drug is optimal for chemotherapy with anthracyclines. A high plasma peak seems to correlate with the liberation of oxygen radicals and cumulative delayed cardiotoxicity, and therefore, should be avoided. On the other hand, its role in attaining the desired therapeutic effect, i.e. induction of apoptosis in tumor cells, has not been clearly elucidated. METHODS: Idarubicin is the only anthracycline that can be applied orally. We measured the DNA-binding of idarubicin and idarubicinol and the induced apoptosis in the human promyelocytic HL-60 leukemia cell line. Various pharmacokinetic profiles, with and without clinically relevant peak concentrations, were simulated in vitro. RESULTS: The concentration necessary for maximal DNA-binding and subsequent induction of apoptosis was 1.5 microg/ml for 20 minutes which is well above the plasma concentration achievable in therapy. A plateau of apoptosis was observed after 90 minutes of incubation; a prolongation above 90 minutes did not increase the rate of apoptosis. We simulated a bolus application and a continuous infusion using two different pharmacokinetic profiles of idarubicin with comparable AUCs (area under the time curve). After 48 hours of total incubation, the viability of HL-60 cells was 56.88% with profile 1 (50 ng/ml idarubicin for 2 hours) and 83.00% with profile 2 (4.25 ng/ml for 24 hours). CONCLUSIONS: Although these in vitro experiments are not directly applicable to the clinical situation, they do indicate that a prolongation of the application time up to at least 90 minutes, either by continuous infusion or by oral application, may be acceptable as a method of increasing apoptosis. On the other hand, the plasma peak seems to be an important factor for the induction of apoptosis. Further studies are in progress to define the minimal plasma peak necessary to induce a maximum of apoptosis.

Antibiotics, Antineoplastic↗
PubMed1999

Linkage between male infertility and trinucleotide repeat expansion in the androgen-receptor gene.

BACKGROUND: Androgens acting via the androgen receptor bring about stimulation and maintenance of spermatogenesis. If mutations in the androgen-receptor gene interfere with the receptor's function, this effect may partly account for impaired spermatogenesis. We aimed to find out whether expansion of a trinucleotide repeat in the androgen-receptor gene is associated with male infertility. METHODS: We analysed 67 coded semen and blood samples from a predominantly white group of male infertility patients and controls. Clinical analyses included cause of infertility, sperm count, and reproductive hormone concentrations. Analysis of trinucleotide (CAG) repeat length and point mutations in the androgen-receptor gene was done by PCR, single-stranded conformational polymorphism, and DNA sequencing. FINDINGS: Screening and characterisation of the androgen-receptor gene in 35 patients and 32 controls showed no point mutations in the gene. 30 of the infertile patients had idiopathic azoospermia or oligozoospermia, and these men had significantly longer CAG repeat tracts than controls (mean 23.2 [SE 0.7] vs 20.5 [0.3], p=0.0001). The odds of having CAG repeat lengths of 20 were six-fold higher for fertile men than for men with a spermatogenic disorder. INTERPRETATION: Our results indicate a relation between CAG repeat length in the androgen-receptor gene and the risk of defective spermatogenesis. With the use of intracytoplasmic sperm injection, this mutation could be inherited, possibly leading to an increase in male infertility in future generations. Should further elongation of the CAG repeat occur in these future generations, there is an added risk of increased severity of male infertility, and potentially an increased incidence of neurodegenerative disease.

Adult↗
PubMed1999

Analysis of the spermine synthase gene region in Fugu rubripes, Tetraodon fluviatilis, and Danio rerio.

A prerequisite to understanding the evolution of the human X chromosome is the analysis of synteny of X-linked genes in different species. We have focused on the spermine synthase gene in human Xp22. 1. We show that whereas the human gene spans a genomic region of 54 kb, the Fugu rubripes gene is encompassed in a 4.7-kb region. However, we could not find conserved synteny between this region of human Xp22 and the equivalent F. rubripes region. A cosmid clone containing the F. rubripes gene does not contain other X-linked genes. Instead we identified homologs of human genes that are autosomally localized: the ryanodine receptor type I (RYRI), which is implicated in malignant hyperthermia and central core disease, and the HE6 gene. Comparison of the F. rubripes, Tetraodon fluviatilis, mouse, human, and Danio rerio 5'UTRs of spermine synthase highlights conserved sequences potentially involved in regulation. Interestingly, pseudogenes of this gene that are present in the human and mouse genomes seem to be absent in the compact F. rubripes genome. Analysis of a D. rerio PAC clone containing spermine synthase shows an intermediate genomic size in this fish. Sequence analysis of this PAC clone did not reveal other known genes: neither the RYRI gene, nor the HE6 gene, nor other human Xp22 genes were identified.

Alternative Splicing↗
PubMed1999

Primary structure, tissue distribution, and expression of mouse phosphoinositide-dependent protein kinase-1, a protein kinase that phosphorylates and activates protein kinase Czeta.

Phosphoinositide-dependent protein kinase-1 (PDK1) is a recently identified serine/threonine kinase that phosphorylates and activates Akt and p70(S6K), two downstream kinases of phosphatidylinositol 3-kinase. To further study the potential role of PDK1, we have screened a mouse liver cDNA library and identified a cDNA encoding the enzyme. The predicted mouse PDK1 (mPDK1) protein contained 559 amino acids and a COOH-terminal pleckstrin homology domain. A 7-kilobase mPDK1 mRNA was broadly expressed in mouse tissues and in embryonic cells. In the testis, a high level expression of a tissue-specific 2-kilobase transcript was also detected. Anti-mPDK1 antibody recognized multiple proteins in mouse tissues with molecular masses ranging from 60 to 180 kDa. mPDK1 phosphorylated the conserved threonine residue (Thr402) in the activation loop of protein kinase C-zeta and activated the enzyme in vitro and in cells. Our findings suggest that there may be different isoforms of mPDK1 and that the protein is an upstream kinase that activates divergent pathways downstream of phosphatidylinositol 3-kinase.

3-Phosphoinositide-Dependent Protein Kinases↗
PubMed1999

Three receptor genes for plasminogen related growth factors in the genome of the puffer fish Fugu rubripes.

Plasminogen related growth factors (PRGFs) and their receptors play major roles in embryogenesis, tissue regeneration and neoplasia. In order to investigate the complexity and evolution of the PRGF receptor family we have cloned and sequenced three receptors for PRGFs in the teleost fish Fugu rubripes, a model vertebrate with a compact genome. One of the receptor genes isolated encodes the orthologue of mammalian MET, whilst the other two may represent Fugu rubripes orthologues of RON and SEA. This is the first time three PRGF receptors have been identified in a single species.

Amino Acid Sequence↗
PubMed1999

Are topoisomerase II inhibitor-induced micronuclei in vitro a predictive marker for the compounds' ability to cause secondary leukemias after treatment?

The inhibition of topoisomerase II (topo II) is a very powerful principle of chemotherapy and topo II inhibiting drugs are the backbone of most chemotherapeutic strategies. However, secondary malignomas can occur after treatment. Typically, secondary acute myeloid leukemia (t-AML) after treatment with topo II inhibitors has a shorter latency period than t-AML following alkylator therapy. Fragments originating from chromosome breakage as well as whole chromosomes which are not correctly distributed during mitosis give rise to micronuclei in the next interphase. Micronucleus formation has become an important endpoint in genotoxicity testing. In an effort to test the suitability of the micronucleus assay for predictive purposes, we have analyzed three human tumor cell lines for cell growth as well as micronucleus induction after treatment with four clinically used topo II inhibitors. Micronuclei were induced at levels of low toxicity by etoposide, mitoxantrone, daunorubicin and idarubicin. The induction of micronuclei was a more sensitive indicator of drug effects than reduction in cell growth. Thus, micronucleus induction may assist in the prediction of the potency of a chemotherapeutic agent for induction of secondary malignomas.

Antineoplastic Agents↗
PubMed1999

Apraxia differs in corticobasal degeneration and left-parietal stroke: A case study.

Corticobasal degeneration (CBD) is a progressive disorder characterized by both cortical and basal ganglia dysfunction such as asymmetrical apraxia, and akinetic rigidity, involuntary movements, and cortical sensory loss. Although apraxia is a key finding for the differential diagnosis of CBD, it has not been determined whether the features of apraxia seen in subjects with CBD are similar to those features exhibited by subjects with left-hemisphere damage from stroke. Therefore, for both clinical purposes and in order to better understand the brain mechanisms that lead to apraxia in CBD, we studied praxis in a patient with CBD and compared him to patients who are apraxic from left-parietal strokes. We used three-dimensional movement analyses to compare the features of apraxic movement. This subject with CBD was a dentist whose initial complaint had been that he "forgot" how to use his tools in the mouths of his patients. Analyses were performed on the trajectories made when using a knife to actually slice bread, and when repetitively gesturing slicing made to verbal command. Movements of the left hand, wrist, elbow, and shoulder were digitized in 3-D space. Although the CBD subject was clearly apraxic, the features of his apraxia differed markedly from those of the subjects with lesions in the left parietal lobe. For movements to command, the CBD subject showed joint coordination deficits, but his wrist trajectories were produced in the appropriate spatial plane, were correctly restricted to a single plane, and, like control subjects, were linear in path shape. However, when he was actually manipulating the tool and object, all of these aspects of his trajectories became impaired. In contrast, the deficits of the apraxic subjects with left-parietal damage were most pronounced to verbal command with their movements improving slightly although remaining impaired during actual tool and object manipulation. Unlike patients with parietal strokes, patients with CBD have degeneration in several systems and perhaps deficits in these other areas may account for the differences in praxic behavior.

Aged↗
PubMed1999

CT of intranasal pleomorphic adenoma.

Intranasal pleomorphic adenoma is rare. We report the CT features this tumor in a 41-year-old woman who presented to us with right nasal obstruction and a 2-day history of epistaxis.

Adenoma, Pleomorphic↗
PubMed1999

The social ecology of syphilis.

Factors affecting the transmission of syphilis can be categorized into those acting at the level of individuals (e.g., number of sex partners) and others at the level of the sociophysical environment (e.g., availability of treatment services for curable infections). In a prior study, we identified several sociophysical factors correlated with the ten-year mean syphilis rate in a regression analysis of United States counties. In the present study we used qualitative methods to investigate additional aspects of some factors in the regression, as well as to identify entirely new factors. Twelve counties with populations less than 100,000 and ten-year mean syphilis rates that were greater or less than expected by the regression model were selected for a three to five day visit. The case study protocol included observations, unstructured interviews with care providers and county residents, and a standardized questionnaire completed by state and local sexually transmitted disease control personnel pertaining to characteristics and practices of the local health department. Comparisons of the field notes and questionnaires revealed patterns of factors of the sociophysical environment that potentially affect county syphilis rates. These included access to the health department STD clinic, race relations, employment opportunities for minorities, interagency coordination, STD outreach activities, the social acceptability of discussing STDs, and intercommunity dynamics. In addition we noted the disproportionate influence of particular individuals on these factors. Some of the factors identified are readily quantifiable and could enhance the predictive power of multivariable models of county syphilis rates. The hypotheses generated by this study may also lead to a better measurement and understanding of potentially important environmental determinants of community syphilis rates, and the development of new or enhanced prevention strategies.

Black or African American↗
PubMed1999

The impact of pregnancy on eating behaviour and aspects of weight concern.

BACKGROUND: Excessive weight gain in pregnancy and retention of this weight gain is a well known problem. How women with a history of dietary restraint adjust to being pregnant, is of interest, as pregnancy epitomises many of the factors known to trigger overeating. OBJECTIVE: To examine the impact of pregnancy on eating behaviour and weight concern and the role of dietary restraint in mediating any changes. METHODS: Primigravid (n = 50) and non-pregnant nulliparous (n = 50) women completed a questionnaire to describe their profile characteristics, current health behaviours, eating behaviour and weight concern. The pregnant women completed additional retrospective items relating to these factors for the period prior to their pregnancy. RESULTS: The pregnant women reported eating more, showed lower levels of dietary restraint, were less dissatisfied with their body shape and showed higher eating self efficacy than non-pregnant women. Compared to the months prior to their pregnancy, the pregnant women rated themselves as less restrained in their eating behaviour and nearly half stated that they were eating more. In terms of the impact of pre pregnancy levels of dietary restraint, the results showed a significant interaction between restrained eating and pregnancy for both hunger and eating self efficacy. The results showed that the restrained eaters, when pregnant, rated themselves as significantly less hungry and reported less difficulty controlling their food intake than the non pregnant restrained eaters but showed comparable hunger and eating control to the other groups. The results showed no effect of restrained eating on weight change. CONCLUSION: The results suggest that pregnancy both legitimises increased food intake and removes any previous intentions to eat less.

Adult↗
PubMed1999

Molecular effects of topoisomerase II inhibitors in AML cell lines: correlation of apoptosis with topoisomerase II activity but not with DNA damage.

We examined the cellular effects of topo II inhibitors in two human myeloid cell lines, HL-60 and KG-1 cells, with the purpose of finding molecular markers for the sensitivity of leukemia cells to topo II inhibitors. These cell lines are widely used, well characterized and they differ in their sensitivities to topo II inhibitors. Despite the fact that HL-60 cells are p53-negative, they are much more sensitive than KG-1 cells. Three different topo II inhibitors with distinct molecular ways of action have been used. Daunorubicin and aclarubicin are DNA intercalators that secondarily interact with topo II; etoposide, on the other hand, directly binds to the enzyme. In contrast to daunorubicin, which induces protein-associated DNA double-strand breaks due to the blockage of topo II action, aclarubicin inhibits the access of DNA by topo II. No correlation could be established between the drug-induced DNA damage and apoptosis. In fact, the amount and pattern of DNA damage examined with the 'comet assay' was characteristic for each drug in both cell lines. The DNA binding of daunorubicin was slightly higher in HL-60 cells, but there was no notable variance between the cell lines for aclarubicin. The most striking difference could be found for the nuclear topo II activity, which was about half in KG-1 cells and, additionally, less than 1% of the nuclear topo II activity was bound to the DNA in KG-1 cells when compared to HL-60 cells. This fraction of topo II interacts with the inhibitors; subsequently these findings might well explain the variance in the cellular sensitivity. Additional factors are alterations of the apoptotic pathways, eg loss of p53 in HL-60 cells. Although we found no differences in the quantity of DNA damage between the cell lines after drug treatment, the quality of DNA damage appeared to be distinct for each topo II inhibitor. The morphological appearance of the comet tails after treatment was characteristic for each drug. Further studies are necessary to decide whether these in vitro data are compatible with the clinical situation.

Aclarubicin↗
PubMed1999

Zebrafish tbx-c functions during formation of midline structures.

Several genes containing the conserved T-box region in invertebrates and vertebrates have been reported recently. Here, we describe three novel members of the T-box gene family in zebrafish. One of these genes, tbx-c, is studied in detail. It is expressed in the axial mesoderm, notably, in the notochordal precursor cells immediately before formation of the notochord and in the chordoneural hinge of the tail bud, after the notochord is formed. In addition, its expression is detected in the ventral forebrain, sensory neurons, fin buds and excretory system. The expression pattern of tbx-c differs from that of the other two related genes, tbx-a and tbx-b. The developmental role of tbx-c has been analysed by overexpression of the full-length tbx-c mRNA and a truncated form of tbx-c mRNA, which encodes the dominant-negative Tbx-c. Overexpression of tbx-c causes expansion of the midline mesoderm and formation of ectopic midline structures at the expense of lateral mesodermal cells. In dominant-negative experiments, the midline mesoderm is reduced with the expansion of lateral mesoderm to the midline. These results suggest that tbx-c plays a role in formation of the midline mesoderm, particularly, the notochord. Moreover, modulation of tbx-c activity alters the development of primary motor neurons. Results of in vitro analysis in zebrafish animal caps suggest that tbx-c acts downstream of early mesodermal inducers (activin and ntl) and reveal an autoregulatory feedback loop between ntl and tbx-c. These data and analysis of midline (ntl-/- and flh-/-) and lateral mesoderm (spt-/-) mutants suggest that tbx-c may function during formation of the notochord.

Amino Acid Sequence↗