Biomedical subjects

W Lester

Publications and source records attributed to W Lester.

At least 19 recordsLinked to original sources

PubMed2002

Outpatient management of DVT using low molecular weight heparin and a hospital outreach service.

In recent years there have been several studies comparing the efficacy and safety of low molecular weight (LMW) and unfractionated heparin for the treatment of deep venous thrombosis (DVT), showing them in the clinical trial setting to be equal in these regards. LMWH has the advantage of once daily subcutaneous injection and daily monitoring of levels is not usually required. This has led many centres to develop outpatient treatment strategies for these patients but evidence for the safety of this approach is scarce. In 1997 we developed a hospital outreach service for the treatment of patients with DVT and, in a retrospective study, have compared the outcome in 172 patients treated at home with 172 age, sex and thrombotic risk factor matched inpatients treated at our institution with unfractionated heparin. Five patients in the home treatment group suffered a haemorrhagic event, compared with six patients in the hospital group. One patient in the home treatment group had a recurrent DVT within the first 3 months of treatment; in the hospital-treated group, six patients had recurrent DVTs and nine developed pulmonary emboli. At 3 months, there were three deaths in the home treatment group, compared with five deaths in the hospital group. There was no difference in re-admission rate at 3 months: 23 in the home treatment group, 24 in the hospital-treated group. Average length of hospital stay for the home-treatment group was 2.1 days and 12 days for the hospital group. Warfarin control was found to be significantly better in those patients treated at home, and only 18% of patients treated in hospital received heparin according to hospital guidelines. In conclusion, outpatient management of patients with DVT using LMWH is as safe as hospitalization and continuous infusion of unfractionated heparin. The complication rate was lower in the home treatment group and, in particular, the incidence of recurrent thrombosis was significantly less in the home treatment group. In addition, warfarin control was better when managed by specialist nurses. Patients expressed a preference for home treatment.

Adult↗

PubMed1999

An unusual eukaryotic protein phosphatase required for transcription by RNA polymerase II and CTD dephosphorylation in S. cerevisiae.

The carboxy-terminal domain (CTD) of the largest subunit of RNA polymerase II is phosphorylated soon after transcriptional initiation. We show here that the essential FCP1 gene of S. cerevisiae is linked genetically to RNA polymerase II and encodes a CTD phosphatase essential for dephosphorylation of RNA polymerase II in vivo. Fcp1p contains a phosphatase motif, psi psi psi DXDX(T/V)psi psi, which is novel for eukaryotic protein phosphatases and essential for Fcp1p to function in vivo. This motif is also required for recombinant Fcp1p to dephosphorylate the RNA polymerase II CTD or the artificial substrate p-nitrophenylphosphate in vitro. The effects of fcp1 mutations in global run-on and genome-wide expression studies show that transcription by RNA polymerase II in S. cerevisiae generally requires CTD phosphatase.

Mutation↗

PubMed1995

Proarrhythmia of a class Ic drug: suppression by combination with a drug prolonging repolarization in the dog late after infarction.

Encainide treatment in patients after myocardial infarction is associated with increased risk of sudden cardiac death. This may relate to drug-induced changes in the electrophysiologic milieu, thus predisposing the patient to sustained ventricular tachyarrhythmias. The goals of this study were to first develop a model of class Ic-induced ventricular tachycardia (VT) and then to design treatments to oppose this prodysrhythmic activity. Dogs with time-dependent loss of inducible sustained VT in the antiarrhythmic drug-free state were studied late after infarction. These dogs received a series of three loading and maintenance infusions of O-demethyl encainide (ODME) to achieve concentrations of 60 +/- 31, 136 +/- 46 and 339 +/- 171 ng/ml. Drug maintenance continued until programmed stimulation induced monomorphic sustained VT. When ODME infusion allowed this induction, barium chloride infusions were added. ODME treatment allowed induction of monomorphic sustained VT in 9 of 10 dogs studied. Prodysrhythmic monomorphic VT was significantly related (P < .01) to prolongation of conduction velocity in the peri-infarct zone. ODME modestly increased ventricular refractoriness at some but not all peri-infarct sites. Infusion of barium chloride in the above nine dogs caused their hearts to return to the noninducible state. Prolongation of refractoriness in the peri-infarct zone was correlated to this suppression of prodysrhythmia. Prolongation of conduction velocity in the absence of substantial prolongation of refractoriness may underlie ODME-facilitated induction of monomorphic VT. Prolongation of refractoriness in the peri-infarct zone by combination treatment with barium chloride reversed prodysrhythmic VT in all of the dogs.

Animals↗

PubMed1993

Kinetics and mechanism of DNA repair: an automated programmable apparatus for fast time-resolved studies of the repair of mammalian DNA after u.v. irradiation.

An automated apparatus, designed and constructed for use in fast time-resolved studies of mammalian DNA repair after u.v. irradiation, is described. The methodology makes use of caged DNA-break-trapping reagents, e.g. [alpha-32P]dideoxyadenosine triphosphate [see Meldrum, Shall, Trentham and Wharton (1990) Biochem J. 266, 885-890] and the apparatus incorporates excimer lasers both for the delivery of u.v. damage and for the photoactivation of the caged reagents. The design is based on a sample-changing turntable which permits the sequential irradiation and quenching of samples. A maximum of eight samples can be processed in a single experiment, the sequence of events being programmed on a microcomputer, which permits a very generalized experimental sequence. Pipettes for addition of cells, nucleotides and quenching agent are driven pneumatically. A pair of pneumatically operated platinum electrodes allows electroporation of cells for loading of negatively charged reagents prior to irradiation. The time resolution of the apparatus is dependent upon the experimental scheme used and can be very short (e.g. 1 ms) when caged reagents are used; a more usual period is 1 s for the shortest incubation.

Animals↗

PubMed1988

Porcine mitral valve interstitial cells in culture.

There are connective tissue cells present within the interstitium of the heart valves. This study was designed to isolate and characterize mitral valve interstitial cells from the anterior leaflet of the mitral valve. Explants obtained from the distal part of the leaflet, having been scraped free of surface endocardial cells, were incubated in medium 199 supplemented with 10% fetal bovine serum. Cells grew out of the explant after 3 to 5 days and by 3 weeks these cells were harvested and passaged. Passages 1 to 22 were characterized in several explant sets. The cells showed a growth pattern reminiscent of fibroblasts. Growth was dependent on serum concentration. Cytoskeletal localization of actin and myosin showed prominent stress fibers. Ultrastructural studies showed many elongated cells with prominent stress fibers and some gap junctions and few adherens junctions. There were as well cells with fewer stress fibers containing prominent Golgi complex and dilated endoplasmic reticulum. In the multilayered superconfluent cultures, the former cells tended to be on the substratum of the dish or surface of the multilayered culture, whereas the latter was generally located within the layer of cells. Extracellular matrix was prominent in superconfluent cultures, often within the layers as well. Labeling of the cells with antibody HHF 35 (Tsukada T, Tippens D, Gordon D, Ross R, Gown AM: Am J Pathol 126:51, 1987), which recognizes smooth muscle cell actin, showed prominent staining of the elongated stress fiber-containing cells and much less in the secretory type cells. These studies show that interstitial mitral valve cells can be grown in culture and that either two different cell types or one cell type with two phenotypic expressions is present in culture.

Actins↗

PubMed1984

Peritoneal epithelial lesions associated with proliferative serous tumours of ovary.

The peritoneal epithelial lesions in 40 cases of proliferating ovarian serous tumour are described. The lesions were varied and of both neoplastic and non-neoplastic form. The most common was serous tumour similar to that in the associated ovarian neoplasm. Tumour of this type was present in some or all of the peritoneal lesions in 77.5% of cases. In nearly two-thirds, the tumour was superficial; in the rest it invaded omentum. Occasionally, the infiltrating tumour was poorly differentiated. Benign tubular lesions resembling endosalpingiosis occurred in 16 (40%) of the 40 cases, but in seven it was associated with serous tumour. Psammoma bodies frequently accompanied serous tumour and endosalpingiosis and in occasional cases the majority of lesions consisted of psammomatous foci. The duration of follow up is too short to adequately assess the biological significance of these findings but it is clear that the peritoneal tumour occasionally may kill the patient within a few years. 'Serous tumour of low malignant potential' is the most appropriate term to describe the general group of ovarian serous tumours of so-called 'borderline malignant' type.

Adolescent↗

PubMed1979