PubMed Health⌕ Search

Biomedical subjects

J R Harper

Publications and source records attributed to J R Harper.

At least 19 recordsLinked to original sources
PubMed2004

Improving thromboprophylaxis in elderly patients with non-valvular atrial fibrillation.

BACKGROUND: Non-valvular atrial fibrillation (NVAF) is more common in elderly people, and is one of the most powerful independent risk factors predisposing to stroke. This risk increases with age. Despite evidence that full dose anticoagulation reduces this risk, and Scottish Intercollegiate Guidelines, warfarin is still being under prescribed, especially in elderly individuals. OBJECTIVES: To audit warfarin prescribing in elderly hospital patients with NVAF, and assess whether audit feedback and evidence based guidelines improved warfarin usage. METHODS: Discharge summaries and medical notes were reviewed, and warfarin prescribing identified, for all patients with NVAF discharged from the Medicine for the Elderly Department between January 2001 and December 2002. This was done before (16 months) and after (7 months) audit results were presented at a departmental meeting, and evidence basedguidelines were produced. RESULTS: Warfarin prescribing significantly increased from 38/121 (31.4%) prior to audit feedback and the introduction of guidelines to 30/55 (54.5%), Chi2-test, p < 0.01. CONCLUSIONS: Older patients with NVAF were under prescribed warfarin. Audit feedback and the introduction of evidence based guidelines significantly increased anticoagulation usage.

Aged↗
PubMed2001

Absence of the outer membrane phospholipase A suppresses the temperature-sensitive phenotype of Escherichia coli degP mutants and induces the Cpx and sigma(E) extracytoplasmic stress responses.

DegP is a periplasmic protease that is a member of both the sigma(E) and Cpx extracytoplasmic stress regulons of Escherichia coli and is essential for viability at temperatures above 42 degrees C. [U-(14)C]acetate labeling experiments demonstrated that phospholipids were degraded in degP mutants at elevated temperatures. In addition, chloramphenicol acetyltransferase, beta-lactamase, and beta-galactosidase assays as well as sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis indicated that large amounts of cellular proteins are released from degP cells at the nonpermissive temperature. A mutation in pldA, which encodes outer membrane phospholipase A (OMPLA), was found to rescue degP cells from the temperature-sensitive phenotype. pldA degP mutants had a normal plating efficiency at 42 degrees C, displayed increased viability at 44 degrees C, showed no degradation of phospholipids, and released far lower amounts of cellular protein to culture supernatants. degP and pldA degP mutants containing chromosomal lacZ fusions to Cpx and sigma(E) regulon promoters indicated that both regulons were activated in the pldA mutants. The overexpression of the envelope lipoprotein, NlpE, which induces the Cpx regulon, was also found to suppress the temperature-sensitive phenotype of degP mutants but did not prevent the degradation of phospholipids. These results suggest that the absence of OMPLA corrects the degP temperature-sensitive phenotype by inducing the Cpx and sigma(E) regulons rather than by inactivating the phospholipase per se.

Bacterial Outer Membrane Proteins↗
PubMed2001

Genetic evidence for parallel pathways of chaperone activity in the periplasm of Escherichia coli.

The periplasm of Escherichia coli contains many proteins proposed to have redundant functions in protein folding. Using depletion analysis, we directly demonstrated that null mutations in skp and surA, as well as in degP and surA, result in synthetic phenotypes, suggesting that Skp, SurA, and DegP are functionally redundant. The Deltaskp surA::kan combination has a bacteriostatic effect and leads to filamentation, while the degP::Tn10 surA::kan combination is bactericidal. The steady-state levels of several envelope proteins are greatly reduced upon depletion of a wild-type copy of surA in both instances. We suggest that the functional redundancy of Skp, SurA, and DegP lies in the periplasmic chaperone activity. Taken together, our data support a model in which the periplasm of E. coli contains parallel pathways for chaperone activity. In particular, we propose that Skp and DegP are components of the same pathway and that SurA is a component of a separate pathway. The loss of either pathway has minimal effects on the cell, while the loss of both pathways results in the synthetic phenotypes observed.

Bacterial Outer Membrane Proteins↗
PubMed2001

Rediscovering the joy of food: the need for long-term review of swallowing ability in stroke patients.

Stroke is commonly associated with dysphagia, which may necessitate the use of enteral feeding best provided by a percutaneous endoscopic gastrostomy (PEG) tube. Resolution of dysphagia complicating stroke is observed in the days, weeks and months following the event. This may allow the resumption of a normal diet, and cessation of enteral feeding. However at the time dysphagia resolves many patients--with enteral feeding still in place--will have been discharged from facilities where expert speech and language therapy is available to assess recovery of swallow. We report three cases of patients with dysphagia following stroke who benefited from long term review of swallowing ability. We then discuss the benefits of such follow-up, and how it might best be achieved in the community.

Aged↗
PubMed2001

Preferences for different high-energy foods in elderly medical in-patients.

Malnourishment is a common finding in hospitalised elderly patients. It is often addressed by the provision of nutritional supplements, in the form of sip-feeds. Patients' intake of these is frequently inadequate. We assessed the palatability of sip-feed nutritional supplements and other high-energy foods to elderly medical in-patients. Using the Lickhert Scale, 49 subjects rated the taste of a previously selected sip-feed supplement and five other high-energy foods, cheese biscuit, plain potato crisps, chocolate, cherry-flavoured cereal bar and stout beer. Subjects rated the taste of sip-feeds as favourably as all other offered foods, with the exception of the lower rated stout beer (p = 0.0001). Taste alone is unlikely to account for the poor intake of sip-feed nutritional supplements by elderly hospital patients.

Aged↗
PubMed1998

Cryopreservation of single-donor platelets with a reduced dimethyl sulfoxide concentration by the addition of second-messenger effectors: enhanced retention of in vitro functional activity.

BACKGROUND: The potential for bacterial contamination limits the storage of platelets at 22 degrees C to 5 days. This creates an inventory problem, which could be overcome by the use of cryopreservation to allow long-term storage of platelets. It has been demonstrated that the addition to platelets of a mixture of second-messenger effectors (platelet storage solution), allows these cells to retain significant in vitro functional activity following cold storage. Analysis is needed of the ability of this second messenger effector mixture both to protect platelets during cryopreservation and to reduce the need for a cryoprotectant. STUDY DESIGN AND METHODS: Fresh single-donor platelet units (n = 8) were divided into three samples and treated with 6-percent dimethyl sulfoxide (DMSO), 2-percent DMSO or the platelet storage solution and 2-percent DMSO. The samples were placed directly into a -80 degrees C freezer and stored for 1 week, after which they were thawed and analyzed for in vitro functional activity. RESULTS: Platelets cryopreserved with the platelet storage solution and 2-percent DMSO displayed statistically higher retention of functional activity and viability--including cell number, percent of discoid cells, extent of shape change, and hypotonic shock response--than did platelets stored by the method using 6-percent DMSO. In addition, the treated platelets displayed statistically lower expression of p-selectin. The treated platelets showed no loss of cell number, > 88-percent retention of discoid morphology, and > 75-percent retention of ristocetin-induced aggregation as compared to values for these measures in fresh platelets. CONCLUSION: The use of this platelet storage solution in the cryopreservation of platelets yields a significant improvement in their postthaw in vitro recovery and allows for a reduction of the DMSO concentration from 6 to 2 percent, with superior maintenance of in vitro viability and function.

Blood Platelets↗
PubMed1997

Antifibrotic effect of decorin in a bleomycin hamster model of lung fibrosis.

We reported previously that treatment with antibody to transforming growth factor-beta (TGF-beta) caused a marked attenuation of bleomycin (BL)-induced lung fibrosis (LF) in mice. Decorin (DC), a proteoglycan, binds TGF-beta and thereby down-regulates all of its biological activities. In the present study, we evaluated the antifibrotic potential of DC in a three-dose BL-hamster model of lung fibrosis. Hamsters were placed in the following groups: (1) saline (SA) + phosphate-buffered saline (PBS) (SA + PBS); (2) SA + DC; (3) BL + PBS; and (4) BL + DC. Under pentobarbital anesthesia, SA (4 mL/kg) or BL was instilled intratracheally in three consecutive doses (2.5, 2.0, 1.5 units/kg/4 mL) at weekly intervals. DC (1 mg/mL) or PBS was instilled intratracheally in 0.4 mL/hamster on days 3 and 5 following instillation of each dose of SA or BL. In week 4, hamsters received three doses of either DC or PBS every other day. The hamsters were killed at 30 days following the first instillation, and their lungs were appropriately processed. Lung hydroxyproline levels in SA + PBS, SA + DC, BL + PBS, and BL + DC groups were 965, 829, 1854, and 1387 microg/lung, respectively. Prolyl hydroxylase activities were 103, 289, and 193% of SA + PBS control in SA + DC, BL + PBS, and BL + DC groups, respectively. The myeloperoxidase activities in the corresponding groups were 222, 890, and 274% of control (0.525 units/lung). Intratracheal instillation of BL caused significant increases in these biochemical markers, and instillation of DC diminished these increases in the BL + DC group. DC treatment also caused a significant reduction in the infiltration of neutrophils in the bronchoalveolar lavage fluid (BALF) of hamsters in the BL + DC group. However, DC treatment had little effect on BL-induced increases in lung superoxide dismutase activity and lipid peroxidation and leakage of plasma proteins in the BALF of the BL + DC group. Hamsters in the BL + PBS group showed severe multifocal fibrosis and accumulation of mononuclear inflammatory cells and granulocytes. In contrast, hamsters in the BL + DC group showed mild multifocal septal thickening with aggregations of mononuclear inflammatory cells. Hamsters in both control groups (SA + PBS and SA + DC) showed normal lung structure. Frozen lung sections following immunohistochemical staining revealed an intense staining for EDA-fibronectin and collagen type I in the BL + PBS group as compared with all other groups. It was concluded that DC potentially offers a novel pharmacological intervention that may be useful in treating pulmonary fibrosis.

Animals↗
PubMed1997

Inhibition of cytokine accumulation and bacterial growth during storage of platelet concentrates at 4 degrees C with retention of in vitro functional activity.

BACKGROUND: The potential for bacterial contamination limits the storage of platelet concentrates (PCs) at 22 degrees C to 5 days. In addition, storage of platelets under conventional protocols for longer times (> 3 days), in the absence of white cell filtration, has been correlated with incidents of cytokine-associated febrile reaction in recipients. It has been demonstrated that the addition of a reagent mixture of second-messenger effectors allows platelets stored at 4 degrees C to maintain significant in vitro functional activity. Thus, the effects of 4 degrees C storage on the growth of bacteria and the accumulation of cytokines by the white cell fraction of PCs were analyzed to demonstrate the benefits of this refrigerated storage system. STUDY DESIGN AND METHODS: The platelet storage solution was added directly to PCs obtained from the blood bank, and these treated PCs were stored at 4 degrees C without agitation. In parallel, control PCs were stored according to standard blood-banking procedures. On Days 1, 3, 5, and 9, the PCs were measured for the plasma concentrations of cytokines. Treated and control PCs stored at 4 degrees C and 22 degrees C were inoculated with low-titer Staphylococcus aureus, and bacterial growth was measured over a 5-day period. RESULTS: Control PCs displayed a time-dependent increase in the plasma concentration of interleukin 6, interleukin 1 beta, and tumor necrosis factor alpha. These conventionally stored PCs also displayed a time-dependent increase in the bacteria titer. In contrast, the treated PCs stored at 4 degrees C displayed no accumulation of the above cytokines in the plasma fraction and no increase in bacteria titer above the initial inoculation. CONCLUSION: The storage of PCs at refrigerated temperatures inhibits the accumulation of white cell-produced cytokines in the PCs, an effect that could alleviate cytokine-associated febrile transfusion reactions The 4 degrees C storage was also bacteriostatic, which indicates that the storage of PCs at that temperature increases safety by decreasing the potential for sepsis. Thus, the ability to store PCs at 4 degrees C may allow extension of the storage limit beyond 5 days.

Bacteria↗
PubMed1994

Manipulation of cellular interactions with biomaterials toward a therapeutic outcome: a perspective.

Manipulation of the wound healing process and the manner in which tissues interact with inert biomaterials were both made possible with the discovery of arginine-glycine-aspartic (RGD) acid as a major cell recognition signal in the extracellular matrix. Whether promoting cell adhesion or selectively inhibiting cell-cell aggregation mediated by integrin cell surface receptors, RGD-containing peptides can be rationally designed to incorporate both stability and integrin specificity. Synthetic peptides containing this sequence have been linked to biodegradable biopolymers and introduced for the enhancement of dermal and corneal would healing. By accelerating the healing reaction using RGD-containing peptides, the quality of regenerated tissue seems to be improved, the extent of fibrosis restricted, and the risk of microbial infection may be reduced. Controlling the degree of fibrosis that often accompanies the healing of wounds and the reaction of tissue to foreign materials can also be achieved by natural antagonists of fibrogenic activity of TGF-beta animal models of kidney fibrosis. These advances in the biotechnology of wound healing and tissue regeneration eventually will have an overall impact on the quality of health care.

Amino Acid Sequence↗
PubMed1993

Effect of rate on changes in conduction velocity and extracellular potassium concentration during acute ischemia in the in situ pig heart.

INTRODUCTION: The purpose of our study was to determine if the slowing of longitudinal intraventricular conduction in the in situ porcine heart during acute regional no-flow ischemia was rate dependent. Further, we investigated whether any rate dependence could be correlated to a rate-dependent component of the ischemia-induced rise in extracellular potassium concentration, [K+]e. METHODS AND RESULTS: We studied in situ hearts in nine anesthetized open chest pigs in which acute no-flow ischemia was induced by occlusion of the left anterior descending coronary artery. To determine the effects of steady-state rate on the slowing of conduction and rise in [K+]e during ischemia, we varied the rate of stimulation during sequential occlusions from 90 to 150 beats/min. Longitudinal conduction velocity was determined by unipolar electrodes embedded in a plaque that was sutured to the epicardial surface in the center of the ischemic zone. Myocardial [K+]e was determined simultaneously by potassium-sensitive electrodes placed at or within 1 to 2 mm of the epicardium in close proximity to the activation recording electrodes. Conduction velocity decreased more rapidly at the more rapid rates of stimulation although the reduction in conduction velocity occurring prior to the onset of conduction block was similar at both rates. The potassium change was not rate dependent and rose at the same rate regardless of the rate of stimulation. CONCLUSION: Our study demonstrates that the steady-state rate-dependent component of the slowing of intraventricular conduction induced by acute ischemia in the in situ porcine heart occurs in the absence of a rate-dependent component in the rise of [K+]e. Between rates of 90 and 150 beats/min, the rate dependence of the conduction slowing may be attributed to one or more potassium-independent factors such as the rate-dependent changes in resting membrane potential, in Vmax of the action potential upstroke, and in cell-to-cell uncoupling, which have been observed in other models of acute ischemia.

Action Potentials↗
PubMed1992

Natural inhibitor of transforming growth factor-beta protects against scarring in experimental kidney disease.

The central pathological feature of human kidney disease that leads to kidney failure is the accumulation of extracellular matrix in glomeruli. Overexpression of transforming growth factor-beta (TGF-beta) underlies the accumulation of pathological matrix in experimental glomerulonephritis. Administration of an antibody raised against TGF-beta to glomerulonephritic rats suppresses glomerular matrix production and prevents matrix accumulation in the injured glomeruli. One of the matrix components induced by TGF-beta, the proteoglycan decorin, can bind TGF-beta and neutralize its biological activity, so decorin may be a natural regulator of TGF-beta (refs 3, 4). We tested whether decorin could antagonize the action of TGF-beta in vivo using the experimental glomerulonephritis model. We report here that administration of decorin inhibits the increased production of extracellular matrix and attenuates manifestations of disease, confirming our hypothesis. On the basis of our results, decorin may eventually prove to be clinically useful in diseases associated with overproduction of TGF-beta.

Animals↗
PubMed1992

In vivo interactions of TGF-beta and extracellular matrix.

TGF-beta, a multifunctional cytokine, plays an important role in embryogenesis and in regulating repair and remodeling following tissue injury. Many of the biological actions of TGF-beta are mediated by widespread effects on deposition of extracellular matrix. TGF-beta stimulates the synthesis of individual matrix components including proteoglycans, collagens and glycoproteins. TGF-beta also blocks matrix degradation by decreasing the synthesis of proteases and increasing the synthesis of protease inhibitors. Finally, TGF-beta increases the synthesis of matrix receptors and alters their relative proportions on the surface of cells in a manner that could facilitate adhesion to matrix. All of these events have largely been demonstrated in vitro in cultured cells. In an experimental model of glomerulonephritis we have shown that TGF-beta is responsible for the accumulation of pathological matrix in the glomeruli following immunological injury. Furthermore, all three of TGF-beta's actions on extracellular matrix--increased synthesis, decreased degradation and modulation of receptors--have now been documented to be involved in matrix deposition in vivo in this model. Administration of the proteoglycan decorin suppressed TGF-beta-induced matrix deposition in the nephritic glomeruli, thus confirming a physiological role for decorin as a regulator of TGF-beta. Inhibitors of TGF-beta may be important future drugs in treating fibrotic diseases caused by overproduction of TGF-beta.

Animals↗
PubMed1991

Isolation and sequence of partial cDNA clones of human L1: homology of human and rodent L1 in the cytoplasmic region.

We have isolated cDNA clones coding for the human homologue of the neuronal cell adhesion molecule L1. The nucleotide sequence of the cDNA clones and the deduced primary amino acid sequence of the carboxy terminal portion of the human L1 are homologous to the corresponding sequences of mouse L1 and rat NILE glycoprotein, with an especially high sequences identity in the cytoplasmic regions of the proteins. There is also protein sequence homology with the cytoplasmic region of the Drosophila cell adhesion molecule, neuroglian. The conservation of the cytoplasmic domain argues for an important functional role for this portion of the molecule.

Animals↗