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Biomedical subjects

J Davenport

Publications and source records attributed to J Davenport.

At least 19 recordsLinked to original sources
PubMed2001

Reduction in stroke with gemfibrozil in men with coronary heart disease and low HDL cholesterol: The Veterans Affairs HDL Intervention Trial (VA-HIT).

BACKGROUND: A low level of HDL cholesterol has been identified as a risk factor for stroke in observational studies. METHODS AND RESULTS: Our objective was to determine whether treatment aimed at raising HDL cholesterol and lowering triglycerides reduces stroke in men with coronary heart disease and low levels of both HDL and LDL cholesterol. The study was a placebo-controlled, randomized trial conducted in 20 Veterans Affairs medical centers. A total of 2531 men with coronary heart disease, with mean HDL cholesterol 0.82 mmol/L (31.5 mg/dL) and mean LDL cholesterol 2.9 mmol/L (111 mg/dL), were randomized to gemfibrozil 1200 mg/d or placebo and were followed up for 5 years. Strokes were confirmed by a blinded adjudication committee. Relative risks were derived from Cox proportional hazards models. There were 134 confirmed strokes, 90% of which were ischemic. Seventy-six occurred in the placebo group (9 fatal) and 58 in the gemfibrozil group (3 fatal), for a relative risk reduction, adjusted for baseline variables, of 31% (95% CI, 2% to 52%, P=0.036). The reduction in risk was evident after 6 to 12 months. Patients with baseline HDL cholesterol below the median may have been more likely to benefit from treatment than those with higher HDL cholesterol. CONCLUSIONS: In men with coronary heart disease, low HDL cholesterol, and low LDL cholesterol, gemfibrozil reduces stroke incidence.

Aged↗
PubMed2000

Nitric oxide synthase and cGMP activity in the salivary glands of the American dog tick Dermacentor variabilis.

We colocalized nitric oxide synthase (NOS) activity in epithelial cells that surround the salivary gland duct in female Dermacentor variabilis with NADPH diaphorase histochemistry and immunohistochemistry using a polyclonal anti-endothelial NOS. Using size-exclusion chromatography, a fraction with a molecular mass of about 185 kDa that had diaphorase activity was eluted from tick salivary gland homogenate. This fraction converted arginine to citrulline with the production of nitric oxide (NO), which was detected by using electron spin resonance spectroscopy. The complete activity of the diaphorase fraction was dependent on NADPH, FAD, tetrahydrobiopterin, calmodulin, (CaM), and Ca(2+), but was not dependent on dithiothreitol. The arginine analog N(G)-monomethyl-L-arginine inhibited the activity of this fraction. NO and arginine activated soluble guanylate cyclase to produce cGMP in dopamine-stimulated isolated salivary glands. Dopamine-stimulated isolated salivary glands treated with tick saline containing either EDTA, the NOS inhibitor N(G)-nitro-L-arginine methyl ester, or the calcium/CaM binding inhibitor W-7 showed no increase in cGMP. The NO donor sodium nitroprusside significantly increased cGMP levels in unstimulated isolated salivary glands. A possible function for NO in salivation by this ixodid tick is discussed.

Animals↗
PubMed2000

Identification of genes potentially involved in LMO2-induced leukemogenesis.

The most common translocations in childhood T cell acute lymphoblastic leukemias involve the LMO2 locus on chromosome 11p13 and cause ectopic expression of the LMO2 gene in thymocytes. Transgenic mice with enforced expression of LMO2 in their thymocytes develop T cell leukemias thus demonstrating the role of LMO2 in leukemogenesis. The physiologic and leukemogenic functions of LMO2 are mediated through its transcriptional regulatory activities, but the identity of the target genes is completely unknown. In this report, we have used cDNA representational difference analysis (cDNA-RDA) to identify genes that are over-expressed and are likely to play a role in the LMO2 induced leukemias. cDNA-RDA was performed using very small amounts of mRNA pool (from 1 microg of total RNA) to reverse transcribe the cDNAs from leukemic cells or normal thymocytes. The cDNA-RDA led to the isolation of nine distinct clones that were specifically overexpressed in the leukemic cells. Sequence analysis revealed that five of the nine clones had identity or homology to known genes that are known to play a role in the pathogenesis of leukemias or other cancers. Three clones had no significant homology to any known genes and thus represent novel candidate genes. Our study demonstrates that cDNA-RDA using very small amounts of total RNA is a highly efficient method to identify novel genes that may play a role in leukemogenesis.

Adaptor Proteins, Signal Transducing↗
PubMed1999

Human corneal epithelial cell adhesion to laminins.

PURPOSE: To analyze alpha-integrin mediated adhesion of human corneal epithelial cells to placental and EHS laminin isoforms. METHODS: Western blot analysis was used to partially characterize commercially available preparations of laminin isolated from the mouse EHS sarcoma and from human placenta. Using the human corneal epithelial cell line HCE-T, adhesion to laminin isoforms and fibronectin was determined using a colorimetric adhesion assay. alpha-integrin sub-unit modulation of corneal epithelial cell interaction with laminin isoforms was analyzed using immunofluorescence microscopy and adhesion assays incorporating functional blocking antibodies. RESULTS: In short-term adhesion assays, the preferred substrate for HCE-T attachment is placental laminin. Immunofluorescence microscopy reveals that alpha-integrin protein localization patterns are not significantly different in HCE-T interacting with EHS or placental laminin. However, in short-term assays alpha3 integrin plays a major role, and alpha2 integrin a minor role, in mediating HCE-T adhesion to laminin. alpha6 integrin does not appear to mediate adhesion to either substrate. CONCLUSIONS: These studies demonstrate that human corneal epithelial cells are capable of rapid adhesion to, and enhanced spreading on, laminin isoforms not characteristically resident in the adult corneal basement membrane. This characteristic of human corneal epithelium may explain, at least in part, why amniotic membrane transplantation is proving to be clinically useful for human ocular surface reconstruction.

Animals↗
PubMed1996

Macrocytic anemia.

In approximately 2 to 4 percent of patients, laboratory evidence of macrocytosis is found. Macrocytic anemias are classified as those resulting from disorders of DNA synthesis of erythrocyte precursors in bone marrow (megaloblastic anemias) or those caused primarily by alcoholism, liver disease and hypothyroidism (nonmegaloblastic anemias). A blood smear should be performed to differentiate the two forms. Neutrophil hypersegmentation is one of the most sensitive and specific signs of megaloblastic anemia. Other testing should include vitamin B12 and red blood cell folate levels, reticulocyte count, and thyroid and liver function tests. The Schilling test can determine if B12 can be absorbed and, if not, whether adding intrinsic factor corrects the malabsorption. The most common form of nonmegaloblastic macrocytic anemia results from alcoholism. Nonmegaloblastic macrocytic anemias may be accompanied by increased reticulocyte counts (hemolysis, hemorrhage) or by normal or decreased reticulocyte counts (alcoholism, liver disease, hypothyroidism and various bone marrow disorders).

Algorithms↗
PubMed1995

Silent cerebral infarction in patients with nonrheumatic atrial fibrillation. The Veterans Affairs Stroke Prevention in Nonrheumatic Atrial Fibrillation Investigators.

BACKGROUND: Cerebral infarction in patients with atrial fibrillation may vary from being clinically silent to catastrophic. The prevalence of silent cerebral infarction and its effect as a risk factor for symptomatic stroke are important considerations for the evaluation of patients with atrial fibrillation. METHODS AND RESULTS: This Veterans Affairs cooperative study was a double-blind controlled trial designed primarily to determine the efficacy of warfarin for the prevention of stroke in neurologically normal patients with nonrheumatic atrial fibrillation. It also was designed to evaluate patients with silent cerebral infarction. Computed tomography scans of the head were performed at entry, at the time of any subsequent stroke, and at termination of follow-up on all patients who completed the study without a neurological event. Of 516 evaluable scans performed at entry, 76 (14.7%) had evidence of one or more silent cerebral infarcts. Age (P = .011), a history of hypertension (P = .003), active angina (P = .012), and elevated mean systolic blood pressure (P < .001) were associated with the presence of this finding. Silent cerebral infarction occurred during the study at rates of 1.01% and 1.57% per year for the placebo and warfarin treatment groups, respectively (NS). Silent cerebral infarction at entry was not an independent predictor of later symptomatic stroke, but active angina was a significant predictor; 15% of the placebo-assigned patients with angina developed a stroke compared with 5% of the placebo-assigned patients without angina. CONCLUSIONS: Silent cerebral infarction is frequently seen in asymptomatic patients with atrial fibrillation. Age, history of hypertension, active angina, and elevated mean systolic blood pressure were associated with silent infarction at entry. The sample size was too small to determine whether warfarin had an effect on the incidence of silent infarction during the trial. Active angina at baseline was the only significant independent predictor for the later development of symptomatic stroke.

Aged↗
PubMed1991

Addison's disease.

Addison's disease is an uncommon endocrine condition manifested by a variety of nonspecific symptoms, such as malaise, anorexia and nausea. Symptoms usually do not occur until most of the adrenal gland has been destroyed. Autoimmune disease has surpassed tuberculosis as the primary cause of Addison's disease. Nevertheless, tuberculosis still accounts for a significant proportion of cases. The rapid adrenocorticotropic hormone (ACTH) stimulation test is useful for identifying adrenal insufficiency. Maintenance therapy consists of hydrocortisone and fludrocortisone.

Addison Disease↗
PubMed1990

Preliminary study of the treatment of advanced breast cancer in postmenopausal women with the aromatase inhibitor CGS 16949A.

Thirty-one postmenopausal women with advanced breast cancer have been treated with the nonsteroidal competitive aromatase inhibitor CGS 16949A at p.o. doses of 0.3, 1, and 2 mg twice a day. All patients were assessed for response. Five patients, all treated with 1 mg twice daily, had objective evidence of response (two complete responses and three partial responses); disease stabilized in 17 patients. Minor side effects were reported by ten patients. Two further patients treated with 2 mg twice a day experienced persistent nausea which improved after dose reduction, and one patient, treated with 0.3 mg twice daily, developed a vasculitic rash requiring discontinuation of CGS 16949A. Estradiol levels measured in 24 patients were significantly suppressed 2 wk after starting CGS 16949A treatment at all doses used. Treatment with 2 mg twice a day lowered estradiol levels to a mean of 29% of pretreatment values which was significantly lower than the corresponding figure of 57% for patients treated with 0.3 mg twice daily. Aldosterone levels were significantly lowered below pretreatment values by the 1- and 2-mg twice daily doses. No clinically apparent cases of adrenocortical insufficiency occurred, although small changes in serum electrolyte levels were noted. The results indicate that CGS 16949A is an effective aromatase inhibitor, requiring further evaluation in the treatment of advanced breast cancer. The optimal dose is likely to be 1 mg twice a day.

Aldosterone↗
PubMed1990

Treatment of advanced breast cancer in postmenopausal women with 4-hydroxyandrostenedione.

4-Hydroxyandrostenedione (4-OHA), a new specific aromatase inhibitor, was used to treat 57 postmenopausal women with advanced breast cancer at a dose of 250 mg by i.m. injection every 2 weeks; 55 women were assessable for response. In all, 18 patients (33%) had objective evidence of a response to treatment, with a median duration of 12 months; the disease stabilised in 8 (14%) patients. Serum oestradiol levels, which were measured weekly in nine of the patients, were found to be suppressed to a mean of between 36% and 51% of pretreatment levels during the first 6 weeks of treatment. Three patients were withdrawn from treatment because of toxicity (pain at injection site, sterile abscess and rash). One patient had an isolated episode of anaphylaxis after 6 months of treatment. In comparison with our previous reports of 4-OHA treatment, a dose of 250 mg given i.m. fortnightly appears to be the optimal dose regimen. The efficacy of the drug seems to be similar to that of tamoxifen and aminoglutethimide.

Adult↗
PubMed1990

Phase I/II study of the anti-oestrogen zindoxifene (D16726) in the treatment of advanced breast cancer. A Cancer Research Campaign Phase I/II Clinical Trials Committee study.

We report a phase I/II study of the indole derivative, zindoxifene, an anti-oestrogen with intrinsic oestrogenic activity. We have treated 28 women with advanced breast cancer of whom 26 had received prior endocrine therapy. Oral zindoxifene doses ranged from 10 to 100 mg daily; doses were escalated in some patients. Twenty-five patients were assessed for response; the remaining three patients completed less than 3 weeks of treatment. There were no objective responses; disease stabilised in seven patients for up to 5 months and progressed in the remaining 18. Five patients (including three treated with tamoxifen) responded to subsequent endocrine therapy. Nausea, which was dose-limiting, affected half of the patients treated with 80 mg daily. Metabolites of zindoxifene were detectable in serum at all doses used, and sex hormone binding globulin (SHBG) levels showed a strong tendency to rise at the higher doses, indicating that zindoxifene is absorbed and has biological activity. We conclude that zindoxifene in the doses used in this study has only marginal therapeutic activity in the treatment of advanced breast cancer.

Aged↗
PubMed1990

Scaphoid fracture: evaluation with flexion-extension tomography.

Assessment of healing of a scaphoid fracture, which may be associated with delayed fusion and nonunion, is a challenging task for the radiologist. Thirty cases of clinically suspected nonunion scaphoid waist fractures with inconclusive plain radiographs were prospectively studied by means of stationary tomography and lateral flexion-extension tomography. The angle between the two scaphoid fragments as seen in extension was measured and compared with the angle as seen in flexion. A difference of 10 degrees or greater between flexion and extension was considered significant. This was noted in 14 of 15 cases of nonunion. Fifteen cases without angle differences were accurately diagnosed as stable. One false-negative case was noted, which on review was attributed to a limited extension view. Flexion-extension tomography is a highly valuable diagnostic modality in evaluating the stability and healing of scaphoid fracture and is superior to conventional (stationary) tomography.

Adolescent↗
PubMed1990

Prosthetic valve endocarditis 1976-1987. Antibiotics, anticoagulation, and stroke.

We retrospectively reviewed the clinical characteristics and outcomes of 61 patients with 62 episodes of prosthetic valve endocarditis, paying particular attention to neurologic complications (stroke). Atypical features of the group included a benign outcome of early postoperative infection (18% mortality) and a high stroke morbidity and mortality rate with Staphylococcus epidermidis infections. Eleven patients (18%) suffered an embolic stroke, most less than or equal to 3 days after diagnosis and before the initiation of antimicrobial therapy; the rate of embolic stroke recurrence was low (9%). The risk of embolic stroke was lower with bioprosthetic than with mechanical valves. No protective effect of anticoagulation therapy with warfarin was observed. Six patients (8%) suffered brain hemorrhage due to septic arteritis, brain infarction, or undetermined causes; no specific risk of hemorrhagic stroke was evident with anticoagulation therapy. Antibiotic treatment appears to be more important than anticoagulation to prevent neurologic complications in patients with prosthetic valve endocarditis.

Anti-Bacterial Agents↗
PubMed1989

Postpericardiotomy syndrome.

The increase in major cardiac operations performed in the United States has been accompanied by an increase in the incidence of postpericardiotomy syndrome. Family physicians must be able to recognize the clinical picture, since patients may present several weeks postoperatively. Symptoms include malaise, pleuritic pain, dyspnea, myalgias, arthralgias and anorexia. Signs include fever, rales, friction rubs, effusions and leukocytosis. Anti-inflammatory drugs are effective.

Heart Diseases↗