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Biomedical subjects

David Anderson

Publications and source records attributed to David Anderson.

At least 37 records · Page 2Linked to original sources
PubMed2005

The strong ion gap predicts mortality in children following cardiopulmonary bypass surgery.

OBJECTIVE: Stewart's strong ion theory quantifies unmeasured tissue acids produced following hypoxia or hypoperfusion, by calculation of the strong ion gap. Our study objectives were as follows: a) to determine the 24-hr profile of the strong ion gap following cardiopulmonary bypass surgery; and b) to compare the prognostic value in terms of intensive care unit mortality of this variable with blood lactate. DESIGN: Prospective, observational study. SETTING: Tertiary pediatric intensive care unit. PATIENTS: Eighty-five children following surgery for congenital heart disease. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Arterial blood samples for lactate and strong ion gap calculation were obtained at intensive care unit admission and at 24 hrs. A raised strong ion gap (>3 mEq/L) was present in 41.1% and 51.7% of admission and 24-hr samples, respectively, being elevated at both time points in 30.5%. Both the strong ion gap and lactate increased with surgical complexity, but neither was correlated with length of bypass (r = .13 and -.02) or aortic cross-clamp (r = .13 and .10). The crude mortality was 5.8% (5/85). Four of the five deaths were associated with a persistently elevated strong ion gap, in contrast to two with ongoing hyperlactatemia (>2 mmol/L). The admission strong ion gap (cutoff, >3.2 mEq/L) was superior to lactate (cutoff, >3.0 mmol/L) as a mortality predictor (area under receiver operating characteristic curve of 0.85 [95% confidence interval, 0.74-0.95] vs. 0.71 [95% confidence interval, 0.44-0.98], respectively). CONCLUSIONS: An elevated strong ion gap occurs commonly following bypass surgery and appears to be superior to lactate as a mortality predictor.

Acid-Base Equilibrium↗
PubMed2005

Does cryosupernatant plasma improve outcome in thrombotic thrombocytopenic purpura? No answer yet.

A randomized prospective trial compared cryosupernatant plasma (CSP) to fresh frozen plasma (FFP) for treatment of thrombotic thrombocytopenic purpura (TTP). A total of 236 patients were required: 28 patients were treated with CSP and 24 with FFP within 30 months. There were no differences in survival at 1 month. By day 9, 17 of 26 patients with CSP and 18 of 24 with FFP had a platelet count >100 x 10(9)/l. At entry, von Willebrand factor (VWF) multimers were normal in all patients (range 1.1-3.95 IU/ml). ADAMTS-13 levels showed large variations ranging from 10% to 100% activity. At entry, no individual had <5% VWF cleaving protease. By day 9 (end of cycle), 89% (FFP) and 67% (CSP) had levels >50% of the controls. At 6 months some patients showed inhibitors to the enzyme in spite of adequate or normal platelet counts. The data from this study do not show an apparent advantage to the use of CSP in TTP. A large number of patients will be required to determine appropriate replacement therapy. We were not able to find a statistically significant relationship between the low level of protease activity at presentation of TTP and response.

ADAM Proteins↗
PubMed2005

Comparison of a new immunochromatographic test to enzyme-linked immunosorbent assay for rapid detection of immunoglobulin m antibodies to hepatitis e virus in human sera.

An immunochromatographic test for rapid detection of IgM antibodies in patients with acute hepatitis E infection was developed utilizing the well-characterized recombinant protein EP2.1 and monoclonal antibody 4B2. The new rapid test based on a novel reverse-flow technology was able to generate a positive result within 2 to 3 min. Our study showed that this test was able to detect anti-HEV IgM antibodies in 96.7% of the patient samples tested (n = 151) while maintaining an excellent specificity of 98.6% with samples from various patient or healthy control groups (total n = 208). Furthermore, this rapid test gave a good specificity of 90.9% when tested with rheumatoid factor (RF)-positive sera (RF value of < or =850 IU/ml; n = 11) although a higher concentration of RF in samples might cause cross-reactivity. The new test has a good agreement of 97.2% with a kappa value of 0.943 when compared with a reference enzyme-linked immunosorbent assay. The positive predictive value and the negative predictive value for the rapid test thus reached 98.0 and 97.6%, respectively. This is the first rapid, point-of-care test for hepatitis E and will be especially useful for the diagnosis of acute hepatitis E virus infection in field and emergency settings and in resource-poor countries.

Antibodies, Viral↗
PubMed2005

Evaluation of a new rapid immunochromatographic assay for serodiagnosis of acute hepatitis E infection.

A rapid and reliable diagnostic assay for acute hepatitis E virus (HEV) infection is needed. We evaluated a rapid, immunochromatographic assay for IgM antibodies to HEV (ASSURE HEV IgM Rapid Test) using acute-phase HEV samples (n = 200) from Indonesia and Nepal and convalescent-phase HEV samples (n = 70) from Nepal. Blood donors in Thailand (n = 100), individuals with hepatitis A (n = 80), hepatitis B (n = 45), and hepatitis C (n = 50) in Thailand and Nepal, acute-phase sera of individuals with Epstein-Barr virus infection (n = 20), and rheumatoid factor-positive blood (n = 26) served as negative controls. The assay had a sensitivity of 93% (95% confidence interval [CI] = 88.5-96.1%) and a specificity of 99.7% (95% CI = 98.3-100%). The positive and negative predictive values were 99.5% (95% CI = 97.1-100%) and 95.8% (95% CI = 93.1-97.7%), respectively. These results suggest that this assay is a sensitive and specific tool for the rapid diagnosis of acute HEV infection.

Acute Disease↗
PubMed2004

A randomized trial to assess the impact of an antithrombotic decision aid in patients with nonvalvular atrial fibrillation: the DAAFI trial protocol [ISRCTN14429643].

BACKGROUND: Decision aids are often advocated as a means to assist patient and health care provider decision making when faced with complicated treatment or screening decisions. Despite an exponential growth in the availability of decision aids in recent years, their impact on long-term treatment decisions and patient adherence is uncertain due to a paucity of rigorous studies. The choice of antithrombotic therapy for nonvalvular atrial fibrillation (NVAF) is one condition for which a trade-off exists between the potential risks and benefits of competing therapies, and the need to involve patients in decision making has been clearly identified. This study will evaluate whether an evidence-based patient decision aid for patients with NVAF can improve the appropriateness of antithrombotic therapy use by patients and their family physicians. DESIGN: A multi-center, two-armed cluster randomized trial based in community family practices in which patients with NVAF will be randomized to decision aid or usual care. Patients will receive one of four decision aids depending on their baseline stroke risk. The primary outcome is the provision of "appropriate antithrombotic therapy" at 3 months to study participants (appropriateness defined as per the 2001 American College of Chest Physicians recommendations for NVAF). In addition, the impact of this decision aid on patient knowledge, decisional conflict, well-being, and adherence will be assessed after 3 months, 6 months, and 12 months.

Atrial Fibrillation↗
PubMed2004

Microstructural disassembly of calcium phosphates.

Microstructural factors may play a role in the osseointegration of calcium phosphates. In this paper, direct microstructural interactions between crystalline calcium phosphates and the biological milieu are reported. Degradation via exposure to osteoblast culture closely resembles in vivo interactions with subcutaneous tissues in a bovine model at early time periods. That these interactions were common to both experiments constitutes one of the few known examples of in vitro-in vivo correspondence. Interestingly, the degradation of phase pure hydroxyapatite (HA) in vitro was more rapid than that of biphasic HA in vivo. In both cases, grain extraction/pullout was frequently observed. This suggests a connection to smaller-scale observations of epitaxial CHA nucleation and growth on pre-existing HA grains. A microstructure in which the grain boundary is dissolving/corroding can apparently be disassembled by forces transmitted through biological structures. These observations are distinct from those of simple non-biological solutions and prove that biological environments can interact with the material beneath the ceramic-cell/ceramic-tissue interface. Many often ignored microstructural factors-grain size, shape, grain boundary strength and the presence of impurity phases-may in fact control degradation. We also suggest that even relatively modest initial grain sizes will, in combination with the mild/absent foreign body response to calcium phosphates, result in lengthy in vivo particle resistence.

Animals↗
PubMed2004

Perinatal transmission of SHIV-SF162P3 in Macaca nemestrina.

We developed a SHIV/macaque model of transmission from infected dams to their infants. Ten pregnant dams were infected intravenously with 100 MID(50) of macaque-titered SHIV-SF162P3 during the second trimester. Nine infants were born; the seven surviving beyond day of birth suckled for 6 months. Four of nine infants were infected (transmission rate = 44.4%), with one infection in utero, and three intrapartum and/or immediately post-birth via suckling. Varying levels of binding and neutralizing antibodies were transplacentally transferred to infants. Passive antibodies were detected in plasma on the day of birth and persisted for 5 weeks. Infants infected at or after birth controlled acute and post-acute viremia. Exposure to maternal SHIV-SF162P3 during birth and suckling in the presence of autologous maternal neutralizing antibodies may have affected transmission or pathogenesis in the infants. This transmission model can allow investigation of key parameters involved in perinatal transmission of HIV.

Animals↗
PubMed2004

Functional outcomes of bone graft substitutes for benign bone tumors.

Benign bone tumors are frequently treated surgically by intralesional excision with grafting. Due to the significant morbidity associated with autogenous graft, there is interest in bone graft substitutes. Ninety-eight consecutive patients with benign bone tumors treated by intralesional excision with bone graft substitutes were retrospectively reviewed. Functional scores using the International Symposium of Limb Salvage (ISOLS) system were obtained at most recent follow-up. The mean functional score was 28.3 out of 30 (94%). Three patients suffered fractures that ultimately healed with management. There were no local recurrences. Based on results of this study, bone graft substitutes are a reasonable alternative to autogenous grafting with a successful functional outcome.

Adolescent↗
PubMed2004

Anticoagulation in atrial fibrillation. Is there a gap in care for ambulatory patients?

OBJECTIVE: Atrial fibrillation (AF) substantially increases risk of stroke. Evidence suggests that anticoagulation to reduce risk is underused (a "care gap"). Our objectives were to clarify measures of this gap in care by including data from family physicians and to determine why eligible patients were not receiving anticoagulation therapy. DESIGN: Telephone survey of family physicians regarding specific patients in their practices. SETTING: Nova Scotia. PARTICIPANTS: Ambulatory AF patients not taking warfarin who had risk factors that made anticoagulation appropriate. MAIN OUTCOME MEASURES: Proportion of patients removed from the care gap; reasons given for not giving the remainder anticoagulants. RESULTS: Half the patients thought to be in the care gap had previously unknown contraindications to anticoagulation, lacked a clear indication for anticoagulation, or were taking warfarin. Patients' refusal and anticipated problems with compliance and monitoring were among the reasons for not giving patients anticoagulants. CONCLUSION: Adding data from primary care physicians significantly narrowed the care gap. Attention should focus on the remaining reasons for not giving eligible patients anticoagulants.

Adult↗
PubMed2003

Lipid-drug association enhanced HIV-1 protease inhibitor indinavir localization in lymphoid tissues and viral load reduction: a proof of concept study in HIV-2287-infected macaques.

Analysis of indinavir levels in HIV-positive patients indicated that drug concentrations in lymph node mononuclear cells (LNMCs) were about 25-35% of mononuclear cells in blood. To enhance lymphatic delivery of anti-HIV drugs, a novel drug delivery strategy was designed consisting of lipid-associated indinavir (50-80 nm in diameter) complexes in suspension for subcutaneous (SC) injection. Due to the pH-dependent lipophilicity of indinavir, practically all the drug molecules are incorporated into lipid phase when formulated at pH 7.4 and 5:1 lipid-to-drug (m/m) ratio. At pH 5.5, about 20% of drugs were found in lipid-drug complexes. Effects of lipid association on the time course of plasma indinavir concentrations were determined in macaques (Macaca nemestrina) administered with either soluble or lipid-associated formulation of indinavir (10 mg/kg, SC). Results yielded about a 10-fold reduction in peak plasma concentration and a 6-fold enhancement in terminal half-life (t1/2beta = 12 vs. 2 hours). In addition, indinavir concentrations in both peripheral and visceral lymph nodes were 250-2270% higher than plasma (compared with <35% with soluble lipid-free drug administration in humans). Administration of lipid-associated indinavir (20 mg/kg daily) to HIV-2287-infected macaques (at 30-33 weeks after infection) resulted in significantly reduced viral RNA load and increased CD4 T cell number concentrations. Collectively, these data indicate that lipid association greatly enhances delivery of the anti-HIV drug indinavir to lymph nodes at levels that cannot be achieved with soluble drug, provides significant virus load reduction, and could potentially reverse CD4 T cell depletion due to HIV infection.

Animals↗
PubMed2003

A comparison of two intensities of warfarin for the prevention of recurrent thrombosis in patients with the antiphospholipid antibody syndrome.

BACKGROUND: Many patients with the antiphospholipid antibody syndrome and recurrent thrombosis receive doses of warfarin adjusted to achieve an international normalized ratio (INR) of more than 3.0. However, there are no prospective data to support this approach to thromboprophylaxis. METHODS: We performed a randomized, double-blind trial in which patients with antiphospholipid antibodies and previous thrombosis were assigned to receive enough warfarin to achieve an INR of 2.0 to 3.0 (moderate intensity) or 3.1 to 4.0 (high intensity). Our objective was to show that high-intensity warfarin was more effective in preventing thrombosis than moderate-intensity warfarin. RESULTS: A total of 114 patients were enrolled in the study and followed for a mean of 2.7 years. Recurrent thrombosis occurred in 6 of 56 patients (10.7 percent) assigned to receive high-intensity warfarin and in 2 of 58 patients (3.4 percent) assigned to receive moderate-intensity warfarin (hazard ratio for the high-intensity group, 3.1; 95 percent confidence interval, 0.6 to 15.0). Major bleeding occurred in three patients assigned to receive high-intensity warfarin and four patients assigned to receive moderate-intensity warfarin (hazard ratio, 1.0; 95 percent confidence interval, 0.2 to 4.8). CONCLUSIONS: High-intensity warfarin was not superior to moderate-intensity warfarin for thromboprophylaxis in patients with antiphospholipid antibodies and previous thrombosis. The low rate of recurrent thrombosis among patients in whom the target INR was 2.0 to 3.0 suggests that moderate-intensity warfarin is appropriate for patients with the antiphospholipid antibody syndrome.

Adult↗
PubMed2003

Guideline for the management of late-life depression in primary care.

OBJECTIVE: To develop a guideline for the primary care management of depression in later life based on best practice. METHOD: Source material included relevant guidelines, literature reviews and consensus documents coupled with an updated literature review covering 1998-October, 2001. This material was summarised as a series of evidence-based statements and recommendations agreed by consensus. RESULTS: Good quality evidence exists for the pharmacological and psychological treatment of depressive episode (major depression), although not specifically in primary care. There is some evidence of efficacy of antidepressants in late-life dysthymia and minor depression associated with poor functional status. In depressive episode, current evidence suggests acute treatment for at least six weeks and a continuation period of at least 12 months. Both tricyclic antidepressants and Selective Serotonin Re-uptake Inhibitors are effective in longterm prevention. There is less data on how to manage patients who do not respond in the acute treatment phase. More data is needed on sub-groups of patients with specific co-morbid medical conditions and those who are frail. Collaborative care is effective in older depressed primary care patients. CONCLUSIONS: There are effective treatments for depression in primary care. More research is needed to address the optimum treatment of depression with medical co-morbidity and to elucidate the role of newer psychological interventions. Collaborative care between primary care and specialist services is a promising new avenue for management.

Aged↗