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Biomedical subjects

J Lloyd

Publications and source records attributed to J Lloyd.

At least 55 records · Page 3Linked to original sources

Prospective randomised open-label comparison of danaparoid with dextran 70 in the treatment of heparin-induced thrombocytopaenia with thrombosis: a clinical outcome study.

AIM: To compare clinical outcomes in a randomised comparison of treatment with danaparoid sodium (a heparinoid), or dextran 70, for heparin-induced thrombocytopaenia (HIT) plus thrombosis. METHODS: Forty-two patients with recent thrombosis and a clinical diagnosis of probable HIT who presented at ten Australian hospitals during a study period of six and one half years were randomly assigned to open-label treatment with intravenous danaparoid or dextran 70, each combined with oral warfarin. Thirty-four patients (83%) had a positive platelet aggregation or 14C-serotonin release test for HIT antibody. Twenty-five received danaparoid as a bolus injection of 2400 anti-Xa units followed by 400 units per hour for 2 h, 300 units per hour for 2 h, and then 200 units per hour for five days. Seventeen received 1000 mL dextran 70 on day one and then 500 mL on days 2-5. Patients were reviewed daily for clinical evidence of thrombus progression or resolution, fresh thrombosis or embolism, bleeding or other complications. The primary trial endpoint was the proportion of thromboembolic events with complete clinical resolution by the time of discharge from hospital. RESULTS: With danaparoid, there was complete clinical recovery from 56% of thromboembolic events compared to 14% after dextran 70 (Odds Ratio 10.53, 95% Confidence Interval 1.6-71.4; p = 0.02). Clinical recovery with danaparoid was complete or partial in 86% of thromboembolic events compared with 53% after dextran 70 (Odds Ratio 4.55, 95% Confidence Interval 1.2-16.7; p = 0.03). Overall clinical effectiveness of danaparoid was rated as high or moderate in 88% of patients compared with 47% for dextran 70 (p = 0.01). One patient given danaparoid died of thrombosis compared with three patients given dextran 70. The platelet count returned to normal after a mean of 6.7 days with danaparoid and 7.3 days with dextran 70. There was no major bleeding with either treatment. CONCLUSION: danaparoid plus warfarin treatment for HIT with thrombosis is effective, safe, and superior to dextran 70 plus warfarin.

Aged↗

Early changes in respiratory compliance and resistance during the development of bronchopulmonary dysplasia in the era of surfactant therapy.

Despite the availability of surfactant treatment, extremely low birth weight (ELBW) infants continue to be at high risk of developing bronchopulmonray dysplasia (BPD). Evidence suggests that pathologic changes occur within the first few days of life. We hypothesized that the changes in early respiratory system compliance and resistance in ELBW infants with or without hyaline membrane disease (HMD) would correlate with BPD severity and aid in its prediction. Respiratory system compliance (Crs) and resistance (Rrs) were measured at the end of weeks 1, 2, 3, and 4 in 46 infants weighing 1,000 g or less at birth, using the single breath airway occlusion method. Twenty-four infants had HMD and 22 did not. Fifteen infants with and 10 infants without HMD developed BPD with radiological changes and oxygen needs at 28 days. Twelve BPD infants required supplemental oxygen beyond 36 weeks, defined as chronic lung disease (CLD). Irrespective of whether the infant initially had HMD, the week 1 results showed that infants who subsequently developed BPD had a significantly higher respiratory system resistance than those who did not (P = 0.0014). Though week 1 compliance was lower, it was not statistical significant. Multiple logistic models consisting of simple neonatal variables and week 1 respiratory mechanics showed that Rrs was independently associated with subsequent BPD (P = 0.026) and CLD (P = 0.016), while compliance was not. Prediction of CLD improved with the inclusion of Rrs results as compared to prediction using clinical variables alone. Throughout the 4-week study period, Rrs was significantly higher in BPD infants than in those without BPD, and resistance was particularly abnormal in those who had CLD or subsequently required corticosteroid treatment. These observations provide rationale for interventions to prevent BPD within the first week of life. Respiratory mechanics measurements could be useful in the assessment of therapeutics in the current surfactant era.

Airway Resistance↗

Preserving transfer independence among individuals with spinal cord injury.

STUDY DESIGN: Literature review. OBJECTIVES: Upper extremity (UE) joint degeneration, particularly at the shoulder, detrimentally influences functional independence, quality of life, cardiovascular disease risk, and life expectancy of individuals following spinal cord injury (SCI). This review (1) describes UE use for transfers among individuals with SCI; (2) describes contributing factors associated with UE joint degeneration and loss of transfer independence; (3) summarizes and identifies gaps in existing research; and (4) provides suggestions for future research. RESULTS: Investigations of wheelchair transfer related UE joint and function preservation among individuals with SCI should consider factors including age and length of time from SCI onset, interface between subject-wheelchair, pain, shoulder joint range of motion (ROM) and muscle strength deficiencies or imbalances, exercise capacity and tolerance for the physical strain of activities of daily living (ADL), body mass and composition, previous UE injury or disease history, and transfer techniques. Existing studies of transfers among individuals with SCI have relied on small groups of either asymptomatic or non-impaired subjects, with minimal integration of kinematic, kinetic and electromyographic data. Descriptions of UE joint ROM, forces, and moments produced during transfers are lacking. CONCLUSIONS: Biomechanical measurement and computer modeling have provided increasingly accurate tools for acquiring the data needed to guide intervention planning to prevent UE joint degeneration and preserve function among individuals with SCI. The identification of stressful sub-components during transfers will enable intervening clinicians and engineers who design and modify assistive and adaptive devices to better serve individuals with SCI.

Activities of Daily Living↗

Status of selected nutrients and progression of human immunodeficiency virus type 1 infection.

BACKGROUND: Immune function is highly dependent on nutritional status because the large mass and high rate of cellular turnover of the immune system make it a major user of nutrients. Furthermore, nutrient requirements may be increased during acute and chronic infections, including HIV-1 infection. OBJECTIVE: The current study was designed to assess relations among HIV-1 progression and 11 nutritional and demographic variables. DESIGN: The participants were 106 HIV-infected outpatients and 29 uninfected control subjects (n = 89 men and 46 women; age range: 35-57 y). The HIV-infected subjects represented a broad range of disease progression. RESULTS: We found lower concentrations of plasma and erythrocyte magnesium and of erythrocyte reduced glutathione beginning early in the course of HIV-1 infection. Significantly decreased hematocrit and increased serum copper concentration developed only late in the course of the disease. Statistically significant univariate associations were found between the CD4(+) T lymphocyte count and hematocrit, plasma magnesium concentration, and plasma zinc concentration. The lowest erythrocyte magnesium concentrations occurred in HIV-infected subjects who consumed alcoholic beverages. Independent variables that were significant joint predictors of CD4(+) cell count in multiple regression analyses were hematocrit and plasma free choline and zinc concentrations. These 3 factors together explained 43% of the variability in CD4(+) cell counts. CONCLUSION: The results provide evidence that compromised nutritional and antioxidant status begin early in the course of HIV-1 infection and may contribute to disease progression.

Adult↗

Experience with continuous infusion of recombinant activated factor VII in the Asia-Pacific region.

There is increasing interest in continuous infusion of recombinant activated factor VII (rFVIIa) as a convenient and safe alternative to intermittent bolus therapy. In the Australian patients reported in this paper, cost savings of up to 25% in the first 12 h of treatment with continuous infusion of rFVIIa have been achieved safely, suggesting that substantial overall savings are possible. However, in the Thai patient reported, a dose reduction of 35% in the first 12 h was associated with poor haemostatic control, suggesting that a dose reduction of >25% may be inadvisable. The indications for treatment in the five Australian patients were: retroperitoneal haemorrhage (n = 3); right forearm compartment syndrome (n = 1); wrist haemarthrosis and median nerve compression (n = 2); sublingual haematoma (n = 1); and cerebral (mid-brain) haemorrhage (n = 1). Treatment was effective in four out of five patients (six bleeding episodes) and there was one treatment failure where treatment had been substantially delayed. The Thai patient was treated as part of a prospective, uncontrolled, observational study of 34 bleeding episodes in 22 patients in the Asia-Pacific region. Treatment was judged ineffective after 24 h, but full haemostatic control was subsequently achieved with intermittent rFVIIa therapy.

Adult↗

Lipoproteins and their subfractions in psoriatic arthritis: identification of an atherogenic profile with active joint disease.

OBJECTIVES: (a) To characterise the lipid profile in psoriatic arthritis and investigate whether there are similarities to the dyslipoproteinaemia reported in rheumatoid arthritis and other inflammatory forms of joint disease; (b) to investigate whether there is an atherogenic lipid profile in psoriatic arthritis, which may have a bearing on mortality. METHODS: Fasting lipids, lipoproteins, and their subfractions were measured in 50 patients with psoriatic arthritis and their age and sex matched controls. RESULTS: High density lipoprotein cholesterol (HDL cholesterol) and its third subfraction, HDL(3) cholesterol, were significantly reduced and the most dense subfraction of low density lipoprotein (LDL), LDL(3), was significantly increased in the patients with psoriatic arthritis. Twenty patients with active synovitis had significantly lower total cholesterol, LDL cholesterol, and HDL(3) cholesterol than their controls. 25% of the patients with psoriatic arthritis had raised Lp(a) lipoprotein levels (>300 mg/l) compared with 19% of controls, but this was not statistically significant. CONCLUSION: Raised levels of LDL(3) and low levels of HDL cholesterol are associated with coronary artery disease. Such an atherogenic profile in a chronic inflammatory form of arthritis is reported, which may be associated with accelerated mortality.

Adult↗

Mammary and extramammary Paget's disease.

Mammary and extramammary Paget's disease are uncommon intraepithelial adenocarcinomas. Both conditions have similar clinical features, which mimic inflammatory and infective diseases. Histological diagnostic confusion can arise between Paget's disease and other neoplastic conditions affecting the skin, with the most common differential diagnoses being malignant melanoma and atypical squamous disease. The glandular differentiation of both mammary Paget's disease and extramammary Paget's disease is indicated by morphological appearances, the presence of intracellular mucin in many cases, and positive immunohistochemical staining for glandular cytokeratins, epithelial membrane antigen, and carcinoembryonic antigen. This article provides an overview of mammary and extramammary Paget's disease and discusses recent evidence regarding the cell of origin. The concepts of primary and secondary Paget's disease are presented and the differential diagnosis is discussed with reference to immunohistochemical markers that might be of diagnostic value.

Breast Neoplasms↗

Understanding and influencing starch biochemistry.

Starch is one of the most important products synthesized by plants that is used in industrial processes. If it were possible to increase production or modify starches in vivo, using combinations or either genetically altered or mutant plants, it may make them cheaper for use by industry, or open up new markets for the modified starches. The conversion of sucrose to starch in storage organs is, therefore, discussed. In particular the roles of the different enzymes directly involved in synthesizing the starch molecules on altering starch structure are reviewed, as well as the different models for the production of the fine structure of amylopectin. In addition, the process of starch phosphorylation, which is also important in determining the physical properties of starches, is reviewed. It is hoped that detailed knowledge of these processes will lead to the rational design of tailored starches. Starch degradation is also an important process, for example, in the cold-sweetening of potato tubers, but outside of cereal endosperm little is known about the processes involved. The enzymes thought to be involved and the evidence for this are discussed.

Glycogen Debranching Enzyme System↗

Integration between GPs and hospitals: lessons from a division-hospital program.

The aim of the study reported here was to evaluate current initiatives in GP-hospital integration and highlight areas where further research, development and evaluation are required. Seven pre-existing GP-hospital programs were selected and given supplementary funding to allow for more effective evaluation. These local evaluations were then incorporated into a national program on GP-hospital collaboration. We found that the seven projects made substantial progress towards their goals, and in the process highlighted important aspects of successful collaboration. The collective evaluation of DHIP identified expected benefits of collaboration for patients (improved access to services, reduced anxiety, and fewer post discharge complications), for GPs (increased involvement in acute care and in hospital decision making), and for service organisations (stronger working relationships, increased capacity, and greater efficiency). Barriers to service integration were also identified, including the different cultures of Divisions and hospitals, their lack of internal coherence and the Commonwealth-state divide. The evaluation showed that much has been achieved in building the relationships and the capacity needed for GP-hospital collaboration, and that effective models exist. The current challenge is to extend successful models across health areas and make effective collaboration part of the normal system of care. Substantial progress towards integrated care relies on a shift from a focus on systems within general practice or hospital environments to a patient centred approach. This will require general practice, hospitals, community services and consumer organisations to form long term partnerships and move beyond their currently disjointed view of acute and community care. The development of practical indicators for integrated care will support the process and facilitate shared learning across Commonwealth and state divides.

Australia↗

The pharmacokinetics of lamivudine phosphorylation in peripheral blood mononuclear cells from patients infected with HIV-1.

OBJECTIVE: To assess the pharmacokinetics of lamivudine phosphorylation in peripheral blood mononuclear cells (PBMC) from patients infected with HIV-1. DESIGN: Single-center, open-label, randomized, two-period, cross-over study in 10 asymptomatic, antiretroviral-experienced, HIV-1-infected patients who had a CD4+ lymphocyte count of 200-500 x 10(6)/l and had received combination treatment with lamivudine 150 mg twice a day plus zidovudine 600 mg a day (divided into two or three doses) for > or = 16 weeks prior to study entry. METHODS: Patients were randomly assigned to receive lamivudine 150 mg twice a day or lamivudine 300 mg twice a day for 14 days, with at least a 48-h washout period between treatments. Serial blood samples were collected over 36 h for determination of lamivudine serum concentrations using liquid chromatography/mass spectrometry and intracellular phosphate PBMC concentrations using high performance liquid chromatography/radioimmunoassay methods. Pharmacokinetic parameters were calculated based on lamivudine and lamivudine anabolite concentration-time data. RESULTS: Intracellular pharmacokinetic parameters were highly variable between patients (coefficient of variations approximately 50%). The two regimens produced lamivudine-total phosphate (totP) values of a similar magnitude. Although the 300-mg regimen tended to produce higher lamivudine-monophosphate (MP) and -triphosphate (TP) values, differences from values produced by the 150-mg regimen were not statistically significant. As lamivudine diphosphate (DP) was the predominant anabolite, accounting for 50-55% of lamivudine-totP (compared with 30-35% for lamivudine-MP and 15-20% for lamivudine-TP), the conversion of lamivudine-DP to lamivudine-TP can be regarded as the rate-limiting step. The median lamivudine-TP intracellular half-life (t1/2) for the 150-mg and 300-mg regimens did not differ significantly (15.3 and 16.1 h, respectively). Serum lamivudine pharmacokinetic parameters were consistent with those observed in previous studies in HIV-1-infected patients. No apparent linear relationships were observed between lamivudine intracellular anabolite and serum data. CONCLUSIONS: The intracellular pharmacokinetics of lamivudine phosphorylation in PBMC from asymptomatic HIV-1-infected patients are highly variable and do not differ statistically between the 150- and 300-mg twice a day regimens. The variations in intracellular lamivudine-TP concentrations following these two lamivudine dosage regimens are unlikely to result in differences in clinical effect. This was confirmed by the results of a large phase III study in HIV-1-infected patients which showed no differences in HIV-1 RNA or CD4+ lymphocyte counts between the 150- and 300-mg lamivudine regimens in combination with zidovudine.

Anti-HIV Agents↗

Serial phospholipid analysis in preterm infants: comparison of Exosurf and Survanta.

The initial clinical response to synthetic or natural surfactant is different and long-term complications from meta-analysis suggest that bronchopulmonary dysplasia and retinopathy of prematurity may be increased in infants given synthetic surfactant. It is possible that this is due to differences in the phospholipid composition of lung fluid following administration of these surfactants. Infants less than 32 weeks gestation with respiratory distress syndrome (RDS) were randomly assigned to receive either Exosurf, an artificial surfactant, or Survanta, a natural surfactant. Endotracheal or hypopharyngeal aspirates were obtained from these infants and from control infants who had normal lungs. The aspirates were taken prior to and up to 28 days following surfactant administration. The different phospholipids were separated by thin layer chromatography and expressed as a percent of total phospholipid measured. Infants with normal lungs had a higher proportion of phosphatidylcholine than those with RDS prior to treatment. The infants with normal lungs had a greater proportion of phosphatidylinositol in their lung aspirates than both treatment groups at 24 h. Infants in the Survanta group had a higher proportion of phosphatidylglycerol at 48 h than the group with normal lungs. No other differences were found in phospholipid composition up to 28 days. There were no major differences in the phospholipid profile in infants with RDS treated with either Exosurf or Survanta. In conclusion, neither the clinical differences initially seen between infants treated with either Exosurf or Survanta, nor the long-term outcome could be explained by the phospholipid composition of serial samples of lung aspirates.

Analysis of Variance↗

Kikuchi-Fujimoto's syndrome masquerading as tuberculosis.

We report a case of a 27-year-old Asian man presenting with the typical features of tuberculous cervical lymphadenitis who was commenced on anti-tuberculous therapy on the strength of the clinical presentation. Histological examination of an excised cervical lymph node however, revealed the diagnosis of Kikuchi's syndrome; a histiocytic necrotizing lymphadenitis which is usually self-limiting.

Adult↗