Valsalva retinopathy associated with riding a motorcycle.
Explore the source record for details and available documents.
Adolescent↗
Biomedical subjects
M Harris
Publications and source records attributed to M Harris.
Effect of laser photocoagulation treatment for diabetic macular oedema on patient's vision-related quality of life.
PURPOSE: To evaluate the effect of laser photocoagulation for diabetic macular oedema (DME) on patients' Vision Related Quality Of Life (VR-QOL) and to investigate associations between changes in self reported VR-QOL and changes in visual acuity following application of laser treatment. METHODS: Prospective cohort study of 55 subjects who underwent laser treatment for DME. Eligible patients with no history of previous laser photocoagulation self-administered the 51-item field-test version of the National Eye Institute Visual Function Questionnaire (NEI-VFQ) prior to treatment and 3 months following the last session of laser application. Visual acuity was measured by means of the Early Treatment of Diabetic Retinopathy (ETDRS) chart. Multi-item scales rating different aspects of VR-QOL were compared prior and after photocoagulation and the change in questionnaire's composite score following treatment was correlated to change in visual acuity and other determinants previously reported as risk factors in the diabetic population. RESULTS: Scale scores associated with general vision, near vision, distance vision, peripheral vision, vision-specific social functioning, vision-specific mental health, expectations for visual function and dependency due to vision were significantly improved following laser treatment. Multivariate models revealed that improvement of the NEI-VFQ composite score was significant in subjects younger than 65 years of age (p = 0.04) who received more laser burns (p = 0.02) and had worse vision-related QOL prior to laser treatment as expressed by the baseline NEI- VFQ composite score (p = 0.03). There was no statistically significant association between change in the composite score following laser treatment and stage of diabetic retinopathy, duration of diabetes or laser settings used during photocoagulation. CONCLUSIONS: Photocoagulation for DME has a beneficial effect on patients' subjective perception of visual function. The use of vision-targeted health status questionnaires in conjunction with the clinical examination appears to provide a more comprehensive overview of individuals' daily well- being following laser treatment.
Aged↗
Post-transplant T-cell lymphoproliferative disorder/T-cell lymphoma: a report of three cases of T-anaplastic large-cell lymphoma with cutaneous presentation and a review of the literature.
AIMS: To report the clinical, pathological and immunohistochemical features of three cases of post-transplant T-cell lymphoproliferative disorder (T-PTLD) T-cell lymphoma with primary cutaneous presentation. METHODS AND RESULTS: Three cases of primary cutaneous post-transplantation anaplastic large-cell lymphomas occurred in renal transplant recipients and were shown to display a T-cell immunophenotype; all were ALK 1 protein and EMA negative and two were Epstein-Barr virus positive using in-situ hybridization. Two displayed a CD4+ phenotype, two were focally CD56+ and all three were negative for the cytolytic enzyme granzyme B. In two cases monoclonality was established by T-cell receptor gene rearrangement study. All presented with nodular cutaneous involvement and all were ultimately fatal. CONCLUSION: T-PTLDs are uncommon histological subtypes both in a general context and associated with cutaneous presentation. Our findings suggest clinicopathological and immunophenotypic similarities to primary cutaneous anaplastic large-cell lymphoma but with a progressive clinical behaviour similar to previously reported T-PTLD and to systemic nodal ALK- anaplastic large-cell lymphoma.
Adult↗
Identification of RANKL in osteolytic lesions of the facial skeleton.
RANKL (receptor activator of nuclear factor kappaB ligand) promotes osteoclast differentiation, stimulates osteoclast activity, and prolongs osteoclast survival and adherence to bone. Abnormalities of the RANKL/RANK/osteoprotegerin system have been implicated in a range of diseases, including osteoporosis. To date, no work has been done in osteolytic lesions of the facial skeleton. In this study, specimens of ameloblastomas, dentigerous cysts, odontogenic keratocysts, and radicular cysts were subjected to immunohistochemical analysis for RANKL and tartrate-resistant acid phosphatase (TRAP). Immunofluorescence staining for TRAP was visualized under confocal microscopy. All specimens demonstrated distinct positive immunoreactivity to RANKL and TRAP. The TRAP-positive cells also stained with in situ hybridization for human calcitonin receptor, a definitive marker for osteoclasts. Mononuclear pre-osteoclasts were observed to migrate from blood to the connective tissue stroma and multinucleate toward the bone surface. It can be concluded that RANKL plays a role in bone resorption in osteolytic lesions of the facial skeleton.
Acid Phosphatase↗
Extensive evaluation of the instrumentation laboratory IL test D-Dimer immunoturbidimetric assay on the ACL 9000 determines the D-Dimer cutoff value for reliable exclusion of venous thromboembolism.
The clinical diagnosis of venous thromboembolism (VTE), which includes both deep vein thrombosis (DVT) and pulmonary embolism (PE), is often difficult and requires a number of imaging tests plus clinical assessment. It is now accepted that pretest clinical probability of disease plus a sensitive, quantitative D-Dimer assay can be used to reliably exclude VTE. In design of diagnostic strategies for VTE it is recommended that the D-Dimer assay be evaluated for sensitivity and specificity in well-designed, blinded studies using a cohort of patients for whom the assay will ultimately be used. Therefore we evaluated the IL Test D-Dimer on the ACL 9000 automated coagulation analyzer for its sensitivity and specificity in the diagnosis of VTE. A total of 512 patients admitted to the emergency department of Providence Hospital with suspected VTE were included in the dataset. Our aim was to find the clinically meaningful IL Test D-Dimer cutoff value, which would give us 100% sensitivity and the highest possible specificity for exclusion of VTE. Patients were categorized clinically into low, medium, or high pretest probability and had computed tomographic and/or ventilation-perfusion scans for investigation of PE and ultrasound studies for suspected DVT, with the laboratory blinded to the clinical findings. Of the 511 patients, 28 (5.4%) had confirmed VTE (PE and/or DVT) based on imaging and clinical studies. Applying receiver operating characteristic curve (ROC) analysis, we determined from our study that a cutoff value of 237 ng/mL IL Test D-Dimer gave a 100% sensitivity with a specificity of 38% for detection of VTE. The findings demonstrate that a diagnostic strategy using the IL Test D-Dimer assay as a first-line test in combination with pretest probability is safe and can be used in patients with suspected VTE. In conclusion, patient analysis results indicating low or moderate pretest probability for VTE and a negative IL Test D-Dimer (cutoff value of 237 ng/mL) assay result on the ACL 9000 reliably exclude VTE (both PE and DVT). We expect that inclusion of the rapid IL Test D-Dimer assay for assessment of suspected VTE in the emergency department at Providence will result in improved patient diagnosis and therapy, reduction in unnecessary radiological investigations, and lowering of overall costs associated with investigation of patients suspected of having VTE disease.
Clinical Laboratory Techniques↗
Intracellular Staphylococcus aureus. A mechanism for the indolence of osteomyelitis.
Staphylococcus aureus is the bacterial pathogen which is responsible for approximately 80% of all cases of human osteomyelitis. It can invade and remain within osteoblasts. The fate of intracellular Staph. aureus after the death of the osteoblast has not been documented. We exposed human osteoblasts to Staph. aureus. After infection, the osteoblasts were either lysed with Triton X-100 or trypsinised. The bacteria released from both the trypsinised and lysed osteoblasts were cultured and counted. Colonies of the recovered bacteria were then introduced to additional cultures of human osteoblasts. The number of intracellular Staph. aureus recovered from the two techniques was equivalent. Staph. aureus recovered from time zero and 24 hours after infection, followed by lysis/trypsinisation, were capable of invading a second culture of human osteoblasts. Our findings indicate that dead or dying osteoblasts are capable of releasing viable Staph. aureus and that Staph. aureus released from dying or dead osteoblasts is capable of reinfecting human osteoblasts in culture.
Cell Death↗
Ultrasound stimulates nitric oxide and prostaglandin E2 production by human osteoblasts.
We have previously shown that the therapeutic range of ultrasound heals osteoradionecrotic bone and induces bone formation in vitro. It is well established that nitric oxide (NO) and prostaglandins are crucial early mediators in mechanically induced bone formation. The therapeutic range of ultrasound may act in the same way; therefore, we have investigated the effect of the therapeutic range of ultrasound on NO induction and prostaglandin E(2) (PGE(2)) production in vitro. Two ultrasound machines were evaluated, "traditional" (1 MHz, pulsed 1:4, tested at four intensities) and a "long-wave" (45 kHz, continuous, also tested at four intensities) devices. Ultrasound was applied to human mandibular osteoblasts for 5 min, and incubated at 37 degrees C for up to 24 h. The control group (sham insonated) was treated in the same way. NO was determined by measuring the nitrite concentration in the culture media colorimetrically, and PGE(2) was assayed by radioimmunoassay. Ultrasound produced a significant increase in both induced nitrite and PGE(2) production. The NO synthesis appeared to be via inducible NO synthase (iNOS) on the basis of the time course and levels of nitrite obtained, although the inhibition of other NOS isoforms by aminoguanidine cannot be excluded. PGE(2) synthesis appeared to be via COX-2. With the 45 kHz machine, a significant increase in NO was achieved at three intensities, 5, 30, and 50 mW/cm(2). The 1 MHz machine stimulated the synthesis of both NO and PGE(2), but was significant at only one dose (0.1 W/cm(2(SAPA))). There was no difference between the two machines with regard to PGE(2) synthesis. The time-course experiment revealed peak production to be 12-18 h for both NO and PGE(2). The therapeutic range of ultrasound stimulates both NO and PGE(2) synthesis by human osteoblasts, and the 45 kHz machine appeared to be more effective than the traditional short-wave length. These results may reflect the healing effect of ultrasound on fractures and osteoradionecrosis.
Cells, Cultured↗
Epstein-Barr virus-positive blastoid nasal T/natural killer-cell lymphoma in a caucasian.
T/natural killer (NK)-cell lymphoma is a subtype of non-Hodgkin's lymphoma, with frequent cutaneous involvement; it follows an aggressive course. Most cases are reported in Asia, and typically present with nasopharyngeal involvement. There is a distinct variant known as blastoid T/NK-cell lymphoma, which affects elderly, non-Asian patients, with absence of nasal involvement. We report a middle-aged caucasian man who had blastoid T/NK-cell lymphoma with nasal involvement.
Epstein-Barr Virus Infections↗
Optic fibre bundle contact imaging probe employing a laser scanning confocal microscope.
A small diameter (600 micro m) fused optic fibre imaging bundle was used as a probe to compare fluorescent specimens by direct contact imaging using both a conventional fluorescence microscope and a laser scanning confocal microscope (LSCM) system. Green fluorescent polyester fibres placed on a green fluorescent cardboard background were used to model biological tissue. Axial displacement curves support the hypothesis that pinhole size in the LSCM system reduces the contribution of non-focal plane light. Qualitative comparison showed that the LSCM system produced superior image quality and contrast over the conventional system. The results indicate that the new LSCM-probe combination is an improvement over conventional fluorescence-probe systems. This study shows the feasibility of employing such a small diameter probe in the investigation of biological function in difficult to access areas.
Anatomy, Cross-Sectional↗
Impact of adherence on duration of virological suppression among patients receiving combination antiretroviral therapy.
OBJECTIVE: To assess the effect of adherence to antiretroviral therapy on the duration of virological suppression after controlling for whether or not the patient ever attained a plasma viral load below the limit of detection of sensitive HIV-1 RNA assays. METHODS: Data were combined from three randomized, blinded clinical trials (INCAS, AVANTI-2, and AVANTI-3) that compared the antiviral effects of two- and three-drug antiretroviral regimens. Virological suppression was defined as maintaining a plasma viral load below 1000 copies/mL. Adherence was defined prospectively and measured by patient self-report. RESULTS: Adherence did not have a major impact on the probability of achieving virological suppression for patients receiving dual therapy. However, for patients receiving triple therapy, adherence increased the probability of virological suppression, whether the plasma viral load nadir was above or below the lower limit of quantification. Compared to adherent patients with a plasma viral load nadir below the lower limit of quantification, the relative risk of virological failure was 3.0 for non-adherent patients with a nadir below the limit, 18.1 for adherent patients with a nadir above the limit, and 32.1 for non-adherent patients with a nadir above the limit. CONCLUSION: For patients receiving current three-drug antiretroviral regimens, adherence to therapy and plasma viral load nadir are important factors determining the duration of virological suppression.
Anti-HIV Agents↗
Management of children after presenting to hospital with acute asthma but not requiring admission.
OBJECTIVE: To examine the treatment of asthma in children aged 4-15 years in the 12 months following presentation to hospital with acute asthma but not requiring admission. METHOD: Questionnaire based survey addressing the child's use of health services, contact with general practitioners before presentation, use of asthma management plans, symptom frequency, and management of asthma. RESULTS: Sixty-six parents (response rate 50%) completed questionnaires. Children usually experienced infrequent episodic symptoms of asthma, and had good or excellent health (68%). Twenty-two children reported no medical follow up post-emergency department (ED). Of the 39 children who had been reviewed by their GP post-ED, 51% (n = 20) recalled discussing the reasons for presentation to ED with the GP, 41% (n = 16) had a lung function measurement and 64% (n = 25) had discussed ways to better manage the child's asthma to avoid the need for future ED attendance. Most parents of children with asthma (n = 57, 86%) recalled the GP explaining how to manage their child's asthma, but only 35 (61.4%) recalled the GP ever writing down these instructions. CONCLUSION: Children with acute asthma who do not require admission may be better managed in the community if there is greater recourse to GP care, use of written management guidelines and opportunities for additional community care are taken up. Further work is needed to identify strategies that will enable GPs to do this.
Acute Disease↗
Do divisions of general practice have a role in and the capacity to tackle health inequalities?
BACKGROUND: General practitioners are concerned with improving the health of the community, and Divisions are an important structure through which this can be achieved. Any focus on health outcomes needs to consider what general practice and Divisions can do to reduce inequalities in health outcomes. METHOD: We analysed 2000-2002 strategic and business plans from 78% of Divisions in NSW and Victoria, to see how Divisions were developing capacity to address health inequalities in the community through appropriate needs assessments, allocation of resources and partnership approaches. RESULTS: Thirty percent of Divisions discussed socioeconomic barriers to people accessing health care within their community. None used equity as a needs priority. Thirty percent specifically committed resources through programs for disadvantaged groups. Thirty-six percent used partnership approaches to improve access, although only 11% used a broad advocacy role. DISCUSSIONS: Divisions see socioeconomic disadvantage as an important issue, and some are developing significant multilevel strategies to address them, although significant gaps exist in the capacity of Divisions to undertake this work.
Australia↗
A compromise strategy for patients with multiple drug failure.
Explore the source record for details and available documents.
Anti-HIV Agents↗
Symptomatic elevations of lactic acid and their response to treatment manipulation in human immunodeficiency virus-infected persons: a case series.
Symptomatic lactic acidemia was seen in 5 human immunodeficiency virus-positive patients receiving combination therapy that included stavudine and > or =1 other nucleoside. Peak venous lactic acid levels of 3.1-7.4 mmol/L (normal range, 0.5-2.1 mmol/L) were associated with fatigue and rapid weight loss, whereas withdrawal of antiretrovirals led to normalization of venous lactic acid levels, symptomatic improvement, and weight gain. Resumption of an altered therapeutic regimen, which did not include stavudine but did include other nucleosides in 4 of 5 cases, did not result in recurrence of the syndrome after up to 126 days.
Adult↗
Relative frequency and morphology of cancers in carriers of germline TP53 mutations.
The spectrum and frequency of cancers associated with germline TP53 mutations are uncertain. To address this issue a cohort of individuals from 28 families with Li-Fraumeni syndrome, segregating germline TP53 mutations was established. Predicted cancers were estimated by applying age, morphology, site and sex-specific UK cancer statistics to person-years at risk. Observed and predicted cancers were compared and two-sided P-values calculated. Cancer types occurring to excess and showing P-values <0.02, were designated strongly associated with germline TP53 mutations. These were removed from the data and a second round of analyses performed. Cancer types with P-values <0.02 and 0.02-0.05 in the second round analyses were considered moderately and weakly associated respectively. Strongly associated cancers were: breast carcinoma, soft tissue sarcomas, osteosarcoma, brain tumours, adrenocortical carcinoma, Wilms' tumour and phyllodes tumour. Carcinoma of pancreas was moderately associated. Leukaemia and neuroblastoma were weakly associated. Other common carcinomas including lung, colon, bladder, prostate, cervix and ovary did not occur to excess. Although breast carcinoma and sarcomas were numerically most frequent, the greatest increases relative to general population rates were in adrenocortical carcinoma and phyllodes tumour. We conclude that germline TP53 mutations do not simply increase general cancer risk. There are tissue-specific effects.
Adolescent↗
Molray--a web interface between O and the POV-Ray ray tracer.
A publicly available web-based interface is presented for producing high-quality ray-traced images and movies from the molecular-modelling program O [Jones et al. (1991), Acta Cryst. A47, 110-119]. The interface allows the user to select O-plot files and set parameters to create standard input files for the popular ray-tracing renderer POV-Ray, which can then produce publication-quality still images or simple movies. To ensure ease of use, we have made this service available to the O user community via the World Wide Web. The public Molray server is available at http://xray.bmc.uu.se/molray.
Internet↗
Development of drug resistance in patients receiving combinations of zidovudine, didanosine and nevirapine.
OBJECTIVE: To evaluate the development of phenotypic and genotypic resistance to zidovudine, didanosine and nevirapine as a function of the virologic response to therapy in a group of drug-naive individuals receiving various combinations of these agents. DESIGN: All patients were enrolled in a double-blind controlled randomized trial (the INCAS study) and were selected for detailed resistance studies based on specimen availability and virologic response. METHODS: Within the three study groups (zidovudine/nevirapine, zidovudine/didanosine or zidovudine/nevirapine/didanosine), 16, 19 and 24 patients, respectively, had evaluable baseline isolates and remained in the study > 24 weeks. Phenotypic resistance to all three drugs was evaluated using the VIRCO recombinant virus assay. Genotypic sequencing was done on selected specimens from patients receiving zidovudine/nevirapine/didanosine. RESULTS: After 24 weeks, all available isolates taken from patients receiving nevirapine were resistant to this agent, while 18/21 (86%) patients receiving triple therapy carried such isolates at 30--60 weeks. At 24 weeks, zidovudine resistance developed in 4/40 isolates but was more frequent after 30--60 weeks, especially in patients on two drugs. The degree of zidovudine resistance (rise in concentration required for 50% inhibition) appeared lower in the triple therapy group compared with zidovudine/didanosine (P = 0.0004). All nevirapine-resistant isolates that were sequenced carried at least one mutation associated with resistance, most often K103N and/or Y181C. CONCLUSION: The use of highly active drug therapies may be associated with a beneficial effect on the development of antiretroviral drug resistance. The characteristics of virologic suppression that must be maintained to avoid resistance are currently being studied in hypothesis-driven clinical trials.
Anti-HIV Agents↗
The steady-state pharmacokinetics of efavirenz and nevirapine when used in combination in human immunodeficiency virus type 1-infected persons.
The steady-state pharmacokinetics of efavirenz and nevirapine, when used in combination to treat human immunodeficiency virus type 1 (HIV-1)-infected subjects, were investigated. HIV-1-infected persons who had used efavirenz (600 mg once daily) for > or =2 weeks were eligible for study inclusion. The plasma pharmacokinetics of efavirenz were determined over 24 h. Subsequently, nevirapine (400 mg once daily) was added to the regimen. After 4 weeks, the pharmacokinetics of efavirenz and nevirapine were assessed over 24 h. The differences between the pharmacokinetic parameters of efavirenz with and without nevirapine were analyzed, and the pharmacokinetics of nevirapine were compared with those in historical control patients. The exposure to efavirenz when combined with nevirapine was significantly decreased by 22% (area under the plasma concentration vs. time curve), 36% (minimum plasma concentration), and 17% (maximum plasma concentration). Nevirapine pharmacokinetics appear to be unaffected by coadministration of efavirenz, compared with data from historical control patients.
Adult↗