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Biomedical subjects

G Burrows

Publications and source records attributed to G Burrows.

At least 19 recordsLinked to original sources

Survival among hospital in-patients with troponin T elevation below levels defining myocardial infarction.

BACKGROUND: Cardiac troponin T (cTnT) has an accepted place in the management of patients presenting with suspected acute coronary syndrome (ACS). Uncertainty remains about the significance and interpretation of elevated cTnT below the cut-off levels defining myocardial infarction (0.1 microg/l). AIM: To compare the mortality risks for elevation of cTnT in the ranges 0.01-0.029 microg/l, 0.03-0.099 microg/l and <0.01 microg/l. DESIGN: Retrospective record study in three hospitals. METHODS: All cTnT measurements with values in the range >0.01-0.099 microg/l analysed during January 2002 were extracted from clinical biochemistry laboratory databases. Following agreed exclusion criteria, 179 patients with cTnT in the range 0.01-0.099 microg/l and 60 patients <0.01 microg/l were selected at random from across the three sites. Six-month follow-up was completed by review of case notes and contact with the patients' GP. RESULTS: There was a graded increase in mortality with increasing cTnT, although only achieving statistical significance for patients in the 0.03-0.099 microg/l range. The graded increase in relative risk with cTnT was weaker after adjustment for potential confounding factors DISCUSSION: We found a trend for worse survival with increasing cTnT within the range 0.01-0.099 microg/l in unselected patient populations presenting with possible acute coronary syndrome. This suggests that the combined effects of assay imprecision and co-morbidity should be taken into account when interpreting borderline elevation of cTnT. The use of a cut-off based on current standards of assay precision should be used to define the sensitivity of cTnT as biochemical evidence of ischaemic cardiac damage and as an indicator of mortality risk. This level is likely to be between 0.03 and 0.1 microg/l.

Aged↗

Oxidised and native low-density lipoproteins induce the release of von Willebrand factor from human endothelial cells in vitro.

Increased low-density lipoprotein (LDL)-cholesterol is a risk factor for atherosclerosis--a disease in which damage to the endothelium is believed to be an important early step. Increased levels of the endothelial marker von Willebrand factor (vWF) in the plasma of patients with hypercholesterolaemia and atherosclerosis probably reflect this process. In this study we seek to link the established observation that oxidised LDL-cholesterol is cytotoxic to human umbilical vein endothelial cells (HUVECs) in vitro with the common finding of raised plasma vWF in patients with atherosclerosis by incubating HUVECs with physiological/pathological levels of native and oxidised LDL-cholesterol for up to 48 h. Microphotography revealed morphological changes in the HUVECs within 24 h, becoming severe at 48 h, which was mirrored by increased levels of vWF (ELISA) and the release of preloaded radioactive (111)indium tracer into culture supernatants. Our data support and extend the hypothesis that oxidised LDL is directly cytotoxic to HUVECs, and, in addition, provide an important link between in vitro studies and clinical studies where endothelial cell markers such as vWF are increased in the plasma of patients with hypercholesterolaemia and atherosclerosis.

Cell Death↗

Postpericardiotomy syndrome and cardiac tamponade as a late complication after pacemaker implantation.

In a 78-year old woman, pacemaker implantation was complicated by a transient perforation of the endocardial lead. The patient was in stable condition for up to 7 weeks after implantation, after which pericardial effusion and subacute cardiac tamponade developed and pericardiocentesis became necessary. This case illustrates that even after initially uneventful pacemaker lead perforation, careful, long-term follow-up is necessary to recognize the potential development of late postpericardiotomy syndrome.

Aged↗

[Tumor cell embolism to pulmonary arteries].

A 69-year-old male presented with symptoms of fulminant lung embolism and, despite immediate therapy with plasminogen activator, died of acute right heart failure. At autopsy multiple tumor cell emboli were detected in small pulmonary vessels in addition to widespread liver metastases from an urothelial carcinoma. - In a 23-year-old female a malignant gastric ulcer and multiple liver metastases were diagnosed at initial presentation. She too died from pulmonary hypertension due to a series of lung embolisms which occurred despite heparin therapy. At autopsy, many small pulmonary arteries were filled with adenocarcinoma cells; the primary gastric tumor and liver metastases were confirmed. These cases demonstrate that the shedding of tumor cells from hepatic metastases can obstruct the pulmonary vessels and lead to acute cor pulmonale. Tumor cell emboli should be considered in the differential diagnosis of acute pulmonary hypertension, especially in patients with a known tumor. They may, however, also represent the first clinical signs of previously unrecognized malignancy.

Adenocarcinoma↗

Sustained response to open-label venlafaxine in drug-resistant major depression.

The aim of this study was to evaluate the response to venlafaxine in patients with treatment-resistant depression during an extension phase of an open-label study of venlafaxine. After completing the initial 8 weeks of the study, patients could continue venlafaxine treatment for an additional period of up to 10 months. Efficacy results are given for 149 patients with treatment-resistant depression. Response was defined as a 50% reduction in scores on the Montgomery-Asberg Depression Rating Scale (MADRS); 69% were responders after 8 weeks of treatment in the initial study phase, and 73% were responders at their final extension-phase visit. The mean MADRS score was 32.8 before treatment, 12.9 by 8 weeks, and 10.8 at the final extension visit. There was a statistically significant reduction of 2.1 MADRS units from entry into the extension phase to the final extension visit. At extension entry, 36.7% patients were in remission, as defined by a MADRS score of less than 12, whereas at the final extension visit, this had increased to 49%. Improvement in Clinical Global Impressions Scale scores (both patient and physician ratings) was maintained throughout the extension period, with 88% of patients reporting some improvement (75% with "very much" or "much") and 92% of doctors noting some improvement in patients (79% with "very much" or "much") at the last extension visit. The safety profile during the extension phase of the study was similar to that found in the initial phase and in other studies. The most common study events were somnolence (21%), headache (18%), insomnia (16%), sweating (16%), constipation (14%), dry mouth (11%), nausea (10%), and dizziness (10%). Patients with resistant depression that was treated with venlafaxine maintained their response for up to 10 months after an 8-week phase of treatment and showed some evidence of further improvement.

Adult↗

Efficacy of venlafaxine and predictors of response in a prospective open-label study of patients with treatment-resistant major depression.

The aim of this study was to replicate the findings of a 1994 study, in which a 30% response rate to venlafaxine was found in patients with treatment-refractory depression, as well as to examine for any predictors of such an outcome. The study was an 8-week, open-label, prospective investigation of venlafaxine in doses up to 300 mg in 312 patients fulfilling criteria for either "absolute" or "relative" treatment resistance. By week 8, 52.6% of the patients had responded, which was defined as a 50% reduction in scores on the Montgomery-Asberg Depression Rating Scale; 49% of those defined with "absolute resistance" demonstrated such an outcome. Forty-five percent of the patients with absolute resistance who had failed to respond to at least one tricyclic antidepressant responded to venlafaxine. Response rates were higher in those with an absence (57.5%) compared with the presence (31.0%) of any comorbid psychiatric disorder (p < 0.001), "marked" (60.3%) compared with "mild or moderate" (51.6%) or "severe" (43.4%) baseline ratings on the patient-rated Clinical Global Impressions Scale (p < 0.05), and "relative" (61%) compared with "absolute" resistance (49%) (p = 0.06). Furthermore, improvement in scores of 20% or 30% at weeks 1 or 2 was associated with higher rates of final response (p < 0.0005). After logistic regression, both comorbid psychiatric illness (p < 0.001) and early improvement (p < 0.0001) remained significant and independent predictors of final response.

Adult↗

An evaluation of the telepsychiatry programme in Victoria, Australia.

We evaluated the use of telepsychiatry in Victoria, a state of Australia with some five million people. There were 39 sites at the time of the survey, 12 metropolitan and 27 rural. Interviews and postal questionnaires were used. A total of 99 staff were surveyed, 69 by post and 30 during visits. There were 37 participants from metropolitan sites and 62 from rural sites. Rural sites conducted an estimated 137 sessions per month (i.e. an average of 5.1 per month per site). The majority (70%) of the usage in Victoria was for clinical purposes, both primary and secondary consultations.

Female↗

Measuring psychological adjustment to HIV infection.

AIMS: A modified version of the Mental Adjustment to Cancer Scale (The Mental Adjustment to HIV Scale--MAHIVS) was used to evaluate patterns of psychological adjustment in response to HIV infection. METHODS: A sample of 164 HIV positive homosexual/bisexual men were recruited across three Australian centers (79 asymptomatic (CDC II/III) and 85 symptomatic HIV infection (CDC IV)). Factor analysis of the MAHIVS was conducted and the predictive validity of the MAHIVS was investigated using the General Health Questionnaire, while The Diagnostic Interview Schedule was used to assess current and lifetime psychiatric disorder. Other measures of adjustment/coping were used to investigate the construct validity of the MAHIVS (neuroticism, locus of control, defense style). RESULTS: Factor analysis of the MAHIVS detected four factors: Hopelessness, Fighting Spirit/Self Efficacy, Personal Control, and Minimization. Hopelessness and Fighting Spirit factors exhibited acceptable levels of internal consistency and validity, with significant correlations detected with psychological symptoms and significant association with other measures of psychological adjustment and personality. Fighting Spirit emerged as a potential indicator of psychological resilience, whereas Hopelessness was significantly associated with psychological symptoms and current major depression (but not past depression). CONCLUSIONS: The findings indicate the validity of the MAHIVS and support the presence of common themes in the psychological adaptation to life-threatening illness that can be detected across disease categories and groups.

Adaptation, Psychological↗

Neutrophil activation and severity of tissue hypoxia during tourniquet-induced forearm ischemia in man.

Neutrophil activation and adhesion to the endothelium are thought to be central in the inflammatory response to reperfusion after ischemia. This study explores whether the severity of tissue hypoxia can be related to a biochemical measure. Venous blood was sampled from 20 volunteers undergoing tourniquet-induced forearm ischemia for 10 min and subsequent reperfusion. Samples were analyzed for neutrophil count, neutrophil hydrogen peroxide generation measured by flow cytometry, plasma thromboxane (a marker of platelet activation), the endogenous antioxidant glutathione peroxidase, and thrombomodulin, a marker of endothelial cell damage. Forearm oxygen saturation by near-infrared spectroscopy was monitored throughout the experiment. Neutrophil hydrogen peroxide generation fell from an initial mean fluorescent intensity (MFI) of 0.91 +/- 0.07 to 0.77 +/- 0.09 (mean +/- SE) during ischemia (P < 0.05) and this reduction correlated with severity of hypoxia (r = 0.56, P < 0.01). Plasma levels of glutathione peroxidase were also reduced during ischemia (P < 0.05) whereas plasma thromboxane levels rose (P < 0.05). There were no significant changes in plasma levels of thrombomodulin or circulating neutrophil count. In conclusion, alterations in a measurement of neutrophil function reflect the changes in tissue oxygenation and may act as a biochemical predictor of the severity of an ischemic injury.

Adult↗

The Royal Melbourne Hospital Lithium Clinic.

The Lithium Clinic at the Royal Melbourne Hospital was an innovative program for the management of mood disorders. The Clinic was a model for teaching and research, as well as a vehicle for expert treatment of patients. Many psychiatrists gained valuable experience and training during their period of involvement and many academics and psychiatric researchers were involved with the Clinic. Important research was performed in the Clinic, some aspects of which are highlighted in this paper.

Antimanic Agents↗

Platelet paroxetine binding in post-traumatic stress disorder.

Sixty-two subjects, 45 with post-traumatic stress disorder (PTSD) and 17 healthy control subjects, were examined in a study of serotonin function measured by [3H]paroxetine binding to platelet membranes. Subjects were selected from male combat exposed veterans. The mean (+/- S.D.) Kd was 0.078 +/- 0.045 nM for the PTSD patient group and 0.064 +/- 0.037 nM for the control group. The mean Bmax was 934 + 238 fmol/mg protein for the PTSD patient group and 1011 +/- 363 fmol/mg protein for the control group. There was no significant difference between the groups for either Kd or Bmax before or after controlling for season of sampling. There were no significant differences between subjects with current PTSD and those with PTSD in the past, or between PTSD subjects with or without concurrent major depressive disorder. This study finds no relationship between PTSD, major depressive disorder and peripheral serotonin function measured by [3H]paroxetine binding to blood platelets.

Adult↗

Posttraumatic stress disorder in response to HIV infection.

This study investigated the psychological impact of HIV infection through assessment of posttraumatic stress disorder in response to HIV infection. Sixty-one HIV-positive homosexual/bisexual men were assessed for posttraumatic stress disorder in response to HIV infection (PTSD-HIV) using a modified PTSD module of the DIS-III-R. Thirty percent met criteria for a syndrome of posttraumatic stress disorder in response to HIV diagnosis (PTSD-HIV). In over one-third of the PTSD cases, the disorder had an onset greater than 6 months after initial HIV infection diagnosis. PTSD-HIV was associated with other psychiatric diagnoses, particularly the development of first episodes of major depression after HIV infection diagnosis. PTSD-HIV was significantly associated with a pre-HIV history of PTSD from other causes, and other pre-HIV psychiatric disorders and neuroticism scores, indicating a similarity with findings in studies of PTSD from other causes. The findings from this preliminary study suggest that a PTSD response to HIV diagnosis has clinical validity and requires further investigation in this population and other medically ill groups. The results support the inclusion of the diagnosis of life-threatening illness as a traumatic incident that may lead to a posttraumatic stress disorder, which is consistent with the DSM-IV criteria.

Adult↗

Negative symptoms, depression, and parkinsonian symptoms in chronic, hospitalised schizophrenic patients.

BACKGROUND: Negative symptoms of schizophrenia are often confounded by overlapping depressive and parkinsonian symptoms. The role of medication as an aetiological factor in the development of these symptoms is an important issue for prevention and treatment. METHODS: A total of 45 inpatients in chronic wards who met RDC criteria for schizophrenia were assessed with the Hamilton depression rating scale (HDRS) and negative symptom rating scale (NSRS) and the targeting abnormal kinetic effect scale (TAKE). RESULTS: No significant correlation was found between the total scores on the vegetative superfactor of the HDRS and the NSRS. Duration of neuroleptic treatment was positively correlated with depressive symptoms (r=0.299, P < 0.05) and negative symptoms (r=0.443, P < 0.001). Dose of antipsychotic was also correlated positively with negative symptoms (r=0.260, P < 0.05). Age was negatively correlated with depressive symptoms as assessed by the HDRS (r=0.306, P <0.05). CONCLUSION: The data suggest that depressive and negative symptoms can be separated in chronic schizophrenia, while pointing to a possible role of antipsychotic medication in the aetiology. LIMITATIONS: The study was conducted in a small chronically hospitalised population treated with relatively high doses of antipsychotics. It is not clear that the results obtained here would be applicable to an acute patient population.

Adult↗

Novel adjuvants for induction of T-cell and antibody responses to encephalitogenic and regulatory determinants in Lewis rats.

Treatment of human autoimmune diseases may be enhanced by using adjuvants that can selectively induce immunoregulatory responses. Two versions of a novel nonionic block copolymer adjuvant suitable for human use, Optivax Oil Formulation (OF) and Optivax Aqueous Formulation (AF), were evaluated for induction of immunity to encephalitogenic and regulatory T-cell receptor (TCR) V-gene determinants. In Lewis rats immunized with myelin basic protein (BP), Optivax OF was more efficient than Optivax AF for inducing delayed type hypersensitivity (DTH), T-cell proliferation, antibodies, and even mild clinical signs of experimental autoimmune encephalomyelitis (EAE). Similarly, Optivax OF was more efficient for inducing inflammatory T-cell and antibody responses to immunoregulatory V beta 8.2 proteins and peptides than Optivax AF, which induced a noninflammatory Th2 response. In general, DTH response to the various immunogens was reflected by increased cellularity and mRNA levels for IFN-gamma in draining lymph nodes, whereas LN cell proliferation without DTH was characterized by increased IL-2 mRNA levels but low or absent IFN-gamma message. These data suggest important differential adjuvant effects of Optivax OF versus Optivax AF on the respective induction of Th1 versus Th2 responses that may be useful in the selective treatment of human immune disorders.

Adjuvants, Immunologic↗

Aggressive behaviour and platelet 3H-paroxetine binding in schizophrenia.

Forty schizophrenic patients were included in a study of the relationship between serotonin function as measured by 3H-paroxetine binding to platelet membranes and aggressive behaviour. Patients classified as either aggressive or non-aggressive were paired by age, sex and duration of illness. 3H-Paroxetine binding variations were avoided by taking samples for each pair between 09:00 and 11:00 h, within 4 days of each other, and by assaying pair of samples together. The mean Kd for the aggressive group was 0.193 +/- 0.126 nM and the mean Kd for the non-aggressive group was 0.176 +/- 0.164 nM. The mean Bmax for the aggressive group was 1451 +/- 386 fmol/mg protein while the mean for the non-aggressive group was 1549 +/- 375 fmol/mg protein. There was no significant difference between the groups for either parameter, Kd or Bmax. There were no significant correlations between psychopathology rating including positive and negative symptoms, depression, suicidal thoughts, impulse control, as well as both past and present history of aggression, hostility and irritability traits, psychopathic deviance and either Bmax and Kd. This study finds no relationship between aggressive behaviour and peripheral serotonin function as measured by 3H-paroxetine binding to platelet membranes.

Adult↗

Antioxidants, von Willebrand factor and endothelial cell injury in hypercholesterolaemia and vascular disease.

The relationship between antioxidants and endothelial cell injury was examined in 119 patients with (n = 48) or without (n = 71) vascular disease who were attending a hyperlipidaemia clinic. Serum levels of total antioxidant capacity, glutathione peroxidase (a protein antioxidant), von Willebrand factor (vWf, a specific endothelial cell product and marker of injury) and routine lipids were measured in the patients and from 58 healthy controls. Compared to controls, total antioxidant capacity (P < 0.01) and glutathione peroxidase (P < 0.0001) were lower whilst vWf was higher (P < 0.0001) amongst the patients. Comparing patients with and without vascular disease, glutathione peroxidase was lower (P < 0.03) and vWf was higher (P < 0.05) in the presence of vascular disease but there was no difference in levels of serum lipids or total antioxidant capacity. vWf and glutathione peroxidase were inversely correlated (r = -0.26, P < 0.005). We conclude that patients with hypercholesterolaemia have reduced antioxidant capacity and this is most severe in patients with clinically apparent vascular disease. This, linked to the finding of increased vWf in hypercholesterolaemia with highest levels in those patients with vascular disease, suggests that loss of antioxidant capacity may expose the vascular endothelium to excess oxidative damage. These results suggest a link between hypercholesterolaemia, impaired ability to resist free radical attack, and the development of atherosclerosis.

Antioxidants↗