Biomedical subjects
P Barnes
Publications and source records attributed to P Barnes.
Difficult/therapy-resistant asthma: the need for an integrated approach to define clinical phenotypes, evaluate risk factors, understand pathophysiology and find novel therapies. ERS Task Force on Difficult/Therapy-Resistant Asthma. European Respiratory Society.
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Leptomeningeal melanoma and Creutzfeldt-Jakob disease in a patient with chronic lymphocytic leukaemia.
A 78-year-old woman with known chronic lymphocytic leukaemia (CLL) was admitted to a psychiatric unit because of rapidly declining cognitive function. Clinical examination also revealed cerebellar signs and she later became akinetic and mute. She deteriorated and died of bronchopneumonia. The histology from the post-mortem confirmed the presence of CLL in the lymph nodes and she was also found to have diffuse leptomeningeal melanoma. In addition, there was extensive prion protein deposition in the cerebral cortex, but without significant spongiosis. The astrocytosis that was present appeared superficial only. Furthermore, prion protein appeared to be co-expressed with betaA4 in the form of plaques. The patient therefore had evidence of sporadic Creutzfeldt-Jakob disease (CJD) in addition to meningeal melanoma and CLL. This case further illustrates the importance of employing prion protein immunohistochemistry in suspected cases of CJD, especially where the histology is atypical.
Helical CT angiography: dynamic cerebrovascular imaging in children.
BACKGROUND AND PURPOSE: The purpose of this study was to assess the feasibility of helical CT cerebrovascular imaging (CTCVI) in children and to make initial comparisons with MR angiography and digital subtraction angiography (DSA). METHODS: Twenty-six patients, ages 3 days to 17 years, were examined with CTCVI. Patients were scanned with 1-mm collimation and 2:1 pitch 30 seconds after the initiation of a hand injection of 2 mL/kg nonionic contrast material (320 mg/dL iodine) with a maximum dose that did not exceed 80 mL (minimum volume, 5 mL in a 2.5-kg infant). Reconstructions were done using maximum intensity projection and integral rendering algorithms. Four patients had CTCVI, MR angiography, and DSA (42 vessels studied) and nine patients had CTCVI and DSA (136 vessels studied). Scores of 1 (not present) to 3 (present in continuity to the first bifurcation) were assigned independently by two radiologists to 32 vessels in each correlated case for each available technique. RESULTS: There were no technical failures. CTCVI depicted 18 thrombosed dural sinuses, three vascular malformations, one intracranial aneurysm, and four tumors. Ninety-five percent of the vessels seen with DSA were also seen with CTCVI. CTCVI identified all vessels seen on MR angiography. CONCLUSION: Helical CTCVI is an effective technique for assessing the intracranial circulation in children. In this initial comparison, CTCVI showed more vascular detail than MR angiography, and had fewer technical limitations.
Quantitation of nucleolar organizer regions by image analysis in glottic squamous cell carcinoma.
OBJECTIVE: To apply computer image analysis as a quantitative method for analyzing interphase nucleolar organizer regions (NORs) to determine whether this proliferative marker provides useful prognostic information in glottic squamous cell carcinoma. DESIGN: Retrospective testing of biopsy samples and resected tissue. SETTING: Nova Scotia Regional Cancer Centre and regional hospitals in Nova Scotia and Prince Edward Island, Canada. PATIENTS: Patients with primary glottic cancer presenting to the cancer centre between 1984 and 1991. INTERVENTIONS: Semiautomated image analysis was used to measure the nuclear area and the NOR area in formalin-fixed paraffin-embedded tumour samples. OUTCOME MEASURES: Mean nuclear area, mean NOR area and NOR percentage of nuclear area, calculated as the mean NOR area divided by the mean nuclear area, expressed as a percentage. RESULTS: Of 154 cases, 90 samples were received; however, 8 paraffin blocks were exhausted and 29 samples stained poorly due to extent of fixation. Analysis of the remaining 53 cases, all primary squamous cell carcinomas, showed no statistically significant association between, on one hand, mean NOR area or NOR percentage of nuclear area and, on the other hand, tumour grade, tumour stage, tumour recurrence or disease-related death. CONCLUSIONS: This study does not demonstrate a prognostic value of NOR measurement as a proliferative marker in primary glottic squamous carcinoma. However, given the small number of cases in this study, further research should be conducted using a larger number of cases from one centre and comparing NOR measures with other markers of cell proliferation.
Altitude training at 2690m does not increase total haemoglobin mass or sea level VO2max in world champion track cyclists.
Haemoglobin mass (Hb mass), maximum oxygen consumption (VO2max), simulated 4000 m individual pursuit cycling performance (IP4000), and haematological markers of red blood cell (RBC) turnover were measured in 8 male cyclists before and after (A) 31 d of altitude training at 2690 m. The dependent variables were measured serially after altitude on d A3-4, A8-9 and A20-21. There was no significant change in Hb mass over the course of the study and VO2max at d A9 was significantly lower than the baseline value (79.3 +/- 0.7 versus 81.4 +/- 0.6 ml x kg(-1) x min(-1), respectively). No increase in Hb mass or VO2max was probably due to initial values being close to the natural physiological limit with little scope for further change. When the IP4000 was analysed as a function of the best score on any of the three test days after altitude training there was a 4% improvement that was not reflected in a corresponding change in VO2max or Hb mass. RBC creatine concentration was significantly reduced after altitude training, suggesting a decrease in the average age of the RBC population. However, measurement of reticulocyte number and serum concentrations of erythropoietin, haptoglobin and bilirubin before and after altitude provided no evidence of increased RBC turnover. The data suggest that for these elite cyclists any benefit of altitude training was not from changes in VO2max or Hb mass, although this does not exclude the possibility of improved anaerobic capacity.
Treated bacterial endocarditis as a histological mimic of fungal infection.
Histological assessment of cardiac valve tissue contributes to the diagnosis of infective endocarditis and is of particular importance in cases in which no organism is cultured. Antibiotic treatment of bacterial endocarditis may lead to abnormal bacterial morphology and staining characteristics. Although in many cases the presence of some residual bacteria of normal appearance makes the diagnosis straightforward, in some only abnormal bacteria may be seen. Unless the appearances of these are interpreted with caution, the presence of larger spherical organisms with the staining properties of a yeast may lead to an erroneous diagnosis of fungal infection.
Development and validation of a computerized screening test for personality disorders in DSM-III-R.
The available self-report instruments designed to measure personality disorder (PD) are time-consuming to administer and/or score and can be impractical for routine clinical use. There is a need for a computerized method of personality assessment based on contemporary systems of classification. A computerized DSM-III-R-based questionnaire was developed and validated against the structured clinical interview for DSM-III-R Axis-II disorders on a sample of 60 subjects. The computerized test showed moderate validity as a diagnostic instrument (mean kappa coefficient = 0.47). With adjusted cut-off scores it was valid as a screening instrument (mean sensitivity = 0.87). Antisocial, borderline and avoidant PD scores were strongly correlated across measures and not subject to significant observer bias.
Prospective study of postoperative magnetic resonance imaging in patients with malignant gliomas.
PURPOSE: We studied the natural history of postoperative enhancement on magnetic resonance (MR) scans in patients with malignant glioma to determine the following: (1) when a postoperative MR scan most accurately shows residual enhancing tumor; and (2) whether repeated doses of the contrast agent gadopentetate dimeglumine (Gd-DTPA) were well tolerated. PATIENTS AND METHODS: Seventeen patients with malignant glioma underwent tumor resection; four (24%) had nonenhancing tumors preoperatively. Serial MR scans were performed on postoperative days 1, 3, 5, 7, 14, and 21 and were analyzed qualitatively and quantitatively. The evolution of enhancement and subacute hemorrhage were described and measured. A uniform schedule of postoperative dexamethasone administration was used in all but four patients (24%) (each required higher doses to maintain neurologic function). RESULTS: Nontumoral, marginal (i.e., postsurgical) enhancement, potentially mimicking residual tumor, developed in eight patients (53%), including tumors that were nonenhancing preoperatively, and was maximal from days 5 to 14. Tumor enhancement was optimally visualized on postoperative days 3 to 5. Nine of 10 patients (90%) with gross residual enhancing tumor showed an increase of enhancing tumor size during the study. Methemoglobin was detected at some time in all patients (100%) and was usually minor, but in six (35%) it interfered with residual tumor assessment. The 97 doses of Gd-DTPA, administered in 17 patients, were well tolerated. CONCLUSION: When accurate assessment of residual enhancing tumor is needed in patients with malignant glioma, an MR scan performed on postoperative days 3 to 5 should minimize the confounding effects of postsurgical enhancement and methemoglobin. The repeated administration of Gd-DTPA over several weeks is well tolerated.
Fast in situ x-ray-diffraction studies of chemical reactions: A synchrotron view of the hydration of tricalcium aluminate.
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Evaluation of complete blood count results from a new, on-site hemocytometer compared with a laboratory-based hemocytometer.
OBJECTIVE: To compare point-of-care results obtained from an on-site hemocytometer with values provided by an institutional laboratory instrument. DESIGN: A prospective laboratory evaluation. SETTING: The central laboratory and cardiac surgical intensive care unit of a university-affiliated tertiary care center. PATIENTS: Normal range comparison was performed using blood specimens routinely obtained from 48 hospitalized patients for complete blood count analysis. The second evaluation was performed on blood specimens routinely obtained (in the intensive care unit) after cardiac surgery involving extracorporeal circulation in a series of 187 consecutive patients. MEASUREMENTS AND MAIN RESULTS: Hemoglobin concentration, platelet count, mean corpuscular volume, mean platelet volume, and red and white blood cell counts were measured with both on-site (MD 16, Coulter Electronics, Hialeah, FL) and laboratory (STKS, Coulter Electronics) instruments. Hematocrit and red cell distribution width were calculated using measured variables. Blood specimens were obtained from two distinct patients series. To evaluate measurement values within the normal range, a series of 48 routinely obtained blood specimens for complete blood count analysis in our institutional laboratory were utilized for concurrent analysis with the on-site hemocytometer. To evaluate measurement values out of the normal range, a second comparison involved measurements performed on blood specimens obtained in the cardiac surgical intensive care unit for complete blood count analysis. Linear regression demonstrated good correlations between on-site and laboratory hemoglobin concentration (r2 = .97), hematocrit (r2 = .95), platelet count (r2 = .97), mean corpuscular volume (r2 = .91), red cell distribution width (r2 = .80), and red (r2 = .95) and white (r2 = .96) blood cell count results. A marginal correlation was observed between mean platelet volume values (r2 = .47). Bias analysis (mean +/- 2 SD) demonstrated similar measurements between on-site and laboratory hemoglobin concentration, hematocrit, platelet count, red blood cell count, white blood cell count, mean platelet volume, mean corpuscular volume, and red cell distribution width. CONCLUSIONS: On-site hemoglobin concentration, hematocrit, white blood cell count, red blood cell count, red cell distribution width, and platelet count values compare well with those results obtained from the laboratory. The MD 16 hemocytometer (Coulter Electronics) provides on-site hematologic results that can provide an accurate and rapid quantitative assessment of platelets, and red and white blood cells. Rapid access to information obtained from this type of system may be clinically useful, especially in critically ill patients.
Structural abnormalities in brain magnetic resonance images of depressed children.
OBJECTIVE: Brain magnetic resonance images (MRIs) of 65 children and adolescents who were hospitalized with depressive disorders (DD) were compared with the brain MRIs of 18 hospitalized psychiatric controls (PC) without a depressive disorder. METHOD: Volumetric analyses were used to measure frontal lobe volumes (FLV), lateral ventricular volumes (VV), and total cerebral volumes (CV) for all subjects. To correct for differences in absolute cerebral volume associated with different body and head size, the ratios of FLV/CV and VV/CV were used to compare differences between the two groups. A multivariate analysis was used to control for the effects of several independent variables (age, sex, diagnosis). RESULTS: Significant differences were seen in the FLV/CV ratio and the VV/CV ratio when the results were compared between the two groups (DD versus PC). The DD group had a significantly smaller FLV/CV ratio (t = 2.148, df = 79, p = .035) and a significantly larger VV/CV ratio (t = -2.093, df = 79, p = .040). CONCLUSION: The findings are consistent with previous reports in depressed adults and may implicate the frontal lobes in the pathogenesis of early-onset depressive disorders.
Neuromyelitis optica in childhood: case report with sequential MRI findings.
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Accuracy of reported family histories of essential tremor.
We studied the accuracy of reported family histories of essential tremor (ET) by questioning the patients in our clinic and subsequently by mail and phone. For individuals who continued to report a negative family history, we mailed a screening questionnaire to their first-degree relatives to further ascertain the presence of ET. On initial assessment, 67.7% of patients reported a positive family history of ET, but following all assessments, 96.0% of patients had a positive family history. We conclude that a negative family history of ET is often inaccurate, and that ET is primarily a hereditary disease.
Modeling cation/anion-water interactions in functional aluminosilicate structures.
A need for the computer simulation of hydration/dehydration processes in functional aluminosilicate structures has been noted. Full and realistic simulations of these systems can be somewhat ambitious and require the aid of interactive computer graphics to identify key structural/chemical units, both in the devising of suitable water-ion simulation potentials and in the analysis of hydrogen-bonding schemes in the subsequent simulation studies. In this article, the former is demonstrated by the assembling of a range of essential water-ion potentials. These span the range of formal charges from +4e to -2e, and are evaluated in the context of three types of structure: a porous zeolite, calcium silicate cement, and layered clay. As an example of the latter, the computer graphics output from Monte Carlo computer simulation studies of hydration/dehydration in calcium-zeolite A is presented.
Microvessel count and cerebrospinal fluid basic fibroblast growth factor in children with brain tumours.
Tumour growth is angiogenesis-dependent; brain tumours have more intense neovascularisation than other tumours and produce basic fibroblast growth factor, a potent angiogenic mediator. Because little is known about the release of basic fibroblast growth factor from brain tumours into extracellular fluids, we tested cerebrospinal fluid (CSF) from 26 children and young adults with brain tumours and 18 controls for basic fibroblast growth factor and for proliferative activity on cultured capillary endothelial cells. We also measured the density of microvessels in tumours by immunohistochemical staining. Basic fibroblast growth factor was detected in the CSF of 62% (16 of 26) patients with brain tumours but in none of the controls. Specimens with basic fibroblast growth factor stimulated DNA synthesis of capillary endothelial cells in vitro. Endothelial proliferative activity was blocked by neutralising antibodies to basic fibroblast growth factor. Basic fibroblast growth factor correlated with mitogenic activity in CSF in vitro (p < or = 0.0001), and with density of microvessels in histological sections (p < or = 0.005). A microvessel count of > or = 68 per 200 x field was associated with tumour recurrence (p = 0.005) and with mortality (p = 0.02). Basic fibroblast growth factor in brain tumours may mediate angiogenesis as measured by microvessel density in histological sections, so has potential as both a marker for neoplasia and a target for tumour treatments. Furthermore, evaluation of cerebrospinal fluid basic fibroblast growth factor, along with microvessel quantitation in biopsied tumours, may provide improved prognostic information for the management of patients with brain tumours.
On-site prothrombin time, activated partial thromboplastin time, and platelet count. A comparison between whole blood and laboratory assays with coagulation factor analysis in patients presenting for cardiac surgery.
BACKGROUND: Although available hemostasis assays from institutional laboratories permit an analytical approach to diagnosis and treatment of coagulation disorders following cardiopulmonary bypass, their clinical utility has been limited by delays in obtaining results. The development of instrumentation for on-site testing allows rapid return of results. This study was designed to compare whole blood (WB) results obtained from on-site coagulation assays with values provided by our institutional laboratory (LAB). METHODS: After Institutional Human Studies Committee approval, 362 patients presenting for cardiac surgery requiring cardiopulmonary bypass were enrolled in this study. Prothrombin time (PT), activated partial thromboplastin time (aPTT), and platelet count (PLT) assays were performed in both WB and LAB systems. PT, aPTT, and PLT measurements were compared between WB and LAB assays using blood specimens obtained from at least two time points for each patient. Normal range values for both PT and aPTT methods were determined by using measurements from a normal reference population. Coagulation factor levels were measured in a subset of patients to characterize the response of PT and aPTT assays to individual and multiple factor levels. To employ Bayes' theorem and calculate predictive indexes (e.g., sensitivity, specificity), the disease or factor deficiency was determined using factor levels. Predictive indexes were used to evaluate the ability of PT and aPTT assays to identify factor deficiency. RESULTS: PLT counts were similar between systems. Linear regression and bias analysis demonstrated similar results for WB and LAB PT and discordant results for aPTT measurements. Both PT assays had a similar normal range, whereas a wider distribution of results was evident for the WB aPTT normal range. Although statistically greater slopes for factor:aPTT regressions were observed for the WB system, WB aPTT correlated better with factor V and with factor V, VIII, and XII levels (multivariate linear regression). Diagnostic performance for factor levels less than 0.3 and 0.4 U/ml was similar for both WB and laboratory PT and aPTT assays. WB and LAB PT and aPTT assays performed similarly in detecting factor deficiency in the period after cardiopulmonary bypass. CONCLUSIONS: WB PT and PLT values correlate well with those obtained from the LAB. The discrepancy between measurement systems in aPTT values is probably a reflection of both different normal ranges and responsiveness to factor deficiency. These WB assays provide coagulation results that can accurately identify patients with quantitative deficiencies in platelets and coagulation factors.