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Biomedical subjects

P Barnes

Publications and source records attributed to P Barnes.

At least 55 records · Page 3Linked to original sources

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.

Aluminum Silicates↗

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.

Adolescent↗

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.

Adult↗

Advances in radiation therapy for craniopharyngiomas.

The overall survival for patients with craniopharyngioma is excellent. However, conventional treatments that include aggressive surgery and standard irradiation have been associated with significant morbidity. Focal radiation treatment with stereotactic radiosurgery has a role in selected cases, but may also be damaging to sensitive normal tissues such as the optic chiasm. Stereotactic radiotherapy (SRT) is a technique that allows for conventionally fractionated radiation under stereotactic guidance. Thus, highly focal and precise radiotherapy is now coupled with fractionation, enabling the treatment of selected tumors with a potentially improved therapeutic index. Dose optimization with SRT for focally discrete tumors should result in equivalent local control and survival compared to patients treated with conventional irradiation. We anticipate a significant decrease in late effects, especially neuropsychological and neuroendocrine sequelae.

Child↗

The pathology of community-acquired pneumonia.

A good understanding of pathologic processes facilitates clinical approaches to the diagnosis of respiratory disorders. The pathology of community-acquired pneumonia is reviewed. The gross appearance and microscopic features of bronchopneumonia, lobar pneumonia, interstitial pneumonia, and mixed patterns are compared. Next, features of lung injury incited by specific microbial agents are discussed. Specific histological clues to diagnosis of the causative agent are highlighted where applicable. Special techniques are available to aid the pathologist in diagnosis of specific microbial agents in biopsy materials. The benefits and pitfalls of using immunohistochemical stains and molecular biologic techniques, such as in situ hybridization and the polymerase chain reaction are briefly presented. Finally, the methods by which material for study are obtained, (open lung biopsy, fine needle aspiration, and bronchoalveolar lavage), are discussed with respect to advantages and limitations.

Bacteria↗

Prospective evaluation and clinical utility of on-site monitoring of coagulation in patients undergoing cardiac operation.

Although laboratory coagulation tests permit a rational approach to both diagnosis and management of coagulation disorders after cardiopulmonary bypass, their clinical utility is limited by delays in obtaining results. This study was designed to evaluate prospectively the impact of on-site coagulation testing on blood product use, operative time, and intraoperative management of microvascular bleeding. Patients who underwent cardiac procedures involving cardiopulmonary bypass and subsequently developed microvascular bleeding were randomly assigned to receive either standard therapy (n = 36) or therapy defined by a treatment algorithm based on results from an on-site coagulation monitoring laboratory (n = 30). No differences were found between treatment groups in hematologic assay data, operative procedures, or duration of cardiopulmonary bypass. Patients treated in accordance with on-site laboratory results (algorithm therapy) received significantly less intraoperative fresh frozen plasma (0.4 +/- 1.1 U versus 2.4 +/- 2.8 U; p = 0.0006) during the treatment interval, had shorter operative times, and had less mediastinal chest tube drainage during the initial perioperative interval (158 +/- 169 ml versus 326 +/- 258 ml; p = 0.003) than did patients in the standard therapy group. Patients who underwent algorithm therapy also received fewer platelet (1.6 +/- 5.9 versus 6.4 +/- 8.2 U; p = 0.02) and red blood cell (1.9 +/- 1.7 U versus 4.1 +/- 4.1 U; p = 0.01) transfusions after the operation. Nine of 36 (25%) standard group patients received initial therapy which differed from that which would have been guided by the on-site algorithm protocol. Our findings indicate that rapid and accurate coagulation test results can guide specific therapy and optimize treatment of microvascular bleeding in patients who undergo cardiac operations.

Blood Coagulation Tests↗

Laparoscopic Nissen fundoplication.

A technique for laparoscopic Nissen fundoplication is described and a series of 11 cases is presented. The technique secures the patient to the operating table with three safety straps and the patient is then placed in a reverse Trendelenburg position with the hips flexed. The surgeon operates from the patient's right side using two midline trocar sites as the main operating ports. Other ports provide retraction and laparoscope access. The liver retractor is held by a mechanical arm. Once the esophageal peritoneum has been opened, the esophagus and diaphragmatic crura are dissected out and elevated by a Penrose drain sling. The short gastrics are divided and the fundus is brought posterior to the esophagus passing from left to right. A large Maloney dilator is placed in the esophagus and the fundal wrap is sutured to the anterior aspect of the stomach by three sutures; the inferior--most of which incorporates the anterior wall of the esophagus. Once the fundoplication is completed, the dilator is replaced by a nasogastric tube. Postoperatively, patients are given clear liquids and when these are tolerated the nasogastric tube is removed. Most patients are discharged on the second or third postoperative day. Operating time averaged 147 min, and all patients returned to unrestricted activity within 2 to 3 weeks. All patients reported complete relief of gastroesophageal reflux. Average follow up was 120 days with a median of 148 days. Long-term follow up is in progress.

Adult↗

Prognostic factors in medulloblastoma, including DNA ploidy.

PURPOSE: DNA ploidy status, completeness of surgical resection, use of chemotherapy, adequacy of radiation therapy, metastatic stage, sex, and age at diagnosis were evaluated as predictors of relapse in 58 patients with cerebellar medulloblastoma. METHODS: Flow cytometry (FCM) and/or image analysis (IA) were used to characterize tumor DNA ploidy. Twelve tumors (21%) were found to be aneuploid, 11 (19%) tetraploid, and 35 (60%) diploid. RESULTS: The most significant predictors of relapse in univariate analyses were the adequacy of radiation (> or = 50 Gy) (P = .02), metastatic staging (P = .05), completeness of resection (P = .085), and DNA ploidy status (diploid/tetraploid v aneuploid; P = .11). When the 52 patients who received > or = 50 Gy were included in a multivariate Cox model analysis, those with diploid/tetraploid tumors had fewer recurrences than those with aneuploid tumors (relative risk, 0.33; 95% confidence interval, 0.12 to 0.89; P = .03). Patients with complete resections (P = .07), or with stage M0 disease (P = .06) had fewer recurrences than other patients, but these factors were not independent predictors of outcome. DNA ploidy status was correlated with age; 10 of the 12 aneuploid tumors were found in children ages 3 to 10 years. Age, sex, and the use of chemotherapy were not prognostically significant in these analyses. CONCLUSION: The adequacy of radiation dose and DNA ploidy were the most important prognostic factors in this series. Contrary to previous reports, when corrected for adequacy of treatment, DNA aneuploidy was associated with a poor outcome. By multivariate analyses, DNA ploidy was an independent variable, even when controlling for extent of surgical resection and metastatic stage.

Aneuploidy↗

Effects of hydrochlorothiazide and captopril on the survival and heart weight of cardiomyopathic hamsters.

The current study investigated the effect of hydrochlorothiazide (HCTZ), and of captopril, on the survival and heart weight of cardiomyopathic hamsters (CMH). Groups of 51 CMH (about 200 days old) were orally treated with HCTZ (6 mg/kg), captopril (30 mg/kg), a combination of both drugs or vehicle alone (control group), for 217 days. Then survivors were sacrificed and the hearts weighed. The survival of the animals treated with HCTZ alone or in combination with captopril was similar, and was clearly increased when compared to controls (more than 70 days increase in median survival time). A more modest increase in survival occurred in animals treated with captopril alone. The efficacy of the diuretic therapy was consistent with fluid retention being the primary cause of death in CMH and demonstrated the usefulness of the model for the testing of new diuretics. HCTZ or captopril alone had no effect on the heart weight of survivors. However a reduction of cardiac hypertrophy (-18%) was seen when captopril and HCTZ were coadministered. This effect of the ACE inhibitor was considered to result from antagonism of the compensatory activation of the renin-angiotensin system occurring in response to diuretic therapy.

Animals↗

Cavernous angiomas of the central nervous system in children.

A surgical series of 19 patients under the age of 18 years with pathologically verified cavernous angioma is presented. Most lesions were located in the cerebral hemispheres, but four were in the pons or midbrain, two in the diencephalon, and one in the spinal cord. Fourteen patients presented with an acute or progressing neurological deficit, three with seizures, one infant with irritability, and one with headache alone. Five patients had family histories of vascular malformations of the central nervous system, and five had multiple lesions. Surgery for small or deep lesions was aided considerably by intraoperative ultrasonographic or stereotactic localization techniques. Pathological examination of the resected malformations revealed a complex histology containing not only typical closely approximated cavernous vessels, but also areas of marked proliferation of granulation tissue and partially re-endothelialized hemorrhage, suggesting a mechanism for the apparent growth of certain cavernous angiomas. The postoperative results were good, with only one patient suffering a permanent worsening of neurological status after surgery. Incomplete resection was initially carried out in five patients, two of whom rebled within 1 year after operation. Long-term follow-up findings in these patients have emphasized the unusual history of certain of these malformations.

Adolescent↗

Clozapine-associated agranulocytosis: risk and aetiology.

This paper reviews the epidemiology and pathogenesis of clozapine-associated agranulocytosis. According to present clinical experience, granulocytopenia can be expected in approximately 3% of patients during clozapine treatment. The risk of serious sequelae of granulocytopenia can be minimised by regular white blood cell count monitoring. Although research suggests that some patient groups may be at higher risk of developing this serious adverse reaction, we cannot yet predict the susceptible patients, so all patients exposed to clozapine should receive regular blood monitoring throughout treatment. Because of the risk of agranulocytosis, clozapine should only be used in schizophrenic patients who are resistant to, or intolerant of, conventional antipsychotic medications. Unless compliance with blood monitoring is assured, clozapine treatment should not be recommended.

Agranulocytosis↗

Cerebral venography with MR.

The authors describe a two-dimensional time-of-flight magnetic resonance (MR) angiography technique to create projection venograms of the head. The technique was applied to 27 healthy volunteers and 39 patients. The superior sagittal and straight sinuses, the internal cerebral veins, and the Galen vein were visualized in all the volunteers. Other veins were seen in a high percentage of subjects. Systematic comparison of digital subtraction angiography (DSA) after intraarterial contrast medium injection and MR venography in patients showed good correlation between the two techniques. MR venography proved helpful in identifying thrombosis or patency of cerebral veins and sinuses and showed collateral venous drainage and venous drainage from arteriovenous malformations. There was good correlation between conventional contrast angiography and MR venography. In conclusion, MR venography is considered reliable for showing the cerebral venous system and provides information additional to that of conventional spin-echo imaging.

Adolescent↗

Natural killer cells in the blood of patients with rheumatoid arthritis treated with azathioprine.

The mode of action of azathioprine in the treatment of rheumatoid arthritis is not known. In this study we showed that azathioprine did not produce any consistent fall of NK cell numbers as detected by the use of the monoclonal antibodies Leu 7 and Leu 11. There was a marked and significant loss of NK cell function. This was not associated with changes in disease activity following treatment. The cause for the loss of NK function is not known.

Antibodies, Monoclonal↗

Limiting dilution analysis of autocytotoxic and autosuppressor T-cells in rheumatoid arthritis.

Limiting dilution analysis has shown that the autologous mixed lymphocyte reaction is regulated by at least two cell populations, the autocytotoxic and the autosuppressor. Limiting dilution analysis in nine patients with rheumatoid arthritis has shown that there is a significant decrease in both populations when compared to 10 control subjects. The mechanism and the consequences of this decrease are not known.

Arthritis, Rheumatoid↗

Characterization of PAF receptors on human neutrophils using the specific antagonist, WEB 2086. Correlation between receptor binding and function.

The antagonism of PAF effects by WEB 2086 and the receptor binding of [3H]WEB 2086 were investigated in isolated human neutrophils. WEB 2086 inhibited PAF-induced beta-glucuronidase release and [3H]WEB 2086 bound specifically to high-affinity sites on the cells. Close concordance between affinity constants for WEB 2086 from functional and radioligand-binding studies suggests that WEB 2086 interacts with the neutrophil PAF receptors and that [3H]WEB 2086 may be a useful ligand in investigation of these receptors.

Azepines↗