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Biomedical subjects

H A Ward

Publications and source records attributed to H A Ward.

At least 19 recordsLinked to original sources

Treatment outcome of multidrug-resistant tuberculosis among Vietnamese immigrants.

OBJECTIVE: To review the outcome for MDR-TB treatment among potential migrants from Vietnam. SETTING: All cases of documented MDR-TB treated by the International Organization of Migration (IOM) in Vietnam from 1989 to 2000 were reviewed. METHODS: MDR-TB was defined as isoniazid- and rifampicin-resistant Mycobacterium tuberculosis. All cases of TB treated by the IOM and recorded in the computerised database were reviewed to identify MDR-TB cases. Demographics, chest radiograph results, drug resistance, drug use and dosage, duration of treatment, and outcome were analysed. RESULTS: Forty-four cases of MDR-TB were identified. Treatment consisted of ambulatory directly observed treatment with an 8-drug protocol: isoniazid, rifampicin, pyrazinamide, ethambutol, capreomycin, ethionamide, ofloxacin and cycloserine. This initial protocol was modified due to drug availability or drug intolerance. Patients were treated with a median of 8 drugs (range 6-12). Mean duration of treatment for MDR-TB was 23.0 (SD+/-11.4) months. Thirty-eight (86%) patients were cured and emigrated, one failed treatment (2%), three were lost to follow-up (7%) and two died (4%). CONCLUSION: Treatment for MDR-TB provided by the IOM was effective in preparing a low-income population for migration.

Capreomycin↗

Extent of pulmonary tuberculosis in patients diagnosed by active compared to passive case finding.

OBJECTIVE: To compare the extent of pulmonary tuberculosis amongst patients detected by screening (active case finding) with that in patients detected by symptoms (passive case finding), and to identify early symptoms of pulmonary tuberculosis. SUBJECTS AND METHOD: In this cross-sectional study, Tuberculosis Control Program records were reviewed for method of detection and extent of disease in Canadian Plains Aborigines between 1 January 1991 and 30 June 1999. RESULTS: Among 903 cases, method of detection was active in 450 (49.8%) and passive in 453 (50.2%). Cough and fever were the most common symptoms in both methods of detection, and were significantly more frequent in passive detection (P < 0.05). Cough was present in 59% and fever in 19% of actively detected cases compared to 84% and 47%, respectively, of passively detected cases. Age was significantly different between the two methods of detection. Hemoptysis, weight loss and method of detection were associated with increased risk of infectiousness among those < or = 19 years, while cough, hemoptysis and weight loss were associated among those >19 years. CONCLUSION: Method of detection rather than age contributed to infectiousness in children and adolescents. Daily cough for more than 1 month and unexplained fever for more than 1 week should raise the suspicion for TB.

Adolescent↗

Comparison of memory fMRI response among normal, MCI, and Alzheimer's patients.

OBJECTIVE: To determine whether an fMRI memory encoding task distinguishes among cognitively normal elderly individuals, patients with mild cognitive impairment (MCI), and patients with early Alzheimer's disease (AD). METHODS: Twenty-nine subjects (11 normal, 9 MCI, 9 AD) were studied with an fMRI memory encoding task. A passive sensory task was also performed to assess potential intergroup differences in fMRI responsiveness. Activation in the medial temporal lobe for the memory task and in the anatomic rolandic area for the sensory task was studied. Intergroup comparisons were performed using receiver operating characteristic (ROC) analyses. The ROC method provides rigorous control of artifactual false-positive "activation." Subjects were tested for recall and recognition of the encoding task stimuli following the fMRI study. RESULTS: Medial temporal lobe activation was greater in normal subjects than MCI and AD patients (p = 0.03 and p = 0.04). There was no difference between AD and MCI patients in fMRI memory performance [corrected]. There was an association between fMRI memory activation (area under the ROC curve) and post-fMRI performance on recognition and free recall. There was no difference among the three groups on the sensory task. CONCLUSIONS: MCI and AD patients had less medial temporal lobe activation on the memory task than the normal subjects but similar activation as normal subjects on the sensory task. These findings suggest decreased medial temporal activation may be a specific marker of limbic dysfunction due to the neurodegenerative changes of AD. In addition, fMRI is sufficiently sensitive to detect changes in the prodromal, MCI, phase of the disease.

Aged↗

Functional inferences vary with the method of analysis in fMRI.

Neuroanatomic substrates of specific cognitive functions have been inferred from anatomic distributions of activated pixels during fMRI studies. With declarative memory tasks, interest has focused on the extent to which various medial temporal lobe anatomic structures are activated while subjects encode new information. The aim of this project was to examine how commonly used variations in fMRI data processing methods affect the distribution of activation in anatomically defined medial temporal lobe regions of interest (ROIs) during a complex scene-encoding task. ROIs were drawn on an MRI anatomic template formed from 3D SPGR scans of eight subjects combined in Talairach space. Separate ROIs were drawn for the posterior and anterior hippocampal formation, parahippocampal gyrus, and entorhinal cortex. Twelve different activation maps were created for each subject by using four correlation coefficients and three cluster volumes. Friedman's two-way ANOVA by ranks was used to test the hypothesis that the distribution of activated pixels among defined anatomic ROIs varied as a function of the data processing method. By simply varying the combination of correlation coefficient and cluster volume, significantly different distributions of activation within named medial temporal lobe structures were obtained from the same fMRI datasets (P < 0.015; P < 0.001). The number of subjects studied (n = 8) is in a range commonly found in the literature yet this clearly resulted in spurious associations between processing parameter variations and activation distribution. Using data processing methods that are independent of the arbitrary selection of cutoff values for thresholding activation maps may reduce the likelihood of obtaining spurious results.

Adult↗

Posttransplant primary cutaneous T-cell lymphoma.

A patient with posttransplant cutaneous lymphoma is described. Although most posttransplant lymphomas are of B-cell origin, this patient's lymphoma is a primary cutaneous lymphoma of T-cell origin. Another report exists of the first case of posttransplant primary cutaneous T-cell lymphoma localized to the lower extremities. Our patient's involvement was generalized with tumor nodules on the face and anterior chest. Reduced immune surveillance, chronic antigenic stimulation caused by transplant grafts, and the direct oncogenic effects of immunosuppressive drugs have all been suggested as mechanisms. Prompt recognition of this condition and initiation of appropriate therapy with reduction of high-dose immunosuppression can lead to better patient outcomes.

Female↗

Prospective multiaxial motion correction for fMRI.

Corruption of the image time series due to interimage head motion limits the clinical utility of functional MRI. This paper presents a method for real-time prospective correction of rotation and translation in all six degrees of rigid body motion. By incorporating an orbital navigator (ONAV) echo for each of the sagittal, axial, and coronal planes into the fMRI pulse sequence, rotation and translation can be measured and the spatial orientation of the image acquisition sequence that follows can be corrected prospectively in as little as 160 msec. Testing of the method using a computerized motion phantom capable of performing complex multiaxial motion showed subdegree rotational and submillimeter translational accuracy over a range of +/-8 degrees and +/-8 mm of motion. In vivo images demonstrate correction of simultaneous through-plane and in-plane motion and improved detection of fMRI activation in the presence of head motion.

Artifacts↗

Assessment of functional MR imaging in neurosurgical planning.

BACKGROUND AND PURPOSE: Presurgical sensorimotor mapping with functional MR imaging is gaining acceptance in clinical practice; however, to our knowledge, its therapeutic efficacy has not been assessed in a sizable group of patients. Our goal was to identify how preoperative sensorimotor functional studies were used to guide the treatment of neuro-oncologic and epilepsy surgery patients. METHODS: We retrospectively reviewed the medical records of 46 patients who had undergone preoperative sensorimotor functional MR imaging to document how often and in what ways the imaging studies had influenced their management. Clinical management decisions were grouped into three categories: for assessing the feasibility of surgical resection, for surgical planning, and for selecting patients for invasive functional mapping procedures. RESULTS: Functional MR imaging studies successfully identified the functional central sulcus ipsilateral to the abnormality in 32 of the 46 patients, and these 32 patients are the focus of this report. In epilepsy surgery candidates, the functional MR imaging results were used to determine in part the feasibility of a proposed surgical resection in 70% of patients, to aid in surgical planning in 43%, and to select patients for invasive surgical functional mapping in 52%. In tumor patients, the functional MR imaging results were used to determine in part the feasibility of surgical resection in 55%, to aid in surgical planning in 22%, and to select patients for invasive surgical functional mapping in 78%. Overall, functional MR imaging studies were used in one or more of the three clinical decision-making categories in 89% of tumor patients and 91% of epilepsy surgery patients. CONCLUSION: Preoperative functional MR imaging is useful to clinicians at three key stages in the preoperative clinical management paradigm of a substantial percentage of patients who are being considered for resective tumor or epilepsy surgery.

Adolescent↗

New laser techniques for diagnosis and treatment of deep-seated brain lesions.

The five years survival rate of deep-seated malignant brain tumors after surgery/radiotherapy is virtually 100% mortality. Special problems include: (1) lesions often present late; (2) position: lesions overlies vital structures, so complete surgical/radiotherapy lesion destruction can damage vital brain-stem functions; and (3) difficulty in differentiating normal brain from malignant lesions. This study aimed to use the unique properties of the laser: (a) to minimize damage during surgical removal of deep-seated brain lesions by operating via fine optic fibers; and (b) to employ the propensity of certain lasers for absorption of (nontoxic) dyes and absorption and induction of fluorescence in some brain substances, to differentiate borders of malignant and normal brain, for more complete tumor removal. A fine laser endoscopic technique was devised for removal of brain lesions, which minimized thermal damage and shock waves. A compatible endoscopic fluoroscopic laser technique was developed to differentiate brain tumor from normal brain.

Brain↗

Phenotypic characterization of chicken thymic stromal elements.

Phenotypic profiles of the thymic stromal components provide an excellent approach to elucidating the nature of the microenvironment of this organ. To address this issue in chickens, we have produced an extensive panel of 18 mAb to the thymic stroma. These mAb have been extensively characterized with respect to their phenotypic specificities and reveal that the stromal cells are equally as complex as the T cells whose maturation they direct. They further demonstrate that, in comparison to the mammalian thymus, there is a remarkable degree of conservation in thymic architecture between phylogenetically diverse species. Eleven mAb reacted with thymic epithelial cells: MUI-73 was panepithelium, MUI-54 stained all cortical and medullary epithelium but only a minority of the subcapsule, MUI-52 was specific for isolated stellate cortical epithelial cells, MUI-62, -69, and -71 were specific for the medulla (including Hassall's corpuscle-like structures), MUI-51, -53, -70, and -75 reacted only with the type-1 epithelium, or discrete regions therein, lining the subcapsular and perivascular regions and MUI-58 demonstrated the antigenic similarity between the subcapsule and the medulla. Seven other mAb identified distinct isolated stromal cells throughout the cortex and medulla. Large thymocyte-rich regions, which often spanned from the outer cortex to medulla, lacked epithelial cells. These mAb should prove invaluable for determining the functional significance of thymic stromal-cell subsets to thymopoiesis.

Animals↗

The effect of infectious bursal disease virus on B lymphocytes and bursal stromal components in specific pathogen-free (SPF) White Leghorn chickens.

The effect of infectious bursal disease virus (IBDV) was studied on adult specific pathogen-free (SPF) white Leghorn chickens through analysis of peripheral blood cell suspensions and histological staining patterns on various tissue types, with specific mAbs. A rapid, progressive loss of B lymphocytes was observed in the bursal cortex and medulla, peripheral blood and thymic medulla. There was, however, a resistant population of MUI-36+ cells at the bursal cortico-medullary junction and scattered around splenic periellipsoidal sheaths. These resistant cells were suggested to be a subpopulation of macrophages which expressed the MUI-36 marker; alternatively these may have phagocytosed virally infected B cells or their remnants. Throughout the period of infection, T lymphocytes appeared nonsusceptible. Further, while the distribution of stromal cell antigens within the bursal cortex remained unaltered, particular epitopes on the surface epithelium and in the medulla were lost as a consequence of viral infection. The data presented therefore suggests that immunodepression of chickens post-IBDV infection, may arise as a direct consequence of infection of B lymphocytes; additionally, it is possible that the elimination of certain crucial elements within the bursal microenvironment may contribute to this state.

Animals↗

High level expression in Chinese hamster ovary cells of soluble forms of CD4 T lymphocyte glycoprotein including glycosylation variants.

The CD4 cell surface antigen is of interest as a marker of T lymphocytes that recognize foreign antigens in the context of MHC Class II antigen, as a receptor for the human immunodeficiency virus (HIV) and as a member of the immunoglobulin superfamily (IgSF) with four Ig-like domains present in the extracellular domain. In order to produce large amounts of soluble CD4 for x-ray crystallography and other molecular studies, a recently developed expression system based on selection via glutamine synthetase was used. Expression was attempted for rat CD4 corresponding to the full extracellular sequence (sCD4; domains 1-4), the NH2-terminal half (domains 1 and 2) and the first domain alone. Stable transfected Chinese hamster ovary cell lines were obtained that expressed sCD4 and sCD4 (half) at typical maximal levels in spent tissue culture supernatant of greater than 80 and 25 mg/liter, respectively. Domain 1 alone was not expressed and introduction of a N-linked glycosylation site did not facilitate expression. The role of glycosylation in the expression of sCD4 was investigated by mutagenesis of the constructs to remove each of the two N-linked glycosylation sites in turn and both together. All three forms were expressed at 60-120 mg/liter. The sCD4 (half) was not expressed after deletion of its N-linked site. The disulfide bonds of sCD4 were determined to be within domains 1, 2, and 4 and isolation of glycopeptides showed that both N-linked sites were glycosylated. Analysis of the hydrodynamic properties of sCD4 suggested that the molecule adopted an extended conformation in solution rather than folding to form a compact structure like an Fab. The possibility of dimerisation of CD4 was investigated but sCD4 dimers were not seen at an affinity cut-off of about 4 x 10(5) M-1.

Amino Acid Sequence↗

Phenotypic characterization of chicken bursal stromal elements.

Many, if not all, of the different phases of intrabursal B-cell maturation are controlled by the stromal components. We have used an extensive panel of mAb to provide a detailed phenotypic profile of these cells. Antigenic specificities were defined for the entire surface epithelium, interfollicular surface epithelium, follicle-associated epithelium, basement membrane, basement membrane-associated epithelium. Several mAb were specific for the medulla, including those reactive with the stellate network of epithelial cells, isolated macrophages, and granular, apparently secreted antigens. One of these, MUI-92, appears to be bursa-specific. Two mAb reacted strongly with stellate cortical macrophages, one of which weakly stained similar cells in the medulla. MHC-class II antigens were expressed on endothelium of the corticomedullary junction, macrophagelike cells in the cortex, and medulla and B lymphocytes predominantly in the cortex. Collectively, these mAb have demonstrated the antigenically distinct nature of discrete regions in the bursa, but also the continuity of the surface epithelium with the corticomedullary junction and medulla. They represent excellent reagents for defining the stromal cell contribution of B-cell development.

Animals↗

Expression of leucocyte antigens by cells from the metrial gland of the pregnant rat.

The function of the metrial gland of the rat, and particularly of its characteristic population of granulated cells, remains unknown. However, several lines of evidence suggest that the granulated cells may derive from lymphocytes, and play a role in the immunology of pregnancy. In this study, antigen expression by granulated and other cell populations from the metrial glands of rats at Days 13 and 14 of pregnancy was studied by an indirect immunoperoxidase method. Acetone-fixed frozen sections, and cytocentrifuge preparations of collagenase-dispersed metrial gland tissue in which numbers of granulated cells had been increased by density-gradient centrifugation, were used. The primary antibodies used recognised, inter alia, B lymphocytes (MRC OX-3, MRC OX-6, MRC OX-12), T lymphocytes (MRC OX-8, W3/25, MRC OX-19), neutrophils (MRC OX-42) and cells of the monocyte/macrophage series (MRC OX-3, MRC OX-6, MRC OX-42, MRC OX-43). The majority of the granulated cells, including smaller, "immature" forms, were unlabelled by any of these antibodies. Some lymphocytes, and varying numbers of larger, non-granulated cells, were labelled by OX-6, OX-12, W3/25, OX-42 and OX-43. In addition to lymphocytes, labelled cells included neutrophils (OX-42), endothelial cells (OX-43), and probably some macrophages (OX-6, OX-43). OX-12, which recognises the kappa chain of rat IgG, labelled some large cells which may have been stromal cells. These findings do not support the concept that the granulated cells are derived from lymphocytes.

Animals↗