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Biomedical subjects

R Long

Publications and source records attributed to R Long.

At least 55 records · Page 3Linked to original sources
PubMed1999

Messa di voce: an investigation of the symmetry of crescendo and decrescendo in a singing exercise.

A classical vocal exercise called "messa di voce" (Italian for "placing the voice") was used to study the symmetry of intensity increase and decrease in six trained singers. Ideally, the exercise is performed as a symmetric triangle, a linear increase in loudness, followed by a linear decrease. Given that some physiologic variables, like lung volume, undergo unidirectional change rather than a symmetric reversal, there is reason to believe that symmetries may not exist. It was found that highly trained singers who use large SPL ranges tend to abbreviate the decrescendo phase in comparison with the crescendo phase. In a few other cases, a plateau in SPL is reached, but an increase in loudness may still be perceived on the basis of a stronger vibrato or changes in timbre.

Adult↗
PubMed1999

Mycobacteriocidal action of exogenous nitric oxide.

We tested the hypothesis that exposure of extracellular Mycobacterium tuberculosis to low concentrations (< 100 ppm) of nitric oxide (NO) for short periods (24 h or less) will result in microbial killing. We observed that NO had both dose- and time-dependent cidal effects that were very significant by two-way analysis of variance (F ratios of 13.4 [P < 0.001] and 98.1 [P < 0.0001], respectively). Conceivably, extracellular bacilli in patients with pulmonary tuberculosis might be vulnerable to exogenous NO.

Anti-Bacterial Agents↗
PubMed1999

Transcontinental spread of multidrug-resistant Mycobacterium bovis.

Globally, the proportion of all cases of tuberculosis (TB) caused by drug-resistant strains is increasing. We report the case of a Canadian citizen who acquired a highly drug-resistant strain of Mycobacterium bovis while visiting a relative with AIDS-related tuberculosis in Spain. The origin of the strain was traced using spoligotyping, a polymerase chain reaction (PCR)-based fingerprint technology, and the European DNA database. The level of primary drug resistance-all five first-line drugs and 19 of 21 second-line drugs-in this case was unprecedented in Canada. Isolation of this strain from a Canadian citizen represents the first report of its appearance in this hemisphere. The infection was contained and combined medical-surgical treatment delivered.

Acquired Immunodeficiency Syndrome↗
PubMed1999

Tuberculous mycotic aneurysm of the aorta: review of published medical and surgical experience.

To define the epidemiology, pathogenesis, pathology, presentation, and management of tuberculous mycotic aneurysm of the aorta (TBAA) in the therapeutic era, we reviewed all of the cases reported in the English language literature from 1945 to the present. To the 39 cases in the published literature, we add two cases of our own. Although it is exceedingly rare, the prevalence of this lesion has remained relatively constant. In 75% of the cases, TBAA appeared to result from erosion of the aortic wall by a contiguous focus; 25% from direct seeding of the aortic intima or of the adventitia or media (via the vasa vasorum). Most of the aneurysms were saccular (90%) and false (88%). The thoracic and abdominal aortas were affected with equal frequency. The mean (+/- SD) age of the patients was 50+/-16 years. Twenty-two were men, and 19 were women. In 63% of the cases, tuberculosis (TB) was diagnosed at presentation. Disseminated TB was present in 46% of the cases. One or more of three clinical scenarios suggested TBAA: persistent pain, major bleeding, and a palpable or radiographically visible para-aortic mass, especially if it is expanding or pulsatile. In turn, each of these findings suggested a complication of TBAA that may be an indication for surgical intervention. Among the patients who were offered both medical and surgical treatment, 20 of 23 (87%) survived. Among those who were offered only one form of treatment or were offered no treatment at all there were no survivors. Both in situ reconstruction with a prosthetic graft, and extra-anatomic bypass appeared to offer excellent results, provided that an effective regimen of antituberculous drugs was delivered postoperatively. We offer our conclusions: (1) symptomatic TBAA is a rare but uniformly fatal lesion if not diagnosed promptly, (2) in the context of active TB, and especially miliary TB, TBAA should be suspected whenever one or more of the three clinical scenarios are present, and (3) combined medical and surgical therapy appears to offer the best chance of a cure.

Adult↗
PubMed1999

The validity of acid-fast smears of gastric aspirates as an indicator of pulmonary tuberculosis.

SETTING: A tuberculosis referral hospital in Canada. OBJECTIVE: To determine the validity of acid-fast (AFB) smears of gastric aspirates (GA) in the diagnosis of pulmonary tuberculosis, and to assess the prevalence of nontuberculous mycobacteria (NTM) in GA isolates from such patients. DESIGN: A retrospective case review of our experience with AFB smears (Kinyoun) and cultures of GA and sputum over a 3-year period. RESULTS: From 1994 to 1996 inclusive, 1155 GA were performed in 889 patients. Mycobacteria were cultured from 109 (9%) GA. Thirteen of these were positive on smear (sensitivity 19%). All GA that were positive on smear were culture positive for Mycobacterium tuberculosis. There were no false positive smears (specificity 100%). The sensitivity and specificity of the sputum smear were 45% and 99%, respectively. Of the 96 culture positive, smear negative GA, 54 grew M. tuberculosis and 42 grew an NTM. Of 13 patients who had sputum and GA studied coincidentally, and in whom the sputum was both smear and culture positive, the GA culture was positive in 13 and the smear was positive in eight (66%). CONCLUSION: AFB smear of GA is a relatively insensitive but highly specific indicator of pulmonary tuberculosis warranting institution of antituberculosis treatment. Gastric AFB smear positivity appears to reflect a high bacillary burden within the respiratory tract.

Adolescent↗
PubMed1999

[In situ enzyme immunoassay for detection of hepatitis A virus].

OBJECTIVE: To establish a more simple and sensitive technique for identification of hepatitis A virus (HAV). METHODS: HAV vaccine strain H2M20-K and wild-type strain He34 were used to infect KMB17 deploid cells in 96-well tissue culture plates and in situ enzyme immunoassay was used to detect viral infection with specific HA monoclonal antibody, A(OD) value of 1.8 was used as positive indicator. RESULTS: Observation of viral replication showed the peak titer of viral infectivity reached at 20-25 days after viral infection, which was 4-6 day searlier than that of ELISA endpoint assay. Comparing the viral infectivity titers of 13 individual samples, the two methods revealed no significant statistic difference (t = 1.13, P > 0.05). Our tests showed that in situ EIA could better reflect the results of neutralization and 5 HAV positive isolates were directly isolated from 12 faecal samples after the first passage culture. CONCLUSION: Although the sensitivities of the two tests were similar, the direct detection of virus/cell system with in situ EIA showed simple, easy to operate and reproducible, it may replace the conventionally used ELISA endpoint assay for identification of HAV, even for the other viruses.

Cell Line↗
PubMed1998

Low cathepsin D and low plasminogen activator type 1 inhibitor in tumor cytosols defines a group of node negative breast cancer patients with low risk of recurrence.

Prognostic factors are highly needed to divide node negative breast cancer patients into groups of low versus high risk of recurrence and death. In order to invade and spread, cancer cells must degrade extracellular matrix proteins. Accordingly, tumor levels of molecules involved in this degradation might be associated with patient outcome. Previous work has demonstrated that high levels of the aspartyl protease cathepsin D in breast cancer are associated with a poor prognosis and similar findings have been reported for molecules involved in the urokinase pathway of plasminogen activation. Interactions between different protease systems have been described and data suggest that several proteolytic enzymes may be operable at the same time in a tumor. In the present study we measured cathepsin D (n=162), uPA (n=116), uPAR (n=109) and PAI-1 (n=135) in tumor cytosols obtained from a population of node negative breast cancer patients. A significant correlation was found between levels of uPA, uPAR, and PAI-1. Levels of cathepsin D were directly related to levels of uPA and uPAR. With a median observation time of 4.81 years, univariate survival analyses showed that high levels of uPA and cathepsin D significantly predicted a shorter disease free survival, while only high levels of cathepsin D were able to significantly predict a shorter overall survival. Tumor levels of uPAR and PAI-1 gave mixed results depending on the cut-off point chosen. Interestingly, multivariate analysis demonstrated that PAI-1 and cathepsin D were independent significant prognostic indicators for disease-free survival while only cathepsin D was helpful in overall survival. The five year relapse rate of patients with low PAI-1 and low cathepsin D was 13% while patients who had greater than the median value for both of these molecules had a 5 year relapse rate of 40%. These data would indicate that at least two different protease systems are active in spread of node negative breast cancer and that measurement of these molecules may aid in the decisions to be made when offering adjuvant treatment to these patients.

Adult↗
PubMed1998

Relationship of nm23 to proteolytic factors, proliferation and motility in breast cancer tissues and cell lines.

Low expression of the antimetastatic gene nm23 has been associated with shorter overall survival in breast cancer. To better understand the mechanism(s) of action of this protein, we compared the levels of the nm23 protein in 152 breast cancer samples with other factors known to be involved in metastasis or related to prognosis. There was no significant relationship between either of the nm23 isoforms and cathepsin D (Cat-D), urokinase plasminogen activator (uPA), its inhibitor (PAI-1), steroid hormone receptors or ploidy status. A marginal inverse correlation was observed between per cent S-phase and nm23-H1 expression (r = -0.193, P = 0.047) and a positive correlation was observed between uPA receptor (uPAR) and both nm23-H1 (r = 0.263, P = 0.0018) and nm23-H2 (r = 0.230, P = 0.0064). The nm23-H1 gene was transfected into MDA-MB-231 human breast cancer cells and 12 clones were selected, of which two were characterized extensively. We found no significant differences in Cat-D, uPA, PAI-1 or uPAR, as a function of nm23 expression in either the MDA-MB-231 cells or the transfected clones. Compared with the parent cell line, we did observe a dose-dependent decrease in growth factor-stimulated motility and a decrease in metastatic potential in two clones with four- and eightfold elevated nm23-H1 expression, whereas the proliferative activities were similar. We conclude that the decreased metastatic potential might be related to down-regulation of growth factor-stimulated motility.

Animals↗
PubMed1998

Pulmonary tuberculosis treated with directly observed therapy: serial changes in lung structure and function.

OBJECTIVES: (1) To correlate structure (CT) with function in pulmonary tuberculosis (TB), and (2) to describe the evolution of structural and functional abnormalities when pulmonary TB is treated with directly observed therapy. SUBJECTS AND METHODS: Twenty-five patients with drug-susceptible pulmonary TB, 15 cavitary and 10 noncavitary, were studied prospectively. Conventional CT and pulmonary function testing (spirometry, diffusing capacity, and arterial blood gases) were performed at baseline, and after 1 and 6 months of directly observed therapy. RESULTS: All but one patient with noncavitary miliary TB had CT evidence of endobronchial disease, and all patients with cavitary disease had coexistent reduced lung attenuation, the latter presumably a result of gas trapping, hypoxic vasoconstriction, and vascular injury. Functional impairment was minimal and in proportion to the number of diseased segments and cavitary volume. Bronchiectasis was significantly more likely to complicate cavitary than noncavitary disease (64 vs 11%; p<0.05). CONCLUSIONS: CT findings correlate well with function in pulmonary TB. Physiologic data were consistent with the concept that pulmonary TB is an endobronchial disease that causes parallel reductions in ventilation and perfusion. This concurrent involvement of both airways and contiguous pulmonary blood supply offers an explanation for the minimal respiratory limitation experienced by these patients despite often extensive lung disease. Supervised therapy of drug-susceptible disease results in minimal structural and functional residua.

Adult↗
PubMed1997

Randomised controlled trial of CDP571 antibody to tumour necrosis factor-alpha in Crohn's disease.

BACKGROUND: Tumour necrosis factor-alpha (TNF alpha) is thought to have a central role in the pathogenesis of Crohn's disease. We tested the hypothesis that CDP571, a genetically engineered human antibody to TNF alpha, is effective in modifying disease activity in patients with moderately active Crohn's disease. METHODS: In this double-blind, placebo-controlled study, 31 patients were randomly assigned to CDP571 (n = 21) or placebo (n = 10). The primary endpoint was change in Crohn's disease activity index 2 weeks after a single infusion of CDP571 (5 mg/kg), or human albumin as placebo. One patient who attended no follow-up assessments was excluded from the analyses (CDP571 group). FINDINGS: The median Crohn's disease activity index fell from 263 (IQR 186.5-323.5) at baseline to 167 (137.5-294.0) at 2 weeks in the CDP571-treated patients (p = 0.0003); the change in the placebo group (253 [240-334] to 247 [183-256]) was not significant. In the treated group, there were also significant differences between baseline and 2 weeks in Harvey-Bradshaw score (p = 0.0005), key symptom score (p = 0.049), alpha 1-glycoprotein concentration (p = 0.012), and erythrocyte sedimentation rate (p = 0.01); concentrations of C-reactive protein fell, but not significantly (p = 0.067). Six patients achieved remission (Crohn's disease activity index < or = 150) and three others had activity indices of 156 or lower. There were no significant changes in the placebo group. INTERPRETATION: A single 5 mg/kg infusion of CDP571 reduced disease activity in Crohn's disease at 2 weeks. These data suggest that antibody neutralisation of TNF alpha is a potentially effective strategy in the management of Crohn's disease. The use of CDP571 in Crohn's disease requires further study.

Adolescent↗
PubMed1997

Biopsy Gleason score: how does it correlate with the final pathological diagnosis in prostate cancer?

OBJECTIVE: To evaluate the role of the Gleason score of needle biopsies of the prostate in predicting the final pathological staging of patients with carcinoma of the prostate treated by radical prostatectomy. PATIENTS AND METHODS: The records of 466 patients with carcinoma of the prostate treated by radical prostatectomy were reviewed, comparing the Gleason scores of the core-needle biopsies with the Gleason score and final pathological staging of the surgical specimens. RESULTS: The biopsy grade was the same as that of the prostatectomy specimen in 54% of the patients. The most common discordance was the upgrading of well-differentiated tumours in 75% of the patients. When the biopsy grade was compared with the surgical pathological stage, 49% of low- and 82% of high-grade lesions in the biopsy had capsular penetration by tumour or locally advanced disease (Stage C and D1). CONCLUSION: Well-differentiated tumours on the biopsy core are not predictive of organ-confined disease, but a poorly differentiated lesion is a good indicator of extracapsular extension of the cancer.

Biopsy, Needle↗
PubMed1997

Pharmacokinetics of antimycobacterial drugs in patients with tuberculosis, AIDS, and diarrhea.

To test the hypothesis that antituberculous drug disposition is altered in patients with AIDS, we studied the steady-state pharmacokinetics of isoniazid (300 mg/d), rifampin (600 mg/d), and pyrazinamide (1,500 mg/d) in 29 adults (14 patients infected with human immunodeficiency virus [HIV] and 15 non-HIV-infected patients) with tuberculosis in Nairobi, Kenya. Intestinal integrity was assessed with xylose. Neither HIV infection nor diarrhea accounted for the interpatient variability in the area-under-the-plasma concentration vs. time curve (AUC), the maximum concentration, or the terminal half-life (t1/2) of isoniazid, rifampin, and pyrazinamide. No significant association between HIV infection or diarrhea and pharmacokinetics was seen for any of the compounds. In addition, neither the AUC nor the t1/2 of any of these drugs reflected interpatient differences in CD4 lymphocyte counts. Xylose absorption was uniformly low. We did not demonstrate that HIV infection, diarrhea, or CD4 lymphocyte counts contributed significantly to the variability in pharmacokinetics of isoniazid, rifampin, and pyrazinamide in TB patients in Nairobi.

AIDS-Related Opportunistic Infections↗
PubMed1997

Screening for carpal tunnel syndrome in the workplace. An analysis of portable nerve conduction devices.

Several devices have been developed for rapid motor or sensory median nerve conduction testing. We evaluated the validity and reliability of the Neurosentinel (NS) and NervePace (NP) electroneurometer for sensory and motor testing, respectively, compared with formal electrodiagnostic studies (EDS), and examined their potential role in workplace screening for carpal tunnel syndrome (CTS). Thirty-two working subjects without CTS were examined and tested with the NS, NP, and EDS, and retested one week later. Subjects were selected who did not have CTS, other hand or nerve problems, or jobs with significant ergonomic risks, in order to decrease the likelihood of changes over time in median nerve function. Mean correlations of NP and NS with EDS latencies ranged from r = 0.069 to r = 0.85, with somewhat better correlation for NS (sensory) than NP (motor). Test-retest reliability was greatest for motor EDS (r = 0.86 to 0.91) and similar for sensory EDS, NS, and NP (r = 0.72 to 0.79); mean results were very similar. Based on the observed relationship between NS or NP and EDS results, confidence intervals were calculated to represent the range of EDS results consistent with a single NS or NP measurement. These intervals ranged from +/- 0.3 milliseconds (ms) for NS to +/- 0.6 msec for NP, with similar ranges for change over time in an individual. The magnitude of these intervals for a single test or individual implies that the NS and NP are unlikely to identify individuals with CTS or to detect changes over time that are not accompanied by symptoms or signs. The screening devices are not likely to be useful in confirming early CTS, when single latency values may be normal, and detailed EDS may be necessary to detect nerve entrapment. Compared with EDS, these devices have moderate validity and similar reliability; they are probably most useful for cross-sectional or longitudinal studies of groups, but care must be taken in using them for pre-placement or surveillance tests of individual workers. False-positive results may lead to discrimination, inappropriate referrals and interventions; false-negative tests can result in inappropriate reassurance and missed opportunities for intervention.

Adult↗
PubMed1997

Disseminated tuberculosis with and without a miliary pattern on chest radiograph: a clinical-pathologic-radiologic correlation.

SETTING: Province of Manitoba, Canada. OBJECTIVE: To describe the characteristics of disseminated tuberculosis (TBD) with and without a miliary pattern on chest radiograph, to determine the mortality, and to identify the demographic and clinical features associated with survival. DESIGN: A retrospective case review. RESULTS: Of 2013 cases of active tuberculosis reported to the Provincial Tuberculosis Registry between January 1979 and December 1993, 56 had disseminated disease. The odds of developing TBD were significantly higher in females. Compared to those with a miliary pattern (n = 42), those without a miliary pattern on chest radiograph (n = 14) were significantly more likely to have a risk factor for tuberculosis (86% vs 52%, P < 0.05) and to die (86% vs 21%, P < 0.001). The diagnosis of TBD was significantly more likely to be made at postmortem in non-miliary compared to miliary patients (43% vs 5%, P < 0.05). Amongst patients with a miliary pattern, the presence of one or more risk factors for tuberculosis was associated with a significantly higher mortality (P < 0.05). Meningitis was very uncommon and did not determine the outcome. CONCLUSION: Disseminated tuberculosis patients without a miliary pattern on chest radiograph have an extremely high mortality rate; those with a miliary pattern may also succumb, especially if co-morbid with a condition known to increase the risk of tuberculosis.

Adult↗