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Biomedical subjects

B Allen

Publications and source records attributed to B Allen.

At least 73 records · Page 4Linked to original sources

Ethical and practical implications of the human genome initiative for family medicine.

Major advances in predictive genetic testing resulting from the Human Genome Initiative could change significantly the routine practice of family medicine. Family physicians should be aware that increased genetic information may affect patients' abilities to acquire and maintain insurance and employment and that interested parties will have incentives to seek this information. The social consequences of genetic information, as well as increased health promotion efforts, may raise problems of informed consent and confidentiality. In addition to their ethical implications, these developments will also affect the practice of family physicians in practical ways such as record keeping. We discuss cases that illustrate the potential impact of these emerging technologies on the practice of family medicine.

Adult↗

An X Window system for statlab results reporting.

We have developed a system that receives "stat" results encoded in Health Level Seven from the Laboratory Information System, prints a report in destination Intensive Care Units (ICUs), and captures the data for review in a custom spreadsheet format at color X-terminals located in ICUs. Available services include a reference nomogram plot of arterial blood gas data, printed summaries, automated access to the Clinical Information System and a Medline database, electronic mail, a simulated electronic calculator, and general news and information. Security mechanisms include an audit trail of user activities on the system. Noteworthy technical aspects and non-technical factors impacting success are discussed.

Clinical Laboratory Information Systems↗

Semi-quantitative SPECT scanning in acute ischaemic stroke.

We performed semi-quantitative SPECT scans using 99mTcm-HMPAO on 34 elderly subjects 10-15 days after ischaemic stroke. Each cerebral hemisphere was divided into five regions of interest. Asymmetry scores were determined for ten slices in each region using activity ratios to the other hemisphere and to the ipsilateral cerebellum. Outcome was assessed by maximal Barthel ADL score during the first two months after stroke. Asymmetry scores in the hemisphere involved by the stroke event were much higher than those in the opposite hemisphere. Subjects with poor outcome (maximal Barthel 0-12) had significantly higher asymmetry scores than those with good outcome (Barthel 13-20). The total asymmetry score (both hemispheres) and the score of the involved hemisphere predicted Barthel ADL score in a general linear model. Total asymmetry score remained a significant predictor of maximal Barthel score in multivariate models. Thus semi-quantitative SPECT scanning is of value in predicting functional recovery after stroke.

Activities of Daily Living↗

The catalase-peroxidase gene and isoniazid resistance of Mycobacterium tuberculosis.

Tuberculosis is responsible for one in four of all avoidable adult deaths in developing countries. Increased frequency and accelerated fatality of the disease among individuals infected with human immunodeficiency virus has raised worldwide concern that control programmes may be inadequate, and the emergence of multidrug-resistant strains of Mycobacterium tuberculosis has resulted in several recent fatal outbreaks in the United States. Isonicotinic acid hydrazide (isoniazid, INH) forms the core of antituberculosis regimens; however, clinical isolates that are resistant to INH show reduced catalase activity and a relative lack of virulence in guinea-pigs. Here we use mycobacterial genetics to study the molecular basis of INH resistance. A single M. tuberculosis gene, katG, encoding both catalase and peroxidase, restored sensitivity to INH in a resistant mutant of Mycobacterium smegmatis, and conferred INH susceptibility in some strains of Escherichia coli. Deletion of katG from the chromosome was associated with INH resistance in two patient isolates of M. tuberculosis.

Amino Acid Sequence↗

New-onset ventricular tachycardia during pregnancy.

During evaluation for palpitations, presyncope, or syncope, seven pregnant women had documented ventricular tachycardia. Before pregnancy none had a history of significant cardiac disease or symptomatic arrhythmia. The tachycardia rate ranged from 117 to 250 beats/min and lasted up to 65 seconds. Arrhythmia evaluation in five of the patients suggested catecholamine-sensitive ventricular tachycardia. This diagnosis was supported by either a positive relation to exercise or isoproterenol infusion, suppression of arrhythmia by beta-blockade or sleep, and lack of induction of arrhythmia by programmed electrical stimulation of the heart. The arrhythmias resolved in one patient soon after evaluation and in one other patient after 2 months of controlling therapy. Five other patients continued to receive therapy throughout pregnancy. Delivery was accomplished in all patients without significant maternal or neonatal complications.

Echocardiography↗

Protein kinase C impairs the coupling of the GTP-binding protein to LTB4 receptor in neutrophil.

In the present study, the mechanism of LTB4 receptor down regulation by protein kinase C (PKC) has been investigated using porcine neutrophil membranes. Pretreatment of intact porcine neutrophils with 12-O-tetradecanoylphorbol-13-acetate (TPA) for 2 min prior to the preparation of plasma membrane, demonstrated a reduced binding sites (Bmax) for LTB4 without altering the receptor affinity (Kd). This effect of TPA on LTB4 receptor binding was found to be due to the activation of PKC as membrane treated with purified PKC (type III) produced the same effect. When membranes from neutrophils pretreated with TPA were exposed to non-hydrolyzable GTP analog, GTP-gamma S, or GMP-PNP, no further decrease in receptor Kd was observed, while the Bmax was reduced to the level observed in TPA treated samples. Treatment of isolated neutrophil membranes with purified PKC reduced the Bmax and blocked the effect of GTP analogs on the receptor affinity. These results suggest that, PKC interrupts the receptor binding to G-protein.

Animals↗

Alterations in the superoxide dismutase gene of an isoniazid-resistant strain of Mycobacterium tuberculosis.

Genetic analysis of a set of six Mycobacterium tuberculosis strains differing in virulence for the guinea pig revealed an altered restriction enzyme fragmentation pattern associated with the superoxide dismutase (SOD) gene in a low-virulence, isoniazid-resistant strain. In addition, it was found that the SOD enzyme produced by the isoniazid-resistant strain differed in its electrophoretic mobility from the SOD of other M. tuberculosis strains. Detailed analysis of these strain-specific differences showed that the restriction fragment length polymorphism resulted from the presence of a copy of a repetitive element 552 bp upstream of the SOD gene and that the anomalous electrophoretic mobility arose from a single nucleotide change, resulting in replacement of an aspartic acid residue by histidine in the SOD enzyme of the isoniazid-resistant strain. Possible relationships between genetic changes and strain-dependent differences in virulence are discussed.

Animals↗

Distinctive western blot antibody patterns induced by infection of mice with individual strains of the Mycobacterium avium complex.

Systemic infection of mice with organisms of the Mycobacterium avium complex (MAC) induced antibody responses, characteristic for each of the three tested individual strains. The influence of host genetic factors was reflected up to 3 months after infection by the finding of generally oligobanded and multibanded Western blot patterns in C57B1/6 and BALB/c mice, respectively. Nevertheless, more bands developed at 6 months in C57BL/6 mice. The response to three antigens of 18,000, 38,000 and 24,000 MW was analysed in greater detail. Antibodies to a protease-resistant 18,000 MW band produced only by BALB/c mice were either strain specific, following infection with M. avium, strain Maa-B2, or cross-reactive within MAC, following infection with M. avium strain Maa-A6 and M. paratuberculosis, strain Map-203. Another protease-resistant antigen of 38,000 MW was immunogenic only in Maa-B2 infected mice. This constituent was found to be related to the protease-sensitive antigen of corresponding molecular weight from M. tuberculosis. Two 24,000 MW proteins of M. paratuberculosis were separated by two-dimensional gel electrophoresis: antibodies to the anodic band were induced by Map-203 infection, whilst the cathodic band was revealed by heteroclitic antibodies from Maa-B2-infected mice. The latter antigen is apparently expressed during in vivo replication, but not during in vitro culture of Maa-B2 bacteria. We generally conclude, that the selective antibody patterns after live infection, could be attributed to differences in the release of native antigens within mycobacterial lesions. In view of a high degree of species specificity, some of the immunogenic constituents identified may also be useful for serodiagnostic application.

Animals↗