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Biomedical subjects

M McGregor

Publications and source records attributed to M McGregor.

10 recordsLinked to original sources

The effect of auxiliary conditions on intestinal unstirred layer diffusion modelled by numerical simulation.

Estimation of intestinal unstirred layer thickness usually involves inducing transmural potential difference changes by altering the content of the solution used to perfuse the small intestine. Osmotically active solutes, such as mannitol, when added to the luminal solution diffuse across the unstirred water layer (UWL) and induce osmotically dependent changes in potential difference. As an alternative procedure, the sodium ion in the luminal fluid can be replaced by another ion. As the sodium ion diffuses out of the UWL, the change in concentration next to the intestinal membrane alters the transmural potential difference. In both cases, UWL thickness is calculated from the time course of the potential difference changes, using a solution to the diffusion equation. The diffusion equation solution which allows the calculation of intestinal unstirred layer thickness was examined by simulation, using the method of numerical solutions. This process readily allows examination of the time course of diffusion under various imposed circumstances. The existing model for diffusion across the unstirred layer is based on auxiliary conditions which are unlikely to be fulfilled in the same intestine. The present simulation additionally incorporated the effects of membrane permeability, fluid absorption and less than instantaneous bulk phase concentration change. Simulation indicated that changes within the physiologically relevant range in the chosen auxiliary conditions (with the real unstirred layer length kept constant) can alter estimates of the apparent half-time. Consequently, changes in parameters unassociated with the unstirred layer would be misconstrued as alterations in unstirred layer thickness.

Gastrointestinal Contents

Processing of the herpes simplex virus assembly protein ICP35 near its carboxy terminal end requires the product of the whole of the UL26 reading frame.

The herpes simplex virus (HSV) type 1 assembly protein ICP35 consists of a family of polypeptides, ranging in molecular weight from about 45,000-39,000. The lower molecular weight forms of ICP35 are derived from the higher molecular weight species by slow post-translational modification. The reading frame of gene UL26 and the region within this gene which exhibited homology to the cytomegalovirus assembly protein, the analogous protein to ICP35, were expressed separately under immediate-early (IE) gene regulation in a HSV vector containing a temperature-sensitive mutation in the major transcriptional regulator Vmw175. Monoclonal antibody specific for ICP35 immunoprecipitated several polypeptides with molecular weights around 75,000 from extracts of cells infected with a recombinant expressing the IE gene UL26 at the nonpermissive temperature (NPT). These results suggested that the UL26 gene specified a protein distinct from ICP35 but which had some antigenic sites in common with ICP35. In extracts of cells infected at the NPT with a recombinant expressing only the carboxy terminal half of UL26 coding sequences, the monoclonal antibody immunoprecipitated large amounts of the high molecular weight forms of ICP35. The lower molecular weight processed forms of ICP35, however, were not detectable. When cells were coinfected with both recombinants ICP35 was processed to its lower molecular weight forms. This processing step, which occurred near the carboxy terminus of ICP35, was not dependent on capsid formation. The work, together with previous information on the processing of the CMV assembly protein, suggests that UL26 product may be a protease.

Animals

Enhanced neutrophil respiratory burst as a biological marker for manipulation forces: duration of the effect and association with substance P and tumor necrosis factor.

A critical need in assessing the clinical utility of manipulative therapy for back pain is the identification of biological changes associated with the forces applied by spinal manipulation. Such changes could then serve as markers for both sham treatment and manipulation. We determined the priming of polymorphonuclear neutrophils for an enhanced respiratory burst and its duration, the priming of mononuclear cells for enhanced endotoxin-stimulated tumor necrosis factor production and plasma levels of substance P following a single thoracic spine manipulation. There was a significant difference in the respiratory burst of polymorphonuclear neutrophils in response to a particulate challenge, depending on the time of blood sample collection. The response of polymorphonuclear neutrophils isolated from blood collected 15 min after manipulation was significantly higher than the response of cells isolated from blood collected 15 min before and 30 and 45 min after manipulation. Mononuclear cells were also primed for enhanced endotoxin-stimulated tumor necrosis factor production by spinal manipulation. Both of these priming effects were accompanied by a slight, but significant elevation in plasma substance P. The mean manipulation force associated with these biological effects was 878 +/- 99 N. These biological effects may provide a means of monitoring the delivery of both sham and manipulative treatment and, therefore, provide a crucial tool for understanding the efficacy of manipulative therapy.

Adult

The reuse of cardiac pacemakers.

OBJECTIVE: To provide decision makers with a synthesis of the relevant information concerning the safety of pacemaker reuse, the ethical and legal issues which it raises and the extent of financial savings which may result. DATA SOURCES: Medline data bank and the bibliographies of review articles in English concerning refurbishment and reuse of cardiac pacemakers published up to June 1991. DATA SYNTHESIS: Since 1978, reports of safe reuse of pacemakers have appeared in 11 countries. By 1984, review of nearly 2000 installations had produced no evidence of increased mortality or morbidity. The norms which must be respected to ensure safety are now well-known. The savings that might result from reuse can only be approximated. In Canada in 1989, 8684 pacemakers were installed. Assuming that 20% might be available for reuse, this practice might save approximately $4,000,000 per year to the Canadian health care system. CONCLUSIONS: Properly carried out, pacemakers can be reused at an acceptably low risk. Any institution contemplating pacemaker reuse should define and approve appropriate guidelines and protocols governing the process. A registry to document the reuse of pacemakers for the next few years is desirable.

Bacterial Infections