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Biomedical subjects

M McGregor

Publications and source records attributed to M McGregor.

At least 19 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

The cost-effectiveness of replacing high-osmolality with low-osmolality contrast media.

OBJECTIVE: Our purpose was to assess the cost-effectiveness of substituting low-osmolality contrast media for high-osmolality media in noncardiac parenteral use in radiology. MATERIALS AND METHODS: Estimates of effectiveness, taken as the reduction in risks of reactions affecting safety and comfort, were based on a recent meta-analysis of data published since 1980. Costs were those of the contrast medium and of treating reactions. RESULTS: One hundred thousand uses of low-osmolality media instead of high-osmolality media would cost an additional $7.7 million. No deaths would be prevented, but there would be 80% fewer life-threatening events and 75% fewer minor reactions. Considering only life-threatening events, complete conversion to low-osmolality media costs $62,000 per event prevented. If only minor reactions are considered, this figure is $800 per event prevented. The cost-effectiveness of partial substitution of low-osmolality media in "high-risk" patients only cannot be estimated with confidence. With one set of assumptions, a 33% reduction in life-threatening reactions at a cost of $22,000 per event prevented is estimated. These estimates are insensitive to all inputs except the cost differential between high- and low-osmolality media: for every dollar decrease in cost differential per use, the cost per life-threatening event prevented drops by $790. CONCLUSION: The allocation of limited resources requires the best available information on the relevant costs and benefits. A policy of substitution of low- for high-osmolality media will not influence mortality and will bring fairly small benefits at a considerable cost.

Contrast Media

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

Differences in treatment history with manipulation for acute, subacute, chronic and recurrent spine pain.

Preference for treatment protocols used in the care of spine disorders are based more upon clinical impressions than upon systematic study of the pathology or treatment efficacy. As social emphasis moves to cost containment strategies, quantitative data is necessary to give guidance for rational policy decisions. This study sets a description of the clinical experience obtained in a group practice, teaching clinic engaged in management of spine disorders. The same subjects were separately reported as being broadly representative of those seen in private using a cash payment policy. Clinical characteristics were quantified on 241 patients. A total of 149 volunteered to complete follow up evaluations. The total number of treatment sessions were tallied to case resolution on all 241 patients and were evaluated by stratifying them according to chronicity of the chief complaint. The range of treatment for all cases was 1-22. Chronic complaints required the most care, with a mean of 8.2 sessions (F = 2.833, p = .014). Thoracic disorders required approximately half the care as lordotic spine regions (F = 2.372, p = .04). No differences were observed based upon descriptive classifications of entrapment, mechanical or muscular pain. All but 25 cases reached resolution well within 6 wk, requiring a mean of 3.8 (range 1-11) additional treatment sessions.

Acute Disease

Clinical features and treatment of obstructive sleep apnea.

OBJECTIVE: To review the clinical features and treatment of obstructive sleep apnea (OSA). DATA SOURCE AND SELECTION: All articles on OSA published in French and English between 1970 and 1990 and indexed in Index Medicus were reviewed. Studies addressing the epidemiologic features and clinical aspects of OSA were selected, and special emphasis was given to articles reporting the effects of treatment on morbidity and mortality rates. MAIN RESULTS: OSA is characterized by episodes of upper airway obstruction during sleep that result in repetitive hypoxemia and sleep disruption. OSA leads to various neuropsychologic and cardiovascular complications, including daytime hypersomnolence, cognitive impairment, systemic and pulmonary hypertension and cardiac arrhythmias. There is suggestive evidence that the death rate among affected people is increased. The true incidence of OSA is unknown, but estimates have varied from 1% upwards among men. The current treatment with the greatest overall effectiveness and acceptability is nasal continuous positive airway pressure. CONCLUSION: This common, readily treatable disorder is associated with serious complications and therefore must be widely recognized by health professionals.

Arrhythmias, Cardiac

The risks of death and of severe nonfatal reactions with high- vs low-osmolality contrast media: a meta-analysis.

Estimates of the risks associated with the use of radiologic contrast agents frequently are based on a subjective review of some of the numerous articles that have been published on the subject. We have chosen instead to synthesize the existing evidence in an objective, quantitative way by statistically combining the data from individual studies through meta-analysis. Although meta-analysis is subject to whatever biases may exist in the underlying data, and may inappropriately pool data from studies with significant differences, the estimates draw proportionately from each original study and, in addition, gain considerable precision owing to the increased amounts of data considered. Using this technique, we analyzed the data from all available original reports appearing since 1980. Crude rates derived from all reports were used to estimate risks with high-osmolality media. Weighted rate differences based on comparative studies only were used in the estimation of the reductions in risk obtainable with low-osmolality media. The risk of death with high-osmolality media was 0.9 per 100,000 uses (95% confidence interval, 0.3-2.6 per 100,000). The difference in risk produced by using low-osmolality media was 0 (95% confidence interval, -1.1 to 1.1 per 100,000). The risk of severe reactions associated with high-osmolality media was 157 per 100,000 uses (95% confidence interval, 144-172 per 100,000). The reduction in risk that can be obtained by the use of low-osmolality media was estimated to be 126 per 100,000 (95% confidence interval, 110-142 per 100,000). This meta-analysis shows that the risk of death is very low with either type of contrast material and that there is no difference between them. Severe nonfatal reactions with high-osmolality media, although more frequent, are still rare; approximately 80% of them can be prevented by using low-osmolality media.

Contrast Media

Enhanced phagocytic cell respiratory burst induced by spinal manipulation: potential role of substance P.

The effect of spinal manipulation on the respiratory burst of polymorphonuclear neutrophils (PMN) and monocytes from treated adults was measured by zymosan-stimulated chemiluminescence (CL). Peripheral blood was collected 15 min before and 15 min after treatment (sham manipulation, thoracic spine manipulation, or soft tissue manipulation), the cells were isolated, challenged with a standardized, opsonized luminol-containing suspension of zymosan, and monitored for CL. Plasma from two subsets of subjects was radioimmunoassayed for Substance P (SP). PMN were also preincubated with SP in vitro over the dose range 5 x 10(-12) M to 5 x 10(-8) M and the CL response monitored. The CL responses of both PMN and monocytes from subjects who received spinal manipulation were significantly higher after than before treatment, and significantly higher than the response in sham or soft-tissue treated subjects. Measurement of the force applied by sham and spinal manipulation suggested a force threshold for the enhancement of the CL response. Plasma levels of SP before and after treatment in sham treated subjects did not differ significantly; however, elevated plasma SP was observed in subjects after spinal manipulation. Preincubation of PMN with 1 x 10(-11) M, 5 x 10(-11) M or 1 x 10(-10) M SP in vitro primed PMN for an enhanced respiratory burst when the cells were subsequently challenged.

Adult

The role of experience in clinical accuracy.

A randomized controlled trial was performed to study the effect of various teaching techniques on students performing sacroiliac motion palpation tests. This trial assessed the interexaminer reliability of interns in their final year at a chiropractic college, and compared their results prior to and following 1 year of clinical experience. The study also compared the intra- and interexaminer reliability of experienced clinicians. The results were analyzed via the Kappa coefficient. Kappa values for interns ranged from 0.00 to 0.30, with no significant differences noted at the end of 1 year of clinical experience. The interexaminer reliability of experienced clinicians was 0.00 to 0.167, whereas their intraexaminer reliability ranged from 0.15 to 1.00. These results question the role of experience in improving clinical accuracy between examiners performing sacroiliac motion palpation. Results analyzed for intraexaminer agreement were moderate to almost perfect. We conclude that experience does not play a significant role in the diagnostic test analyzed, but rather that clinicians may establish their own criteria by which to determine the standards of a given test.

Chiropractic

New growth elicited in adult leech mechanosensory neurones by peripheral axon damage.

1. New growth in cutaneous mechanosensory neurones elicited by axotomy or axon crush was studied using intracellular injection of horseradish peroxidase at different times after the lesion, ranging from a few days to over a year. 2. Cutting or crushing major, large-calibre axon branches of mechanosensory neurones elicits sprouting of new processes, either centrally within the ganglion neuropile or at the site of the lesion in the peripheral nerve. In contrast, cutting or crushing fine-calibre axon branches supplying accessory parts of the receptive field does not elicit sprouting of the main arbor or main axon branches. 3. Different modalities of mechanosensory neurone respond differently to lesions of their axons. Cutting the axons of high-threshold units responding to noxious stimulation of the skin elicits sprouting of additional processes from the axon hillock region within the central nervous system (CNS), whereas cutting or crushing the axons of low-threshold cells responding to light touch of the skin elicits sprouting at the site of the lesion only, and not within the CNS. 4. In addition to the new growth directed into the peripheral nerve, damaged nociceptive neurones also form new processes that wrap the somata of particular cells within the ganglion. 5. Sprouted processes of axotomized neurones are retained for long periods after the lesion (up to 425 days). 6. The electrical properties of touch and nociceptive cells were studied between 1 and 60 days after axotomy, by intracellular recording from the centrally located cell bodies. The amplitude, width and maximum dV/dt of the action potential and after-hyperpolarization, as well as the resting potential and input resistance, did not change significantly after axotomy, despite the considerable process sprouting known to occur during this time.

Action Potentials

Restoration of flow in acute coronary obstructive syndromes: consequences of different management strategies.

Although much necessary evidence is not yet available, there is sufficient information from recent therapeutic trials to necessitate a nationwide review of the management of acute coronary obstructive syndromes. On the basis of present information it is evident that, in addition to heparin, all patients suffering from suspected acute myocardial infarction should receive immediate low dose aspirin which should be continued for one to six months. This treatment, if generally applied, can be expected to save 1200 lives per year in Canada at negligible cost. Addition of intravenous streptokinase infusion to all patients (in whom there are no contraindications) available for treatment from 0 to 24 h from the onset, can be expected to save an additional 1088 lives at an additional cost of approximately $11,000 per life. Other thrombolytic agents involve additional cost and the gains in terms of mortality are not yet demonstrated. The evidence for thrombolytic treatment in acute unstable angina is still uncertain but the treatment of all cases with aspirin from the earliest possible moment is clearly indicated.

Angina Pectoris