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Biomedical subjects

D H Lewis

Publications and source records attributed to D H Lewis.

At least 73 records · Page 4Linked to original sources

Lipid peroxidation products in postischemic skeletal muscle and after treatment with hyperbaric oxygen.

Earlier studies from our laboratory have shown that hyperbaric oxygen (HBO) treatment reduces edema, enhances aerobic metabolism and improves the recovery of the phosphorylase activity in postischemic rat skeletal muscle. However, as it has become increasingly apparent that oxygen in excess may have harmful effects, it was of interest to study if HBO caused an increased formation of oxygen free radicals. Toxic peroxides, as a result of oxygen free radicals, were quantitated in the postischemic skeletal muscle of rat and with HBO treatment by measuring the thiobarbituric acid reaction which includes the lipid peroxides and the alkydes including malondialdehyde (MDA), a key intermediate in the formation of peroxides. A tourniquet model of temporary ischemia of the rat hindlimb was used for 3 hours. Muscle biopsies were taken at various intervals before and after tourniquet release with and without hyperbaric oxygen at 2.5 atmospheres absolute (ATA) for 45 min after tourniquet release. Three hours of anesthesia caused a significant rise of thiobarbituric acid reactive material (TBAR) concentration in muscle compared to normal controls without anesthesia. An increase of similar magnitude was seen after 3 hours of ischemia, with or without reperfusion. These values were normalized after 45 min. HBO in the postischemic phase did not cause a further increase in the TBAR concentration in muscle immediately postischemically. However, the levels remained increased at 45 min after the onset of reperfusion, immediately after HBO treatment and had returned to normal values 2 hours postischemically.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

The effect of trauma to the leg on the first-pass uptake of bacteria by the lung.

Our previous studies have shown that the first-pass pulmonary uptake of lidocaine and serotonin were not impaired by bullet wounding of the leg. Since there is decreased resistance to bacterial infection with trauma, it was of interest to study the uptake of bacteria. First-pass pulmonary uptake of 51-chromium-labeled, killed Salmonella typhimurium bacteria was studied in 26 pigs. In 16 controls, four injections at hourly intervals revealed an initial uptake of 84.5% +/- 1.5 (Mean +/- S.E.M.) and a 95% first-pass uptake of 78.6% +/- 2.4, and no significant change with time. In the ten traumatized animals only the values at 5 hours were significantly lower than the controls. It is concluded that repeated injections of killed Salmonella typhimurium bacteria without trauma do not interfere with the ability of the lung to remove these bacteria during their first passage through the lung, but that with trauma to the leg do to a slight degree.

Animals↗

Effects of endotoxin-induced lung injury on the pharmacokinetics of prostaglandin E2 and adenosine in rat isolated lung.

Endotoxin injected intraperitoneally caused leucopenia and pulmonary oedema in rats. These effects were spontaneously reversed over the 28 h after the single dose of endotoxin. The pharmacokinetics of three substrates, 14C-sucrose, 3H-prostaglandin E2 (PGE2) and 3H-adenosine, were measured in perfused lungs isolated from rats at different times after treatment with endotoxin. The efflux kinetics of radiolabel derived from sucrose and adenosine were little affected, but that from PGE2 was markedly changed. The metabolism of PGE2 was also decreased. The change in PGE2 pharmacokinetics preceded the pulmonary oedema, but both pharmacokinetics and oedema returned to normal at the same time (28 h after endotoxin). It may be feasible to use PGE2 pharmacokinetics as a biochemical index for early warning of acute lung injury caused by sepsis.

Adenosine↗

Fine structure of the human skeletal muscle capillary. A morphometric analysis.

Capillary dimensions in muscle biopsies from human musculus quadriceps femoris, sectioned at right angle to the muscle fibers, were analysed with a computerized planimetric technique giving distributions of dimensional parameters with statistics. Without corrections for estimated preparative shrinkage mean maximal diameter of lumen was 3.82 +/- 0.82 microns (5.31 +/- 1.14 micron shrinkage corrected), mean second maximal diameter, at right angle to maximal, 2.61 +/- 0.72 microns (3.62 +/- 1.00 microns corr.) and mean endothelial thickness in nuclear free sections 0.35 micron (0.49 micron corr.) micron. Using a capillarity of 360/mm2 for the human m. quadriceps femoris, the total surface area of skeletal muscle capillaries was calculated to be 5.50 X 10(3) cm2/100g and the total volume of the capillary network in the muscle to be 0.48 cm3/100g.

Adolescent↗

The effect of prolonged total ischemia on the ultrastructure of human skeletal muscle capillaries. A morphometric analysis.

Human skeletal muscle shows reflow impairment after prolonged tourniquet ischemia of 1-3 hours, increasing with the duration of ischemia. A sample of 275 cross-sectioned capillary profiles from muscle biopsies of human m. quadriceps femoris made totally ischemic by tourniquet for 90-180 minutes (mean 110 min.) from 5 patients during surgery, show frequent evidence of ultrastructural damage to microvascular membranes and organelles. Frequency analyses demonstrate a significant increase in damage during ischemia (p = 0.03), but not increasing further following 5 min of reperfusion. One of the signs of ischemic damage was endothelial swelling, found in some endothelial cells, lying next to ultrastructurally intact ones. The swelling found cannot be explained by a general loss of volume control of the microvascular endothelium during ischemia, since a computerized morphometry on the entire sample shows a preserved capillary wall thickness during ischemia and following reperfusion. During reperfusion the capillaries dilate with an increase in median max. diameter from 3.4 micron (4.7 micron shrinkage-corrected) to 3.9 micron (5.4 corr.) (p less than 0.001), despite reported reperfusion impairment. However, since capillaries in skeletal muscle consist of 20-40 endothelial cells, a distribution of such localized endothelial swelling or luminal membrane changes in a few percent of the microvascular endothelial population after ischemia, trapping leucocytes, would affect microvascular hydraulic conductance to reperfusion.

Adult↗

The surgical and orthodontic management of unerupted teeth in cleidocranial dysostosis.

A common feature of patients with cleidocranial dysostosis is delayed shedding of deciduous teeth and failure of eruption of the permanent dentition. This article describes a method whereby orthodontic forces may be applied to these unerupted permanent teeth to move them into a satisfactory functional and aesthetic position with good periodontal support whilst maintaining their vitality. This method of treatment avoids the need for overdentures or other prosthetic aids which have often been used in the past.

Adolescent↗

Skin blood flow in relation to external pressure and temperature in the supine position on a standard hospital mattress.

The purpose of this investigation was to study the relationship between skin blood flow, external pressure and temperature in the skin over bony prominences and muscle padded areas, when healthy individuals and patients with hemiplegia were lying in the supine position on a standard hospital mattress. The pressure values under the gluteus maximus muscle and the sacrum increased significantly in the supine position with bent knees. The heels resting on the mattress gave very high pressure values. Some patients had no observable skin blood flow in the skin over the sacrum and the gluteus maximus muscle. In many individuals there was no observable blood flow in the skin over the heel among both healthy individuals and patients, which was confirmed by very high post-ischemic reactive hyperaemia. There is also a heat accumulation when lying on the mattress which increases the requirement for skin blood flow.

Adult↗

Hemodynamic and biochemical changes in severe induced subtotal ischemia of the leg. Studies with a pig model.

To investigate hemodynamic and biochemical changes in acutely ischemic leg muscle, the arterial flow to one hind leg was reduced to 5% of resting flow in nine pigs. Blood sampled from the aortic arch and femoral vein before and during ischemia and during 2.5 hours of reperfusion was analyzed and blood flow was measured in the femoral artery. The flow increased to 140% of preischemic values after 10 min of reperfusion and thereafter normalized. Efflux of potassium, magnesium, CK, LDH and ASAT increased only slightly during ischemia, but responded immediately to reperfusion, with maxima at 2-10 min, and thereafter declined to around normal values. Venous pH in the leg fell in the first 2.5 hours of ischemia (7.32-7.11), then remained constant until reperfusion started, when a nadir of 6.99 was reached, and rose to 7.29 by the end of the study. O2 consumption in the leg increased 3.8 times from preischemia to 1 min after reperfusion. Control pigs did not show the mentioned changes. This standardized ischemic trauma resembles the situation in humans with severe unilateral leg ischemia and can facilitate investigations of response to medication.

Animals↗

Muscle metabolic changes in induced subtotal ischemia of the leg in a pig model.

In nine pigs the arterial blood flow to one hind leg was reduced to 5% of resting values during 8 hours in order to study changes in muscle energy metabolism. Biopsy samples from the gastrocnemius muscle were analyzed for ATP, ADP, AMP, PC, Cr, lactate, pyruvate, glycogen and pH before ischemia, at the end of the ischemic period and during 2.5 hours of reperfusion. During ischemia ATP/TCr decreased to 25%, ECP to 80% and PC/TCr to 6% of preischemic values. Lactate increased eightfold and glycogen fell to 40%. In the reperfusion period, lactate decreased to 1/3 of the end-ischemic value, PC/TCr showed threefold rise and ATP/Cr doubled. TCr fell to 66% of preischemic value. Other changes were not significantly affected by reperfusion. The end-ischemic values indicated severe ischemia, but some improvement of metabolism occurred during early reperfusion. The pig model is suitable for further studies aiming to improve the energy state of the cells during ischemia.

Animals↗

The ethics of animal experimentation in the field of shock and trauma research.

This is a personal review of the concepts used in deciding ethical questions as to the use of animals in research in the field of shock and trauma. There are for me ethical considerations since I feel animals can and should be used experimentally to advance the cause of the alleviation of pain and suffering amongst severely injured patients. The framework within which such decisions are to be made has been provided for us in Sweden by laws enacted some years ago. Even with ethical review by specially appointed, regional Ethical Committees there still remain problems for the individual research scientist to resolve after the dictates of his own conscience. I operate under the dictum that human life is more valuable than animal life and that I can offer up animal lives to improve the health and welfare of humans. Research in the area of shock and trauma is important, since lives are lost due to our ignorance of many aspects of the pathophysiology of the problem. The injured are often relatively young who can be restored completely to health and gainful employment. The problem is also of interest for the emerging nations of the third world, since it is often their elite who are carried from the scene prematurely. New impetus to research has been provided by the realization that the trauma itself sets in motion events which can add to the final result. Better understanding here should lead to better treatment modalities.

Animal Welfare↗

Locally applied 133Xenon for the measurement of regional cerebral blood flow (rCBF): an experimental study in the pig.

A method for measuring regional cerebral blood flow has been developed. On pig brain cortex a 1 cm2 size polyester film was placed, under which 0.6-1.3 mCi of 133Xenon in 2-4 microliter of saline was applied atraumatically. The wash-out process was registered with an external detector, and can be described as a sum of monoexponential functions. The first component of the curve, obtained by curve resolution, indicates blood flow in grey matter and the second slow component indicates blood flow in white matter. When total ischaemia was induced, there was no wash-out of the isotope. Freezing the brain after isotope application at different stages during the wash-out showed isotope in both grey and white matter. The isotope did not diffuse into the polyester film. This technique was also used in studies on the spinal medulla where white matter is outermost and grey innermost. The wash-out curve obtained consisted of only one monoexponential function; blood flow from grey matter was not present in the wash-out curve. For calculation of cerebral blood flow a modified two-compartment model was used. It is concluded that this method measures local cerebral blood flow in both grey and white matter. The method can be used clinically to measure the local cerebral blood flow during neurosurgical operations.

Animals↗