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Biomedical subjects

I C MacDonald

Publications and source records attributed to I C MacDonald.

54 records · Page 3Linked to original sources
PubMed1982

Direct arteriovenous connections and the intermediate circulation in dog spleen, studied by scanning electron microscopy of microcorrosion casts.

The exact nature of the circulatory pathways in dog spleen, particularly with reference to the intermediate circulation and the possible existence of direct arteriovenous connections, has been studied by scanning electron microscopy (SEM) of microcorrosion casts. A new casting procedure was developed in which minimal amounts of material were injected into contracted spleens, thus filling preferentially the faster channels for flow. Extensive filling of the red pulp was thereby avoided, leaving an open view of blood vessels and their connections. The depth of focus of the SEM, incomparably greater than those of transmission electron or light microscopes, enabled vascular pathways to be traced over considerable distances. Using this approach, we have obtained clear evidence for abundant connections between arterial capillaries and venous sinuses (i.e., "closed" circulation). Typically, the terminal arteriole bifurcates repeatedly, in quick succession, giving rise to as many as twelve short capillaries, each leading directly to at least one sinus. However, an "open" circulation also exists, inasmuch as the majority of all capillaries end in the marginal zone around lymphatic nodules. In the dilated spleen, direct connections to sinuses are rarely visible but endings in the red pulp are found, in addition to those going to the marginal zone.

Animals↗
PubMed1981

Daily energy expenditure of young boys as related to maximal aerobic power.

Daily energy expenditure, and participation in regular physical activity over one year, were determined in 28 boys (age 12.3 years) by (1) heart rate (fh) recorded on an oxford Medilog tape recorder and used to approximate energy expenditure using individual fh-VO2 relationships established from a standard step test; total daily average energy expenditure, time spent, and energy expended in activity above a defined threshold, training fh = (.6 (fh max - fh rest) + fh rest) and, (2) a questionnaire designed to determine involvement in regular physical activities over the preceeding year. Maximal oxygen uptake (2.47 +/- 0.36 l-min-1) was measured on a treadmill test. A step-wise multiple regression analysis was used to describe the association between maximal aerobic power and the measures of body size (wt. - 43.8 kg, ht. - 152.2 cm), fatness (sum of skinfolds -67.4 mm), daily energy expenditure (11.66 MJ), and participation in regular physical activity. Body mass and fatness made the only significant contributions to the variance (R2 = 0.77). The relationship was VO2 (l.min-1) = 0.47 (body mass- kg) -0.04 (sum of 6 skinfolds) + 0.71. Measures of daily energy expenditure, the time the heart rate was above a training threshold, and the number of regular physical activities, added little to the measured variance (R2 = 0.78) above that accounted for by body mass amd fatness.

Adolescent↗
PubMed1980

Comparison of reactive hyperemia in warm and cool human forearms over a range of ischemic periods.

The characteristics of reactive hyperemia in the warm human forearm are well documented but comparable data at lower temperatures are sparse. The present study was designed to examine reactive hyperemia in the forearms of 8 subjects using a range of ischemic periods of 0.5, 1, 2, 4, and 8 min at plethysmograph temperatures of 34 degrees and 14 degrees C. The peak flow rates and hyperemic volumes following all of the durations of ischemia were significantly lower at 14 degrees C. There was a proportional relationship between the hyperemic volume and the duration of ischemia at both temperatures. The difference noted in the magnitude of the responses at the two temperatures may be explained by a reduction in the rate of metabolism in the forearm at the lower temperature, but reduced vascular distensibility cannot be excluded.

Adult↗
PubMed1978

Abnormalities of the gait occurring during recovery from fractures of the lower limb and their improvement during rehabilitation.

The gait patterns of 19 patients recovering from fractures of the lower limb were analysed using a metal track on which patients walked in shoes fitted with metal contacts. The technique demonstrated marked abnormalities of the gait when patients were admitted to a rehabilitation unit, with an overall reduction of the extent of these abnormalities during treatment. Marked improvements of gait occurred whilst the patients were walking with the aid of crutches. However, little improvement occurred whilst the patients walked with sticks, but when sticks were discarded further marked improvements occurred.

Adolescent↗
PubMed1977

Accidental hypothermia and impaired temperature homoeostasis in the elderly.

A longitudinal study of the age-related decline in thermoregulatory capacity was made in 47 elderly people to try to identify those at risk from spontaneous hypothermia. During the winters of 1971-2 and 1975-6 environmental and body temperature profiles were obtained in the home, and thermoregulatory function was investigated by cooling and warming tests. Environmental temperature and socioeconomic conditions had not changed but the body core-shell temperature gradients were smaller in 1976, indicating progressive thermoregulatory impairment. People at risk of developing hypothermia also seem to have low resting peripheral blood flows, a nonconstrictor pattern of vasomotor response to cold, and a higher incidence of orthostatic hypotension.

Aged↗
PubMed1977

A study of exercise performance and heart rate: the response to exercise of a small group of manual workers before and after retirement.

Measurements of walking pattern, exercise performance, heart rate response to exercise and body composition have been made in 13 male manual workers at retirement and again one and two years later. The exercise consisted of walking, in accordance with standard instructions; heart rate and footfall signals were recorded on magnetic tape during the test using body-borne tape recorders. After the first year highly significant reductions in walking speed were found but no significant changes in walking pattern, heart rate response or body composition. When the measurements made at the end of one year of retirement were compared with those made at the end of two years no significant changes were found.

Aged↗
PubMed1976

Self-paced walking as a method for exercise testing in elderly and young men.

1. An exercise test has been developed which is suitable for elderly or frail subjects. It is based on free walking at three different speeds on a level indoor course of 256m. The subject sets his own pace in accord with simple instructions. 2. Twenty-four elderly men and ten young men took part in the study. 3. The time and number of paces taken to cover two sections of 100m within the course were used to establish that the subjects walked steadily. Walking speed, pace frequency and stride length were then calculated. 4. Heart rate was obtained with body-borne tape recorders and related to the walking speed. The heart rate at a standard walking speed could then be obtained by interpolation. This is an assessment of the cardiovascular response to exercise (physical condition). The variation on repeating the test was +/-5 per cent and there was no significant difference between the two age groups. 5. The assessment was found to correlate moderately well with a conventional assessment of physical condition based on oxygen uptake from tests on a bicycle ergometer. 6. The test could also be used as a performance index since walking speed was characteristic for the subject. The younger group walked significantly faster than the older group. As a performance index the test is therefor sensitive to age differences.

Adult↗
PubMed1976

Energy expenditure during walking in patients recovering from fractures of the leg.

The oxygen consumption during walking has been studied in 13 patients recovering from fractures of the leg and in 8 control subjects. Oxygen consumption of normal subjects when walking at velocities of 0.5, 1.0 and 1.5 m sec-1 was 8.0, 9.8 and 13.6 ml kg-1 min-1 respectively. For subjects walking on crutches with the leg encased in a Plaster of Paris cast, the oxygen consumption at these velocities was 12.0, 17.5 and 25.3 ml kg-1 min-1 respectively. The energy cost of walking was reduced when the cast was removed, when the crutches were replaced by sticks and when all aides were discarded. When all aids had been discarded the energy expenditure was normal at 0.5 and 1.0 m sec-1 but was still significantly higher at faster velocities.

Adult↗
PubMed1975

Thermoregulation during marathon running in cool, moderate, and hot environments.

A well-trained subject, age 38, ran continously for periods ranging from 60 to 165 min on a motor-driven treadmill at 255.7 m/min while confronted with an airflow equivalent to running speed in cool, moderate, and hot environments. After a period of intensive heat acclimatization, treadmill runs were repeated in the moderate and hot conditions. Measurements were also obtained outdoors in a competitive marathon race. Sweat rate (SR) and mean skin temperature (Ts) were linearly related to Tdb. Acclimatization did not alter VO2max or metabolic rate during the treadmill runs, but heart rat (HR),rectal temperature (Tre), and Ts were lower, SR was higher, and maximal run duration longer in the hot environment, postacclimatization. Maximum runs in the hot environment were terminated by a spiralling increase in Tre to hyperthermic levels, due largely to a marked reduction in cutaneous blood flow, probably reflecting cardiovascular overload from the combined muscular and thermoregulatory blood flow demands, coupled with the effects of progressive dehydration. Utilizing partitional calorimetry and the subject's metabolic heat production, two examples of limiting environmental conditions for his marathon running speed were given.

Acclimatization↗
PubMedDate not supplied

Morphologic sites for regulating blood flow in the exocrine pancreas.

The exocrine pancreas has a lobular structure and an intricate capillary network supplies the lobules. Casts of these capillaries are either straight and of constant width, provided with many shallow crests, or undulating and of varying diameter, provided with bulges and deeper constrictions. The mean capillary cast diameter is 6.32 microns (SD 0.53) and 3.91 microns (SD 0.84) at constriction sites. The first type corresponds to non-fenestrated capillaries, makes 24% of capillaries and is more frequently provided with pericytes (2.7 +/- 0.9 pericytes per capillary profile). The second type corresponds to fenestrated capillaries, comprises 76% of the capillaries and is less frequently provided with pericytes (1.5 +/- 0.6 pericytes per capillary profile). The endothelial cells of capillaries regularly form intermediate junctions and microvilli and contain microtubuli and cytoplasmic filaments. Intravital observations show that capillaries are capable of contracting and narrowing the capillary lumen. This contractility is accomplished by endothelial cells both at and apart from their nuclear regions while pericytes never contracted spontaneously during our in vivo observations. The capillary diameters estimated by intravital measurements, 3.53 microns (SD 1.05), are similar to cast measurements but differ at constricted segments from cast measurements. Flow reduction shows more variability in smaller capillaries and the flow is more reduced in capillaries of 5 microns diameter to about 40% of open capillaries vs. 68% in capillaries with 7.5 microns diameter. Veins are either provided with smooth muscle sphincters or with valves. These results indicate that corrosion casting accurately shows the geometry of capillaries. However, where the capillaries are drastically constricted, they might not be filled and therefore may be underestimated during measurements. Since none of the intravital luminal constrictions are small enough to reduce flow (smaller than 1 micron luminal diameter) and because many constrictions are effective to reduce flow, we conclude that capillaries of the exocrine pancreas are always capable of maintaining continuous blood flow yet can influence blood perfusion. The presence of venous valves in association with venous sphincters constitutes a new situation concerning blood drainage regulation in the exocrine pancreas.

Animals↗
PubMedDate not supplied

Preclinical assessment of anti-cancer therapeutic strategies using in vivo videomicroscopy.

Preclinical in vivo studies of agents targeted against metastasis have to date been based primarily on end-point assays. Such assays can determine whether a treatment affects the number or size of metastases in an organ at a given time, but are poorly suited to determining how and at what stage in the process the treatment affected the end point. High resolution in vivo videomicroscopy permits direct observation of the process of metastasis as it occurs in living animals over time. Studies based on this technique and a cell accounting procedure we have devised, have shown that early steps in the metastatic process (survival in the circulation, extravasation) contribute relatively little to cell loss and metastatic inefficiency. Steps that occur after extravasation appear to be primarily responsible for the significant losses that result in metastatic inefficiency, and these steps may represent good targets for the design of new antimetastatic therapies. Matrix metalloproteinases have been implicated functionally in metastasis, and are viewed as an appropriate target in the development of inhibitors of metastasis. Using both endogenous and synthetic exogenous metalloproteinase inhibitors, we have shown that the inhibition of metastasis which these agents produce is not due to inhibition of cell extravasation from the circulation into the tissue, but to reduction of angiogenesis within metastases. A similar conclusion was reached concerning the mechanism of action, on metastasis, of carboxyamidotriazole, an inhibitor of calcium-mediated signal transduction which is currently in Phase II single agent clinical trials. In vivo videomicroscopy of sequential steps in metastasis, coupled with methods that allow precise quantification of cell loss at specific steps in the metastatic process, as well as standard histological assessment at stages identified as crucial, allow characterization of the details of metastasis as an ongoing process. This provides a powerful complement to end-point assays, for it allows mechanistic information to be obtained from in vivo experiments, an approach which provides better understanding of how and when a drug may function in vivo to inhibit metastasis.

Animals↗