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Biomedical subjects

I C Normand

Publications and source records attributed to I C Normand.

36 records · Page 2Linked to original sources
PubMed1971

Permeability of lung capillaries and alveoli to non-electrolytes in the foetal lamb.

1. Two sets of experiments were performed on intact foetal lambs exteriorized at Caesarean section; in one set radioactively labelled test substances (inulin, sucrose, mannitol, erythritol, urea) were injected I.V. either singly or in pairs and then followed in plasma, lung lymph and alveolar liquid; in the other set labelled test substances (inulin, sucrose, mannitol, erythritol, D-serine, L-serine, D-alpha-alanine, urea, water, thiourea, N-ethylthiourea) were introduced singly, in pairs, or sequentially into alveolar liquid and their concentration followed in alveolar liquid and plasma.2. Inulin was found to cross lung capillary walls but not alveolar walls. Measurements of its concentration following injection into alveolar liquid were used to determine the volume of foetal alveolar liquid (mean = 30 ml./kg) and its rate of formation (mean = 0.036 ml./min.kg). The volume of the lung interstitial space was determined from previous experiments in which [(125)I]PVP had been injected I.V. then measured after 2 hr in lung tissue and lung lymph (mean = 10.4% foetal lung weight after withdrawal of liquid; approximately 20% wet lung tissue weight).3. Transfer constants (min(-1)) for lung capillaries (K(C)) and alveoli (K(0)) were obtained from the experimental results by compartmental analysis. Permeability constants (P(C) and P(O), cm/sec) were derived from them using estimates for capillary and alveolar areas. For lipid insoluble molecules P(C) and P(O) both increased with decreasing molecular radius, the effect being much greater for P(O) than P(C). P(O) was also shown to increase with lipid solubility of the test molecule even though molecular size increased with lipid solubility in the series tested (urea, thiourea, N-ethylthiourea).4. Analysis of the results for the lipid insoluble substances in terms of pore theory gave a value of pore radius for lung capillaries of 150 A and for alveolar walls of 5.5 A. The smallness of the pores in alveolar walls is thought to prevent proteins and other plasma solutes from penetrating alveoli, and to determine the forces which operate in the osmotic flow of water across alveolar walls.

Alanine↗
PubMed1970

Effect of asphyxia due to umbilical cord occlusion in the foetal lamb on leakage of liquid from the circulation and on permeability of lung capillaries to albumin.

1. Experiments were performed on foetal lambs, exteriorized at Caesarean section, to determine the effects of asphyxia on the leakage of liquid from the circulation and on the permeability of lung capillaries to albumin. Following a period of control observation (30-120 min) the foetus was asphyxiated by occlusion of the umbilical cord for 5-10 min and then allowed to recover while observations were continued for a further 20-80 min.2. Measurements were made of the lymph flow from the lungs, that had drained via the thoracic duct; of protein concentration in lymph and plasma; of arterial blood haematocrit, pH, P(O2) and P(CO2); and of arterial and left atrial pressures and heart rate. Human serum albumin labelled with (125)I was infused intravenously during the control period and (125)I count rates were followed in plasma and lymph throughout the experiment. Values for the transfer coefficient of albumin (E/V min(-1), i.e. interstitial fluid clearance of albumin per unit of lung interstitial fluid volume) were determined during control, cord-occlusion and post-occlusion periods.3. During cord occlusion arterial and left atrial pressure, haematocrit and plasma protein concentration all rose, returning to the control value by 20 min after release of cord occlusion. The haematocrit values indicated that about 9% of the blood volume was temporarily lost from the circulation. Lung lymph flow also increased, reaching a maximum in the 5 min period after release of occlusion and returning to the control level 15 min later. Values for E/V of albumin were at no time significantly different from those during the control period.4. It was concluded that acute foetal asphyxia produced by umbilical cord occlusion caused an increased leakage of liquid from the circulation in general. This effect was temporary and was probably due to an increase in capillary pressure during cord occlusion. The asphyxia had no persistent effect on the permeability of lung capillaries to albumin.

Albumins↗
PubMed1970

Passage of macromolecules between alveolar and interstitial spaces in foetal and newly ventilated lungs of the lamb.

1. Experiments were performed on exteriorized foetal lambs to measure transfer of macromolecules (proteins and [(125)I]PVP) between lung alveolar liquid (A(l)) and lung interstitial liquid as represented by lung lymph (L(ly)). Transfer was measured in the foetus and during a 2 hr period of positive pressure ventilation.2. In thirteen experiments [(125)I]PVP was introduced into A(l) and, after a control period, the lungs were ventilated for 2 hr. In six other experiments the [(125)I]PVP was injected intravenously; and in two of these the lungs were ventilated for 2 hr. Measurements were made of protein and of [(125)I]PVP concentration in plasma and L(ly) collected at intervals throughout the experiment, as well as in A(l) obtained before ventilation and at the end of ventilation after degassing the lung. [(125)I]PVP in the samples was separated into fractions of different Stokes-Einstein radius by gel filtration using Sephadex G-200.3. Before ventilation there was evidence of a negligible transfer of protein from L(ly) to A(l) (mean protein A(l)/L(ly) = 0.014) or of [(125)I]PVP from A(l) to L(ly) (mean [(125)I]PVP L(ly)/A(l) = 0.00017). The effect of ventilation for 2 hr was to produce an increase in both ratios, but by a variable amount (after 2 hr ventilation mean protein A(l)/L(ly) = 0.70 +/- 0.08 (S.E. of mean) and mean [(125)I]PVP L(ly)/A(l) = 0.48 +/- 0.09). By calculating L(ly)/A(l) ratios for [(125)I]PVP fractions obtained by gel filtration it was shown that in transfer from A(l) to L(ly) during ventilation molecular sieving could be detected, the degree of which was expressed by means of a Relative Sieving Index (RSI). Significant correlations were found between the minimum surface tension of lung extracts, and two other indicators of lung maturity on the one hand, and the protein and [(125)I]PVP ratios and RSI on the other; so that the more mature the lamb the less the transfer of macromolecules during ventilation and the greater the degree of molecular sieving.4. By comparing concentrations of [(125)I]PVP gel filtration fractions in lymph and plasma, when the [(125)I]PVP had been placed in A(l), we demonstrated some sieving of molecules (in the range 34-15 A) in their absorption from interstitial space to plasma.5. It was concluded that in the lungs of the foetal lamb there is an almost complete barrier to the transfer of macromolecules between alveolar and interstitial spaces; that positive pressure ventilation for 2 hr causes a very variable degree of break-down in this barrier, and that the degree of break-down is usually greater in immature than in mature lungs.

Age Factors↗
PubMed1969

Permeability of lung capillaries to macromolecules in foetal and new-born lambs and sheep.

1. The permeability of lung capillaries to macromolecules was investigated in immature and mature foetal lambs, new-born lambs and young sheep. The placental circulation of the foetal animals was maintained intact after delivery by Caesarian section. New-born lambs and sheep were mechanically ventilated. Samples of plasma and lymph that had drained from the lung via the thoracic duct were collected over a period of 1-5 hr.2. The proteins in plasma and lymph samples were separated by fractionation on columns of Sephadex G-200. Plasma yielded three peaks of protein concentration. The K(av) value of each peak was determined, and, by calibrating the columns with known proteins, the mean radius of equivalent sphere (a) of the proteins in peak I was shown to be similar to that of fibrinogen >/= 110 A, peak II to gamma-globulin approximately 54 A and peak III to albumin approximately 34 A. Lung lymph contained the same three constituent peaks as plasma but in lower concentration. In all four groups mean lymph/plasma concentration (L/P) ratio was significantly different for each of the three peaks, being lowest for the largest molecules (peak I) and highest for the smallest (peak III).3. In five mature foetal lambs polydisperse polyvinylpyrrolidone labelled with (125)I ([(125)I]PVP) was injected I.V. early in the experiment: count rates in fractionated samples showed for plasma a continuous decline with time after injection, and for lung lymph an increase to a maximum then a decline. Steady-state L/P ratios for eleven fractions of PVP of differing molecular size ranging from 110 to 17 A were derived by compartmental analysis. For a given molecular size PVP L/P ratios were similar to protein L/P values.4. The regression of PVP L/P ratio on K(av) was linear (correlation coefficient r = 0.99), and the slope of the regression of protein L/P ratio on K(av) was significantly steeper for new-born lambs than for mature foetuses (P < 0.025) and sheep (P < 0.005), and steeper for immature foetuses than sheep (P < 0.01).5. PVP and protein L/P ratios (mature foetuses) plotted against a showed a sigmoid relation with agreement between the two sets of L/P ratios. The goodness of fit between our experimental results and Landis & Pappenheimer's (1963) capillary pore theory (eqn. (1)) was examined: L/P ratios for the larger molecules (>/= 75 A) appeared to be too high. By recalculating ratios on the assumption that the largest molecules (110 A) escape unrestricted from the capillary via leaks, the discrepancy disappears.6. Values for pore radius (r), and pore area per unit path length (A/Deltax) have been calculated for each of the four groups; r ranged from 90 to 150 A, A/Deltax from 3.3 to 0.2 cm x 10(3).kg(-1). In new-born lambs the value of r was significantly smaller, and A/Deltax larger than that of any other group. The inferences to be drawn from these results are discussed.

Albumins↗
PubMed1967

Pulmonary lymph flow and the uptake of liquid from the lungs of the lamb at the start of breathing.

1. Lymph from the lungs of lambs and sheep was found to enter both the right lymph duct and the thoracic duct. Right lymph duct flow was collected by constructing a venous sac, the venous tributaries of which were ligated but which the right lymph duct entered; thoracic duct flow was collected by cannulating the duct. Lymph from sites other than the lungs was excluded from the collections.2. Measurements were made of the surface tension characteristics of lung extracts and of the liquid present in foetal lungs. These values were used together with gestational age and crown-rump length to designate the foetal lambs into mature and immature groups.3. Lymph flow from the lungs averaged 0.99 ml./kg body wt./hr in immature foetal lambs, and 1.81 ml./kg/hr in mature foetal lambs before the start of ventilation. Lymph flow from the lungs of spontaneously delivered new-born lambs (mean age 51 hr) averaged 0.86 ml./kg/hr. In adult ewes right lymph duct flow averaged 0.11 ml./kg/hr and total lung lymph flow was estimated indirectly to be 0.33 ml./kg/hr. Calculated rates of protein flow in lung lymph (flow x protein concentration) were greater in foetal lambs than in adult sheep.4. Total thoracic duct flow averaged 2.48 ml./kg/hr in immature foetal lambs, 5.30 ml./kg/hr in mature foetal lambs, 3.65 ml./kg/hr in new-born lambs, and 2.92 ml./kg/hr in adult ewes.5. At the start of ventilation there was an increase in lymph flow from the lungs, which at 15-30 min reached a mean of 6.4 ml./kg/hr in mature lambs and 2.6 ml./kg/hr in immature lambs. At the same time the protein concentration of lymph decreased but the calculated protein flow increased.6. The lungs of foetal lambs weighed more than the lungs of spontaneously delivered new-born lambs, and the difference could be accounted for by liquid which could be aspirated through the trachea of the foetal lamb. On ventilation of the lungs for 2 hr, without first allowing the escape of any lung liquid, lung weight measurements indicated that about 66% of the lung liquid had been taken up in mature lambs and about 50% in immature lambs.7. It was concluded that the rate at which lymph is formed in the lungs is greater per kilogram body weight in foetal than in new-born lambs and greater in them than in ewes. The increase in lymph flow at the start of ventilation could account for the removal of about 40% of the liquid present in the lungs of the mature foetus and about 25% of the liquid in the lungs of the immature foetus.

Journal Article↗
PubMedDate not supplied

Trimethoprim-sulfamethoxazole and trimethoprim alone in the prophylaxis of childhood urinary tract infection.

In 1975 trimethoprim-sulfamethoxazole (TMP-SMZ) was found effective in the prophylaxis of childhood urinary tract infection. The rate of recurrence in 130 children who received prophylaxis was only 0.05 infections per year. No fecal coliforms were found in 70% of rectal swabs, and only 10% of the isolates of coliform organisms were resistant to TMP. During effective, low-dose urinary prophylaxis with TMP-SMZ in 130 children for periods of two to 10 years, no effects of the drug on hematologic or renal function were observed, and somatic growth was normal. However, the frequency of resistance to TMP among fecal coliforms increased from less than 10% in 1970-1975 to 34% in 1980. This increase was not related to the duration of prophylaxis and appeared to represent a secular increase in TMP resistance among coliforms. TMP alone also was effective in urinary prophylaxis; only three of 39 children experienced a recurrence of urinary tract infection during a total of 309 months of prophylaxis in 1978-1980. The effect of TMP prophylaxis on the bowel flora was similar to that of TMP-SMZ prophylaxis. Resistance to TMP was found in 16% of isolates from rectal swabs from children receiving TMP alone.

Child↗