PubMed Health⌕ Search

Biomedical subjects

N H Holstein-Rathlou

Publications and source records attributed to N H Holstein-Rathlou.

At least 91 records · Page 5Linked to original sources
PubMed1987

A comparison of the effects of sodium cromoglycate and beclomethasone dipropionate on pulmonary function and bronchial hyperreactivity in subjects with asthma.

After a run-in period of 2 weeks, receiving a regimen of inhaled beta 2-agonists and/or theophyllines, 38 atopic patients with asthma with perennial symptoms were randomly allocated to receive an 8-week treatment of additional inhalation treatment with either sodium cromoglycate (SCG), 2 mg four times daily, and placebo beclomethasone dipropionate (BDP), or BDP, 200 micrograms twice daily, and placebo SCG. After crossover, each group received the opposite treatment for the final 8 weeks. FEV1, FVC, and provocation concentration of histamine causing a 20% fall in FEV1 (PC20) were determined monthly and peak expiratory flow (PEF) daily throughout the study. A significant increase in FEV1, FVC, and PEF (p less than 0.01) was observed after BDP treatment was started, and likewise, in the second period, an increase in both FEV1 and PEF (p less than 0.05) was observed. The total effect on logarithm-natural (Ln) (PC20), i.e., the mean effects of the two periods, was also significant (p less than 0.01). SCG, however, was most effective when it was used as the first drug, indicated by a significant increase in FVC in the first period (p less than 0.05). Neither in the first nor in the second period did SCG treatment influence the Ln (PC20) value positively, and the SCG treatment administered in the second period could not maintain the improvement in the pulmonary function (i.e., FEV1, FVC, and PEF) obtained initially with the BDP treatment. When the effect of BDP on FEV1, FVC, PEF, and Ln (PC20) was compared to the effect of SCG in the first 8-week treatment period, no significant difference was observed (p greater than 0.1).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1987

Effect of cisplatin on renal haemodynamics and tubular function in the dog kidney.

Administration of cisplatin (5 mg/kg) to dogs results in polyuric renal failure due initially to a proximal tubular functional impairment. 48-72 h after the cisplatin administration the depressed renal function can be attributed to impairment of proximal as well as distal tubular reabsorptive capacities associated with increased renal vascular resistance. The polyuria seems to be due to the impaired reabsorption rate in the distal nephron segments.

Animals↗
PubMed1987

Oscillations in the proximal intratubular pressure: a mathematical model.

This study presents a dynamic continuous time model of the regulation of the renal proximal intratubular pressure in the rat. The model integrates a functional model of the glomerulus, a tubular model, a feedback model, and an afferent arteriolar model. The model has one equilibrium solution for the dependent variables (equilibrium point) for each set of independent variables. An equilibrium point, chosen to be in accordance with experimental data from Sprague-Dawley rats, was used as the initial value for the dependent variables. The model is shown to have parameter ranges in which sustained stable oscillations in proximal pressure are present. For sustained oscillations to appear, it is necessary for the system's operating point to be located on a sufficiently steep portion of the tubuloglomerular feedback curve. The model analyses are compared with various experimental recordings of the proximal intratubular pressure. The model simulations show both spontaneous and induced oscillations in the proximal pressure in close agreement with the experimental results; but the steady-state mean pressure regulation is found to be less efficient in the model than that apparent from the experimental recordings, suggesting the involvement of additional pressure-regulating mechanisms other than those included in the present model. It is concluded that the dynamic systems approach used in the present study yields new insight into the mechanisms underlying the proximal intratubular pressure oscillations and that it can be of further value for the study of the factors regulating the proximal intratubular pressure.

Animals↗
PubMed1987

Functional and histopathological changes in dog kidneys after administration of cisplatin.

The nephrotoxic effect of cisplatin (5 mg/kg i.v.) was evaluated in 8 dogs 48-72 h after administration. The lithium clearance method was used for assessing the absolute and fractional reabsorption rates of sodium and water in proximal as well as in more distal segments of the total nephron population, before and during saline loading (infusion of 5 ml/kg of isotonic saline i.v.). Histological examinations of the kidney biopsies were used to evaluate the degree of renal tissue injury. During 48-72 h after administration of cisplatin blood urea nitrogen and plasma creatinine increased significantly from 3.9 +/- 0.2 to 11.7 +/- 1.4 mmol/l and 96 +/- 3 to 178 +/- 10 mumol/l, respectively. Mean values of renal blood flow, glomerular filtration rate, filtration fraction and lithium clearance in cisplatin-treated animals (143 +/- 14 ml/min, 10.7 +/- 1.1. ml/min, 0.14 +/- 0.01 and 6.3 +/- 0.6 ml/min, respectively) were significantly lower than in 6 control animals (212 +/- 8 ml/min, 49.0 +/- 2.0 ml/min, 0.36 +/- 0.001 and 10.1 +/- 1.3 ml/min, respectively). In contrast, urinary excretion rates of sodium, potassium and water were significantly higher, while fractional as well as absolute proximal and distal reabsorption rates were significantly lower in cisplatin-treated animals compared to controls. Saline loading caused an increase in the output of tubular fluid from the proximal tubules (lithium clearance) in the cisplatin-treated animals, while the fractional distal reabsorption rate of sodium decreased significantly. The histological changes are in agreement with the physiological data which point to the proximal tubules as the more severely damaged segment. In conclusion, the depressed renal function 48-72 h after administration of cisplatin can be attributed to impairment of proximal as well as distal tubular reabsorptive capacities associated with increased renal vascular resistance. The polyuria seems to be due to impaired reabsorption rates in the distal nephron segments, which will affect the concentration mechanism.

Animals↗
PubMed1987

The renal handling of sodium and water is not affected by the standard-dose cisplatin treatment for testicular cancer.

Renal clearances of 51Cr-EDTA, lithium, sodium and potassium were measured before and after each of four consecutive treatment series with cisplatin in 15 men with testicular cancer. Since lithium is reabsorbed like sodium and water in the proximal tubules, but not reabsorbed to any measurable degree in the remainder of the nephron, lithium clearance equals the amount of fluid delivered from the end of the proximal straight segment to the thin descending limb of the loop of Henle. From the clearances of lithium and sodium, distal tubular reabsorption can be calculated. Lithium clearance and all other parameters of glomerular filtration and renal sodium handling remained normal throughout the study (with the exception of a fall in fractional sodium excretion after the first treatment series). Plasma magnesium declined during all four treatment periods, signifying renal magnesium wasting.

Adult↗
PubMed1986

BAY K 8644-induced oscillations in rabbit gall-bladder transepithelial potential difference.

The effects of the Ca2+-channel activator BAY K 8644 (a novel dihydropyridine) on transepithelial potential difference (Pd), electrical resistance (Rt), and unidirectional Na+-fluxes were studied in the rabbit gall-bladder. It was observed that BAY K 8644 at concentrations between 10(-7) and 10(-5) M induced regular oscillations in the transepithelial Pd, without affecting the mean value of Pd (or Rt). The mean oscillatory frequency was 18 mHz (approximately 1 cycle per min), and the mean amplitude was 30-35 microV. Oscillations were predominantly elicited from the serosal side. 10(-5) M BAY K 8644 reduced net Na+ -absorption by 16% by inhibiting the mucosa-to-serosa flux. Nifedipine blocked the Pd-oscillations but did not reverse the Na+-transport inhibition. The observed effects of BAY K 8644 are consistent with activation of Ca2+-channels and an increase in intracellular Ca2+-concentration.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
PubMed1986

Effects of various transport inhibitors on oscillating TGF pressure responses in the rat.

The present study examines the effect in free flow microperfusion experiments of various diuretics with different sites of action on an oscillating tubular pressure response to changes in Henle loop flow rate. Amiloride (1 mM) and bendroflumethiazide (0.1 mM) had no effect outside the stimulation caused by the solvent (Ringer solution). Acetazolamide (0.5 mM) stimulated a slow (30 mHz) oscillation and often activated a fast (130-190 mHz) rhythm. Furosemide (FUR) (0.1-2.0 mM) abolished the slow oscillation and caused the intratubular pressure to rise by 2-3 mm Hg. FUR (0.05 mM) caused partial inhibition of the slow rhythm, which usually became irregular. Bumetanide (BUM) (0.05 mM) elicited a biphasic response. Initially the pressure decreased, while the slow rhythm was amplified; then the fast oscillation was activated; after 4-6 min the oscillations disappeared, while the pressure increased. In the recovery period the oscillations often became irregular. The results confirm that the oscillating pressure response is mediated by a transport function of the macula densa (MD); and, thus, has the character of a tubulo-glomerular feedback (TGF) response. The data suggest 1. that BUM inhibition of NaCl co-transport in the cortical thick ascending limb of Henle (TAL) is delayed as compared to the medullary TAL; and 2. that FUR action at the MD interferes with more than one carrier mechanism. Partial inhibition gives rise to irregular oscillations.

Absorption↗
PubMed1986

Bambuterol: dose response study of a new terbutaline prodrug in asthma.

The bronchodilator activity and side-effects of treatment for 4 days with either 0.085, 0.170 or 0.34 mg/kg bambuterol b.i.d. (a prodrug of terbutaline) or 0.071 mg/kg terbutaline t.i.d. have been evaluated over 12 h, in a double-blind, randomized crossover trial in 19 asthmatic out-patients. Plasma terbutaline concentrations after bambuterol administration were smoother, with a ratio between the maximum and minimum values of about 1.4 compared to 2.6 for terbutaline. The plasma terbutaline level rose with dose, but by less than the increase in dose. The bronchodilator effect was related to the plasma terbutaline concentration in each treatment group, so bambuterol produced more prolonged bronchodilatation than treatment with terbutaline. Tremor and cardiac side-effects were most pronounced after administration of bambuterol 0.34 mg/kg. No severe side-effects were seen. Bambuterol produced stable plasma levels of terbutaline, indicating that as a prodrug of terbutaline it might possibly be administered once daily with good antiasthmatic effect.

Adult↗
PubMed1986

Bronchial histamine challenge in the diagnosis of asthma. The predictive value of changes in airway resistance determined by the interrupter method.

The predictive value of a bronchial challenge with histamine was determined in a prospective survey on a population with a high prevalence of asthma (0.62). Without knowledge of the bronchial responsiveness 133 patients were classified as asthmatics (83) or non-asthmatics (50) according to variation in peak expiratory flow rate and medical history. Response to challenge was determined by the interrupter method, and the concentration of histamine inducing a 40% increase in resistance to breathing (PC40-Rt) was calculated from the log dose response curve. When defining a positive test as a test giving PC40-Rt-values below 2.00 mg/ml, the predictive value of a positive test was 0.75 and the predictive value of a negative test was 0.72. By decreasing the limit for a positive test to 0.25 mg/ml the corresponding predictive value was increased to 0.91. When further increasing the limit to 4.00 mg/ml the predictive value of a negative test in the diagnosis of asthma was increased to 0.81. The interrupter technique is suitable for diagnostic purposes in the detection and exclusion of bronchial asthma.

Adolescent↗
PubMed1986

Effect of renal nerve activity on tubular sodium and water reabsorption in dog kidneys as determined by the lithium clearance method.

The reliability of the lithium clearance method in studies of the effect of renal nerve activity upon tubular sodium and water handling in the dog kidney was investigated. Following unilateral acute surgical denervation of the kidney a significant increase in urinary flow rate (40 +/- 7%), sodium clearance (26 +/- 4%), lithium clearance (9 +/- 2%) and fractional lithium clearance (8 +/- 2%) was seen, as compared to the contralateral kidney with preserved innervation. Calculated absolute proximal reabsorption rate decreased significantly by 7 +/- 2%, while calculated absolute rates of distal reabsorption of sodium and water increased significantly by 9 +/- 2% and 8 +/- 2%. Low-frequency electrical stimulation of the distal nerve bundle of the denervated kidney caused a significant decrease in urine flow rate (37 +/- 6%), sodium clearance (31 +/- 4%), lithium clearance (17 +/- 5%) and in fractional lithium clearance (18 +/- 5%). Calculated absolute proximal reabsorption rate increased significantly by 17 +/- 3%, while calculated absolute rates of distal sodium and water reabsorption decreased significantly by 16 +/- 5% and 16 +/- 5%. These changes in tubular sodium and water reabsorption during alterations in renal nerve activity occurred without measurable changes in renal blood flow (RBF) and glomerular filtration rate (GFR). Administration of amiloride had no significant effect either on the lithium clearance, RBF or GFR, while the sodium excretion rate increased and potassium excretion rate decreased, supporting that significant distal lithium reabsorption did not occur under the present experimental conditions.(ABSTRACT TRUNCATED AT 250 WORDS)

Amiloride↗
PubMed1986

TGF-mediated oscillations in the proximal intratubular pressure: differences between spontaneously hypertensive rats and Wistar-Kyoto rats.

A highly sensitive oscillatory tubulo-glomerular feedback (TGF) response has previously been demonstrated in normotensive Sprague-Dawley rats. The purpose of the present study was to examine whether such as oscillating TGF-response could be elicited in Wistar-Kyoto rats (WKY) and genetically hypertensive rats (SHR) and furthermore if any differences in the TGF-response characteristics between SHR and WKY rats could be detected. The closed loop function of the TGF-system was studied. In 12-18-week-old WKY rats regular oscillations in the intratubular pressure occurred spontaneously. The median frequency were 29.7 mHz (range 20-46.7 mHz). In SHR rats, spontaneous oscillations also occurred, but these were highly irregular. Spontaneous oscillations were more frequent in WKY than in SHR (88% vs. 54%). In both strains, oscillations could be elicited by free flow microperfusion with artificial tubular fluid (ATF). When furosemide was added to the ATF in a concentration of 0.1 mM, the oscillations were abolished in both strains of rats. It is concluded that, in both strains of rats the oscillatory phenomena depend upon TGF activity. It is suggested that the irregular pattern of the oscillations observed only in SHR rats may represent a chaotic process.

Animals↗
PubMed1986

A study of proximal tubular compliances in normotensive and spontaneously hypertensive rats, and the effect of anaesthesia on the compliance.

Proximal tubular compliance (C) was measured in free flow microperfusion experiments from the initial slope of the increase in proximal luminal pressure divided by the step input of volume flow delivered from a microperfusion pipette inserted in a downstream proximal convolution. Five groups of rats were studied: Munich Wistar (WU, n = 11) and Sprague-Dawley rats (SPRD, n = 6) anaesthetized with inactin; and SPRD (n = 11), Wistar Kyoto (WKY, n = 9), and spontaneously hypertensive rats (SHR, n = 11) anaesthetized with halothane. In the inactin groups, C was: 0.309 +/- 0.161 and 0.266 +/- 0.136 nl mm Hg-1, respectively. In the halothane groups, C was: 0.125 +/- 0.023, 0.125 +/- 0.029, and 0.119 +/- 0.0127 nl mm Hg-1, respectively. The means in the inactin groups were significantly higher than those from the halothane groups (P less than 0.001). It is concluded that the choice of anaesthetics has a profound influence on the proximal tubular compliance in the rat, and that the compliance of SHR is equal to that of normotensive rats.

Anesthesia, Inhalation↗
PubMed1986

Acute effect of cisplatin on renal hemodynamics and tubular function in dog kidneys.

The present study was designed to investigate the early hemodynamic and tubular effects of cisplatin administration on dogs. To localize the nephrotoxic actions of cisplatin, we have taken advantage of the lithium clearance method. After infusion of 5 mg of cisplatin per kg, an immediate and significant increase in urinary flow rate (from 0.39 +/- 0.07 ml/min to 0.73 +/- 0.12 ml/min), sodium clearance (from 0.33 +/- 0.11 ml/min to 0.65 +/- 0.14 ml/min), potassium clearance (from 9.23 +/- 0.48 ml/min to 10.77 +/- 0.95 ml/min), lithium clearance (from 15.55 +/- 2.21 ml/min to 23.76 +/- 4.00 ml/min) and fractional lithium clearance (from 0.31 +/- 0.03 to 0.44 +/- 0.04) was seen. This occurred without measurable changes in glomerular filtration rate and renal blood flow. The calculated fractional as well as absolute rates of proximal reabsorption of sodium decreased significantly from 0.68 +/- 0.03 to 0.56 +/- 0.04 and from 4.76 +/- 0.32 mmol/min to 3.92 +/- 0.23 mmol/min, respectively. The results show that administration of cisplatin causes an acute, mainly proximal tubular impairment in dogs without alterations in renal hemodynamics.

Animals↗
PubMed1986

A rapid challenge protocol for determination of non-specific bronchial responsiveness.

A rapid method for determination of non-specific bronchial hyperreactivity was developed. Resistance to breathing was determined by a modified expiratory airway interrupter technique and combined with a dosimeter-controlled nebulizer which made continuous determination of response possible during challenge. The patients inhaled histamine chloride 8 mg/ml at every eighth breath until resistance to breathing (Rt) was increased by 60%. The number of inhalations (NI) or the provocative concentration (PC60-Rt) of histamine increasing Rt by 60% were determined in 68 patients. The new method correlated well to a non-cumulative standard protocol and could be terminated either within 10 min or within 20 inhalations. The results of this new challenge procedure enables us to predict the responsiveness to inhaled histamine precisely enough to separate patients into hyperreactive or normal reactive patients. Furthermore, the repeatability of the new method is comparable or superior to that of standard methods. The 95% confidence interval for the difference between replicates was the observed value +/- 2.4 NI. Thus this new method will be suited for studies of drug modifying effect on bronchial hyperreactivity since individual dose titration is easily performed, and the method could be valuable in epidemiological and occupational surveys as well.

Adolescent↗
PubMed1985

Bronchial histamine challenge. A combined interrupter-dosimeter method compared with a standard method.

We compared the provocative concentration (PC) values obtained by two different methods of performing bronchial histamine challenge. One test was done on an APTA, an apparatus which allows simultaneous provocation with histamine and measurement of airway resistance (Rtot) by the interrupter method. The second test was a conventional tidal breathing method, with measurement of the FEV1. There was a high correlation between the PC20-FEV1 and the PC30-, PC40- and PC50-Rtot values. The correlation coefficients were 0.85, 0.71 and 0.70 (P less than 0.05) respectively. We further tested the reproducibility of the histamine challenge done on the APTA. When the PC30-Rtot values were compared, a correlation coefficient of 0.56 (NS) was found. For the PC40- and PC50-Rtot values the correlation coefficients were 0.65 (P less than 0.05) and 0.70 (P less than 0.02) respectively. We conclude that the APTA is useful for routine bronchial histamine challenge when 40-50% increase in basal Rtot is used as endpoint.

Adolescent↗