Comparison of continuous left ventricular volumes by transthoracic two-dimensional digital echo quantification with simultaneous conductance catheter measurements in patients with cardiac diseases

Automated border detection enables real-time tracking of left ventricular (LV) volume by 2-dimensional transthoracic echocardiography. This technique has not been previously compared with simultaneously measured continuous LV volumes at rest or during transients in humans. We performed 18 studies in 16 patients (age 50 +/- 15 years, range 22 to 70; ejection fraction 63 +/- 20%, range 15% to 85%) in which continuous LV volumes acquired by digital echo quantification (DEQ) were compared with simultaneous conductance catheter volume obtained by cardiac catheterization. Both volume signals were calibrated by thermodilution-derived cardiac output and ventriculogram-derived ejection fraction. Volume traces acquired at rest were averaged to generate a comparison cycle. The averaged volume waveforms acquired by DEQ and by conductance catheter were similar during all phases of the cardiac cycle and significantly correlated (conductance catheter = slope. DEQ + intercept, slope = 0.94 +/- 0.09, intercept = 5 +/- 8 ml, r2 = 0.86 +/- 0.12, all p <0.0001). Steady-state hemodynamic parameters calculated using either averaged volume signal were significantly correlated. Transient obstruction of the inferior vena cava yielded a 45 +/- 13% decrease in end-diastolic volume. Successful recordings of DEQ volume during preload reduction were obtained in only 50% of studies. End-diastolic volumes from the 2 methods were significantly correlated (mean slope 0.88 +/- 0.31, mean intercept 14 +/- 37 ml, average r2 = 0.89 +/- 0.11, all p <0.01), as were end-systolic volumes: mean slope 0.80 +/- 0.43, intercept = -20 +/- 26 ml, r2 = 0.67 +/- 0.18, all p <0.05). We conclude that automated border detection technique by DEQ is reliable for noninvasive, transthoracic, continuous tracking of LV volumes at steady state, but has limitations in use during preload reduction maneuvers in humans.     

A simple radioimmunoassay for plasma cortisol: comparison with the fluorimetric method of determination

A quick and simple method for the radioimmunoassay of plasma cortisol is described. The mean morning plasma cortisol concentration in 43 normal subjects was 9.8 +/- 3.1 (S.D.) microgram/100 ml with a range of 5.0-19.5 microgram/100 ml. Mean midnight concentration in 24 normal subjects was 4.3 +/- 2.3 (S.D.) microgram/100 ml with a range of 1.4-9.6 microgram/100 ml. When compared with the fluorimetric method the mean results by radioimmunoassay of 154 routine specimens were 23% lower. In samples from unstimulated patients, regression analysis of results obtained by the two methods gave a correlation coefficient (r) of 0.93, regression line slope of 1.1, and intercept of 1.4 microgram. Mean radioimmunoassay results were 15% lower. When plasma cortisol concentration was above the normal range (greater than 30 microgram/100 ml) the regression line slope was 0.87, the intercept 17.9 microgram, r = 0.87 and mean radio immunoassay results were 37% lower. Plasma cortisol concentration in patients after insulin or Synacthen stimulation exhibited similar responses when measured by either method. Plasma cortisol concentration in normal subjects given metyrapone was lower when measured by radioimmunoassay (mean +/- S.D. = 8.7 +/- 2.7 microgram/100 ml) than when measured by fluorimetry (18.5 +/- 10.8 microgram/100 ml). The diagnostic usefulness of the two methods, ease of assay, and costs are compared.     

Renal reserve filtration capacity in growth hormone deficient subjects

In normal subjects, the glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) acutely increase in response to infusion of amino acids and to low doses of dopamine. It is uncertain whether circulatory growth hormone (GH) is a permissive factor for these stimulatory effects. GFR and ERPF (constant infusion technique using 125I-iothalamate and 131I-hippuran, respectively) were measured before and during the infusion of dopamine and amino acids in 8 GH deficient subjects. The clearance study was repeated during concomitant administration of octreotide to investigate whether this somatostatin analogue would modify the amino acid and dopamine-induced renal haemodynamic changes. Dopamine increased baseline GFR from 89 +/- 3 (mean +/- SEM, n = 8) to 102 +/- 4 ml min-1 1.73 m-2 and ERPF from 352 +/- 19 to 476 +/- 26 ml min-1 1.73 m-2, P less than 0.001 for both. During amino acid infusion GFR and ERPF increased to 108 +/- 3 and 415 +/- 23 ml min-1 1.73 m-2, respectively, P less than 0.001 for both. Octreotide did not significantly decrease baseline and dopamine-stimulated renal haemodynamics but lowered the amino acid-stimulated GFR (98 +/- 4 ml min-1 1.73 m-2, P less than 0.05) and ERPF (381 +/- 18 ml min-1 1.73 m-2, P less than 0.05). Basal plasma glucagon concentrations were not suppressed by octreotide, whereas the amino acid-induced increments in plasma glucagon were partially inhibited. It is concluded that GH is not a necessary factor for the stimulatory effects of amino acids and dopamine on renal haemodynamics.(ABSTRACT TRUNCATED AT 250 WORDS)     

Experimental basis of determining maximum coronary, myocardial, and collateral blood flow by pressure measurements for assessing functional stenosis severity before and after percutaneous transluminal coronary angioplasty

BACKGROUND: Severity of coronary artery stenosis has been defined in terms of geometric dimensions, pressure gradient-flow relations, resistance to flow and coronary flow reserve, or maximum flow capacity after maximum arteriolar vasodilation. A direct relation between coronary pressure and flow, however, may only be presumed if the resistances in the coronary circulation are constant (and minimal) as theoretically is the case during maximum arteriolar vasodilation. In that case, pressure measurements theoretically can be used to predict maximum flow and assess functional stenosis severity. METHODS AND RESULTS: A theoretical model was developed for the different components of the coronary circulation, and a set of equations was derived by which the relative maximum flow or fractional flow reserve in both the stenotic epicardial artery and the myocardial vascular bed and the proportional contribution of coronary arterial and collateral flow to myocardial blood flow are calculated from measurements of arterial, distal coronary, and central venous pressures during maximum arteriolar vasodilation. To test this model, five dogs were acutely instrumented with an epicardial, coronary Doppler flow velocity transducer. Distal coronary pressures were measured by an ultrathin pressure-monitoring guide wire (0.015 in.) with minimal influence on transstenotic pressure gradient. Fractional flow reserve was calculated from the pressure measurements and compared with relative maximum coronary artery flow measured directly by the Doppler flowmeter at three different levels of arterial pressure for each of 12 different severities of stenosis at each pressure level. Relative maximum blood flow through the stenotic artery (Qs) measured directly by the Doppler flowmeter showed an excellent correlation with the pressure-derived values of Qs (r = 0.98 +/- 0.01, intercept = 0.02 +/- 0.03, slope = 0.98 +/- 0.04), of the relative maximum myocardial flow (r = 0.98 +/- 0.02, intercept = 0.26 +/- 0.07, slope = 0.73 +/- 0.08), and of the collateral blood flow (r = 0.96 +/- 0.04, intercept = 0.24 +/- 0.07, slope = -0.24 +/- 0.06). Moreover, the theoretically predicted constant relation between mean arterial pressure and coronary wedge pressure, both corrected for venous pressure, was confirmed experimentally (r = 0.97 +/- 0.03, intercept = 9.5 +/- 13.3, slope = 4.4 +/- 1.2). CONCLUSIONS: These results provide the experimental basis for determining relative maximum flow or fractional flow reserve of both the epicardial coronary artery and the myocardium, including collateral flow, from pressure measurements during maximum arteriolar vasodilation. With a suitable guide wire for reliably measuring distal coronary pressure clinically, this method may have potential applications during percutaneous transluminal coronary angioplasty for assessing changes in the functional severity of coronary artery stenoses and for estimating collateral flow achievable during occlusion of the coronary artery.     

Estimation of glomerular filtration rate with 99Tc(m)-DTPA: a comparative assessment of simplified methods

In 40 adult patients undergoing gamma camera renography, glomerular filtration rate (GFR) was measured using simplified 99Tc(m)-DTPA methods (i.e. a personal modification of the 'slope' method which does not require dose calibration, Gates' method and Carlsen's method) and compared to reference results (obtained using Sapirstein's formula and Russell's two-sample method with 51Cr-EDTA). Estimation of GFR from plasma creatinine (the Cockroft-Gault formula) was also carried out. Bias and imprecision of the simplified estimates were determined by the Bland-Altman method. The GFR values of the 'slope' method correlated best with the reference values (R2 = 0.88, S.E.E. = 11.3 ml min[-1]). Correlation of the two methods based on external determination with the gamma camera was no better at estimating GFR than that from plasma creatinine. Moreover, Gates' method underestimated GFR at all levels between 25 and 150 ml min(-1), while Carlsen's method overestimated at low levels and underestimated at high levels. The bias was as follows (ml): Cockroft-Gault 2.4; 'slope' -4.1; Carlsen 7.5; Gates 16.7. The imprecision was as follows (ml): 'slope' 11.8; Cockroft-Gault 16.4; Carlsen 20.5; Gates 22.8. We conclude that our modification of the slope method correlated best with the reference results, and would appear suitable for routine practice because of the small error involved. When performing sequential renal scintigraphy, it can also be used for a quick check of dubious data based on gamma camera methods.     

Lack of effect of captopril on glomerular hyperfiltration in normoalbuminuric normotensive insulin-dependent diabetic patients

The aim of the present study was to evaluate the effects of captopril on the glomerular filtration rate (GFR) and urinary albumin excretion rate (UAER) of normoalbuminuric normotensive insulin-dependent diabetes mellitus (IDDM) patients with and without glomerular hyperfiltration. Eleven normoalbuminuric (UAER < 30 micrograms/min) patients (age: 34.3 +/- 4.6 years: diabetes duration: 9.5 +/- 6.4 years) participated in the study. Six patients were considered to be hyperfiltering (GFR > or = 134 ml/min/ 1.73m2). GFR (51Cr-EDTA single injection technique), extracellular volume (ECV; distribution volume of 51Cr-EDTA), UAER (RIA) and metabolic and biochemical parameters were measured at baseline, after 6 weeks on captopril (25 mg p.o. twice daily) and after 6 weeks off captopril. Plasma renin activity (PRA; RIA), plasma aldosterone (RIA) and blood volume (51Cr red cell labeled) were measured at baseline and after 6 weeks on captopril. The baseline clinical and laboratory characteristics of hyperfiltering and normofiltering IDDM patients were similar. GFR did not change during the study (144.1 +/- 28.8; 139.7 +/- 21.8; 132.8 +/- 29.9 ml/min/1.73 m2) either in patients with hyperfiltration (164.6 +/- 20.7; 153.8 +/- 18.3; 148.6 +/- 31.0 ml/min/1.73 m2; n = 6) or without hyperfiltration (119.6 +/- 11.1; 123.2 +/- 11.9; 113.8 +/- 14.4 ml/min/1.73 m2; n = 5). Also, ECV (22.2 +/- 3.6; 21.5 +/- 4.3; 21.5 +/- 3.5 L/1.73 m2), UAER (3.9 [0.4-22.1]; 4.0 [0.2-11.4]; 3.7 [2.0-26.2] micrograms/min), systolic (112 +/- 13; 105 +/- 10; 111 +/- 11 mmHg) and diastolic (76 +/- 12; 72 +/- 9; 73 +/- 12 mmHg) blood pressure did not change. No difference in blood volume (60.8 +/- 10.4; 62.3 +/- 8.4 ml/kg) or plasma aldosterone (10.4 +/- 4.9; 7.7 +/- 3.8 ng/dl) was observed between baseline values and values after captopril use. PRA increased (2.4 [0.4-22.1]; 12.9 [2.2-41.1]ng/ml/h) at the end of 6 weeks on captopril (P = 0.002). Fasting plasma glucose, glycated hemoglobin, fructosamine, plasma cholesterol and potassium, 24 h urinary urea and sodium were similar during the study. These results were unchanged when patients with and without hyperfiltration were analyzed as separate groups. From baseline to the end of 6 weeks on captopril there was no correlation between change in GFR and change in glycated hemoglobin (r = 0.02, P = 0.96), systolic (r = 0.23; P = 0.49) and diastolic (r = -0.32, P = 0.32) blood pressure, urinary urea (r = 0.21; P = 0.53) and UAER (r = -0.16; P = 1.00). In conclusion, captopril has no effect on the GFR and UAER of normoalbuminuric normotensive IDDM patients irrespective of the presence of glomerular hyperfiltration.     

The effect of felodipine on renal function and blood pressure in cyclosporin-treated renal transplant recipients during the first three months after transplantation

BACKGROUND: Due to their vasodilatory effect, calcium antagonist may have a renoprotective against cyclosporin (CsA)-induced nephrotoxicity and rise in blood pressure (BP) seen in renal transplantation. METHODS: In order to evaluate the effect of the calcium antagonist felodipine on renal function and BP during cyclosporin treatment, 79 CsA-treated renal transplant recipients were investigated during the first 3 months after transplantation in a randomized, double-blind, placebo-controlled study with two parallel groups. Felodipine (ER tablets, 10 mg) or placebo was given prior to transplantation and each day during the study period. The patients were assessed twice, i.e. at 4-6 weeks and at 10-12 weeks after transplantation. Renal plasma flow (RPF) and glomerular filtration rate (GFR) were measured by constant infusion technique. Tubular function was estimated from clearance of lithium. RESULTS: At 6 weeks after transplantation, felodipine caused a significantly higher RPF [felodipine: 219 +/- 70 ml/min; placebo: 182+/-56 ml/min (mean+/-1 SD); P=0.03]. No differences were found in GFR, filtration fraction (FF), tubular sodium handling, or sodium excretion. Felodipine lowered BP significantly. At 12 weeks after transplantation, felodipine caused a significantly higher GFR (felodipine: 49+/-18 ml/min; placebo: 40+/-16 ml/min; P=0.05) and RPF (felodipine: 225+/-77 ml/min; placebo: 175+/-48 ml/min; P<0.01). No difference was found in FF. Felodipine lowered BP significantly. No differences were found with regard to duration of primary anuria, hospitalization time, number of rejection episodes, plasma creatinine day 7 post-transplant, or treatment doses of CsA. CONCLUSIONS: It is concluded that in renal transplant recipients treated with CsA, felodipine significantly increased both GFR and RPF 3 months after transplantation when compared with placebo, despite a concomitant lowering of BP. A possible antagonizing affect of felodipine against CsA-induced nephrotoxicity in these patients is suggested.     

The central visual field in homonymous hemianopia. Evidence for unilateral foveal representation

Renal functional reserve (RFR) after an oral protein load was evaluated in 36 cyclosporine-treated children following kidney transplantation (Tx), in 15 kidney donors (Don), and in 15 children with single kidneys (Nx/Ag). Glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) were determined by clearances of inulin (and creatinine) and para-aminohippurate during water diuresis. Baseline and stimulated GFR and ERPF were determined and RFR was calculated as the difference between stimulated and baseline values. Baseline GFR and ERPF in Tx were lower than in Don and Nx/Ag. Both GFR and ERPF increased significantly in all groups from baseline to stimulated values. RFR GFR was 23% +/- 3%, 20% +/- 3% and 15% +/- 3% in Tx, Don, and Nx/Ag and RFR ERPF 35% +/- 4% in Tx, which was significantly higher than 20% +/- 4% and 15% +/- 3% in the two other groups respectively. Stimulated GFR and ERPF in Tx correlated with kidney length. No differences were seen in recipient-donor pairs, except for higher fractional increases of ERPF in recipients. There was no correlation between RFR measured by clearance of creatinine and clearance of inulin. In conclusion, cyclosporine-treated children following renal Tx were found to have a renal reserve capacity.     

Measurement of glomerular filtration rate (GFR) after administration of iodine contrast medium with the Renalyzer PRX90 in healthy cats and cats with kidney diseases

In the present study, the measurement of the glomerular filtration rate (GFR) in the cat with the aid of an iodine contrast medium clearance with the renalyzer PRX90 is introduced. Investigations on the accuracy of measurement showed that even repeated measurement of plasma samples after two days of storage at room temperature yielded reproducible clearance results. Also, partial dilution of the plasma sample (2 ml with 1 ml Aqua bidest.) to reduce the volume of blood withdrawn still produced reliable results. Further dilution of the plasma volume (1 ml with 2 ml Aqua bidest.) however did not allow for accurate measurements. A total of 59 cats of different age and sex were included in the study. 31 cats had healthy kidneys with urea and creatinine values within the reference range, unchanged urine findings and physiologic urine protein patterns (SDS-PAGE). These cats served as reference group. The GFR reference value ascertained for these animals was 2.1 ml/min/kg BW (mean = 3.45 ml/min/kg with s = +/- 1.0 ml/min/kg). 28 cats had elevated values of urea and creatinine in the blood, as well as partially changed urine findings. For further diagnosis of renal disease, separation of urine proteins was done with the SDS-PAGE in the PhastSystem, which in all cases yielded a pathologic urine protein pattern. In 11 cases the renal disease could be further confirmed by histological investigation. GFR in these patients was clearly lowered compared with healthy cats, with measured values between 0 and 1.8 ml/min/kg. It can be concluded that the renalyzer allows reliable determination of the GFR also in the cat. To what extent measurement of the GFR is also helpful to diagnose nephropathies in the stage of compensation needs to be further investigated. In cats with high grade uremia and a GFR below 1 ml/min however, an exact calculation is not possible, since the accuracy of measurement within this range is inadequate. Thus, in severe disease no correct assessment is possible, and no statement concerning prognosis can be made.     

Role of the donor in post-transplant renal function

BACKGROUND: The donor, i.e. adult or paediatric, might influence the outcome of the graft function. METHODS: The glomerular filtration rate (GFR) of 120 transplanted children (47 girls) aged 10.4+/-4.6 years (0.7-17.2) was prospectively assessed over a 5-year period. The patients were divided into two groups according to the age of donor: adult (donor age > 18 years; n=33) and paediatric (donor age < 18 years; n=87). GFR was assessed by inulin clearance at 3, 6 and 12 months and yearly thereafter. RESULTS: The average GFR was stable in the range of 70 ml/min/1.73 m2 for the whole follow-up period. The adjusted GFR in adult graft recipients was significantly higher at 3 months post-transplantation: 80.6+/-36.9 vs 65.1+/-22.0, P=0.02. However, from the second year post-transplantation, the adjusted GFR in paediatric graft recipients became significantly higher than that of adult graft recipients. Such results could be due to an improvement in the absolute GFR (ml/min) of paediatric graft recipients with time (P=0.0001) whereas that of the adult graft recipients remained stable despite the children's growth. CONCLUSIONS: The adjusted GFR of adult graft recipients was significantly higher than that of paediatric graft recipients in the early post-transplant period. In the long-term, a progressive decrease in adjusted GFR was noted in adult graft recipients. On the one hand, this may be due to a functional adaptation and/or inadequate compensatory growth of the graft. On the other hand, the absolute GFR of paediatric graft recipients increased, suggesting an ongoing capacity for growth and/or compensatory hypertrophy after child-to-child renal transplantation.     

Terazosin in the treatment of hypertension and symptomatic benign prostatic hyperplasia: a primary care trial

In vitro experimental data show that magnesium increases beta-receptor affinity to agonists. We studied the effect of a mild increase in serum magnesium level on the bronchial dose-response curve to salbutamol in six patients with asthma (age 54 +/- 3.6 years, FEV1 49.2 +/- 4.9 per cent of predicted), with a normal serum magnesium level, in a double blind placebo-controlled design. The salbutamol dose-response curve was obtained on two separate days, starting 30 min after an intravenous infusion of saline or MgSO4 (20 mg/kg over 10 min, followed by 10 mg/kg/h). The baseline FEV1 values and the values after 30 min infusion on the two test days were not significantly different. During MgSO4 infusion, the serum magnesium level increased significantly from 0.86 +/- 0.01 to 1.31 +/- 0.19 mmol/litre after 30 min and 1.29 +/- 0.17 mmol/litre at the end of the study. FEV1 values after salbutamol were significantly higher during MgSO4 than during saline infusion at the low doses of salbutamol: 1480 +/- 253 vs. 1368 +/- 212 ml, P < 0.05, after 5 micrograms, and 1596 +/- 585 vs. 1378 +/- 532 ml, P < 0.01, after 10 micrograms of salbutamol. The maximum increase in FEV1 obtained after the maximum dose of salbutamol (400 micrograms) was not significantly different during saline and MgSO4 infusion. In conclusion, a mild sustained increase in serum magnesium level increases the bronchodilating effect of low doses of salbutamol, possibly through an increased beta-receptor affinity. There was no effect on the maximum bronchodilating effect of salbutamol.     

Cloning of the rat brain cDNA encoding for the SLC-1 G protein-coupled receptor reveals the presence of an intron in the gene

OBJECTIVE: Glomerular filtration rate (GFR) can be estimated in patients with renal disease from plasma creatinine concentration, age, sex, and body weight according to the formula of Cockcroft and Gault. The hypothesis that this method can be improved when tubular secretion of creatinine is inhibited by cimetidine was studied in NIDDM patients. RESEARCH DESIGN AND METHODS: In 30 outpatients with NIDDM and normo- (n = 10), micro- (n = 9), or macroalbuminuria (n = 11), GFR was measured as the urinary clearance during continuous infusion of 125I-labeled iothalamate. Plasma creatinine concentration was analyzed with an enzymatic assay before and after 800 mg t.i.d. oral cimetidine was given during a 24-h period. RESULTS: Plasma creatinine rose in all patients after cimetidine administration and, as a consequence, the clearance calculated with the Cockcroft-Gault formula fell. The ratio of this formula and GFR decreased from 1.16 +/- 0.20 to 0.97 +/- 0.16 (means +/- SD). This ratio tended to be smaller in the normo- (0.93) than in the micro- (0.98) and macroalbuminuric (1.00) groups. Also, 20 patients with a BMI < 30 kg/m2 had a smaller ratio than those with a BMI > 30 kg/m2 (0.92 vs. 1.07; P < 0.05). Bland and Altman analysis showed a difference of the Cockcroft-Gault formula and GFR of 12.0 +/- 17.4 ml.min-1 (1.73 m2)-1, which decreased to -3.8 +/- 14.8 ml.min-1.(1.73 m2)-1. The same analysis of 24-h creatinine clearance with urine collection and GFR showed larger standard deviations. CONCLUSIONS: GFR can be estimated in an acceptable way from plasma creatinine concentration after cimetidine administration in outpatients with NIDDM. Despite a nonsignificant underestimation in normoalbuminuric and overestimation in overweighted patients, this method is superior to 24-h creatinine clearance with outpatient urine collection.     

Cyclosporin does not inhibit the tubular secretion of creatinine

BACKGROUND: The immunosuppressive drug cyclosporin is known to impair renal function. The degree of renal dysfunction is usually estimated from the clearance of creatinine (CCr). Theoretically however, a fall in CCr can be caused by a decrease of GFR, an inhibition of the tubular secretion of creatinine, or the combination of both. CsA has convincingly been shown to decrease GFR, but detailed information on the effects of CsA on tubular secretion of creatinine is lacking. METHODS: We performed two studies to investigate the influence of CsA on tubular creatinine secretion. In study A we simultaneously measured CCr and GFR (using inulin) immediately before and 4 weeks after cessation of CsA therapy in 17 renal transplant patients. In study B, the rise in serum creatinine after administration of cimetidine, which blocks the tubular secretion of creatinine, was compared in renal transplant patients treated with either CsA (in whom secretion might already be inhibited) or azathioprine. RESULTS: Study A: After cessation of CsA there was an increase of GFR (54+/-15 vs 63+/-16 ml/min/1.73 m2, PCr (71+/-21 vs 82+/-23 ml/min/1.73 m2; PCr and GFR (a measure of the relative contribution of tubular secretion to the clearance of creatinine) did not change significantly (1.33+/-0.21 vs 1. 32+/-0.30). Study B: In nine couples of patients matched for GFR the relative rises in serum creatinine after administration of cimetidine were 26+/-21% and 22+/-7% for CsA and azathioprine treated patients respectively (NS). CONCLUSION: CsA does not substantially inhibit the tubular secretion of creatinine. A rise in serum creatinine after administration of CsA can thus be attributed completely to a fall in GFR.     

Reduction of renal functional reserve in kidney transplant recipients: a possible role of arachidonic acid metabolism alterations

AIM: Renal functional reserve (RFR), resulting from an increase in glomerular filtration (GFR) after protein load, is a matter of debate. In kidney transplant recipients most studies have failed to show conclusive results, reporting either the absence, the reduction or the presence of renal reserve in normo-functioning kidneys. The aim of this study was to investigate RFR in kidney transplant patients as well as the possible hormonal vasoactive alterations underlying the reduction of renal reserve reported in some patients. PATIENTS AND METHODS: We studied 8 controls and 25 patients, the latter with no history of acute rejection for at least 12 months and GFR >50 ml/min. The 25 patients were divided into 2 groups based on the presence (10) or the absence (15) of RFR. RESULTS: Both the RFR group and the controls experienced a similar increase of GFR after oral protein load: 24.3 +/- 15.57% vs 24.4 +/- 10.8%. The group without RFR showed a paradoxical reduction of GFR after oral protein load: 13.3 +/- 13.2% (p <0.001). We analyzed the filtration fraction (FF) and observed that the group without RFR had higher values than the group with RFR and the controls: 0.35 +/- 0.11 vs 0.29 +/- 0.07 (p = 0.01) and vs 0.26 +/- 0.02 (p = 0.04). The hyperfiltration state observed in the group without RFR was sustained by a high level of thromboxane. The urine ratio TxB2/6ketoPgF1alpha was higher in the group without RFR than in the RFR group 0.78 +/- 0.2 vs 0.64 +/- 0.1 (p = 0.01). This ratio decreased only in the RFR group after a meat meal. In all the patients, changes of TxB2/6ketoPGF1alpha were inversely correlated to changes of GFR after a meat meal (r = -0.6, p = 0.01). CONCLUSIONS: In conclusion, these data demonstrate that kidney transplant recipients with good organ function can be grouped according to the presence of RFR. RFR appears to be inversely correlated with the TxB2/6ketoPGF1alpha ratio, and its decrease seems to be linked to the failure of thromboxane to decrease and prostacycline to increase after a meat meal.     

Radioisotopic evaluation of renal function in cyclosporine-treated pediatric and adult renal transplant recipients and their living donors. A study of 152 donor-recipient pairs

Renal function was studied in 2 groups of renal transplant recipients and their donors by technetium-99m diethylenetriamine pentaacetic acid and a gamma camera. The pediatric group (group A) comprised 40 children and their adult kidney donors. The adult group (group B) consisted of 112 consecutive adult renal transplant recipients and their adult donors. All patients received kidneys from living donors and were given the same immunosuppression protocol (PRED plus CSA). Donor glomerular filtration rate (GFR) was determined before nephrectomy and at a mean period of 30 (range 10-50) months after nephrectomy. The graft GFR was measured at 1, 3, 6, and 12 months and at the most recent follow-up visit. Moreover, the functional reserve of the graft was assessed by infusion of dopamine and an amino acid. The postnephrectomy GFR of donors in groups A and B were 74 +/- 18 and 72 +/- 20 ml/min/1.73 m2, respectively. The GFR of pediatric recipients was significantly lower than that of adult recipients at corresponding time points along the course of follow-up. The mean values of graft GFR were 47.6 +/- 20 and 63.8 +/- 29.6 ml/min/1.73 m2 for pediatric and adult recipients, respectively (P < 0.001). Moreover, the graft functional reserve was significantly lower in pediatric recipients. These data demonstrate that adult kidneys transplanted into pediatric recipients have lower GFR than those transplanted into adults, despite corrections for body surface area. Although the reason for this phenomenon is unknown, the observation may have important implications for management of pediatric recipients.     

Compartmental analysis of colonic transit reveals abnormalities in constipated patients with normal transit

Previous studies had concluded that the treadmill velocity-endurance time hyperbolic relationship for runs could be accuratly approached with a regression at condition that bouts of exercise duration were included between 2 and 12 min. This regression allows to calculate the critical speed (CS) defined as the slope of the regression of work (distance) on time to exhaustion, the anaerobic running capacity (ARC) being the intercept of this line (Monod & Scherrer, 1965). The purpose of this investigation was to give practical indication concerning the choice of the velocities in reference to the maximal aerobic speed (MAS i.e. the minimum speed which elicits VO2max). Subjects were fourteen elite male long-distance runners (27 +/- 3 years old; VO2max = 74.9 +/- 2.9 ml.kg-1.min-1, MAS = 22.4 +/- 0.8 km.h-1, CS = 19.3 +/- 0.7 km.h-1 and 86.2 +/- 1.5% MAS). tlim 100 values (321 +/- 83 s) were negatively correlated with MAS (r = -0.538, p < 0.05) and with CS (km.h-1) (r = -0.644, p < 0.01). tlim 90 (1015 +/- 266 s) was positively correlated with CS when expressed in % MAS (r = 0.645, p < 0.01) and not when expressed in km.h-1 (r = -0.095, P > 0.05). tlim 105 (176 +/- 40 s) only was correlated with ARC (r = 0.526, p < 0.05). These data demonstrate that running time to exhaustion at 100 and 105% of MAS in a homogeneous elite male long-distance runners group is inversely related to MAS. Moreover, tlim 90 is positively correlated with CS (%MAS) but neither with tlim 100 and 105 nor with maximal aerobic speed. So from a practical point of view, the velocities chosen to determine the critical speed, would be closed to the maximal aerobic speed (time to exhaustion around 6 min), taking into account that the tlim 105 is correlated with the anaerobic capacity, whereas tlim 90 is correlated with the critical speed.     

Direct binding of CDC20 protein family members activates the anaphase-promoting complex in mitosis and G1

The mechanisms regulating coronary collateral circulation are largely unknown owing to both the complex and variable nature of clinical models and the difficulty to obtain quantitative and differentiated flow measurements within the various coronary tree portions. With the aim of assessing collateral flow reserve, we studied 19 patients with effort angina, without myocardial infarction and with isolated occlusion of either the left anterior descending coronary artery (n = 14) or the circumflex coronary artery (n = 5). Flow values were measured basally, during atrial pacing induced tachycardia and following ev dipyridamole infusion (0.56 mg/kg of body weight in 4 min), by means of positron emission tomography and nitrogen-13 ammonia as flow tracer, within both regions depending on collateral circulation and the remote ones. Results have been compared with those obtained in 13 normal subjects. Basal flow values in regions depending on collateral circulation and in the remote regions (0.61 +/- 0.11 vs 0.63 +/- 0.17 ml/min/g) were found to be similar, but lower than in normal subjects (1.00 +/- 0.20 ml/min/g, p < 0.01). During atrial pacing, flow increased to 0.83 +/- 0.25 and to 1.11 +/- 0.39 ml/min/g, in the regions depending on collateral circulation and in the remote regions, respectively (p < 0.05 as compared to baseline); again, values were lower than in normal subjects (1.86 +/- 0.61 ml/min/g, p < 0.01). Dipyridamole infusion further increased flow in the remote regions (1.36 +/- 0.57 ml/min/g, p < 0.01 as compared to atrial pacing) but it did not in the regions depending on collateral circulation (0.94 +/- 0.37 ml/min/g, NS as compared to atrial pacing); both values were lower than in normal subjects (3.46 +/- 0.78 ml/min/g, p < 0.01). Flow reserve in the regions depending on collateral circulation was found to have a direct linear correlation with the one in the remote regions (r = 0.83; p < 0.01). In conclusion, in spite of basal hypoperfusion, collateral circulation maintains a flow reserve which, even if reduced, is able to cope with moderate increments in oxygen consumption. An analogous flow reduction can be observed in the remote regions, suggesting that the entire coronary tree is involved, beyond the obstructive lesions of the main arterial branches.     

Effects of smoking on renal hemodynamics in healthy volunteers and in patients with glomerular disease

Patients with renal disease who smoke have a poor renal functional prognosis, but the mechanisms involved have not been explored. In this controlled study, the effects of smoking and sham smoking were compared in 15 healthy normotensive volunteers. All were occasional smokers and abstained from smoking for 48 h as documented by urinary cotinine measurements. These data were compared with those of seven patients with biopsy-confirmed IgA glomerulonephritis, also occasional smokers. Renal clearance examinations were obtained after hydration in the supine position before and while smoking two cigarettes or sham cigarettes in random order on 2 consecutive days. GFR and effective renal plasma flow were determined using In111-diethylenetriamine penta-acetic acid and 131I-hippurate with a dual tracer infusion clearance technique. In an ancillary study with six volunteers, the effect of smoking was compared with the effect of nicotine-containing chewing gum. In healthy volunteers, sham smoking caused a minor but significant increase of mean arterial pressure (MAP) and GFR with no significant change of effective renal plasma flow, filtration fraction (FF), or renovascular resistance. Smoking caused a significant and more marked increase of MAP (from baseline 92.8+/-8.98 to 105+/-7.78 mmHg) and heart rate (from 61.7+/-7.52 to 86.4+/-9.87 min(-1)), accompanied by a significant increase in arginine vasopressin (from 1.27+/-0.72 to 19.9+/-27.2 pg/ml) and epinephrine (from 37+/-13 to 140+/-129 pg/ml). During smoking, GFR decreased in all but one volunteer (from 120+/-17.7 to 102+/-19.3 ml/min per 1.73 m2), and this was accompanied by a significant decrease of FF (from 21.3+/-4.24 to 17.4+/-3.41%) and an increase in renovascular resistance (from 97.6+/-27.2 to 108+/-30.4 mmHg x min/ml per 1.73 m2). These findings were reproduced with nicotine-containing chewing gum. In contrast, when patients with IgA glomerulonephritis smoked, a similar increment in MAP was noted, the changes of FF were not uniform, and a small but consistent increase of urinary albumin/creatinine ratio was observed. An additional 20 volunteers were subjected to the smoking arm of the study for statistical evaluation of the GFR change in patients. The difference between the change of GFR between all volunteers (n = 35) and patients (n = 7) was significant (P < 0.005). It is concluded that the known effects of smoking and nicotine on the sympathetic nervous system and on systemic hemodynamics are accompanied by significant acute changes in renal hemodynamics and albuminuria. These findings are of interest because of the known effects of smoking on progression of renal disease.     

Alfentanil slightly increases the sweating threshold and markedly reduces the vasoconstriction and shivering thresholds

BACKGROUND: Hypothermia is common in surgical patients and victims of major trauma; it also results from environmental exposure and drug abuse. In most cases, hypothermia results largely from drug-induced inhibition of normal thermoregulatory control. Although opioids are given to a variety of patients, the thermoregulatory effects of opioids in humans remain unknown. Accordingly, the hypothesis that opioid administration impairs thermoregulatory control was tested. METHODS: Eight volunteers were studied, each on 3 days: (1) a target total plasma alfentanil concentration of 100 ng/ml, (2) control (no drug), and (3) a target alfentanil concentration of 300 ng/ml. Each day, skin and core temperatures were increased sufficiently to provoke sweating. Temperatures subsequently were reduced to elicit peripheral vasoconstriction and shivering. Mathematical compensations were made for changes in skin temperature using the established linear cutaneous contributions to control of sweating (10%) and to vasoconstriction and shivering (20%). From the calculated thresholds (core temperatures triggering responses at a designated skin temperature of 34 degrees C) and unbound plasma alfentanil concentrations, the individual concentration-response relationship was determined. The concentration-response relationship for all the volunteers was determined similarly using total alfentanil concentrations. RESULTS: In terms of unbound concentration, alfentanil increased the sweating threshold (slope = 0.021 +/- 0.016 degrees C.ng-1.ml; r2 = 0.92 +/- 0.06). Alfentanil also significantly decreased the vasoconstriction (slope = -0.075 +/- 0.067 degrees C.ng-1.ml; r2 = 0.92 +/- 0.07) and shivering thresholds (slope = -0.063 +/- -0.037 degrees C.ng-1.ml; r2 = 0.98 +/- 0.04). In terms of total alfentanil concentration (degrees C.ng-1.ml), the sweating threshold increased according to the equation: threshold (degrees C) = 0.0014[alfentanil] + 37.2 (r2 = 0.33). In contrast, alfentanil produced a linear decrease in the core temperature, triggering vasoconstriction: threshold (degrees C) = -0.0049[alfentanil] + 36.7 (r2 = 0.64). Similarly, alfentanil linearly decreased the shivering threshold: threshold (degrees C) = -0.0057[alfentanil] + 35.9 (r2 = 0.70). CONCLUSIONS: The observed pattern of thermoregulatory impairment is similar to that produced by most general anesthetics: a slight increase in the sweating threshold and a substantial, linear decrease in the vasoconstriction and shivering thresholds.     

Effects of prostaglandins and nitric oxide on the renal effects of angiotensin II in the anaesthetized rat

1. The potential influences of nitric oxide (NO) and prostaglandins on the renal effects of angiotensin II (Ang II) have been investigated in the captopril-treated anaesthetized rat by examining the effect of indomethacin or the NO synthase inhibitor, N(omega)-nitro-L-arginine methyl ester (L-NAME), on the renal responses obtained during infusion of Ang II directly into the renal circulation. 2. Intrarenal artery (i.r.a.) infusion of Ang II (1-30 ng kg(-1) min(-1)) elicited a dose-dependent decrease in renal vascular conductance (RVC; -38+/-3% at 30 ng kg(-1) min(-1); P < 0.01) and increase in filtration fraction (FF; +49+/-8%; P < 0.05) in the absence of any change in carotid mean arterial blood pressure (MBP). Urine output (Uv), absolute (UNaV) and fractional sodium excretion (FENa), and glomerular filtration rate (GFR) were unchanged during infusion of Ang II 1-30 ng kg(-1) min(-1) (+6+/-17%, +11+/-17%, +22+/-23%, and -5+/-9%, respectively, at 30 ng kg(-1) min(-1)). At higher doses, Ang II (100 and 300 ng kg(-1) min(-1)) induced further decreases in RVC, but with associated increases in MBP, Uv and UNaV. 3. Pretreatment with indomethacin (10 mg kg(-1) i.v.) had no significant effect on basal renal function, or on the Ang II-induced reduction in RVC (-25+/-7% vs -38+/-3% at Ang II 30 ng kg(-1) min(-1)). In the presence of indomethacin, Ang II tended to cause a dose-dependent decrease in GFR (-38+/-10% at 30 ng kg(-1) min(-1)); however, this effect was not statistically significant (P=0.078) when evaluated over the dose range of 1-30 ng kg(-1) min(-1), and was not accompanied by any significant changes in Uv, UNaV or FENa (-21+/-12%, -18+/-16% and +36+/-38%, respectively). 4. Pretreatment with L-NAME (10 microg kg(-1) min(-1) i.v.) tended to reduce basal RVC (control -11.8+/-1.4, +L-NAME -7.9+/-1.8 ml min(-1) mmHg(-1) x 10(-2)), and significantly increased basal FF (control +15.9+/-0.8, +L-NAME +31.0+/-3.7%). In the presence of L-NAME, renal vasoconstrictor responses to Ang II were not significantly modified (-38+/-3% vs -35+/-13% at 30 ng kg(-1) min(-1)), but Ang II now induced dose-dependent decreases in GFR, Uv and UNaV (-51+/-11%, -41+/-14% and -31+/-17%, respectively, at an infusion rate of Ang II, 30 ng kg(-1) min(-1)). When evaluated over the range of 1-30 ng kg(-1) min(-1), the effect of Ang II on GFR and Uv were statistically significant (P < 0.05), but on UNaV did not quite achieve statistical significance (P=0.066). However, there was no associated change in FENa observed, suggesting a non-tubular site of interaction between Ang II and NO. 5. In contrast to its effects after pretreatment with L-NAME alone, Ang II (1-30 ng kg(-1) min(-1)) failed to reduce renal vascular conductance in rats pretreated with the combination of L-NAME and the selective angiotensin AT1 receptor antagonist, GR117289 (1 mg kg(-1) i.v.). This suggests that the renal vascular effects of Ang II are mediated through AT1 receptors. Over the same dose range, Ang II also failed to significantly reduce GFR or Uv. 6. In conclusion, the renal haemodynamic effects of Ang II in the rat kidney appear to be modulated by cyclooxygenase-derived prostaglandins and NO. The precise site(s) of such an interaction cannot be determined from the present data, but the data suggest complex interactions at the level of the glomerulus.