Biomedical subjects
Publications and source records attributed to A Mandelbaum.
The isomeric 2-, 3-, 5-, 6- and 8-quinolinylphthalimides give rise to different electron impact ionization mass spectra, which permit easy distinction. The specific fragmentation process are rationalized in terms of proximity effects and stabilization of cyclic ion structures. Collision-induced dissociation spectra were used to support the proposed ion structures of major fragment ions.
A bilateral, exercise-mediated renal functional abnormality was first described more than a decade ago. The disturbance is specific for hypertension, is seen in different forms of hypertension, and has been studied most extensively in hypertensives with renovascular disease. The bilateral-abnormal exercise renogram identifies the disturbance. Hypertensives with unilateral renovascular disease were studied in the continuing evaluation of the bilateral function disturbance. We examined 31 hypertensives with documented unilateral renovascular disease, all of whom had renography at rest and during 60 to 80 W ergometric exercise. An additional seven normotensives and 17 essential hypertensives served as controls, and had the same sequence of studies. All patients reported upon continued on to an infusion clearance with 131I-hippurate and 111In-diethylenetriamine pentaacetic acid to determine glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) at rest, and during 25 W ergometric exercise. Eighteen of 31 hypertensives with unilateral renovascular disease were found to have a bilateral-abnormal exercise renogram. Clearance examinations in these identified a prominent reduction of the GFR and a lesser decrease in the ERPF during exercise. Hypertensives with normal exercise renograms did not have the exercise mediated abnormal clearance pattern. Similar results were observed in the control population of essential hypertensives, 65% of whom developed the functional disturbance. The seven normotensives controls did not exhibit the exercise mediated function changes. We conclude that an exercise-mediated bilaterally occurring functional disturbance exists in certain hypertensives, who then have a bilateral-abnormal exercise renogram. Associated with this is a distinctly abnormal clearance during exercise which is characterized by a low filtration fraction.
A correct estimation of volume status and so-called dry weight in dialysis patients remains a difficult clinical problem. Clinical status and chest X-ray are not sensitive enough, while invasively measured central venous pressures are not routinely available. Recently, the sonographic determination of the diameter and collapse of the inferior vena cava (IVC) has been proposed as a noninvasive method for estimating intravascular volume. We tried to evaluate the clinical relevance of this method in dialysis patients by comparing it with central venous pressures (CVP) and atrial natriuretic peptide (ANP). To establish a normal range and to control for confounding variables, we examined a large number of healthy controls. Furthermore, the influence of tricuspid insufficiency was examined echocardiographically. Measurements of the IVC diameters were well reproducible, with a coefficient of variation for interobserver error of 2.2%, and a coefficient of variation of 1.4% for intraobserver error. The collapse index was less well reproducible and therefore not used for further analysis. In 86 normal controls (age 18 to 76 years), IVC diameters showed a wide variation, and they were not correlated to age, height, weight, or body surface area. However, there was a significant correlation of IVCex to heart rate (r = 0.63, P < 0.001). Therefore, we calculated percentiles of the heart rate-IVCex relation in normals, and compared the results in patients to these. In 10 overhydrated haemodialysis patients, CVP was closely correlated to IVCex (r = 0.72, P < 0.001), but there was a wide interindividual variation of the slope of this relation. An IVCex above the 95th percentile of normal was a good predictor of an elevated CVP (i.e. > 12 cmH2O). In another 39 stable, chronic haemodialysis patients, there was a significant correlation of the intradialytic decrease of ANP and IVCex (r = 0.69, P < 0.001). However, this correlation existed only in patients without tricuspid insufficiency. In summary, sonography of the inferior vena cava is a valuable tool for estimating dry weight in dialysis patients, provided that some caveats are kept in mind: (i) there is a wide variation of IVC diameters in normals, and single measurements are not helpful in individual patients; (ii) there is a significant, inverse correlation between IVC diameters and heart rate, and the precision of intravascular volume assessment is enhanced by interpreting heart rate corrected diameters; (iii) the presence of tricuspid insufficiency leads to unreliable results, as it influences IVC diameters per se. Intravascular volume changes are reflected by IVC measurements, as shown by the correlation to other indices of intravascular volume, such as CVP and alpha-hANP. IVC sonography is noninvasive and easily available; serial measurements allow an estimation of changes of intravascular volume in patients without cardiac filling impairment. However, unlike with body impedance, interstitial volume is not reflected by IVC diameters.
Explore the source record for details and available documents.
BACKGROUND: Hypertensives may develop bilateral trapping of para-aminohippurate analogues in the tissue of the kidneys during light exercise, as can be demonstrated using radioactively labelled [131I]-hippurate or [99mTc]-mercaptoacetyl-triglycine. Tracer accumulation in the kidneys during exercise results in a typical renographic pattern, the bilateral-abnormal exercise renogram. The disturbance is common during exercise, being found in almost 60% of all hypertensives, regardless of aetiology. OBJECTIVE: To determine whether bilateral-abnormal exercise renograms are spurious phenomena, or whether the results of exercise renography are reproducible. DESIGN: We reviewed the renographic examinations of 27 hypertensive patients, each of whom had undergone at least one resting and two [131I]-hippurate or [99mTc]-mercaptoacetyl-triglycine gamma-camera exercise renograms. The status of the renal artery at the time of scintigraphy was documented, using available arteriograms. The causes of vascular lesions were noted, as were revascularization procedures and the antihypertensive medication being taken at the time of scintigraphy. RESULTS: The average time between exercise renograms was 15.5 months, and 24 of the 27 hypertensive patients had comparable results in the first and the follow-up exercise renogram, divergent results being noted for the other three patients. Re-evaluation of the scintigrams of the three hypertensive patients with divergent results suggested that intermittent pelvic retention might have caused errors of interpretation in two. We found it notable that neither revascularization nor a change in antihypertensive drug therapy influenced the results of exercise renography. Exercise renograms were reproducible over long periods, and potential extraneous influences on blood flow, such as antihypertensive drugs or revascularization, failed to alter the results. CONCLUSION: The results are considered relevant, because a direct relationship appears probable between hypertension and the disturbance investigated. Reproducible results suggest that the exercise-mediated disturbance is fixed to the kidneys, that it can be reactivated repeatedly and that it may play a role in maintaining hypertension.
The application of pH-zone-refining counter-current chromatography (CCC) to the preparative separation of stereoisomeric acids is described. The separation was accomplished on the basis of the difference in acidity of the two stereoisomers. pH-Zone-refining CCC of 400 mg of a crude synthetic mixture of stereoisomeric 1-methyl-4-methoxymethylcyclohexanecarboxylic acids yielded 49.5 and 40 mg of the pure Z- and E-stereoisomers respectively. The two-phase solvent system consisted of hexane-ethyl acetate-methanol-water (1:1:1:1). Trifluoro acetic and octanoic acids were used as retainer acids. The eluent base was aqueous ammonia. The eluted fraction were monitored by gas chromatography-mass spectrometry.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Vena cava diameter (VCD) was measured by ultrasonography in 10 acutely hypervolemic dialysis patients (6 men, 4 women; mean age 61.3 +/- 15.4 years), results being compared with the level of the central venous pressure (CVP) and, in 39 long-term dialysis patients (18 men, 21 women; mean age 56 +/- 15 years), with the plasma concentration of atrial natriuretic peptide (ANP). In 86 subjects without renal disease (43 men, 43 women; mean age 39.4 +/- 14.6 years) there was a statistically highly significant correlation between the end-expiratory VCD and heart rate (r = -0.63; P < 0.001). These data were used to construct a VCD/heart rate (HR) nomogram. In the ten dialysis patients HR-adjusted VCD correlated significantly at various hydration states (54 measurements) with the CVP (r = 0.72; P < 0.001). The steep slope for the relationship between CVP and VCD showed marked interindividual variations. However, in all patients (except one) with a raised CVP (> 12 cm H2O) the HR-adjusted VCD was above the 95th percentile. In the 39 patients on long-term dialysis (13 with, 25 without predialysis tricuspid regurgitation [TR] there occurred a parallel decrease in VCP and ANP during removal of fluid. In the 25 patients without TR, the fall in ANP concentration and VCD correlated significantly (r = 0.70; P < 0.001). These results indicate that, in patients with renal failure but normal cardiac function, measurement of the VCD by ultrasonography provides an adequate index of hydration.
Twelve children (< 15 yr) and 12 young adults with autosomal dominant polycystic kidney disease (ADPKD) confirmed by ultrasonography and 24 nonaffected individuals matched for age, sex, and body surface area were examined with ambulatory blood pressure monitoring and echocardiography. All patients and controls had normal renal function (median serum creatinine, 0.85 mg/dL; range, 0.5 to 1.1). In children, daytime and nighttime blood pressures were not significantly different from those of controls; the median left ventricular mass index (in grams per square meter) was higher in patients (66.6 g/m2) than in controls (61.3 g/m2; P < 0.002), although all values remained within the normal range. In young adults with ADPKD, mean arterial blood pressure was significantly higher than that in controls both during daytime (98.3 mm Hg; range, 74 to 126 versus 90.6 mm Hg; range, 73 to 116; P < 0.006) and during nighttime (83.2 mm Hg; range, 66.5 to 125 versus 79.0 mm Hg; range, 63 to 91; P < 0.05). In parallel, the median left ventricular mass index was significantly higher in young adults (81.8 g/m2; range, 62 to 174 versus 64.3 g/m2; range, 52 to 102; P < 0.02). The results document that ambulatory daytime and nighttime blood pressures and left ventricular mass indices are higher in asymptomatic carriers of the ADPKD trait compared with controls, although most values are still within the normal range.
A bilateral, exercise-mediated, hippurate transport disturbance was previously described when patients with fixed renovascular hypertension were imaged with o-iodo-hippurate. This study sought to test the hypothesis that patients with an abnormal exercise scintigram have a perfusion abnormality characterized by dysregulation of renal blood flow. We imaged 23 patients with hypertension and angiographically documented renovascular disease in the supine position, as well as during upright exercise. Seven normotensive volunteers served as controls. We measured the resting glomerular filtration rate (GFR) and the effective renal plasma flow (ERPF) with a single compartment radiotracer infusion clearance. The clearance examination also included a measurement period with 25 watt ergometric exercise. Nine hypertensive patients had normal exercise renograms. These patients had age-appropriate clearance values at rest and during exercise, as well as age-appropriate best-organ (generally without stenosis) GFR and ERPF values. The filtration fraction (FF) was 0.21 at rest and 0.22 during exercise. Fourteen hypertensive patients had a bilateral, exercise-induced disturbance of hippurate transport. In these patients, the global resting GFRs and ERPFs were decreased 40% from age-appropriate predicted values. The FF remained at 0.20. Light exercise caused a pronounced contraction of GFR and a less severe reduction in the ERPF. During exercise the mean filtration fraction was only 0.12. The exercise-induced reduction in the clearance values was bilateral, which indicated that the perfusion of nonstenosed organs was compromised as well. We suggest that the described perfusion abnormality occupies a relevant position during the maintenance phase of fixed renovascular hypertension.
Arachidonylethanolamide, an arachidonic acid derivative in porcine brain, was identified in a screen for endogenous ligands for the cannabinoid receptor. The structure of this compound, which has been named "anandamide," was determined by mass spectrometry and nuclear magnetic resonance spectroscopy and was confirmed by synthesis. Anandamide inhibited the specific binding of a radiolabeled cannabinoid probe to synaptosomal membranes in a manner typical of competitive ligands and produced a concentration-dependent inhibition of the electrically evoked twitch response to the mouse vas deferens, a characteristic effect of psychotropic cannabinoids. These properties suggest that anandamide may function as a natural ligand for the cannabinoid receptor.
Autosomal dominant polycystic kidney disease (ADPKD) is the most frequent inherited kidney disorder leading to terminal renal failure. About 8% of the dialysis patients suffer from ADPKD, the gene frequency in the general population being about 1:1000. Many facts contribute to the hypothesis that arterial hypertension plays a major role in the pathophysiology of ADPKD. We observed a prevalence of 30% of hypertension in patients with ADPKD and normal serum-creatinine, and of 80% in patients with terminal renal failure. The time of onset of abnormalities of blood pressure regulation is of great interest, since an increase of blood pressure, even in the normotensive range, accelerates the rate of progression. To answer this question, we examined the time of onset of abnormalities in blood-pressure regulation in 23 probands and 23 control patients in a cross-sectional study. The results document abnormal circadian blood-pressure changes and higher blood pressures, although still within the normotensive range, in asymptomatic carriers of the ADPKD-trait, even before and more definitely after onset of puberty. Even at an age when circadian blood pressure is not significantly different, there is an increased LVM as evidence of target organ damage. The findings suggest that (intermittent) increases in blood pressure and blood-pressure-dependent target organ damage precede overt hypertension and renal failure by years or decades.
Explore the source record for details and available documents.
We used Doppler echocardiographic techniques firstly to examine left ventricular (LV) filling patterns in dialysis patients, secondly to analyse whether Doppler echocardiographic left ventricular filling pattern is different in patients with recurrent intradialytic hypotension, and thirdly to study the relation between blood pressure decrease during volume subtraction and left ventricular filling pattern. Indices of left ventricular filling patterns of 47 dialysis patients were consistently different when compared to normotensive healthy controls. To further assess the relation of left ventricular filling pattern to blood pressure stability on dialysis, we first compared 24 patients with stable intradialytic blood pressure (BP) and 23 patients with one or more episodes or intradialytic hypotension per month. Patients with recurrent intradialytic hypotension had lower predialysis blood pressure (MAP 89 +/- 13 vs 96 +/- 14 mmHg), more severe concentric hypertrophy (left ventricular mass/volume ratio 2.7 +/- 1.4 vs 2.0 +/- 0.7), and impaired left ventricular filling (Doppler) as indicated by the ratio of early diastolic vs late (atrial) filling (0.66 +/- 0.2 vs 0.95 +/- 0.22). Subsequently we assessed by Doppler technique the effect of a predetermined rate of volume subtraction (during one dialysis session) in patients with or without recurrent intradialytic hypotension. Diastolic filling indices deteriorated consistently prior to the reduction in blood pressure (early diastolic filling 26.8 +/- 15.2 vs 45.4 +/- 10.9% of diastolic filling). It is suggested that impaired left ventricular filling, presumably reflecting disturbed left ventricular compliance, is common in dialysis patients. Findings by noninvasive Doppler techniques suggest a role of abnormal left ventricular distensibility in recurrent dialysis hypotension.
In the past, cardiac changes in renal failure have commonly been ascribed to hypertension and poorly specified toxic effects ('uraemic cardiomyopathy'). Our recent experimental and clinical studies suggest (a) that cardiac hypertrophy can be dissociated from hypertension and that blood pressures may have only a permissive role, (b) that experimental uraemia is associated with specific activation of pericytes and intermyocardiocytic fibrosis. Cardiac hypertrophy not correlated with elevated blood pressure, and intermyocardiocytic fibrosis not observed in similarly hypertensive non-uraemic patients, have recently been documented in dialysis patients. The implications of these findings may be (a) electrical instability and predisposition to a sudden cardiac death and (b) diastolic cardiac malfunction with impaired LV filling and predisposition to dialysis hypotension. Some evidence for the latter possibility is provided.
Explore the source record for details and available documents.
Explore the source record for details and available documents.