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Biomedical subjects

J Rapoport

Publications and source records attributed to J Rapoport.

At least 73 records · Page 4Linked to original sources

Vascular hypersensitivity to noradrenaline: a possible mechanism of hypertension in rats with chronic uraemia.

Studies were performed to evaluate the mechanism involved in the hypertension of moderate renal failure in partially (five-sixth) nephrectomized rats. Cardiac index (CI) was studied by means of the microsphere technique, and systemic vascular resistance (SVR) calculated from the mean arterial resistance MAP/CI, in four groups of experimental animals: (A) partially nephrectomized rats; (B) group A rats chronically treated with the calcium channel blocker verapamil; (C) sham-operated rats; (D) sham-operated rats treated with verapamil. The results demonstrate a significant increase in MAP in group A rats, which was due to a 72% increase in SVR as compared with groups C and D. In group B rats, MAP decreased significantly owing to a marked decrease in SVR (40%) as compared with group A. However, MAP remained higher in group B than in group C. The vascular responsiveness to noradrenaline was studied in group A, group C and group A rats after parathyroidectomy (group A1). An increased pressor responsiveness to noradrenaline was indicated by a shift of the noradrenaline dose-response curve to the left in group A rats as compared with group C rats. This change was corrected after partial nephrectomy. We conclude that hypertension in nephrectomized rats is due to an increase in SVR, and that an increased pressor responsiveness to catecholamines may play a role in this phenomenon. Furthermore, verapamil reduced the hypertension, and parathyroidectomy improved the abnormal sensitivity to noradrenaline in group A rats. These results raise the possibility that an abnormality in calcium metabolism, possibly due to secondary hyperparathyroidism, may be implicated in the hypertension of mildly uraemic rats.

Animals↗

Losses of 1,25- and 24,25-dihydroxycholecalciferol in the peritoneal fluid of patients treated with continuous ambulatory peritoneal dialysis.

We measured peritoneal losses of the active vitamin D metabolites 1,25(OH)2D3 and 24,25(OH)2D3 in patients receiving continuous ambulatory peritoneal dialysis (CAPD). The serum concentration of 24,25(OH)2D3 was considerably lower than in hemodialysis patients. The serum concentration of 1,25(OH)2D3 was undetectable and rose to levels similar to those in hemodialysis patients only after loading with much higher oral doses of 1-alpha-vitamin D3 than those received by hemodialysis patients. Losses of both metabolites in peritoneal fluid were considerable, averaging approximately 6-8% of the plasma pool per day. These losses lead to low serum levels of these active vitamin D metabolites in CAPD patients, which may be an important factor in exacerbating renal osteodystrophy. Our results indicate the need for increased replacement doses of vitamin D metabolites in CAPD patients.

24,25-Dihydroxyvitamin D 3↗

X-ray microanalysis of uremic nephrocalcinosis.

The nature of uremic nephrocalcinosis was studied by means of X-ray microanalysis in 5/6 nephrectomized rats. The data show that calcified deposits in the renal parenchyma of uremic rats contained substantial amounts of calcium, magnesium, aluminum and silicon. Since calcificates did not reveal a uniform composition they were arbitrarily divided into 3 categories: 'high-calcium' with Mg:Al:Si: Ca molar ratios 7:3:8:37; 'low-calcium' particles were characterized by Fe:Mg:Al:Ca:Si molar ratios 7:3:5:6:13; while 'intermediate-calcium' particles showed Al:Mg:Si:Ca molar ratios equivalent to 2:4:6:7. The variability of calcified deposits in the renal parenchyma of 5/6 nephrectomized rats might be due to different sources, different environmental conditions along the nephron and different stages of calcification process. It is suggested that aluminum and silicon content of deposits may be of value in further characterization of uremic nephrocalcinosis.

Aluminum↗

Active metabolites of imipramine and desipramine in man.

Active hydroxy metabolites of imipramine (IMI) and desipramine (DMI) have been quantified in plasma and cerebrospinal fluid (CSF) from patients at steady-state. In plasma of prepubescent boys and adults the concentration of unconjugated 2-hydroxyimipramine is only 15% to 25% that of IMI; 2-hydroxydesipramine (OH-DMI) concentration, however, is usually 50% that of DMI and in some cases OH-DMI is the predominant compound. In CSF from adult patients the ratio of concentrations of OH-DMI/DMI is higher than in plasma. Judging from the CSF/plasma ratio 12% of DMI exists in the free form at steady state, whereas 16% of OH-DMI is free (P less than 0.02). There is no evidence for saturation of hydroxylation within the therapeutic dose and concentration ranges investigated. On the basis of a steady-state OH-DMI/DMI ratio of less than 1/30 in plasma 5% of the population studied could be classified as deficient DMI hydroxylators. This in the same as the incidence of deficient debrisoquine hydroxylators reported in other populations.

Adolescent↗

Retention of antidiuretic hormone-induced particle aggregates by luminal membranes separated from toad bladder epithelial cells.

Aggregates of intramembrane particles appear in the luminal membranes of renal collecting duct and amphibian bladder cells after stimulation by antidiuretic hormone (ADH). We undertook this freeze-fracture study to determine whether particle aggregates, once in place, remain in the luminal membrane of the amphibian bladder after the membrane is physically separated from the rest of the cell. We found that the aggregates do remain in high yield in isolated membranes stabilized with a bifunctional imidoester (DTBP) followed by fixation with glutaraldehyde, or unfixed but stabilized with DTBP. These findings support the view that the particles are intrinsic membrane components and that their organization in the form of aggregates does not depend on the presence of the intact cell. In addition, the availability of isolated membranes containing particle aggregates provides a starting point for the isolation of the water-conducting proteins.

Animals↗

Tubular handling of sodium following immersion to the neck and salt-induced volume expansion.

We wished to compare the natriuretic and diuretic effect of extracellular volume expansion (ECVE) with 0.9% NaCl to that obtained with up-to-the-neck immersion (NI) in healthy volunteers. Clearance techniques during maximal antidiuretic hormone suppression were utilized to pinpoint the sites of tubular NaCl reabsorption. Mean glomerular filtration rate (GFR) did not differ significantly between ECVE and NI; mean rate of sodium excretion during ECVE was significantly greater than during NI, whereas mean water clearance for a given rate of distal delivery was higher with NI than with ECVE. Our findings suggest that ECVE is associated with greater natriuresis than NI, despite the equality of filtered sodium loads and of distal deliveries under both these procedures.

Adult↗

Stabilization of vasopressin-induced membrane events by bifunctional imidoesters.

Vasopressin increases the water permeability of the luminal membrane of the toad bladder epithelial cell. This change in permeability correlates with the occurrence in luminal membranes of intramembrane particle aggregates, which may be the sites for transmembrane water flow. Withdrawal of vasopressin is ordinarily associated with a rapid reduction of water flow to baseline values and a simultaneous disappearance of the particle aggregates. The bifunctional imidoesters dithiobispropionimidate (DTBP) and dimethylsuberimidate (DMS), which cross-link amino groups in membrane proteins and lipids, slow the return of water flow to baseline after vasopressin withdrawal. Cross-linking is maximal at pH 10, and is reduced as pH is lowered. Freeze-fracture studies show persistence of luminal membrane particle aggregates in cross-linked bladders and a reduction in their frequency as water flow diminishes. Fusion of aggregate-containing cytoplasmic tubular membrane structures with the luminal membrane is also maintained by the imidoesters. Reductive cleavage of the central S-S bond of DTBP by beta-mercaptoethanol reverses cross-linking, permitting resumption of the rapid disappearance of the vasopressin effect. Bladders that have undergone DTBP cross-linking and beta-mercaptoethanol reduction respond to a second stimulation by vasopressin. Thus, the imidoesters provide a physiologic and reversible means of stabilizing normally rapid membrane events.

Animals↗

Childhood obsessive-compulsive disorder.

The authors collected clinical diagnostic, neurophysiological, electrophysiological, and biochemical data on 9 adolescents who had primary obsessive-compulsive disorder. The results indicate considerable descriptive validity of the syndrome in childhood and its independence from obsessional traits; however, all of the children had a history of major depressive disorder, and their sleep EEG measures resembled those of young adults with primary depressive disorder. The patients' families did not have a more consistent pattern of anxiety disorder or any other psychiatric disorder than do families of adult obsessive patients. Psycholinguistic test results showed a lack of normal laterality, which has been reported for other psychiatric illness.

Adolescent↗

Lithium-induced nephrogenic diabetes insipidus: studies of tubular function and pathogenesis.

We describe a patient with lithium-induced nephrogenic diabetes insipidus in whom detailed investigations of distal tubular function were performed. Clearance of free water during water diuresis was found to be augmented. This suggests proximal suppression of sodium reabsorption by lithium. Reabsorption of free water during high solute clearance was impaired. Acidification of the urine following ammonium chloride loading was abnormal, and this was corrected by sodium sulfate infusion. The cellular mechanism of lithium was investigated by means of indomethacin, an inhibitor of prostaglandin synthesis. Indomethacin caused a partial reversal of the nephrogenic diabetes insipidus, suggesting that the primary cellular action of lithium may be to inhibit the formation of cyclic AMP in the collecting duct cell, although a direct action of indomethacin in increasing solutes in the renal medulla could not be ruled out. It is possible that the lithium-induced polyuria is partially due to an enhancement by lithium of renal prostaglandin action.

Ammonia↗

Echocardiography in infective endocarditis. Lack of specificity in patients with valvular pathology.

59 patients with suspected infective endocarditis on a natural valve were studied by M-Mode echocardiography to determine the specificity of the ultrasonic technique in detecting valvular vegetations. All echocardiograms were read independently by two observers who were unaware of the final diagnosis. Among 40 patients who later proved not to have infective endocarditis, two (5%) were diagnosed by echocardiography as having either possible or probably vegetation by at least one observer. Both patients with a false positive diagnosis of vegetation had pre-existing valvular pathology, the presence of which greatly complicated the interpretation of the echocardiogram. Inter-observer disagreement occurred in 5 of the 59 studies (8.5%). The results of this study suggest that caution should be exerted in the echocardiographic diagnosis of vegetation in patients with pre-existing valvular pathology.

Adolescent↗

Patients' expectations and intention to self-medicate.

I studied patients' expectations of receiving a prescription after a consultation with their general practitioner and their intention to buy a remedy from the chemist after leaving the surgery.Of a group of 368 patients, 56 per cent expected to receive a prescription and 24 per cent intended to self-medicate. A striking variation was found among patients attending each of the five doctors participating in the study. Patient expectation closely agreed with the prescribing rate per partner. No consistent relationship was found between a low prescribing rate and high self-medication rates. I suggest that by reducing prescribing and encouraging patients to be self-reliant in the management of minor ailments, it might be possible to reduce a general practitioner's workload and the amount of money spent on prescribing in general practice.

Adolescent↗