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Biomedical subjects

A Röckel

Publications and source records attributed to A Röckel.

At least 19 recordsLinked to original sources

Prevalence of adrenal and extra-adrenal Conn syndrome in hypertensive patients.

BACKGROUND: Primary aldosteronism (PA) is caused by an adrenal aldosterone-producing tumor (A-APT) or adrenal hyperplasia. An extra-adrenal APT (E-APT) as a cause of PA has been reported in 5 cases. Autopsy studies show a high incidence of ectopic adrenocortical tissue. We did a prospective study of the prevalence of A-APTs and E-APTs and the biochemical features of E-APTs in patients with PA. METHODS: Hypertensive patients (N = 3900) referred to our unit were screened for PA by measuring renin activity, urinary aldosterone-18-glucuronide, tetrahydroaldosterone, and 18-hydroxycorticosterone (18-OH-B). Primary aldosteronism was found in 257 cases. The differentiation between A-APTs and adrenal hyperplasia was based on the results of postural response of renin, plasma aldosterone, 18-OH-B, computed tomography, isotope scanning, or adrenal venous aldosterone. Ultrasound examination of the abdomen was used to screen for E-APT. RESULTS: The cause of PA was bilateral adrenal hyperplasia in 101 cases, unilateral adrenal hyperplasia in 2, an A-APT in 146, and an E-APT in 1. The site of aldosterone production was uncertain in 7 patients who had normal adrenal glands on computed tomography but refused to undergo isotopic scanning and adrenal venous catheterization. Ultrasound examination disclosed normal retroperitoneum in 4 of the 7 cases but could not rule out E-APT in 3 cases. The biochemical features of the patient with the E-APT were similar to classic A-APT, with low renin, high aldosterone, and high 18-OH-B values without appropriate response to posture or to short-term volume expansion. The excision of the E-APT in the right kidney resulted in normalization of blood pressure and renin, aldosterone, and 18-OH-B levels. CONCLUSION: Although E-APT is rare, it should be considered in the interests of specific therapy for PA because aldosterone-secreting malignant ovarian tumors also have been reported.

Adrenal Cortex Neoplasms

A new subset of mineralocorticoid hypertension with excess of 21-deoxyaldosterone and Kelly's-M1 steroid: clinical and morphological findings.

Ten cases of adrenal adenomas, one case with unilateral adrenal hyperplasia, and another case with apparent bilateral are reported, in whom an alternative pathway of aldosterone via 21-deoxyaldosterone is operative. They all manifested hypertension, low renin activity, low normal potassium values, as well as high urinary excretion rates of 21-deoxyaldosterone and its related metabolite Kelly's-M1 steroid. In all cases, urinary aldosterone metabolites (aldosterone-18-glucuronide and tetrahydroaldosterone) and aldosterone precursor 18-hydroxycorticosterone levels were normal. Hence, the adrenal lesions give rise to hyper-21-deoxyaldosteronism. 21-Deoxyaldosterone is a weak mineralocorticoid, and its elevated production in the presence of normal aldosterone can induce a pathological state of hypermineralocorticoidism. Adrenalectomy resulted in normalization of hypertension in six of eight and amelioration in two of eight cases. Six of seven adenoma cases examined as well as the case of unilateral adrenal hyperplasia were sensitive to ACTH. One of the seven adenomas and, as expected, the case with apparent bilateral hyperplasia were angiotensin responsive. Histologically and electron microscopically, the operated adenomas consisted predominantly of clear cells, characterized by mitochondria with tubulo-vesicular internal structure similar to those of the zona fasciculata (in contrast, our classical Conn's adenoma with normal 21-deoxyaldosterone excretion exhibited a more heterogenous histological appearance and were, in terms of ultrastructure, more similar to cells of the zona glomerulosa). Ultrastructurally and immunocytochemically, the clear cells of 21-deoxyaldosterone adenomas showed features of both the zona glomerulosa and the zona fasciculata and are, hence, considered to be hybrid cells. We conclude that the determination of 21-deoxyaldosterone and Kelly's-M1 should be considered in the diagnosis of mineralocorticoid-induced forms of hypertension, especially when an adrenal adenoma has been detected with an imaging procedure.

Adenoma

Role of 21-deoxyaldosterone in human hypertension.

21-Deoxyaldosterone has been postulated to be a precursor of aldosterone in an alternative biosynthesis pathway and Kelly's-M1 is considered to be its metabolite. In healthy volunteers, the excretion rate of 21-deoxyaldosterone and of Kelly's-M1 are significantly lower than the aldosterone metabolites, aldosterone-18-glucuronide and tetrahydro-aldosterone and than the aldosterone precursor 18-OH-corticosterone. Essential hypertension patients (with low and normal renin) excrete comparable values of 21-deoxyaldosterone and Kelly's-M1 as normotensives. In 66% of aldosterone-producing adenoma cases (APA) and in 60% of idiopathic hyperaldosteronism (IHA) patients, significantly raised values of 21-deoxyaldosterone and Kelly's-M1 were found. The patients with the high excretion rates of both steroids showed only moderately increased values of the aldosterone metabolites, aldosterone-18-glucuronide and tetrahydro-aldosterone, as well as of the aldosterone precursor 18-OH-corticosterone. In contrast, the latter mentioned steroids were excreted in higher amounts in those patients with normal excretion of 21-deoxyaldosterone and Kelly's-M1. Hence, it is suggested that aldosterone is produced alternatively either via 18-OH-corticosterone alone or additionally via 21-deoxyaldosterone. Furthermore, in three cases of "incidentally" discovered adrenal adenomas, 21-deoxyaldosterone and Kelly's-M1 were the only elevated steroids. After adrenalectomy, excretion of 21-deoxyaldosterone and of Kelly's-M1 and blood pressure returned to normal, which proves that these steroids play a role in blood pressure regulation. In essential hypertension, ACTH infusion induced a significant increase of 21-deoxyaldosterone and Kelly's-M1. However, the increase after angiotensin II was 3- to 6-fold higher than after ACTH. IHA patients proved to be more responsive to angiotensin II; and, in contrast, APA cases proved to be more sensitive to ACTH. The data suggest that beside the main route of aldosterone biosynthesis via 11-deoxycorticosterone, corticosterone and 18-OH-corticosterone an alternative pathway exists via 21-deoxyaldosterone in healthy and in hypertensive patients. There are similarities between the regulation of 21-deoxyaldosterone and the regulation of aldosterone. The determination of 21-deoxyaldosterone and its possible metabolite Kelly's-M1 might be appropriate in the diagnosis of mineralocorticoid-induced forms of hypertension, especially when an adrenal adenoma is discovered.

Adenoma

Dialyzer permeability for low-molecular-weight proteins. Comparison between polysulfone, polyamide and cuprammonium-rayon dialyzers.

The aim of the study was to compare under in vivo conditions the new polyamide (Polyflux 160, Gambro) and cuprammonium-rayon dialyzers (AM-FP-17, Asahi; Clirans SE15NL, Terumo) with the polysulfone dialyzer (F60, Fresenius) regarding their permeability for beta-2-microglobulin (11.8 kD), retinol binding protein (21 kD), alpha-1-microglobulin (26.7 kD), alpha-1-glycoprotein (41 kD), alpha-1-antitrypsin (54 kD), albumin (66.3 kD) and transferrin (90 kD). The marker substances were measured by nephelometry or radioimmunoassay. To evaluate the membrane permeability, sieving coefficients 20 min after the start of hemodialysis were calculated using the concentration in the afferent and efferent blood line and in the ultrafiltrate. To get an idea about convective protein loss during a hemofiltration session, the values were computed in milligrams per 20 liters ultrafiltrate. Concerning the permeability of beta-2-microglobulin, the F60, AM-FP-17 and the Polyflux 160 hemofilter were comparable. In the molecular weight range of 20-60 kD both synthetic hemofilters were nearly impermeable. However, the cuprammonium-rayon dialyzers showed in this range a higher cutoff. The calculated albumin and transferrin loss is lower than those of CAPD patients or patients with nephrotic syndrome.

Aged

Characterization of "refilling types" by continuous blood volume monitoring during hemodialysis.

Fluid removal during HD is frequently associated with acute hypotension due to insufficient mobilization of extravascular fluid and subsequent hypovolemia. Large variability in vascular refilling makes dialysis therapy difficult and requires a better understanding of fluid distribution in the individual hemodialysis (HD) patient. Blood volume monitoring was performed by continuous measurement of blood density with a DMA 46 Density Meter (Fa. Chempro, PAAR, Austria) in six patients on regular HD treatment. A body filtration coefficient (CF = extra/intravascular fluid shift) was calculated using a computer model by Schneditz et al (1990) and blood density was measured during a 60-minute ultrafiltration period (1/3 x delta kg/hr = 19 +/- 4 ml/min). Concerning blood density differences (delta f%) and body filtration coefficient (CF) there was a wide inter-individual range (delta f = 2.8-8.0%, CF = 3-9 ml/mm Hg/min), but there was a good intraindividual reproducibility of delta f and CF. A negative correlation (r = -0.95) between delta f and CF could be established. The severity of hypotensive episodes and frequency of interventions correlated well with delta f and CF; severe symptoms occurred with a delta f > 6% and a CF < 4 ml/mm Hg/min. These results suggest that improvement in dialysis therapy can be achieved by blood volume monitoring and classification of "refilling types." By blood volume-controlled computerized sodium and UF profiles, a reduction of hypotensive episodes and emergency intervention might be possible.

Blood Volume

Low-molecular-weight protein-permeable cuprammonium rayon haemofilter.

Searching for a dialyser membrane with a cut-off similar to that of the human glomerulus, a modified cuprammonium rayon (AM-75-UP) and a polyacrylonitrile (PAN-15-DX) haemofilter were tested in vivo for the ability to eliminate substances of a molecular weight (MW) of 10-65 kilodaltons (kDa). Endogenous marker substances of a defined MW (beta-2-microglobulin 11.8 kDa; retinol binding protein 21 kDa; alpha-1-microglobulin 26.7 kDa; alpha-1-glycoprotein 41 kDa; alpha-1-antitrypsin 54 kDa; albumin 66.3 kDa) were measured by laser nephelometry or immunosorbent assay; sieving coefficients (SC) and protein elimination (PE) per 20 l haemofiltration were calculated for each low-MW protein. The PAN haemofilter shows elimination characteristics comparable to those of earlier tested haemofilters (polysulphone, AN69, cellulose triacetate) with a sharp cut-off in the MW range of 10-15 kDa. The cuprammonium rayon haemofilter is permeable for proteins with a higher MW; especially for alpha-1-microglobulin a relevant removal (SC 0.2; PE 0.56 g/20 l) was established. This membrane has a cut-off more similar to that of the human glomerulus; but far from the demanded quality with a relevant removal of substances in the MW range up to 60 kDa. Calculated albumin loss (2.4 +/- 0.2 g/20 l) seems to be tolerable for stable haemodialysis patients.

Acrylic Resins

Allergy to dialysis materials.

One hundred and six unselected patients were screened for allergic symptoms, specific IgE against ethylene oxide (ETO), isocyanates (ISO), formaldehyde (FA), phthalates (PHT), total IgE and eosinophil count. Complement activation was measured during cellulosic dialysis in atopic patients and in a control group. Sixteen patients demonstrated mild allergic symptoms during dialysis treatment. Ten of them had IgE elevation and eosinophilia. Eight of these patients had positive RASTs (ETO: n = 5, ETO-ISO(?)-FA: n = 2, ISO-PHT: n = 1) against dialysis material. All eight had an eosinophilia and seven showed an IgE elevation. An amelioration of symptoms could be obtained in three patients with elevated (greater than 15%) ETO-binding values after switching to ETO-free dialysers; avoiding PHT- and ISO-containing dialysis materials allergic symptoms remained constant. Cuprammonium rayon-induced complement activation had a more rapid onset and was more pronounced in atopic patients. The study confirms the role of ETO, but not of the other dialysis materials in the allergic sensitisation of haemodialysis patients.

Complement Activation

Transmembranous transport and adsorption of beta-2-microglobulin during hemodialysis using polysulfone, polyacrylonitrile, polymethylmethacrylate and cuprammonium rayon membranes.

Beta-2-microglobulin (b2M) was identified as a causative agent of amyloidosis associated with long-term hemodialysis (HD). Therefore, we examined handling of b2M during a 4-hour hemodialysis session. We compared b2M adsoprtion and diffusive/convective elimination between high-flux membranes such as polysulfone (PS; F 60, Fresenius), polyacrylonitrile (AN 69; Filtral, Hospal) and polyacrylonitrile (PAN, PAN 12CX2, Asahi) and less permeable membranes such as cuprammonium rayon (CR; AM 160 H, Asahi) and polymethylmethacrylate (PMMA; BK-1.6 U, Toray). To calculate total elimination, arterio-venous differences of b2M were measured at 0, 5, 20, 60 and 240 minutes; dialysate concentration was analyzed to evaluate diffusive/convective transport. Differences between recovery in dialysate and total removal were regarded as amount removed by adsorption. Total elimination per 4-hour hemodialysis session and per m2 membrane surface was 154.7 +/- 12.3 mg for the PS, 137.8 +/- 28.4 mg for the AN 69, 179.8 +/- 47.5 mg for the PAN, 130.8 +/- 11.8 mg for the PMMA and 14.4 +/- 16.0 mg for the CR membrane. Diffusive/convective transport was 128.0 +/- 18.1 mg for PS, 54.7 +/- 8.1 mg for AN 69 and 106.5 +/- 20.8 mg for PAN and insignificant for PMMA and CR. Adsorption was 26.7 +/- 4.3 mg for PS, 83.1 +/- 29.0 mg for AN 69 and 59.8 +/- 17.2 mg for PAN. Besides transmembranous transport sorption is an important mode of elimination. Weekly endogenous generation rate is about twice as high as b2M elimination.

Acrylic Resins

Beta-2-microglobulin adsorption and release in-vitro: influence of membrane material, osmolality and heparin.

We studied the effects of cuprammonium rayon (CR), polyacrylonitrile (PAN), polysulfone (PS), changes in osmolality, and heparin dosage on beta-2-microglobulin (b2M) handling in an in-vitro model that excluded convective transport and minimized diffusive transport. Both PAN and PS exhibited high adsorption capacity for b2M. Osmolality changes had no effect on b2M adsorption or release. CR membrane adsorption was minimal but increased slightly when higher heparin doses were used. In experiments with CR and high heparin doses (4 U/ml) b2M release occurred during the first 15 minutes of in-vitro dialysis, but this increase was inhibited by removing the leukocytes from the blood, indicating that b2M is released from leukocytes.

Acrylic Resins

[Hypokalemia as the principal symptom of covert vomiting. Clinical and diagnostic aspects].

In ten adults (nine females), referred for hypokalemia as the cardinal symptom of uncertain etiology and normal blood pressure, surreptitious self-induced vomiting was demonstrated as the main cause. In the majority of such patients, the pathognomonic pattern of serum and urine electrolytes (in the unstable phase--loss of gastric juice) allows diagnosis without hospitalization. If there are atypical urinary electrolyte values or the patients deny vomiting, hospitalization or part-hospitalization is recommended, with parenteral administration of 1 litre physiological saline daily under weight control, and (if necessary) toxicological urine tests for diuretics if there is a high urinary chloride level. In this manner a sufficiently accurate diagnosis is possible.

Adolescent

Polyacrylonitrile complement activation attenuated by simultaneous ultrafiltration and adsorption.

The highly permeable synthetic polyacrylonitrile (PAN) membrane (Filtral; Hospal, Basle) is regarded as biocompatible for its slight complement activation and leucocyte sequestration. The low C3a and C5a concentrations during PAN dialysis may be due to a lack of complement activation potential of this polymer, but also to elimination of activated complement components by the dialyser through adsorption and/or ultrafiltration (mol wt of C3a and C4a 9000 daltons; of C5a 11,000 daltons). Comparing arteriovenous differences throughout the study, higher concentrations of C3a (+23%; n.s.) and C5a (+80%; P less than 0.05) were measured in the efferent blood lines, suggesting a slight complement activation by the alternate pathway. A significantly lower C4a concentration in the efferent blood lines (-30%, P less than 0.05) indicates an elimination within the dialyser. Significantly higher arteriovenous concentration differences at the beginning of dialysis and increasing sieving coefficients suggest elimination by adsorption, mainly in the first 20 min of haemodialysis. The continuous decrease of C3a and C4a plasma concentrations in the afferent blood line suggests transport across the membrane and removal by the dialysate. Accordingly, measurable amounts of these complement components were detected in ultrafiltrate.

Acrylic Resins

Regulation of parotid kallikrein secretion-role of the alpha 2- and beta-adrenergic system.

The effects of pharmacologically induced alterations of alpha 1, alpha 2 and beta-adrenergic system on kallikrein secretion - measured as amidolytic activity - in rat parotid gland were tested in vivo. Beta and alpha 1/2-adrenergic stimulation (Orciprenaline, alpha-methylnorepinephrine) caused a comparably significant increase of parotid kallikrein secretion. Alpha 2-receptor blockade (yohimbine) but not the alpha 1-antagonist prazosin, partly abolished the effect of alpha-methylnorepinephrine. The effects of the alpha 1-adreno-receptor agonist norfenephrine on kallikrein secretion were significantly lower compared to alpha 1/2-adreno-receptor-stimulation.

Adrenergic alpha-Agonists

Permeability and secondary membrane formation of a high flux polysulfone hemofilter.

It has been assumed that the molecular weight (MW) cut-off of a newly fabricated polysulfone capillary dialyzer (F60, Fresenius, FRG) is similar to that of the human glomerulus. We recently tested the device in vivo and found this not to be so, based on the device's ability to eliminate substances of a MW of 10,000 to 60,000 daltons. One of the reasons for this discrepancy was found to be the influence of secondary membrane formation on solute permeability. Endogenous marker substances of a defined MW (beta 2-microglobulin, myoglobin, RBP, alpha 1-microglobulin, acid alpha 1-glycoprotein, alpha 1-antitrypsin, prealbumin, and albumin were measured by laser nephelometry or radioimmune assay; sieving coefficients (SC) and protein eliminations were calculated for each low MW protein.

Blood

Pharmacokinetics of the loop diuretic piretanide in renal failure.

Piretanide 60 mg was administered intravenously over 30 min to 15 men with different degrees of renal failure. The mean piretanide serum concentration at the end of the infusion period was 5.72 +/- 1.51 micrograms/ml. Serum piretanide concentration-time curves declined biexponentially and 24 hours after medication the serum level had fallen to less than twice the detection limit. The terminal half-life ranged from 1.63 to 3.44 h. A relationship to creatinine clearance was not demonstrable. The mean metabolic clearance of piretanide was 107.7 +/- 47.6 ml/min/1.73 m2 body surface area and was the same as that reported for healthy subjects. The renal clearance of piretanide ranged from 3.33 to 43.9 ml/min/1.73 m2 body surface area and very closely correlated with the creatinine clearance (p less than 0.01). Its renal clearance depended principally on active secretion of the drug into the tubule, and glomerular filtration appeared unimportant. There was a close relationship between the amount of piretanide excreted in the urine and the creatinine clearance. Because the diuretic effect of piretanide depends on the concentration of the drug in the tubule, the observed correlation might be of use in evaluating the appropriate dosage of piretanide in patients with renal failure. The present data suggest that single daily doses of piretanide will not result in accumulation, even when high doses are administered to patients with advanced renal failure.

Adult