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.

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.

[The clinical value of sequential renal scans with 131 iodo-hipuran and renal perfusion with 99mtc compounds using computer analysis (author's transl)]. / Klinischer Wert der Nierensequenzszintigraphie mit 131Jod-Hippuran und der Nierenperfusion mit 99mTc-Präparaten nach Computerverarbeitung

Two methods of sequential scintigraphy are considered critically: a) Quantitative computer evaluation of nephrograms obtained by a gamma camera using 131Iodo-Hipuran. b) Quantitative flow studies of the kidneys after bolus injections of 99mTc preparations. Statistical evaluation of data from 171 patients examined by both methods has shown that the isotope nephrogram is not sufficiently sensitive for diagnostic purposes. Isotope nephrography combined with estimations of effective renal plasma flow on each side separately is of value to the urological surgeon by providing important information regarding severe degrees of renal functional impairment. Perfusion measurements, using a gamma camera and 99mTc preparations, are a promising survey method for the diagnosis of renal artery stenosis. (Much of this work is contained in a dissertation by C. Knick).

Three cases of hemodialysis-associated hypersensitivity reactions.

According to the United States Food and Drug Administration, untoward reactions to capillary hemodialyzers occur at a rate of 3.5 of every 100,000 dialyzers sold. Allergic symptoms immediately after initiation of dialysis consist of burning retrosternal pain, sensation of diffuse heat, cold perspiration, periorbital and facial edema, flushing, laryngeal stridor, bronchial hypersecretion, hypotension, bradycardia, and loss of consciousness. In 1982 Popli et al. reported four patients suffering from such allergic manifestations; three were successfully managed after being taken off dialysis. These investigators thought that inadequate rinsing of cuprammonium cellulose capillary dialyzers was responsible for the reactions, and recommended rinsing the blood compartment with 2 liters of normal saline, and the dialysate compartment with 10 liters of dialysate, both in a single-pass fashion over 20 minutes. Nichols and Platts (1982) (3) reported 15 patients with urticaria, severe bronchospasm, and shock occurring immediately after the blood had been returned from the dialyzer. These authors suggested that the sterilizing agent, ethylene oxide (ETO), was responsible. Poothullil et al. (1975) (4) described a patient with pruritus, severe dyspnea, and hypotension during dialysis. On the basis of a positive skin prick test (dermal reaction to ETO-exposed human albumin) and of antigen-induced histamine release from peripheral leucocytes, these workers suggested that ETO was responsible for the allergic reactions. Marshall et al. (1984) (5) reported that 8.9% of hemodialysis patients had positive skin tests to ETO and that 12.1% were ETO-radioallergosorbent test (RAST) positive.(ABSTRACT TRUNCATED AT 250 WORDS)

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.

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.

[Retroperitoneal fibrosis]. / Retroperitonealfibrose.

A 53-year-old man without previous significant illness developed severe backache. Neither physiotherapy nor nonsteroidal anti-inflammatory drugs improved his condition so that he had been regularly taking pain-killing medication. 6 months later elevated retention values were detected and the patient was admitted to hospital. On admission the erythrocyte sedimentation rate (ESR) was markedly elevated in the presence of a normocytic anaemia, serum creatinine concentration of 3.71 mg/dl (blood urea of 112 mg/dl) and haematuria. Sonography demonstrated bilateral hydronephrosis, stage III, and a weekly echogenic para-aortic mass. Abdominal computed tomography showed a half-moon-shaped density anterior to the aorta. The middle segments of both ureters were displaced medially and the proximal parts dilated. Other causes (tumour, drug therapy, inflammation) having been largely excluded, idiopathic retroperitoneal fibrosis was diagnosed. The marked urinary obstruction necessitated the implantation of double-J-stents. Immunosuppressive treatment was started with daily 150 mg azathioprine and, initially, 50 mg prednisone. Within one week the serum creatinine concentration and ESR had fallen and the signs of urinary obstruction regressed.

Pharmacokinetics of azlocillin in persons with normal and impaired renal functions.

The pharmacokinetics of azlocillin, a new wide-spectrum antibiotic of the N-substituted group of ureidomethyl penicillins, was investigated in 10 subjects with normal and in 32 subjects with impaired renal functions. After intravenous injection of 2 g of azlocillin, serum concentrations of drug were measured microbiologically. The half-lives of azlocillin were 47 +/- 8.8 min in patients with normal renal function, and 293.3 min in patients with severely impaired renal function. The correlation of half-life to renal functions is shown by the equation: t/2 = 425.03.Cl(In) (-0.4509), where Cl(In) is inulin clearance. The volume of distribution of the azlocillin was 17.7% of the body weight. Protein binding was similar in patients with normal renal function and in those with severely impaired renal functions. The urinary excretion rate of azlocillin in patients with normal renal function was 64.8 +/- 8.8% in 24 h.

[Opisthorchis felineus--the cat liver fluke. Differential diagnosis of right-side upper abdominal pain]. / Opisthorchis felineus--der kleine Katzenleberegel. Differentialdiagnose des rechtsseitigen Oberbauchschmerzes.

For several weeks a 58-year-old woman had suffered from intermittent right upper abdominal and flank pain, loss of appetite, weight loss (2 kg in 8 weeks), as well as constipation. She had a mild eosinophilia of 0.48/nl, while the blood picture and differential count were normal. There was no evidence of cholestasis, liver disease or an inflammatory process. Upper abdominal ultrasound examination demonstrated a gall-bladder polyp with cholelithiasis and sludge. Although the intrahepatic biliary tract was normal, the gallbladder was much enlarged and contracted only moderately after a test meal. A parasitological disease was included in the differential diagnosis because the patient had lived in Tomsk, Siberia, until the previous year. Examination of faeces and duodenal secretion discovered eggs of Opisthorchis felineus, a liver fluke especially common in Siberia and the Ukraine. It was successfully treated by a single-day administration of praziquantel, 3 times 25 mg/kg after meals. A week later the patient was symptom-free and no eggs were found in the stool.

[Cor triatriatum sinistrum--value of pulmonary vein flow in hemodynamic assessment]. / Cor triatriatum sinistrum--Wertigkeit des Lungenvenenflusses bei der hämodynamischen Beurteilung.

We report on two patients (a 52-year-old female and a 32-year-old male) with cor triatriatum sinistrum, both clinically inconspicuous. The former had undergone strenuous athletic training without difficulty for eight years of her youth. In both cases, cor triatriatum sinistrum was found by chance during transthoracic echocardiography undertaken for hypertension. The exact insertion-site of the left atrial membrane only became apparent by using biplane transoesophageal echocardiography. Neither of the patients showed associated cardiac malformation. Hemodynamics were evaluated by pulsed waved Doppler analysis of pulmonary venous flow profile; no signs of inflow obliteration into the left atrium were found in either case.

[Plasma-cAMP in primary and secondary hyperparathyroidism (author's transl)]. / Plasma-cAMP bei primärem und sekundärem Hyperparathyreoidismus

3 patients with operatively proven primary hyperparathyroidism showed normal plasma cAMP concentrations. 5 patients in chronic dialysis treatment independent of the level of parathyroid hormone had increased plasma cAMP concentrations. These observations suggest that there is under these circumstances no regulation of plasma cAMP by the parathyroid hormone.

Effect of diazoxide on left ventricular performance in hypertension.

The effect of diazoxide on left ventricular performance during rest and isometric exercise (handgrip) was examined in 16 unselected hypertensive patients, 6 of whom had been pretreated with the beta-adrenergic blocking agent pindolol. Diazoxide regularly and promptly produced a fall in left ventricle systolic and end diastolic pressures, and an increase in heart rate and left ventricular dp/dtmax. Haemodynamic changes were maximal 2 minutes after injection of the drug and decreased little over the next 8 minutes. After beta-adrenergic blockade, diazoxide caused a more pronounced reduction in left ventricular systolic pressure and a less marked fall in end-diastolic pressure, whilst the diazoxide-induced rise in heart rate was partially and the increase of dp/dtmax was completly inhibited. The increase in systolic pressure during isometric exercise was not influenced by diazoxide, but the positive inotropic reaction was augmented. The findings appear to show that cardiac stimulation by diazoxide is due to a reflex mechanism transmitted by baroreceptors, and that improvement of cardiac performance is mainly due to a reduction of left ventricular after-load.

Pharmacokinetics of intravenous enoximone in dialysis patients.

The new vasodilator and inotropic drug enoximone was given to dialysis patients as a single intravenous dose of 1 mg/kg. Plasma concentrations were measured up to 240 min. The mother compound enoximone reached a high plasma concentration intravenously, followed by a quick decline of the plasma concentration curve (t1/2 = 1.5 h), comparable to that of normal volunteers. The sulfoxide metabolite, however, had a tremendously prolonged half-life (t1/2 = 7.8 h) in comparison to healthy volunteers (t1/2 = 2.2 h). The volume of distribution of enoximone varies from 0.7-4.8 L/kg with a mean of 2.11 L/kg in comparison to 1.6 L/kg in healthy individuals. The area under the curve (AUC) of enoximone was 815.2 ng/ml/h, and that of the sulfoxide metabolite was 10,200.1 ng/ml/h.

Vascular calcifications under maintenance hemodialysis.

In a cross-sectional study X-rays of the forefoot and the pelvis of 101 adult dialysis patients were taken. Vascular calcifications (forefoot) were observed in 20 patients. The incidence was higher in patients who had been started on dialysis several years ago. However, in a longitudinal prospective study de novo appearance of vascular calcificaitons was observed only in 1 out of 50 dialysed patients, although hyperparathyreoidism and moderate hyperphosphatemia persisted. Vascular calcifications were seen only once in 138 uremic children (56 uremic children without dialysis; 82 uremic children on maintenance hemodialysis). However at autopsy visceral calcifications of the lung were found in three (out of 11) children who did not have vascular calcificaitons on X-rays.

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.

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.