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The purpose of this study was to examine the effects of the angiotensin-converting enzyme (ACE) inhibitor cilazapril on the elastic properties of the aorta. A standard diuretic antihypertensive drug, hydrochlorothiazide, served for comparisons. Increased aortic stiffness leads to a reduction of the buffering windkessel function and is a major component in the pathophysiology of systolic hypertension, inducing an increase in left ventricular afterload and arterial pulsatile stress as well as a decrease in the subendocardial blood supply. Stiffness of arteries increases with age and blood pressure, and depends on the functional elastic structures of the aortic wall. ACE inhibitors have been shown to directly influence elastic properties of peripheral arteries. Seventeen patients with mild to moderate essential hypertension (age 45-67 years) were treated for 3 months double-blind randomized with either cilazapril (C) 5 mg daily (n = 9) or hydrochlorothiazide (HCTZ) 25 mg daily (n = 8). Aortic elastic properties were noninvasively assessed by measurement of pulse wave velocity along the aorta at rest and during isometric handgrip stress. Accelerated pulse wave velocity indicates elevated arterial stiffness and vice versa. A pressure standardized index of aortic cross-sectional distensibility (2 m) was calculated from arterial mean pressure and pulse wave velocity. Compared with pretreatment values, both therapies significantly reduced blood pressure and pulse wave velocity at rest (C: 9.4 +/- 0.9 vs. 7.7 +/- 0.7 m/sec; HcTZ: 8.9 +/- 0.3 vs. 7.8 +/- 0.4 m/sec; means +/- SEM p < 0.05). During isometric stress only C showed a significant decrease in pulse wave velocity (C: 11.3 +/- 0.8 vs. 9.1 +/- 0.8 m/sec; HCTZ: 9.9 +/- 0.5 vs. 9.0 +/- 0.5 m/sec; means +/- SEM p < 0.05). The index 2m at rest and during handgrip increased significantly (p < 0.05) after C but not after HCTZ. With cilazapril we obtained steeper slopes for the treatment-induced reductions in blood pressure and pulse wave velocity for both rest and handgrip stress values. Correlation of the data at rest and during stress revealed a direct relationship between blood pressure and pulse wave velocity. HCTZ linearly extended the relation observed before treatment toward lower values of blood pressure and corresponding pulse wave velocity without changing the relation per se. Cilazapril, in contrast, moved the relation between these variables and decelerated the pulse wave velocities to a greater extent than would have been expected from the corresponding blood pressure reduction (delta approximately 1 m/sec). These results in patients with mild to moderate essential hypertension support the idea that ACE inhibitors, in addition to reducing blood pressure, may exert an additional hemodynamic effect in improving the elastic properties of the aorta.

Two noninvasive methods for assessment of the compliance (1/E') of the aortic windkessel in man are presented and were tested for their ability to detect increases in stiffness of the aorta induced by atropine (0.012 and 0.024 mg/kg sequentially) in the presence and absence of a beta-blockade with propranolol 240 mg (n = 9). Method A, based on the calculation of the relation between pulse pressure and systolic storage volume of the aorta, requires measurement of blood pressure, systolic and diastolic time intervals and stroke volume. Method B, based on measurement of pulse wave velocity along the aorta also requires several anthropometric data (body surface area, age). Both methods were able to detect a dose-dependent increase in E' following atropine injections; method A has greater relative changes than method B. The average maximal increases were 90 and 40 percent of the baseline before atropine. The daily baselines of E' averaged 0.6 Torr x cm-3 for method A and 0.9 Torr x cm-3 for method B. Propranolol itself did not influence E' but dampened the atropine effects. The results from method A and B were correlated with r = 0.70 and 0.60 resp. (p < 0.01). The results suggest the use of these relatively simple techniques for evaluation of aortic compliance under influence of varying pathophysiological conditions or/and pharmacological interventions.

In 135 patients with different glomerular diseases but normal glomerular filtration rates (CCr and In = 103 +/- 2ml/min) correlations between morphological tubular lesions (tic) and changes in tubular function were investigated. Between the extent of tubular lesions and the impairment of specific tubular functions (formula; see text) exists a highly significant correlation. The combined diminution in Uosmmax and UNH4 + V reflects in 72 per cent the appearance of a severe tubular lesion and should be used for its clinical recognition.

In 237 patients with chronic glomerulonephritis and according to the serum creatinine level of functional compensation tubular and tubulointerstitial renal functions, respectively, were investigated and compared with the light-microscopic findings of the renal interstice. A distinct structural tubulointerstitial lesion (tiK) was found in 30%. The diagnostic predictivity for the recognition and the exclusion of the tiK was tested for single or paired data of the renal function. As a result it is possible with a suitable combination of parameters in on an average more than 80% of the cases to establish or to exclude function-diagnostically a tubulointerstitial structural lesion even in still inconspicuous creatinine values. From the clinical point of view thus the information value of functional diagnostic investigations of the renal water treatment is confirmed (concentration power, dilution ability, water diuresis), in which case the differentiated test of the renal acidification may supplement the informations about the tiK-situation.

For the judgment of the success of the immunosuppressive therapy of chronic glomerulonephritis 400 patients (242 males and 158 females) at an average age of 31.2 years were examined after an average duration of treatment of 31.9 months. Apart from the renal function (serum creatinine), the histological and immunohistological form of the glomerulonephritis for the valuation further clinico-paraclinical data were taken into consideration: proteinuria, nephrotic syndrome, arterial hypertension and the combination of nephrotic syndrome and arterial hypertension. At the beginning of the treatment 293 of 400 patients (73.2%) had a normal renal function, 107 of 400 patients (26.8%) were initially renal-insufficient. 16 of 400 patients (4.0%) had additionally a pyelonephritis and 12 of 400 patients (3.0%) had a lupus nephritis. 27 of 400 patients (6.9%) developed a terminal renal insufficiency after an average duration of observation of 40.5 months. Complications caused by therapy were registered in 104 of 400 patients (26.0%). Recommendations for the present therapy of chronic glomerulonephritis are formulated.

In 366 patients with bioptical verified and functional compensated chronic glomerulonephritis the relations between the clinical course types of glomerulonephritis according to Ratner, the histological changes and the tubular homoeostatic parameters of renal function, respectively, were investigated. A reliable connection was found between the clinical course type and special tubular functional parameters. With reference to histological changes the occurrence of a tubulo-interstitial lesion (tiK) is the cause of an excessive disturbance of the renal tubular function. Independently of this, however, the clinical course type of chronic glomerulonephritis may be responsible for the pathological reactive failure of tubular functional parameters. In the case of renal tubular dysfunction in the active nephritic type (ANT) and the nephrotic type with hypertension (NHT), respectively, the occurrence of a tik is much likely. By the lack of reno-tubular dysfunction in ANT and NHT a tik be cannot excluded. In contrast to this, in the inactive nephrotic type (INT) and the nephrotic type without hypertension (NHT), respectively, a tik be can excluded by lack of tubular dysfunction. On the other side, a tubular dysfunction in these groups is not a certain proof of a tik.

Freshly isolated rat hepatocytes maintained as monolayers in a serum-free medium synthesize sulphated glycosaminoglycans, most of which behave as heparan sulphate and are mainly distributed into intracellular compartments. Cyclic AMP, dibutyryl cyclic AMP, glucagon, noradrenaline, prostaglandin E(1), and theophylline, all drugs and hormones known to increase intracellular cyclic AMP concentrations, decreased the incorporation of (35)SO(4) (2-) into heparan sulphate of intra-, extra- and peri-cellular pools. The inhibition mediated by dibutyryl cyclic AMP was dose-dependent and observed as early as 2h after exposure to the drug. In the presence of 1mm-dibutyryl cyclic AMP, incorporation of (35)SO(4) (2-) or [(14)C]glucosamine into heparan sulphate was decreased to 40-50%, suggesting that dibutyryl cyclic AMP interfered with the synthesis of heparan sulphate. This was further supported by pulse-chase experiments, where dibutyryl cyclic AMP had no effect on the degradation of sulphated glycosaminoglycans. Heparan sulphates synthesized and secreted into the extracellular pool in the presence of dibutyryl cyclic AMP were smaller in size, whereas the degree of sulphation and molecular size of the heparan sulphate chains released by beta-elimination from these proteoglycans were not different from control values. In the presence of 1mm-cycloheximide, (35)SO(4) (2-) incorporation was decreased to 5%. Addition of p-nitrophenyl beta-d-xyloside, an artificial acceptor of glycosaminoglycan chain synthesis, enhanced this incorporation to 18%. Dibutyryl cyclic AMP did not have any inhibitory effect on the synthesis of chains initiated on p-nitrophenyl beta-d-xylosides. Incorporation of [(3)H]serine into heparan sulphate was not affected by dibutyryl cyclic AMP, whereas the degree of substitution of serine residues with heparan sulphate chains was less in heparan sulphate synthesized in the presence of dibutyryl cyclic AMP, suggesting that cyclic AMP exerts its effect on the metabolism of sulphated glycosaminoglycans by affecting the transfer of xylose on to the protein core.

The results of a 6-month Prednisone therapy (initial 60 mg/d with later reduction of dose) are given as the immediate results of therapy (after 6 months in 128 patients) and as a late result (after 11 years in 107 patients). The course is evaluated on the basis of clinical symptoms. The early effect proved to be an improvement in 2/3 of all cases, whereby 22% were total remissions. In the late results patients with primary total remission showed the best functional results. This therapy is justified in nephrotic, proteinuric-hypertonic, purely proteinuric and proteinuric-haematuric forms of mesangioproliferative glomerulonephritis.

The Hanausek apparatus has been used for reposition and retention of luxation of the hip joint in the Orthopädische Klinik Hessisch Lichtenau in 37 cases aged up to 2 years, if there was no hindrance of reposition in arthrography. It is a functional method which avoids the extreme Lorenz position that is claimed to endanger the caput femoris respecting necrosis. In a retrospective roentgenological observation it became evident, that the method of Hanausek leads generally to a good development of the acetabulum. The rate of necrosis in our patients was high (17%). Our patients started treatment later (38% aged more than one year). 2/3 of the patients had a high luxation of the hip joint.

The correlation analysis of the relationship between blood lead levels and lead-in-air concentrations measured in three winter periods showed a highly significant association despite a generally loose dependence of the variables. The regression equations clearly show that there would be a finite residual blood lead value even with completely lead-free air. In the case of the populations exposed to motor traffic in this study, this residual blood lead value is 80--90% of the initial value prior to the decrease in immission. The regression equations, statistically yield results which compare convincingly with ones obtained from model calculations based on studies of metabolism and respiratory physiology. The correlation between the observed changes in blood lead and the initial absolute values of blood lead concentration demonstrates with high statistical certainty that the higher the initial level, the greater was the observed change. This type of association also implies that there is a lower limit value of blood lead below which the decrease in blood lead changes to an increase despite reduction of lead-in-air.

In 110 patients with mesangioproliferative glomerulonephritis the treatment (n = 48) with chlorambucil, warfarin, dipyridamol and prednisone (CAA) and the treatment with imuran and prednisone (CP, n = 23) are compared with the conditions of an untreated control group. The CAA-therapy is above all suited for active clinical pictures without sclerosis with short duration of the disease, even when the renal function is already restricted. The CP-therapy is suitable in non-active forms with sclerosis also in a longer duration of the disease.

In a retrospective study involving 97 patients with histologically confirmed glomerulonephritis the complications which led to the breaking off or changing of an immunosuppressive therapy [Prednison monotherapy (n = 39), Prednison cyclophospohamide therapy (n = 13), Prednison azathioprin therapy (n = 49), Indometazin therapy (n = 25)] were examined. Of 97 patients treated repeatedly over long periods, 22 suffered complications which caused the therapy to be broken off or changed. Because of the risk involved, immunosuppressive therapy of glomerulonephritis should only be practised by institutions specializing in nephrology.

As a result of the long-term treatment of 360 patients with histologically ascertained glomerulonephritis including 41 dead patients who had suffered from uraemia a clinical classification of the chronic glomerulonephritis (Ratner, M.) is presented. In detail 5 types of clinical course are characterized: Nephritic types of course: maximally active nephritic type of course, active nephritic type of course, inactive nephritic type of course. Nephrotic types of course: nephrotic type of course without hypertension, nephrotic type of course with hypertension. The elaborated clinical classification allows conclusions to underlying renal histology, tendency of the progression of the disease and prognosis, including survival time.

The indication and effectiveness of the immunosuppressive therapy of chronic glomerulonephritis is now as ever controversial. As a result of a retrospective therapy study in an at least one-year therapy with cytostatics, thrombocyte aggregation inhibitors and anticoagulants (CAA-therapy, n = 27), additional prednisone therapy (CAAP-therapy, n = 95) and cytostatic-prednisone therapy (CP-therapy, n = 33) we find favourable results for the CAA/CAAP-therapy in the nephrotic syndrome and glomerulonephritides with distinct clinical exacerbation also in sclerosations in histology. Clinically inactive nephritides with exclusive urinary findings and sclerosations cannot be influenced therapeutically.

By epicutaneous skin test by means of 1-monochlorine-2,4-dinitrobenzene (DNCB) the primary cell-conditioned immunity is induced and is provable by the allergic skin reaction of late type. The examination of 125 clinically healthy persons of either sex at the age of 17-57 years confirms the suitability of self-produced, welded into foil skin test plasters layered with DNCB in various stages of concentration for clinical use. A 48-hour skin contact with 0.049 molar DNCB-solution (1,000 microgram DNCB: 100 microliter Ol. oliv.) leads to a late reaction in 84% of the cases, in the repeated case in 98% of the cases. The valuation of the eczema-typical symptoms is suitable for the characterization and quantification. There were no differences in age and sex. Ultrastrong reactions were not registered.

Glomerular perm selectivity can be approximately estimated from the apparent glomerular protein clearance in terms of molecular weight since the relative protein clearance is approximately identical with the corresponding screen coefficient relation. Systematic relativization of individual protein clearances by reference to albumin (or transferrin) clearance requires the application of special calculations to find out the regression coefficients relevant to functional diagnosis. A PAH load influences tubular protein reabsorption so that the clearance of higher-molecular proteins (IgA alpha 2-macroglobuli, IgM) rises. Taking the changes in protein clearance under renotubular PAH load into account allows a more precise estimation of glomerular permeability to be made, in comparison with protein analyses not using PAH load.

Primary cultures of rat hepatocytes grown in a serum-free medium supplemented with [35S]sulfate synthesize 35S-labelled glycosaminoglycans at an almost constant rate for 58 h. Approx. 57% of the newly synthesized 35S-labelled glycosaminoglycans remain within the hepatocytes, approx. 30% become associated with the cell surface and only 13% are secreted into the medium. The amount of cell-surface-associated 35S-labelled glycosaminoglycans became constant within 36 h, whereas no equilibrium was reached in the intra- and extracellular pool. During a 24 h chase more than 50% of the intracellular and cell-surface-associated 35S-labelled glycosaminoglycans disappears, more than 80% of this material is degraded and radioactivity is recovered as inorganic sulfate. A minor part is released into the medium in a macromolecular form. Heparan sulfate accounts for more than 95% of the 35S-labelled glycosaminoglycans in each of the three pools. It is distinguished from heparan sulfates from other sources by the presence of unsubstituted glucosamine residues. In all three pools, heparan sulfate chains of mean molecular weights between 24 000 and 30 000 are part of an alkali labile proteoglycan. Intra- and extracellularly, however, part of the heparan sulfate appears to have little, if any, protein attached. Hepatocytes contain heparan sulfate-degrading endoglycosidase activity, which may contribute to the variation of molecular weights observed for the heparan sulfate.

Patients with bioptically ascertained glomerulonephritis of the years 1969-1981 were examined. At the time of the kidney biopsy etiology, onset of the disease and data of the findings were evaluated. Moreover, in 160 out of 300 patients after-examinations were performed. Especially also the examination of patients with erythrocyturia was carried out with the help of the phase contrast microscopy. In a second part of the examinations which we report on 2 therapy studies were performed. In the first therapy study the effectiveness of the therapy with prednisolone (n = 33), prednisolone + cytostatic drug (n = 43) as well as the indomethacin treatment (n = 52) in patients with and without nephrotic syndrome was examined. We found that an initial prednisolone dose of more than 50 mg/die for at least over 1 month is more successful than a low prednisolone dose. Indomethacin has no clinically provable therapeutic effect in the nephrotic syndrome. In normal renal function the duration of the disease has no ascertained influence on the results of the therapy. In the second therapy study the effectiveness of the CAA- (n = 27) and the CAAP-therapy, respectively, (n = 98) (cytostatic drugs, anticoagulant drugs, thrombocyte aggregation inhibitors and prednisolone) was investigated. The results of the therapy depending upon the clinical course and the morphological findings revealed that there is an indication to the CAA-CAAP-therapy in nephrotic syndromes in glomerulonephritis with and without sclerosation as well as in glomerulonephritis with relapsing exacerbations with and without sclerosations. No indication for this therapy is given in chronic courses of glomerulonephritis with slight proteinuria and in nephrotic syndromes with hypertension.