Cardiac function in experimental uremia.

In acutely uremic animals, the contractile force of the heart is consistently increased; such an increase can be dissociated from changes of afterload or catecholaminergic drive. It is associated with diminished sarcolemmal Na,K-ATPase activity in the heart which, in turn, may be related to increased levels of endogenous digitalis-like substances (endigens) that have been postulated to represent a natriuretic factor. In patients with chronic uremia, myocardial contractility is usually normal, but occasionally there may be heart failure unrelated to pre-existing hypertension, coronary heart disease, anemia, fluid overload, or other recognizable factors. So far, the experimental basis for this clinical observation is uncertain. Possible causes for the clinical syndrome include an excess of parathyroid hormone or cardiodepressor substances. There is experimental evidence of impaired cardiac response to beta adrenergic agonists, e.g., decreased isoproterenol-dependent calcium uptake, diminished inotropic and chronotropic responses. In acutely uremic rats, cardiac cyclic AMP levels are high but can be reversed by beta blockers. Heart calcium content is variable and heart weight is constantly increased in acutely uremic rats, despite decreased skeletal muscle mass. The change in heart weight is not related to anemia, to an excess of parathyroid hormone, or to sympathetic activity; its cause remains unknown. Experimental studies to date have shown a variety of abnormalities, but do not provide a uniform concept of the mechanisms or an explanation for the cardiac dysfunction so often observed in patients with uremia.

[Brucellosis with fatal endotoxic shock]. / Bruzellose mit tödlichem Endotoxinschock.

BACKGROUND: Brucellosis is a zoonosis with good prognosis in cases of early diagnosis. To make the diagnosis is still a problem today. CASE REPORT: A 60-year-old butcher was admitted with undulating fever, sweats, arthralgia and weight loss. Further examination revealed hepatosplenomegaly with laboratory findings of a hepatitis and multiple focal liver lesions shown by abdominal ultrasound and CT. Histologically, these lesions corresponded to caseous granulomas. Diagnosis of brucellosis was confirmed by detection of brucella species in prolonged incubation in blood culture. After the beginning of antibiotic resistance-tested therapy with tetracycline and quinolones, an endotoxic shock occurred during the first 24 hours of treatment and the patient died after multiorgan failure with disseminated intravascular coagulation. CONCLUSION: In cases of undulating fever with liver involvement, a brucellosis should be considered. Good teamwork of the internal, pathological and microbiological departments is necessary for early and correct diagnosis. This is the first report of human brucellosis in association with lethal endotoxic shock.

Treatment of hypertension in dialysis patients.

Hypertension is common in hemodialyzed patients and constitutes an important cardiovascular risk factor. Fluid retention, inappropriate stimulation of the renin-angiotensin system, sympathetic overactivity and changes of vessel wall structure have been shown to be important factors in its pathogenesis. It has been claimed that hemofiltration permits a better control of hypertension in the interdialytic interval, although the evidence is not perfectly convincing; blood pressure tends to be lower with continuous ambulatory peritoneal dialysis. While fluid withdrawal and - within certain limits - adjustment of dialysate sodium concentration constitutes a primary line of therapy, antihypertensive medication is necessary in approximately 20% of patients. Specific problems with dialysis patients are cumulation of drugs (some cardioselective beta-blockers, alpha-methyldopa, captopril), altered dose-response relationship (diuretics) and particularly interaction with cardiovascular stability during fluid withdrawal.

[24-hour blood pressure measurement in type-2 diabetic patients with and without nephropathy]. / 24-Stunden-Blutdruckmessung bei Typ-2-Diabetikern mit und ohne Nephropathie.

24-hour ambulatory blood-pressure measurements were obtained according to criteria of the German Hypertension League in 61 non-insulin-dependent diabetic patients after admission to hospital under clinical routine conditions. 30 patients had no signs of nephropathy; 15 patients showed signs of proteinuria of more than 0.5 g/d and/or renal insufficiency, and 16 patients were on chronic hemodialysis renal replacement therapy. Despite antihypertensive therapy, the majority of NIDDM patients with nephropathy and/or dialysis therapy were hypertensive. Hypertension of non-nephropathic patients showed a better response to therapy. About 50% of all patients with nephropathy had a higher mean arterial blood pressure at night than during the daytime. In about 25% of all diabetics with nephropathy, we found, during night time, an especially pronounced increase of both systolic and diastolic blood pressure of more than 5% above the daytime values. Diabetic patients without nephropathy already show a reduced night/daytime variation of blood pressure, however, inverse circadian rhythm as a sign of prognostically non-favorable autonomic neuropathy was found almost exclusively in the nephropathic diabetic patients.

Clinical course and symptomatic prediagnostic period of patients with Wegener's granulomatosis and microscopic polyangiitis.

The clinical course of 15 patients with Wegener's granulomatosis (WG) and eight patients with microscopic polyangiitis (MPA) from one nephrological clinical center is presented for the period from 1984 to 1993, when testing for antineutrophil cytoplasmic antibodies (ANCA) was gradually introduced into routine clinical practice. We found a high degree of prolonged time periods with symptoms attributable to WG or MPA until the specific diagnosis was made. Nine patients with WG and one patient with MPA had symptomatic prediagnostic periods of more than three years, which extended in one case up to twenty years. In these prediagnostic periods, often even severe flares of vasculitic activity resulted in spontaneous remission without immunosuppressive therapy. One patient on chronic dialysis for four months because of rapidly progressive glomerulonephritis, experienced sufficient spontaneous regain of residual renal function to stay off dialysis for 6 years. Despite a high amount of spontaneous recovery, recurrent flares of disease eventually led to death in those cases without sufficient immunosuppressive therapy. Contrary to long courses of disease, one patient with WG had a fulminate exacerbation of disease with lethal hemoptysis after a prediagnostic period of only three months. Renal disease, respiratory and other symptoms did not occur sequentially, but each could precede the other. We conclude in agreement with published former experience, that WG and MPA show a highly variable spontaneous disease course, that requires extended observational periods for evaluating maintenance therapies.

Calciuric response to 1,25-(OH)2D3 in early renal failure.

In 10 patients with early renal failure (glomerular filtration rate between 30 and 80 ml/min/1.73 m2) without nephrotic syndrome and in 13 controls the calciuric response to increasing oral doses of calcitriol [1,25-(OH)2D3] (0.25; 0.5; 1.0; 1.5 micrograms/day) was evaluated. Patients had initially normal plasma calcitriol levels, normocalcemia and hypocalciuria. With calcitriol doses up to 1 microgram/day, the increment of UVCa was less in patients. Only at 1.5 micrograms/day the calciuria of patients reached the baseline calciuria of controls. The data document that 1.0 microgram calcitriol per day is required to normalize UVCa in patients with early renal failure and normal calcitriol levels. Blunted calciuric response to low doses of calcitriol is compatible with an altered dose-response relationship.

Response of alkaline phosphatase to zinc repletion in hypozincemic hemodialysis patients.

The response of serum alkaline phosphatase (AP), a zinc-dependent metalloenzyme, to zinc administration via the dialysate (400 micrograms/l) was examined in 14 hypozincemic (less than 30th percentile of dialysis patients) hemodialysis patients and in 14 placebo-treated matched dialysis control patients. Plasma zinc and serum AP were measured three times: prior to, once weekly during (5 weeks), and 2 weeks after addition of zinc to the dialysate. The serum zinc levels remained stable in placebo-treated controls (initial 87.7 +/- 12.5; final 78.6 +/- 8.3 micrograms/dl) and increased in zinc-treated patients (initial 76.4 +/- 8.3; 5th week 96.9 +/- 13.3; 2 weeks after zinc withdrawal 82.3 +/- 12.2 micrograms/dl). There was a slight increase of AP with time in placebo controls (initial 90.2 +/- 26.5; 5th week 100 +/- 29 U/l) and a more pronounced increase in zinc-treated patients (initial 90.8 +/- 19.9; 5th week 113 +/- 20.9 U/l). The difference between the two groups was marginally significant (p less than 0.05; analysis of variance). It is concluded that zinc repletion via dialysate with documented increase of serum zinc levels in initially hypozincemic dialysis patients causes a reversible increase of serum AP. The result is compatible with some tissue zinc deficiency in hypozincemic dialysis patients.

[Effects of various forms of myocardial protection on cardiac function, metabolism, and blood flow (author's transl)]. / Funktion, Stoffwechsel und Durchblutung des Myokards bei verschiedenen Formen des Myokardschutzes.

The myocardial protective effect of two cardioplegic solutions was studied after an ischemic period of 2 h in eight dogs. Group I received a high potassium solution (St. Thomas Hospital) and group II a sodium withdrawal solution with high colloid osmotic pressure (Eppendorf solution). With the exception of a prolonged myocardial K+ washout (10 min) in group I, which was presumably responsible for fibrillation in the early reperfusion period, no major metabolic or perfusion differences between the two groups were observed. After 30 min of reperfusion, postischemic LV function (-43%) and O2 uptake (-43%) were equally reduced in both groups.

Efficiency of cardioplegia in the presence of coronary occlusion.

Myocardial tissue pH and temperatures (MT) were continuously measured in dogs on total cardio-pulmonary bypass (CPB) after acute distal coronary artery occlusion. Measurements were performed in a collateralized area with myocardial blood flow (MBF) ranging from 20 to 80 ml/100 g-min (microspheres). Immediately after coronary artery occlusion the aorta was clamped and the heart perfused with a cardioplegic solution (Bretschneider HP, 41 ml/kg, 4 degrees C). Prolonged regional fibrillation was observed and MT fell to 20 degrees C in 10 min in the low perfusion area (LPA) and in 2 min in the control area (CA). Whereas MTs were practically identical 15 min after termination of cardioplegic perfusion the magnitude of H+ accumulation continued to be greater in the LPA. During blood reperfusion with the coronary snare released MBF was significantly lower in the LPA as opposed to the CA indicating a microcirculatory derangement. Accordingly the bipolar ECG revealed signs of regional ischemia even after 30 min of reperfusion. We conclude that myocardial protection may be inadequate in areas located distal to coronary occlusion. This is true not only in cases of acute severe ischemia but also when collateral resistance is sufficiently high to impede the flow of cold viscous cardioplegic solutions. Results derived from intermittent MT measurements may be erroneous because intramyocardial heat equilibration may mask the inhomogeneous cardioplegic perfusion.

Primary bilateral renal centrocytic non-Hodgkin's lymphoma as a cause of renal failure.

We present a patient whose cause of renal failure was primary and isolated bilateral renal manifestation of centrocytic non-Hodgkin's lymphoma. The treatment options for bilateral primary renal lymphoma are discussed against the background of published data concerning this topic.

Mycophenolate mofetil for maintenance therapy of Wegener's granulomatosis and microscopic polyangiitis: a pilot study in 11 patients with renal involvement.

Successful maintenance therapy with mycophenolate mofetil (MMF) 2 g/d and low-dose oral corticosteroids (OCS) over a period of 15 mo was given to patients with Wegener's granulomatosis (WG) (n = 9) and microscopic polyangiitis (MPA) (n = 2). All patients had severe generalized disease with pauci-immune necrotizing glomerulonephritis and received standard induction therapy with oral cyclophosphamide and OCS for a mean of 14 wk until remission was achieved. Of 11 patients, only one WG patient relapsed in the 14th month of maintenance therapy. Maintenance therapy with MMF was able to further reduce grumbling disease activity as measured by the Birmingham vasculitis activity score (BVAS2) and proteinuria that were still present by the end of induction therapy. OCS could be reduced to a median daily dose of 5 mg and discontinued in three patients. Possible drug-related adverse effects were transient and included abdominal pain, respiratory infection, diarrhea, leukopenia, and a cytomegalovirus-colitis in one patient that was successfully treated with ganciclovir. It is concluded that MMF in combination with low-dose OCS is well tolerated and effective for maintenance therapy of WG and MPA. Long-term treatment with MMF in these diseases is attractive because of its low toxicity. MMF will have to be studied further and compared with cyclophosphamide or azathioprine maintenance therapy in randomized trials.

Experience with zinc protoporphyrin as a marker of endogenous iron availability in chronic haemodialysis patients.

BACKGROUND: Ferritin and the percentage of transferrin saturation (TS) are established parameters with which to evaluate endogenous iron availability during treatment of renal anaemia with recombinant human erythropoietin (rHuEpo). Zinc protoporphyrin (ZPP) has been proposed as another valid marker in this setting. METHODS: We determined the following parameters in 127 patients, including 117 haemodialysis patients: haemoglobin, erythrocytes, haematocrit, mean corpuscular volume (MCV), iron, ferritin, transferrin saturation and ZPP. Of the patients treated in a cross-sectional study, 38.5% were treated with rHuEpo; 30.7% with intravenous iron; and 13.6% with intravenous iron and rHuEpo simultaneously. Median ferritin was 304 ng/ml and median transferrin saturation was 21.2%. RESULTS: Including cases with manifest storage iron deficiency, a concordant elevated ZPP ( > 40 mumol/mol haem) and a decreased transferrin saturation ( < 20%) were found in 23 of our dialysis patients (19.6%) while 55 cases (47%) were classified as concordantly negative. However, as many as 39 cases (33.3%) showed discrepant results: in 16 cases (13.6%) ZPP was elevated but transferrin saturation was in the normal range, while in 23 cases (19.6%) the opposite results were observed. CONCLUSIONS: We conclude that beyond the border of manifest storage iron deficiency, defined as a ferritin < 30 ng/ml in male and < 15 ng/ml in female patients, ZPP and TS cover different ranges of functional iron deficiency which is reflected in the lack of a correlation of ZPP to any other of the above-mentioned parameters. Our data suggest that a TS < 20% as a diagnostic, and thus intervention, criterion in the evaluation of functional iron deficiency and iron substitution beyond manifest storage iron deficiency might result in overestimation of iron requirements. It remains to be shown in a longitudinal study, also reflecting the course of haemoglobin and the mean rHuEpo dose, whether ZPP or TS is the more appropriate parameter in the evaluation of functional iron availability.