K. W. Rumpf

Increased ammonia production during forearm ischemic work test in McArdle's disease

SummaryA patient with typical features of late onset McArdles disease is described. During forearm ischemic work test the patient exhibited an exaggerated increase in ammonia release, largely exceeding normal values. It is suggested, that this is due to an activation of the myokinase/myoadenylate deaminase pathway. Besides lack of lactate release increased ammonia release during ischemia may be a typical feature of McArdles disease.ZusammenfassungEs wird ein Patient mit einem typischen “late onset” McArdle-Syndrom beschrieben. Während ischämischer Arbeit fand sich bei dem Patienten ein exzessiver Anstieg des Ammoniaks im Plasma. Dies dürfte auf einer Aktivierung der Myokinase/Myoadenylat-Deaminase-Reaktionen beruhen. Neben dem charakteristischerweise fehlenden Laktatanstieg unter ischämischer Arbeit scheint eine vermehrte Ammoniak-Freisetzung für das McArdle-Syndrom typisch zu sein.

Treatment of polycythemia vera by isovolemic large-volume erythrocytapheresis

SummaryExcess red blood cells (RBC) in patients with polycythemia vera (PV) are usually removed by repeated phlebotomy. In order to improve the efficacy of this treatment, we used isovolemic large-volume erythrocytapheresis (EA) by a cell separator. A retrospective analysis of our experience with 69 PV patients (206 EA procedures) is reported. EA induced a rapid, well-tolerated, and long-lasting reduction of Hct, Hb, and RBC counts, as well as an immediate disappearance or reduction of clinical symptoms of PV, while tissue oxygen tension — as measured in 8 patients — increased. Hct was reduced by EA from 56.8% ±5.6% to 41.9% ±6.6%, Hb from 17.5±2.3 to 12.7±2.4 g%, RBC counts from 7.±0.9 to 5.4±0.9×106/mm3. The mean volume of the apherisate was 1410±418 ml, (mean Hct 79.7%±9.3%), and the actual RBC volume removed 1113±367 ml. The isovolemic procedure was well tolerated and the acceptance by patients seemed to be better than with repeated phlebotomy. In 21 patients whose Hct values (Hct before and after EA 58%±5.7% and 41.5%±4.9%) were regularly followed after EA the mean period with Hct<50% after a single EA procedure was 6.1±4.1 months (median, 6); in 14 out of these 21 patients a Hct of <43% after EA was reached and their mean period with Hct<50% after EA was 7.6±4.0 months (median, 7.5). For three patients this period was 11, 13, and 15 months, respectively. In our experience large-volume isovolemic EA is a feasible, very effective, and welltolerated alternative treatment modality for PV patients. It may be superior to repeated phlebotomy, especially for patients with excessively increased RBC mass. Only a controlled prospective trial can answer the question, whether EA, due to its rapid effect and due to the long-lasting lower RBC mass, leads to a lower rate of thromboembolic events, and whether EA may delay the necessity for treatment of PV by cytotoxic drugs or P32.

[The effect of indomethacin on basal and stimulated plasma renin activity in normal subjects (author's transl)].

SummaryThe influence of indomethacin, a potent inhibitor of prostaglandin synthesis, on basal and stimulated plasma renin activities in normal human subjects was determined. Stimulation of the renin activity was achieved by orthostasis or by furosemide. Indomethacin led to a considerable decrease of both basal and stimulated plasma renin activity in chronic and acute experiments. Our experiments provide no evidence that major changes in the sodium balance are responsible for the effects observed. It is concluded that some antagonistic function of the renin angiotensin system and prostaglandins seems probable. These antagonistic actions might play a role in the regulation of the kidney circulation or the arterial blood pressure.ZusammenfassungEs wurde der Einfluß des Hemmstoffes der Prostaglandinsynthese Indomethacin auf die basale und stimulierte Plasmareninaktivität bei gesunden Versuchspersonen untersucht. Die Stimulation der Reninaktivität wurde durch Orthostase beziehungsweise durch Furosemid erzielt. Indomethacin führte bei chronischer und bei einmaliger Medikation zu einer deutlichen Senkung sowohl der basalen als auch der stimulierten Plasmareninaktivität. Eine wesentliche Natriumretention scheint als Mechanismus der Senkung der Reninaktivität durch Indomethacin nicht wahrscheinlich. Es werden antagonistische Funktionen von Renin-Angiotensin-System und Prostaglandinen für möglich gehalten, die bei der Regulation der Nierendurchblutung oder der Blutdruckregulation eine Rolle spielen könnten.The influence of indomethacin, a potent inhibitor of prostaglandin synthesis, on basal and stimulated plasma renin activities in normal human subjects was determined. Stimulation of the renin activity was achieved by orthostasis or by furosemide. Indomethacin led to a considerable decrease of both basal and stimulated plasma renin activity in chronic and acute experiments. Our experiments provide no evidence that major changes in the sodium balance are responsible for the effects observed. It is concluded that some antagonistic function of the renin angiotensin system and prostaglandins seems probable. These antagonistic actions might play a role in the regulation of the kidney circulation or the arterial blood pressure.

Complications of plasma exchange in patients with neurological diseases

SummaryPlasma exchange has proven to be effective in diseases of established or presumed autoimmune etiology as well as in hyperviscosity syndromes and some rare metabolic disorders. Its application is thought to be relatively safe; nevertheless, severe complications may occur. We therefore analyzed the complications of 291 exchanges in 39 patients with neurological diseases. Minor complications developed in 4.8% and major complications in 2.7% of procedures, including one death. Severe infections and technical problems have been the most serious side effects, sometimes followed by organ failure or even death.

Serumspiegel und Urinausscheidung von L-Carnitin bei Patienten mit normaler und eingeschränkter Nierenfunktion

SummaryThe influence of age, sex, and renal function on serum levels and urinary excretion of free carnitine was studied in 187 subjects. Sixty-one subjects with normal renal function (creatinine clearance >100 ml/min) showed a serum carnitine level of 72.2±23.2 µmol/l. The carnitine values of males (76.8±23.3 µmol/l,n=39) were higher (p<0.05) than those of females (64.0±21.0 µmol/l, n=22). Carnitine levels did not correlate with age. Values in patients with normal renal function did not differ from serum carnitine levels in healthy controls (74.7±17.5 µmol/l,n=49). The mean urinary carnitine excretion per day was 163.5 µmol (range 63.7–419.6 µmol) in patients with intact renal function. Extreme impairment of glomerular filtration rate (creatinine clearance <20 ml/min) resulted in higher carnitine concentrations in serum (108.9±39.4 µmol/l,n=18,p<0.05), lower carnitine elimination per day (78.5 µmol, range 14.5–424.3 µmol,n=18,p<0.05) and a decreased carnitine clearance (0.8 ml/min, range 0.2–3.8 ml/min).These data together with earlier results obtained in dialysis patients suggest that carnitine metabolism in renal failure is altered by reduction of both endogenous carnitine biosynthesis and renal carnitine clearance.The influence of age, sex, and renal function on serum levels and urinary excretion of free carnitine was studied in 187 subjects. Sixty-one subjects with normal renal function (creatinine clearance greater than 100 ml/min) showed a serum carnitine level of 72.2 +/- 23.2 mumol/l. The carnitine values of males (76.8 +/- 23.3 mumol/l, n = 39) were higher (p less than 0.05) than those of females (64.0 +/- 21.0 mumol/l, n = 22). Carnitine levels did not correlate with age. Values in patients with normal renal function did not differ from serum carnitine levels in healthy controls (74.7 +/- 17.5 mumol/l, n = 49). The mean urinary carnitine excretion per day was 163.5 mumol (range 63.7-419.6 mumol) in patients with intact renal function. Extreme impairment of glomerular filtration rate (creatinine clearance less than 20 ml/min) resulted in higher carnitine concentrations in serum (108.9 +/- 39.4 mumol/l, n = 18, p less than 0.05), lower carnitine elimination per day (78.5 mumol, range 14.5 - 424.3 mumol, n = 18, p less than 0.05) and a decreased carnitine clearance (0.8 ml/min, range 0.2 - 3.8 ml/min). These data together with earlier results obtained in dialysis patients suggest that carnitine metabolism in renal failure is altered by reduction of both endogenous carnitine biosynthesis and renal carnitine clearance.

[Elevated serum myoglobin in renal failure (author's transl)].

SummaryIn 44 patients with chronic renal failure of varied etiology serum immunoreactive myoglobin was measured and compared to values obtained in patients with normal renal function. Irrespective of the underlying disease a highly significant linear correlation was found between serum immunoreactive myoglobin and serum creatinine concentration. In patients with serum creatinine concentrations above 550 µmol/1 (6.2 mg%) serum myoglobin was as a rule elevated above the range found in the controls with normal renal function. This was also true in dialysis patients. These result demonstrate that serum myoglobin may only be used with restrictions in the diagnosis of myocardial infarction in patients suffering from advanced chronic renal failure.ZusammenfassungBei 44 Patienten mit chronischer Niereninsuffizienz unterschiedlicher Äthiologie wurde das immunreaktive Serum-Myoglobin bestimmt und mit den Werten von Probanden mit normaler Nierenfunktion verglichen. Es fand sich — unabhängig von der Grunderkrankung — eine hoch signifikante lineare Korrelation zwischen dem Serum-Myoglobin und der Serum-Kreatinin-Konzentration. Bei Patienten mit Serum-Kreatinin-Werten über 550 µMol/1 (6,2 mg-%) lagen die Serum-Myoglobin Konzentrationen fast regelmäßig im pathologischen Bereich. Dies gilt auch für chronische Dialysepatienten. Die Befunde zeigen, daß bei Patienten mit höhergradiger, chronischer Niereninsuffizienz das Serum-Myoglobin nur mit Einschränkung zur Infarktdiagnostik geeignet ist.In 44 patients with chronic renal failure of varied etiology serum immunoreactive myoglobin was measured and compared to values obtained in patients with normal renal function. Irrespective of the underlying disease a highly significant linear correlation was found between serum immunoreactive myoglobin and serum creatinine concentration. In patients with serum creatinine concentrations above 550 mu mol/1 (6.2 mg%) serum myoglobin was as a rule elevated above the range found in the controls with normal renal function. This was also true in dialysis patients. These result demonstrate that serum myoglobin may only be used with restrictions in the diagnosis of myocardial infarction in patients suffering from advanced chronic renal failure.

[Plasma angiotensin-I-converting-enzyme activity after inhibition of prostaglandin synthesis (author's transl)].

SummaryIn 18 normal human volunteers plasma angiotensin-I-converting-enzyme (ACE) activity was measured before and after inhibition of prostaglandin synthesis by indomethacin. ACE activity did not change significantly after treatment. It is concluded that renin is probably the only component of the renin angiotensin system, which is influenced by prostaglandins.ZusammenfassungBei 18 gesunden Versuchspersonen wurde die Aktivität des Angiotensin-I-converting-enzyme (ACE) im Plasma vor und nach Hemmung der Prostaglandinsynthese durch Indomethacin gemessen. Die ACE-Aktivität blieb durch die Behandlung unbeeinflußt. Es wird geschlossen, daß das Renin selbst wahrscheinlich die einzige Komponente des Renin-Angiotensin-Systems darstellt, die Beziehungen zu Prostaglandinen aufweist.In 18 normal human volunteers plasma angiotensin-I-converting-enzyme (ACE) activity was measured before and after inhibition of prostaglandin synthesis by indomethacin. ACE activity did not change significantly after treatment. It is concluded that renin is probably the only component of the renin angiotensin system, which is influenced by prostaglandins.

N-acetylation of p-amino-hippurate in kidneys with renal artery stenosis and in patients suffering from severe essential hypertension

SummaryRoutine PAH-clearance studies were carried out on patients with (a) glomerulonephritis, (b) secondary impairment of renal function, (c) essential hypertension, and (d) patients with unilateral renal artery stenosis. Renal excretion of N-acetyl-PAH was significantly lower in patients with unilateral artery stenosis or with essential hypertension, while the other groups showed no impairment of the PAH-metabolism. The implications of these findings are discussed.ZusammenfassungRoutinemäßige PAH-Clearance-Untersuchungen wurden durchgeführt bei Patienten mita)Glomerulonephritis,b)sekundärer Beeinträchtigung der Nierenfunktion,c)essentieller Hypertonie undd)bei Patienten mit einseitiger Nierenarterien-Stenose. Die renale Ausscheidung von N-Acetyl-PAH war signifikant erniedrigt bei Patienten mit Nierenarterien-Stenose oder mit essentieller Hypertonie, während die anderen Gruppen keine Störung des PAH-Metabolismus aufwiesen.Die Bedeutung dieser Befunde wird diskutiert.