Zusammenfassung
Es ist bekannt, dass Patienten mit schizophrenen Psychosen erhöhte kardiale Morbiditäts- und Mortalitätsraten aufweisen. Häufige kardiovaskuläre Erkrankungen lassen sich zum einen durch Lebensgewohnheiten wie Inaktivität, Ernährungsfehler, Nikotinabusus, aber auch durch eine verminderte Inanspruchnahme vorsorgender medizinischer Angebote erklären. Zum anderen ist belegt, dass insbesondere atypische Neuroleptika in unterschiedlicher Weise zu hohen Prävalenzraten für Adipositas, Hypertriglyzeridämie und Diabetes mellitus beitragen. Hier ist eine standardisierte Erfassung entsprechender Parameter angezeigt. Ggf. ist eine Umstellung der antipsychotischen Medikation vorzunehmen. Auch sollte eine diätetische Beratung des Patienten und seiner Angehörigen erfolgen. Neben medikamentösen Ansätzen zur Normalisierung von Dyslipidämien sind verhaltenstherapeutische Programme entwickelt worden, mit denen gezielt metabolische Parameter beeinflusst werden können. Bedrohliche kardiale Komplikationen im Langzeitverlauf lassen sich darüber hinaus auch auf direkte Nebenwirkungen unter Antipsychotika wie QT-Verlängerungen mit Induktion schwerer Arrhythmien zurückführen. Zur Prävention sind prädisponierende Risikofaktoren wie z. B. Elektrolytstörungen und kardiale Vorerkrankungen zu beachten, wie auch die Begleitmedikation in Hinblick auf QT-verlängernde Nebenwirkungen und Interaktionen über das Cytochrom P450 System.
Abstract
It is well known, that patients with schizophrenia exhibit increased rates of cardiac morbidity and mortality. Frequent cardiovascular diseases are only partially explained by lifestyle, inactivity, dietary habits and nicotine abuse, but also by reduced compliance in prevention programs. On the other hand, it has been shown that particularly atypical antipsychotic agents are differentially responsible for high rates of obesity, hypertriglyceridemia, and diabetes. Therefore, a standardized evaluation of corresponding parameters is indicated in every patient. If needed, modulation of the medication regimen has to be performed. Additionally, a dietary counselling of the patient and his family should be offered. Besides pharmacological approaches to normalize dyslipidemia, specific behavioural therapy programmes are an option that may alter metabolic parameters. Threatening cardiac complications in long-term treatment of schizophrenia may also be the result of direct side effects under treatment with antipsychotics, like QT-prolongation triggering major arrhythmias. For prevention, predisposing risk factors like electrolyt disturbances, pre-existing cardiac diseases, co-medication with QT prolonging drugs and medication with potential cytochrome P450 interaction have to be taken into consideration.
Schlüsselwörter
Atypische Antipsychotika - Koronare Herzkrankheit - QT-Verlängerung - Schizophrenie
Key words
atypical antipsychotics - coronary heart disease - QT-prolongation - schizophrenia
Literatur
-
1
Newman S C, Bland R C.
Mortality in a cohort of patients with schizophrenia: a record linkage study.
Can J Psychiatry.
1991;
36
239-245
-
2
Goff D C, Heckers S, Freudenreich O.
Schizophrenia.
Med Clin North Am.
2001;
85
663-689
-
3
Osby U, Correia N, Brandt L, Ekbom A, Sparen P.
Mortality and causes of death in schizophrenia in Stockholm county, Sweden.
Schizophr Res.
2000;
45
21-28
-
4
Koran L M, Sox Jr H C, Marton K I.
Medical evaluation of psychiatric patients, 1: results in a state mental health system.
Arch Gen Psychiatry.
1989;
46
733-740
-
5
Mokdad A H, Ford E S, Bowman B A.
Prevalence of obesity, diabetes, and obesity-related health risk factors, 2001.
JAMA.
2003;
289
76-79
-
6
Allison D B, Mentore J L, Heo M, Chandler L P, Capelliri J C, Infante M C, Weiden P J.
Antipsychotic-induced weight gain: a comprehensive research synthesis.
Am J Psychiatry.
1999;
156
1686-1696
-
7
Homel P, Casey D, Allison D B.
Changes in body mass index for individuals with and without schizophrenia, 1987 - 1996.
Schizophr Res.
2002;
55
277-284
-
8 Kraepelin E. Psychiatrie. Ein Lehrbuch für Studierende und Ärzte. 8., vollständig umgearbeitete Auflage. IV. Band. Klinische Psychiatrie. III. Teil. Leipzig: Barth Verlag 1915
-
9
Thakore J H, Mann J N, Vlahos I, Martin A, Reznek R.
Increased visceral fat distribution in drug-naiv and drug-free patients with schizophrenia.
Int J Obes Relat Metab Disord.
2002;
26
137-141
-
10
Wolf A M, Colditz G A.
Current estimates of the economic cost of obesity in the United States.
Obes Res.
1998;
6
97-106
-
11
Henderson D C, Cagliero E, Copeland P M, Borba C P, Evins E, Hayden D, Weber M T, Anderson E J, Allison D B, Daley T B, Schoenfeld D, Goff D C.
Glucose metabolism in patients with schizophrenia treated with atypical antipsychotic agents: a frequently sampled intravenous glucose tolerance test and minimal model analysis.
Arch Gen Psychiatry.
2005 Jan;
62 (1)
19-28
-
12
Wirshing D A, Wirshing W C, Kysar L.
Novel antipsychotics: comparison of weight gain liabilities.
J Clin Psychiatry.
1999;
60
358-363
-
13
Eaton W W, Mortensen P B, Herrman H.
Long-term course of hospitalization for schizophrenia, pt 1: risk for rehospitalization.
Schizophr Bull.
1992;
18
217-228
-
14
Hummer M, Kemmler G, Kurz M, Kurzthaler I, Oberbauer H, Fleischhacker W W.
Weight gain induced by clozapine.
Eur Neuropsychopharmacol.
1995;
5
437-440
-
15
Osser D N, Najarian D M, Dufresne R L.
Olanzapine increases weight and serum triglyceride levels.
J Clin Psychiatry.
1999;
60
767-770
-
16
Tollefson G D, Beasley Jr C M, Tran P V, Street J S, Krueger J A, Tamura R N, Graffeo K A, Thieme M E.
Olanzapine versus haloperidol in the treatment of schizophrenia and schizoaffective and schizophreniform disorders: results of an international collaborative trial.
Am J Psychiatry.
1997;
154
457-465
-
17
Gupta S, Droney T, Al Samarrai S, Keller P, Frank B.
Olanzapine: weight gain and therapeutic efficacy.
J Clin Psychopharmacol.
1999;
19
273-275
-
18
McQuade R D, Stock E, Marcus R, Jody D, Gharbia N A, Vanveggel S, Archibald D, Carson W H.
A comparison of weight change during treatment with olanzapine or aripiprazole: results from a randomized, double-blind study.
J Clin Psychiatry.
2004;
65 (suppl 18)
47-56
-
19
Tran P V, Dellva M A, Tollefson G D, Wentley A L, Beasley Jr C M.
Oral olanzapine versus oral haloperidol in the maintenance treatment of schizophrenia and related psychoses.
Br J Psychiatry.
1998;
172
499-505
-
20
Conley R R, Mahmoud R.
A randomized double-blind study of risperidone and olanzapine in the treatment of schizophrenia or schizoaffective disorder.
Am J Psychiatry.
2001;
158
765-774
-
21
Claus A, Bollen J, De Cuyper H, Heneman M, Malfroid M, Peuskens J, Heylen S.
Risperidone versus haloperidol in the treatment of chronic schizophrenic inpatients: a multicenter double-blind comparative study.
Acta Psychiatr Scand.
1992;
85
295-305
-
22
Peuskens J.
Risperidone in the treatment of patients with chronic schizophrenia: a multi-national, multi-centre, double-blind, parallel-group study versus haloperidol.
Br J Psychiatry.
1995;
166
712-726
-
23
Borison R L, Arvanitis L A, Miller B G.
ICI 204,636, an atypical antipsychotic: efficacy and safety an a multicenter, placebo-controlled trial in patients with schizophrenia.
J Clin Psychopharmacol.
1996;
16
158-169
-
24
Arvanitis L A, Miller B G. and the Seroquel Trial 13 study group .
Multiple fixed doses of “Seroquel” (quetiapine) in patients with acute exacerbation of schizophrenia: a comparison with haloperidol and placebo.
Biol Psychiatry.
1997;
42
233-246
-
25
Small J G, Hirsch S R, Arvanitis L A, Miller B G, Link C.
Quetiapine in patients with schizophrenia: a high- and low-dose double-blind comparison with placebo.
Arch Gen Psychiatry.
1997;
54
549-557
-
26
Keck Jr P, Buffenstein A, Ferguson J, Feighner J, Jaffe W, Harrigan E P, Morrisey M R.
Ziprasidone 40 and 120 mg/day in the acute exacerbation of schizophrenia and schizoaffective disorder: a 4-week placebo-controlled trial.
Psychopharmacology (Berl).
1998;
140
173-184
-
27
Daniel D G, Zimbroff D L, Potkin S G, Reeves K R, Harrigan E P, Lakshminarayanan M.
Ziprasidone 80 mg/day and 160 mg/day in the acute exacerbation of schizophrenia and schizoaffective disorder: a 6-week placebo-controlled trial.
Neuropsychopharmacology.
1999;
20
491-505
-
28
Cohen S, Fitzgerald B, Okos A, Khan S, Khan A.
Weight, lipids, glucose, and behavioral measures with ziprasidone treatment in a population with mental retardation.
J Clin Psychiatry.
2003;
64
60-62
-
29
Potkin S G, Saha A R, Kujawa M J, Carson W H, Mirza A, Stock E, Stringfellow J, Ingenito G, Marder S.
Aripiprazole, an antipsychotic with a novel mechanism of action, and risperidone vs placebo in patients with schizophrenia and schizoaffective disorder.
Arch Gen Psychiatry.
2003;
60
681-690
-
30
Marder S R, McQuade R D, Stock E, Kaplita S, Marcus R, Safferman A Z, Saha A, Ali M, Iwamoto T.
Aripiprazol in the treatment of schizophrenia: safety and tolerability in short-term, placebo-controlled trials.
Schizopr Res.
2003;
61
123-136
-
31
Sargent P A, Sharpley A L, Williams C, Goodall E M, Cowen P J.
5-HT2C receptor activation decreases appetite and body weight in obese subjects.
Psychopharmacology (Berl).
1997;
133
309-312
-
32
Zhang Z J, Yao Z J, Liu W, Fang Q, Reynolds G P.
Effects of antipsychotics on fat deposition and changes in leptin and insulin levels.
Br J Psychiatry.
2004;
184
58-62
-
33
Melkersson K I, Hultin A-L, Brismar K E.
Elevated levels of insulin, leptin, and blood lipids in olanzapine-treated patients with schizophrenia or related psychoses.
J Clin Psychiatry.
2000;
61
742-749
-
34
Gordon T, Castelli W P, Hjortland M C.
High density lipoprotein as a protective factor against coronary heart disease: the Framingham Study.
Am J Med.
1977;
62
707-714
-
35
Baymiller S P, Ball P, McMahon R P, Buchanan R W.
Serum glucose and lipid changes during the course of clozapine treatment: the effect of concurrent beta-adrenergic antagonist treatment.
Schizophr Res.
2003 Jan 1;
59 (1)
49-57
-
36
Lindenmayer J P, Czobor P, Volavka J, Citrome L, Sheitman B, McEvoy J P, Cooper T B, Chakos M, Lieberman J A.
Changes in glucose and cholesterol levels in patients with schizophrenia treated with typical or atypical antipsychotics.
Am J Psychiatry.
2003;
160
290-296
-
37
Wirshing D A, Boyd J A, Meng L R, Ballon J S, Marder J C, Wirshing R C.
The effects of novel antipsychotics on glucose and lipid levels.
J Clin Psychiatry.
2002;
63
856-865
-
38
Gaulin B D, Markowitz J S, Caley C, Nesbitt L A, Dufresne R L.
Clozapine associated elevation in serum triglycerides.
Am J Psychiatry.
1999;
156
1270-1272
-
39
Spivak B, Lamschtein C, Talmon Y, Guy N, Mester R, Feinberg I, Kotler M, Weizman A.
The impact of clozapine treatment on serum lipids in chronic schizophrenic patients.
Clin Neuropharmacol.
1999;
22
98-101
-
40
Ghaeli P, Dufresne R L.
Serum triglyceride levels in patients treated with clozapine.
Am J Health Syst Pharm.
1996;
53
2079-2081
-
41
Meyer J M.
Effects of atypical antipsychotics on weight and serum lipid levels.
J Clin Psychiatry.
2001;
62 (suppl 27)
27-34
-
42
Koro C E, Fedder D O, L'Italien G J, Weiss S S, Magfer I D, Kreyenbuhl J, Revick D A, Buchanan R W.
An assessment of the independent effects of olanzapine and risperidone exposure on the risk of hyperlipidemia in schizophrenic patients.
Arch Gen Psychiatry.
2002;
59
1021-1026
-
43
Zajecka J M, Weisler R, Sachs G, Swann A C, Wozniak P, Sommerville K W.
A comparison of the efficacy, safety, and tolerability of divalproex sodium and olanzapine in the treatment of bipolar disorder.
J Clin Psychiatry.
2002;
63
1148-1155
-
44
Domon S E, Cargile C S.
Quetiapine-associated hyperglycemia and hypertriglyceridemia.
J Am Acad Child Adolesc Psychiatry.
2002;
41
495-496
-
45
Shaw J A, Lewis J E, Pascal S, Sharma R K, Rodriguez R A, Guillen R, Pupo-Guillen M.
A study of quetiapine: efficacy and tolerability in psychotic adolescents.
J Child Adolesc Psychopharmacol.
2001;
11
415-424
-
46
Simpson G M, Weiden P, Pigott T.
Ziprasidone olanzapine in schizophrenia: 6-month continuation study.
Eur Neuropsychopharmacol.
2002;
12 (suppl 3)
S311
-
47
Kingsbury S J, Fayek M, Trufasiu D, Zada J, Simpson G M.
The apparent effects of ziprasidone on plasma lipids and glucose.
J Clin Psychiatry.
2001;
62
347-349
-
48
Romano S, Cutler N, Weiden P J.
Ziprasidone's effects on weight and lipids in patients with schizophrenia.
Int J Neuropsychopharmacol.
2002;
5
S171
-
49
Kane J M, Carson W H, Saha A R, McQuade R D, Ingenito G G, Zimbroff D L, Ali M W.
Efficacy and safety of aripiprazole and haloperidol versus placebo in patients with schizophrenia and schizoaffective disorder.
J Clin Psychiatry.
2002;
63
763-777
-
50
American Diabetes Association .
Consensus Development Conference on Antipsychotic Drugs and Obesity and Diabetes.
Diabetes Care.
2004;
27
596-601
-
51
Waitzkin L.
A survey for unknown diabetics in a mental hospital, 1: men under age fifty.
Diabetes.
1966;
15
97-104
-
52
Ryan M C, Collins P, Thakore J H.
Impaired fasting glucose tolerance in first-episode, drug-naïve patients with schizophrenia.
Am J Psychiatry.
2003;
160
284-289
-
53
Lambert B L, Chou C H, Chang K Y, Tafesse E, Carson W l.
Assessing the risk of antipsychotic-induced type 2 diabetes among schizophrenics: a matched case-control study.
Eur Neuropsychopharmacol.
2002;
12
S307
-
54
Koro C E, Fedder D O, L'Italien G J, Weiss S S, Magder L S, Kreyenbuhl J, Revicki D A, Buchanan R W.
Assessment of independent effect of olanzapine and risperidone on risk of diabetes among patients with schizophrenia: population based nested case-control study.
BMJ.
2002;
325
243-247
-
55
Gianfrancesco F D, Grogg A L, Mahmoud R, Wang R H, Nasrallah H A.
Differential effects of risperidone, olanzapine, clozapine, and conventional antipsychotics on type 2 diabetes: findings from a large health plan database.
J Clin Psychiatry.
2002;
63
920-930
-
56
Henderson D C, Cagliero E, Gray C, Nasrallah R A, Hayden D L, Schoenfeld D A, Goff D C.
Clozapine, diabetes mellitus, weight gain, and lipid abnormalities: a five-year naturalistic study.
Am J Psychiatry.
2000;
157
975-981
-
57
Dwyer D S, Lu X H, Bradley R J.
Cytotoxicity of conventional and atypical antipsychotic drugs in relation to glucose metabolism.
Brain Res.
2003;
971
31-39
-
58
Hughes J R, Hatsukami D K, Mitchell J E, Dahlgren L A.
Prevalence of smoking among psychiatric outpatients.
Am J Psychiatry.
1986;
143
993-997
-
59
Kelly C, McCreadie R G.
Smoking habits, current symptoms, and premorbid characteristics of schizophrenic patients in Nithsdale, Scotland.
Am J Psychiatry.
1999 Nov;
156 (11)
1751-1757
-
60
Buckley N A, Sanders P.
Cardiovascular adverse effects of antipsychotic drugs.
Drug Saf.
2000;
23
215-228
-
61
Jurko M, Jost H, Hill S.
Pathology of the energy system. An experimental clinical study of physiological adaptive capacities in a non-patient, a psychoneurotic, and an early paranoid schizophrenic group.
J Psychol.
1952;
33
183-198
-
62
Akselrod S, Gordon D, Ubel F A, Shannon D C, Barger A C, Cohen R J.
Power spectrum analysis of heart rate fluctuation: a quantitative probe of beat-to-beat cardiovascular control.
Science.
1981;
213
220-222
-
63
Dalack G W, Roose S P.
Perspectives on the relationship between cardiovascular disease and affective disorder.
J Clin Psychiatry.
1990 Jul;
51 Suppl
4-11
-
64
Kleiger R E, Miller P J, Bigger T J, Moss A J. and the Multicenter Post-Infarction Research Group .
Decreased heart-rate variability and its association with increased mortality after acute myocardial infarction.
Am J Cardiol.
1987;
59
256-262
-
65
Nolan J, Batin P D, Andrews R, Lindsay S J, Brooksby P, Mullen M, Baig W, Flapan A D, Cowley A, Prescott R J, Neilson J M, Fox K A.
Prospective study of heart rate variability and mortality in chronic heart failure: results of the United Kingdom heart failure evaluation and assessment of risk trial (UK-heart).
Circulation.
1998 Oct 13;
98 (15)
1510-1516
-
66
Birkhofer A, Schmidt G, Förstl H.
Herz und Hirn - Die Auswirkungen psychischer Erkrankungen und ihrer Therapie auf die Herzfrequenzvariabilität.
Fortschr Neurol Psychiatr.
2005 Apr;
73 (4)
192-205
-
67
Bonnemeier H, Hartmann F, Wiegand U K, Bode F, Katus H A, Richardt G.
Course and prognostic implications of QT interval and QT interval variability after primary coronary angioplasty in acute myocardial infarction.
J Am Coll Cardiol.
2001 Jan;
37 (1)
44-50
-
68
Vrtovec B, Starc V, Starc R.
Beat-to-beat QT interval variability in coronary patients.
J Electrocardiol.
2000 Apr;
33 (2)
119-125
-
69 Haverkamp W, Deuschle M. Antipsychotikainduzierte QT-Verlängerung. Nervenarzt 2006 im Druck
-
70
Harrigan E P, Miceli J J, Anziano R, Watsky E, Reeves K R, Cutler N R, Sramek J, Shiovitz T, Middle M.
A randomized evaluation of the effects of six antipsychotic agents on QTc, in the absence and presence of metabolic inhibition.
J Clin Psychopharmacol.
2004;
24
62-69
-
71
Reilly J G, Ayis S A, Ferrier I N, Jones S J, Thomas S H.
QTc-interval abnormalities and psychotropic drug therapy in psychiatric patients.
Lancet.
2000;
355
1048-1052
-
72
Fulop G, Phillips R A, Shapiro A K, Gomes J A, Shapiro E, Nordlie J W.
ECG changes during haloperidol and pimozide treatment of Tourette's disorder.
Am J Psychiatry.
1987;
144
1673-1675
-
73
Flockhart D A, Drici M D, Kerbusch T, Soukhova N, Richard E, Pearle P L, Mahal S K, Babb V J.
Studies on the mechanism of a fatal clarithromycin-pimozide interaction in a patient with Tourette Syndrome.
J Clin Psychopharmacol.
2000;
20
317-324
-
74
Glassmann A H, Bigger J T.
Antipsychotic drugs: prolonged QTc interval, Torsade de Pointes and sudden death.
Am J Psychiatry.
2001;
158
1774-1782
-
75
Sharma N D, Rosman H S, Padhi I D, Tisdale J E.
Torsades de pointes associated with intravenous haloperidol in critically ill patients.
Am J Cardiol.
1998;
81
238-240
-
76
Wilt J L, Minnema A M, Johnson R F.
Torsade de pointes associated with the use of intravenous haloperidol.
Ann Intern Med.
1993;
119
391-394
-
77
Roden D M.
Torsade de pointes.
Clin Cardiol.
1993;
16
683-686
-
78
Woosley R L, Chen Y, Freiman J P, Gillis R A.
Mechanism of the cardiotoxic actions of terfenadine.
JAMA.
1993;
269
1532-1536
-
79
Mehtonen O P, Aranko K, Malkonen L, Vapaatalo H.
A survey of sudden death associated with the use of antipsychotic or antidepressant, drugs: 49 cases in Finland.
Acta Psychiatr Scand.
1991;
84
58-64
-
80
Kelly H G, Fay J E, Laverty S G.
Thioridazine hydrochloride (Mellaril): its effect on the electrocardiogram and a report on two fatalities with electrocardiographic abnormalities.
Can Med Assoc J.
1963;
89
546-554
-
81
Fowler N O, McCall D, Chou T C, Holmes J C, Hanenson I B.
Electrocardiographic changes and cardiac arrhythmias in patients receiving psychotropic drugs.
Am J Cardiol.
1976 Feb;
37 (2)
223-230
-
82
Lewis R, Bagnal A, Leitner M.
Sertindole for schizophrenia.
Cochrane Database Syst Rev.
2005 Jul 20;
(3)
CD001715
-
83 Psychopharmacological Drugs Advisory Committee .Sertindole NDA 20-644. Rockville, Md., Food and Drug Administration 1996
-
84
Ray W A, Meredith S, Thapa P B, Meador K G, Hall K, Murray K T.
Antipsychotics and the risk of sudden cardiac death.
Arch Gen Psychiatry.
2001;
58
1161-1167
-
85
Hennessy S, Bilker W B, Knauss J S, Margolis D J, Kimmel S E, Reynolds R F, Glasser D B, Morrison M F, Strom B L.
Cardiac arrest and ventricular arrhythmia in patients taking antipsychotic drugs: cohort study using administrative data.
BMJ.
2002 Nov 9;
325 (7372)
1070
-
86
Liperoti R, Gambassi G, Lapane K L, Chiang C, Pedone C, Mor V, Bernabei R.
Conventional and atypical antipsychotics and the risk of hospitalization for ventricular arrhythmias or cardiac arrest.
Arch Intern Med.
2005 Mar 28;
165 (6)
696-701
-
87
Mensink R P, Katan M B.
Effect of dietary fatty acids on serum lipids and lipoproteins: a meta-analysis of 27 trials.
Arterioscler Thromb.
1992;
12
911-919
-
88
Tuomilehto J, Lindstrom J, Eriksson J G, Valle T T, Hamalainen H, Ilanne-Parikka P, Keinanen-Kiukaanniemi S, Laakso M, Louheranta A, Rastas M, Salminen V, Uusitupa M. Finnish Diabetes Prevention Study Group .
Prevention of type 2 diabetes mellitus by changes in lifestyle among subjects with impaired glucose tolerance.
N Engl J Med.
2001;
344
1343-1350
-
89
Furst B A, Champion K M, Pierre J M, Wirshing D A, Wirshing W C.
Possible association of QTc interval prolongation with co-administration of quetiapine and lovastatin.
Biol Psychiatry.
2002;
51
264-265
-
90
Hofer A, Fleischhacker W W, Hummer M.
Worsening of psychosis after replacement of adjunctive valproate with topiramate in a schizophrenia patient.
J Clin Psychiatry.
2003;
64
1267-1268
-
91
Taflinski T, Chojnacka J.
Sibutramine-associated psychotic episode.
Am J Psychiatry.
2000;
157
2057-2058
-
92
Reinstein M J, Sirotovskaya A, Jones L E, Mohan S, Chasanov M A.
Effect of clozapine-quetiapine combination therapy on weight and glycaemic control.
Clin Drug Invest.
1999;
18
99-104
Priv.-Doz. Dr. med. Ulrich Meincke
Klinik für Psychiatrie und Psychotherapie Klinikum Niederberg
Robert Koch-Str. 2
42549 Velbert
eMail: Meincke@Klinikum-Niederberg.de
