Zur Bestimmung der Serumlipoproteide mit der Zonenelektrophorese im Stärkemedium

Zusammenfassung 1. Die Elektrophorese im Stärkemedium läßt beim normalen Menschen die reproduzierbare Bestimmung alters- und geschlechtsabhängiger Lipoproteidklassen zu.2. Für die sog. idiopathischen und symptomatischen Lipoidstoffwechselstörungen werden bestimmte Lipoid-und Lipoproteidkonstellationen mitgeteilt.3. Der Arteriosklerose des Menschen kommen keine spezifischen Lipoproteidkonstellationen zu.4. Überhaupt hat die einmalige Bestimmung von Lipoiden oder Lipoproteiden im allgemeinen geringen klinischen Wert. Wir geben wiederholten Bestimmungen möglichst umfassender Lipoid- und Lipoproteidspektren den Vorzug.5. Bei nachgewiesenen Coronarinfarkten und bei stenosierenden Arterienprozessen auf arteriosklerotischer Grundlage finden wir Veränderungen der Serumlipoproteide.6. Die Bestimmung der Serumlipoproteide erlaubt im Einzelfalle keine Voraussage drohender Coronarinfarkte.7. Die Schwere der Serumlipoproteidveränderungen gibt keine Hinweise auf das Ausmaß der pathologischanatomischen Läsionen.8. Die Bedeutung von Fettstoffwechselstörungen für die Pathogenese der Arteriosklerose des Menschen, insbesondere für die Sonderform der Atherosklerose, wird durch diese Feststellungen nicht beeinträchtigt.Mit Unterstützung der Deutschen Forschungsgemeinschaft.     

Körperliche Aktivität und Fettstoffwechsel

Zusammenfassung Untersuchungen in den letzten Jahren haben gezeigt, daß der Fettstoffwechsel durch körperliche Aktivität günstig beeinflußt wird. Diese Veränderungen betreffen sowohl die Serumlipide als auch Lipide im Fettgewebe und in der Skelettmuskulatur.Körperliches Training führt zu einer ausgeprägten Senkung der Serumtriglyzeride. Eine Erniedrigung des Serumcholesterins und der freien Fettsäuren ist umstritten. Die Konzentrationen der very low density Lipoproteine (VLDL) und der low density Lipoproteine (LDL) werden vermindert, die der high density Lipoproteine (HDL) vermehrt. Dadurch erniedrigt sich der LDL:HDL-Quotient und nach derzeitigen Vorstellungen das Arterioskleroserisiko. Entsprechend zeigen epidemiologische Untersuchungen eine negative Korrelation zwischen körperlicher Aktivität und koronarer Herzkrankheit.Die Körperfettmasse kann durch körperliches Training aufgrund einer Verminderung der Fettzellgröße reduziert werden. In vitro-Untersuchungen am Fettgewebe zeigen, daß die Lipogenese auf mehreren Stufen gehemmt wird. Untersuchungsergebnisse hinsichtlich der Lipolyse sind aufgrund methodischer Probleme nicht einheitlich.Beim Vergleich trainingsbedingter Adaptationsmechanismen im Fettgewebe und in der Skelettmuskulatur finden sich divergierende Stoffwechselveränderungen. Während im Fettgewebe Fetteinbau und Fettspeicherung eher vermindert sind, ist die Aufnahme und Oxydation von Lipiden in der Skelettmuskulatur des Trainierten beschleunigt. Dadurch kommt es bei trainierten Patienten mit Fettstoffwechselstörungen über einen beschleunigten Umsatz von Lipiden in der Muskulatur zu einer Senkung der Serumtriglyzeride und der Transportlipoproteine.Körperliches Training kann bei Patienten empfohlen werden, bei denen eine Senkung der Triglyzeride in den VLDL und LDL, eine Erhöhung der HDL und eine Reduktion der Fettmasse wünschenswert ist, sofern keine Kontraindikationen gegen eine Bewegungstherapie bestehen.     

Psychosocial disability in the course of bipolar I and II disorders: a prospective, comparative, longitudinal study

CONTEXT: Evidence of psychosocial disability in bipolar disorder is based primarily on bipolar I disorder (BP-I) and does not relate disability to affective symptom severity and polarity or to bipolar II disorder (BP-II). OBJECTIVE: To provide detailed data on psychosocial disability in relation to symptom status during the long-term course of BP-I and BP-II. DESIGN: A naturalistic study with 20 years of prospective, systematic follow-up. SETTING: Inpatient and outpatient treatment facilities at 5 US academic centers.Patients One hundred fifty-eight patients with BP-I and 133 patients with BP-II who were followed up for a mean (SD) of 15 (4.8) years in the National Institute of Mental Health Collaborative Depression Study. MAIN OUTCOME MEASURES: The relationship, by random regression, between Range of Impaired Functioning Tool psychosocial impairment scores and affective symptom status in 1-month periods during the long-term course of illness from 6-month and yearly Longitudinal Interval Follow-up Evaluation interviews. RESULTS: Psychosocial impairment increases significantly with each increment in depressive symptom severity for BP-I and BP-II and with most increments in manic symptom severity for BP-I. Subsyndromal hypomanic symptoms are not disabling in BP-II, and they may even enhance functioning. Depressive symptoms are at least as disabling as manic or hypomanic symptoms at corresponding severity levels and, in some cases, significantly more so. At each level of depressive symptom severity, BP-I and BP-II are equally impairing. When asymptomatic, patients with bipolar disorder have good psychosocial functioning, although it is not as good as that of well controls. CONCLUSIONS: Psychosocial disability fluctuates in parallel with changes in affective symptom severity in BP-I and BP-II. Important findings for clinical management are the following: (1) depressive episodes and symptoms, which dominate the course of BP-I and BP-II, are equal to or more disabling than corresponding levels of manic or hypomanic symptoms; (2) subsyndromal depressive symptoms, but not subsyndromal manic or hypomanic symptoms, are associated with significant impairment; and (3) subsyndromal hypomanic symptoms appear to enhance functioning in BP-II.     

The value of bone marrow examination for tumor staging in breast cancer

Summary The purpose of our study was to investigate the value of cytokeratin antibodies for identifying bone marrow involvement in breast cancer patients who showed no evidence of distant metastases using noninvasive tumor staging procedures. Bone marrow for histological (biopsy) and immunocytochemical (aspiration) evaluation was obtained from the anterior iliac crest from 50 unselected consecutive women during surgical treatment of the primary tumor. The histological examination was done on nondecalcifed bone sections. The immunocytochemical studies were carried out on interface smears of the bone marrow aspirates. For staining, cytokeratin antibodies (PKK 1) and the immune alkaline phosphatase method was used. Cytokeratin-positive cells were found in 4 of the 50 cases (8%). Of those 4 patients, however, 2 also showed evidence of neoplastic bone marrow infiltration histologically. We thus were able to prove that immunocytochemistry on aspirates is superior to conventional histology in identifying tumor in bone marrow. Nonetheless, our results clearly fell below the rate found in previous studies where epithelial membrane antigen antibodies were used.     

First Steps Toward the Establishment of a German Low‐Density Lipoprotein‐Apheresis Registry: Recommendations for the Indication and for Quality Management

Abstract: New recommendations for the indication of treatment with selective extracorporeal plasma therapy low‐density lipoprotein apheresis (LDL‐apheresis) in the prevention of coronary heart disease are urgently needed. The following points are the first results of the ongoing discussion process for indications for LDL‐apheresis in Germany: all patients with homozygous familial hypercholesterolemia with functional or genetically determined lack or dysfunction of LDL receptors and plasma LDL cholesterol levels >13.0 mmol/L (>500 mg/dL); patients with coronary heart disease (CHD) documented by clinical symptoms and imaging procedures in which over a period of at least 3 months the plasma LDL cholesterol levels cannot be lowered below 3.3 mmol/L (130 mg/dL) by a generally accepted, maximal drug‐induced and documented therapy in combination with a cholesterol‐lowering diet; and patients with progression of their CHD documented by clinical symptoms and imaging procedures and repeated plasma Lp(a) levels >60 mg/dL, even if the plasma LDL cholesterol levels are lower than 3.3 mmol/L (130 mg/dL). Respective goals for LDL cholesterol concentrations for high‐risk patients have been recently defined by various international societies. To safely put into practice the recommendations for LDL‐apheresis previously mentioned, standardized treatment guidelines for LDL‐apheresis need to be established in Germany that should be supervised by an appropriate registry.     

The distinct temperament profiles of bipolar I, bipolar II and unipolar patients

BACKGROUND: Despite a plethora of studies, controversies abound on whether the long-term traits of unipolar and bipolar patients could be differentiated by temperament and whether these traits, in turn, could be distinguished from subthreshold affective symptomatology. METHODS: 98 bipolar I (BP-I), 64 bipolar II (BP-II), and 251 unipolar major depressive disorder (UP-MDD) patients all when recovered from discrete affective episodes) and 617 relatives, spouses or acquaintances without lifetime RDC diagnoses (the comparison group, CG) were administered a battery of 17 self-rated personality scales chosen for theoretical relevance to mood disorders. Subsamples of each of the four groups also received the General Behavior Inventory (GBI). RESULTS: Of the 436 personality items, 103 that significantly distinguished the three patient groups were subjected to principal components analysis, yielding four factors which reflect the temperamental dimensions of "Mood Lability", "Energy-Assertiveness," "Sensitivity-Brooding," and "Social Anxiety." Most BP-I described themselves as near normal in emotional stability and extroversion; BP-II emerged as labile in mood, energetic and assertive, yet sensitive and brooding; MDD were socially timid, sensitive and brooding. Gender and age did not have marked influence on these overall profiles. Within the MDD group, those with baseline dysthymia were the most pathological (i.e., high in neuroticism, insecurity and introversion). Selected GBI items measuring hypomania and biphasic mood changes were endorsed significantly more often by BP-II. Finally, it is relevant to highlight a methodologic finding about the precision these derived temperament factors brought to the UP-BP differentiation. Unlike BP-I who were low on neuroticism, both BP-II and UP scored high on this measure: yet, in the case of BP-II high neuroticism was largely due to mood lability, in UP it reflected subdepressive traits. LIMITATION: We used self-rated personality measures, a possible limitation generic to the paper-and-pencil personality literature. It is therefore likely that BP-I may have over-rated their "sanguinity"; or should one consider such self-report as a reliable reflection of one's temperament? One can raise similar unanswerable questions about "depressiveness" and "mood lability." CONCLUSION: As contrasted to CG and published norms, the postmorbid self-described "usual" personality is 1) sanguine among many, but not all, BP-I; 2) labile or cyclothymic among BP-II; and 3) subanxious and subdepressive among UP. It is further noteworthy that with the exception of BP-II, the temperament scores of BP-I and MDD were within one SD from published norms. Rather than being pathological, these attributes are best conceived as subclinical temperamental variants of the normal, thereby supporting the notion of continuity between interepisodic and episodic phases of affective disorders. These findings overall are in line with Kraepelin's views and contrary to the DSM-IV formulation of axis-II constructs as being pathological and sharply demarcated from affective episodes.     

A Case Report of Darbepoetin Treatment in a Patient With Sickle Cell Disease and Chronic Renal Failure Undergoing Regular Hemodialysis Procedures That Induce a Dose-Dependent Extension of Blood Transfusion Intervals

Abstract: In this case, a female Nigerian patient suffered from sickle cell disease (SCD, hemoglobin SS)-induced chronic renal failure and was undergoing hemodialysis treatment. Due to SCD crisis and renal anemia the patient received regular blood transfusions when the hemoglobin concentration fell below 5.0 g/L. Blood transfusion associated iron-overload was noticed. To reduce the iron-overload side effects, we started an erythropoietin therapy (darbepoetin) to extend the blood transfusion interval, using 30–150 µg/week. As a result of our investigation we observed that darbepoetin can significantly extend blood transfusion intervals without increasing SCD crisis. To substantiate our observation, further investigations are needed with more SCD patients undergoing regular hemodialysis treatment.     

NMR‐based lipoprotein analysis for patients with severe hypercholesterolemia undergoing lipoprotein apheresis or PCSK9‐inhibitor therapy (NAPALI‐Study)

Taking into account the discordance between low‐density lipoprotein cholesterol (LDL‐C) and LDL particle (LDL‐P) number, cardiovascular risk more closely correlates with LDL‐P in patients. The aim of our study was to evaluate the number of lipid particles in patients with severe hypercholesterolemia treated with different lipid‐lowering regimens. Four groups of patients differing with respect to lipid‐lowering therapy were recruited from hypercholesterolemic outpatients and lipoprotein apheresis (LA) facilities, and were treated with statins alone (group A), with statins and proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors (PCSK9i) (group B), with statins and LA (group C), or with statins, PCSK9i, and LA (group D). Cholesterol, triglycerides, LDL‐C, high‐density lipoprotein cholesterol (HDL‐C), LDL‐P number and size, HDL‐P number and size were determined using nuclear magnetic resonance spectroscopy. The lowest LDL‐P number was achieved at the end of LA sessions in combination with statins or in combination with statins and a monoclonal PCSK9i (median; 25th and 75th percentile) (group C: 244 nmoL/L: 237, 244, P < 0.05; group D: 244 nmoL/L: 99, 307, P < 0.05). Comparing LDL‐P number at the start of LA (group C: 978 nmoL/L: 728, 1404; group D: 954 nmoL/L: 677, 1521) to the other patient groups (groups A and B), the lowest LDL‐P number was measured in patients treated with PCSK9i and a statin (group B): LDL‐P (762 nmoL/L: 604, 1043, P < 0.05), large LDL‐P (472 nmoL/L: 296, 574, P < 0.05), and small LDL‐P (342 nmoL/L: 152, 494, P < 0.05). Very low‐density lipoprotein and HDL particle sizes remained approximately the same in all groups. LA in combination with statins or in combination with statins and PCSK9i most reduced LDL‐P numbers in hypercholesterolemic patients.