Differential cytotoxicity of an ether lipid on lymphoma and bone marrow cells and its role in purging malignant lymphoid cells from remission bone marrow contaminated with tumor cells.

Four human clonogenic malignant lymphoid cell lines (CEM, Su-DHL-4, Li-A, and Raji) as well as normal human bone marrow stem cell progenitor cells were investigated for clonal in vitro growth before and after incubation with the ether lipid ET-18-OCH3 for various times (1, 4, and 18 h) and at increasing concentrations of the drug (25, 50, 75, and 100 micrograms/ml). The clonal growth of the malignant lymphoid cell lines was inversely correlated with concentrations and times of drug incubation. The antineoplastic effect of ET-18-OCH3 was further amplified by subsequent cryopreservation. In a situation of 4-h exposure to less than or equal to 50 micrograms/ml ET-18-OCH3 and subsequent cryopreservation, in which greater than 50% of the normal human bone marrow progenitor cells survived, 1-3 logs of the malignant lymphoblastoid cells were killed, indicating a potential value of this drug for bone marrow purging in lymphoid malignancy. In order to simulate the situation of autologous bone marrow transplantation (ABMT) in complete remission of the disease, we contaminated normal human bone marrow cells with malignant CEM or Su-DHL-4 lymphoid cells at a ratio of 100:1. Results show that 4 h of incubation with 75 micrograms/ml ET-18-OCH3 and subsequent cryopreservation can eliminate 2-3 logs of clonogenic cells of the malignant lymphoblastoid cell lines under conditions that allow recovery of greater than 50% of the normal human hematopoietic progenitors.     

Pulmonale Thrombendarterektomie: Die Therapie der chronisch thromboembolischen pulmonalen Hypertension— Initiale chirurgische Erfahrung

Zusammenfassung Grundlagen Die pulmonale Thrombendarterektomie stellt eine effektive Therapie zur Behandlung von Patienten mit chronisch thromboembolischer pulmonalar Hypertonie dar. Wir berichten über unsere Erfahrungen mit dieser Operationstechnik bei den ersten 9 Patienten. Methodik Zwischen 1992 und Oktober 1994 wurde bei 9 Patienten eine pulmonale Thrombendarterektomie durchgeführt. über eine mediane Sternotomie wurden die Pulmonalarterien beider Seiten bis in ihre subsegmentalen Aufzweigungen im Sinne einer echten Endarterektomie vom organisierten thromboembolischen Material befreit. Zumeist waren Perioden des totalen Kreislaufstillstandes in tiefer Hypothermie notwendig, wobei diese zunehmend verkürzt werden konnten und 3 Patienten vollst?ndig ohne Kreislaufstopp operiert wurden. Ergebnisse Die perioperative Mortalit?t betrug 11%, wobei der 1. Patient am 14. postoperativen Tag an den Folgen eines Reperfusions?dems verstarb. Alle anderen Patienten sind 4 bis 22 Monate (im Mittel 13 Monate) nach dem Eingriff am Leben und zeigen eine Hochsignifikante Verbesserung ihrer h?modynamischen Situation (mean PAP pr?operativ: 62 mm Hg, postoperativ: 30 mm Hg p<0,001; Cardiac Index pr?operativ: 2,1 1/min/m², postoperativ: 3,6 l/min/m² p=0,001). W?hrend pr?operativ alle Patienten in NYHA-Klasse III oder IV waren, sind die 8 überlebenden jetzt alle in Klasse I oder II. Schlu?folgerungen Die pulmonale Thrombendarterektomie bietet eine erfolgreiche Therapiem?glichkeit für Patienten mit chronisch thromboembolischer pulmonaler Hypertonie mit einer in Anbetracht fehlender konservativer Altermativen akzeptablen Mortalit?t und ausgezeichneten funktionellen Langzeitergebnissen.      

Incidence of cancer in a cohort of magnesium production workers

The results from a cohort study on the incidence of cancer and the mortality in a cohort of 2391 male workers producing magnesium metal are presented. The study population was restricted to employees with more than one year of work experience in the study plant between 1951 and 1974 and the cohort was observed from 1953 to 1984. Altogether 152 new cases of cancer were observed versus 132.6 expected. Six cases of cancer of the lip were found against 2.3 expected, 21 of stomach cancer against 12.8 expected, and 32 of lung cancer against 18.2 expected. A possible causal relation between exposure to factors in the work environment and the development of cancer is discussed.     

Foix-Chavany-Marie-syndrome — neurological,neuropsychological, CT,MRI, and SPECT findings in a case progressive for more than 10 years

Summary In a 66-year-old woman signs and symptoms of bilateral opercular syndrome (Foix-Chavany-Marie-syndrome) developed progressively over a period of more than 10 years. Facio-linguo-velo-pharyngeo-masticatory diplegia with automatic-vol-untary dissociation was accompanied by motor aphasia and oral apraxia leading to a state of almost complete anarthria. Although it initially resembled the anterior biopercular syndrome there are also features indicating involvement of the posterior opercula. Although the aetiology remains obscure without pathological data, a bilateral focal brain atrophy is assumed. This is probably the first case documented by MRI and SPECT.Supported by the Hirnliga, Heidelberg, Federal Republic of Germany     

Effect of converting enzyme inhibitors on tissue converting enzyme and angiotensin II: therapeutic implications

Local tissue renin-angiotensin systems have recently been discovered in various organs, and evidence is accumulating that inhibition of these local renin-angiotensin systems may contribute to the actions of converting enzyme (CE) inhibitors. Measurements of CE activity and angiotensin II concentrations revealed that after oral administration of CE inhibitors, CE was inhibited not only in lung vascular endothelium and blood, but also in the heart, kidney, vascular wall, brain and other organs. The functional significance of tissue CE inhibition is suggested first by the antihypertensive effect of brain CE inhibition in spontaneously hypertensive rats, second by the concomitant persistence of blood pressure decrease and CE inhibition in vascular wall and kidney after long-term oral CE inhibitor treatment and third by ex vivo experiments demonstrating marked effects of oral CE inhibitor pretreatment on cardiac function in isolated rat hearts. Local inhibition of tissue renin-angiotensin systems may be an important factor involved in the beneficial effects of CE inhibitors in such cardiovascular diseases as arterial hypertension, congestive heart failure and cardiac arrhythmias.     

Clival chordoma presenting with acute brain stem hemorrhage.

The authors present a case of a 29-year-old man who developed rapidly progressive cranial nerve palsies and a right hemiparesis secondary to a pontine hemorrhage. The rare but correct diagnosis of a clival chordoma which had invaded the brain stem and subsequently hemorrhaged was based on computed tomography and magnetic resonance imaging. The diagnosis was confirmed at surgery when the patient underwent a successful operative decompression of tumor and clot from the pons via a sub-occipital craniotomy. This represents the first case of a clival chordoma to hemorrhage into the brain stem, which was diagnosed preoperatively and the patient survived.     

Spinal Trabecular Bone Loss and Fracture in American and Japanese Women

This study examined trabecular bone mineral density (BMD) in Japanese women with and without spinal fracture, and compared the results to American women with and without fracture. The quantitative computed tomography (QCT) systems used at the University of California, San Francisco (UCSF) and at Nagasaki University were cross-calibrated. Normative BMD was assessed with the K₂HPO₄ liquid phantom in 538 Americans aged 20–85 years, and with the B-MAS200 phantom in 577 Japanese aged 20–83 years. These BMD were adjusted for use with the Image Analysis solid phantom using the result of cross-calibration. The trabecular BMD in 111 postmenopausal American women (55 with fracture), and in 185 postmenopausal Japanese women (67 with fracture) were compared for investigation of the difference in BMD values relative to fracture status. The absolute BMD values in Japanese were lower than those in Americans, and the differences were greater with advancing age. The magnitude of the BMD difference was 8.6, 20.5, 38.1 mg/cm³ in women aged 20–24 years, 40–44 years, 60–64 years, respectively. In premenopausal women, BMD began to decrease at the age of 20 in Japanese, whereas the peak bone mass was maintained until the age of 35 in the American women. In immediate postmenopausal women, BMD significantly decreased in both populations. In later postmenopausal women, BMD significantly decreased with age in the Japanese women but decreased less rapidly in the American women. The aging decrease of BMD was 1.4% and 2.2% per year in the later postmenopausal American and Japanese women, respectively. The fracture threshold is considered to be lower in Japanese women. However, the BMD difference between American and Japanese women with fracture was similar to that without fracture. The Z-scores of fracture subjects versus controls were 2.9 in American and 1.8 in Japanese women. In conclusion, Japanese women were found to have a lower BMD and lower fracture threshold than American women. The significant decrease of spinal trabecular BMD in late postmenopause is potentially responsible for the higher prevalence of spinal fracture in Japanese women. Received: 18 December 1995 / Accepted: 23 September 1996