Nucleoside analogues: 8. Some isomers of B.3839, the original 5-fluorouracil/nitrosourea molecular combination, and their effect on colon, breast and lung tumours in mice

This study describes the manipulation of secondary products arising from the synthesis of the prototypical molecular combination of 5-fluorouracil (5-FU) and chloroethylnitrosourea (CNU), B.3839, in order to investigate the effects produced by connecting the C-S-C-C-CNU chain to the 5-FU ring in different ways. The isolation of phthalimide precursors of these compounds and the transformation into CNUs is described. Anti-tumour activity of these molecular combinations against a series of experimental murine colon, lung and mammary tumours is presented. The spectrum of anti-tumour activity displayed is interesting but defies simple explanation without further detailed in vivo pharmacokinetic and metabolism studies in order to define optimal profiles for activity.     

Truncus Arteriosus With Patent Ductus Arteriosus and Normal Aortic Arch

In hearts with a common arterial trunk (truncus arteriosus), there is almost always an inverse development of the aortic arch and the ductus arteriosus. Truncus with a normal aortic arch and a patent ductus is a rare echocardiographic and surgical finding. In this report, we describe 2 neonates in whom truncus arteriosus with a normal aortic arch and a medium or large patent ductus was diagnosed by preoperative echocardiography (without catheterization) and confirmed intraoperatively.     

Nucleoside analogues. 4. Molecular combinations of anti-tumour drugs: synthesis of 5-fluorouracil seco-nucleosides with N-(2-chloroethyl)-N-nitrosourea residues by using aryl N-nitrosocarbamates

The biological study of molecular combination of anti-tumour drugs remains unexplored. Some drugs prepared earlier, seco-nucleosides with 5-fluorouracil as base and incorporating a N-(2-chloroethyl)-N-nitrosourea (CNU) residue in the linear 'sugar' moiety, have now been obtained much more readily by using aryl N-nitrosocarbamates. These include the more reactive S-oxide of the original combination, B 3839. The structure of a compound with the CNU in the 'alcohol' arm of the seco-nucleoside has been clarified. Isomeric combinations having hydroxyl groups in either the 'alcohol' or the 'aldehyde' arm, with different hydrolysis rates, have been synthesized. Results of anti-tumour testing are reported in the proceeding paper.     

环孢菌素A阻断人HL－60抗药性细胞于G_1期而诱导敏感细胞凋亡

进一步研究了抗三尖杉酯碱的ＨＬ－６０细胞（ＨＲ２０）抗细胞凋亡的机制及该抗性和抗药性的关系。结果表明，环孢菌素Ａ（ＣｓＡ）２０，１０μｇ·ｍｌ￣（－１）诱导ＨＬ－６０细胞发生凋亡，而阻断ＨＲ２０细胞于Ｇ＿１期，就不能诱导细胞发生凋亡。低浓度的ＣｓＡ明显增加柔红霉素在ＨＲ２０细胞内的积聚，其逆转抗药性作用与阻断细胞周期运行无关。ＣｓＡ１０μｇ·ｍｌ￣（－１）处理ＨＲ２０细胞，可引起５０ｋＤａ的蛋白质高度磷酸化。结果提示：环孢菌素Ａ阻断抗三尖杉酯碱的ＨＬ－６０细胞于Ｇ＿１期，而诱导敏感的ＨＬ－６０细胞发生凋亡，其阻断作用与抗药性无关     

Microsurgical anatomy of VII and VIII cranial nerves and related arteries in the cerebellopontine angle

Summary The relationships of VII and VIII cranial nerves and related arteries are reviewed in 26 preparations by microdissection techniques. These vessels may be grouped in large (AICA, PICA), medium (LA, SA, CSA, RPI) and small calibre (vasa nervorum, radicullar and medullar branches). The importance of these structures in acoustic neuroma surgery, vestibular neurectomy and cross-compression syndromes is discussed. Vascular loops and elongated arteries are normal structures present at birth.This work was supported by a grant from the AJ Roemmers Foundation     

Differential pattern of DNA-aneuploidy in human malignancies

The differential pattern of DNA-aneuploidy, detected by flow cytometry (FCM) regarding its frequency, grade and multiclonality, was investigated and correlated to tumor type, malignancy grade, tumor stage and prognosis in a multi-institutional study at the University of Münster. High resolution measurements using admixed normal blood reference cells were undertaken in 2413 cases of 13 different malignant diseases and in 776 benign lesions or samples. The incidence of DNA-aneuploidy was highest in melanomas, carcinomas, testicular tumors, sarcomas (75%-95%) and myelomas (65%). Acute leukemias showed an intermediate DNA-aneuploidy rate of 40% with special subgroups represented by common ALL (44%), p less than 0.05) and myelomonocytic/monocytic AML (47%, p less than 0.01). The lowest DNA-aneuploidy-rate was found in basal cell skin carcinomas (19%) and congenital melanocytic nevi (9%). No case of DNA-aneuploidy was observed in the 776 benign lesions or samples.--DNA-indices giving the grade of DNA-aneuploidy with 1.0 for normal diploid G1/0 cells were found distributed predominantly between 1.0 and 2.0 in the solid tumors, except testicular tumors, clustering around a triploid maximum at 1.5. DNA-indices of myelomas and acute leukemias generally ranged below 1.25 with lower DNA-aneuploidy grades in AML than in ALL (p less than 0.01).--In melanomas the aneuploidy rate was higher (86%) in metastases than in the primary tumors (54%, p = 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)     

Osteosarcomatosis

A review of the 690 cases of osteosarcoma in the radiographic file of the Armed Forces Institute of Pathology revealed 29 cases of "osteosarcomatosis" (multiple skeletal sites of osteosarcoma). Fifteen of these patients were 18 years old and under and manifested rapidly appearing, usually symmetric, sclerotic metaphyseal lesions. The remaining 14 patients were more than 18 years old and had fewer, asymmetric sclerotic lesions. In most patients (28 of 29), a radiographically dominant skeletal tumor was seen. Pulmonary metastases occurred in the majority of patients and were detected at the same time as the bone lesions. These 29 patients were studied with regard to demographic data and skeletal distribution and radiographic appearance of their lesions. As a result of the findings, a metastatic origin from a primary dominant osteosarcoma is favored over a multifocal origin as the basis for osteosarcomatosis. Osteosarcomatosis is more commonly encountered in the mature skeleton than has been previously recognized.     

Common brachiocephalic trunk: strategies for revascularization

BACKGROUND: A common brachiocephalic trunk, in which both common carotid arteries and the right subclavian artery arise from a single trunk off the arch, is a normal variant of aortic arch branching that occurs in approximately 10% of the population. Because three of the four primary sources of cerebral blood flow arise from a single aortic branch, stenosis or occlusion of a common trunk can cause severe ischemic consequences. Common trunk revascularization has been described, but there have been no reports focusing on the management options for occlusive disease of this vascular anatomy. METHODS: A retrospective review of our experience with innominate artery revascularization identified 6 patients who underwent revascularization of a common brachiocephalic trunk between 1977 and 1997. All patients were symptomatic, with either total occlusion (n = 3) or critical stenosis (n = 3) caused by atherosclerosis (n = 5) or Takayasu's arteritis (n = 1). Revascularization was achieved by a prosthetic bypass graft from the ascending aorta to the innominate or left common carotid arteries or both (n = 5); or transarterial endarterectomy (n = 1). Concomitant endarterectomy of branch vessels was performed in 3 patients. RESULTS: There was one perioperative death from myocardial infarction, and one perioperative stroke, with death occurring 1 month after hospital discharge. One patient developed cerebral hyperperfusion syndrome 1 week after endarterectomy that resolved without sequelae with antihypertensive medications. During a follow-up period ranging from 1 to 20 years, there was one late death from congestive heart failure 5 years after operation. All surviving patients are alive and free from symptomatic recurrence. CONCLUSIONS: Revascularization for occlusive disease of a common brachiocephalic trunk can be achieved with effective and durable relief of symptoms using either a prosthetic bypass graft or endarterectomy. However, neurologic complications in 2 patients, which were fatal in 1, attest to the potential cerebral ischemic threat posed by occlusive disease of a common brachiocephalic trunk.