Holo-transcobalamin is an early marker of changes in cobalamin homeostasis. A randomized placebo-controlled study

BACKGROUND: We examined the effect of oral vitamin B(12) treatment on fluctuations in plasma total cobalamin and its binding proteins transcobalamin (TC) and haptocorrin (HC). METHODS: Patients (n = 88; age range, 38-80 years) undergoing coronary angiography (part of the homocysteine-lowering Western Norway B-Vitamin Intervention Trial) were allocated to daily oral treatment with (a) vitamin B(12) (0.4 mg), folic acid (0.8 mg), and vitamin B(6) (40 mg); (b) vitamin B(12) and folic acid; (c) vitamin B(6); or (d) placebo. EDTA blood was obtained before treatment and 3, 14, 28, and 84 days thereafter. RESULTS: The intraindividual variation for patients not treated with B(12) was approximately 10% for plasma total cobalamin, total TC, apo-TC, and apo-HC, and <20% for holo-TC and TC saturation. In B(12)-treated patients, the maximum change in concentrations was observed already after 3 days for total TC (-16%), holo-TC (+54%), and TC saturation (+82%). At this time holo-HC (+20%) and plasma total cobalamin (+28%) showed an initial burst, but had increased further at 84 days. All changes were highly significant compared with the control group (P <0.0001). CONCLUSIONS: Oral vitamin B(12) treatment produces maximal effects on total TC, holo-TC, and TC saturation within 3 days, whereas maximal increases in holo-HC and plasma total cobalamin occur later. The results support the view that holo-TC is an early marker of changes in cobalamin homeostasis.     

A practical approach to guide clinicians in the evaluation of male patients with breast masses

Breast cancer must be considered in the evaluation of breast masses in men, although various benign causes are more common, including gynecomastia and conditions of the skin and subcutaneous tissue. A patient's history may identify key features suspicious for malignancy or reassuring for benign disease. Physical examination has been documented to be as effective as mammography in distinguishing benign from malignant lesions, and both have been reported as highly accurate for the identification of malignancy. Mammography is therefore best used when the physical examination findings are indeterminate. Ultrasonography may be used as an adjunct to mammography; no evidence supports the use of magnetic resonance imaging in male breast patients. If clinical or mammographic features are suspicious or indeterminate for malignancy, tissue diagnosis is warranted and may be achieved surgically or via core-needle biopsy or fine-needle aspiration cytology. Given the lack of uniformity in the clinical recommendations for the evaluation of breast masses in men, a practical approach is proposed.     

Assessment of periadventitial adipose tissue in abdominal aortic aneurysm with computed tomography and its challenges

The International Journal of Cardiovascular Imaging -     

Toxic effects of paracetamol and related structures in V79 Chinese hamster cells

Exposure of V79 Chinese hamster cells to non-cytotoxic concentrationsof paracetamol (4-hydroxyacetanilide, 4-HAA) increased sisterchromatid exchange (SCE) in the absence of an external activationsystem. Furthermore, a selective inhibition of DNA synthesiswas observed at low 4-HAA concentrations. The inhibition couldbe counteracted by the addition of ascorbate, indicating thatthe effect is caused by an oxidation product of 4-HAA. In attemptto clarify possible relationships between cytotoxicity, inhibitionof DNA synthesis and increased SCE, we studied the effect of4-HAA and some related structures on these parameters. The relativeposistion of the amino group and the hydroxyl group on the aromaticringappear to be important for the inhibition of DNA synthesis.Removal of either of the two groups, N-acetylation and/or alkylationof the aromatic ring or phenolic oxygen decreased the effectof the aromatic amine on DNA synthesis. A significant responseon SCE was observed with 4-aminophenol, 4-HAA, 2-HAA, 3, 5-dimethyl-4-HAA,3-HAA and 2, 6-dimethyl-4-HAA (none of the other compounds weretested). The increase in SCE frequency caused by 4-HAA and itsanalogs does not seem to be related to more general cytotoxiceffects. The relative potencies of the compounds for SCE inductionparalleled, for the most part, their effects on DNA synthesis.However, the induction of SCE and the inhibition of DNA synthesisdid not occur at comparable concentrations. Thus, the possibilitythat 4-HAA increases the frequency of SCE through some othermechanism cannot be excluded.     

In Vitro Induction of Lymphokine-Activated Killer (Lak) Activity in Patients with Neuroblastoma

Therapy of disseminated neuroblastoma remains an unsolved problem in pediatric oncology. Therefore, new therapeutic approaches have to be developed for this malignancy. In this paper, we investigated the possibility of the in vitro generation and expansion of lymphokine-activated killer (LAK) cells in patients with disseminated neuroblastoma. Although the patients had very low Natural Killer (NK) activity, it was possible to induce LAK activity in peripheral mononuclear lymphocytes (PMNC) by incubation with Interleukin-2 (IL-2). Moreover, the PMNCs could be expanded up to 50-fold in the presence of Interleukin-2 while maintaining or even increasing their LAK activity. The target cells were neuroblastoma cell lines and, in one case, autologous neuroblastoma cells. Additionally, it was possible to induce LAK cell activity against autologous neuroblastoma cells in bone marrow-derived mononuclear cells.     

抗高血压药物与罹患癌症的风险:324168例参与随机临床试验病人的荟萃分析和试验序贯分析

长期以来,一直存在抗高血压药物是否有致癌作用的争议.自从在年龄>50岁的妇女中使用萝芙碱提取物造成乳腺癌发病率增加的报道后[1],这一争议已持续了30年.Sipahi和同事们最近的研究显示:血管紧张素受体拮抗剂(angiotensin receptor-blockers,ARB)有较高的致癌风险.这一发现再次引发了抗...