The effect of intravenous disodium ethylenediaminetetraacetic acid (EDTA) plus supportive multivitamin/trace mineral supplementation upon fasting serum calcium

A literature search disclosed only very limited published material suggesting that EDTA therapy when given slowly does not seem to derange serum calcium metabolism. This report summarizes the observations of eighty private practice patients treated with EDTA and supportive multivitamin/trace mineral supplementation and its effects upon serum calcium. The evidence indicates that, in general, this form of chelation therapy does not alter serum calcium concentration. Additionally, and perhaps more importantly, the evidence here suggests the so-called high normals declined slightly, the low normals rise slightly, and those in the intermediate range remain unchanged.     

Pr?vention des Suizidsin der Armee

Ohne Zusammenfassung     

Aziridine-2,3-dicarboxylic Acid Derivatives as Inhibitors of Papain

Aziridine-2,3-dicarboxylates and N-acylated derivatives have been evaluated as potential irreversible inhibitors of the cysteine proteinase papain. Dependence of inhibition activity on stereo-chemistry of the aziridine moiety has been analyzed. Whereas unsubstituted (R,R)- and (S,S)- diethyl aziridine-2,3-dicarboxylates ( 5 ) and ( 2 ) show no significant difference in inactivation the derivative acylated with BOC-(S)-Phe (BOC-(S)-Phe-(S,S)-Azi) ( 10 ) shows a 6 fold higher activity than the diastereomer BOC-(S)-Phe-(R,R)-Azi ( 11 ). Analogs acylated with Z- or BOC-(S)-Ala ( 9, 8 ) have lower second-order rate constants, indicating binding of the amino acid moiety of the inhibitors to the S2 subsite of the enzyme.     

Postnatal decline in pyridoxal phosphate and riboflavin. Accentuation by phototherapy

Riboflavin is a cofactor in the conversion of pyridoxine (vitamin B6) to pyridoxal phosphate (PALP), an essential coenzyme in numerous metabolic pathways, including neurotransmitter synthesis. Riboflavin and pyridoxine are light sensitive in vitro, and conflicting results have been reported on the in vivo effects of phototherapy on riboflavin. We studied 25 full-term neonates receiving phototherapy and 16 healthy controls to evaluate their riboflavin and PALP status. Both vitamin cofactors decreased in both sets of infants, but significantly more so in the irradiated group. While the biologic or clinical importance of a modest biochemical decline in the level of PALP has not been established, it is possible that transient behavioral changes in irradiated, jaundiced neonates could be mediated by decreased availability of PALP. The mechanism for the postnatal decline and the desirability of routine supplementation with pyridoxine, especially in irradiated infants, require further study.     

Development of a reverse transcription-PCR assay to detect porcine circovirus type 2 transcription as a measure of replication

Porcine circovirus type 2 (PCV2) is a non-enveloped, single-stranded, circular DNA virus. In situ hybridization and PCR assays have detected PCV2 DNA in multiple organs and cell types from infected pigs; however, it is not clear if this represents replicating virus or virion DNA. We describe the development of a single-tube RT-PCR assay to differentiate PCV2 replication products and virus DNA. Primers targeted to the open-reading frame 2 (ORF2) of PCV2 were designed to amplify both virus DNA (984 bp) and the spliced Cap mRNA (594 bp). The 984 bp fragment, but not the 594 bp fragment, was amplified from PCV2 stock, confirming that the spliced Cap mRNA was not present in the PCV2 stock. The 594 bp fragment was amplified from DNase-treated RNA extracted from PCV2-infected PK-15 cells, and was detected as early as 14 h post-infection. No products were amplified from either the PCV1 stock or PCV1-infected PK-15 cells, or from cells infected with UV-inactivated PCV2. Therefore, the presence of the 594 bp fragment is specific for PCV2 replication. This assay will be useful in assessing cell populations that support PCV2 replication in vivo or in vitro and advance the understanding of PCV2 replication and pathogenesis.     

Peptide-oligonucleotide conjugates for the delivery of antisense and siRNA

Conjugation of oligonucleotides to certain types of peptides provides an interesting approach for enhancing delivery of antisense and siRNA to cells and tissues. This article will provide a perspective on issues in oligonucleotide delivery, and will examine recent literature on the preparation and use of several types of peptide-oligonucleotide conjugates.     

Vascular endothelial cell growth factor receptor 3-mediated activation of lymphatic endothelium is crucial for tumor cell entry and spread via lymphatic vessels

Lymphangiogenic growth factors vascular endothelial growth factor (VEGF)-C and VEGF-D have been shown to promote lymphatic metastasis by inducing tumor-associated lymphangiogenesis. In this study, we have investigated how tumor cells gain access into lymphatic vessels and at what stage tumor cells initiate metastasis. We show that VEGF-C produced by tumor cells induced extensive lymphatic sprouting towards the tumor cells as well as dilation of the draining lymphatic vessels, suggesting an active role of lymphatic endothelial cells in lymphatic metastasis. A significant increase in lymphatic vessel growth occurred between 2 and 3 weeks after tumor xenotransplantation, and lymph node metastasis occurred at the same stage. These processes were blocked dose-dependently by inhibition of VEGF receptor 3 (VEGFR-3) signaling by systemic delivery of a soluble VEGFR-3-immunoglobulin (Ig) fusion protein via adenoviral or adeno-associated viral vectors. However, VEGFR-3-Ig did not suppress lymph node metastasis when the treatment was started at a later stage after the tumor cells had already spread out, suggesting that tumor cell entry into lymphatic vessels is a key step during tumor dissemination via the lymphatics. Whereas lymphangiogenesis and lymph node metastasis were significantly inhibited by VEGFR-3-Ig, some tumor cells were still detected in the lymph nodes in some of the treated mice. This indicates that complete blockade of lymphatic metastasis may require the targeting of both tumor lymphangiogenesis and tumor cell invasion.     

Intraoperative radiotherapy (IORT) for breast cancer using the Intrabeam system

INTRODUCTION: Intraoperative radiotherapy (IORT) with low-energy X-rays (30-50 KV) is an innovative technique that can be used both for accelerated partial breast irradiation (APBI) and intraoperative boosting in patients affected by breast cancer. Immediately after tumor resection the tumor bed can be treated with low-distance X-rays by a single high dose. Whereas often a geographic miss in covering the boost target occurs with external beam boost radiotherapy (EBRT), the purpose of IORT is to cover the tumor bed safely. This report will focus on the feasibility and technical aspects of the Intrabeam device and will summarize our experience with side effects and local control. MATERIALS AND METHODS: Between February 2002 and June 2003 57 breast cancer patients, all eligible for breast conserving surgery (BCS), were treated at the Mannheim Medical Center with IORT using the mobile X-ray system Intrabeam. The patient population in this feasibility study was not homogeneous consisting of 49 patients with primary stage I or II breast cancer, seven with local recurrence after previous EBRT and one with a second primary in a previously irradiated breast. The selection criteria for referral for IORT included tumor size, tumor cavity size, margin status and absence of an extensive intraductal component. The previously irradiated patients with local recurrences and 16 others received IORT as single modality. In all other cases IORT was followed by EBRT with a total dose of 46 Gy in 2-Gy fractions. The intraoperatively delivered dose after tumor resection was 20 Gy prescribed to the applicator surface. EBRT was delivered with a standard two-tangential-field technique using linear accelerators with 6- or 18-MV photons. Patients were assessed every three months by their radiation oncologist or surgeon during the first year after treatment and every six months thereafter. Breast ultrasound for follow-up was done every six months and mammographies once yearly. Acute side effects were scored according to the CTC/EORTC score and late side effects according to the Lent-Soma classification. RESULTS: Twenty-four patients received IORT only; eight patients because they had received previous radiotherapy, 16 because of a very favorable risk profile or their own preference. Thirty-three patients with tumor sizes between 1 and 30 mm and no risk factors were treated by IORT as a boost followed by EBRT. The Intrabeam system was used for IORT. The Intrabeam source produces 30-50 KV X-rays and the prescribed dose is delivered in an isotropic dose distribution around spherical applicators. Treatment time ranged between 20 and 48 minutes. No severe acute side effects or complications were observed during the first postoperative days or after 12 months. One local recurrence occurred 10 months after surgery plus IORT followed by EBRT. In two patients distant metastases were diagnosed shortly after BCS. DISCUSSION: IORT with the Intrabeam system is a feasible method to deliver a single high radiation dose to breast cancer patients. As a preliminary boost it has the advantage of reducing the EBRT course by 1.5 weeks, and as APBI it might be a promising tool for patients with a low risk of recurrence. The treatment is well tolerated and does not cause greater damage than the expected late reaction in normal tissue.