Transcatheter Occlusion of Residual Patent Ductus Arteriosus After Surgical Ligation

The reported frequency of residual leaks after surgical ligation of patent ductus arteriosus (PDA) varies from 6% to 23%. Reports on percutaneous closure of PDA also involve patients with residual PDA after ligation, but specific data regarding this type of PDA are rare. Our objective was to assess retrospectively the characteristics of residual PDA relevant to transcatheter closure and occlusion results using three types of occluders. Twelve consecutive patients underwent transcatheter occlusion of residual PDA after surgical ligation at a median age of 4.6 years (range 3.2–44.6 years) and median weight 16.5 kg (range 13–62 kg). Three types of occluder were used: Gianturco coils, detachable Cook PDA coils, and the new Amplatzer duct occluder. The median diameter of residual PDA after ligation was 1.5 mm (range 0.9–4.2 mm). All PDAs were of type A morphology. Thirteen devices were successfully placed in the 12 patients, without embolization. There were no complications. At 1 month and 1 year follow-up all residual shunts were completely closed. Coils are particularly suitable for complete closure of residual leaks after surgical ligation of PDA. A 100% closure rate was achieved with a low number of implanted coils.     

Angiosarcoma of the testis

 A primary angiosarcoma of the testis in a 74-year-old patient was a highly anaplastic epthelioid angiosarcoma, which was positive for endothelial markers immunohistochemically. The tumour was unrelated to testicular germ cell neoplasm; the patient had received no previous radiation or chemotherapy. Received: 18 August 1998 / Accepted: 16 November 1998     

Interactions of Aminopropyl–Azithromycin Derivatives,Precursors in the Synthesis of Bioactive Macrozones,with E. coli Ribosome: NMR and Docking Studies

The structure and interactions of several aminopropyl–azithromycin derivatives (1a–c) have been studied by using NMR spectroscopy and docking calculations. Compounds 1a–c are precursors in the synthesis of macrozones, novel bioactive azithromycin–thiosemicarbazone conjugates active against some resistant bacterial strains. Today, bacterial resistance is considered as one of the major threats to human health. Knowledge on drug binding mode and conformations is one of the key factors in the process of designing molecules to fight resistance. In solution state, compounds 1a and 1c exist in the 3-endo-folded-out conformation, while 1b adopts a classical folded-out conformation. ¹³C and ¹⁵N CPMAS NMR spectra pointed towards similar structures in the solid state. The transferred NOESY NMR spectra confirmed binding to the E. coli ribosome and suggest that dominant conformations in the bound state resemble those in the free one. STD experiments identified reactive groups of 1a–c in close contact with the ribosome resembling binding epitopes observed for the related 15-membered macrolides. Docking studies revealed that the studied compounds bind to the same ribosome binding pocket similarly to erythromycin in the crystal state, and that the binding is achieved through H-bonds and van der Waals interactions. The bound conformation is the same as determined by NMR. STD enhancements observed for methylene protons in the aminopropyl side chain indicate additional interactions which contribute to the overall binding energy.     

Intrathecal Synthesis of Specific Antibodies in Patients with Invasion of the Central Nervous System by Mycoplasma pneumoniae

 Mycoplasma pneumoniae commonly causes respiratory tract infections in humans, but it may also be associated with central nervous system manifestations. The aim of the present study was to determine whether the cerebrospinal fluid taken from patients with neurologic symptoms due to Mycoplasma pneumoniae infection contains specific antibodies and whether the detection of these antibodies can be used for diagnosis. Mycoplasma pneumoniae was isolated from the cerebrospinal fluid taken from nine patients with central nervous system symptoms on admission to the hospital. In addition, Mycoplasma pneumoniae was detected in cerebrospinal fluid using polymerase chain reaction in four other patients. Antibodies to Mycoplasma pneumoniae were detected using the enzyme immunosorbent assay, indirect immunoperoxidase assay and immunoblotting in cerebrospinal fluid samples from 14 of 19 patients included in the study. The indirect immunoperoxidase assay showed high titers of Mycoplasma pneumoniae immunoglobulin G₁ (IgG₁) and IgM antibodies in cerebrospinal fluid samples of some patients with meningoencephalitis or meningitis. Titers of specific IgA, IgG₂ and IgG₃ antibodies were lower, while specific IgG₄ was not detectable. Cerebrospinal fluid samples with higher antibody titers also contained IgA, IgG₁, IgG₂, IgG₃ and IgM antibodies that recognized the P1 adhesin (170 kDa protein) of Mycoplasma pneumoniae. A comparison of antibody titers of concomitant serum/cerebrospinal fluid samples to Mycoplasma pneumoniae and those to measles virus by enzyme immunosorbent assay suggested the intrathecal synthesis of IgG and IgM antibodies to Mycoplasma pneumoniae in patients with acute meningoencephalitis. Data from this study clearly reinforce previous findings that Mycoplasma pneumoniae is an etiologic agent of central nervous system infections in humans.     

Content and stability of B complex vitamins in commercial cosmetic products

Background

Individual B vitamins have many favorable effects on the skin and are common cosmetic ingredients. However, their formulation is demanding due to stability issues, which consequently affect the products’ quality.

Aims

We aimed to determine the quality (labeling accuracy, content determination, and content-related quality control) and stability under long-term and accelerated storage conditions of a representative sample of commercial cosmetics containing the most common B vitamins – nicotinamide, dexpanthenol, pyridoxine, and cyanocobalamin.

Methods

Cyanocobalamin was determined by a previously published stability-indicating HPLC– diode array detector (DAD) method for the simultaneous determination of all hydrophilic vitamins. This method was additionally simplified and adjusted for the time-effective analysis of nicotinamide, dexpanthenol, and pyridoxine. Both methods were properly validated.

Results

All labeled B vitamins were present in the 36 tested products, mostly in contents, reported effective on the skin. Thus, a straightforward correlation between vitamin contents and product prices were not observed. The content-related quality control of eight products, which quantitively specify their content, revealed significantly lower nicotinamide contents (47% and 57%) in two products and appropriate or higher nicotinamide (102%–112%) and dexpanthenol (100%–104%) contents than declared in the remaining products. The 6-month long-term and accelerated stability studies demonstrated the products’ physical stability, but also revealed dexpanthenol, pyridoxine, and cyanocobalamin degradation, while nicotinamide was mostly stable in the tested products.

Conclusions

The obtained results provide an inside into the quality of commercial vitamin B cosmetics and highlight the importance of stability testing in the formulation of quality, efficient, and safe cosmetics.     

Quality assurance guidelines for interstitial hyperthermia

Quality assurance (QA) guidelines are essential to provide uniform execution of clinical hyperthermia treatments and trials. This document outlines the clinical and technical consequences of the specific properties of interstitial heat delivery and specifies recommendations for hyperthermia administration with interstitial techniques. Interstitial hyperthermia aims at tumor temperatures in the 40–44?°C range as an adjunct to radiation or chemotherapy. The clinical part of this document imparts specific clinical experience of interstitial heat delivery to various tumor sites as well as recommended interstitial hyperthermia workflow and procedures. The second part describes technical requirements for quality assurance of current interstitial heating equipment including electromagnetic (radiative and capacitive) and ultrasound heating techniques. Detailed instructions are provided on characterization and documentation of the performance of interstitial hyperthermia applicators to achieve reproducible hyperthermia treatments of uniform high quality. Output power and consequent temperature rise are the key parameters for characterization of applicator performance in these QA guidelines. These characteristics determine the specific maximum tumor size and depth that can be heated adequately. The guidelines were developed by the ESHO Technical Committee with participation of senior STM members and members of the Atzelsberg Circle.     

LIPG-promoted lipid storage mediates adaptation to oxidative stress in breast cancer

Endothelial lipase (LIPG) is a cell surface associated lipase that displays phospholipase A1 activity towards phosphatidylcholine present in high-density lipoproteins (HDL). LIPG was recently reported to be expressed in breast cancer and to support proliferation, tumourigenicity and metastasis. Here we show that severe oxidative stress leading to AMPK activation triggers LIPG upregulation, resulting in intracellular lipid droplet accumulation in breast cancer cells, which supports survival. Neutralizing oxidative stress abrogated LIPG upregulation and the concomitant lipid storage. In human breast cancer, high LIPG expression was observed in a limited subset of tumours and was significantly associated with shorter metastasis-free survival in node-negative, untreated patients. Moreover, expression of PLIN2 and TXNRD1 in these tumours indicated a link to lipid storage and oxidative stress. Altogether, our findings reveal a previously unrecognized role for LIPG in enabling oxidative stress-induced lipid droplet accumulation in tumour cells that protects against oxidative stress, and thus supports tumour progression.