Anthracycline-induced cardiotoxicity - are we about to clear this hurdle?

Anthracyclines have contributed significantly to remarkable improvements in overall survival and are regarded as the most effective cytostatic drug for cancer treatment in various malignancies. However, anthracyclines are a significant cause of acute and chronic cardiotoxicity in cancer patients, and long-term cardiotoxicity can lead to death in about one-third of patients. Several molecular pathways have been implicated in the development of anthracycline-induced cardiotoxicity, although the underlying mechanisms of some molecular pathways are not fully elucidated. It is now generally believed that anthracycline-induced reactive oxygen species (resulting from intracellular metabolism of anthracyclines) and drug-induced inhibition of topoisomerase II beta are the key mechanisms responsible for the cardiotoxicity. To prevent cardiotoxicity, several strategies are being followed: (i) angiotensin-converting enzyme inhibitors, sartans, beta-blockers, aldosterone antagonists, and statins; (ii) iron chelators; and (iii) by development of new anthracycline derivatives with little or no cardiotoxicity. This review will discuss clinically evaluated doxorubicin analogues that were developed as potentially non-cardiotoxic anticancer agents and include recent development of a novel liposomal anthracycline (L-Annamycin) for the treatment of soft-tissue sarcoma metastatic to the lung and acute myelogenous leukaemia.

A Review on Novel Channel Materials for Particle Image Velocimetry Measurements-Usability of Hydrogels in Cardiovascular Applications.

Particle image velocimetry (PIV) is an optical and contactless measurement method for analyzing fluid blood dynamics in cardiovascular research. The main challenge to visualization investigated in the current research was matching the channel material's index of refraction (IOR) to that of the fluid. Silicone is typically used as a channel material for these applications, so optical matching cannot be proven. This review considers hydrogel as a new PIV channel material for IOR matching. The advantages of hydrogels are their optical and mechanical properties. Hydrogels swell more than 90 vol% when hydrated in an aqueous solution and have an elastic behavior. This paper aimed to review single, double, and triple networks and nanocomposite hydrogels with suitable optical and mechanical properties to be used as PIV channel material, with a focus on cardiovascular applications. The properties are summarized in seven hydrogel groups: PAMPS, PAA, PVA, PAAm, PEG and PEO, PSA, and PNIPA. The reliability of the optical properties is related to low IORs, which allow higher light transmission. On the other hand, elastic modulus, tensile/compressive stress, and nominal tensile/compressive strain are higher for multiple-cross-linked and nanocomposite hydrogels than single mono-cross-linked gels. This review describes methods for measuring optical and mechanical properties, e.g., refractometry and mechanical testing.

[Traditional Chinese medicine and cancer recurrence]. / Médecine traditionnelle chinoise et rechutes de cancers.

Being diagnosed with cancer and having to undergo gruelling treatment is an ordeal. A recurrence of the disease is equally traumatic and can have a profound impact on the patient's balance. In this context, traditional Chinese medicine can strengthen vitality and help to improve the patient's quality of life.

Phase-contrast MRI for detection of mild systemic hemodynamic response after segmental allergen challenge in asthmatic patients.

RATIONALE AND OBJECTIVES: Detection of a systemic hemodynamic response in patients suffering from allergic asthma after segmental endobronchial allergen challenge using phase-contrast magnetic resonance imaging (MRI). MATERIALS AND METHODS: Nine asthma patients and four healthy volunteers were examined using MRI (1.5T) before (0 hour), 6 hours, and 24 hours after segmental allergen challenge. Two-dimensional phase-contrast MRI measurements were performed in the aorta (AO) and in the pulmonary artery (PA). In addition, short-axis balanced steady state free precession cardiac cine MRI was performed. Maximum systolic flow, maximum flow acceleration, acceleration volume, acceleration time, distensibility, ejection fraction, stroke volume, end-systolic/diastolic volume, cardiac mass, heart rate (HR), and cardiac output (CO) were determined. Spirometry and bronchoalveolar lavage were also performed. RESULTS: In patients with asthma, maximal systolic flow and maximal flow acceleration increased 6 hours after provocation in the AO (112.3% and 118.9%, respectively) and PA (113.9% and 116.0%, respectively) compared to baseline (100%, P < .05). HR and CO increased significantly at 6 hours (115% and 118%, respectively) compared to baseline (100%, P = .003). In healthy subjects, almost all MRI-derived hemodynamic parameters did not significantly change at 6 hours and were significantly lower than baseline values at 24 hours (P < .02). Twenty-four hours after allergen challenge, all MRI-derived flow parameters were significantly lower in the control group compared to the asthma group (P < .05). HR, CO, and cardiac function parameters measured at 24 hours showed no significant difference comparing the two groups (P > .05). CONCLUSIONS: In asthmatic patients, MRI-derived hemodynamic parameters using phase-contrast MRI are slightly altered after segmental allergen provocation compared to normal controls indicating a mild systemic reaction to local allergen challenge.

[Unidirectional axillary lymph node swelling in a 31-year-old woman]. / Einseitige axilläre Lymphknotenschwellung bei einer 31-jährigen Frau.

BACKGROUND: Swelling in the lymph nodes leads one to think at first in terms of diagnostic differentials such as local inflammation, tumor metastases, or lymphomas. Kikuchi-Fujimoto lymphadenitis is a rare cause of feverish lymphadenitis. CASE REPORT: A 31-year-old woman was admitted with painful axillary feverish swelling of the lymph nodes. There had been no previous illnesses and n the case history of her mother, a mammary carcinoma could be found. Ultrasonic and MRI tests showed the lymph node conglomerate to be located in the left axilla. Laboratory tests revealed a constellation of inflammation with lymphomonocytosis. Serologic tests for viral causes were negative. A necrotizing lymphadenitis of the Kikuchi-Fujimoto type was described in the histological reclamation of a lymph node. Within 2 weeks, spontaneous regression of the feverish lymphadenitis occurred. CONCLUSIONS: In cases of unclear lymphadenitis, an attempt at achieving histological reclamation of a lymph node is desirable in order to realize rare differential diagnosis such as Kikuchi-Fujimoto lymphadenitis.

[Value of malarone in therapy of malaria tropica]. / Stellenwert von Malarone in der Therapie der Malaria tropica.

BACKGROUND: A widespread resistance of falciparum malaria to common antimalaria drugs is observed during the last years. Long-distance travel to high-risk destinations of falciparum malaria will contribute to increased exposition of travelers to highly resistant parasites. PHARMACOLOGY: Malarone (GlaxoSmithKline) is a fixed combination of atovaquone and proguanil licensed for prophylaxis and treatment of falciparum malaria. Both atovaquone and proguanil demonstrate synergistic activity against liver and blood schizonts. Malarone is well tolerated with a low rate of side effects. Malarone has an excellent efficacy profile in nonimmune subjects. CONCLUSIONS: Malarone appears to be a valuable alternative malaria prophylaxis in case of intolerance of other antimalaria drugs. Atovaquone/proguanil is effective in treating acute uncomplicated malaria caused by multiresistant strains of Plasmodium falciparum.

[Fever after travel to the tropics]. / Fieber nach Tropenaufenthalt.

BACKGROUND: Fever in travellers returning from the tropics may be caused not only by tropical infection but also by travel associated non-specific infections and cosmopolitan infective diseases. DIAGNOSTIC PROCEDURE: A rational out-patient step by step procedure needs clinical data and a small account of laboratory investigations. A parasitological screening is mandatory. The results refer to parasitological, bacterial or viral diseases. Epidemiological aspects of the travelled country and incubation periods of tropical or other diseases have to be considered. CONCLUSIONS: Plasmodium falciparum infection has to be excluded first because of vital damage. Following malaria (30%) respiratory infections (11%) are common. Fever as a symptom of non-infective disease occurred in 9%. Other diseases (typhus, Dengue fever, tuberculosis) are rare but have to be considered.

[Autochthonous strongyloidosis in an 81-year-old woman]. / Autochthone Strongyloidose bei einer 81-jährigen Frau.

Strongyloidosis is an parasitic disease, caused by an intestinal nematode endemic in tropic and subtropic regions. In Central Europe it occurs only sporadically. The infective larvae in the soil penetrate the human skin. Following circulation through the lungs the larvae settle in the small intestine and mature into adult worms. Chronic strongyloidosis recurring up to 15 years is possible through endogenous autoinfection. Clinical feature of the disease are gastrointestinal symptoms, hypereosinophilia and skin rashes. We describe the case of an 81-year-old woman who presented with scaly exanthema, fever and perianal fistulation. A microscopic examination of a stool sample demonstrated filariform larvae of Strongyloides stercoralis. An autochthonous mode of infection was assumed. After starting treatment with mebendazole eosinophilia and rash gradually disappeared. The laboratory finding of eosinophilia in patients with gastrointestinal symptoms or exanthema should prompt the differential diagnosis of a parasitosis. Stool examination is necessary to find rare autochthonous infections by intestinal nematodes. Pathogenesis, clinical manifestation and treatment of strongyloidosis are discussed along with the clinical picture.