Diagnosis and successful management of calciphylaxis in a pancreas-kidney transplant patient.

Sir, We would like to refer to a case of fatal calciphylaxis developed2 years after kidney transplantation published in the December2004 issue of Nephrology Dialysis Transplantation [1]. We report a case of a 49-year-old woman     

Axilläre akzessorische Brustdrüse

Zusammenfassung Bei einer 34j?hrigen Patientin hatte sich w?hrend 8 Jahren in der linken vorderen Achsellinie eine hühnereigro?e, die Haut vorw?lbende knospen- bzw. warzenhoflose überz?hlige Brustdrüse entwikkelt. Die vornehmlich nur ?sthetische Beschwerden verursachende Vorw?lbung wurde exzidiert. Die Bedeutung der axill?ren akzessorischen Brustdrüsen besteht darin, da? sie entarten und klinisch ein Lipom vort?uschen k?nnen. Eine frühe Diagnose und korrekte Exzision sind erwünscht.      

DEGRO-ÖGRO 2008

BACKGROUND AND PURPOSE: Tumor-induced anemia often occurs in cancer patients, and is corrected by recombinant human erythropoietins (rHuEPOs). Recent studies indicated that, besides erythroid progenitor cells, tumor and endothelial cells express erythropoietin receptor (EPOR) as well; therefore, rHuEPO may affect their functions. Here, the effect of rHuEPOalpha on irradiation in EPOR-positive human squamous cell carcinoma xenograft was tested. MATERIAL AND METHODS: A431 tumor-bearing SCID mice were treated from the tumor implantation with rHuEPOalpha at human-equivalent dose. Xenografts were irradiated (5 Gy) on day 14, and the final tumor mass was measured on day 22. The systemic effects of rHuEPOalpha on the hemoglobin level, on tumor-associated blood vessels and on hypoxia-inducible factor-(HIF-)1alpha expression of the tumor xenografts were monitored. The proliferation, apoptosis and clonogenic capacity of A431 cancer cells treated with rHuEPOalpha and irradiation were also tested in vitro. RESULTS: In vitro, rHuEPOalpha treatment alone did not modify the proliferation of EPOR-positive A431 tumor cells but enhanced the effect of irradiation on proliferation, apoptosis and clonogenic capacity. In vivo, rHuEPOalpha administration compensated the tumor-induced anemia in SCID mice and decreased tumoral HIF-1alpha expression but had no effect on tumor growth. At the same time rHuEPOalpha treatment significantly increased the efficacy of radiotherapy in vivo (tumor weight of 23.9 +/- 4.7 mg and 34.9 +/- 4.6 mg, respectively), mediated by increased tumoral blood vessel destruction. CONCLUSION: rHuEPOalpha treatment may modulate the efficacy of cancer radiotherapy not only by reducing systemic hypoxia and tumoral HIF-1alpha expression, but also by destroying tumoral vessels.     

Silymarin and vitamin E reduce amiodarone-induced lysosomal phospholipidosis in rats

Several antioxidants have been shown to reduce lysosomal phospholipidosis, which is a potential mechanism of amiodarone toxicity, and prevent amiodarone toxicity by antioxidant and/or non-antioxidant mechanisms. The aim of this study was to test whether the co-administration of two structurally different antioxidants vitamin E and silymarin with amiodarone can reduce amiodarone-induced lysosomal phospholipidosis, and if yes, by reducing the tissue concentration of amiodarone and desethylamiodarone or by their antioxidant action. To this end, male Fischer 344 rats were treated by gavage once a day for 3 weeks and randomly assigned to the following four experimental groups: 1, control; 2, amiodarone (150 mg/(kg per day)); 3, amiodarone (150 mg/(kg per day)) plus vitamin E (100 mg/(kg per day)); 4, amiodarone (150 mg/(kg per day)) plus silymarin (60 mg/(kg per day)) treated groups. Total plasma phospholipid (PL), liver-conjugated diene, thiobarbituric acid reactive substances (TBARSs), amiodarone and desethylamiodarone concentrations were determined and the extent of lysosomal phospholipidosis in the liver was estimated by a semi-quantitative electron microscopic method. Amiodarone treatment increased significantly the liver-conjugated diene (P<0.001), TBARS (P=0.012), plasma total PL (P<0.001) concentrations compared with control. Antioxidants combined with amiodarone significantly decreased the liver-conjugated diene (P<0.001 for both), TBARS (P=0.016 for vitamin E, P=0.053 borderline for silymarin) and plasma total PL (P=0.058 borderline for vitamin E, P<0.01 for silymarin) concentrations compared with amiodarone treatment alone. Silymarin significantly (P=0.021) reduced liver amiodarone, but only tended to decrease desethylamiodarone concentration; however, vitamin E failed to do so. Amiodarone treatment increased lysosomal phospholipidosis (P<0.001) estimated by semi-quantitative electron microscopic method and both antioxidants combined with amiodarone reduced significantly (P<0.001 for both) the amiodarone-induced lysosomal phospholipidosis. In conclusion, silymarin presumably reduced lysosomal phospholipidosis by both antioxidant action and its liver amiodarone concentration decreasing effect, while vitamin E exerted similar effect by antioxidant action alone. Thus, both antioxidant action and inhibition of tissue uptake of amiodarone might have an important role in the preventative effect of antioxidants against amiodarone toxicity.     

Tritium labelling and degradation studies of Dmt1‐endomorphin 2

Two tritiated derivatives of Dmt¹‐endomorphin 2 (Dmt¹‐EM2) were prepared by the catalytic tritiodehalogenation of 3′,5′‐diiodo‐Dmt¹‐EM2 and the saturation of ^3,4ΔPro²‐Dmt¹‐EM2, resulting in [3′,5′‐³H₂]Dmt¹‐EM2 and [³H₂]Pro²‐Dmt¹‐EM2 with specific activities of 2.88 TBq/mmol (77.8 Ci/mmol) and 1.95 TBq/mmol (52.8 Ci/mmol), respectively. 3′,5′‐Diiodo‐Dmt¹‐EM2 was synthesized by the chloramine T method from Dmt¹‐EM2. ^3,4ΔPro²‐Dmt¹‐EM2 was synthesized by using the Merrifield solid‐phase method. The distributions of the tritium in the labelled peptides were investigated by reversed‐phase high‐performance liquid chromatography after acidic hydrolysis. The stability of Dmt¹‐EM2 in a rat brain membrane homogenate was also determined. Copyright © 2007 John Wiley & Sons, Ltd.     

Utility of B-type natriuretic peptide in children

Serum brain natriuretic peptide (BNP) has been reported to indicate ventricular dysfunction, however, in children it has not been studied yet in our country. PURPOSE: 157 BNP tests were performed in 107 children, on the one hand, to evaluate its clinical value, to assess LV or systemic RV function in patients with transposition of great arteries after Senning operation, on the other hand, to prove the relation between BNP, MRI and echocardiographic ventricular function parameters. PATIENTS' AGE: 4 months-20 years, mean 12.5 yrs. Group I: Senning patients, Groups II and III: patients with dilated or hypertrophic cardiomyopathy, Group IV: patients with aortic insufficiency. METHODS: BNP was determined using the electrochemiluminesce method (Elycsys-10 Roche). During the functional MRI Mass- Medis software RV LV EF, end-diastolic, end-systolic volumes were calculated. Echo M-mode, TEI index were calculated. RESULTS: BNPs were significantly as higher compared to normal in each group of patients. Group I: 318 +/- 285 pg/ml, p < 0.01, Group II: 7262 +/- 10970 pg/ml, p < 0.01, Group III: 1558 +/- 2765 pg/ml, p < 0.01, Group IV: 1076 +/- 2791 pg/ml, p < 0.00l, vs 58 +/- 31 pg/ml. BNP were negatively correlated with MRI RV EF (r: -0.51, p < 0.05) and showed good correlation with TEI index (0.43 +/- 0.18, p < 0.05). After 3 weeks of medical or surgical treatment BNP decreased significantly. 4 patients died during the follow-up period, these had the highest BNP levels in each patients group. CONCLUSIONS: BNP is a useful, prognostically valuable method in children to monitor ventricular function. BNP levels reflect the severity of the impairment of systemic RV function in Senning patients in whom a complex RV geometry is present causing the assessment of RV function more difficult, so we recommend BNP measurements as a longitudinal test in this patient group.     

5-Ethyl-2′-deoxyuridine, a modulator of both antitumour action and pharmacokinetics of 5-fluorouracil

The aim of the present studies was to elucidate the effects and optimal modulatory conditions of 5-ethyl-2′-deoxyuridine (EtdUrd) on the antitumour efficacy, pharmacokinetics and catabolism of 5-fluorouracil (5-FU) on Colon-26 and Colon-38 murine tumours. HPLC and GC-MS techniques were used to measure the concentrations of 5-FU, dihydro-5-fluorouracil, EtdUrd, 5-ethyluracil and uridine in the plasma and that of 5-FU and 5-fluoro-2′-deoxyuridine monophosphate (FdUMP) in the tumours. It was shown that EtdUrd, given 1 h before 5-FU, selectively enhanced the antitumour action of 5-FU, without significantly increasing its toxic side-effects, thus resulting in an approximately three times higher therapeutic index. Pharmacokinetic studies revealed that 1 h after 400 mg/kg EtdUrd administration – i.e. at the time of 5-FU treatment – the plasma concentration of EtdUrd was 269 μM, and that of 5-ethyluracil, as the major metabolite of EtdUrd, was 421 μM. It is of interest that EtdUrd pretreatment did not change the maximal plasma concentration of 5-FU; however, the half-life of the terminal elimination increased from 114.5 min to 171.2 min and thus the mean residence time of 5-FU rose significantly (P < 0.05). After the combined treatment, the maximal concentration of dihydro-5-fluorouracil in the plasma decreased from 61.06 μM to 29.70 μM (P < 0.01). The intratumoral concentrations of 5-FU were 34%–158% higher 6–96 h after the combined treatment than after the single 5-FU treatment. EtdUrd also caused a moderate increase in the intratumoral level of FdUMP. It is noteworthy, that EtdUrd increased the endogenous uridine concentration in the plasma from 18 μM to a maximum of 249 μM, and the level remained high for longer than 6 h. The present studies indicate that EtdUrd enhances the therapeutic index of 5-FU by reducing the catabolism, prolonging the plasma and intratumoral concentrations of 5-FU and, at the same time, offering protection to normal organs by increasing the endogenous uridine level. Received: 24 March 1999 / Accepted: 21 June 1999