10 years of experience with thalidomide in multiple myeloma patients: Report of the Czech Myeloma Group

We analyzed 1156 multiple myeloma (MM) patients treated with thalidomide. The overall response rate was 63.6%, with complete remission in 13.4%. Combined regimens had better outcomes than thalidomide plus dexamethasone or single agent thalidomide. Thalidomide was not able to overcome adverse cytogenetics. Superior results were seen in patients undergoing subsequent autologous stem cell transplantation. The rate of adverse events was low.     

Use of Modeling and Simulation Tools for Understanding the Impact of Formulation on the Absorption of a Low Solubility Compound: Ciprofloxacin

This study explored the utility of mechanistic absorption models to describe the in vivo performance of a low solubility/low permeability compound in normal healthy subjects. Sixteen healthy human volunteers received three oral formulations and an intravenous infusion in a randomized crossover design. Plasma ciprofloxacin concentrations were estimated by HPLC. In vitro ciprofloxacin release from the oral tablets was tested under a variety of conditions. A mechanistic model was used to explore in vivo dissolution and intestinal absorption. Although dissolution rate influenced the location of drug release, absorption challenges appeared to be associated with permeability limitations in the lower small intestine and colon. The apparent relationship between drug solubilization within the upper small intestinal and formulation overall bioavailability suggested the presence of an intestinal absorption window in many individuals. Failure to absorb drug within this window appeared to be linked with the likelihood of in vivo drug precipitation. Challenges encountered during this modeling exercise included large intersubject variability in product in vivo dissolution and the apparent limitations in ciprofloxacin absorption. Although transporter activity was not included as a model parameter, this evaluation demonstrated how identifying the location of drug absorption across several formulations provided an opportunity to identify factors to consider when formulating similar low solubility/low permeability compounds. The use of mechanistic models was invaluable for our understanding of in vivo product performance and for the assessment of individual profiles rather than means. The latter was essential for understanding the potential challenges that may be encountered when introducing a formulation into a patient population.     

Long‐term Treatment with Hesperidin Improves Endothelium‐dependent Vasodilation in Femoral Artery of Spontaneously Hypertensive Rats: The Involvement of NO‐synthase and Kv Channels

Hesperidin is the most common flavonoid found in citrus fruits and is expected to exert vasodilation action relevant to its health benefits. The present study aimed to explore the effect of hesperidin on the vascular responses in normotensive and hypertensive rats and the involvement of NO‐synthase and K_v channels. The 15‐week‐old Wistar and spontaneously hypertensive rats (SHR) were randomized to orally receive either hesperidin (50 mg/kg/day) or a corresponding volume of the water for 4 weeks. Vascular responses of isolated femoral arteries were studied with myograph in control conditions and during inhibition of NO‐synthase with l ‐NNA and K_v channels with 4‐AP. Hesperidin had no effect on blood pressure. Endothelium‐dependent vasodilation in Wistar and SHR was significantly improved by the treatment with hesperidin. The contraction responses after l ‐NNA were increased in all groups of rats to similar extent, but relaxatory responses were significantly attenuated only in SHR. The inhibition of K_v channels significantly reduced endothelium‐dependent vasodilatory responses in only in SHR administered with hesperidin. The results of our experiment indicate that hesperidin might improve the endothelium‐dependent vasodilation during hypertension, possibly through the enhancement of K_v channels function. Copyright © 2016 John Wiley & Sons, Ltd.     

Combined use of the cardiofemoral index and middle cerebral artery Doppler velocimetry for the prediction of fetal anemia

Objective

To assess the accuracy of the combined use of the cardiofemoral index (CFI) and the middle cerebral artery peak systolic velocity (MCA-PSV), converted to multiples of the median (MoM), as noninvasive means to detect severe fetal anemia.

Method

We measured CFI and MCA-PSV MoM in 37 fetuses just before their first (n = 37), second (n = 22), and third (n = 14) cordocenteses and transfusions. Then, using 2 different criteria for severe fetal anemia detection (Hb deficit ≥ 7 g/dL and hemoglobin level ≤ 0.55 of MoM), we assessed their hemoglobin status during cordocentesis and the accuracy of CFI and MCA-PVS was determined.

Results

At the first cordocentesis the mean hemoglobin level was 8.5 ± 3.6 g/dL and 15 fetuses (40.5%) had hydrops. In a total of 81 fetal evaluations, 58 (71.6%) of the CFIs and 34 (42.0%) of the MCA-PSV MoM measurements were abnormal. The result of one of these tests was abnormal in 65 evaluations (80.3%) and the results of both tests were abnormal in 27 evaluations (33.3%). All fetuses diagnosed as being severely anemic by at least one of the hemoglobin criteria during cordocentesis had an abnormal result by at least one of the noninvasive tests. Before the second and third transfusions, the combined use of the CFI and MCA-PSV MoM predicted severe fetal anemia with 100% sensitivity. When the CFI and MCA-PSV MoM measurements were normal, the negative likelihood ratio was zero.

Conclusion

When associated, CFI and MCA-PSV MoM were accurate predictors of severe fetal anemia.     

Intrabile duct metastasis from colonic adenocarcinoma without liver parenchyma involvement: contrast enhanced ultrasonography detection

It is well-known that biliary duct invasion with intraluminal growth is one of the developmental patterns of primary liver tumors, and macroscopic intrabiliary growth of liver metastases in colorectal cancer is found with high frequency. Surgical treatment is the only potential curative therapy. However, many patients die of intrahepatic and/or extrahepatic recurrence after the resection. One of the causes of high recurrence rate after resective surgery, particularly surgical margin recurrences, is the invasion of biliary ducts mainly due to intraluminal tumor growth. We describe the first recorded case of a metastasis from colorectal cancer involving solely the common hepatic biliary duct, without invasion of contiguous liver parenchyma. A correct diagnosis was obtained by means of contrast enhanced ultrasound and ultrasound-guided fine needle aspiration biopsy.     

Reproducibility of the German and Slovakian Versions of the Dietary Habits and Nutrition Beliefs Questionnaire (KomPAN)

Purpose. The aim of this study was to assess the reproducibility and reliability of the KomPAN questionnaire among two groups of university students from Germany and Slovakia. Methods. A total of 422 individuals (mean age 21.4 years, SD 4.0), including 197 from Slovakia (men 26.2%) and 225 from Germany (men 22.3%), were tested using the self-administered (SA-Q) version of the KomPAN questionnaire and then retested two weeks later. A cross-classification analysis, kappa coefficients, Cronbach’s ɑ coefficients, and a test-retest result comparison were conducted separately for each group of students to assess the reproducibility and reliability of the questionnaire. Results. The cross-classification values were higher than 46.2% among the German students and higher than 55.8% among the Slovakian students. The kappa coefficients ranged from 0.21 to 0.90 in the German students and from 0.38 to 0.94 in the Slovakian students. Cronbach’s ɑ ranged from 0.58 to 0.78. Conclusion. The questionnaire displayed a moderate to very good reproducibility, which was slightly higher in the Slovakian group than in the German group. Therefore, the questionnaire can be recommended for further analysis and comparison of the dietary habits among Germans and Slovakians on a larger scale.