Botulinum Toxin as Preventive Treatment for Migraine: A Randomized Double-Blind Study

Aim: To determine if botulinum toxin type A (BoNT-A) injections can reduce the frequency and severity of migraines. Methods: Patients (n = 127) were randomized to receive placebo or two doses of BoNT-A (Dysport (R)). The primary endpoint was reduction in number of migraine attacks up to week 8 and between weeks 8 and 12 after injection. Patient diaries were used to record secondary endpoints, including frequency, severity and duration of migraine attacks. Results: There was a mean reduction of 0.54 and 0.94 attacks/month with placebo and BoNT-A, respectively, and absolute attack count was less in the verum group (3.6 vs. 4.2 attacks/month), but this was not statistically significant. The patients' global assessment of efficacy was significantly better than placebo in the high-dose group (p = 0.02) but no effects were seen for the other secondary efficacy parameters. Conclusion: Our study showed a trend towards a reduced attack rate with verum but did not show any statistically significant efficacy of BoNT-A in the prophylactic treatment of migraine. Copyright (C) 2009 S. Karger AG, Base

Life stage differences in mammary gland gene expression profile in non-human primates

Breast cancer (BC) is the most common malignancy of women in the developed world. To better understand its pathogenesis, knowledge of normal breast development is crucial, as BC is the result of disregulation of physiologic processes. The aim of this study was to investigate the impact of reproductive life stages on the transcriptional profile of the mammary gland in a primate model. Comparative transcriptomic analyses were carried out using breast tissues from 28 female cynomolgus macaques (Macaca fascicularis) at the following life stages: prepubertal (n=5), adolescent (n=4), adult luteal (n=5), pregnant (n=6), lactating (n=3), and postmenopausal (n=5). Mammary gland RNA was hybridized to Affymetrix GeneChip® Rhesus Macaque Genome Arrays. Differential gene expression was analyzed using ANOVA and cluster analysis. Hierarchical cluster analysis revealed distinct separation of life stage groups. More than 2,225 differentially expressed mRNAs were identified. Gene families or pathways that changed across life stages included those related to estrogen and androgen (ESR1, PGR, TFF1, GREB1, AR, 17HSDB2, 17HSDB7, STS, HSD11B1, AKR1C4), prolactin (PRLR, ELF5, STAT5, CSN1S1), insulin-like growth factor signaling (IGF1, IGFBP1, IGFBP5), extracellular matrix (POSTN, TGFB1, COL5A2, COL12A1, FOXC1, LAMC1, PDGFRA, TGFB2), and differentiation (CD24, CD29, CD44, CD61, ALDH1, BRCA1, FOXA1, POSTN, DICER1, LIG4, KLF4, NOTCH2, RIF1, BMPR1A, TGFB2). Pregnancy and lactation displayed distinct patterns of gene expression. ESR1 and IGF1 were significantly higher in the adolescent compared to the adult animals, whereas differentiation pathways were overrepresented in adult animals and pregnancy-associated life stages. Few individual genes were distinctly different in postmenopausal animals. Our data demonstrate characteristic patterns of gene expression during breast development. Several of the pathways activated during pubertal development have been implicated in cancer development and metastasis, supporting the idea that other developmental markers may have application as biomarkers for B

“overestimation” of catheter gradients by doppler ultrasound in patients with aortic stenosis: a predictable manifestation of pressure recovery

AbstractOBJECTIVESThis study sought to evaluate whether pressure recovery can cause significant differences between Doppler and catheter gradients in patients with aortic stenosis, and whether these differences can be predicted by Doppler echocardiography.BACKGROUNDPressure recovery has been shown to be a source of discrepancy between Doppler and catheter gradients across aortic stenoses in vitro. However, the clinical relevance of this phenomenon for the Doppler assessment of aortic stenosis has not been evaluated in patients.METHODSTwenty-three patients with various degrees of aortic stenosis were studied with Doppler echocardiography and catheter technique within 24 h. Using an equation previously validated in vitro, pressure recovery was estimated from peak transvalvular velocity, aortic valve area and cross-sectional area of the ascending aorta and compared with the observed differences between Doppler and catheter gradients. Doppler gradients were also corrected by subtracting the predicted pressure recovery and then were compared with the observed catheter gradients.RESULTSPredicted differences between Doppler and catheter gradients due to pressure recovery ranged from 5 to 82 mm Hg (mean ± SD, 19 ± 16 mm Hg) and 3 to 54 mm Hg (12 ± 11 mm Hg) for peak and mean gradients, respectively. They compared well with the observed Doppler-catheter gradient differences, ranging from −5 to 75 mm Hg (18 ± 18 mm Hg) and −7 to 48 mm Hg (11 ± 13 mm Hg). Good correlation between predicted pressure recovery and observed gradient differences was found (r = 0.90 and 0.85, respectively). Both the noncorrected and the corrected Doppler gradients correlated well with the catheter gradients (r = 0.93–0.97). However, noncorrected Doppler gradients significantly overestimated the catheter gradients (slopes, 1.36 and 1.25 for peak and mean gradients, respectively), while Doppler gradients corrected for pressure recovery showed good agreement with catheter gradients (slopes, 1.03 and 0.96; standard error of estimate [SEE] 8.1 and 6.9 mm Hg; mean difference ± SD 0.4 ± 8.0 mm Hg and 1.1 ± 6.8 mm Hg for peak and mean gradients, respectively).CONCLUSIONSSignificant pressure recovery can occur in patients with aortic stenosis and can cause discrepancies between Doppler and catheter gradients. However, pressure recovery and the resulting differences between Doppler and catheter measurements may be predicted from Doppler velocity, aortic valve area and size of the ascending aorta

Interventional oncological treatment of breast cancer liver metastasis (BCLM): single center long-term evaluation over 26 years using thermoablation techniques like LITT, MWA and TACE in a multimodal application

AbstractThe purpose of the study is to retrospectively evaluate the development and technological progress in local oncological treatments of patients with breast cancer liver metastasis (BCLM) using LITT (laser interstitial thermotherapy), MWA (microwave ablation) and TACE (transarterial chemoembolization) ablation techniques in a multimodal application. The study uses data generated between 1993 and 2020. Therapy results were evaluated using the Kaplan–Meier survival estimate, Cox proportional hazard regression and log-rank test. Cox regression analysis showed that the different treatment methods are statistically significant predictors of survival of patients. Median survival times for groups treated with LITT (212 patients) and LITT + TACE (215 patients) were 2.2 years and 2.1 years respectively; median survival times for groups treated with MWA (17 patients) and MWA + TACE (143 patients) were 5.6 and 2.4 years respectively. For LITT only treatments, the 1-, 3- and 5-year survival probability scored 80%, 37%, 22%. Results for combined LITT + TACE treatments were 76%, 34% and 15%. In group MWA, the 1-/3-/5-year survival probability rates were calculated as 89%, 89%, 89% (however, they should be interpreted carefully due to a relatively small sample size of n = 17 patients). Group MWA + TACE offered values of 77%, 38% and 22%. A separate group of 549 patients was analyzed with TACE monotherapy treatment. The estimated median survival time in this group was 0.8 years. The 1-/3-/5-year survival probability rates were 37%, 8% and 4%. Treatments with combined MWA and MWA + TACE resulted in the best median survival time estimations in this study

Interventional oncological treatment of hepatocellular carcinoma (HCC) - a single-center long-term evaluation of thermoablation techniques like LITT, MWA, and TACE in a multimodal application over 26 years

Purpose: The purpose of the study is to retrospectively evaluate the development and technological progress in local oncological treatments of hepatocellular carcinoma (HCC) by means of ablation techniques like laser interstitial thermal therapy (LITT), microwave ablation (MWA) and transarterial chemoembolization (TACE) in a multimodal application. Method: This retrospective single-center study uses data generated between 1993 and 2020 (1,045 patients). Therapy results are evaluated using survival rates of Kaplan-Meier estimator, Cox proportional hazard regression and log-rank test. Results: Median survival times in group LITT (25 patients) are 1.6 years, and, 2.6 years for LITT + TACE (67 patients). For LITT only treatments 1-/3-/5-year survival rates scored 64%, 24% and 20%. Results for combined LITT + TACE treatments were 84%, 37% and 14%. Median survival time in group MWA (227 patients) is 4.5 years. Estimated median survival time for MWA + TACE (108 patients) leads to a median survival time of 2.7 years. In group MWA the 1-/3-/5-year survival rates are 85%, 54%, 45%. Group MWA + TACE shows values of 79%, 41% and 25%. A separate group of 618 patients has been analyzed with TACE as monotherapy. Median survival time of 1 year was estimated in this group. 1-/3-/5-year survival rates are 48%, 15% and 8%. - Cox regression analysis showed that the different treatment methods are statistically significant predictors for survival of patients. Conclusions: Treatments with MWA resulted in best median survival rates, followed by MWA + TACE in combination. Survival rates of MWA only are significantly higher vs. LITT, vs. LITT + TACE and vs. TACE monotherapy

Life stage differences in mammary gland gene expression profile in non-human primates

Breast cancer (BC) is the most common malignancy of women in the developed world. To better understand its pathogenesis, knowledge of normal breast development is crucial, as BC is the result of disregulation of physiologic processes. The aim of this study was to investigate the impact of reproductive life stages on the transcriptional profile of the mammary gland in a primate model. Comparative transcriptomic analyses were carried out using breast tissues from 28 female cynomolgus macaques (Macaca fascicularis) at the following life stages: prepubertal (n = 5), adolescent (n = 4), adult luteal (n = 5), pregnant (n = 6), lactating (n = 3), and postmenopausal (n = 5). Mammary gland RNA was hybridized to Affymetrix GeneChip(®) Rhesus Macaque Genome Arrays. Differential gene expression was analyzed using ANOVA and cluster analysis. Hierarchical cluster analysis revealed distinct separation of life stage groups. More than 2,225 differentially expressed mRNAs were identified. Gene families or pathways that changed across life stages included those related to estrogen and androgen (ESR1, PGR, TFF1, GREB1, AR, 17HSDB2, 17HSDB7, STS, HSD11B1, AKR1C4), prolactin (PRLR, ELF5, STAT5, CSN1S1), insulin-like growth factor signaling (IGF1, IGFBP1, IGFBP5), extracellular matrix (POSTN, TGFB1, COL5A2, COL12A1, FOXC1, LAMC1, PDGFRA, TGFB2), and differentiation (CD24, CD29, CD44, CD61, ALDH1, BRCA1, FOXA1, POSTN, DICER1, LIG4, KLF4, NOTCH2, RIF1, BMPR1A, TGFB2). Pregnancy and lactation displayed distinct patterns of gene expression. ESR1 and IGF1 were significantly higher in the adolescent compared to the adult animals, whereas differentiation pathways were overrepresented in adult animals and pregnancy-associated life stages. Few individual genes were distinctly different in postmenopausal animals. Our data demonstrate characteristic patterns of gene expression during breast development. Several of the pathways activated during pubertal development have been implicated in cancer development and metastasis, supporting the idea that other developmental markers may have application as biomarkers for BC

Effect of Stove Technology and Combustion Conditions on Gas and Particulate Emissions from Residential Biomass Combustion

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