tbuckley/cabot-search huggingface dataset:
Higher tibial quantitative ultrasound in young female swimmers
Authors: B Falk, Z Bronshtein, L Zigel, N Constantini, A Eliakim
Journal: British Journal of Sports Medicine (2004)

It has been found that swimming, a non-impact sport, generally has no effect on bone mineral density.To examine bone properties, as measured by quantitative ultrasound, among female swimmers in comparison with control girls and women.Subjects included 61 swimmers and 71 controls aged 8.5 to 26.5 years. None of the swimmers was at the elite level and none had included resistance training in her schedule. Bone speed of sound (SOS) was measured bilaterally at the distal radius and the mid-tibia.No differences were observed between swimmers and controls in body mass (mean (SD): 49.7 (12.3) v 50.7 (12.4) kg, respectively), although swimmers were taller (159 (12) v 155 (12) cm) and had lower body fat (18.3 (4.2)% v 22.3 (5.4)%). No difference was found in time since menarche (5.2 (4.0) and 4.5 (2.9) years in swimmers and controls, respectively; 21 swimmers and 25 control were premenarcheal). Radial speed of sound (SOS) increased with age but did not differ between swimmers and controls (non-dominant: 3904 (172) and 3889 (165) m/s for swimmers and controls, respectively). Tibial SOS also increased with age and was significantly higher in swimmers than in controls (non-dominant: 3774 (155) v 3712 (171) m/s). No differences were found between dominant and non-dominant sides.Swimming appears to be associated with higher bone SOS in the lower but not in the upper extremities. Further studies are needed to assess whether this difference reflects higher habitual activity among the swimmers or swimming specific mechanisms.
The yield of different pleural fluid volumes for<i>Mycobacterium tuberculosis</i>culture: Table 1
Authors: Florian von Groote-Bidlingmaier, Coenraad Frederik Koegelenberg, Chris T Bolliger, Pui Khi Chung, Cornelia Rautenbach, Elizabeth Wasserman, Maurizio Bernasconi, Sven Olaf Friedrich, Andreas Henri Diacon
Journal: Thorax (2012)

We prospectively compared the culture yields of two pleural fluid volumes (5 and 100 ml) inoculated in liquid culture medium in 77 patients of whom 58 (75.3%) were diagnosed with pleural tuberculosis. The overall fluid culture yield was high (60.3% of cases with pleural tuberculosis). The larger volume had a faster time to positivity (329 vs 376 h, p=0.055) but its yield was not significantly higher (53.5% vs 50%; p=0.75). HIV-positive patients were more likely to have positive cultures (78.9% vs 51.5%; p=0.002).
Induction of endogenous γ-globin gene expression with decoy oligonucleotide targeting Oct-1 transcription factor consensus sequence
Authors: Xiaoxin S Xu, Xin Hong, Gan Wang
Journal: Journal of Hematology & Oncology (2009)

Human β-globin disorders are relatively common genetic diseases cause by mutations in the β-globin gene. Increasing the expression of the γ-globin gene has great benefits in reducing complications associated with these diseases. The Oct-1 transcription factor is involved in the transcriptional regulation of the γ-globin gene. The human γ-globin genes (both Aγ and Gγ-globin genes) carry three Oct-1 transcription factor consensus sequences within their promoter regions. We have studied the possibility of inducing γ-globin gene expression using decoy oligonucleotides that target the Oct-1 transcription factor consensus sequence. A double-stranded 22 bp decoy oligonucleotide containing the Oct-1 consensus sequence was synthesized. The results obtained from our in vitro binding assay revealed a strong competitive binding of the decoy oligonucleotide for the Oct-1 transcription factor. When K562 human erythroleukemia cells were treated with the Oct-1 decoy oligonucleotide, significant increases in the level of the γ-globin mRNA were observed. The results of our western blots further demonstrated significant increases of the fetal hemoglobin (HbF, α2γ2) in the Oct-1 decoy oligonucleotide-treated K562 cells. The results of our immunoprecipitation (IP) studies revealed that the treatment of K562 cells with the Oct-1 decoy oligonucleotide significantly reduced the level of the endogenous γ-globin gene promoter region DNA co-precipitated with the Oct-1 transcription factor. These results suggest that the decoy oligonucleotide designed for the Oct-1 transcription factor consensus sequence could induce expression of the endogenous γ-globin gene through competitive binding of the Oct-1 transcription factor, resulting in activation of the γ-globin genes. Therefore, disrupting the bindings of the Oct-1 transcriptional factors with the decoy oligonucleotide provides a novel approach for inducing expression of the γ-globin genes. It also provides an innovative strategy for the treatment of many disease conditions, including sickle cell anemia and β-thalassemia.
Evoked release of endogenous norepinephrine in the canine saphenous vein. Inhibition by acetylcholine.
Authors: P M Vanhoutte, E P Coen, W J De Ridder, T J Verbeuren
Journal: Circulation Research (1979)

Most of the information concerning adrenergic neurotransmission in the blood vessel wall has been obtained from isolated blood vessels previously incubated with radiolabeled norepinephrine.In the present study, we determined the tissue content of norepinephrine and dopamine in the dog's saphenous vein using a radioenzymatic assay; tissue content of dopamine was 30 times less than tissue content of norepinephrine, and no epinephrine could be detected.During superfusion of isolated canine saphenous vein preparations, superfusate samples were collected for subsequent radioenzymatic analysis of norepinephrine, epinephrine, and dopamine.The basal efflux of endogenous norepinephrine declined slightly with time.Nerve stimulation caused frequency-dependent increases in tension, paralleled by increases in efflux of endogenous norepinephrine.The changes in tension were correlated significantly with the changes in norepinephrine overflow.Acetylcholine at 5 x 10~7M had no effect on basal tension or basal norepinephrine overflow.During nerve stimulation at 2 Hz and at 5 Hz, it significantly depressed the contractile response and the evoked overflow of endogenous norepinephrine.Neither dopamine nor epinephrine was detected during these superfusion studies.The present experiments introduce the means for measuring endogenous norepinephrine overflow in the canine saphenous vein, validate earlier work on this blood vessel, and, in particular, provide direct evidence for the inhibitory effect of acetylcholine on adrenergic neurotransmission in the blood vessel wall.
A Single-Chain Fv Diabody against Human Leukocyte Antigen-A Molecules Specifically Induces Myeloma Cell Death in the Bone Marrow Environment
Authors: Etsuko Sekimoto, Shuji Ozaki, Takashi Ohshima, Hironobu Shibata, Toshihiro Hashimoto, Masahiro Abe, Naoki Kimura, Kunihiro Hattori, Shigeto Kawai, Yasuko Kinoshita, Hisafumi Yamada-Okabe, Masayuki Tsuchiya, Toshio Matsumoto
Journal: Cancer Research (2007)

Abstract Cross-linked human leukocyte antigen (HLA) class I molecules have been shown to mediate cell death in neoplastic lymphoid cells. However, clinical application of an anti-HLA class I antibody is limited by possible side effects due to widespread expression of HLA class I molecules in normal tissues. To reduce the unwanted Fc-mediated functions of the therapeutic antibody, we have developed a recombinant single-chain Fv diabody (2D7-DB) specific to the α2 domain of HLA-A. Here, we show that 2D7-DB specifically induces multiple myeloma cell death in the bone marrow environment. Both multiple myeloma cell lines and primary multiple myeloma cells expressed HLA-A at higher levels than normal myeloid cells, lymphocytes, or hematopoietic stem cells. 2D7-DB rapidly induced Rho activation and robust actin aggregation that led to caspase-independent death in multiple myeloma cells. This cell death was completely blocked by Rho GTPase inhibitors, suggesting that Rho-induced actin aggregation is crucial for mediating multiple myeloma cell death. Conversely, 2D7-DB neither triggered Rho-mediated actin aggregation nor induced cell death in normal bone marrow cells despite the expression of HLA-A. Treatment with IFNs, melphalan, or bortezomib enhanced multiple myeloma cell death induced by 2D7-DB. Furthermore, administration of 2D7-DB resulted in significant tumor regression in a xenograft model of human multiple myeloma. These results indicate that 2D7-DB acts on multiple myeloma cells differently from other bone marrow cells and thus provide the basis for a novel HLA class I–targeting therapy against multiple myeloma. [Cancer Res 2007;67(3):1184–92]
Significance of the microbiome in obstructive lung disease
Authors: MeiLan K Han, Yvonne J Huang, John J LiPuma, Homer A Boushey, Richard C Boucher, William O Cookson, Jeffrey L Curtis, John Erb-Downward, Susan V Lynch, Sanjay Sethi, Galen B Toews, Vincent B Young, Matthew C Wolfgang, Gary B Huffnagle, Fernando J Martinez
Journal: Thorax (2012)

The composition of the lung microbiome contributes to both health and disease, including obstructive lung disease. Because it has been estimated that over 70% of the bacterial species on body surfaces cannot be cultured by currently available techniques, traditional culture techniques are no longer the gold standard for microbial investigation. Advanced techniques that identify bacterial sequences, including the 16S ribosomal RNA gene, have provided new insights into the depth and breadth of microbiota present both in the diseased and normal lung. In asthma, the composition of the microbiome of the lung and gut during early childhood development may play a key role in the development of asthma, while specific airway microbiota are associated with chronic asthma in adults. Early bacterial stimulation appears to reduce asthma susceptibility by helping the immune system develop lifelong tolerance to innocuous antigens. By contrast, perturbations in the microbiome from antibiotic use may increase the risk for asthma development. In chronic obstructive pulmonary disease, bacterial colonisation has been associated with a chronic bronchitic phenotype, increased risk of exacerbations, and accelerated loss of lung function. In cystic fibrosis, studies utilising culture-independent methods have identified associations between decreased bacterial community diversity and reduced lung function; colonisation with <i>Pseudomonas aeruginosa</i> has been associated with the presence of certain CFTR mutations. Genomic analysis of the lung microbiome is a young field, but has the potential to define the relationship between lung microbiome composition and disease course. Whether we can manipulate bacterial communities to improve clinical outcomes remains to be seen.
Regorafenib-associated hand–foot skin reaction: practical advice on diagnosis, prevention, and management
Authors: B. McLellan, F. Ciardiello, M.E. Lacouture, S. Segaert, E. Van Cutsem
Journal: Annals of Oncology (2015)

BackgroundRegorafenib is an orally available, small-molecule multikinase inhibitor with international marketing authorizations for use in colorectal cancer and gastrointestinal stromal tumors. In clinical trials, regorafenib showed a consistent and predictable adverse-event profile, with hand–foot skin reaction (HFSR) among the most clinically significant toxicities. This review summarizes the clinical characteristics of regorafenib-related HFSR and provides practical advice on HFSR management to enable health care professionals to recognize, pre-empt, and effectively manage the symptoms, thereby allowing patients to remain on active therapy for as long as possible.DesignThis review is based on a systematic literature search of the PubMed database (using synonyms of HFSR, regorafenib, and skin toxicities associated with targeted therapies or cytotoxic chemotherapy). However, as this search identified very few articles, the authors also use their clinical experience as oncologists and dermatologists managing patients with treatment-related HFSR to provide recommendations on recognition and management of HFSR in regorafenib-treated patients.ResultsRegorafenib-related HFSR is similar to that seen with other multikinase inhibitors (e.g. sorafenib, sunitinib, cabozantinib, axitinib, and pazopanib) but differs from the hand–foot syndrome seen with cytotoxic chemotherapies (e.g. fluoropyrimidines, anthracyclines, and taxanes). There have been no controlled trials of symptomatic management of regorafenib-related HFSR, and limited good-quality evidence from randomized clinical trials of effective interventions for HFSR associated with other targeted therapies. Recommendations on prevention and management of regorafenib-related HFSR in this review are therefore based on the expert opinion of the authors (dermatologists and oncologists with expertise in the management of treatment-related skin toxicities and oncologists involved in clinical trials of regorafenib) and tried-and-tested empirical experience with other multikinase inhibitors and cytotoxic chemotherapies.ConclusionsAs recommended in this review, treatment modifications and supportive measures to prevent, reduce, and manage HFSR can allow patients to continue regorafenib at the optimal dose to derive benefit from treatment.
Dual Phosphoinositide 3-Kinase/Mammalian Target of Rapamycin Blockade Is an Effective Radiosensitizing Strategy for the Treatment of Non–Small Cell Lung Cancer Harboring <i>K-RAS</i> Mutations
Authors: Georgia Konstantinidou, Erik A. Bey, Andrea Rabellino, Katja Schuster, Michael S. Maira, Adi F. Gazdar, Augusto Amici, David A. Boothman, Pier Paolo Scaglioni
Journal: Cancer Research (2009)

Non-small cell lung cancer (NSCLC) is a leading cause of cancer-related death worldwide. NSCLC often harbors oncogenic K-RAS mutations that lead to the aberrant activation of several intracellular networks including the phosphoinositide 3-kinase (PI3K)/AKT/mammalian target of rapamycin (mTOR) signaling pathway. Oncogenic K-RAS predicts poor prognosis and resistance to treatment with ionizing radiation (IR). Oncogenic K-Ras expression in the respiratory epithelium is sufficient to initiate NSCLC tumorigenesis, which requires the catalytic subunit of PI3K. Thus, effective inhibition of the PI3K signaling should lead to significant antitumor effects. However, therapy with rapamycin analogues has yielded disappointing results due in part to compensatory up-regulation of AKT. We hypothesized that dual PI3K/mTOR blockade would overcome these limitations. We tested this hypothesis with BEZ235, a novel dual PI3K/mTOR inhibitor that has recently entered clinical development. We found that BEZ235 induces a striking antiproliferative effect both in transgenic mice with oncogenic K-RAS-induced NSCLC and in NSCLC cell lines expressing oncogenic K-RAS. We determined that treatment with BEZ235 was not sufficient to induce apoptosis. However, we found that dual PI3K/mTOR blockade effectively sensitizes NSCLC expressing oncogenic K-RAS to the proapoptotic effects of IR both in vitro and in vivo. We conclude that dual PI3K/mTOR blockade in combination with IR may benefit patients with NSCLC expressing oncogenic K-RAS. These findings may have general applicability in cancer therapy, because aberrant activation of PI3K occurs frequently in human cancer.
Epirubicin–cyclophosphamide adjuvant chemotherapy plus tamoxifen administered concurrently versus sequentially: randomized phase III trial in postmenopausal node-positive breast cancer patients. A GEICAM 9401 study
Authors: C. Pico, M. Martin, C. Jara, A. Barnadas, A. Pelegri, A. Balil, C. Camps, A. Frau, A. Rodriguez-Lescure, J.M. Lopez-Vega, J. de la Haba, A. Tres, I. Alvarez, E. Alba, A. Arcusa, A. Oltra, N. Batista, T. Checa, R. Perez-Carrion, J. Curto
Journal: Annals of Oncology (2003)

<h2>Abstract</h2><h3>Background</h3> A prospective randomized clinical trial was implemented to assess whether the concomitant or the sequential addition of tamoxifen to chemotherapy provides improved clinical benefit in the adjuvant treatment of breast cancer in postmenopausal patients. <h3>Patients and methods</h3> Four-hundred and eighty-five patients with node-positive operable disease were randomized to receive tamoxifen (20 mg/day) concomitantly (CON) or sequentially (SEQ) to EC chemotherapy (epirubicin 75 mg/m<sup>2</sup> + cyclophosphamide 600 mg/m<sup>2</sup> on day 1, every 21 days for four cycles). <h3>Results</h3> In the 474 fully evaluable patients there were 96 events; eight being second neoplasms and 88 being related to the breast cancer. Of these, 48 of 88 occurred in the CON arm and 40 of 88 in the SEQ arm. The Kaplan–Meier estimation of disease-free survival (DFS) at 5 years was 70% in the CON and 75% in the SEQ group (log-rank test, <i>P</i> = 0.43). Adjusted hazard ratio for treatment was 1.11 (95% confidence interval 0.71–1.73; <i>P</i> = 0.64). <h3>Conclusion</h3> This study fails to show an advantage of one treatment arm over the other, but a trend, albeitnon-significant, appears to favor the sequential addition of tamoxifen to epirubicin + cyclophosphamide and, as such, warrants further investigation.
Reperfusion induces myocardial apoptotic cell death
Authors: Z Zhao
Journal: Cardiovascular Research (2000)

The purpose of the present study was to investigate whether apoptosis is triggered during ischemia (I) and reperfusion (R) and whether I/R-induced apoptosis is correlated with changes in expression of Bcl-2 and Bax.Anesthetized open-chest dogs were divided into two groups. Group I: 7 h of permanent I without R (PI, n = 7); Group II: 60 min I followed by 6 h R (I/R, n = 8). Apoptosis was identified as "DNA ladder" by agarose gel electrophoresis or confirmed histologically using the terminal transferase UTP nick end labeling (TUNEL) assay.Collateral myocardial coronary blood flow during I, confirmed by colored microspheres was comparable in both groups. Although PI caused 72 +/- 5% infarct size, very few TUNEL-positive cells were detected in the necrotic area (0.2 +/- 0.1% of total normal nuclei), consistent with an absence of DNA laddering. In contrast, the appearance of TUNEL-positive cells was significantly displayed after 6 h R in the necrotic area in I/R group (26 +/- 4%, P < 0.001 vs. PI group), and DNA ladder occurred in all experimental animals, suggesting that myocardial apoptosis is primarily elicited by R. Densitometrically, Western blot analysis showed significant reduction in expression of Bcl-2 (16 +/- 1%) and increase in Bax (29 +/- 8%) after 6 h R in the necrotic area compared with normal tissue while expression of these two proteins was not changed in the PI group. Polymorphonuclear neutrophil (PMN) accumulation in the necrotic area determined either by immunohistochemistry with anti-CD18 antibody or by myeloperoxidase activity was significantly increased in the I/R group compared to the PI group (358 +/- 24 vs. 24 +/- 2, mm2 myocardium, P < 0.01) and (2.9 +/- 0.3 vs. 0.4 +/- 0.1, U/100 mg tissue, P < 0.01). There was a significant linear relationship between CD18-positive PMNs and TUNEL-positive cells (P < 0.05) in the I/R group.These results indicate that (1) PI without R did not induce apoptotic cell death, while two types of cell death, necrosis and apoptosis were found after I/R, (2) the Bcl-2 family may participate in early R-induced myocardial apoptosis, (3) PMN accumulation may play a role in the development of apoptosis.
Renal Failure, Rhabdomyolysis, and Phenylpropanolamine-Reply
Authors: Thomas A. Golper
Journal: JAMA (1983)

<h3>In Reply.—</h3> Drs Blewitt and Siegel draw attention to several interesting issues. First, they state that we did not cite examples of phenylpropanolamine-associated complications in patients using the drug<i>responsibly</i>. Our patient 1, the patient described by Lee et al,<sup>1</sup>and several patients described in the<i>Lancet</i>editorial,<sup>2</sup>all were using phenylpropanolamine as directed and suffered side effects possibly associated with its use. Thus, the responsible use of phenylpropanolamine does not inevitably protect a person from an untoward reaction, although it might change the odds in that direction. Drs Blewitt and Siegel claim that several "controlled clinical studies" have not shown these adverse effects. If they have such data, they should provide specific citations. It is well known that adverse reactions to drugs may occur so infrequently that they would be observed only after a large patient population is exposed. Such a situation could be the case for
Cardiovascular response to orthostatic tilt in patients with severe congestive heart failure
Authors: E. KASSIS
Journal: Cardiovascular Research (1987)

Baroreflex mediated haemodynamic responses and aortic pulsatile stretch were studied in patients with congestive heart failure due to ischaemia. Seven patients with severe congestive heart failure (baseline angiographic ejection fraction 21(3)% (mean(SEM); left ventricular end diastolic volume and pressure 351(43) ml and 22(3) mmHg respectively) were compared with seven control subjects whose angiographic ejection fraction was 74(3)%. Passive 45° upright tilt was used to unload baroreceptors. Aortic pulsatile stretch (pulsatile distension as percentage of diastolic diameter) was calculated from echocardiographic measurements of aortic diameters. Upright tilt caused a significant decrease in cardiac filling pressures in patients with congestive heart failure, as in control subjects. During tilt control subjects had substantially increased systemic vascular resistance and heart rate and decreased stroke volume, but arterial pressures, cardiac index, and aortic pulsatile stretch were maintained constant. Patients with congestive heart failure developed peripheral vasodilatation, had no increase in heart rate, and failed to maintain arterial mean and systolic pressures in the tilted position. They had, however, maintained a constant pulse pressure and increased cardiac index, stroke volume, and aortic pulsatile stretch. The response to upright tilt in patients with congestive heart failure may be explained by faulty sympathetic reflexes, causing vasodilatation and hypotension rather than vasoconstriction, and a rise in stroke volume due to the decrease in afterload.
Dynamics of asthma prevalence in children in the Novosibirsk (preliminary results)
Authors: Elena Kondiurina, Tatiana Elkina, Natalia Gulevskaia, Maria Shably, Andrei Likhanov
Journal: European Respiratory Journal (2012)

Background: The study of the asthma epidemiology according to the ISAAC program (Phase Three) was over in 2002. Afterwards the studies with the use of standardized methods have not been carried out in the world.  Aim: To study the dynamics of asthma prevalence among the 6-7 years old children in the Novosibirsk.  Methods: According to the ISAAC 3249 children were examined in 2002 and about 3000 children aged 6-7 years old were examined in the years of 2011-12. This abstract introduce the preliminary results based on the questioning of 970 parents in the years of 2011-12.  Results: There decreased the prevalence of wheezing from 24,1% to 17,3% (p  Conclusion: The obvious trend in the first decade of the XXI century is the decrease in the prevalence of the asthma symptoms among 6-7 years old children in the Novosibirsk with some improvement in the disease diagnostics.
Treatment outcome with mTOR inhibitors for metastatic renal cell carcinoma with nonclear and sarcomatoid histologies
Authors: M.H. Voss, D.A. Bastos, C.A. Karlo, A. Ajeti, A.A. Hakimi, D.R. Feldman, J.J. Hsieh, A.M. Molina, S. Patil, R.J. Motzer
Journal: Annals of Oncology (2014)
Modem Transmission of Glucose Values Reduces the Costs of and Need for Clinic Visits
Authors: H. Peter Chase
Journal: Diabetes Care (2003)

We thank Perlemuter and Yomtov (1) for their comments in this issue of Diabetes Care regarding our article (2). It seems that their previous study (3) and our study show similar results. They did not provide the ages of their participants, but “nine men and one woman” are mentioned, and our …