tbuckley/cabot-search huggingface dataset:
<i>BJSM</i>reviews: A–Z of nutritional supplements: dietary supplements, sports nutrition foods and ergogenic aids for health and performance Part 4
Authors: L M Burke, L M Castell, S J Stear, P J Rogers, E Blomstrand, S Gurr, N Mitchell, F B Stephens, P L Greenhaff
Journal: British Journal of Sports Medicine (2009)

Welcome to Part 4 in our A–Z of nutritional supplement series. One of the enjoyable aspects of reviewing the many supplements in a fairly logical order from A to Z means that, every now and then, a review comprises a real assortment of supplements, and Part 4 is certainly one of them!

In Part 4, the review takes us from aspartame, a sweetening ingredient found in many foods and drinks, to BCAA, the three branched chain essential amino acids; then onto bee pollen, marketed as a “superfood,” followed by the ultra trace element boron, known more for its association with bone health, and finally to l-carnitine, a supplement which is widely used in the sporting arena and seems to be gaining in popularity. We are grateful for the excellent contributions from our invited reviewers, which facilitate the provision of access to impartial advice on the value of these individual ingredients and supplements. These contributions are establishing that, for some, the performance evidence is limited or simply does not yet exist.

In the January 2010 issue, we will be turning our attention to “buffers,” where we will be covering the key ones used by many athletes, such as beta-alanine and carnosine, together with the two more established compounds of sodium bicarbonate and sodium citrate.

### PJ Rogers

Aspartame (C14H18N2O5) is an example of an intense or non-nutritive sweetener and an ingredient of many thousands of drink and food products consumed worldwide. It is a methyl ester of a dipeptide composed of the amino acids aspartic acid and phenylalanine, which are constituents of all protein-containing foods. Aspartame is about 180 times sweeter than sucrose with, for most individuals, minimal bitterness and a good quality of sweet taste. Being composed of amino acids, it has an energy value …
Human mesenchymal stromal cells decrease the severity of acute lung injury induced by E. coli in the rat
Authors: J. Devaney, S. Horie, C. Masterson, S. Elliman, F. Barry, T. O'Brien, G. F. Curley, D. O'Toole, J. G. Laffey
Journal: Thorax (2015)

<h3>Background</h3> Mesenchymal stromal cells (MSCs) demonstrate considerable promise in preclinical acute respiratory distress syndrome models. We wished to determine the efficacy and mechanisms of action of human MSCs (hMSCs) in the setting of acute lung injury induced by prolonged <i>Escherichia coli</i> pneumonia in the rat. <h3>Methods</h3> Adult male Sprague Dawley rats underwent intratracheal instillation of <i>E. coli</i> bacteria in all experiments. In <i>Series 1,</i> animals were randomised to intravenous administration of: (1) vehicle (phosphate buffered saline (PBS), 300 μL); (2) 1×10<sup>7</sup> fibroblasts/kg; (3) 1×10<sup>7</sup> hMSCs/kg or (4) 2×10<sup>7</sup> hMSCs/kg. <i>Series 2</i> determined the lowest effective hMSC dose. <i>Series 3</i> compared the efficacy of intratracheal versus intravenous hMSC administration, while <i>Series 4</i> examined the efficacy of cryopreserved hMSC. <i>Series 5</i> examined the efficacy of the hMSC secretome. Parallel in vitro experiments further assessed the potential for hMSCs to secrete LL-37 and modulate macrophage phagocytosis. <h3>Results</h3> hMSC therapy reduced the severity of rodent <i>E. coli</i> pneumonia, improving survival, decreasing lung injury, reducing lung bacterial load and suppressing inflammation. Doses as low as 5×10<sup>6</sup> hMSCs/kg were effective. Intratracheal hMSC therapy was as effective as intravenous hMSC. Cryopreserved hMSCs were also effective, while the hMSC secretome was less effective in this model. hMSC therapy enhanced macrophage phagocytic capacity and increased lung and systemic concentrations of the antimicrobial peptide LL37. <h3>Conclusions</h3> hMSC therapy decreased <i>E. coli</i> induced pneumonia injury and reduced lung bacterial burden, potentially via enhanced macrophage phagocytosis and increased alveolar LL-37 concentrations.
Targeting of 111In-Labeled Dendritic Cell Human Vaccines Improved by Reducing Number of Cells
Authors: Erik H.J.G. Aarntzen, Mangala Srinivas, Fernando Bonetto, Luis J. Cruz, Pauline Verdijk, Gerty Schreibelt, Mandy van de Rakt, W. Joost Lesterhuis, Maichel van Riel, Cornelius J.A. Punt, Gosse J. Adema, Arend Heerschap, Carl G. Figdor, Wim J. Oyen, I. Jolanda M. de Vries
Journal: Clinical Cancer Research (2013)

Anticancer dendritic cell (DC) vaccines require the DCs to relocate to lymph nodes (LN) to trigger immune responses. However, these migration rates are typically very poor. Improving the targeting of ex vivo generated DCs to LNs might increase vaccine efficacy and reduce costs. We investigated DC migration in vivo in humans under different conditions.HLA-A*02:01 patients with melanoma were vaccinated with mature DCs loaded with tyrosinase and gp100 peptides together with keyhole limpet hemocyanin (NCT00243594). For this study, patients received an additional intradermal vaccination with (111)In-labeled mature DCs. The injection site was pretreated with nonloaded, activated DCs, TNFα, or Imiquimod; granulocyte macrophage colony-stimulating factor was coinjected or smaller numbers of DCs were injected. Migration was measured by scintigraphy and compared with an intrapatient control vaccination. In an ex vivo tissue model, we measured CCL21-directed migration of (19)F-labeled DCs over a period of up to 12 hours using (19)F MRI to supplement our patient data.Pretreatment of the injection site induced local inflammatory reactions but did not improve migration rates. Both in vitro and in vivo, reduction of cell numbers to 5 × 10(6) or less cells per injection improved migration. Furthermore, scintigraphy is insufficient to study migration of such small numbers of (111)In-labeled DCs in vivo.Reduction of cell density, not pretreatment of the injection site, is crucial for improved migration of DCs to LNs in vivo.
Historical Perspectives of the Ethical Practice of Psychiatry
Authors: FRANCIS J. BRACELAND
Journal: American Journal of Psychiatry (1969)

That subtle governing of the relations between physician and patient designated as medical ethics is, in the author's opinion, of the essence of medical practice. The ethical principles passed down from generation to generation of physicians are derived from the simultaneous pursuit of knowledge and love of one's fellow man. As such, they determine the nature of the art of medicine and cannot be altered or ignored lest the profession itself lose the qualities that have made it a noble art.
PATHOGENESIS AND HOST RESPONSE IN<i>Pneumocystis carinii</i>PNEUMONIA
Authors: Tony H. Su, M.D, William J. Martin II, M.D
Journal: Annual Review of Medicine (1994)

▪ Abstract Pneumocystis carinii (PC) pneumonia is recognized as the leading cause of opportunistic pulmonary infections in immunocompromised hosts during the past decade. Although much remains unknown about pathogenesis and host response in PC, in recent years, studies of PC have provided us with an increasing base of knowledge about this organism and its relationship to the host. These studies have led to a better understanding of mechanisms of PC attachment and injury to host cells. New information about the interaction of PC with pulmonary surfactant provides insight about the pathophysiology of PC pneumonia. The interplay of the organism, host inflammatory cells, release of cytokines, generation of toxic metabolites, and involvement of both cellular and humoral immunity is complex, but understanding the pathogenesis of PC pneumonia is necessary in order to develop new therapies for this disorder.
Ongoing increasing temporal and geographical trends of the incidence of extended-spectrum beta-lactamase-producing Enterobacteriaceae infections in France, 2009 to 2013
Authors: Isabelle Arnaud, Sylvie Maugat, Vincent Jarlier, Pascal Astagneau
Journal: Eurosurveillance (2015)

Extended-spectrum beta-lactamase-producing Enterobacteriaceae (ESBL-E) are a major focus of multidrug-resistant organisms (MRO) surveillance programmes in France. To describe the temporal and geographical trends of these pathogens, we conducted an epidemiological study based on data extracted from the nationwide MRO surveillance network from 2009 to 2013. During this time, the incidence of ESBL-E infections in French hospitals increased by 73%, from 0.35 to 0.60 per 1,000 patient days (PD) (p<0.001) and ESBL-E bacteraemia by 77%, from 0.03 to 0.05 per 1,000 PD (p<0.001). The incidence of ESBL-E infections was higher in intensive-care units (1.62 to 2.44 per 1,000 PD (p<0.001)) than in recovery and long-term care facilities (0.20 to 0.31 per 1,000 PD (p<0.001)). Escherichia coli was the most frequent extended-spectrum beta-lactamase-producing (ESBL) pathogen, representing 59% (26,238/44,425) of all ESBL isolates, followed by Klebsiella pneumoniae (20%; 8,856/44,425) in 2013. The most frequent infection was urinary tract infection, for all species. The incidence of ESBL-E varied by region but showed an upward trend overall. Reinforcement of control measures for halting the spread of such MRO is crucial.
Prognostic Significance of Mammographic Density Change After Initiation of Tamoxifen for ER-Positive Breast Cancer
Authors: Sarah J Nyante, Mark E Sherman, Ruth M Pfeiffer, Amy Berrington de Gonzalez, Louise A Brinton, Erin J Aiello Bowles, Robert N Hoover, Andrew Glass, Gretchen L Gierach
Journal: JNCI Journal of the National Cancer Institute (2015)

A prior analysis of postmenopausal breast cancer patients linked a decline in mammographic density (MD) following the initiation of tamoxifen treatment with improved survival, but excluded premenopausal women, for whom tamoxifen is the primary anti-endocrine therapy. Therefore, we evaluated change in MD after tamoxifen and breast cancer death among patients age 32 to 87 years.This case-control study included 349 estrogen receptor (ER)-positive breast cancer patients who were treated with tamoxifen at Kaiser Permanente Northwest (1990-2008): 97 who died from breast cancer (case patients) and 252 who did not (control patients), matched on age and year at diagnosis and disease stage. Percent MD in the unaffected breast was measured at baseline (mean six months before tamoxifen initiation) and follow-up (mean 12 months after initiation). Associations between change in MD and breast cancer death were estimated using conditional logistic regression.Patients in the highest tertile of MD decline had a lower risk of breast cancer death when compared with women in the lowest tertile (odds ratio [OR] = 0.44, 95% confidence interval [CI] = 0.22 to 0.88); results were similar after adjustment for baseline MD (OR = 0.49, 95% CI = 0.23 to 1.02). Reductions in death were observed only among patients in the middle and upper tertiles of baseline MD. Associations did not differ by age, tamoxifen use duration, estrogen and/or progestin use, body mass index, or receipt of chemotherapy or radiotherapy.These data suggest that younger and older ER-positive breast cancer patients who experience large reductions in MD following tamoxifen initiation have an improved prognosis.
B cell non-Hodgkin's lymphoma of the trachea mimicking COPD
Authors: V Johnson
Journal: Thorax (2004)

A 65 year old woman with a 15 pack year smoking history had recently been diagnosed in the community with chronic obstructive pulmonary disease (COPD). She was admitted to hospital with progressive breathlessness and wheeze; her exercise tolerance had decreased from 800 metres to less than 50 metres over the last year. Her peak expiratory flow rate on admission was 150 l/min increasing to …
Influence of farm exposure and pets ownership during pregnancy on cord blood mononuclear cells (CBMC) with intracellular production of interferon (IFN)-γ
Authors: Sergey Tereshchenko, Ivan Novitzkiy, Lyudmila Vasilieva
Journal: European Respiratory Journal (2012)

Some epidemiological and observational data suggest that farm and pets exposure in early childhood may be conducive to reduced atopy. Currently, there is a lack of consensus regarding underlying immunological mechanisms, especially in prenatal period.   AIM:  We hypothesized the influence of farm exposure and pets ownership during pregnancy on intracellular IFN-γ production by CBMC.   METHODS:  Intracellular IFN-γ expressions as well as early activation marker CD69 (absolute cells count) were examined using flow cytometry after PHA stimulation of CBMC obtained from 93 full-term newborns. The Kruskal-Wallis and Mann–Whitney tests were used.   RESULTS:  We revealed that newborns from rural mothers (n=14) have higher amount of both nonactivated (INFγ+/CD69–, p=0.02) and activated (INFγ+/CD69+, p=0.028) CBMC, producing IFN-γ, as compared with newborns from urban mothers (n=79). Only for newborns from urban mothers we calculated the influence of pets exposure during pregnancy on intracellular IFN-γ production (Fig. 1).  Noteworthily, that only amount of activated (INFγ+/CD69+) CBMC was elevated in dog (but not in cat) exposure group.   CONCLUSION:  Thus, external and home environment factors such as farm exposure and dog ownership may act prenatal affecting Th1/Th2 balance. These findings can leastwise partially explain previously reported epidemiological data.
Hypercalcaemia and hypokalaemia in tuberculosis.
Authors: G W Bradley, G M Sterling
Journal: Thorax (1978)

In two patients with extensive pulmonary tuberculosis who developed hypercalcaemia and hypokalaemia the hypercalcaemia appeared related to the use of small doses of vitamin D, which suggested patients with tuberculosis were hypersensitive to vitamin D. They were thus similar to patients with sarcoidosis, and it is interesting that the Kveim test result was positive in both cases. The hypercalcaemia was quickly suppressed with steroids. Hyperparathyroidism, thyrotoxicosis, Addison9s disease, and multiple myeloma were excluded on clinical grounds and by the appropriate tests. The hypokalaemia was associated with increased renal excretion of potassium, and was probably due to distal tubular damage from hypercalcaemia.
Possible ocular involvement in pulmonary alveolar proteinosis
Authors: P. Perri, C. Campa, S. D'Angelo, C. Costagliola, C. Incorvaia, A. Sebastiani
Journal: European Respiratory Journal (2006)

To the Editors: 

Pulmonary alveolar proteinosis (PAP) is a rare lung disease characterised by lipoproteinaceous material accumulation in the alveoli. In the most frequent form of the disease (acquired PAP), a neutralising auto-antibody against granulocyte-macrophage colony-stimulating factor (GM-CSF) causes defects in the functioning of alveolar macrophages, including impairment of the catabolism of surfactant lipids and proteins 1.

The clinical manifestations of PAP are progressive dyspnoea, cough or fatigue. Available reports have never disclosed any ocular involvement.

Herein, we describe, in a patient with acquired PAP, a retinal …
Longitudinal Serum Testosterone, Luteinizing Hormone, and Follicle-Stimulating Hormone Levels in a Population-Based Sample of Long-Term Testicular Cancer Survivors
Authors: Mette Sprauten, Marianne Brydøy, Hege S. Haugnes, Milada Cvancarova, Trine Bjøro, Johan Bjerner, Sophie D. Fosså, Jan Oldenburg
Journal: Journal of Clinical Oncology (2014)

To assess longitudinal long-term alterations of testosterone, luteinizing hormone (LH), and follicle-stimulating hormone (FSH) in testicular cancer survivors (TCSs).In all, 307 TCSs treated from 1980 to 1994 provided blood samples after orchiectomy but before further treatment, at Survey I (SI; 1998-2002), and Survey II (SII; 2007-2008). Levels of sex hormones were categorized according to quartiles and reference range (2.5 and 97.5 percentiles) of 599 controls for each decadal age group. TCSs were categorized according to treatment: surgery, radiotherapy (RT), or chemotherapy (CT). The risk of higher (LH) or lower (testosterone) levels was assessed with χ(2) test (FSH) or ordinal logistic regression analysis and expressed as odds ratios (ORs) with 95% CIs.Risk of lower testosterone and higher LH and FSH levels was significantly increased for TCSs at all time points after RT or CT. At SII, ORs were 3.3 (95% CI, 2.3 to 4.7) for lower testosterone categories and 5.2 (95% CI, 3.5 to 7.9) for RT and CT. ORs for increased LH and FSH were 4.4 (95% CI, 3.1 to 6.5) and 18.9 (95% CI, 11.0 to 32.6) for RT, respectively, and 3.6 (95% CI, 2.4 to 5.3) and 14.2 (95% CI, 8.3 to 24.4) for CT, respectively. The cumulative platinum dose was significantly associated with risk of higher LH levels at both surveys and higher FSH at SI. In total, half the TCSs had at least one of three sex hormone levels outside the reference range at SII.Long-term TCSs are at risk of premature hormonal aging. Our findings may pertain to cancer survivors in general, underlining the importance of extended follow-up.
BLOOD VOLUME IN WOUNDED SOLDIERS
Authors: Oswald H. Robertson, Arlie V. Bock
Journal: The Journal of Experimental Medicine (1919)

Blood volume tests made on a number of soldiers recovering from hemorrhage have shown that in many instances dilution of the blood occurs very slowly. The principal reasons for this seem to be (a) an initial lack of reserve fluid of the tissues, and (b) the absence of any subsequent attempt by the body to make up this fluid deficiency. By putting such patients on a large fluid intake by mouth and rectum it has been found that their blood volume can be promptly and greatly increased. Hemorrhage cases transfused, yet still showing a low blood volume, were first treated in this way. Then the effect of forced fluids without transfusion was tried. Immediately after a hemorrhage, or as soon as the patient came under observation, he was given large quantities of water by mouth, and salt solution by rectum. Under such treatment the blood pressure soon began to show a progressive rise, the volume increased, and the red cells became more evenly redistributed, as shown by the relative hemoglobin percentages of the capillary and venous blood. These changes were often well marked after only 2 or 3 hours of the treatment. More than this, forcing fluids in cases where the amount of bleeding is difficult to estimate on account of the presence of a high hemoglobin percentage is of distinct value, since the dilution of the blood which results serves to show the extent of the hemorrhage through the drop in hemoglobin that it entails. In attempting to determine the condition of the patient after hemorrhage with a view to deciding the most suitable form of treatment, it is of much importance to learn the total blood loss—which is often not even indicated by the hemoglobin concentration of the remaining blood. With a total hemoglobin reduced to 25 per cent or under transfusion is needful. New blood is necessary, not only to supply more oxygen-carrying cells, but also because it actually enables the circulation to increase its volume. For, as has been pointed out in Paper I, the hemoglobin percentage must be above a certain point if a rapid restoration of the blood volume by means of the organism's own activities is to come about. With the total hemoglobin above 25 per cent the chief need is for increased blood volume, and if the patient's condition demands an immediate and large addition of circulating fluid, gum acacia solution should be given. If the condition is not so urgent, forced fluids by the alimentary tract are indicated. The blood volume can be considerably reduced and yet a normal blood pressure maintained. It is pointed out that the vasomotor mechanism which, has adapted itself to the diminished blood bulk may in any individual case be very near the margin of its compensatory power. Increased strain in such instances may cause a failure of this mechanism with a resulting fall in blood pressure. The beneficial results of forced fluids after secondary hemorrhage suggest the value of the early use of fluids by the alimentary tract in cases of primary hemorrhage.
Synthetic Lethal Vulnerabilities of Cancer
Authors: Ferran Fece de la Cruz, Bianca V. Gapp, Sebastian M.B. Nijman
Journal: The Annual Review of Pharmacology and Toxicology (2014)

The great majority of targeted anticancer drugs inhibit mutated oncogenes that display increased activity. Yet many tumors do not contain such actionable aberrations, such as those harboring loss-of-function mutations. The notion of targeting synthetic lethal vulnerabilities in cancer cells has provided an alternative approach to exploiting more of the genetic and epigenetic changes acquired during tumorigenesis. Here, we review synthetic lethality as a therapeutic concept that exploits the inherent differences between normal cells and cancer cells. Furthermore, we provide an overview of the screening approaches that can be used to identify synthetic lethal interactions in human cells and present several recently identified interactions that may be pharmacologically exploited. Finally, we indicate some of the challenges of translating synthetic lethal interactions into the clinic and how these may be overcome.
Efficacy and Safety of a New HMG-CoA Reductase Inhibitor, Atorvastatin, in Patients With Hypertriglyceridemia
Authors: Rebecca G. Bakker-Arkema
Journal: JAMA (1996)

To assess the lipid-lowering effect of atorvastatin (a new 3-hydroxy-3-methylglutaryl coenzyme A [HMG-CoA] reductase inhibitor) on levels of serum triglycerides and other lipoprotein fractions in patients with primary hypertriglyceridemia, determine if atorvastatin causes a redistribution of triglycerides in various lipoprotein fractions, and assess its safety by reporting adverse events and clinical laboratory measurements.Randomized double-blind, placebo-controlled, parallel-group, multicenter trial.Community- and university-based research centers.A total of 56 patients (aged 26 to 74 years) with a mean baseline triglyceride level of 6.80 mmol/L (603.3 mg/dL) and a mean baseline low-density lipoprotein cholesterol (LDL-C) level of 3.07 mmol/L (118.7 mg/dL).Cholesterol-lowering diet (National Institutes of Health National Cholesterol Education Program Step I Diet) and either 5 mg, 20 mg, or 80 mg of atorvastatin, or placebo.Percent change from baseline in total triglycerides for three dose levels of atorvastatin compared with placebo.Mean reductions in total triglycerides between 5 mg, 20 mg, and 80 mg of atorvastatin and placebo after 4 weeks of treatment were -26.5%, -32.4%, -45.8%, and -8.9%, respectively. Mean reductions in LDL-C were -16.7%, -33.2%, -41.4%, and -1.4%, respectively, and very low-density lipoprotein cholesterol (VLDL-C) were -34.3%, -45.9%, -57.7%, and -5.5%, respectively. Similar mean changes in total apolipoprotein B (apo B) (-16.9%, -32.8%, -41.7%, and +1.0%), apo B in LDL (-14.8%, -29.8%, -42.0%, and -3.1%), and apo B in VLDL (-23.8%, -35.8%, -34.4%, and +11.7%) were observed. In addition, comparable mean changes in LDL triglycerides (-22.5%, -30.7%, -39.9%, and +3.9%) and VLDL triglycerides (-28.1%, -34.0%, -47.3%, and -10.8%) were seen.In atorvastatin treatment groups, total serum triglyceride levels decreased in a dose-dependent manner, reductions in the 20-mg and 80-mg groups were statistically significant (P < .05) compared with placebo. Atorvastatin did not cause a redistribution of triglycerides but consistently lowered triglycerides in all lipoprotein fractions. Atorvastatin was well tolerated.