tbuckley/cabot-search huggingface dataset:
Drug-resistant tuberculosis in the WHO European Region: An analysis of surveillance data
Authors: Matteo Zignol, Masoud Dara, Anna S. Dean, Dennis Falzon, Andrei Dadu, Kristin Kremer, Harald Hoffmann, Sven Hoffner, Katherine Floyd
Journal: Drug Resistance Updates (2013)

To review the latest information about levels of anti-tuberculosis (TB) drug resistance in the European Region of the World Health Organization (WHO) and time-trends in multidrug-resistant TB (resistance to isoniazid and rifampicin; MDR-TB) over the past fifteen years. We analysed data on drug resistance among new and previously treated TB cases reported from 1997 to 2012. Data are collected in surveys of representative samples of TB patients or from surveillance systems based on diagnostic drug susceptibility testing. A total of 15.7% (95% confidence limits (CI): 9.5–21.9) of new and 45.3% (95%CI: 39.2–51.5) of previously treated TB cases are estimated to have MDR-TB in the Region. Extensively drug-resistant TB (MDR-TB and resistance to fluoroquinolones and second-line injectables; XDR-TB) had been reported by 38 of the 53 countries of the region (72%). The proportion of MDR-TB cases with XDR-TB is 11.4% (95%CI: 8.6–14.2). Between 1997 and 2012, population rates of MDR-TB declined in Estonia, Latvia and Germany and increased in the United Kingdom, Sweden and Tomsk Oblasts of the Russian Federation. Surveillance of drug resistance has been strengthened in the WHO European Region, which has the highest proportions of MDR-TB and XDR-TB ever reported globally. More complete data are needed particularly from the Russian Federation.
Increased tissue concentrations of 5-hydroxytryptamine in the duodenal mucosa of patients with coeliac disease.
Authors: D N Challacombe, P D Dawkins, P Baker
Journal: Gut (1977)

Tissue concentrations of 5-HT have been measured in the duodenal mucosa of adults and children with coeliac disease and were found to be significantly higher than those from a control group. This finding may be associated with hyperactivity or hyperplasia of enterochromaffin (EC) cells in the duodenum of patients with coeliac disease and could also be directly related to described abnormalities of 5-HT metabolism in this disease.
THE SKIN MANIFESTATIONS ASSOCIATED WITH LEUKAEMIA AND ALLIED CONDITIONS. *
Authors: HUMPHRY ROLLESTON
Journal: British Journal of Dermatology (1924)

Journal Article THE SKIN MANIFESTATIONS ASSOCIATED WITH LEUKAEMIA AND ALLIED CONDITIONS. Get access HUMPHRY ROLLESTON, BT., K.C.B. M.D., D.Sc., P.R.C.P. Sir HUMPHRY ROLLESTON, BT., K.C.B. M.D., D.Sc., P.R.C.P. Sir Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology and Syphilis, Volume 36, Issue 10, 1 October 1924, Pages 407–427, https://doi.org/10.1111/j.1365-2133.1924.tb09137.x Published: 01 October 1924
CS-04 * STAT3 INVOLVEMENT IN AN EMT-LIKE PROCESS IN GLIOBLASTOMA BRAIN TUMOR INITIATING CELLS
Authors: C. Chesnelong, A. Luchman, J. Gregory Cairncross, S. Weiss
Journal: Neuro-Oncology (2014)

Glioblastoma Multiforme (GBM) is the most aggressive subtype of brain tumour with a median survival of 15 months. Currently, GBM is managed by a combination of maximal safe resection followed by radiation and chemotherapy. However, GBM invariably recurs, highlighting the need to better delineate the basis of recurrent disease and develop novel more effective and targeted therapies. The Signal Transducer and Activator of Transcription 3 (STAT3) is abnormally active in GBM. A growing body of evidence supports the hypothesis that STAT3 is a major oncogenic molecular hub in patient-derived Brain Tumor Initiating Cells (BTICs) leading to stemness, proliferation, invasion and therapeutic resistance. Recently, there has been an increasing awareness that Epithelial to Mesenchymal Transition (EMT) is an essential process promoting the generation of highly tumorigenic cells with stem-like characteristics. The mesenchymal GBM profile, characterized by significantly shortened progression-free and overall survival, suggests that an EMT-like process has clinical relevance in GBM. Moreover, recent studies support a possible role for STAT3 in an EMT-like process in GBM. Here we show in that SLUG (encoded by SNAI2) appears to be expressed at higher levels than other EMT regulators in patient samples and matching BTICs. High SLUG protein level is observed in a large number of BTIC lines and positively correlates with activated STAT3. Moreover, SLUG is significantly decreased after pharmacological inhibition of STAT3 signalling using a well-characterized STAT3 inhibitor (Stattic) and a novel clinically relevant JAK2 inhibitor. Furthermore, IL-6 treatment or overexpression of a constitutively active form of STAT3 promote SLUG expression. SLUG and the subsequent EMT-like process may play an important role in the aggressive mesenchymal phenotype of GBM and the archetypal characteristics of BTICs: self-renewal, invasion, tumorigenicity and therapeutic resistance. We propose that STAT3-dependent EMT-like process and the key regulator SLUG are interesting novel therapeutic targets in GBM.
Esophageal Transit of Liquid in Chronic Alcoholism in Patients With Cirrhosis Influence of Esophageal Varices
Authors: HAMPHREY R. HAM, DANIEL URBAIN
Journal: Clinical Nuclear Medicine (1994)

Disturbances of esophageal motility are often encountered in chronic alcoholism, and numerous physiopathologic mechanisms responsible for this alteration have been documented. The exact role of esophageal varices, however, in inducing esophageal transit abnormalities remains unclear. In this study using scintigraphy, the authors studied esophageal transit in a large number of patients with cirrhosis to assess the direct effect of esophageal varices. Esophageal transit was found altered in 58 out of 141 patients with cirrhosis (41.1%). It was prolonged in 47.3% of patients with esophageal varices and in 29.2% of patients without varices (P < 0.05). The frequency of esophageal transit alteration was also related to the Child-Turcotte-Pugh (CTP) score, an index of the severity of liver disease (P < 0.01). The relationship between CTP class and transit alteration remained statistically significant in the group of patients with esophageal varices (P < 0.05). Conversely, when patients in each CTP class were analyzed separately, the frequency of esophageal transit abnormalities was not different in patients with and without esophageal varices. These results suggest that the severity of cirrhosis, rather than the presence of esophageal varices, constitutes the major factor in inducing esophageal transit alteration in patients with cirrhosis.
Regulating herbal medicine and acupuncture: author's reply
Authors: R. M Pittilo
Journal: BMJ (2008)

In the same week that the report to ministers from the Department of Health steering group on the statutory regulation of acupuncture, herbal medicine, traditional Chinese medicine. and other traditional medicine systems practised in the UK was published,1 the Medicines and Healthcare products Regulatory Agency (MHRA) issued a further alert on poor practice causing serious harm in the herbal medicines sector.2 Colquhoun (previous letter) …
Changing Concepts in the Epidemiology of Viral Hepatitis
Authors: Raymond S. Koff, Kurt J. Isselbacher
Journal: New England Journal of Medicine (1968)

DURING the past decade advances in virology and vaccine development have resulted in a striking decline in the incidence of a number of common viral diseases. Whereas viral hepatitis has attracted increasing attention as a public-health problem, progress in hepatitis virology has been exceedingly slow. At present the etiologic agent of viral hepatitis has not been identified, and no vaccine is available for prevention of the disease. On the basis of the past experience with poliomyelitis and measles vaccines, it is likely that even after isolation of the hepatitis virus or viruses, five to 10 years will probably elapse before . . .
THE EFFECTS OF DRY ATMOSPHERE ON CHRONIC INFLAMMATION OF THE LARYNX AND NARES.Read before the meeting of the American Climatological Association held in Denver, September 2 to 5, 1890.
Authors: E. FLETCHER INGALS
Journal: JAMA (1890)

In this paper it is my object to invite your attention to a subject upon which unfortunately we have little precise information, hoping thereby to elicit a discussion in which the observation of others may help to remove the deficiencies which I am obliged to confess. The views which I shall here express are based on the study of a large number of cases, but I shall make no attempt to present the histories of these cases in substantiation. Most of my patients live in low altitudes, many of which are damp; though I frequently see patients who live in a high and dry atmosphere. In trying to analyze these cases I have been unable to decide satisfactorily what particular phases of the disease are benefited and what injured by the dry atmosphere. In the majority, I presume at least four-fifths, dryness of the atmosphere seems beneficial, but in some
Biofilms, Antimicrobial Resistance, and Airway Infection
Authors: Alice S Prince
Journal: New England Journal of Medicine (2002)

The use of susceptibility testing to identify appropriate antimicrobial agents has long been an important element of the practice of infectious-disease medicine. In most clinical settings, the finding that a strain of bacteria is susceptible to a specific antibiotic is a reliable indicator of the effectiveness of that drug. An exception is the treatment of pulmonary infection in patients with cystic fibrosis. Once chronic Pseudomonas aeruginosa infection is established in the lungs of these patients, the bacteria are rarely, if ever, eradicated despite treatment with combinations of antimicrobial agents with demonstrated potency in vitro. Even direct administration of aerosolized antibiotics . . .
Diathermy resection and radioactive gold grains for palliation of obstruction due to recurrence of bronchial carcinoma after external irradiation.
Authors: S J Ledingham, P Goldstraw
Journal: Thorax (1989)

OBJECTIVE: To compare bone density with polymorphisms in the calcitonin receptor (CTR) and vitamin D receptor (VDR) genes in 50 patients with juvenile idiopathic arthritis and 80 matched controls. METHODS: Bone mineral density (BMD) was measured by dual energy x-ray absorptiometry at the lumbar spine. Genomic DNA was isolated from EDTA blood samples by standard procedures. Polymerase chain reaction was performed using genomic DNA and 100 pmol of each oligonucleotide primer for VDR and CTR genes. Products from genomic PCR were digested by Alu I enzyme for CTR polymorphism and Fok I enzyme for VDR polymorphism. RESULTS: In the total population, higher prevalence of CC genotype (41.5%) for the CTR gene and FF genotype (59.8%) for the VDR gene was found, in agreement with data for Caucasian populations. No significant differences in distribution of CTR and VDR genotypes were observed between patients and controls. However, patients with TT genotype had lumbar BMD (L-BMD) that was lower in comparison to those with CC genotype (p = 0.04). For VDR gene polymorphism, we observed that patients with ff genotype had lower L-BMD in comparison with FF genotype (p = 0.02). Patients with heterozygosity for the 2 genotypes showed intermediate L-BMD. The differences in L-BMD among these groups did not seem to be related to corticosteroid therapy. CONCLUSION: Our data suggest that patients with particular VDR and CTR genotypes may be at higher risk to lose bone mass.
The daily energy expenditure in stable chronic obstructive pulmonary disease.
Authors: O Hugli, Y Schutz, J W Fitting
Journal: American Journal of Respiratory and Critical Care Medicine (1996)

Resting energy expenditure is frequently increased in chronic obstructive pulmonary disease (COPD), but it is unknown if this hypermetabolism holds true over 24 h. The aim of this study was to measure the actual 24-h energy expenditure (24-h EE) in patients with stable COPD. Energy expenditure was measured by indirect calorimetry, using a metabolic chamber for 24-h EE and a canopy for basal metabolic rate (BMR). Physical activity was detected in the chamber by a radar system, and its duration was quantified. Two groups matched for age and height were studied: 16 male ambulatory patients with stable COPD and 12 male normal subjects. Body weight was 92 +/- 12% of ideal body weight in the group with COPD and 108 +/- 11% in the control group (p = 0.01). BMR was 120 +/- 7% of predicted in the group with COPD and 108 +/- 12% in the control group (p < 0.01). However, 24-h EE was similar in the two groups, amounting to 1,935 +/- 259 kcal in patients with COPD and 2,046 +/- 253 kcal in the control group (NS). This corresponded to 145% and 137% of predicted BMR, and to 121% and 126% of measured BMR in patients with COPD and the control group, respectively (NS). Patients were allowed to pursue their usual treatment within the chamber, and a positive correlation existed between 24-h EE and the daily dose of inhaled beta 2-agonists (p < 0.03). During daytime, physical activity was lower in patients with COPD. This study shows that patients with stable COPD are characterized by a normal daily energy expenditure in controlled conditions in spite of an increased basal metabolic rate. They appear to save energy by reducing their spontaneous level of physical activity.
Phase II Study of Biweekly Pemetrexed and Gemcitabine in Patients with Previously Untreated Advanced Non-small Cell Lung Cancer
Authors: David R. Spigel, John D. Hainsworth, John H. Barton, Jeffrey F. Patton, John D. Zubkus, Lisa Simons, Paula Griner, Howard A. Burris, F. Anthony Greco
Journal: Journal of Thoracic Oncology (2010)
Please Don't Eat the Salads
Authors: Jack S. Remington, Stephen C. Schimpff
Journal: New England Journal of Medicine (1981)

Nearly half the infections in patients who have cancer with prolonged, severe granulocytopenia have been shown to be caused by hospital-acquired organisms that have colonized the alimentary canal.1 Some acquired organisms are particularly virulent in the granulocytopenic patient; for example, bacteremia may develop in 40 to 70 per cent of such patients who are colonized with Pseudomonas aeruginosa. Hospital sources of aerobic bacteria that are major causes of infection in these patients have been emphasized in numerous publications, but there appears to be insufficient appreciation of the potential role of food as a major source of these organisms, with . . .
The End of an Era in Otitis Research
Authors: Stephen Berman
Journal: New England Journal of Medicine (2007)

Retrospective studies carried out in the 1950s, 1960s, and 1970s suggested an association between otitis media early in life and subsequent developmental impairments in children. Although these studies were not designed to establish a cause-and-effect relationship, many prominent physicians, audiologists, and speech pathologists thought that a cause-and-effect relationship did exist, because severe, bilateral sensorineural hearing loss was known to cause irreversible developmental impairments. Therefore, aggressive intervention to restore normal hearing became the standard of care, and the placement of tympanostomy tubes became the second most frequent surgical procedure performed in the United States (after neonatal circumcision). In July 1994, the . . .
Variant Hemodynamic Patterns in Mitral Stenosis
Authors: G. H. CARMAN, R. L. LANGE
Journal: Circulation (1961)

Of a total group of 86, 11 cases of proved significant mitral stenosis with cardiovascular hemodynamic data are presented. Four had normal pulmonary wedge and pulmonary artery pressures at rest and low cardiac index at rest and after mild exercise. It is postulated that such persons respond to mitral valve obstruction primarily by lowering cardiac output. The cardiac index in seven was normal at rest and after mild exercise. Thus there was no evidence that alteration of blood flow had occurred in response to the lesion. The values for pulmonary arteriolar resistance in three of these were qualitatively normal when flow was increased. These are considered to be examples of absent or inadequate changes in pulmonary vascular reactivity. The existence in a significant percentage of patients with mitral stenosis of a low cardiac output with normal resting pulmonary, arteriolar, and wedge pressures, or normal cardiac output despite elevation of these pressures infers that potent flow-regulating factors tors can operate independently of the obstructive lesion.
Ascorbate Depletion: A Critical Step in Nickel Carcinogenesis?
Authors: Konstantin Salnikow, Kazimierz S. Kasprzak
Journal: Environmental Health Perspectives (2005)

Nickel compounds are known to cause respiratory cancer in humans and induce tumors in experimental animals. The underlying molecular mechanisms may involve genotoxic effects; however, the data from different research groups are not easy to reconcile. Here, we challenge the common premise that direct genotoxic effects are central to nickel carcinogenesis and probably to that of other metals. Instead, we propose that it is formation of metal complexes with proteins and other molecules that changes cellular homeostasis and provides conditions for selection of cells with transformed phenotype. This is concordant with the major requirement for nickel carcinogenicity, which is prolonged action on the target tissue. If DNA is not the main nickel target, is there another unique molecule that can be attacked with carcinogenic consequences? Our recent observations indicate that ascorbate may be such a molecule. Nickel depletes intracellular ascorbate, which leads to the inhibition of cellular hydroxylases, manifested by the loss of hypoxia-inducible factor (HIF)-1alpha and -2alpha hydroxylation and hypoxia-like stress. Proline hydroxylation is crucial for collagen and extracellular matrix assembly as well as for assembly of other protein molecules that have collagen-like domains, including surfactants and complement. Thus, the depletion of ascorbate by chronic exposure to nickel could be deleterious for lung cells and may lead to lung cancer. Key words: ascorbate, carcinogenesis, collagens, extracellular matrix, hypoxia-inducible transcription factor, metals, nickel, protein hydroxylation.
Electrophysiological Mechanism of Enhanced Susceptibility of Hypertrophied Heart to Acquired Torsade de Pointes Arrhythmias
Authors: Dmitry O. Kozhevnikov, Keiji Yamamoto, Dionyssios Robotis, Mark Restivo, Nabil El-Sherif
Journal: Circulation (2002)

Background — Cardiac hypertrophy is associated with increased incidence of sudden death and susceptibility to proarrhythmic effects of antiarrhythmic agents. However, the in vivo electrophysiologic mechanism of the arrhythmias has not been investigated in detail. Methods and Results — Dose-dependent susceptibility to Torsade de Pointes (TdP) by class III drug dofetilide, 3, 10, and 30 μg/kg, was compared in 6 control dogs (C) and in 5 dogs 6 to 8 weeks after induction of complete atrioventricular block (AVB) that resulted in ventricular hypertrophy (H). Tridimensional ventricular activation and repolarization (R) patterns were simultaneously analyzed from unipolar extracellular electrograms, and local R was measured from activation recovery intervals. Both R and transmural dispersion of R (TDR) were significantly greater in dogs with H compared with C. Dofetilide resulted in cycle length–dependent and dose-dependent prolongation of R, which was more marked in left ventricular endocardium/midmyocardium compared with epicardium, resulting in significant increase of TDR. These changes were more accentuated in dogs with H compared with C. All 5 dogs with H developed TdP at a dose of 3 to 10 μg/kg, whereas only 1 of 6 C dogs developed TdP at 30 μg/kg. TdP was initiated by subendocardial focal activity that infringed on TDR, resulting in functional conduction block and reentrant excitation. Conclusions — Enhanced susceptibility of hypertrophied heart to class III drugs is attributable to baseline increased TDR and greater dose-related accentuation of TDR compared with nonhypertrophied heart. This provides the electrophysiologic substrate for drug-induced TdP.
Kosovo refugees spared epidemics so far
Authors: J. Ciment
Journal: BMJ (1999)

For all the horrific scenes emerging out of the refugee camps on the borders of Kosovo, one nightmare seems so far to have been avoided: a major epidemic of infectious disease. Officials from the World Health Organisation on the scene and in New York reported last week that there has, as yet, been no been no major outbreak of disease in the makeshift camps.

“We have heard of no major epidemics in the camps,” commented Robyn Groves, senior external relations officer for the WHO. “The only …
Sunlight-induced basal cell carcinoma tumor cells and ultraviolet-B-irradiated psoriatic plaques express Fas ligand (CD95L).
Authors: C Gutierrez-Steil, T Wrone-Smith, X Sun, J G Krueger, T Coven, B J Nickoloff
Journal: Journal of Clinical Investigation (1998)

The skin is constantly exposed to sunlight and frequently develops sun-induced skin cancers such as basal cell carcinoma (BCC). These epidermal-derived tumors escape local immune surveillance and infiltrate the dermis, requiring surgical removal. We report here that in contrast to keratinocytes in normal skin (n = 4), BCC tumor cells (n = 6) strongly and diffusely express Fas ligand (CD95L), but not Fas antigen (CD95). This CD95L expression in vivo by BCC tumor cells is associated with peritumoral T lymphocytes that are undergoing apoptosis. Moreover, CD95L can be induced on normal cultured keratinocytes after exposure to ultraviolet-B light (UV-B) irradiation. This induction of CD95L was confirmed at the mRNA and protein levels using multipassaged human keratinocytes and a keratinocyte cell line. Keratinocytes induced to express CD95L acquired the functional capacity to kill a CD95-positive lymphocyte cell line. Whereas hyperplastic keratinocytes in untreated psoriatic plaques do not express CD95L on their plasma membrane, after UV-B treatment there is strong and diffuse keratinocyte CD95L expression that coincided in a temporal fashion with depletion of intraepidermal T cells in all five patients studied. Our data suggest a novel molecular pathway by which UV light can contribute to the ability of a skin cancer to escape from immune attack by cytotoxic T lymphocytes, and a previously unrecognized therapeutic mechanism of action for UV-B light in psoriasis via keratinocyte CD95L expression. Such immunological events involving CD95L provide new insight and opportunity for novel treatment approaches not only for cutaneous neoplasms but also for various T cell-mediated dermatoses such as psoriasis.