tbuckley/cabot-search huggingface dataset:
Syphilis: old problem, new strategy
Authors: L. Doherty
Journal: BMJ (2002)

Syphilis is on the increase again. Lorraine Doherty and colleagues report on four recent localised outbreaks and recall the features of infectious syphilis, its treatment, and the public health measures needed to contain it

Infectious syphilis is a disease of considerable public health importance, with overwhelming health effects if it is not treated. These include cardiovascular and neurological disease and adverse pregnancy outcomes, such as stillbirth and congenital syphilis. Further, concurrent infection with syphilis can facilitate transmission of HIV.1 Syphilis is most infectious through sexual contact during the primary or secondary stages (see box 1), but transmission can also occur during the early latent stage.2 Syphilis is preventable, and treatable with effective and inexpensive antibiotics. The possible resurgence of infectious syphilis, a disease previously believed to be close to eradication, is a matter of increasing global concern.3–6

This article outlines recent changes in the epidemiology of infectious syphilis in England, including the features of a number of outbreaks. It aims to increase health professionals' awareness of the clinical features of infectious syphilis, and to consider approaches to the investigation and control of syphilis and other outbreaks of sexually transmitted infection.

#### Summary points

Untreated infectious syphilis may have a number of very serious health effects

Recently there has been an upward trend in incidence, partly due to several localised outbreaks affecting homosexual men and heterosexual men and women

These outbreaks have emphasised the importance of investigating wider sexual networks as well as tracing individual contacts to identify further cases and prevent further spread

The general public, certain groups at risk, and relevant health professionals should be aware of the risks of acquiring syphilis and the symptoms and signs of acute infection

Between the 1960s and the late 1970s homosexually acquired syphilitic infection increased, in keeping with liberalisation of …
Augmentation of fibroblast proliferation by bleomycin.
Authors: P L Moseley, C Hemken, G W Hunninghake
Journal: Journal of Clinical Investigation (1986)

Bleomycin-induced lung disease is characterized by fibroblast proliferation and pulmonary fibrosis. In these studies, we demonstrate that fibroblasts are relatively resistant to clinically relevant amounts (below 10(-4) U/ml) of bleomycin and that these levels of bleomycin augment fibroblast proliferation in response to various fibroblast growth factors. These observations suggest that one mechanism by which bleomycin causes pulmonary fibrosis is augmentation of fibroblast proliferation.
Abstract 481: Dualistic regulation of NF-kB signaling by CD99 and EWS-FLI1 in Ewing sarcoma: impact on cell differentiation
Authors: Selena Ventura, Chiara Manzalini, Dave Aryee, Piero Picci, Heinrich Kovar, Katia Scotlandi
Journal: Cancer Research (2014)

Abstract Introduction: Ewing sarcoma (ES) is a high-grade rare malignant bone tumor in children and adolescents. This disease is primarily characterized by: i) Chromosomal translocations that fuse EWS gene and a gene of the ETS family of transcription factors (around 85% EWS-FLI1 and 10% EWS-ERG, respectively) which are the oncogenic drivers of this tumor; ii) High expression of CD99, a cell surface glycoprotein virtually present in all of ES cells. EWS-FLI1 and CD99 were reported to have divergent roles in modulating ES malignancy and neural differentiation In this study we investigated the possible role of nuclear factor-kappa B (NF-kB) signaling pathway on the neural differentiation of ES cells and its relationship with EWS-FLI1 and CD99. Materials and Methods: Transcriptional activity of several transcription factors (AP1, SRE, CREB, E2F and NF-kB) were evaluated by gene reporter assay. Using a knockdown approach in stable and transient conditions we silenced CD99, EWS-FLI1 and NF-kB itself, alone or in combination, in three ES cell lines (TC-71, IOR/CAR and ASP14). NF-kBp65 was also transiently overexpressed in TCshCD99 and CARshCD99 clones with pCMVp65 construct. Neural differentiation was detected evaluating β-III tubulin by immunofluorescence microscopy. Results: NF-kB was found heterogeneously expressed in a panel of ES cell lines. Stable CD99 silencing was found to decrease NF-kB activity (pValue &amp;lt;0.05) without any differences at RNA and protein levels. On the contrary, EWS-FLI1 knockdown increased NF-kB transactivation (pValue &amp;lt;0.01). CD99 affects NF-kBp65 activity and its effect are dominant with respect to EWS-FLI1. Accordingly, EWS-FLI1 silencing was not able to revert the reduction of NF-kB activity observed after CD99 deprivation. In addition cells silenced for CD99 but not for EWS-FLI1 (TCshCD99 and CARshCD99 clones) showed a neural differentiated phenotype, which was lost when cells were induced to re-express NF-kB. Conclusion: Our findings support the concept that inhibition of NF-kB is able to induce terminal neural differentiation of ES cells. This identifying NF-kB as a potential therapeutic target against Ewing sarcoma progression. (Supported by AIRC_2013_IG 14049 and Liddy Shriver Foundation) Citation Format: Selena Ventura, Chiara Manzalini, Dave Aryee, Piero Picci, Heinrich Kovar, Katia Scotlandi. Dualistic regulation of NF-kB signaling by CD99 and EWS-FLI1 in Ewing sarcoma: impact on cell differentiation. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 481. doi:10.1158/1538-7445.AM2014-481
Endotoxin, reticuloendothelial function, and liver injury
Authors: James P. Nolan
Journal: Hepatology (1981)

Endotoxin is a toxic cell-wall component of Gramnegative bacteria consisting of lipopolysaccharide (LPS) and is present in large quantities in the intestine as a result of bacterial death and release during active growth.Small amounts of these LPSs are regularly absorbed but are rapidly detoxified by the liver which stands as a barrier to bacterial toxins which arise in the gut.For years, investigators have been intrigued by the possibility that failure to perform normally this function of detoxification might initiate or perpetuate liver injury, or result in systemic effects (1).This article reviews experimental and clinical evidence for a relationship between hepatic reticuloendothelial cells, endotoxin of gut origin, and liver injury.The hypothesis to be examined is as follows: as is illustrated in Figure 1.(a) Portal vein endotoxemia of gut origin represents a normal physiologic state.(b) The hepatic sinusoidal cells, particularly fixed macrophages, are critical to normal endotoxin detoxification.(c) The initial damage in a number of injuries is to sinusoidal cells, which seriously impair the ability of the liver to handle the ordinarily innocuous amount of LPS coming from the gut.(d) This marked increase in sensitivity to LPS (which may be of a magnitude of 10-to 1,000-fold) leads to further hepatocyte damage and spillover of LPS into the systemic circulation which results in extrahepatic manifestations including hypergammaglobulinemia. EVIDENCE FOR SYNERGISMSeveral studies suggest a relationship between the intestinal tract and liver injury.In 1941, Leach showed that sulfonamides protected again carbon tetrachloride (CCL) liver injury (2).In 1954, a relationship was established between diet-induced liver injury and the presence of intestinal flora.Rats fed the necrogenic diet of Himsworth regularly died of liver necrosis in 35 days, whereas
New in JAMA—Reader's Choice CME
Authors: Thomas B. Cole
Journal: JAMA (1997)

Beginning with this issue, continuing medical education (CME) credit will be offered for reading reviews and original research articles in<i>JAMA</i>. To earn credit, readers will be expected to engage in a self-directed, evidence-based, adult learning activity designed to improve the practice of medicine. Those who wish to read<i>JAMA</i>solely to obtain medical information of the highest quality may continue to so as always, but those who wish to take the additional step of using this information to change their medical practices for the better<sup>1</sup>may earn category 1 CME credit toward the American Medical Association Physician's Recognition Award.<sup>2</sup>This is the type of credit that is required by many states and professional societies for licensure, accreditation, or membership. Recent reviews<sup>3,4</sup>have concluded that the most effective CME activities are tailored to the specific needs of physicians, use techniques such as reminder systems to reinforce their
One More Variety of 'Storage Pool Disease'
Authors: Mario G. Baldini
Journal: JAMA (1980)

In 1882, Bizzozero,<sup>1</sup>an Italian pathologist, first described platelets as they appear in small blood vessels and demonstrated their adhesive quality, their participation in thrombi, and their role in blood coagulation. Progress did not soon follow these astounding contributions. Only during the past 15 years has an explosion of interest and knowledge in platelets and their disorders been witnessed. It is now known that platelet structure, metabolism, and function are all important in the participation of platelets in hemostasis and that abnormalities in these can lead to specific bleeding disorders of varying severity. Structural physiology has gradually become a precise science. Different zones and various organelles in the platelet body have now been related to well-defined platelet functions. The so-called platelet storage granules have intrigued investigators for years, and only recently has their role been clarified. Two types of storage granules are present within platelets—the alpha granules and the
Rupture of the Aorta During Closed-Chest Cardiac Massage
Authors: Dewey A. Nelson
Journal: JAMA (1965)

IN 1960, Kouwenhoven, Jude, and Knickerbocker<sup>1</sup>described the technique of closed-chest cardiac massage. They advocated it as a safe and simple method of cardiac resuscitation, available to physicians both in and out of the hospital. Since 1960, other reports have appeared attesting to the efficacy of the techinique.<sup>2-5</sup>Cotlar et al<sup>2</sup>reported that compared to operating room survival rates of 10% to 20% when open-chest massage was exclusively used, closed-chest massage is presently giving a 50% to 70% survival. The procedure is not without complications.<sup>4,6,7</sup>Most of these are rib or sternal fractures, but bone marrow emboli, hemothorax, hemopericardium, pneumothorax, mediastinal emphysema, gastric rupture, and lacerations of spleen, liver, and blood vessels also occur. It is difficult to ascertain the percentage of patients who have one or more of these complications. Baringer et al<sup>4</sup>reported autopsy results of 46 patients. Fifteen had rib fractures, six
Prevention of neurological damage during open-heart surgery.
Authors: M A Branthwaite
Journal: Thorax (1975)

A previous study of neurological damage related to open-heart surgery suggested that the onset of cardiopulmonary bypass is a time of particular hazard, and there is evidence that both microemboli from the extracorporeal circulation and inadequate cerebral perfusion may be contributory factors. Measures to eliminate or minimize these hazards have been introduced, and a clinical survey has been undertaken to evaluate their efficacy. There has been a very highly significant decrease in the incidence of neurological damage as judged by comparison with the results of a similar survey carried out before these measures were introduced. In spite of limitations imposed by differences in workload, perfusion techniques, and methods of data collection, it is concluded that the prophylactic measures have been responsible for the reduction in the incidence of neurological damage.
ETIOLOGY OF CEREBRAL PALSIES IN CHILDREN.
Authors: WILLIAM J. BUTLER
Journal: JAMA (1906)

right hemisphere again yielded the same organism isolated at the two previous spinal punctures.BACTERIOLOGY OF THE CASE.As has been already stated, the same organism was isolated from the spinal fluid at the two spinal punctures and again at the postmortem, as also from the throat, and a description of one will serve for all four strains.Morphology.-The organism is a short bacillus meas- uring 2.5x0.5 microns.It stains readily by all anilin dyes, also retaining Gram's.Preparations from 48-hour cultures show a beaded appearance of the organisms when stained with Loeffler's méthylène blue.There were also marked involution forms, such as club-shaped and dumb-bell-shaped organisms of variable size.Culture Characteristics.-Theorganisms grow well on all the ordinary culture media, but best on blood serum, where at the end of 10 hours a creamy slightly elevated layer is formed.On blood-agar plates we find at the end of 24 hours pinhead colonies without hemolysis, though when glucose blood-agar was used often a zone of greenish tinge developed about the colonies.Animal Experiments.-Guinea-pigswere inoculated subcutaneously with 1/20 of a 24-hour blood serum cul- ture suspended in normal salt solution.The animals appeared sick at the nd of 12 hours, with beginning evi- dence of local infiltration.Death occurred in from 48 to 56 hours.At autopsy there was found locally marked edema and bloody exúdate into the subcutaneous tissues, extending some distance beyond the point of inoculation.The internal organs, as a rule, showed some pallor, while the adrenals were usually large and deep red in color.Cultures from the heart's blood and internal organs re- mained sterile, while the organism was always recovered in pure culture from the local process.Unfortunately we were forced to discontinue the work for two months, and on resuming it the organisms had lost their virulence so that it was impossible to test the protective influence of diphtheria antitoxin.To differentiate the bacillus isolated from the B. xyrosis and B. pseudodiphtherioe, the method of Knopf1 was adopted.Serum sugar media were prepared with inulin, dextrose, saccharose and dextrin and inoculated with several strains of B. diphtheria and also the bacillus C, described above, with the results as shown in the table.
Biomarkers for early detection of sickle nephropathy
Authors: Nambirajan Sundaram, Michael Bennett, Jamie Wilhelm, Mi‐Ok Kim, George Atweh, Prasad Devarajan, Punam Malik
Journal: American Journal of Hematology (2011)

Renal complications affect nearly 30-50% of adults with sickle cell anemia (SCA), causing significant morbidity and mortality. Standard renal function tests like serum creatinine and glomerular filtration rate become abnormal in this disease only when renal damage has become extensive and largely irreversible. Moreover, not all patients develop sickle nephropathy (SN). Therefore, noninvasive biomarkers that predict early onset of SN are necessary. We performed a cross-sectional analysis for nephropathy in 116 patients with sickle cell disease, analyzing urinary kidney injury molecule-1 (KIM-1), liver-type fatty acid binding protein (L-FABP), N-acetyl-b-D-glucosaminidase (NAG), neutrophil gelatinase-associated lipocalin (NGAL) and transforming growth factor-β1 (TGF-β), together with conventional renal biomarkers (urine albumin and osmolality, and serum creatinine and cystatin C estimated GFR) during routine clinic visits when patients were at steady-state/baseline. We observed a distinct biomarker pattern: KIM-1 and NAG emerged as biomarkers with a strong association with albuminuria. Surprisingly, and in contrast to other acute/chronic renal disorders, NGAL, L-FABP, and TGF-β levels did not show any relationship with albuminuria in patients with SCA. Our study identifies potential biomarkers for SN, and suggests longitudinal validation of these biomarkers for early detection of SN, so that therapeutic interventions can be applied before renal damage becomes irreversible.
Problem drug use in a central London general practice.
Authors: J. Cohen, A. Schamroth, I. Nazareth, M. Johnson, S. Graham, D. Thomson
Journal: BMJ (1992)

OBJECTIVE--To describe the profile of problem drug users presenting in general practice and to determine whether they can be cared for in general practice. DESIGN--Study of consultations by problem drug users. SETTING--Central London general practice. SUBJECTS--150 problem drug users presenting over two years. MAIN OUTCOME MEASURES--Stopping drug use, alterations in lifestyle, obtaining paid work, and stopping drug related crime. RESULTS--Of the 150 patients, 111 were men and 39 women, and 106 were unemployed. 121 patients used heroin, 112 of whom injected. 145 patients accepted a methadone reduction programme and 81 completed it. A further 25 were stabilised on reducing doses of methadone, until places became available for them as inpatients at drug dependency units or rehabilitation projects. CONCLUSION--Withdrawal programmes for patients who misuse drugs can be successfully managed in general practice.
268 Transarterial therapy for hepatocellular carcinoma (HCC) in cirrhosis: Is embolization as effective as chemoembolization? Systematic review of cohort and randomized studies
Authors: L. Marelli, R. Stigliano, C. Triantos, M. Senzolo, E. Cholongitas, N. Davies, J. Tibbals, T. Meyer, D. Patch, A. Burroughs
Journal: Journal of Hepatology (2006)
Abstract 3265: Dual specificity phosphatase 4 gene expression in triple negative breast cancer
Authors: Michelle L. Baglia, Qiuyin Cai, Ying Zheng, Jie Wu, Yinghao Su, Fei Ye, Ping-Ping Bao, Hui Cai, Zhiguo Zhao, Wei Zheng, Wei Lu, Xiao-Ou Shu
Journal: Cancer Research (2014)

Abstract Background Triple negative breast cancer (TNBC) is an aggressive cancer with limited treatment options. A recent report suggested that dual specificity phosphatase 4 (DUSP4) may be a potential marker of chemotherapy resistance for TNBC. Methods We measured the DUSP4 gene expression levels in breast cancer tissue from 469 TNBC patients who participated in the Shanghai Breast Cancer Survival Study and evaluated their association with breast cancer recurrence/breast cancer mortality and total mortality. Study participants were diagnosed with incident breast cancer between March 2002 and April 2006 and aged between 20 and 75 years. Information on breast cancer diagnosis and treatment, as well as demographic, lifestyle, and disease progression information, were collected approximately 6 months after cancer diagnosis and reassessed at 18, 36, and 60 months after diagnosis in follow-up interviews. Expression levels of transcript variant 1 (NM_001394) and transcript variant 2 (NM_057158) of DUSP4 gene were measured by the NanoString nCounter assay using RNA obtained from formalin-fixed, paraffin-embedded tissue sections. Cox regression analysis was applied in the data analyses with adjustment for clinical and demographic factors. Results Of the 469 TNBC participants in this study, 100 deaths and 92 recurrences/breast cancer deaths were documented over a median follow-up of 5.3 years (range, 0.7-8.9 years). The expression of the two DUSP4 isoforms were highly correlated (r=0.76). Low DUSP4, particularly variant 1 (NM_001394), expression levels were associated with increased recurrence/breast cancer mortality and overall mortality. After adjustment for age at diagnosis and TNM stage, the hazard ratios comparing those with DUSP4 (variant 1) expression levels below the median to those above the median were 1.97 (95% confidence interval (CI): 1.27, 3.05) for recurrence/breast cancer mortality and 2.09 (95% CI: 1.38, 3.17) for overall mortality. Adjustment for expression levels of MKI67 and TP53, common treatment types, breast cancer subtype, or grade did not materially alter the observed association. Conclusion Low DUSP4 expression levels predict recurrence and mortality in TNBC patients independently from known clinical and molecular predictors. Citation Format: Michelle L. Baglia, Qiuyin Cai, Ying Zheng, Jie Wu, Yinghao Su, Fei Ye, Ping-Ping Bao, Hui Cai, Zhiguo Zhao, Wei Zheng, Wei Lu, Xiao-Ou Shu. Dual specificity phosphatase 4 gene expression in triple negative breast cancer. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3265. doi:10.1158/1538-7445.AM2014-3265
Doctors demand release of postmortem findings on David Kelly
Authors: C. Dyer
Journal: BMJ (2010)

Lawyers for six doctors seeking an inquest into the death of the weapons inspector David Kelly have written to the Ministry of Justice demanding to see the results of postmortem examinations of his body.

The move follows a decision by Lord Hutton, the senior judge who led the inquiry into Dr Kelly’s death, to lift a previously undisclosed 70 year ban he had imposed on release of the postmortem findings, pictures of the body and other medical evidence.

Dr Kelly was found dead near his Oxfordshire home …
Microangiopathic Hemolytic Anemia and the Development of the Malignant Phase of Hypertension
Authors: H. GAVRAS, W. C. B. BROWN, J. J. BROWN, A. F. LEVER, A. L. LINTON, R. F. MACADAM, G. P. MCNICOL, J. I. S. ROBERTSON, C. WARDROP
Journal: Circulation Research (1971)

Evidence of microangiopathic hemolytic anemia (MHA) was found in 14 of 22 patients with malignant phase hypertension, and in one of these, a patient with proliferative glomerulonephritis, MHA and m...
Governments needs to explore alternative to prohibitionist drug policies, says report
Authors: M. Sweet
Journal: BMJ (2012)

In Australia, two former federal health ministers who served in conservative governments, other senior public figures, and leading health experts have put their names to a new report calling for an end to prohibitionist drug policies.

The report was released this week by not for profit think tank Australia21. It arose out of a round table meeting held earlier this year in response to a 2011 statement by the Global Commission on drug policy urging all countries to revisit their drug policies in view of the failure of the “war on drugs.”

The report calls on governments to explore alternatives to prohibition and says: “By maintaining prohibition and suppressing or avoiding debate about its costs and benefits, it can be argued justifiably that our governments and other community leaders are standing idly by while our children …
Specialization in Health Care
Authors: Thomas Plochg, Niek S. Klazinga
Journal: JAMA (2012)

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