tbuckley/cabot-search huggingface dataset:
CCN6 Modulates BMP Signaling via the Smad-Independent TAK1/p38 Pathway, Acting to Suppress Metastasis of Breast Cancer
Authors: Anupama Pal, Wei Huang, Xin Li, Kathy A. Toy, Zaneta Nikolovska-Coleska, Celina G. Kleer
Journal: Cancer Research (2012)

CCN6 (WISP3) is an extracellular matrix protein that exerts tumor suppressive functions in breast cancer, where its decreased expression is a feature of advanced disease. However, neither its role nor mechanism of action in breast cancer metastasis has been established. Bone morphogenetic proteins (BMPs), which constitute ligands of the TGF-β superfamily, are multifunctional cytokines that induce epithelial-mesenchymal transition, cell invasion, and metastasis. In this study, we identify a CCN6-BMP4-TAK1 kinase signaling pathway that controls the ability of the p38 MAP kinase to regulate acinar morphogenesis and invasion of breast cells. ShRNA-mediated attenuation of CCN6 in human mammary epithelial cells led to BMP4 upregulation as a major response to exposure to the TGF-β superfamily. CCN6 attenuation also induced BMP4-mediated activation of the Smad-independent TAK1 and p38 kinases. Conversely, ectopic expression of CCN6 in breast cancer cells antagonized BMP4-mediated TAK1/p38 activation and invasive capacity, both by binding BMP4 protein as well as decreasing BMP4 protein levels. Effects on BMP4 and p38 were confirmed in vivo where they correlated with decreased metastasis. In clinical specimens, we found that CCN6 expression was inversely associated with BMP4 and phospho-p38 levels in 69% of invasive breast carcinomas examined, consistent with the functional results. Together our findings identify a novel modifier pathway through which CCN6 acts to limit breast cancer invasion and metastasis.
Dust to Dust: A Doctor's View of Famine in Africa
Authors: T. Keith Edwards
Journal: JAMA (1992)

An African proverb says that, when God finished creating the world, he was pleased with everything in it except the baobab tree. He yanked the tree out of the ground, turned it upside down, and jammed it back into the earth, so that only the dry roots can be seen. In<i>Dust to Dust</i>David Heiden depicts his experience as a relief physician in the Sudan with refugees from the Ethiopian famine of 1985. It brought back a flood of memories of my time in Africa. Dr Heiden's photographs and word pictures show humanity yanked up by its roots and displayed as starving grotesque figures. We see a dry, dusty, desolate world where life and death are juxtaposed. We are treated to the pathos of famine relief, not simply through the camera's eye but through the sensitive and caring eyes of a handful of American relief workers. One of the
The Clinical Management of Hysteria
Authors: George E. Murphy
Journal: JAMA (1982)

Hysteria, as classically defined (before Freud), is a chronic polysymptomatic illness chiefly affecting women. A dramatic and complicated medical history is the rule. Although the etiology of this condition remains unclear, its implications for physicians are different from those of other illnesses. Clinical management is generally difficult and often unsatisfactory. As with other diseases, diagnosis precedes and directs treatment. This article discusses the basis on which a reliable diagnosis of hysteria can be made, and offers guidelines for conservative management, based on the clinical literature and the author's experience.
Nancy Clark's sports nutrition guidebook.: 2nd ed. N Clark. (Pp 455; pound12.92.) Leeds: Human Kinetics Europe Ltd, 1997. ISBN 0-87322-730-1
Authors: Helen M Isaacs
Journal: British Journal of Sports Medicine (2000)

Bone density in elderly womenEDITOR,-In the article by Rhodes et al 1 "EVects of one year of resistance training on the relation between muscular strength and bone density in elderly women", I was surprised to see no mention of HRT status in the women in the trial.Given the relatively small number of women taking part, surely this is quite an important variable?
Role of Tc-99m Pertechnetate for Remnant Scintigraphy Post-Thyroidectomy
Authors: Sherman S. H. Kueh, Paul J. Roach, Geoffrey P. Schembri
Journal: Clinical Nuclear Medicine (2010)

Current surgical techniques in patients with differentiated thyroid cancer can leave little or no remnant tissue. Coupled with favorable prognostic factors, this subgroup of patients might not require radioablative remnant ablation with Iodine-131 (I-131). Postoperative scanning may help to identify this subgroup, however low dose I-131 can lead to stunning and suboptimal response to ablative therapy. Iodine-123 (I-123) can be used but is expensive and supply can be limited. We investigate technetium-99m pertechnetate (pertechnetate) as a potential alternative for remnant scintigraphy post-thyroidectomy.Seventy consecutive post-total-thyroidectomy patients were evaluated retrospectively. Preablative pertechnetate scans of the thyroid bed were viewed blindly then directly compared with postablative I-131 scans.For patients with unequivocally positive pertechnetate uptake, the sensitivity was 81% (patients), 61% (sites), and the PPV was high (100% patients, 95% sites). In patients with either definite or equivocal pertechnetate uptake, the sensitivity was 90% (patients), 68% (sites), and the PPV was also high (100% patients, 81% sites).Pertechnetate had reasonable correlation with postablative I-131 scans with a moderately high sensitivity and a very high PPV. A positive pertechnetate scan is therefore sufficient to guide progression to I-131 ablation in most patients. When the scan is equivocal or negative, diagnostic imaging with radioiodine may be required. Pertechnetate scintigraphy may be of particular benefit if it is considered desirable to avoid I-131 in post-thyroidectomy remnant imaging.
Designated Areas Allowance
Authors: J. M. Bevan, J. R. Butler, R. C. Taylor
Journal: BMJ (1970)

Cardiac Failure and Folate Deficiency SIR,-Your interesting leading article on cardiac failure and folate deficiency (24 January, p. 188) commented on the possible causes of this association, and factors like impaired dietary intake and gastrointestinal malabsorption were mentioned.A contributory cause could well be excessive folate loss in the urine.Urinary folate excretion has been poorly studied, but we recently re- ported an unexpected increase of urinary folate in association with congestive cardiac failure.'As much as 61 6,tg.folate was lost per day, while normal controls excreted 0-1-18-0,ug.folate per day.Urinary folate loss is unlikely to be the sole cause of folate deficiency in these patients, but could well be an important contributory factor in a patient with pro- longed anorexia.One could speculate that excessive urinary folate results from ab- normal folate liberation secondary to the liver damage of chronic congestive failure.Urinary folate excretion is increased in cirrhosis and acute hepatitis' and also after surgical trauma.2-Iam, etc.,
Effect of cyclic 3',5'-AMP on the (Na + K)-ATPase of myocardial sarcolemma
Authors: C. J. LIMAS, A. V. NOTARGIACOMO, J. N. COHN
Journal: Cardiovascular Research (1973)

A dose-related inhibition of the (Na+K)-ATPase of canine heart sarcolemma was found in the presence of cyclic 3', 5'-AMP (maximal inhibition at 10 -4 M cyclic AMP), while 5'-AMP did not affect the enzyme. A similar inhibition of the ATPase was seen after incubation of the sarcolemma preparation with NaF adrenaline and theophylline. None of these substances affected the activity of the Ca++-stimulated ATPase.
The Association Between a Family History of Type 2 Diabetes and Coronary Artery Disease in a Type 1 Diabetes Population
Authors: John R Erbey, Lewis H Kuller, Dorothy J Becker, Trevor J Orchard
Journal: Diabetes Care (1998)

OBJECTIVE To examine whether a potential marker for type 2 diabetes (family history) is related to CAD in type 1 diabetic subjects. The two major types of primary diabetes, type 1 and type 2, are both associated with an increased risk of developing coronary artery disease (CAD). However, the etiology and associated risk factors may differ by type of diabetes. In type 2 diabetes, CAD is likely to be linked with the insulin resistance associated with the type 2 “process,” while CAD in type 1 diabetes has, so far, been more closely linked to renal disease. Because the etiologies of type 1 and type 2 diabetes are different, it is possible that some CAD in type 1 diabetes may be related to the coexistence of type 2 diabetes susceptibility (i.e., insulin resistance). RESEARCH DESIGN AND METHODS We evaluated the interrelationships between family history of type 2 diabetes (age at onset &amp;gt;30 years, no insulin for 1st year) and presence of CAD in a cohort of childhood-onset type 1 diabetic subjects using the Pittsburgh Epidemiology of Diabetes Complications study (n = 658). RESULTS A first-degree family history of type 2 diabetes was reported in 112 subjects, and CAD was present in 119 subjects. Those subjects reporting a family history of type 2 diabetes were significantly older, had a longer duration of type 1 diabetes, had higher triglyceride and LDL cholesterol levels, and had a borderline significantly increased Beck depression inventory. Sex differences in CAD risk factors were also noted. Using logistic regression analysis, the odds ratio (95% CI) for the presence of CAD in association with a family history of NIDDM was 1.89 (1.27–2.84). The odds ratio (95% CI) after adjusting for disease duration, triglycerides, hypertension, Beck depression, and nephropathy status was 1.45 (0.87–2.28). CONCLUSIONS We conclude that a family history of type 2 diabetes is a risk factor for CAD in type 1 diabetic subjects. This supports the concept that insulin resistance may contribute to development of CAD in type 1 diabetes.
Mozart ear and Mozart death.
Authors: L Karhausen
Journal: BMJ (1987)

not stated, but when asked if this might have been due to unrelieved aortic stenosis they declined to comment.In addition, and as in the present report, most patients had significant residual aortic stenosis.Clearly these results are not as good as those which can be expected with current surgical techniques.The presenter of the French experience then went on to claim that he had not referred a patient for surgery for over a year.The mortality for this group, and the functional results, were not available.This widening indication for valvuloplasty in the absence ofverifiable data and in the light of published surgical results over many years concerns us.As a caveat we would like to point out from our own intraoperative studies that if this technique is to be used a balloon inflation time of one minute is not necessary, and is probably dangerous.4Prolonged obstruction to ventricular outflow must result in further dilatation of an already over- stretched myocardium.It has been known for many years that this may cause irreversible damage.Several of the reported deaths with this technique appear to have been due to this mechanism.We found that an initial inflation time of 15 seconds was sufficient to open the valve orifice by a measurable amount.Further short periods of inflation could then be used.This problem may in part be avoided by the use oftrefoil shaped balloons.We are anxious to join with Dr Jackson and coUeagues to counsel against the uncontrolled and unrestricted spread of this procedure to the detri- ment of patients with aortic stenosis in Britain.
EXTRA-SCIENTIFIC INFLUENCES IN THE HISTORY OF CHILDHOOD PSYCHOPATHOLOGY
Authors: M. B. MACMILLAN
Journal: American Journal of Psychiatry (1960)

This paper attempts to account for the peculiarities in the development of 19th century knowledge of the psychotic child in terms of both scientific and extra-scientific factors. It is argued that extra-scientific factors determined the early interest in the defective child with whom the psychotic child was first classed. A combination of both scientific and extra-scientific factors is claimed to account for the almost complete lack of interest in the problem in the second half of the century. An attempt is also made to account for the differences between the views of Griesinger and Maudsley.
Jeffrey Joseph Cream
Authors: Chris Bunker
Journal: BMJ (2008)

<h3>Abstract</h3> <h3>Background</h3> People with multimorbidity have reduced functional capacity, lower quality of life, and higher mortality rates and use healthcare resources more intensively than healthy people or those with a single chronic condition. The aim of this study was to explore associations between multimorbidity and use of healthcare services and the impact of socioeconomic status on utilization of hospitalizations and bed days. <h3>Methods</h3> The study population included all individuals aged 16 years and older who lived in the Capital Region of Denmark on January 1st, 2012. Data on chronic conditions, use of healthcare services and demographics were obtained from Danish national administrative and health registries. Zero-inflated models were used to calculate anticipated annual use of hospitalizations and bed days. <h3>Findings</h3> The study population comprised 1,397,173 individuals; the prevalence of multimorbidity was 22%. Prevalence was inversely related to educational attainment. For people with multimorbidity, utilization of hospitalizations and bed days increased approximately linearly with the number of chronic conditions. However, a steep increase in utilization of bed days was observed between five and six or more chronic conditions. An educational gradient in hospitalization rates and use of bed days was observed regardless of the number of chronic conditions. Educational attainment was strongly associated with healthcare utilization. <h3>Conclusion</h3> Multimorbidity was associated with a significant increase in utilization of all healthcare services in Denmark. In addition, a socioeconomic gradient was observed in utilization of hospitalizations and bed days.
THYMUS CELL MIGRATION
Authors: Irving L. Weissman
Journal: The Journal of Experimental Medicine (1967)

The preceding studies have established the following points: Intrathymic labeling of thymic lymphocytes provides an adequate marker system to detect the migration of thymus cells to peripheral lymphoid sites. In the newborn, this comprises a major portion of the total lymphocyte population in lymph nodes and spleen. In the adult, this migration is limited to specific portions of lymph nodes and spleen, i.e., those portions which serve the recirculating pool of small lymphocytes. Kinetic studies of labeling within the adult thymus indicate that large cells give rise to medium and small cells, which then migrate to the specific sites noted above. In the newborn, the kinetic pattern is similar to that of adults, with the single distinction that large cells also migrate, accelerating the tempo of migration in these hosts. The long-term fate and function of thymus cell migrants has not yet been determined.
Ectopic pregnancy and miscarriage: summary of NICE guidance
Authors: E. Newbatt, Z. Beckles, R. Ullman, M. A. Lumsden
Journal: BMJ (2012)

Many women will experience complications in early pregnancy. The loss of a pregnancy can cause considerable emotional distress for women and their families, as well as physical morbidity that results in over 50 000 inpatient admissions in the UK annually.1 The mortality associated with ectopic pregnancy is decreasing but remains at an estimated 0.2 per 1000 ectopic pregnancies. Of the women who died during 2006–08, half were from minority ethnic groups—and so may have accessed care later or experienced difficulty in communication—and most deaths were associated with substandard care due to failure to consider ectopic pregnancy when presentation was atypical.2 Therefore, it is vital that healthcare professionals in all specialties are alert to the possibility of ectopic pregnancy in order to avoid missed opportunities for diagnosis. This article summarises the most recent recommendations from the National Institute for Health and Clinical Excellence (NICE) on the care for women with ectopic pregnancy and miscarriage.3 NICE recommendations are based on systematic reviews of the best available evidence and explicit consideration of cost effectiveness. When minimal evidence is available, recommendations are based on the Guideline Development Group's experience and opinion of what constitutes good practice. Evidence levels for the recommendations are given in italics in square brackets. ### Support and information giving
Healthy pregnant women still don't need routine iron supplementation
Authors: P. J. Steer
Journal: BMJ (2013)

It seems odd that Krafft’s associated editorial adopts such a celebratory tone. He says that many years have been spent “looking for better evidence favouring iron supplementation in pregnancy”1 but does not consider the possibility that the failure of so many studies to find a significant advantage might mean that the value is marginal.

Despite the large number …
Infections Due to Beta-Lactamase-producing, High-Level Gentamicin-resistant <i>Enterococcus faecalis</i>
Authors: Virginia D. Wells, Edward S. Wong, Barbara E. Murray, Philip E. Coudron, Denise S. Williams, Sheldon M. Markowitz
Journal: Annals of Internal Medicine (1992)

To investigate the risk factors, clinical features, molecular epidemiology, and treatment outcomes associated with an outbreak of infections due to beta-lactamase-producing, high-level gentamicin-resistant Enterococcus faecalis.Case-control and molecular genetics study.Tertiary care Veterans Affairs hospital.Sixty-five patients infected or colonized with beta-lactamase-producing high-level gentamicin-resistant E. faecalis (case patients) were matched and compared with 65 randomly selected patients infected or colonized with beta-lactamase-negative, gentamicin-susceptible E. faecalis.During the 20-month study period, 124 of 1506 isolates (8.2%) of E. faecalis from 70 patients were found to produce beta-lactamase. Univariate analysis showed older age, higher APACHE II score, nosocomial acquisition, recent surgical procedure, total parenteral nutrition, and antibiotic treatment to be significantly associated with the acquisition of beta-lactamase-producing, high-level gentamicin-resistant E. faecalis. A multivariate analysis, done using stepwise multiple logistic regressions, showed that only two variables remained significant: an APACHE II score greater than 6 (odds ratio, 9.5; 95% CI, 4.4 to 20.3) and antibiotic treatment (odds ratio, 10.2; CI, 4.5 to 23.2). The mortality rate for case patients was 7.7% (5 of 65 patients; CI, 1.2% to 14.2%); no control patient died. Of 23 infections occurring in case patients, 13 were treated with "inappropriate" antibiotics (regimens that included a beta-lactamase-unstable antibiotic); 2 patients improved and 11 had complete resolution of disease. "Appropriate" treatments (regimens that included a beta-lactamase-stable antibiotic) were used in 10 patients; 5 of 10 infections were fatal. Restriction enzyme digests of total chromosomal DNA showed nearly identical patterns for selected isolates of beta-lactamase-producing, high-level gentamicin-resistant E. faecalis, suggesting dissemination through the hospital of a single strain of E. faecalis.Fatal infections were observed despite treatment with beta-lactamase-stable antibiotics. The risk for infection or colonization with beta-lactamase-producing, high-level gentamicin-resistant E. faecalis was strongly associated with severe underlying disease (acute physiology and chronic health evaluation [APACHE] II score, greater than 6) and previous antibiotic treatment. These results may be useful in targeting high-risk patients for infection-control interventions.
Surgery in Adults With Congenital Heart Disease
Authors: A.C. Zomer, C.L. Verheugt, I. Vaartjes, C.S.P.M. Uiterwaal, M.M. Langemeijer, D.R. Koolbergen, M.G. Hazekamp, J.P. van Melle, T.C. Konings, L. Bellersen, D.E. Grobbee, B.J.M. Mulder
Journal: Circulation (2011)

Background— A significant proportion of patients with congenital heart disease require surgery in adulthood. We aimed to give an overview of the prevalence, distribution, and outcome of cardiovascular surgery for congenital heart disease. We specifically questioned whether the effects of surgical treatment on subsequent long-term survival depend on sex. Methods and Results— From the Dutch Congenital Corvitia (CONCOR) registry for adults with congenital heart disease, we identified 10 300 patients; their median age was 33.1 years. Logistic and Cox regression models were used to assess the association of surgery in adulthood with sex and with long-term survival. In total, 2015 patients (20%) underwent surgery for congenital heart disease in adulthood during a median follow-up period of 15.1 years; in 812 patients (40%), it was a reoperation. Overall, both first operations and reoperations in adulthood were performed significantly more often in men compared with women (adjusted odds ratio=1.4 [95% confidence interval, 1.2–1.6] and 1.2 [95% confidence interval, 1.0–1.4], respectively). Patients with their third and fourth or more surgery in adulthood had a 2- and 3-times-higher risk of death compared with patients never operated on (adjusted hazard ratio=1.9 [95% confidence interval, 1.0–3.6] and 2.7 [95% confidence interval, 1.1–6.3], respectively). Men with a reoperation in adulthood had a 2-times-higher risk of death than women (adjusted hazard ratio=1.9; 95% confidence interval, 1.0–3.5). Conclusions— Of predominantly young adults with congenital heart disease, one fifth required cardiovascular surgery during a 15-year period; in 40%, the surgery was a reoperation. Men with congenital heart disease have a higher chance of undergoing surgery in adulthood and have a consistently worse long-term survival after reoperations in adulthood compared with women.
Family Medicine: The Need for Research
Authors: Robert E. Rakel
Journal: JAMA (1983)

In this issue ofThe Journal(p 63), Culpepper and Franks have succinctly identified the problems facing research in family medicine in its second decade. Although the federal government has recognized the need for improved primary care, such improvement cannot occur without an equivalent emphasis on research to develop new knowledge and improved skills in this area. Unfortunately, this need occurs at a time when the federal government is reducing its commitment to research and is unlikely to shunt remaining funds away from other areas. If primary care is to be the base for an efficient health care system, however, adequate resources must be devoted to improving the knowledge and developing the skills to do this well. Residency training has improved the quality of care provided by family physicians. We now need to pursue vigorously the expansion of knowledge in family medicine. Federal research funds have traditionally gone to academic
A double-blind study of Grenz ray therapy in chronic eczema of the hands
Authors: B. LINDELOF, K. WRANGSJO, S. LIDEN
Journal: British Journal of Dermatology (1987)

The effect of Grenz ray therapy as an adjunct to topical therapy in chronic symmetrical eczema of the hands was assessed in 24 patients by randomly allocating active treatment to one hand while the other, which received simulated therapy, served as a control. Three Gy of Grenz rays were applied on six occasions at intervals of I week. There was a significantly better response to active treatment 5 and 10 weeks after the start of treatment compared with the untreated control.
Can Medicine and the Sciences Be Unified?
Authors: William R. Barclay
Journal: JAMA (1977)

Irvine Page, MD, has made a strong and convincing plea for ecumenism in medicine and science.<sup>1</sup>He has voiced a concern that most physicians share: that government control of medicine and science will lead to a decline in the quality and the slowing of the progress in these fields of endeavor. Page declares that if the scientific community will unite, will not permit petty self-interests to divide it, and will speak with one voice, then it can deal with the political pressures that now are eroding away its power base and self-determination. Unfortunately each field of science seems to have its own