tbuckley/cabot-search huggingface dataset:
Repeat Bone Mineral Density Screening and Prediction of Hip and Major Osteoporotic Fracture
Authors: Sarah D. Berry, Elizabeth J. Samelson, Michael J. Pencina, Robert R. McLean, L. Adrienne Cupples, Kerry E. Broe, Douglas P. Kiel
Journal: JAMA (2013)

<h3>Importance</h3> Screening for osteoporosis with bone mineral density (BMD) is recommended for older adults. It is unclear whether repeating a BMD screening test improves fracture risk assessment. <h3>Objectives</h3> To determine whether changes in BMD after 4 years provide additional information on fracture risk beyond baseline BMD and to quantify the change in fracture risk classification after a second BMD measure. <h3>Design, Setting, and Participants</h3> Population-based cohort study involving 310 men and 492 women from the Framingham Osteoporosis Study with 2 measures of femoral neck BMD taken from 1987 through 1999. <h3>Main Outcomes and Measures</h3> Risk of hip or major osteoporotic fracture through 2009 or 12 years following the second BMD measure. <h3>Results</h3> Mean age was 74.8 years. The mean (SD) BMD change was −0.6% per year (1.8%). Throughout a median follow-up of 9.6 years, 76 participants experienced an incident hip fracture and 113 participants experienced a major osteoporotic fracture. Annual percent BMD change per SD decrease was associated with risk of hip fracture (hazard ratio [HR], 1.43 [95% CI, 1.16 to 1.78]) and major osteoporotic fracture (HR, 1.21 [95% CI, 1.01 to 1.45]) after adjusting for baseline BMD. At 10 years' follow-up, 1 SD decrease in annual percent BMD change compared with the mean BMD change was associated with 3.9 excess hip fractures per 100 persons. In receiver operating characteristic (ROC) curve analyses, the addition of BMD change to a model with baseline BMD did not meaningfully improve performance. The area under the curve (AUC) was 0.71 (95% CI, 0.65 to 0.78) for the baseline BMD model compared with 0.68 (95% CI, 0.62 to 0.75) for the BMD percent change model. Moreover, the addition of BMD change to a model with baseline BMD did not meaningfully improve performance (AUC, 0.72 [95% CI, 0.66 to 0.79]). Using the net reclassification index, a second BMD measure increased the proportion of participants reclassified as high risk of hip fracture by 3.9% (95% CI, −2.2% to 9.9%), whereas it decreased the proportion classified as low risk by −2.2% (95% CI, −4.5% to 0.1%). <h3>Conclusions and Relevance</h3> In untreated men and women of mean age 75 years, a second BMD measure after 4 years did not meaningfully improve the prediction of hip or major osteoporotic fracture. Repeating a BMD measure within 4 years to improve fracture risk stratification may not be necessary in adults this age untreated for osteoporosis.
Generation of transgenic mice using lentiviral vectors: a novel preclinical assessment of lentiviral vectors for gene therapy
Authors: Masahito Ikawa, Nobushige Tanaka, Winston W.-Y Kao, Inder M Verma
Journal: Molecular Therapy (2003)

Lentiviral vectors have become attractive delivery vehicles for gene therapy investigators. Specifically, the ability of lentiviral vectors to integrate into nondividing cells and provide stable and long-term gene expression in vivo is a desirable attribute of gene therapy approaches. We report here a simple method for generating transgenic mice using lentiviral vectors, which could be useful models for gene therapy. After removal of the zona pellucida, fertilized eggs were co-incubated with oncoretroviral or lentiviral vectors. The resulting blastocysts were transferred into uteri of pseudo-pregnant females. In both cases, around 60-70% of founder pups were transgenic as determined by PCR analysis. Southern blot analysis revealed that the transgenes were integrated at different genetic loci and transmitted through the germ line. Most of the transgenes delivered by lentiviral vectors were expressed in transgenic mice, although those delivered by oncoretroviral vectors were completely silenced. When the upstream sequences of the rhodopsin gene and the red pigment gene were used as tissue-specific promoters, consistent enhanced green fluorescent protein (EGFP) expression was observed in rod and cone photoreceptor cells, respectively, in retina. However, mice generated with the corneal epithelium-specific keratin-12 promoter displayed EGFP expression not only in cornea but also in other tissues of the mouse. We conclude that the generation of transgenic mice using lentiviral vectors is a simple and robust method to evaluate the promoter specificity in lentiviral vectors in vivo prior to undertaking a gene therapy strategy.
Epidemiology as a Guide to Clinical Decisions
Authors: Stephen B. Hulley, Ray H. Rosenman, Richard D. Bawol, Richard J. Brand
Journal: New England Journal of Medicine (1980)

The hypothesis that triglyceride is a cause of coronary heart disease, although unconfirmed and never universally accepted, has nonetheless strongly influenced the practice of preventive medicine. We have examined the epidemiologic association between triglyceride and coronary heart disease to evaluate the validity of inferring that there is a causal relation between the two. Neither the evidence from published studies nor an analysis of data from the Western Collaborative Group Study provides strong support for the causal hypothesis. Information from other scientific disciplines is also meager, contrasting with the coherence of diverse evidence supporting the hypothesis that cholesterol is a cause of coronary heart disease. These arguments fall short of disproving the belief that lowering triglyceride will prevent coronary heart disease, especially since triglyceride and cholesterol are inextricably associated through mutual lipoprotein carriers. But we propose that the ethics of preventive medicine place the burden of proof on the proponents of intervention. We therefore recommend that widespread screening and treatment of healthy persons for hypertriglyceridemia be abandoned until more persuasive evidence becomes available.
Are Lower Fasting Plasma Glucose Levels at Diagnosis of Type 2 Diabetes Associated With Improved Outcomes?
Authors: Stephen Colagiuri, Carole A. Cull, Rury R. Holman
Journal: Diabetes Care (2002)

OBJECTIVE—Type 2 diabetes may be present for several years before diagnosis, by which time many patients have already developed diabetic complications. Earlier detection and treatment may reduce this burden, but evidence to support this approach is lacking. RESEARCH DESIGN AND METHODS—Glycemic control and clinical and surrogate outcomes were compared for 5,088 of 5,102 U.K. Diabetes Prospective Study participants according to whether they had low (&amp;lt;140 mg/dl [&amp;lt;7.8 mmol/l]), intermediate (140 to &amp;lt;180 mg/dl [7.8 to &amp;lt;10.0 mmol/l]), or high (≥180 mg/dl [≥10 mmol/l]) fasting plasma glucose (FPG) levels at diagnosis. Individuals who presented with and without diabetic symptoms were also compared. RESULTS—Fewer people with FPG in the lowest category had retinopathy, abnormal biothesiometer measurements, or reported erectile dysfunction. The rate of increase in FPG and HbA1c during the study was identical in all three groups, although absolute differences persisted. Individuals in the low FPG group had a significantly reduced risk for each predefined clinical outcome except stroke, whereas those in the intermediate group had significantly reduced risk for each outcome except stroke and myocardial infarction. The low and intermediate FPG groups had a significantly reduced risk for progression of retinopathy, reduction in vibration sensory threshold, or development of microalbuminuria. CONCLUSIONS—People presenting with type 2 diabetes with lower initial glycemia who may be earlier in the course of their disease had fewer adverse clinical outcomes despite similar glycemic progression. Since most such people are asymptomatic at diagnosis, active case detection programs would be required to identify them.
Neural Tube Defects
Authors: Andrew Czeizel
Journal: JAMA (1988)

<h3>To the Editor.</h3> —The Jan 22/29 issue of<i>JAMA</i>contains a STATE OF THE ART/REVIEW about neural tube defects (NTD) by Dr Lemire.<sup>1</sup>This review presented some interesting ideas, eg, the separation of neurulation and postneurulation defects. However, I was surprised to read that "worldwide, an average prevalence of one case per 1000 births for both anencephaly and meningomyelocele exists, but France, Norway, Hungary, Czechoslovakia, Yugoslavia, and Japan have a low prevalence (0.1 to 0.6/1000 births)." In Hungary, epidemiologic studies provide valid and complete birth prevalences of different congenital anomalies. During the 1960s the birth prevalences per 1000 total births of anencephaly and meningomyelocele (spina bifida cystica) were 1.03 (isolated and multiple cases, 1.10) and 155 (1.63), respectively, while those of encephalocele and congenital hydrocephalus were 0.20 (0.22) and 0.57 (0.76), respectively.<sup>2</sup>The birth prevalences of neurulation defects, ie, anencephaly and spina bifida cystica, decreased to 0.9 and
Abstract 5009: The expression pattern of claudin-1, claudin-3, claudin-4, claudin-5 and claudin-7 in penile squamous cell carcinoma
Authors: Adriana Bulgarelli, Silvia V. Lourenço, Cláudia M. Coutinho-Camillo, Marcilei EC Buim, Maria Dirlei F.S. Begnami, Fernando A. Soares, José Vassallo
Journal: Cancer Research (2011)

Abstract Claudins are a family of proteins that are structural and functional components of tight junctions and have crucial roles in the maintenance of cellular arrangement, adhesion and paracellular transport. Recent studies have shown that changes and/or loss of claudin expression plays an important role in tumorigenesis and tumor progression, and altered expression of claudins has been reported in various human carcinomas. Penile squamous cell carcinoma (SCC) is a major health problem in Brazil, corresponding to 2,1% of all brazilian men tumors and 5-year survival rate drops dramatically in patients with lymph node metastasis. Purpose: The aim of this study was to investigate claudins expression profile in penile SCC. Method: We analyzed expressions of claudin-1, -3, -4, -5 and -7 in 14 cases of penile SCC by relative gene expression method using real time PCR. Results: The expression of claudin-1, -4 and -5 was downregulated 15.9-, 6.9- and 9.1-fold, respectively, in 72% of penile SCC cases in comparison to normal penile squamous cells (p=0.0052 for both claudin-1 and -4 and p=0.0002 for claudin-5). Claudin-3 expression was variable, with 7 of the 14 cases (50%) showing low expression of claudin-3. Claudin-7 was upregulated 101.4-fold in 10 of 14 cases analyzed (p=0.067). Conclusion: Our data suggests that loss of claudin-1,-4 and -5 expression and gain of claudin-7 expression might be associated with the tumorigenic process in penile SCC. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 5009. doi:10.1158/1538-7445.AM2011-5009
Clinical Control and Histopathologic Outcome of Asthma when Using Airway Hyperresponsiveness as an Additional Guide to Long-Term Treatment
Authors: JACOB K. SONT, LUUK N. A. WILLEMS, ELISABETH H. BEL, J.HAN J. M. van KRIEKEN, JAN P. VANDENBROUCKE, PETER J. STERK
Journal: American Journal of Respiratory and Critical Care Medicine (1999)

According to international guidelines, the level and adjustment of antiinflammatory treatment for asthma are based solely on symptoms and lung function. We investigated whether a treatment strategy aimed at reducing airway hyperresponsiveness (AHR strategy) in addition to the recommendations in the existing guidelines (reference strategy) led to: (1) more effective control of asthma; and (2) greater improvement of chronic airways inflammation. To accomplish this, we conducted a randomized, prospective, parallel trial involving 75 adults with mild to moderate asthma who visited a clinic every 3 mo for 2 yr. At each visit, FEV1 and AHR to methacholine were assessed, and subjects kept diaries of symptoms, β2-agonist use, and peak expiratory flow (PEF). Medication with corticosteroids (four levels) was adjusted according to a stepwise approach (reference strategy), to which four severity classes of AHR were added (AHR strategy). At entry and after 2 yr, bronchial biopsies were obtained by fiberoptic bronchoscopy. Patients treated according to the AHR strategy had a 1.8-fold lower rate of mild exacerbations than did patients in the reference strategy group (0.23 and 0.43 exacerbation/yr/patient, respectively). FEV1 also improved to a significantly greater extent in the AHR strategy group (p ⩽ 0.05). In bronchial biopsies this was accompanied by a greater reduction in thickness of the subepithelial reticular layer in the AHR strategy group than in the reference strategy group (mean difference [95% confidence interval (CI): 1.7 μ m (0.2 to 3.1) μ m]). The changes in AHR in both strategy groups were correlated with eosinophil counts in the biopsies (r = − 0.48, p = 0.003). We conclude that reducing AHR in conjunction with optimizing symptoms and lung function leads to more effective control of asthma while alleviating chronic airways inflammation. This implies a role for the monitoring of AHR or other surrogate markers of inflammation in the long-term management of asthma.
Biomarker-based strategy for screening right ventricular dysfunction in patients with non-massive pulmonary embolism
Authors: Damien Logeart, Lucien Lecuyer, Gabriel Thabut, Jean-Yves Tabet, Jean-Michel Tartière, Christophe Chavelas, François Bonnin, Jean-Louis Stievenart, Alain Cohen Solal
Journal: Intensive Care Medicine (2006)
Modulation of monocyte activation in patients with rheumatoid arthritis by leukapheresis therapy.
Authors: G Hahn, B Stuhlmüller, N Hain, J R Kalden, K Pfizenmaier, G R Burmester
Journal: Journal of Clinical Investigation (1993)

One of the hallmarks in rheumatoid arthritis (RA) is the intense activation of the monocyte-macrophage system. In the present investigation, the modulation of blood monocyte activation was studied with regard to the secretion of cytokines and inflammatory mediators, and to the expression of cytokine receptors. Patients with severe active RA underwent repeated leukapheresis procedures that removed all circulating monocytes. Highly enriched monocyte preparations from the first and third leukapheresis were studied. There were striking differences between the two monocyte populations. Cells obtained from the first leukapheresis constitutively released large amounts of prostaglandin E2 (PGE2), neopterin, interleukin 1 beta (IL-1 beta) and tumor necrosis factor-alpha (TNF-alpha). In particular, IL-1 beta and neopterin production were further enhanced by stimulation with either interferon-gamma (IFN-gamma) or TNF-alpha without a synergistic effect. In contrast, cells derived from the third leukapheresis procedure showed a close to normal activation status with only low levels of cytokine and mediator production as well as a reduced response to cytokine stimulation. The number of the receptors for IFN-gamma and TNF-alpha was not changed between first and third leukapheresis. However, TNF-binding capacity was only detectable upon acid treatment of freshly isolated monocytes. A further upregulation was noted upon 24 h in vitro culture, suggesting occupation of membrane receptors and receptor down-regulation by endogenously produced TNF-alpha. Northern blot analysis of cytokine gene expression was in good correlation with the amount of mediators determined on the protein level. These data indicate that cells of the monocyte-macrophage system are already highly activated in the peripheral blood in RA patients with active disease. These cells can be efficiently removed by repeated leukapheresis and are replenished by monocytes that have, with respect to cytokine and mediator production, a considerably lower activation status.
Exercise Capacity Predicts Health Status in α<sub>1</sub>-Antitrypsin Deficiency
Authors: LEE J. DOWSON, CLARE NEWALL, PETER J. GUEST, SUSAN L. HILL, ROBERT A. STOCKLEY
Journal: American Journal of Respiratory and Critical Care Medicine (2001)

Resting lung function is only weakly related to health status in chronic obstructive pulmonary disease, reflecting the multifactorial causes of impairment and the heterogeneous nature of the condition. The current study examined whether density mask analysis of high-resolution computed tomography (HRCT) or exercise capacity were better surrogates for health status in a well-defined, homogeneous group of patients with α1-antitrypsin deficiency (PiZ). Twenty-nine patients with predominantly lower zone emphysema on HRCT were studied. Exercise was assessed by incremental treadmill (V˙ o 2 peak) and shuttle walking tests (ISWT) and health status by the St. George's Respiratory Questionnaire (SGRQ) and SF-36. Although lower zone expiratory HRCT was related to exercise capacity (rho = − 0.64 and − 0.63 for V˙ o 2 peak and ISWT, respectively, p < 0.001), multiple regression analysis suggested that FEV1 was a marginally better predictor (rho = − 0.64 and − 0.65, p < 0.001). HRCT also related significantly to health status (rho = − 0.37 for SGRQ activity, p < 0.05), although again FEV1 showed a stronger relationship (rho = − 0.43, p = 0.01). However, exercise capacity was the best predictor of health status with the ISWT accounting for up to 55% of the variability seen in SGRQ total and up to 53% of the SF-36 domain scores (physical functioning). Although both HRCT and lung function relate to health status, exercise capacity is the best predictor of patients disability in these patients with predominantly lower zone emphysema.
Case 50-1978
Authors: David J. Kanarek, Eugene J. Mark
Journal: New England Journal of Medicine (1978)

Presentation of CaseA 72-year-old woman was admitted to the hospital because of cough and fever.She was well until 7 1/2 years earlier, when fever, chills and pleurisy developed. An x-ray film of the chest (Fig. 1) revealed segmental consolidation in the posterior basal segment of the right lower lobe. The patient improved on antibiotic treatment. A repeated x-ray film of the chest showed partial clearing, with a residual atelectatic density. One year later she returned to the hospital because of fever, with cough and sputum production. X-ray films of the chest disclosed recurrent consolidation of the posterior basal . . .
Platelet activating factor and Crohn's disease.
Authors: Y Denizot, S Chaussade
Journal: Gut (1994)

EDITOR,-We are glad that Dr Jolobe agreed with the importance of considering coeliac disease in patients with iron deficiency anaemia, even when symptomatology is atypical.The precaution of taking endoscopic biopsy specimens prevents oversight of the diagnosis.We also note his comment on the abnormal appearance of duodenal folds in coeliac disease.We indeed routinely comment on such abnormalities having previously pub- lished evidence' supporting the data of Brocchi et al.'
Aqueous solubilisation of vitamin D3 in normal man.
Authors: M Rautureau, J C Rambaud
Journal: Gut (1981)

Jejunal aqueous solubilisation of vitamin D3 was assessed in eight normal subjects, after ingestion of a standard liquid test meal. Percentages and total concentrations of vitamin D3 in the aqueous phase were significantly higher in the first post-prandial 30 minutes than during the following two hours, as were bile salts, total lipids, and free fatty acids. As shown by partial correlation analysis, a statistically significant relationship was found between aqueous concentrations of free fatty acids and of vitamin D3 in the jejunal content during all the 2 1/2 hours of the study. From these data it is concluded that, in healthy man, vitamin D3 is solubilised in vivo in mixed micelles only, and is governed in the aqueous phase.
Public health messages that invoke disgust work best for men, study finds
Authors: Z. Kmietowicz
Journal: BMJ (2009)

When it comes to communicating the dangers of faeces men are most likely to take notice of messages that invoke disgust, but women respond best to notices that impart knowledge, a study has found ( American Journal of Public Health 2009;99(suppl):S405-11, doi:10.2105/AJPH.2009.164160).

Researchers from the London School of Hygiene and Tropical Medicine in London tested the impact of different messages on handwashing with soap that were flashed on to screens at the entrance to toilets at UK service station. Sensors were used to monitor the use of soap by 200 000 people who used the facilities.

Several messages were tested, ranging from “Water doesn’t kill germs, soap does” …
The Handbook of Residential Care
Authors: N Baldwin
Journal: BMJ (1994)

John Burton Routledge, £12.99, pp 201 ISBN 0-415-08636-1

The wisdom of experience is the essence of this book. It conveys the living, feeling experience of being cared for and of trying to care in residential settings.

John Burton demystifies some of the current fashions in the management of caring services:

By elevating the planning, contracting and bidding process to the highest form of managerial ritual, government has diverted the energy of social organisations away from service.

The whole person can easily be lost sight of in the manipulation of targeted …
552 Primary biliary cirrhosis (PBC) specific antinuclear antibodies (ANA) have prognostic value and a distinct immunoglobulin isotype profile
Authors: E.I. Rigopoulou, E.T. Davies, D.P. Bogdanos, G. Koukoulis, G.N. Dalekos, D. Vergani
Journal: Journal of Hepatology (2004)
Intestinal Polyposis associated with Pigmentation and Intussusception in Triplets
Authors: W. P. Crone, A. L. Light
Journal: BMJ (1954)

At laparotomy on May 30, 1949, an ileo-ileal intus- susception was reduced; no resection.On April 20, 1950, laparotomy revealed an irreducible ileo-ileal intussuscep- tion; 12 in.(30 cm.) of ileum was resected.In November, 1950, and January and July, 1951, he was admitted with intestinal obstruction and intussusceptions were palpated, but spontaneous reduction occurred shortly after admission.He often suffers from both mild and severe attacks of colic, but so far has required no further admission to hospital.CASE 2 A boy aged 12 attended in February, 1951, with a rectal polyp.He had had an operation for intussusception in 1939.There was no relevant family history.He was a sallow child with typical pigmentation of the lips and oral mucosa.A polyp was removed from the rectum.Barium enema and sigmoidoscopy revealed no further polyps at that time.A second polyp was removed in July 1951, and in May, 1952, examination revealed a third rectal polyp and mass in the ascending colon.An exploratory laparotomy on July 9, 1952, revealed a polyp in the jejunum, 12 in.(30 cm.) from the duodeno- jejunal flexure, a polypoid mass in the caecum, a polyp in the appendix, a polypoid mass in the descending colon, where a chronic intussusception was present, and a polyp in the sigmoid colon; the mucosa of tbp terminal ileum was nodular, but no true polyps were present.Resection of 6 in.(15 cm.) of upper jejunum and total colectomy, ana- stomosing the lower ileum to the rectum, were carried out.The pathological report stated " benign adenomatous polyps."Post-operative progress was complicated in October, 1952, by intestinal obstruction due to adhesions, which were divided.No further polyps have developed in the 4 in.(10 cm.) of rectum remaining.I wish to thank Mr. Ridley Thomas and Mr.
Mechanisms of ectopic bone formation by human osteoprogenitor cells on CaP biomaterial carriers
Authors: Yoke Chin Chai, Scott J. Roberts, Eline Desmet, Greet Kerckhofs, Nick van Gastel, Liesbet Geris, Geert Carmeliet, Jan Schrooten, Frank P. Luyten
Journal: Biomaterials (2012)