tbuckley/cabot-search huggingface dataset:
The Diagnosis and Prognosis of Autosomal Dominant Polycystic Kidney Disease
Authors: Patrick S. Parfrey, John C. Bear, Janet Morgan, Benvon C. Cramer, Patrick J. McManamon, Mathew H. Gault, David N. Churchill, Manoj Singh, Richard Hewitt, Stefan Somlo, Stephen T. Reeders
Journal: New England Journal of Medicine (1990)

Autosomal dominant polycystic kidney disease is usually caused by a mutant gene at the PKD1 locus on the short arm of chromosome 16, but in about 4 percent of families with the disorder it is caused by unknown mutations elsewhere in the genome. The natural course of the disease in both genetic forms is not well characterized.We studied 17 families with autosomal dominant polycystic kidney disease to compare presymptomatic diagnosis by ultrasonography with diagnosis by genetic-linkage studies and to relate clinical variation of the disease to whether the PKD1 mutation was implicated.In 10 families the disorder was found to cosegregate with polymorphic DNA markers flanking the PKD1 locus, in 2 families it did not, and in 5 families linkage could not be determined. In the 10 families with the PKD1 mutation, 46 percent of the members less than 30 years old who had a 50 percent risk of inheriting a mutation had renal cysts, as compared with 11 percent of the members of the two families without linkage (P less than 0.001). In the PKD1 families, all 67 diagnoses made by ultrasonography were confirmed by determination of the genotype as inferred from linkage. Forty of 48 members (83 percent) less than 30 years old who inherited the PKD1 mutation had renal cysts. All 27 members 30 years old or older who inherited the mutation had renal cysts, suggesting that the probability of a false negative diagnosis did not exceed 0.13 in this age group (P less than 0.05). The mean (+/- SE) age at the onset of end-stage renal disease among members of the PKD1 families was 56.7 +/- 1.9 years, as compared with 69.4 +/- 1.7 years among members with cysts in the families without linkage (P = 0.0025). Hypertension and renal impairment were less frequent and occurred later in the families without the PKD1 mutation.At present, in most persons with a 50 percent risk of autosomal dominant polycystic kidney disease, imaging techniques are the only mode of reaching a diagnosis before symptoms appear. In such persons a negative ultrasonographic study during early adult life indicates that the likelihood of inheriting a PKD1 mutation is small. In the few who inherit a non-PKD1 mutation for polycystic kidney disease, renal failure is likely to occur relatively late in life.
Recession has not affected access to prescription drugs in US
Authors: B. Roehr
Journal: BMJ (2011)

The economic recession has had no effect on the ability of US citizens to access prescription drugs, show the results of a new survey from the independent Center for Studying Health System Change in Washington, DC.

Health insurance in the United States is generally provided through the workplace. As the number of uninsured persons has soared by more than 20%, from 42.7 million in 2007 to 51.7 million in 2010, the assumption has been that the proportion of people having difficulty paying for prescription drugs would rise. However, this does not seem to have …
Site of principal metabolic defect in idiopathic haemochromatosis: insights from transplantation of an affected organ.
Authors: P L Dabkowski, P W Angus, R A Smallwood, J Ireton, R M Jones
Journal: BMJ (1993)

Idiopathic haemochromatosis is an inherited defect of iron metabolism characterised by excessive iron absorption and deposition in the tissues leading to damage in the liver and other organs.' The nature of the fundamental metabolic abnormality remains unknown, but the liver and the gut have both been proposed as the principal site of expression of the metabolic defect.' We recently had the opportunity to study this question when a liver was transplanted from a donor who subsequently proved to have had presymptomatic idiopathic haemochromatosis into a young woman with normal iron metabolism. We describe here the changes in iron status observed in our patient in the first 29 months after liver transplantation.
Intrauterine Devices-Reply
Authors: Robin Miller-Catchpole
Journal: JAMA (1990)

In Reply.—  Both Drs Mishell and Alvarez-Sanchez emphasize the effects that IUDs may have on the reproductive processes that occur outside the body of the uterus.  As mentioned in the article, spermatozoa do decrease in number, at least with copper IUDs. How significant this is or what relative proportion of contraception is due to a spermicidal effect of IUDs is still under investigation.1-3The recent report by Dr Alvarez-Sanchez and colleagues4suggests that IUDs somehow affect the number and transport of unfertilized ova, resulting in fewer ova being present in the fallopian tube. They also found that among 14 IUD users who had intercourse during their fertile period and who had evidence of spermatozoa in the cervical mucus, no fertilized ova were recovered. This may be due to either spermatozoa not reaching the oocyte or the oocyte being damaged by an adverse tubal environment.  Whether the inflammatory reaction
Family history of liver cancer and hepatocellular carcinoma
Authors: Federica Turati, Valeria Edefonti, Renato Talamini, Monica Ferraroni, Matteo Malvezzi, Francesca Bravi, Silvia Franceschi, Maurizio Montella, Jerry Polesel, Antonella Zucchetto, Carlo La Vecchia, Eva Negri, Adriano Decarli
Journal: Hepatology (2011)

Familial clustering of hepatocellular carcinoma (HCC) has been frequently reported in eastern Asiatic countries, where hepatitis B infection is common. Little is known about the relationship between family history of liver cancer and HCC in Western populations. We carried out a case-control study in Italy, involving 229 HCC cases and 431 hospital controls. Data on family history were summarized through a binary indicator (yes/no) and a family history score (FHscore), considering selected family characteristics. Odds ratios (ORs) and the corresponding 95% confidence intervals (CIs) were obtained from unconditional multiple logistic regression models, including terms for age, sex, study center, education, tobacco smoking, alcohol drinking, hepatitis B surface antigen, and/or anti-hepatitis C virus positivity. We also performed a meta-analysis on family history of liver cancer and liver cancer updated to April 2011 using random-effects models. After adjustment for chronic infection with hepatitis B/C viruses, family history of liver cancer was associated with HCC risk, when using both the binary indicator (OR, 2.38; 95% CI, 1.01-5.58) and the FHscore, with increasing ORs for successive score categories. Compared to subjects without family history and no chronic infection with hepatitis B/C viruses, the OR for those exposed to both risk factors was 72.48 (95% CI, 21.92-239.73). In the meta-analysis, based on nine case-control and four cohort studies, for a total of approximately 3,600 liver cancer cases, the pooled relative risk for family history of liver cancer was 2.50 (95% CI, 2.06-3.03).A family history of liver cancer increases HCC risk, independently of hepatitis. The combination of family history of liver cancer and hepatitis B/C serum markers is associated with an over 70-fold elevated HCC risk.
Proteolytic cleavage of granulocyte colony‐stimulating factor and its receptor by neutrophil elastase induces growth inhibition and decreased cell surface expression of the granulocyte colony‐stimulating factor receptor
Authors: Melissa G. Hunter, Lawrence J. Druhan, Pam R. Massullo, Belinda R. Avalos
Journal: American Journal of Hematology (2003)

Abstract Neutrophil elastase (NE) is a serine protease stored in the primary granules of neutrophils that proteolytically cleaves multiple cytokines and cell surface proteins on release from activated neutrophils. Recent reports of mutations in the gene encoding this enzyme in some patients with neutropenic syndromes prompted us to investigate whether granulocyte colony‐stimulating factor (G‐CSF) and its receptor (G‐CSFR) are also substrates for NE. To further address this, we examined the effect of NE on G‐CSF and the G‐CSFR both in solution and on intact cells. Incubation of recombinant G‐CSF or a G‐CSFR form corresponding to its extracellular domain with purified NE resulted in rapid proteolytic cleavage of both proteins. Addition of NE to tissue culture medium or pretreatment of G‐CSF with NE before its addition to media suppressed the growth of G‐CSF–responsive cells. NE also cleaved the G‐CSFR on the surface of intact cells resulting in a time‐dependent reduction in cell surface expression of the G‐CSFR. Notably, decreased G‐CSFR surface expression resulting from treatment of cells with NE was also associated with a reduction in cell viability and proliferation in response to G‐CSF. These results are the first to demonstrate that G‐CSF and G‐CSFR are proteolytically cleaved by NE and that NE‐induced degradation of these proteins correlates with a reduction in the biologic activity of the cytokine and a decrease in the signaling function of the receptor because of decreased G‐CSFR surface expression. These findings provide additional insights into mechanisms by which G‐CSF/G‐CSFR interactions may be modulated. Am. J. Hematol. 74:149–155, 2003. © 2003 Wiley‐Liss, Inc.
The Effect of Female Sex Hormones on Cancer Survival
Authors: Hans-Olov Adami
Journal: JAMA (1990)

The hypothesis that the female survival advantage in many cancers is dependent on sexual maturity was tested in a population-based cohort. Complete follow-up through 1986 was achieved in virtually all 6262 individuals in Sweden who were diagnosed from 1960 through 1984 as having a malignant disease before the age of 20 years. Proportional hazards analysis revealed a 22% lower death rate overall in females than in males. The difference was unrelated to age at diagnosis for tumors arising in the nervous system and the hematopoietic system (lymphomas and leukemias) but strongly dependent on age for sarcomas and, notably, for all remaining cancers—mostly epithelial. Males and females had similar hazard rates for epithelial cancers before the age of 11 years. At ages 11 to 19 years, the rates in females were 55% to 65% lower than in males. One conceivable explanation for these findings is that female sex hormones prevent the establishment of distant metastases in certain malignant diseases. (<i>JAMA</i>. 1990;263:2189-2193)
Coronary Arterial Flow-Velocity Dynamics in Children With Angiographically Normal Coronary Arteries
Authors: Kenji Hamaoka, Zenshiro Onouchi, Yutaka Ohmochi, Kohichi Sakata
Journal: Circulation (1995)

Background There have been few reports about coronary hemodynamics in children during the process of growth. In the present study, to assess the characteristics of coronary flow dynamics in children, we examined the phasic coronary flow-velocity (CFV) patterns at rest and during peak hyperemic responses in children with angiographically normal coronary arteries. Methods and Results Spectral Doppler phasic coronary flow velocity was recorded with a 0.018-in intracoronary Doppler guidewire at rest and during peak responses after intracoronary bolus injection of ATP in 30 patients with Kawasaki’s disease (age, 8.2±5.1 years; 24 boys and 6 girls) without angiographic coronary lesions. Average peak velocity (APV), maximum peak velocity (MPV), and diastolic-to-systolic velocity ratio (DSVR) were evaluated in the left anterior descending coronary artery (LAD), left circumflex artery (LCx), and right coronary artery (RCA). Coronary vasodilator reserve (coronary flow reserve [CFR]) was calculated as the ratio of ATP-induced hyperemic to baseline APV. Flow-velocity parameters in RCA were significantly lower than those in the LAD and LCx in both proximal and distal portions. Although the distal LCx had significantly lower values of APV and MPV than did the proximal LCx, there was no significant difference between the proximal and distal portions of the LAD and RCA for APV and MPV. All three coronary vessels showed a diastolic dominant flow pattern in each segment. This coronary flow pattern was less marked in the RCA than in the LCA. All three coronary vessels showed a significant increase in APV and a significant decrease in DSVR after ATP administration. CFR was significantly lower in the LCx than in the LAD or RCA ( P &lt;.01: 1.93±0.34 in LCx versus 2.32±0.42 in LAD and 2.37±0.44 in RCA). From the view of aging, it was revealed that APV values in three vessels were higher in the younger group than in the older group. CFR values in the LAD and LCx were significantly lower in the younger group than in the older group ( P &lt;.001 in LAD: 2.01±0.28 in the younger versus 2.53±0.37 in the older; P &lt;.01 in LCx: 1.61±0.15 in the younger versus 2.06±0.31 in the older). In addition, intracoronary injection of ATP did not increase the absolute angiographic coronary luminal diameter. Conclusions With the use of an intracoronary Doppler guidewire, we demonstrated that there are some characteristic findings in CFV dynamics in childhood. These physiological characteristics in CFV dynamics that occur with aging and occur in each vessel must be taken into consideration in the study of the coronary circulation in children.
Are Environmental Levels of Bisphenol A Associated with Reproductive Function in Fertile Men?
Authors: Jaime Mendiola, Niels Jørgensen, Anna-Maria Andersson, Antonia M. Calafat, Xiaoyun Ye, J. Bruce Redmon, Erma Z. Drobnis, Christina Wang, Amy Sparks, Sally W. Thurston, Fan Liu, Shanna H. Swan
Journal: Environmental Health Perspectives (2010)

Rodent and in vitro studies have demonstrated the estrogenicity of bisphenol A (BPA). However, few studies have examined the relationship between human exposure to BPA and male reproductive function.We investigated the relationships between environmental BPA exposure and reproductive parameters, including semen quality and male reproductive hormones, in prospectively recruited fertile men.Participants (n = 375) were partners of pregnant women who participated in the Study for Future Families in four U.S. cities, and all of the men provided blood, semen, and urine samples. BPA was measured in urine. Serum samples were analyzed for reproductive hormones, including follicle-stimulating hormone, luteinizing hormone (LH), testosterone, inhibin B, estradiol, and sex hormone-binding globulin (SHBG), as well as the free androgen index (FAI). Semen analyses were performed according to World Health Organization criteria. Pearson correlations were used for unadjusted analyses, and multiple linear regression analyses were used to examine associations controlling for age, body mass index, smoking, ethnicity, urinary creatinine concentration, time of sample collection, and duration of abstinence.After multivariate adjustment, we observed no significant associations between any semen parameter and urinary BPA concentration. However, a significant inverse association was found between urinary BPA concentration and FAI levels and the FAI/LH ratio, as well as a significant positive association between BPA and SHBG.Our results suggest that, in fertile men, exposure to low environmental levels of BPA may be associated with a modest reduction in markers of free testosterone, but any effects on reproductive function are likely to be small, and of uncertain clinical significance.
A selective microRNA-based strategy inhibits restenosis while preserving endothelial function
Authors: Gaetano Santulli, Anetta Wronska, Kunihiro Uryu, Thomas G. Diacovo, Melanie Gao, Steven O. Marx, Jan Kitajewski, Jamie M. Chilton, Kemal Marc Akat, Thomas Tuschl, Andrew R. Marks, Hana Totary-Jain
Journal: Journal of Clinical Investigation (2014)

Drugs currently approved to coat stents used in percutaneous coronary interventions do not discriminate between proliferating vascular smooth muscle cells (VSMCs) and endothelial cells (ECs). This lack of discrimination delays reendothelialization and vascular healing, increasing the risk of late thrombosis following angioplasty. We developed a microRNA-based (miRNA-based) approach to inhibit proliferative VSMCs, thus preventing restenosis, while selectively promoting reendothelialization and preserving EC function. We used an adenoviral (Ad) vector that encodes cyclin-dependent kinase inhibitor p27(Kip1) (p27) with target sequences for EC-specific miR-126-3p at the 3' end (Ad-p27-126TS). Exogenous p27 overexpression was evaluated in vitro and in a rat arterial balloon injury model following transduction with Ad-p27-126TS, Ad-p27 (without miR-126 target sequences), or Ad-GFP (control). In vitro, Ad-p27-126TS protected the ability of ECs to proliferate, migrate, and form networks. At 2 and 4 weeks after injury, Ad-p27-126TS-treated animals exhibited reduced restenosis, complete reendothelialization, reduced hypercoagulability, and restoration of the vasodilatory response to acetylcholine to levels comparable to those in uninjured vessels. By incorporating miR-126-3p target sequences to leverage endogenous EC-specific miR-126, we overexpressed exogenous p27 in VSMCs, while selectively inhibiting p27 overexpression in ECs. Our proof-of-principle study demonstrates the potential of using a miRNA-based strategy as a therapeutic approach to specifically inhibit vascular restenosis while preserving EC function.
Validation of the IASLC/ATS/ERS Lung Adenocarcinoma Classification for Prognosis and Association with EGFR and KRAS Gene Mutations: Analysis of 440 Japanese Patients
Authors: Akihiko Yoshizawa, Shinji Sumiyoshi, Makoto Sonobe, Masashi Kobayashi, Masakazu Fujimoto, Fumi Kawakami, Tatsuaki Tsuruyama, William D. Travis, Hiroshi Date, Hironori Haga
Journal: Journal of Thoracic Oncology (2012)
The posterior aortic wall echocardiogram. Its relationship to left atrial volume change.
Authors: B L Strunk, J W Fitzgerald, M Lipton, R L Popp, W H Barry
Journal: Circulation (1976)

The normal posterior aortic wall echocardiogram shows anterior motion during left ventricular systole and predominantly posterior motion in three phases during left ventricular diastole. In six patients undergoing simultaneous left atrial angiograms and posterior aortic wall echocardiograms, there was excellent correlation between the posterior aortic wall motion and the change in the left atrial angiographic area showing the value of the posterior aortic wall echocardiogram in describing the left atrial volume curve. Left atrial and left ventricular pressures were measured with manometer tip catheters and correlated with simultaneous posterior aortic wall and mitral valve echocardiograms in four patients with atrial septal defects. These echocardiographic, angiographic, and hemodynamic correlations, as well as other evidence reported in this paper suggest that a major portion of posterior aortic wall motion is related to left atrial events and describes the left atrial volume curve.
Older Adults’ Attitudes Toward Enrollment of Non-competent Subjects Participating in Alzheimer’s Research
Authors: Jason Karlawish, Jonathan Rubright, David Casarett, Mark Cary, Thomas Ten Have, Pamela Sankar
Journal: American Journal of Psychiatry (2008)

Research that seeks to enroll noncompetent patients with Alzheimer's disease without presenting any potential benefit to participants is the source of substantial ethical controversy. The authors used hypothetical Alzheimer's disease studies that included either a blood draw or a blood draw and lumbar puncture to explore older persons' attitudes on this question.Face-to-face interviews were conducted with 538 persons age 65 and older. Questions explored participants' understanding of research concepts, their views on enrolling persons with Alzheimer's disease in research, and their preferences regarding having a proxy decision maker, granting advance consent, and granting their proxy leeway to override the participant's decision. Additional questions assessed altruism, trust, value for research, and perceptions of Alzheimer's disease.The majority (83%) were willing to grant advance consent to a blood draw study, and nearly half (48%) to a blood draw plus lumbar puncture study. Most (96%) were willing to identify a proxy for research decision making, and most were willing to grant their proxy leeway over their advance consent: 81% for the blood draw study and 70% for the blood draw plus lumbar puncture study. Combining the preferences for advance consent and leeway, the proportion who would permit being enrolled in the blood draw and lumbar puncture studies, respectively, were 92% and 75%. Multivariate models showed that willingness to be enrolled in research was most strongly associated with a favorable attitude toward biomedical research.Older adults generally support enrolling noncompetent persons with Alzheimer's disease into research that does not present a benefit to subjects. Willingness to grant their proxy leeway over advance consent and a favorable attitude about biomedical research substantially explain this willingness.
General practitioner training in paediatrics
Authors: S. Leff
Journal: BMJ (1989)

Peer review for hospitals SIR, -Lewisham Health Authority has no powers to require protocols for new treatments in independent hospitals, nor can it insist on using its own ethics committee.'It can satisfy itself that the hospital has an adequate system in place, but the system itself is for the hospital to decide.Many will be satisfied with extending the role of the medical advisory committee.In fact, most independent hospitals provide facilities for elective surgery that is well established.For these hospitals an ethics committee would be
Topical corticosteroids in atopic dermatitis
Authors: D. J Atherton
Journal: BMJ (2003)

Recent research reassures that they are safe and effective in the medium term 

Topical corticosteroids have been the mainstay of treatment for atopic dermatitis over the past 40 years. Hydrocortisone was the first to be used; some 30 additional corticosteroid compounds have now been licensed for treatment of atopic dermatitis. The recent development of the topical immuno-modulators, tacrolimus and pimecrolimus, has provided alternatives to topical corticosteroids, but these remain expensive and are not effective in every case.1 Atopic dermatitis remains a therapeutic challenge, and topical corticosteroids continue to have an important role.

Topical applications containing corticosteroid compounds vary greatly in potency. In general the more potent ones are associated with the greater risk of adverse effects. When one of the more potent topical corticosteroids is applied for the first time by a patient with atopic dermatitis the benefit is likely to be rapid and striking, often resulting in clearance of the rash within a few days. The snag is that persistent application of a potent preparation will put the patient at risk of unwanted local effects on the skin. These effects vary from barely perceptible, fully reversible thinning, to irreversible telangiectasiae and striae distensae. Worse still, patients find that the initial benefit is generally rather rapidly lost because …