tbuckley/cabot-search huggingface dataset:
Classifying childhood arthritis
Authors: T R SOUTHWOOD
Journal: Annals of the Rheumatic Diseases (1997)

The year 1997 marks the 100th anniversary of the publication of Sir George Frederic Still’s landmark paper “On a form of chronic joint disease in children”.1 In recognising childhood arthritis as distinct from adult arthritis, Still fired the first shots in the war of words about its nomenclature and classification which continues to this day. It is now well recognised that childhood arthritis covers a heterogeneous group of diseases, many of which (but not all) have important differences from adult arthritides. Unfortunately, the names of the diseases, and their classification criteria, remain problematic. Still warned against the pitfalls of such debates in the preface to the fourth edition of his paediatric textbook; “… we must be careful lest we mistake words for things, and think that new nomenclature means new discovery, and that difference of terms is equivalent to distinction of kind”.2 

The aim of this leader is to discuss the classification of childhood arthritis. Over recent times this has been the focus of several papers,3 4 a couple of lively debates,5 and many heated private arguments! It has been difficult to reach agreement on the need for a new classification, let alone arrive at a consensus on the classification itself. However, most paediatric rheumatologists now recognise that the disparities between the European designation “JCA” …
Medical Abortion and the Risk of Subsequent Adverse Pregnancy Outcomes
Authors: Jasveer Virk, Jun Zhang, Jørn Olsen
Journal: New England Journal of Medicine (2007)

The long-term safety of surgical abortion in the first trimester is well established. Despite the increasing use of medical abortion (abortion by means of medication), limited information is available regarding the effects of this procedure on subsequent pregnancies.We identified all women living in Denmark who had undergone an abortion for nonmedical reasons between 1999 and 2004 and obtained information regarding subsequent pregnancies from national registries. Risks of ectopic pregnancy, spontaneous abortion, preterm birth (at <37 weeks of gestation), and low birth weight (<2500 g) in the first subsequent pregnancy in women who had had a first-trimester medical abortion were compared with risks in women who had had a first-trimester surgical abortion.Among 11,814 pregnancies in women who had had a previous first-trimester medical abortion (2710 women) or surgical abortion (9104 women), there were 274 ectopic pregnancies (respective incidence rates, 2.4% and 2.3%), 1426 spontaneous abortions (12.2% and 12.7%), 552 preterm births (5.4% and 6.7%), and 478 births with low birth weight (4.0% and 5.1%). After adjustment for maternal age, interval between pregnancies, gestational age at abortion, parity, cohabitation status, and urban or nonurban residence, medical abortion was not associated with a significantly increased risk of ectopic pregnancy (relative risk, 1.04; 95% confidence interval [CI], 0.76 to 1.41), spontaneous abortion (relative risk, 0.87; 95% CI, 0.72 to 1.05), preterm birth (relative risk, 0.88; 95% CI, 0.66 to 1.18), or low birth weight (relative risk, 0.82; 95% CI, 0.61 to 1.11). Gestational age at medical abortion was not significantly associated with any of these adverse outcomes.We found no evidence that a previous medical abortion, as compared with a previous surgical abortion, increases the risk of spontaneous abortion, ectopic pregnancy, preterm birth, or low birth weight.
The 1945 St Helena Poliomyelitis Epidemic after 40 Years
Authors: A B Cross
Journal: Journal of the Royal Society of Medicine (1989)

Twenty-six of the 28 patients known to have been paralysed by poliomyelitis on St Helena over 40 years ago were traced. All had led fulfilled lives. Nine had since died but no deaths were attributable to the disease. The satisfactory outcome of these people's lives was due to a combination of factors. Initially early diagnosis and immediate appropriate treatment minimized contracture formation. Early intensive rehabilitation and return of the patient in an upright and ambulant position to a caring community established the pattern of their future lives. The later lack of surveillance resulted in six of the patients reverting to crawling and only two still using their calipers. In remote and poor areas appliances where possible should be made and maintained locally.
Meralgia Paraesthetica
Authors: E. Wayne Massey
Journal: JAMA (1977)

THE SYNDROME of burning, tingling, and numbness of the anterolateral thigh was described by Bernhardt 1 in 1895. It was named meralgia paraesthetica the same year.  Many causes for this syndrome involving the distribution of the lateral femoral cutaneous nerve of the thigh have been suggested. It has been implied that it can be caused by intrapelvic disease, herpes zoster, and a congenitally tight foramen where the nerve passes through the inguinal ligament just medial to the anterior superior iliac portion of the spine. It has also been associated with osteoarthritis of the lumbar spine and herniated disk on the opposite side, the symptom secondary to muscle spasm. Most often, it is caused from various kinds of trauma secondary to mechanical causes.  Mechanical causes were suggested by Stookey 2 in 1928. He was impressed by the accentuation of the symptoms when patients stood or walked and the relief of symptoms
Reply to F. Crea et al
Authors: Hisae Iinuma, Toshiaki Watanabe, Koshi Mimori, Junko Tamura, Miki Adachi, Naoko Hayashi, Keijiro Nozawa, Soichiro Ishihara, Keiji Matsuda, Hideo Baba, Ryoji Fukushima, Kota Okinaga, Mitsuru Sasako, Masaki Mori
Journal: Journal of Clinical Oncology (2011)
Defective DNA Replication Impairs Mitochondrial Biogenesis In Human Failing Hearts
Authors: Georgios Karamanlidis, Luigino Nascimben, Gregory S. Couper, Prem S. Shekar, Federica del Monte, Rong Tian
Journal: Circulation Research (2010)

Rationale : Mitochondrial dysfunction plays a pivotal role in the development of heart failure. Animal studies suggest that impaired mitochondrial biogenesis attributable to downregulation of the peroxisome proliferator-activated receptor γ coactivator (PGC)-1 transcriptional pathway is integral of mitochondrial dysfunction in heart failure. Objective : The study sought to define mechanisms underlying the impaired mitochondrial biogenesis and function in human heart failure. Methods and Results : We collected left ventricular tissue from end-stage heart failure patients and from nonfailing hearts (n=23, and 19, respectively). The mitochondrial DNA (mtDNA) content was decreased by &gt;40% in the failing hearts, after normalization for a moderate decrease in citrate synthase activity ( P &lt;0.05). This was accompanied by reductions in mtDNA-encoded proteins (by 25% to 80%) at both mRNA and protein level ( P &lt;0.05). The mRNA levels of PGC-1α/β and PRC (PGC-1–related coactivator) were unchanged, whereas PGC-1α protein increased by 58% in the failing hearts. Among the PGC-1 coactivating targets, the expression of estrogen-related receptor α and its downstream genes decreased by up to 50% ( P &lt;0.05), whereas peroxisome proliferator-activated receptor α and its downstream gene expression were unchanged in the failing hearts. The formation of D-loop in the mtDNA was normal but D-loop extension, which dictates the replication process of mtDNA, was decreased by 75% in the failing hearts. Furthermore, DNA oxidative damage was increased by 50% in the failing hearts. Conclusions : Mitochondrial biogenesis is severely impaired as evidenced by reduced mtDNA replication and depletion of mtDNA in the human failing heart. These defects are independent of the downregulation of the PGC-1 expression suggesting novel mechanisms for mitochondrial dysfunction in heart failure.
Expression and regulation of scavenger receptor class B type I (SR-BI) in gall bladder epithelium
Authors: J. F. Miquel, M. Moreno, L. Amigo, H. Molina, P. Mardones, Ignacio Ivan Wistuba, A. Rigotti
Journal: Gut (2003)

<b>Background and aims:</b> Biliary lipid absorption by the gall bladder mucosa and the cholesterol content of the gall bladder wall appear to play a role in cholesterol gall stone formation. As the scavenger receptor class B type I (SR- BI) regulates cellular cholesterol uptake, we studied its expression in human and murine gall bladders, its regulation by increased biliary lipid content, and its role in gall stone formation. <b>Methods and results:</b> Using immunohistochemistry, SR-BI was found in the apical domain of human gall bladder epithelial cells. Immunoblotting of isolated membranes from gall bladder epithelial cells showed a specific signal for the 82 kDa SR-BI protein. In C57BL/6 mice, SR-BI was also found in the gall bladder epithelium. Using western blot analysis, an inverse relationship was observed between biliary cholesterol concentration and SR-BI expression in murine gall bladder mucosa. By comparing lithogenic diet fed wild-type and SR-BI deficient mice, gall bladder wall cholesterol content and gall stone formation were not found to be dependent on SR-BI expression. <b>Conclusions:</b> (i) SR-BI is expressed in both human and murine gall bladder epithelium; (ii) biliary cholesterol hypersecretion is associated with decreased gall bladder SR-BI expression in mice; and (iii) murine SR-BI is not essential in controlling gall bladder wall cholesterol content and gall stone formation during diet induced cholelithiasis.
Src Inhibition with Saracatinib Reverses Fulvestrant Resistance in ER-Positive Ovarian Cancer Models <i>In Vitro</i> and <i>In Vivo</i>
Authors: Fiona Simpkins, Pedro Hevia-Paez, Jun Sun, Wendy Ullmer, Candace A. Gilbert, Thiago da Silva, Ali Pedram, Ellis R. Levin, Isildinha M. Reis, Brian Rabinovich, Diana Azzam, Xiang-Xi Xu, Tan A. Ince, Ji-Yeon Yang, Roel G.W. Verhaak, Yiling Lu, Gordon B. Mills, Joyce M. Slingerland
Journal: Clinical Cancer Research (2012)

More effective, less toxic treatments for recurrent ovarian cancer are needed. Although more than 60% of ovarian cancers express the estrogen receptor (ER), ER-targeted drugs have been disappointing due to drug resistance. In other estrogen-sensitive cancers, estrogen activates Src to phosphorylate p27 promoting its degradation and increasing cell-cycle progression. Because Src is activated in most ovarian cancers, we investigated whether combined Src and ER blockade by saracatinib and fulvestrant would circumvent antiestrogen resistance.ER and Src were assayed in 338 primary ovarian cancers. Dual ER and Src blockade effects on cell cycle, ER target gene expression, and survival were assayed in ERα+ ovarian cancer lines, a primary human ovarian cancer culture in vitro, and on xenograft growth.Most primary ovarian cancers express ER. Src activity was greater in ovarian cancer lines than normal epithelial lines. Estrogen activated Src, ER-Src binding, and ER translocation from cytoplasm to nucleus. Estrogen-mediated mitogenesis was via ERα, not ERβ. While each alone had little effect, combined saracatinib and fulvestrant increased p27 and inhibited cyclin E-Cdk2 and cell-cycle progression. Saracatinib also impaired induction of ER-target genes c-Myc and FOSL1; this was greatest with dual therapy. Combined therapy induced autophagy and more effectively inhibited ovarian cancer xenograft growth than monotherapy.Saracatinib augments effects of fulvestrant by opposing estrogen-mediated Src activation and target gene expression, increasing cell-cycle arrest, and impairing survival, all of which would oppose antiestrogen resistance in these ER+ ovarian cancer models. These data support further preclinical and clinical evaluation of combined fulvestrant and saracatinib in ovarian cancer.
In Goodpasture's Disease, CD4+ T Cells Escape Thymic Deletion and Are Reactive with the Autoantigen α3(IV)NC1
Authors: ALAN D. SALAMA, AFZAL N. CHAUDHRY, JAMES J. RYAN, EFRAM EREN, JEREMY B. LEVY, CHARLES D. PUSEY, LIZ LIGHTSTONE, ROBERT I. LECHLER
Journal: Journal of the American Society of Nephrology (2001)

Abstract. Goodpasture's disease is characterized by rapidly progressive glomerulonephritis and pulmonary hemorrhage, in association with circulating and deposited anti-glomerular basement membrane antibodies that recognize the α3 chain of type IV collagen [α3(IV)NC1] (known as the Goodpasture antigen). Unlike many other autoimmune diseases, recurrences are rare. In experimental models and human studies, both humoral and cellular mechanisms have been demonstrated to be involved in disease pathogenesis. However, there are few data on the characteristics of the autoreactive T cells or the mechanisms of tolerance to the autoantigen in human patients. It was demonstrated, using immunohistochemical analyses and reverse transcription-PCR, that the Goodpasture antigen is expressed in normal human thymus. Using limiting dilution analyses, the frequencies of circulating autoreactive T cells in patients and control subjects were assessed. During acute disease, there were increased frequencies of CD4+ T cells reactive with α3(IV)NC1 (ranging from 1:6300 to 1:65,000), which decreased with time. There was a significant difference between patients during their acute disease phase and control subjects with respect to the frequency index for α3(IV)NC1-specific CD4+ T cells (P < 0.05, Mann Whitney U test). The decrease in autoreactive CD4+ T-cell numbers during recovery may be the reason why recurrences are infrequent and may explain the loss of pathogenic autoantibodies with time, because of a lack of T-cell help.
Childhood Trauma and Children's Emerging Psychotic Symptoms: A Genetically Sensitive Longitudinal Cohort Study
Authors: Louise Arseneault, Mary Cannon, Helen L. Fisher, Guilherme Polanczyk, Terrie E. Moffitt, Avshalom Caspi
Journal: American Journal of Psychiatry (2010)

Objective: Using longitudinal and prospective measures of trauma during childhood, the authors assessed the risk of developing psychotic symptoms associated with maltreatment, bullying, and accidents in a nationally representative U.K. cohort of young twins. Method: Data were from the Environmental Risk Longitudinal Twin Study, which follows 2,232 twin children and their families. Mothers were interviewed during home visits when children were ages 5, 7, 10, and 12 on whether the children had experienced maltreatment by an adult, bullying by peers, or involvement in an accident. At age 12, children were asked about bullying experiences and psychotic symptoms. Children's reports of psychotic symptoms were verified by clinicians. Results: Children who experienced mal-treatment by an adult (relative risk=3.16, 95% CI=1.92-5.19) or bullying by peers (relative risk=2.47, 95% CI=1.74−3.52) were more likely to report psychotic symptoms at age 12 than were children who did not experience such traumatic events. The higher risk for psychotic symptoms was observed whether these events occurred early in life or later in childhood. The risk associated with childhood trauma remained significant in analyses controlling for children's gender, socioeconomic deprivation, and IQ; for children's early symptoms of internalizing or externalizing problems; and for children's genetic liability to developing psychosis. In contrast, the risk associated with accidents was small (relative risk=1.47, 95% CI=1.02−2.13) and inconsistent across ages. Conclusions: Trauma characterized by intention to harm is associated with children's reports of psychotic symptoms. Clinicians working with children who report early symptoms of psychosis should inquire about traumatic events such as maltreatment and bullying.
Role of Detection Method in Predicting Breast Cancer Survival: Analysis of Randomized Screening Trials
Authors: Yu Shen, Ying Yang, Lurdes Y. T. Inoue, Mark F. Munsell, Anthony B. Miller, Donald A. Berry
Journal: JNCI Journal of the National Cancer Institute (2005)

Screening mammography detects breast cancers earlier than those detected symptomatically, and so mammographically detected breast cancers tend to have better prognoses. The so-called stage shift that results from screen detection is subject to lead-time and length biases, and so earlier detection may not translate into longer survival. We used data from three large breast cancer screening trials--Health Insurance Plan (HIP) of New York and two Canadian National Breast Cancer Screening Studies (CNBSS)--to investigate survival benefits of breast cancer screening beyond stage shift. We also address whether method of detection is an independent prognostic factor in breast cancer.The HIP trial randomly assigned approximately 62,000 women to screening and control groups. The two CNBSS trial cohorts CNBSS-1 and CNBSS-2 included a total of 44,970 women in the screening group and 44,961 in the control group. After adjusting for stage and other tumor characteristics in a Cox proportional hazards model, survival distributions were compared by method of breast cancer detection with both univariate and multivariable analyses. All P values are two-sided.Breast cancers detected by screening mammography had a shift in stage distribution to earlier stages (for HIP, P < .001; for CNBSS-1, P = .03; and for CNBSS-2, P < .001). After adjusting for tumor size, lymph node status, and disease stage in a Cox proportional hazards model, method of detection was a statistically significant independent predictor of disease-specific survival. Patients with interval cancers had a 53% (95% confidence interval [CI] = 17% to 100%) greater hazard of death from breast cancer than patients with screen-detected cancers, and patients with cancer in the control groups had a 36% (95% CI = 10% to 68%) greater hazard of death than patients with screen-detected cancer.There was an apparent survival benefit beyond stage shift for patients with screen-detected breast cancers compared with patients with breast cancers detected otherwise. Method of detection appears to be an important prognostic factor, even after adjusting for known tumor characteristics. This finding suggests that clinical trialists should routinely collect information about method of detection.
Effect of Dietary Patterns on Measures of Lipid Peroxidation
Authors: Edgar R. Miller, Lawrence J. Appel, Terence H. Risby
Journal: Circulation (1998)

Background —Free radical–mediated oxidative damage to lipids is thought to be an important process in the pathogenesis of atherosclerosis. Although previous studies have demonstrated a beneficial impact of antioxidant vitamin supplements on lipid peroxidation, the effect of dietary patterns on lipid peroxidation is unknown. Methods and Results —During the 3-week run-in period of a randomized trial, 123 healthy individuals were fed a control diet, low in fruits, vegetables, and dairy products, with 37% of calories from fat. Participants were then randomized to consume for 8 weeks: (1) the control diet, (2) a diet rich in fruits and vegetables but otherwise similar to the control diet, and (3) a combination diet rich in fruits, vegetables, and low-fat dairy products and reduced in fat. Serum oxygen radical–absorbing capacity, malondialdehyde (an in vitro measure of lipid peroxidation), and breath ethane (an in vivo measure of lipid peroxidation) were measured at the end of run-in and intervention periods. Between run-in and intervention, mean (95% CI) change in oxygen radical–absorbing capacity (U/mL) was −35 (−93, 13) in the control diet, 26 (−15, 67) in the fruits and vegetables diet ( P =0.06 compared with control), and 19 (−22, 54) in the combination diet ( P =0.10 compared with control). Median (interquartile range) change in ethane was 0.84 (0.10, 1.59) in the control diet, 0.02 (−0.61, 0.83) in the fruits and vegetables diet ( P =0.04 compared with control), and −1.00 (−1.97, 0.25) in the combination diet ( P =0.005 compared with control). Change in malondialdehyde did not differ between diets. Conclusions —This study demonstrates that modification of diet can favorably affect serum antioxidant capacity and protect against lipid peroxidation.
Intrarenal Insulin-Like Growth Factor-1 Axis after Unilateral Nephrectomy in Rat
Authors: FERNANDO C. FERVENZA, TANNY TSAO, FAY HSU, RALPH RABKIN
Journal: Journal of the American Society of Nephrology (1999)

Abstract. It has been suggested that insulin-like growth factor-1 (IGF-1) may play a role in early compensatory renal growth. Since IGF-1 action is influenced by IGF binding proteins (IGFBP), this study was conducted to characterize the changes in gene expression not only of IGF-1 and its receptor, but also of IGFBP in the hypertrophying kidney of adult and weanling rats 1 wk after removal of the other kidney. At this time, there were distinct age-dependent changes in the renal IGF-1 axis. In the mature kidney, IGF-1 mRNA levels fell without a change in kidney IGF-1 peptide content. Likewise, although IGFBP-2, -3, and -5 mRNA levels fell, membrane-associated IGFBP did not change. IGF-1 receptor mRNA levels and IGF-1 receptor number both fell. In the weanling kidneys, IGF-1 mRNA and peptide levels and IGF-1 receptor binding were unaltered. However, IGFBP-3, -4, and -5 mRNA levels were increased, as were plasma membrane-associated IGFBP. Although these changes in the intrarenal IGF-1 axis were distinct, it is difficult to conceive how in either the mature or immature rat they could contribute to the ongoing compensatory renal growth that occurs 1 wk after loss of kidney mass unless IGF-1 were acting in a synergistic manner with other growth promoters.
Hepatocellular carcinoma in Richardson's ground squirrels(Spermophilus richardsonii): Evidence for association with hepatitis B–like virus infection
Authors: Bud C. Tennant, N. Mrosovsky, Kirsteen McLean, Paul J. Cote, Brent E. Korba, Ronald E. Engle, John L. Gerin, Janet Wright, Gail R. Michener, Elizabeth Uhl, John M. King
Journal: Hepatology (1991)

During studies of seasonal obesity, a high frequency of hepatic neoplasms was observed in Richardson's ground squirrels. Of 12 Richardson's ground squirrels examined thoroughly, 7 had mild or moderate degrees of chronic portal hepatitis and 6 (50%) had hepatocellular carcinoma. Serological tests for hepadnavirus surface antigen, anti-core antibody and virion DNA that recognize the ground squirrel hepatitis virus of California ground squirrels (Spermophilus beecheyi) were uniformly negative. Southern blot analyses of EcoRI digests of liver cell DNA demonstrated 3.2 kb fragments that hybridized with a ground squirrel hepatitis virus-specific probe in nontumorous liver tissue from 6 of 10 ground squirrels and in hepatocellular carcinoma specimens from 2 of 5 squirrels indicating infection with a hepadnavirus related to ground squirrel hepatitis virus. Failure, however, to detect serum antibody to ground squirrel hepatitis core antigen suggested probable antigenic differences between the ground squirrel hepatitis virus of California ground squirrels and the putative Richardson's ground squirrel agent. Further studies are required to fully characterize the hepadnavirus of Richardson's ground squirrels and to determine its relationship to hepatocarcinogenesis in this species.