tbuckley/cabot-search huggingface dataset:
[18F]Fluorothymidine Positron Emission Tomography before and 7 Days after Gefitinib Treatment Predicts Response in Patients with Advanced Adenocarcinoma of the Lung
Authors: Hee-Jung Sohn, You-Jung Yang, Jin-Sook Ryu, Seung Jun Oh, Ki Chun Im, Dae Hyuk Moon, Dae Ho Lee, Cheolwon Suh, Jung-Shin Lee, Sang-We Kim
Journal: Clinical Cancer Research (2008)

Abstract Purpose: To evaluate the usefulness of 3′-deoxy-3′-[18F]fluorothymidine (FLT)-positron emission tomography (PET) for predicting response and patient outcome of gefitinib therapy in patients with adenocarcinoma of the lung. Experimental Design: Nonsmokers with advanced or recurrent adenocarcinoma of the lung were eligible. FLT-PET images of the thorax were obtained before and 7 days after the start of gefitinib (250 mg/d) therapy, the maximum standardized uptake values (SUVmax) of primary tumors were measured, and the percent changes in SUVmax were calculated. After 6 weeks of therapy, the responses were assessed by computed tomography of the chest. Results: Among 31 patients who were enrolled, we analyzed 28 patients for whom we had complete data. Chest computed tomography revealed partial response in 14 (50%), stable disease in 4 (14%), and progressive disease in 10 (36%) after 6 weeks of treatment. Pretreatment SUVmax of the tumors did not differ between responders and nonresponders. At 7 days after the initiation of therapy, the percent changes in SUVmax were significantly different (−36.0 ± 15.4% versus 10.1 ± 19.5%; P &amp;lt; 0.001). Decrease of &amp;gt;10.9% in SUVmax was used as the criterion for predicting response. The positive and negative predictive values were both 92.9%. The time to progression was significantly longer in FLT-PET responders than nonresponders (median, 7.9 versus 1.2 months; P = 0.0041). Conclusion: FLT-PET can predict response to gefitinib 7 days after treatment in nonsmokers with advanced adenocarcinoma of the lung. The change in tumor SUVmax obtained by FLT-PET seems to be a promising predictive variable.
Difference in Heat Stability of Antigens Associated with Epstein-Barr Virus, Demonstrated by Immunofluorescence 2
Authors: Aberra Demissie, Arne Svedmyr
Journal: JNCI Journal of the National Cancer Institute (1973)

Journal Article Difference in Heat Stability of Antigens Associated with Epstein-Barr Virus, Demonstrated by Immunofluorescence Get access Aberra Demissie, Aberra Demissie Virus Department, Central Microbiological Laboratory of the Stockholm County, P.O. Box 177, S-101 22 Stockholm, Sweden Search for other works by this author on: Oxford Academic PubMed Google Scholar Arne Svedmyr Arne Svedmyr Virus Department, Central Microbiological Laboratory of the Stockholm County, P.O. Box 177, S-101 22 Stockholm, Sweden Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 50, Issue 1, January 1973, Pages 63–67, https://doi.org/10.1093/jnci/50.1.63 Published: 01 January 1973 Article history Received: 03 August 1972 Accepted: 31 August 1972 Published: 01 January 1973
Medication use during pregnancy
Authors: J. D. Cragan
Journal: BMJ (2014)

Evaluating risk is an ongoing challenge

Medication use during pregnancy is remarkably common. In the linked paper in this issue (doi:10.1136/bmj.g5159), Bech and colleagues assess the risk of spontaneous abortion and stillbirth after antiepileptic drug use during pregnancy, utilizing national health registers in Denmark from 1997 to 2008.1 The findings are largely reassuring, but studying the effects of drug use in pregnancy is always a challenge and confident conclusions about safety are rarely possible.

Estimates of prescription drug use including vitamins and minerals during the first trimester have ranged from 33% to 69% in developed countries.2 The average number of over the counter and prescription drugs used by pregnant women in the United States increased from 2.5 in 1976-78 to 4.2 in 2006-08.3 And yet the quantity and quality of information about the risk to the fetus of medication use during pregnancy remains poor. A review of 172 medications approved by the US Food and Drug Administration between 2000 and 2010 found that for 97.7% the teratogenic risk in human pregnancy was undetermined; for 73.3% there were no available data about the risk in pregnancy.4 However, because many pregnancies occur unintentionally, women who take medications can be exposed in …
Paraneoplastic myasthenia gravis correlates with generation of mature naive CD4+ T cells in thymomas
Authors: Philipp Ströbel, Markus Helmreich, Georgios Menioudakis, Sharon R. Lewin, Thomas Rüdiger, Andrea Bauer, Viola Hoffacker, Ralf Gold, Wilfred Nix, Berthold Schalke, Olaf Elert, Michael Semik, Hans Konrad Müller-Hermelink, Alexander Marx
Journal: Blood (2002)
X-linked nephrogenic diabetes insipidus mutations in North America and the Hopewell hypothesis.
Authors: D G Bichet, M F Arthus, M Lonergan, G N Hendy, A J Paradis, T M Fujiwara, K Morgan, M C Gregory, W Rosenthal, A Didwania
Journal: Journal of Clinical Investigation (1993)

In X-linked nephrogenic diabetes insipidus (NDI) the urine of male patients is not concentrated after the administration of the antidiuretic hormone arginine-vasopressin. This disease is due to mutations in the V2 receptor gene that maps to chromosome region Xq28. In 1969, Bode and Crawford suggested that most NDI patients in North America shared common ancestors of Ulster Scot immigrants who arrived in Halifax in 1761 on the ship Hopewell. A link between this family and a large Utah kindred was also suggested. DNA was obtained from 17 affected male patients from the "Hopewell" kindred and from four additional families from Nova Scotia and New Brunswick who shared the same Xq28 NDI haplotype. The Utah kindred and two families (Q2, Q3) from Quebec were also studied. The "Hopewell" mutation, W71X, is a single base substitution (G-->A) that changes codon 71 from TGG (tryptophan) to TGA (stop). The W71X mutation was found in affected members of the Hopewell and of the four satellite families. The W71X mutation is the cause of X-linked NDI for the largest number of related male patients living in North America. Other families (Utah, Q2 and Q3) that are historically and ethnically unrelated bear other mutations in the V2 receptor gene.
Resectional surgery of hilar cholangiocarcinoma: a multivariate analysis of prognostic factors.
Authors: J Klempnauer, G J Ridder, R von Wasielewski, M Werner, A Weimann, R Pichlmayr
Journal: Journal of Clinical Oncology (1997)

To define the prognostic factors after surgical resection of bile duct carcinomas at the hepatic bifurcation.The retrospective single-center experience details 151 patients after surgical resection of central bile duct carcinoma performed between 1971 and 1995. Tumor removal was accomplished by resection of the bile duct bifurcation either alone (group I, n = 33), in combination with hepatic resection (group II, n = 77), or combined with hepatic and vascular resection (group III, n = 41). Survival analysis was performed by the Kaplan-Meier method and the relationship between each of the clinicopathologic variables and survival was assessed by the log-rank test. Multivariate results were confirmed using Cox regression.The overall hospital mortality rate was 9.9% and depended on the extent of resection (group 1, 6.1%; group II, 7.8%; group III, 17.1%). After exclusion of hospital deaths, the overall patient survival rate was 28.4% at 5 and 15.5% at 10 years, with a median survival duration of 2.05 +/- 0.23 years. Univariate survival analysis identified tumor size, lymph node metastases, residual tumor stage, and tumor grading as factors with a statistically significant prognostic impact. Survival prognosis was not influenced by the site of the tumor according to the classification of Bismuth and Corlette, extent of resection, International Union Against Cancer (UICC) stage, perineural and vascular invasion, age, or sex. In a multivariate Cox analysis, only lymph node metastases and residual tumor stage proved to be of independent prognostic significance.Resection of central bile duct carcinoma is feasible in many patients and a favorable outcome after resection is mainly determined by curative resection and the absence of lymph node metastases.
Updated overall survival (OS) results for BRIM-3, a phase III randomized, open-label, multicenter trial comparing BRAF inhibitor vemurafenib (vem) with dacarbazine (DTIC) in previously untreated patients with <i>BRAF<sup>V600E</sup></i>-mutated melanoma.
Authors: Paul B. Chapman, Axel Hauschild, Caroline Robert, James M. G. Larkin, John B. A. G. Haanen, Antoni Ribas, David Hogg, Omid Hamid, Paolo Antonio Ascierto, Alessandro Testori, Paul Lorigan, Reinhard Dummer, Jeffrey Alan Sosman, Claus Garbe, Michele Maio, Keith B. Nolop, Betty J Nelson, Andrew K. Joe, Keith T. Flaherty, Grant A. McArthur
Journal: Journal of Clinical Oncology (2012)

8502^ Background: We previously reported results of the planned OS interim analysis for BRIM-3 (50% of the planned 196 deaths required for final analysis) at which time the independent Data Safety Monitoring Board recommended release of results due to compelling efficacy (hazard ratio [HR] for death, 0.37 [95% CI 0.26–0.55]); p&lt;0.0001 and PFS HR 0.26 [95% CI 0.20–0.33]; p&lt;0.0001) and that DTIC-treated patients be permitted to cross over to receive vem. Median follow-up for vem patients was 3.75 months, and longer follow-up would estimate median OS more reliably. Updated OS with median 6.2 months follow-up and 199 total deaths showed HR for death 0.44 (95% CI 0.33–0.59) favoring vem and median OS for vem not reached. We report here the results of an updated OS analysis performed in Nov 2011 with ~10 months median follow-up on vem. Methods: 675 patients with previously untreated, unresectable Stage IIIC or IV melanoma that tested positive for BRAF V600E mutation by the cobas 4800 BRAF V600 Mutation Test were randomized (1:1) from Jan to Dec 2010 to vem (960 mg po bid) or DTIC (1000 mg/m 2 IV q3w). Co-primary endpoints were OS and PFS. OS data for DTIC patients who crossed over to vem were censored at the time of crossover. Results: Median lengths of follow-up on vem and DTIC were 10.5 months (range 0.4–18.1) and 8.4 months (range &lt;0.1–18.3), respectively. There were 334 deaths. Median OS rates with vem and DTIC were 13.2 months (95% CI 12.0–15.0) and 9.6 months (95% CI 7.9–11.8), respectively. 12-month OS rates were 55% for vem and 43% for DTIC. HR for death was 0.62 (95% CI 0.49–0.77) in favor of vem. 81 DTIC patients crossed over to vem. 44 (13%) vem and 65 (19%) DTIC patients received ipilimumab post-progression. Conclusions: With longer follow-up, vem treatment continues to be associated with improved OS in the BRIM-3 study. An updated analysis, with estimated median follow-up of ~13 months and including response data, will be conducted in Apr 2012 and presented at the meeting.
Soil Amendments That Slow Cancer Growth
Authors: Clare M. Isacke, Mary Helen Barcellos-Hoff
Journal: Cancer Discovery (2014)

Abstract Summary: The recognition that the tumor microenvironment contributes to tumor survival, growth, and response to therapy provides the rationale for considering it a therapeutic target. The article by Alspach and colleagues in this issue provides evidence that p38MAPK acts posttranscriptionally to promote the tumor-permissive secretory phenotype of both cancer-associated and senescent fibroblasts, and that p38MAPK inhibitors already in clinical trials have significant therapeutic potential. Cancer Discov; 4(6); 637–9. ©2014 AACR. See related article by Alspach et al., p. 716
Bronchial carcinoid with osteoblastic metastases.
Authors: M H Ashraf
Journal: Thorax (1977)

Bony metastases in association with a lesion in the lung are usually regarded as secondary to bronchial carcinoma. This is generally true when the metastases are osteolytic. However, in the presence of a solitary lung lesion with osteoblastic metastases, the diagnosis of bronchial carcinoid should be considered. The following case illustrates this point.
Finasteride for the Treatment of Hidradenitis Suppurativa in Children and Adolescents
Authors: Harkamal Kaur Randhawa, Jill Hamilton, Elena Pope
Journal: JAMA Dermatology (2013)

Hidradenitis suppurativa (HS) is a chronic debilitating cutaneous disease for which there is no universally effective treatment. Patients typically present at puberty with tender subcutaneous nodules that can progress to dermal abscess formation. Antiandrogens have been used in the treatment of HS, and studies have primarily focused on adult patients.We present a case series of 3 pediatric patients with HS who were successfully treated with oral finasteride, resulting in decreased frequency and severity of disease flares with no significant adverse effects.Finasteride is a therapeutic option that provides benefit for pediatric patients with HS. Further prospective data and randomized controlled studies will provide helpful information in the management of this disease.
Statin Use Associates with a Lower Incidence of Acute Kidney Injury after Major Elective Surgery
Authors: Amber O. Molnar, Steven G. Coca, Phillip J. Devereaux, Arsh K. Jain, Abhijat Kitchlu, Jin Luo, Chirag R. Parikh, J. Michael Paterson, Nausheen Siddiqui, Ron Wald, Michael Walsh, Amit X. Garg
Journal: Journal of the American Society of Nephrology (2011)

Statins abrogate ischemic renal injury in animal studies but whether they are renoprotective in humans is unknown. We conducted a population-based retrospective cohort study that included 213,347 older patients who underwent major elective surgery in the province of Ontario, Canada from 1995 to 2008. During the first 14 postoperative days, 1.9% (4020 patients), developed acute kidney injury and 0.5% (1173 patients), required acute dialysis. The 30-day mortality rate was 2.8% (5974 patients). Prior to surgery, 32% of patients were taking a statin. After statistical adjustment for patient and surgical characteristics, statin use associated with 16% lower odds of acute kidney injury (OR, 0.84; 95% CI, 0.79 to 0.90), 17% lower odds of acute dialysis (OR, 0.83; 95% CI, 0.72 to 0.95), and 21% lower odds of mortality (OR, 0.79; 95% CI, 0.74 to 0.85). Propensity score matching produced similar results. These data suggest that statins may protect against renal complications after major elective surgery and reduce perioperative mortality.
Relationship of glioblastoma multiforme to neural stem cell regions predicts invasive and multifocal tumor phenotype
Authors: Daniel A. Lim, Soonmee Cha, Mary C. Mayo, Mei-Hsiu Chen, Evren Keles, Scott VandenBerg, Mitchel S. Berger
Journal: Neuro-Oncology (2007)

Neural stem cells with astrocyte-like characteristics exist in the human brain subventricular zone (SVZ), and these cells may give rise to glioblastoma multiforme (GBM). We therefore analyzed MRI features of GBMs in specific relation to the SVZ. We reviewed the preoperative and serial postoperative MR images of 53 patients with newly diagnosed GBM. The spatial relationship of the contrast-enhancing lesion (CEL) with the SVZ and cortex was determined preoperatively. Classification was as follows: group I, CEL contacting SVZ and infiltrating cortex; group II, CEL contacting SVZ but not involving cortex; group III, CEL not contacting SVZ but involving cortex; and group IV, CEL neither contacting SVZ nor infiltrating cortex. Patients with group I GBMs (n = 16) were most likely to have multifocal disease at diagnosis (9 patients, 56%, p = 0.001). In contrast, group IV GBMs (n = 14) were never multifocal. Group II (n = 14) and group III (n = 9) GBMs were multifocal in 11% and 29% of cases, respectively. Group I GBMs always had tumor recurrences noncontiguous with the initial lesion(s), while group IV GBM recurrences were always bordering the primary lesion. Group I GBMs may be most related to SVZ stem cells; these tumors were in intimate contact with the SVZ, were most likely to be multifocal at diagnosis, and recurred at great distances to the initial lesion(s). In contrast, group IV GBMs were always solitary lesions; these may arise from non-SVZ, white matter glial progenitors. Our MRI-based classification of GBMs may further our understanding of GBM histogenesis and help predict tumor recurrence pattern.
Y Chromosome Analysis of Dingoes and Southeast Asian Village Dogs Suggests a Neolithic Continental Expansion from Southeast Asia Followed by Multiple Austronesian Dispersals
Authors: Benjamin N. Sacks, Sarah K. Brown, Danielle Stephens, Niels C. Pedersen, Jui-Te Wu, Oliver Berry
Journal: Molecular Biology and Evolution (2013)

Dogs originated more than 14,000 BP, but the location(s) where they first arose is uncertain. The earliest archeological evidence of ancient dogs was discovered in Europe and the Middle East, some 5–7 millennia before that from Southeast Asia. However, mitochondrial DNA analyses suggest that most modern dogs derive from Southeast Asia, which has fueled the controversial hypothesis that dog domestication originated in this region despite the lack of supporting archeological evidence. We propose and investigate with Y chromosomes an alternative hypothesis for the proximate origins of dogs from Southeast Asia—a massive Neolithic expansion of dogs from this region that largely replaced more primitive dogs to the west and north. Previous attempts to test matrilineal findings with independent patrilineal markers have lacked the necessary genealogical resolution and mutation rate estimates. Here, we used Y chromosome genotypes, composed of 29 single-nucleotide polymorphism (SNPs) and 5 single tandem repeats (STRs), from 338 Australian dingoes, New Guinea singing dogs, and village dogs from Island Southeast Asia, along with modern European breed dogs, to estimate the evolutionary mutation rates of Y chromosome STRs based on calibration to the independently known age of the dingo population. Dingoes exhibited a unique haplogroup characterized by a single distinguishing SNP mutation and 14 STR haplotypes. The age of the European haplogroup was estimated to be only 1.7 times older than that of the dingo population, suggesting an origin during the Neolithic rather than the Paleolithic (as predicted by the Southeast Asian origins hypothesis). We hypothesize that isolation of Neolithic dogs from wolves in Southeast Asia was a key step accelerating their phenotypic transformation, enhancing their value in trade and as cargo, and enabling them to rapidly expand and replace more primitive dogs to the West. Our findings also suggest that dingoes could have arrived in Australia directly from Taiwan, independently of later dispersals of dogs through Thailand to Island Southeast Asia.
Emergence of Cardiovascular Risk Factors From Mild Obesity in Japanese Elementary School Children
Authors: Masao Yoshinaga, Koji Sameshima, Michihisa Jougasaki, Hideki Yoshikawa, Yuji Tanaka, Jun Hashiguchi, Hirofumi Tahara, Takeo Ichiki, Shinichiro Shimizu, Kazuhiko Nakamura
Journal: Diabetes Care (2006)

Clustering of individual cardiovascular risk factors, such as central obesity, insulin resistance, hypertension, and dyslipidemia, together known as metabolic syndrome, is largely confined to obese populations in both children and adults (1,2). The underlying pathophysiology of metabolic syndrome is thought to be related to insulin resistance (3).

In Asian countries, especially Japan, obesity-associated disorders arise in mildly to moderately obese adults (4,5). The association between mild obesity in children and individual risk factors in Asian countries is not well defined. The purpose of the present study is to determine the prevalence of, and sex differences in, abdominal obesity and insulin resistance, key features of metabolic syndrome, and assess whether risk of these factors is associated with mild obesity in Japanese elementary school children.

Subjects were elementary school children aged 6–12 years who were screened as having a percent relative body weight (%RBW) ≥35% (6). A total of 863 children (561 boys, 302 girls) participated in a screening program for comorbidity of obesity conducted in 2002 and 2003 by the Kagoshima City Board of Education and Kagoshima City Medical Association, Japan. Of these, 754 obese children (490 boys, 264 girls) were included in the present study. One hundred nine subjects were excluded: 9 subjects (6 boys, 3 girls) were excluded because they had normal %RBW, and 100 subjects (65 boys, 35 girls) were excluded because of incomplete information. For 146 subjects (93 boys, …
Predicting survival in pulmonary arterial hypertension: time to move forward
Authors: S. Provencher, R. Souza
Journal: European Respiratory Journal (2010)

In the early 1980s, the National Institutes of Health (NIH) established a prospective, multicenter registry to characterise the long-term outcomes of consecutive patients with primary pulmonary hypertension (PPH) 1, which included idiopathic, heritable and anorexigens-associated pulmonary arterial hypertension (PAH) 2. Another important objective of this registry was to determine variables predicting survival. This registry, initiated when no therapy for PAH was available, confirmed the dramatic prognosis of PPH on supportive therapy alone. Multiple variables associated with poor prognosis were documented, including poor functional capacity, low carbon monoxide diffusion capacity, presence of Raynaud phenomenon and pulmonary haemodynamics. From this, a formula that estimated a patient's chance of survival was developed, using three hemodynamic variables (right atrial and pulmonary artery pressures and cardiac index) chosen somewhat arbitrarily. This equation was subsequently validated in an independent cohort of patients with PPH 3.

The demonstration of the devastating nature of PAH has justified resources for the development of new therapies, the prioritisation of PAH patients for lung transplantation 4 and the need for specialised PAH centres. Since the NIH registry was established, other variables have been increasingly recognised as potent prognostic factors in PAH, including PAH type, functional capacity and other surrogate markers of right heart function. With the advent of new treatments, a better prognostication certainly led to refinements in treatment approaches, with the most aggressive options being proposed to patients with more severe disease 2. Ultimately, the NIH equation has been useful to document higher survival on PAH-specific therapies …
Closing the door on hepatitis B
Authors: C.‐Thomas Bock, Joseph Torresi, Kris Kowdley, Geoffrey McCaughan, Christian Trautwein
Journal: Hepatology (2008)

360 million people are chronically infected with the human hepatitis B virus (HBV) and are consequently prone to develop liver cirrhosis and hepatocellular carcinoma. As approved therapeutic regimens—which modulate patients' antiviral defenses or inhibit the viral reverse transcriptase—are generally noncurative, strategies interfering with other HBV replication steps are required. Expanding on our demonstration that acylated peptides derived from the large HBV envelope protein block virus entry in vitro, we show their applicability to prevent HBV or woolly monkey hepatitis B virus infection in vivo, using immunodeficient urokinase-type plasminogen activator (uPA) mice repopulated with primary human or Tupaia belangeri hepatocytes. Accumulation of the peptides in the liver, their extraordinary inhibitory potency and specific mode of action permit subcutaneous delivery at very low doses. Inhibition of hepadnavirus entry thus constitutes a therapeutic approach to prevent primary HBV infection, such as after liver transplantation, and might also restrain virus spread in chronically infected patients.