tbuckley/cabot-search huggingface dataset:
Cytotechnologists' Proficiency and Laboratory Regulations-Reply
Authors: Loyd R. Wagner
Journal: JAMA (1990)

In Reply.—  The comments to which Mr Eells refers were made in the context of a discussion of the potential adverse effects of the proficiency testing requirements for cytotechnologists and cytopathologists in the March 14, 1990, Final Rule. They were not intended to denigrate the professional capabilities of cytotechnologists, who are needed and valued members of the medical team that provides essential cytology services.  The March 14, 1990, final regulations for the first time apply proficiency testing requirements to individuals and treat cytotechnologists and cytopathologists the same. To hold cytotechnologists to the same standard of performance in diagnostic expertise as a pathologist is unrealistic and is not consistent with the way cytology is practiced in the real world. Proficiency testing that focuses on the laboratory as a totality would be more realistic, for it is the quality of the diagnostic information provided to the physician for the treatment of the
Effect of Alcohol on Acute Ventilatory Adaptation to Mild Hypoxia at Moderate Altitude
Authors: Georg Roeggla
Journal: Annals of Internal Medicine (1995)

Objective: To evaluate the influence of alcohol on acute adaptation to mild hypoxia at moderate altitude. Design: Randomized, double-blind, placebo-controlled crossover trial. Setting: University clinic and mountaineering resort at altitudes of 171 m and 3000 m, respectively, in the Austrian Alps. Participants: 10 healthy male alpinists, 22 to 24 years of age. Intervention: Single dose of 50 g of alcohol or placebo at altitudes of 171 m and 3000 m. Main Outcome Measures: Arterial oxygen pressure (Pao 2) and arterial carbon dioxide pressure (Paco 2) before and 1 hour after consumption of alcohol or placebo. Results: At an altitude of 171 m, 50 g of alcohol caused no statistical change in Pao 2 and Paco 2 (median Pao 2, 91.5 compared with 90.5 mm Hg [P = 0.89]; median Paco 2, 37.5 compared with 36.0 mm Hg [P = 0.41]). At an altitude of 3000 m, the median Pao 2 decreased from 69.0 to 64.0 mm Hg, a median decrease in the paired difference of 4.0 mm Hg (95.1% CI, 1.5 to 6.5 mm Hg; P < 0.01), and the median Paco 2 increased from 32.5 to 34.0 mm Hg, a median increase in the paired difference of 3.0 mm Hg (95.1% CI, 2.0 to 4.0 mm Hg; P < 0.01) 1 hour after drinking 50 g of alcohol. Placebo did not influence Pao 2 or Paco 2 at either altitude. Conclusion: Alcohol inhibits the initial stages of adequate acute ventilatory adaptation to mild hypoxia at moderate altitude. Caution in the use of alcoholic beverages at moderate altitude is therefore necessary.
Lack of Neointimal Proliferation After Implantation of Sirolimus-Coated Stents in Human Coronary Arteries
Authors: J. Eduardo Sousa, Marco A. Costa, Alexandre Abizaid, Andrea S. Abizaid, Fausto Feres, Ibraim M. F. Pinto, Ana C. Seixas, Rodolfo Staico, Luiz A. Mattos, Amanda G. M. R. Sousa, Robert Falotico, Judith Jaeger, Jeffrey J. Popma, Patrick W. Serruys
Journal: Circulation (2001)

Background —Restenosis remains an important limitation of interventional cardiology. Therefore, we aimed to determine the safety and efficacy of sirolimus (a cell-cycle inhibitor)-coated BX Velocity stents. Methods and Results —Thirty patients with angina pectoris were electively treated with 2 different formulations of sirolimus-coated stents (slow release [SR], n=15, and fast release [FR], n=15). All stents were successfully delivered, and patients were discharged without clinical complications. Independent core laboratories analyzed angiographic and 3D volumetric intravascular ultrasound data (immediately after procedure and at 4-month follow-up). Eight-month clinical follow-up was obtained for all patients. There was minimal neointimal hyperplasia in both groups (11.0±3.0% in the SR group and 10.4±3.0% in the FR group, P =NS) by ultrasound and quantitative coronary angiography (in-stent late loss, 0.09±0.3 mm [SR] and −0.02±0.3 mm [FR]; in-lesion late loss, 0.16±0.3 mm [SR] and −0.1±0.3 mm [FR]). No in-stent or edge restenosis (diameter stenosis ≥50%) was observed. No major clinical events (stent thrombosis, repeat revascularization, myocardial infarction, or death) had occurred by 8 months. Conclusions —The implantation of sirolimus-coated BX Velocity stents is feasible and safe and elicits minimal neointimal proliferation. Additional placebo-controlled trials are required to confirm these promising results.
MASS CANCER INCIDENCE NEAR BAKERIES AND IN OTHER PLACES WHERE RATS ABOUND
Authors: Willy Meyer
Journal: JAMA (1926)

<h3>To the Editor:</h3> —In the Paris letter (The Journal, Sept. 12, 1925, p. 838) there was a report of investigations by Negre in the French Tarn district on mass cancer incidence near bakeries and other places where rats abound. The matter constitutes apparently further corroborative evidence for parallel observations found in the literature. It seems that various worms can be among the cancer-inciting factors, and that rats can be the carriers of these worms and their larvae and the disseminators of their ova. As others may also be interested in the matter, I cite some references: In "Some Notes on Cancer" (<i>J. Cancer Research</i><b>8</b>:45 [April] 1924) I mentioned certain cancer districts. L. W. Sambon (The Elucidation of Cancer,<i>J. Cancer</i><b>2</b>:37 [Jan.] 1925) showed the coincidence of a high cancer rate, old bakeries, cockroaches and rats. In a second article entitled "Some Notes on Cancer" (<i>Am. J.</i>
Dietary Protein and Blood Pressure
Authors: Eva Obarzanek
Journal: JAMA (1996)

<h3>Objective.</h3> —To review published and presented data on the relationship between dietary protein and blood pressure in humans and animals. <h3>Data Sources.</h3> —Bibliographies from review articles and books on diet and blood pressure that had references to dietary protein. The bibliographies were supplemented with computerized MEDLINE search restricted to English language and abstracts presented at epidemiologic meetings. <h3>Study Selection.</h3> —Observational and intervention studies in humans and experimental studies in animals. <h3>Data Extraction.</h3> —In human studies, systolic or diastolic blood pressure were outcome measures, and dietary protein was measured by dietary assessment methods or by urine collections. In animal studies, blood pressure and related physiological effects were outcome measures, and experimental treatment included protein or amino acids. <h3>Data Synthesis.</h3> —Historically, dietary protein has been thought to raise blood pressure; however, studies conducted in Japan raised the possibility of an inverse relationship. Data analyses from subsequent observational studies in the United States and elsewhere have provided evidence of an inverse relationship between protein and blood pressure. However, intervention studies have mostly found no significant effects of protein on blood pressure. Few animal studies have specifically examined the effects of increased dietary protein on blood pressure. <h3>Conclusions.</h3> —Because of insufficient data and limitations in previous investigations, better controlled and adequately powered human studies are needed to assess the effect of dietary protein on blood pressure. In addition, more research using animal models, in which experimental conditions are highly controlled and detailed mechanistic studies can be performed, is needed to help provide experimental support for or against the protein—blood pressure hypothesis. (<i>JAMA</i>. 1996;275:1598-1603)
Hyponatremia Due to Chlorpropamide
Authors: DANIEL FINE
Journal: Annals of Internal Medicine (1970)

A syndrome resembling inappropriate secretion of antidiuretic hormone (ADH) occurred in a 78-year-old diabetic woman receiving chlorpropamide; it abated when the drug therapy was stopped and water intake was reduced. Water retention, hyponatremia, natriuresis, and symptoms of water intoxication reappeared when chlorpropamide therapy was reinstituted and were reversed by withdrawal of the drug or restriction of water intake. This disorder develops from the ADH-like action of chlorpropamide in a susceptible patient maintaining a generous intake of water. This syndrome may not be uncommon and may aggravate the abnormal handling of water by the kidneys which, because it is also seen in other disorders, may lead to an erroneous diagnosis.
Muscle and Heart Function Restoration in a Limb Girdle Muscular Dystrophy 2I (LGMD2I) Mouse Model by Systemic FKRP Gene Delivery
Authors: Chunping Qiao, Chi-Hsien Wang, Chunxia Zhao, Peijuan Lu, Hiroyuki Awano, Bin Xiao, Jianbin Li, Zhenhua Yuan, Yi Dai, Carrie Bette Martin, Juan Li, Qilong Lu, Xiao Xiao
Journal: Molecular Therapy (2014)

Mutations in fukutin-related protein (FKRP) gene cause a wide spectrum of disease phenotypes including the mild limb-girdle muscular dystrophy 2I (LGMD2I), the severe Walker-Warburg syndrome, and muscle-eye-brain disease. FKRP deficiency results in α-dystroglycan (α-DG) hypoglycosylation in the muscle and heart, which is a biochemical hallmark of dystroglycanopathies. To study gene replacement therapy, we generated and characterized a new mouse model of LGMD2I harboring the human mutation leucine 276 to isoleucine (L276I) in the mouse alleles. The homozygous knock-in mice (L276I(KI)) mimic the classic late onset phenotype of LGMD2I in both skeletal and cardiac muscles. Systemic delivery of human FKRP gene by AAV9 vector in the L276I(KI) mice, at either neonatal age or at the age of 9 months, rendered body wide FKRP expression and restored glycosylation of α-DG in both skeletal and cardiac muscles. FKRP gene therapy ameliorated dystrophic pathology and cardiomyopathy such as muscle degeneration, fibrosis, and myofiber membrane leakage, resulting in restoration of muscle and heart contractile functions. Thus, these results demonstrated that the treatment based on FKRP gene replacement was effective.
Impact of Chronic Graft-versus-Host Disease on Late Relapse and Survival on 7,489 Patients after Myeloablative Allogeneic Hematopoietic Cell Transplantation for Leukemia
Authors: Michael Boyiadzis, Mukta Arora, John P. Klein, Anna Hassebroek, Michael Hemmer, Alvaro Urbano-Ispizua, Joseph H. Antin, Brian J. Bolwell, Jean-Yves Y. Cahn, Mitchell S. Cairo, Corey S. Cutler, Mary E. Flowers, Robert P. Gale, Roger Herzig, Luis M. Isola, David A. Jacobsohn, Madan H. Jagasia, Thomas R. Klumpp, Stephanie J. Lee, Effie W. Petersdorf, Stella Santarone, Stephen R. Spellman, Harry C. Schouten, Leo F. Verdonck, John R. Wingard, Daniel J. Weisdorf, Mary M. Horowitz, Steven Z. Pavletic
Journal: Clinical Cancer Research (2014)

Malignancy relapse remains a major obstacle for successful allogeneic hematopoietic cell transplantation (HCT). Chronic graft-versus-host disease (cGVHD) is associated with fewer relapses. However, when studying effects of cGVHD on relapse, it is difficult to separate from acute GVHD effects as most cases of cGVHD occur within the first year after transplant at the time when acute GVHD is still active.This study based on CIBMTR registry data investigated cGVHD and its association with the incidence of late relapse and survival in 7,489 patients with acute myelogenous leukemia (AML), acute lymphoblastic leukemia (ALL), chronic myelogenous leukemia (CML), and myelodysplastic syndromes (MDS), who were leukemia free at 12 months after myeloablative allogeneic HCT.Forty-seven percent of the study population was diagnosed with cGVHD at 12 months after transplant. The protective effect of cGVHD on late relapse was present only in patients with CML [RR, 0.47; 95% confidence interval (CI), 0.37-0.59; P < 0.0001). cGVHD was significantly associated with higher risk of treatment-related mortality (TRM; RR, 2.43; 95% CI, 2.09-2.82; P < 0.0001) and inferior overall survival (RR, 1.56; 95% CI, 1.41-1.73; P < 0.0001) for all diseases. In patients with CML, all organ sites and presentation types of cGVHD were equally associated with lower risk of late relapse.These results indicate that clinically relevant antileukemia effects of cGVHD on late relapses are present only in CML but not in AML, ALL, or MDS. Chronic GVHD in patients who are 1-year survivors after myeloablative allogeneic HCT is primarily associated with higher TRM and inferior survival.
Chlorinated Persistent Organic Pollutants, Obesity, and Type 2 Diabetes
Authors: Duk-Hee Lee, Miquel Porta, David R. Jacobs, Laura N. Vandenberg
Journal: Endocrine Reviews (2014)

Persistent organic pollutants (POPs) are lipophilic compounds that travel with lipids and accumulate mainly in adipose tissue. Recent human evidence links low-dose POPs to an increased risk of type 2 diabetes (T2D). Because humans are contaminated by POP mixtures and POPs possibly have nonmonotonic dose-response relations with T2D, critical methodological issues arise in evaluating human findings. This review summarizes epidemiological results on chlorinated POPs and T2D, and relevant experimental evidence. It also discusses how features of POPs can affect inferences in humans. The evidence as a whole suggests that, rather than a few individual POPs, background exposure to POP mixtures—including organochlorine pesticides and polychlorinated biphenyls—can increase T2D risk in humans. Inconsistent statistical significance for individual POPs may arise due to distributional differences in POP mixtures among populations. Differences in the observed shape of the dose-response curves among human studies may reflect an inverted U-shaped association secondary to mitochondrial dysfunction or endocrine disruption. Finally, we examine the relationship between POPs and obesity. There is evidence in animal studies that low-dose POP mixtures are obesogenic. However, relationships between POPs and obesity in humans have been inconsistent. Adipose tissue plays a dual role of promoting T2D and providing a relatively safe place to store POPs. Large prospective studies with serial measurements of a broad range of POPs, adiposity, and clinically relevant biomarkers are needed to disentangle the interrelationships among POPs, obesity, and the development of T2D. Also needed are laboratory experiments that more closely mimic real-world POP doses, mixtures, and exposure duration in humans.
Abstract P3-14-14: Activation of SRC and MAPK Mediates Resistance to Lapatinib in ER-/ERBB2+ Breast Cancer
Authors: A-M Jegg, T Ward, E Iorns, M Gallas, M. Pegram
Journal: Cancer Research (2010)

Abstract Background Resistance to lapatinib represents a significant problem in the treatment of ERBB2+ breast cancer, especially after failure of prior trastuzumab therapy. A number of resistance mechanisms have been identified in recent years that limit the anti-tumor effects of lapatinib. These mechanisms include the activation of ERα signaling, and sustained activation of AKT either through coexpression of receptor tyrosine kinases (IGF-IR, AXL, MET, ERBB3), loss of PTEN or activating mutations in PIK3CA. However, these mechanisms have been shown to confer resistance primarily in ER+/ERBB2+ breast cancer cells; the mechanisms of resistance to lapatinib in ER-/ERBB2+ breast cancer (∼ 50% of ERBB2+ breast cancers) remain poorly understood. We hypothesized that resistance to lapatinib in ER-/ERBB2+ breast cancer cells can be mediated by activation of alternative signaling pathways which bypass the PI3K/AKT signaling axis. Materials and Methods To investigate the mechanisms of acquired resistance to lapatinib we generated ER-/ERBB2+ and ER+/ERBB2+ breast cancer cells resistant to lapatinib at the clinically relevant concentration of 2.6 uM (SK-lapR and BT-lapR). Resistance to lapatinib was achieved by exposure of SKBR3 and BT474 cells to increasing concentrations of the drug, and resistant cells were selected through serial passage. The activation status of multiple signaling pathways in lapatinib sensitive and resistant cells was determined by western blot analysis, and the role of individual signaling pathways in promoting resistance to lapatinib was investigated in cell proliferation assays using selective small molecule inhibitors. Results and Discussion Consistent with previous studies, we show that inhibition of ERα signaling using 100 nM fulvestrant in combination with lapatinib restored lapatinib sensitivity and effectively leads to growth arrest and cell death in ER+/ERBB2+ BT-lapR cells (P&amp;lt;0.001). However, none of the previously proposed mechanisms of resistance to lapatinib were apparent in our SK-lapR cells (ER-/ERBB2+). Strikingly, these cells which are stably resistant to lapatinib show no activation of AKT even in the absence of lapatinib. Rather, they exhibit increased phosphorylation of SRC kinase (3.9 fold, analyzed with ImageJ) and no inhibition of ERK1/2 after treatment with lapatinib compared to sensitive SKBR3 cells. Inhibition of SRC activity with 1uM AZD0530 in combination with lapatinib significantly reduced growth of SK-lapR cells compared to treatment with lapatinib alone (P&amp;lt;0.05). These data reveal potential novel mechanisms for lapatinib resistance in ER-/ERBB2+ breast cancer, and may indicate therapeutic strategies to prevent or overcome lapatinib resistance. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P3-14-14.
Distal transposition of rat caecum does not render it susceptible to carcinogenesis.
Authors: J B Rainey, M Maeda, R C Williamson
Journal: Gut (1985)

As the relative resistance of rat caecum to chemical carcinogens could reflect its luminal environment, caecal mucosa was exposed to the distal faecal stream in male Sprague-Dawley rats (n = 50) previously treated with azoxymethane (total dose 90 mg/kg sc). After colonic transection at the pelvic brim, the caecum was inserted isoperistaltically between colocaecal and caecorectal anastomoses (n = 30); an ileocolic anastomosis restored intestinal continuity. Controls (n = 20) had transection and reanastomosis at equivalent points of the bowel, plus caecotomy and resuture. Caecal crypt cell production rate, as determined stathmokinetically at 28 weeks, was not consistently affected by transposition. No tumors developed in either transposed or orthotopic caecum, apart from three suture-line tumours found at the caecotomy site in controls. The colonic tumour yield in controls (1.4 +/- 0.3 per rat : mean +/- SEM) matched that after transposition (1.5 +/- 0.2), but anastomotic tumours were twice as common after transposition (p less than 0.05) and rectal tumours were increased four-fold (p less than 0.05). The caecum remains resistant to carcinogenesis despite transposition to a distal colonic environment. Local epithelial defence mechanisms are more important than luminal contents in maintaining this resistance.
NEW INSTRUMENT FOR SUBPERIOSTEAL COSTECTOMY
Authors: John Alexander
Journal: JAMA (1924)

Separation of the periosteum from the rib edges, beneath the tenacious attachments of the intercostal muscles, as a step in the operation of subperiosteal rib resection, is notoriously tedious and time consuming. It is especially so in elderly or muscular subjects and in those whose pleuroperiosteum has been inflamed and thickened. At present, it is done with various types of periosteal elevators designed for general bone surgery; but none of them are satisfactory. The rapidly increasing number of thoracoplastic operations involving subperiosteal rib resection, especially for chronic empyema and pulmonary tuberculosis, has created a demand for an instrument that will strip the rib edges speedily, cleanly and without danger of wounding the pleura. I have designed such an instrument,<sup>1</sup>which has proved itself in practice. The instrument may be called a rib-edge periosteum stripper (<i>A</i>in the illustration). At the opposite end of the handle is the well known
Abstract 3742: P7170: A potent and oral phosphoinositide 3-kinase (PI3K)-mammalian target of rapamycin (mTOR) and activin receptor-like kinase 1 (ALK1) inhibitor with anti-tumor and anti-angiogenic activity
Authors: Veena R. Agarwal, Asavari Joshi, Magesh Venkataraman, Nikesh Desai, Dimple Bhatia, Sarika Chaudhari, Julie Bose, Lakshmi Sireesha Kolla, Vijaykumar Deore, Nilambari Yewalkar, Sanjay Kumar, Rajiv Sharma, Anagha Damre, Avinash More, Parkash Gill, Somesh Sharma
Journal: Cancer Research (2012)

Abstract The PI3K/mTOR pathway plays an important role in regulating cancer cell proliferation, growth, survival and metabolism. Activation of the PI3K/mTOR pathway by multiple mechanisms is one of the most frequently observed defects in human malignancies. The objective of these studies was to identify a small molecule that has anti-angiogenic activity in addition to PI3K and mTOR activity. P7170, a novel small molecule, inhibits PI3Kα and mTOR enzyme activity with IC50 value of 2.2 nM and 4.4 nM respectively. P7170 also inhibits a number of PI3Kα mutants. The Inhibition of PI3K-mTOR pathway in different cancer cell lines was demonstrated by 80 to 100% inhibition of the expression of phosphorylated AKT (pAKT), S6 ribosomal protein (pS6), and 4EBP1 (p4EBP1) upon treatment with P7170 in a western blot assay. P7170 also inhibited ALK1, an important enzyme involved in angiogenesis, and DNA-PK, an enzyme involved in DNA repair with the IC50 values of 47 and 1.5 nM, respectively. P7170 exhibited potent cytotoxic activity with IC50 values ranging from 2 to 22 nM in a number of cancer cell lines eg. ovarian (A2780), prostate (PC3), triple negative breast (MDA-MB-231 and MDA-MB-468), ER positive breast (MCF7), hepatocellular (HuH-7), renal (786-O), pancreatic (Panc1, AsPC1, and BxPC3), and colon (HCT116, HCT115, SW480) cancer cell lines. More interestingly, P7170 inhibited pAKT and pS6 in stem-like cells isolated from tumor samples of colon, breast, and head and neck cancer patients. P7170 also inhibited anchorage independent colony formation of tumor cells isolated from 39 different human tumor xenografts derived from tumors of patients with different cancers. In addition, P7170 inhibited angiogenesis in vitro in a tube formation assay, and in a matrigel plug assay in animals. It also inhibited metastasis of breast cancer cells. P7170 demonstrated significant in vivo efficacy when administered orally in three human xenograft tumor models. Tumor growth inhibition of 79% at 15 mg/kg in prostate (PC3), 78% at 10 mg/kg in ovarian (A2780), and 64% at 10 mg/kg in triple negative breast (MDA-MB-231) xenografts. Conclusion: P7170 has a unique profile of PI3K-mTOR pathway inhibition along with anti-angiogenic and anti- DNA repair activities. Combined with its effect on stem-like cells, P7170 may prove to be an effective anti-cancer drug. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 3742. doi:1538-7445.AM2012-3742
HIV and AIDS, other sexually transmitted diseases, and tuberculosis in ethnic minorities in United Kingdom: Is surveillance serving its purpose?
Authors: K. M De Cock, N. Low
Journal: BMJ (1997)

Experience of disease differs across ethnic groups, and ethnicity is a relevant personal characteristic for descriptive epidemiology. Information about ethnicity and country of birth is omitted from the routine notification of many diseases. HIV infection and AIDS, other sexually transmitted diseases, and tuberculosis have different incidence rates in different ethnic groups in the United Kingdom. Omission of ethnic data from surveillance activities allows such differences in incidence to go undetected and unaddressed. Surveillance data that included ethnic details could guide interventions to reduce inequalities in health between different subpopulations.