tbuckley/cabot-search huggingface dataset:
To define virological response in hepatitis B e antigen-negative patients
Authors: Resat Ozaras, Hakan Leblebicioglu, Cafer Eroglu
Journal: Hepatology (2008)

To the Editor: Hou et al. compared the efficacies of telbivudine and lamivudine in patients with hepatitis B e antigen (HBeAg)-positive and HBeAg-negative chronic hepatitis B. 1 Virological response definition in the study (Ͻ5 log 10 copies/mL) can not be applied to HBeAg-negative patients.HBeAg-negative patient usually harbor lower hepatitis B virus (HBV) DNA levels. 2Also in the study, median HBV DNA levels of HBeAg-positive patients are more than 100-fold (Ͼ2 log 10 copies/mL) higher than those of HBeAgnegative patients.Defining the virological response as Ͻ5 log 10 copies/mL in both HBeAg-negative and HBeAg-positive patients might overestimate the response rate in HBeAg-negative patients.Accordingly, the authors reported the therapeutic response of telbivudine as 100% whereas the polymerase chain reaction (PCR)-negative HBV DNA rate was 85% in this small study population.What should be the virological response definition in HBeAgnegative patients?A recent review defined it as "decrease of serum HBV DNA to PCR-undetectable levels (preferably) or Ͻ2000 IU/mL (4 log 10 copies/mL)." 3 The entecavir study used "HBV DNA Ͻ300 copies/mL by PCR assay" 4 and the adefovir study used "Ͻ400 copies/mL". 5A recent clevudine study, finally, used hybride capture with a lower limit of detection of Ͻ4700 copies/mL and then, if it remains undetectable, used PCR with a lower limit of detection of 300 copies/mL. 6Instead of an arbitrary limit, HBV DNA levels should have some clinical or virological predictive roles.For example, in an adefovir study, decrease of HBV DNA levels to Ͻ 10 3 copies/mL at week 48 of therapy has been found to be highly predictive of maintenance of the response at year 3 with a probability of HBV resistance as low as Ͻ 4%. 2,7 Clinical trials of HBV treatment in the current literature are not easy to compare directly.Patient demographics, baseline viral load, genotypes, and many other features already differ.However, at leastinclusion criteria and response definitions should allow making simple comparisons.
Mercury Granuloma With Systemic Absorption
Authors: Frank B. Kern
Journal: JAMA (1972)

<h3>To the Editor.—</h3> Mortalities from metallic mercury poisoning are rare. Less than three dozen cases have been described in the literature during the past 80 years. Morbidity, on the other hand, is high. Johnson and Koumides<sup>1</sup>reported a death as a result of self-administration of between 1 and 2 ml of metallic mercury injected subcutaneously in the left forearm by a 23-year-old female laboratory technician. Others have been more fortunate and, despite localized and systemic symptoms, have survived.<sup>2</sup>Some patients have had only local complications, and though elevated levels of mercury have been found in the urine, no clinical features of either acute or chronic mercury poisoning ensued. Such a case was reported by Hill<sup>3</sup>in a 21-year-old psychiatric patient who injected mercury into both her thighs. The majority of cases of mercury poisoning are accidental. Several cases have been described as the result of broken thermometers,
Requirement of enhanced Survival Motoneuron protein imposed during neuromuscular junction maturation
Authors: Shingo Kariya, Teresa Obis, Caterina Garone, Turgay Akay, Fusako Sera, Shinichi Iwata, Shunichi Homma, Umrao R. Monani
Journal: Journal of Clinical Investigation (2014)

Spinal muscular atrophy is a common motor neuron disease caused by low survival motoneuron (SMN), a key protein in the proper splicing of genes. Restoring the protein is therefore a promising therapeutic strategy. Implementation of this strategy, however, depends on defining the temporal requirements for SMN. Here, we used controlled knockdown of SMN in transgenic mice to determine the precise postnatal stage requirements for this protein. Reducing SMN in neonatal mice resulted in a classic SMA-like phenotype. Unexpectedly, depletion of SMN in adults had relatively little effect. Insensitivity to low SMN emerged abruptly at postnatal day 17, which coincided with establishment of the fully mature neuromuscular junction (NMJ). Mature animals depleted of SMN eventually exhibited evidence of selective neuromuscular pathology that was made worse by traumatic injury. The ability to regenerate the mature NMJ in aged or injured SMN-depleted mice was grossly impaired, a likely consequence of the inability to meet the surge in demand for motoneuronal SMN that was seen in controls. Our results demonstrate that relative maturity of the NMJ determines the temporal requirement for the SMN protein. These observations suggest that the use of potent but potentially deleterious SMN-enhancing agents could be tapered in human patients once the neuromuscular system matures and reintroduced as needed to enhance SMN for remodeling aged or injured NMJs.
Symposium: reproduction in baboons. The baboon oviduct: characteristics of an oestradiol-dependent oviduct-specific glycoprotein
Authors: H. Verhage
Journal: Human Reproduction Update (1997)

The baboon oviductal epithelium differentiates into a tall columnar epithelium consisting of ciliated and secretory cells during the follicular phase of the menstrual cycle in response to rising oestradiol levels. The apical tips of these secretory cells are filled with membrane-bound secretory granules. During the luteal phase when progesterone levels are elevated, the epithelium regresses and deciliation occurs. Analysis of secretory proteins obtained from explant culture media by SDS-PAGE followed by fluorography or Western Blots has revealed that the baboon oviduct synthesizes and secretes a high molecular weight glycoprotein during the follicular phase of the cycle. Immunocytochemistry demonstrated that the oviductal glycoprotein is localized to the secretory granules of epithelial secretory cells, is oviduct specific, and that following secretion the oviductal glycoprotein binds to the zona pellucida and periviteline space of ovulated oocytes and embryos within the oviduct. Similar proteins have been characterized in other mammalian species. cDNA data show that the complete coding sequence is 2228 bp for a protein of 623 amino acids. A Genbank search showed that baboon oviductal glycoprotein has high homology to other oviductal glycoprotein sequences at both the nucleotide and amino acid levels. Studies conducted to date probing the biological function of oviductal glycoprotein indicate that this protein plays a role in prefertilization reproductive events (sperm capacitation; sperm-zona binding; zona penetration). Additional experiments are needed to reveal a specific function and mechanism for this molecule.
Christine Anne Ellington (née Wellard)
Authors: Mary J Lloyd
Journal: BMJ (2004)

Former general practitioner Altrincham (b 1940; q Royal Free Hospital, London, 1964), died from cardiomyopathy on 2 January 2004.

Christine held house appointments at the Royal Free and in Sheffield, where she started her interest in paediatrics. She moved to Altrincham to join a practice housed in an old school attached to the church where her husband, David, was the vicar. She was forced to leave general practice because of prolonged physical debility; this was later followed by intractable depressive illness, but for some time she trained and participated in a counselling career. She leaves David, her children, and her grandchildren.
Abstract 5541: The dual effects of H6D polymorphism of NAG-1/GDF15 in prostate cancer carcinogenesis
Authors: Xingya Wang, Zongli Xu, Kali Chrysovergis, Rachelle Bienstock, Minsub Shim, Jeannette T. Bensen, Elizabeth Fontham, Gary J. Smith, James Mohler, Jack Taylor, Thomas E. Eling
Journal: Cancer Research (2011)

Abstract Nonsteroidal anti-inflammatory drug-activated gene (NAG-1) is a divergent member of the transforming growth factor beta superfamily. NAG-1 has been implicated in many cellular processes, including inflammation, early bone formation, apoptosis, and tumorigenesis, in several types of cancers. Evidence from recent clinical studies suggests that a C to G single nucleotide polymorphism at position 6 (histidine to aspartic acid substitution, or H6D (G) of the NAG-1 protein is associated with lower incidence, but higher rate of mortality, of prostate cancer. The objective of the current study was to determine the activity of the NAG-1 H6D variant in prostate cancer using two different approaches. First, DU145 cells stably transfected with the H6D NAG-1 gene, wild-type NAG-1 gene, and empty pLXIN vector were injected into nude mice subcutaneously and tumor growth monitored for eight weeks. The H6D variant was less tumorigenic than the wild-type NAG-1, and significantly inhibited tumor growth, 67% by volume and 59% by tumor weight compared to control mice. The growth inhibition by the H6D variant of NAG-1 was associated with significant reduction of serum levels of adiponectin, leptin, and IGF-1, and expression of Cyclin D1 in tumor samples. Second, we examined whether the sequence variant in the NAG-1 gene was associated with prostate cancer tumor aggressiveness in blood samples from the North Carolina-Louisiana Prostate Cancer Project (PCaP). A total of 449 Caucasians Americans and 413 African Americans were examined for allele frequencies using Taqman SNP genotyping assay. Although statistically insignificant, African Americans carrying the H6D (G) allele had an increased risk of more aggressive prostate cancer than those carrying two copies of the C allele (Odds ratio, 1.63; 95% CI, 0.903-2.95; P = 0.25). This result may help to explain the higher mortality rate of prostate cancer in African Americans. In conclusion, our data suggest that the H6D polymorphism of NAG-1 may have a dual effect during the early and late stages of prostate cancer carcinogenesis. More studies are needed to further examine the association of H6D variant of NAG-1 with prostate cancer incidence and progression. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 5541. doi:10.1158/1538-7445.AM2011-5541
Potential health effects of indoor radon exposure.
Authors: E P Radford
Journal: Environmental Health Perspectives (1985)

Radon-222 is a ubiquitous noble gas arising from decay of radium-226 normally present in the earth's crust. Alpha radiation from inhaled short-lived daughters of radon readily irradiates human bronchial epithelium, and there is now good evidence of excess risk of lung cancer in underground miners exposed to higher concentrations. In homes, radon levels are highly variable, showing approximately log-normal distributions and often a small fraction of homes with high concentrations of radon and radon daughters. Factors affecting indoor concentrations include type of bedrock under dwellings, house foundation characteristics, radon dissolved in artesian water, and ventilation and degree of air movement in living spaces. Despite much recent work, exposures to radon daughters by the general public are not well defined. From application of risk assessments in miners to home conditions, it appears that about 25% or more of lung cancers among nonsmokers over the age of 60, and about 5% in smokers, may be attributable to exposure to radon daughters at home. It may be necessary to take remedial action to reduce this hazard in those dwellings with elevated levels of radon, and new construction should take account of this problem.
Androgen Suppression and Radiation vs Radiation Alone for Prostate Cancer
Authors: Anthony V. D’Amico, Ming-Hui Chen, Andrew A. Renshaw, Marian Loffredo, Philip W. Kantoff
Journal: JAMA (2008)

Comorbidities may increase the negative effects of specific anticancer treatments such as androgen suppression therapy (AST).To compare 6 months of AST and radiation therapy (RT) to RT alone and to assess the interaction between level of comorbidity and all-cause mortality.At academic and community-based medical centers in Massachusetts, between December 1, 1995, and April 15, 2001, 206 men with localized but unfavorable-risk prostate cancer were randomized to receive RT alone or RT and AST combined. All-cause mortality estimates stratified by randomized treatment group and further stratified in a postrandomization analysis by the Adult Comorbidity Evaluation 27 comorbidity score were compared using a log-rank test.Time to all-cause mortality.As of January 15, 2007, with a median follow-up of 7.6 (range, 0.5-11.0) years, 74 deaths have occurred. A significant increase in the risk of all-cause mortality (44 vs 30 deaths; hazard ratio [HR], 1.8; 95% confidence interval [CI], 1.1-2.9; P = .01) was observed in men randomized to RT compared with RT and AST. However, the increased risk in all-cause mortality appeared to apply only to men randomized to RT with no or minimal comorbidity (31 vs 11 deaths; HR, 4.2; 95% CI, 2.1-8.5; P < .001). Among men with moderate or severe comorbidity, those randomized to RT alone vs RT and AST did not have an increased risk of all-cause mortality (13 vs 19 deaths; HR, 0.54; 95% CI, 0.27-1.10; P = .08).The addition of 6 months of AST to RT resulted in increased overall survival in men with localized but unfavorable-risk prostate cancer. This result may pertain only to men without moderate or severe comorbidity, but this requires further assessment in a clinical trial specifically designed to assess this interaction.clinicaltrials.gov Identifier: NCT00116220.
No more top-down reorganisation in mental health but much more funding, experts urge
Authors: M. Limb
Journal: BMJ (2015)

Mental health experts have called on all political parties to commit to radically boosting mental healthcare spending and cautioned against further major structural reorganisation.

They said that the quality of services varied too much and that patients needed far better access to treatments including psychological therapies, community support, and crisis care.

Paul Farmer, chief executive of the mental health charity Mind, estimated that a minimum 10% increase in real terms spending on mental health was required by the end of the next parliament. He said, “We can do all kinds of efficiencies, we can do all kinds of things to try and make the system as good as it can be, but there quite simply isn’t enough resource in the system.”

Claire Murdoch, chief executive of Central and North West London NHS Foundation Trust, said it was a “disgrace” that mental healthcare had suffered from real terms “disinvestment” in recent years and from “fractured commissioning.” Calling for a new revolution in mental healthcare, she said, “The answer is not big structural reorganisation; it’s about developing pathways of care that are truly integrated.”

The pair spoke on …
Clinical and the Prognostic Characteristics of Lung Adenocarcinoma Patients with ROS1 Fusion in Comparison with Other Driver Mutations in East Asian Populations
Authors: Yen-Fu Chen, Min-Shu Hsieh, Shang-Gin Wu, Yih-Leong Chang, Jin-Yuan Shih, Yi-Nan Liu, Meng-Feng Tsai, Tzu-Hsiu Tsai, Chong-Jen Yu, James Chih-Hsin Yang, Pan-Chyr Yang
Journal: Journal of Thoracic Oncology (2014)
Improving the results of treating gastric cancer.
Authors: P. J. Milewski, J. Bancewicz
Journal: BMJ (1989)

Organisation, establishing a national drugs list, importing generic drugs at low cost, and ensuring proper storage and distribution.A further objection to the scheme is the almost inevitable deterioration of rational prescribing: paying patients will see it as their right to demand drugs and injections, which may be inappropriate; and health staff will be under pressure to prescribe if their salary depends on drug profits.Unicef recognises the enormous problems of implementing the policy, yet its solutions and strategies remain vague.Community management of revolving drug funds is dealt with by initial training courses, but there is no commitment to continued support and evaluation locally.Unicef still expects to scale up schemes rapidly in participating countries to nationwide implementation; yet suddenly introducing the initiative with so many changes and little attention to detail is likely to be counterproductive.Unicef has been criticised before for dreaming up global solutions organised from the top down.7Much basic spade work must be done locally to ensure that the scheme is properly understood.Other sources of funding -whether through risk sharing, insurance schemes, or taxation-need to be considered.8Host governments should commit themselves to continued financial and supervisory input and to maintaining control over their own health services.Avenues of communication between participating staff and governments need to be established and maintained to share the experiences of financing schemes.Gradual and sensitive introduction, with careful monitoring of equity,' utilisation, and rational drug use from the outset, is essential to prevent failure of this important proposal.
The Inhibitory Effect of (−)-Epigallocatechin Gallate on Activation of the Epidermal Growth Factor Receptor Is Associated with Altered Lipid Order in HT29 Colon Cancer Cells
Authors: Seiji Adachi, Tomokazu Nagao, Helgi I. Ingolfsson, Frederick R. Maxfield, Olaf S. Andersen, Levy Kopelovich, I. Bernard Weinstein
Journal: Cancer Research (2007)

Abstract (−)-Epigallocatechin gallate (EGCG), a major biologically active constituent of green tea, inhibits activation of the epidermal growth factor (EGF) receptor (EGFR) and downstream signaling pathways in several types of human cancer cells, but the precise mechanism is not known. Because several plasma membrane-associated receptor tyrosine kinases (RTK) including EGFR are localized in detergent-insoluble ordered membrane domains, so-called “lipid rafts,” we examined whether the inhibitory effect of EGCG on activation of the EGFR is associated with changes in membrane lipid order in HT29 colon cancer cells. First, we did cold Triton X-100 solubility assays. Phosphorylated (activated) EGFR was found only in the Triton X-100–insoluble (lipid raft) fraction, whereas total cellular EGFR was present in the Triton X-100–soluble fraction. Pretreatment with EGCG inhibited the binding of Alexa Fluor 488–labeled EGF to the cells and also inhibited EGF-induced dimerization of the EGFR. To examine possible effects of EGCG on membrane lipid organization, we labeled the cells with the fluorescent lipid analogue 1, 1′-dihexadecyl-3,3,3′,3′-tetramethylindocarbocyanine perchlorate, which preferentially incorporates into ordered membrane domains in cells and found that subsequent treatment with EGCG caused a marked reduction in the Triton X-100–resistant membrane fraction. Polyphenon E, a mixture of green tea catechins, had a similar effect but (−)-epicatechin (EC), the biologically inactive compound, did not significantly alter the Triton X-100 solubility properties of the membrane. Furthermore, we found that EGCG but not EC caused dramatic changes in the function of bilayer-incorporated gramicidin channels. Taken together, these findings suggest that EGCG inhibits the binding of EGF to the EGFR and the subsequent dimerization and activation of the EGFR by altering membrane organization. These effects may also explain the ability of EGCG to inhibit activation of other membrane-associated RTKs, and they may play a critical role in the anticancer effects of this and related compounds. [Cancer Res 2007;67(13):6493–501]
Identifying Stage III Colorectal Cancer Patients: The Influence of the Patient, Surgeon, and Pathologist
Authors: Eva Judith Ann Morris, Nicola Joanne Maughan, David Forman, Philip Quirke
Journal: Journal of Clinical Oncology (2007)

Nodal yields from resected colorectal cancers vary greatly. This study sought to determine what patient, tumor, and management factors influence the number of nodes retrieved and to determine if the extent of lymphadenectomy affects stage allocation and influences survival.Retrospective study of the nodal yields of 7,062 surgically resected colorectal cancer patients for whom colorectal pathology minimum data sets had been collected. The percentage of patients diagnosed as stage III was compared across nodal yield categories. A threshold for an adequate lymphadenectomy was defined as retrieval of 12 nodes. Binary logistic regression was used to determine factors associated with obtaining an adequate lymphadenectomy.Median nodal yields increased over the study period from 7 (interquartile range [IQR], 4 to 11) in 1995 to 13 (IQR 8 to 19) in 2003. There was no difference in yield by cancer site or sex, but yields were lower in older patients. Yields increased with increasing local invasion and stage of tumor. The percentage of patients diagnosed as stage III increased as yields increased. Five-year survival was lower in those patients who did not have an adequate lymphadenectomy. Adequate lymphadenectomy was significantly more likely in patients with advanced tumors and when the surgery and pathology was undertaken by a specialist. Older patients were significantly less likely to receive an adequate lymphadenectomy.Variations in nodal yield are due to idiosyncratic patient and tumor characteristics and differences in the quality of surgery and pathology undertaken. Adequate lymphadenectomy is essential to ensure correct stage allocation and optimal survival.
APPENDICITIS; WITH ORIGINAL REPORT AND ANALYSIS OF ONE HUNDRED AND FORTY-ONE HISTORIES AND LAPAROTOMIES FOR THAT DISEASE UNDER PERSONAL OBSERVATION.
Authors: J. B. MURPHY
Journal: JAMA (1894)

(Concluded from page S89). Case 110.—Date of operation Aug. 17,1893. Operator, Dr. Murphy. Case occurred in practice of Dr. Pigall. R. S. B., aged 33 years; male. Post-Graduate Hospital. Patient was kicked on July 31 in the right side by a man. The same night, at 2 a.m., he was attacked with sudden pain in right iliac region, followed by fever, tenderness and tympanites. These symptoms continued up to the time of operation. Examination: Large tumor in right iliac region, extending almost to umbilicus; no fluctuation could be detected; no edema or redness of the wall; dull on percussion, both superficial and deep. A differential diagnosis was made between rupture of kidney, rupture of cecum and appendicitis in favor of the latter. Operation: Lateral incision; abscess wall adherent to anterior wall of abdomen; general peritoneal cavity not opened. Abscess circumscribed; drained; appendix not removed; recovery. Case 111.—Date of operation Aug.