tbuckley/cabot-search huggingface dataset:
Preparedness and phobias: Specific evolved associations or a generalized expectancy bias?
Authors: Graham C. L. Davey
Journal: Behavioral and Brain Sciences (1995)

Abstract Most phobias are focussed on a small number of fear-inducing stimuli (e.g., snakes, spiders). A review of the evidence supporting biological and cognitive explanations of this uneven distribution of phobias suggests that the readiness with which such stimuli become associated with aversive outcomes arises from biases in the processing of information about threatening stimuli rather than from phylogenetically based associative predispositions or “biological preparedness.” This cognitive bias, consisting of a heightened expectation of aversive outcomes following fear-relevant stimuli, generates and maintains robust learned associations between them. Some of the features of such stimuli which determine this expectancy bias are estimates of how dangerous they are, the semiotic similarity between them and their aversive outcomes, and the degree of prior fear they elicit. Ontogenetic and cultural factors influence these features of fear-relevant stimuli and are hence important in determining expectancy bias. The available evidence does not exclude the possibility that both expectancy biases and specific evolved predispositions coexist, but the former can explain a number of important findings that the latter cannot.
Human recombinant granulocyte-macrophage colony stimulating factor and interleukin 3 have overlapping but distinct hematopoietic activities.
Authors: S G Emerson, Y C Yang, S C Clark, M W Long
Journal: Journal of Clinical Investigation (1988)

The hematopoietic stimulatory activities of human recombinant IL-3 and granulocyte-macrophage colony stimulating factor (GM-CSF) were directly compared using highly enriched human bone marrow progenitor target cells. IL-3 supported a larger number of erythroid and megakaryocytic progenitor cells than did GM-CSF, while GM-CSF supported more myeloid progenitors. IL-3 directly stimulated the division and migration of primitive erythroid burst forming units, while GM-CSF merely sustained their net survival in culture without promoting division and expansion. IL-3 promoted the formation of larger numbers of multipotential granulocyte-erythroid-macrophage-megakaryocyte colony forming unit--derived colonies than did GM-CSF. These data indicate that human IL-3 and GM-CSF have overlapping but distinct hematopoietic activities, and suggest a potential role for the clinical application of combined IL-3/GM-CSF therapy.
Ciprofloxacin or Trimethoprim-Sulfamethoxazole as Initial Therapy for Travelers' Diarrhea
Authors: Ericsson Cd, Johnson Pc, Dupont Hl, Morgan Dr, Bitsura Ja, de la Cabada Fj
Journal: Annals of Internal Medicine (1987)

The efficacy of ciprofloxacin was compared with that of trimethoprim-sulfamethoxazole in a placebo-controlled trial of the 5-day treatment of acute diarrhea among 181 adults recently arrived in Guadalajara, Mexico. Both antimicrobial agents were significantly (p < 0.0001) more efficacious than placebo in the treatment of diarrhea, with the average duration of diarrhea being 29, 20, and 81 hours, respectively, in the ciprofloxacin, trimethoprim-sulfamethoxazole, and placebo treatment groups. The antimicrobial agents were also more efficacious than placebo in treating diarrhea caused by enterotoxigenic Escherichia coli, invasive enteropathogens, and unknown pathogens. Both antimicrobials were effective in treating mild-to-moderate and moderate-to-severe disease, and both were well tolerated. Ciprofloxacin appears to be a logical alternative to trimethoprim-sulfamethoxazole in the initial treatment of acute travelers' diarrhea.
Effects of short-term administration of verapamil on left ventricular relaxation and filling dynamics measured by a combined hemodynamic-ultrasonic technique in patients with hypertrophic cardiomyopathy.
Authors: F J TenCate, P W Serruys, S Mey, J Roelandt
Journal: Circulation (1983)

The effects of short-term administration of verapamil on left ventricular isovolumetric relaxation and early and late diastolic filling dynamics were studied in 10 patients with hypertrophic cardiomyopathy by a combined hemodynamic-ultrasonic technique. Left ventricular pressures (recorded with high-fidelity micromanometers) were determined simultaneously with M mode echocardiography. After 10 mg of verapamil was given intravenously (2 mg/min), left ventricular contractility and systolic pressure dropped significantly (p less than .05). Left ventricular dP/dt fell from 1947 +/- 544 to 1489 +/- 334 mm Hg/sec, maximal velocity of the contractile element at zero load fell from 50 +/- 17 to 42 +/- 15 1/sec, peak velocity contraction of the contractile element fell from 37 +/- 10 1/sec to 29 +/- 10 1/sec (p less than .05), and left ventricular systolic pressure fell from 149 +/- 30 to 127 +/- 22 mm Hg. Left ventricular negative dP/dt increased from 1770 +/- 479 to 1477 +/- 377 mm Hg/sec (p less than .05), and the time constant of isovolumetric pressure decay was prolonged from 48 +/- 9 to 64 +/- 15 msec (p less than .05). Left ventricular end-diastolic pressure rose from 21 +/- 7 to 23 +/- 6 mm Hg (p less than .05). The time constant of isovolumetric pressure decay was calculated in three different ways, but none of these measurements was influenced by verapamil. Time of isovolumetric relaxation, duration of rapid ventricular filling, and peak rate of left ventricular lengthening were not significantly influenced by verapamil and remained highly abnormal. In contrast, peak rate of left ventricular posterior wall thinning declined further after verapamil from 2.9 +/- 1.2 to 2.4 +/- 1.4 1/sec (p less than .05).(ABSTRACT TRUNCATED AT 250 WORDS)
Smallpox Vaccination vs Inoculation
Authors: Geoffrey Edsall
Journal: JAMA (1964)

<h3>To the Editor:—</h3> In the Aug 17 issue ofThe Journal(<b>189:</b>588, 1964) there appears a letter telling of smallpox "vaccination" in Fairfield in 1782. What it describes, though, is not vaccination but inoculation. It might be well to emphasize the differences between the two. Vaccination, introduced by Jenner in 1798, was based upon the use of a mild, attenuated virus (cowpox virus) which produced a local infection at the site of inoculation yet led to a high level of immunity to smallpox. This procedure was called "vaccination" because the material used came from cows (Latin<i>vacca,</i>cow). Inoculation, however, is what was performed in 1782. Smallpox inoculation, or variolation, as it was often called, was carried out by inoculating the smallpox virus itself into the skin. This procedure, or variations of it, had been practiced since ancient times in Asia and perhaps in Africa, but was not introduced
Sleep Deprivation and Performance of Residents
Authors: Jeffrey M. Feldman
Journal: JAMA (1989)

<h3>To the Editor.—</h3> The study entitled "Sleep Deprivation and Resident Performance" by Deaconson et al<sup>1</sup>provides insight into the impact of sleep deprivation on performance during psychometric testing. I find it reassuring that sleep deprivation would not impair one's performance on cognitive and psychomotor tests. I do, however, take exception to the conclusion that, "by implication, performance in the provision of patient care" is not impaired. My objections are based on several concerns. First, the authors did not present any evidence other than conjecture that performance on these psychometric tests is relevant to caring for patients. Certainly, cognitive and psychomotor skills are required for patient care. However, caring for patients also requires compassion, empathy, and the ability to establish a patient/physician relationship and to exercise complex medical judgment. None of these skills were evaluated in this study by psychometric testing. Another issue not addressed by Deaconson et al is
Over half the world will face water shortages by 2032
Authors: A. Vass
Journal: BMJ (2002)

More than half of the world's population will be affected by water shortages by 2032, causing severe health consequences, unless urgent action is taken, says an international report published last week.

The findings are part of a 450 page United Nations document that analyses almost every aspect of environmental degradation over the last 30 years and looks forward at the likely prospects for the next 30. It is designed to set the framework for the …
Cholera could infect 400 000 Haitians if interventions are not stepped up
Authors: J. Zarocostas
Journal: BMJ (2010)

The World Health Organization and UN relief agencies have drastically revised upwards the number of additional medical personnel needed to help contain the spread of the cholera outbreak in Haiti, which continues to spread in all of the island’s 10 departments.

WHO and its regional arm—Pan American Health Organization (PAHO)—estimate that an additional 350 doctors and 2000 nurses are needed mainly to run cholera treatment centres. An extra …
Oklahoma suspends executions for lack of drugs and medical personnel
Authors: O. Dyer
Journal: BMJ (2014)

The state of Oklahoma has suspended scheduled executions until 15 January 2015 “at the earliest,” saying that it can procure neither the lethal injection drugs nor the qualified medical personnel needed to carry them out.

The announcement came as a physician who took part in the state’s last, badly botched execution was named as a defendant in a federal lawsuit by the prisoner’s family, despite state legislation making execution team doctors’ identities an Oklahoma state secret.

As a drug industry embargo on selling lethal drugs to state corrections departments continues to bite, Delaware, with no executions scheduled, declared early this year that it would cease trying to find lethal injection drugs, and Washington state suspended the death penalty in February. But …
Trust is Not Enough: Bringing Human Rights to Medicine
Authors: Berna Arda
Journal: BMJ (2006)

One of my professors used to say, “Today's actuality is tomorrow's history.” This aphorism highlights the dynamic nature of history but also reminds us that we need to be conscientious concerning events occurring in our own time, as we will be judged by tomorrow's observers. In this book the Rothmans, two social historians, cover the actuality today of the balance between medicine and human rights. 

At the beginning of the 21st century we look back to the earlier decades of the 20th as a time of gross examples of the collision between medicine and human rights: the Nazis' experiments on humans, …
Induction of Toll-like receptor 2 and 4 expression on CD4+ and CD8+ T cells in G-CSF-mobilized unrelated peripheral blood stem cell grafts during leukapheresis: impact on patient outcome
Authors: U Platzbecker, J Stoehlmacher, C Pabst, E Goekkurt, U Oelschlägel, H Schirutschke, K Hölig, C Theuser, U Mogck, G Ehninger, M Bornhäuser
Journal: Leukemia (2007)
Ethical Constraints and Imperatives in Medical Research
Authors: Thomas K. McElhinney
Journal: JAMA (1976)

This book attempts to reverse a trend in the discussion of ethical questions associated with medical research. Instead of concentrating on the ways in which modern research methods raise problems about individual rights, the author's main premise is that such research is morally justified in order that medicine may better understand how to avoid injury. Visscher says, "If it is, as seems obvious, obligatory upon physicians to learn how to do no harm, then scientific investigation, including that on human subjects becomes a necessity for an ethical medical profession." Although brevity is not ipso facto to be commended, the precise statements of the major ethical issues in medical research found in this writing are indeed worthy of praise. In only 112 pages, Visscher is able to inform his readers of the problems in a number of important areas, including genetic engineering, studies on children, studies in psychology and psychiatry, research
Abstract 1446: Dissecting the role of PTEN/Akts in metastatic melanoma
Authors: Yanlin Yu, Ziyang Liu, Yixin Yu, Arnulfo Mendoza, Chand Khanna, Glenn Merlino
Journal: Cancer Research (2011)

Abstract Melanoma is an aggressive human cancer whose incidence is increasing more rapidly than any other cancer in the United States. It is characterized by an extremely high potential to develop metastases and poor response to current therapy. Although the genetic studies indicated that melanoma genesis related with molecular lesions in c-MET, INK4a, Ras/Raf, p53 and PTEN pathways, the molecular mechanism inciting metastatic melanoma are poorly understood. PTEN is a major tumor suppressor in humans. To study the role of PTEN in progression of human melanoma, we first used tissue microarrays to examine PTEN expression in 30 lymph node melanoma metastases, 30 primary melanomas, and 9 normal skin tissues. Our results showed that PTEN loss was significantly correlated with progression to the metastatic state. Moreover, analysis of various human melanoma cell lines demonstrated that PTEN expression was related to metastatic behavior, supporting the notion that PTEN is involved in the metastatic regulation of melanoma. PTEN has phosphatase activity that can act upon both polypeptide and phosphoinositide substrates. The PTEN lipid phosphatase is a ubiquitous regulator of PI3K signaling pathway. The loss of expression or mutational inactivation of PTEN protein enhances the phosphorylation of PKB/AKT and thus influences cell survival signaling. Interestingly, a PTEN mutant, which loses lipid but not protein phosphatase activity, lacks the ability to induce either G1 arrest or apoptosis, but nonetheless retains the ability to inhibit cell spreading and motility, suggesting that PTEN protein phosphatase activity is important for these behaviors. To further dissect the role of this PTEN activity in metastasis, we have established a model system containing exploiting mutant PTEN proteins with various phosphatase activities. We found that wild type PTEN can inhibit cell motility and invasiveness, while PTEN mutants cannot. Notably, wild type PTEN was able to reduce the metastatic potential of melanoma cells, whereas phosphatase deficient PTEN could promote the melanoma cell metastatic behavior. We found that PTEN mediates metastatic activity through the AKT pathway. We further determined that Akt 3 was key mediators of metastatic potential in melanoma cells in vivo. Akt3 could also rescue PTEN-mediated inhibition of metastasis. PTEN loss and Akt3 overexpression functioned synergistically to promote metastasis. Our data demonstrate that metastatic behavior in melanoma cells is dependent on the status of PTEN protein phosphatase activity and downstream Akt3, and suggest that AKT/PTEN signaling should be considered as a therapeutic target in metastatic melanoma 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 1446. doi:10.1158/1538-7445.AM2011-1446
Association between diabetes, family history of diabetes, and risk of nonalcoholic steatohepatitis and fibrosis
Authors: Rohit Loomba, Maria Abraham, Aynur Unalp, Laura Wilson, Joel Lavine, Ed Doo, Nathan M. Bass
Journal: Hepatology (2012)

Previous studies have shown familial aggregation of insulin resistance and nonalcoholic fatty liver disease (NAFLD). Therefore, we aimed to examine whether family history of diabetes mellitus (DM) is associated with nonalcoholic steatohepatitis (NASH) and fibrosis in patients with NAFLD. This was a cross-sectional analysis in participants of the NAFLD Database study and PIVENS trial who had available data on family history of DM. One thousand and sixty-nine patients (63% women), with mean age of 49.6 (± 11.8) years and body mass index (BMI) of 34.2 (± 6.4) kg/m2, were included. Thirty percent had DM, and 56% had a family history of DM. Both personal history of DM and family history of DM were significantly associated with NASH, with an odds ratio (OR) of 1.93 (95% confidence interval [CI]: 1.37–2.73; P &lt;0.001) and 1.48 (95% CI: 1.11–1.97; P = 0.01) and any fibrosis with an OR of 3.31 (95% CI: 2.26–4.85; P &lt; 0.001) and 1.66 (95% CI: 1.25–2.20; P &lt; 0.001), respectively. When the models were adjusted for age, sex, BMI, ethnicity, and metabolic traits, the association between diabetes and family history of DM with NASH showed an increased adjusted OR of 1.76 (95% CI: 1.13–2.72; P &lt; 0.001) and 1.34 (95% CI: 0.99–1.81; P = 0.06), respectively, and with any fibrosis with a significant adjusted OR of 2.57 (95% CI: 1.61–4.11; P &lt; 0.0001) and 1.38 (95% CI: 1.02–1.87; P = 0.04), respectively. After excluding patients with personal history of diabetes, family history of DM was significantly associated with the presence of NASH and any fibrosis with an adjusted OR of 1.51 (95% CI: 1.01–2.25; P = 0.04) and 1.49 (95% CI: 1.01–2.20; P = 0.04), respectively. Conclusions: Diabetes is strongly associated with risk of NASH, fibrosis, and advanced fibrosis. Family history of diabetes, especially among nondiabetics, is associated with NASH and fibrosis in NAFLD.
Abstract 2387: Activation of Inhibin A signaling is associated with a basal-like HER2 subtype and resistance to lapatinib in breast cancer cell lines.
Authors: James E. Korkola, Juha Rantala, Nora Bayani, Laura Heiser, Nicholas Wang, Obi Griffith, Joe Gray
Journal: Cancer Research (2013)

Abstract HER2 amplification occurs in ∼20% of all breast cancers, and is associated with poor prognosis. Targeted therapeutics such as trastuzumab and lapatinib have been developed and have improved outcomes for patients with HER2+ disease. However, a significant proportion of patients have tumors that either develop resistance or simply fail to respond to these therapies at all. To better understand the mechanism of resistance, we screened a panel of 22 HER2+ breast cancer cell lines with lapatinib. Of these, 6 showed significant resistance, failing to reach 50% growth inhibition (GI50) even at 5uM, the highest dose tested. The resistant lines were all more basal-like in expression patterns, and were more responsive to MEK inhibitors than their luminal-like counterparts. These two patterns of expression are similar to the different HER2 subtypes recently identified by the TCGA project. Differential expression analysis utilizing t-tests with Benjamini-Hochberg correction for multiple comparisons identified approximately 150 transcripts that were more highly expressed in resistant cell lines. We performed high-throughput screening using siRNA knockdown of the target genes in combination with lapatinib treatment. Staining for markers of proliferation (Ki67), apoptosis (cleaved PARP), and activity of the PI3K-AKT pathway showed that silencing of inhibin A resulted in a decrease in the ratio of proliferative to apoptotic cells in the resistant cell lines 21-NT and 21-PT. Concurrent with this decrease was a down-regulation of both p-MAPK and p-AKT. GO analysis revealed a strong enrichment for Inhibin A signaling amongst the 150 resistance associated transcripts. Mining of tumor databases revealed that there was a trend between high levels of Inhibin A expression and poor outcome in HER2 positive tumors (p=0.08). These data suggest that activation of Inhibin A signaling is associated with a more basal like subclass of HER2+ tumors, resistance to HER2 targeted therapeutics such as lapatinib, and that corresponding over-expression of Inhibin A is associated with poor outcome in HER2+ patients. Citation Format: James E. Korkola, Juha Rantala, Nora Bayani, Laura Heiser, Nicholas Wang, Obi Griffith, Joe Gray. Activation of Inhibin A signaling is associated with a basal-like HER2 subtype and resistance to lapatinib in breast cancer cell lines. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2387. doi:10.1158/1538-7445.AM2013-2387
Military Medicine Faces at Least 4 More Months of Supporting US, Other Peacekeepers in Somalia
Authors: Phil Gunby
Journal: JAMA (1993)

THIS YEAR'S meeting of the Association of Military Surgeons of the United States (AMSUS)—which ended just over a week ago—was held in San Antonio, Tex. But the thoughts of many of those present, whether active ser-vice personnel, reservists, or retirees, were on Somalia, where US military medicine continues to cope with appalling and often dangerous conditions. In addition to combat wounds, other injuries, and disease among US personnel, the US Army's 46th Combat Support Hospital/Medical Task Force 46 in the Somali capital of Mogadishu also provides some medical support for some of the other nations' United Nations (UN) peacekeeping troops and treats Somali civilians when circumstances dictate and permit. Although there are a great many sources of disease in Somalia, US military medical people have encountered just one case of HIV infection among the patients seen to date. That was a Somali who underwent testing before US military physicians performed
End-organ resistance to growth hormone and IGF-I in epiphyseal chondrocytes of rats with chronic renal failure
Authors: Robert H.K. Mak, Youngmi K. Pak
Journal: Kidney International (1996)

We tested the hypothesis that there is direct end-organ resistance to growth hormone (GH) and IGF-I in chronic renal failure (CRF) independent of circulating inhibitors. Male Sprague-Dawley rats underwent 5/6 nephrectomy and were pair-fed with weight matched (100 g) sham operated controls for two weeks. Rats with CRF had significantly higher serum creatinine and blood urea nitrogen (P < 0.01 in both cases) and gained significantly less weight and length (P < 0.01 in both cases) compared with controls. Epiphyseal chondrocytes were grown in 10% fetal calf serum (FCS). Both CRF cells and control cells maintained chondrogenic phenotypes, and showed immunohistochemical staining with antibodies to collagen II and proteoglycan (aggrecan). Distribution of the cell subpopulations according to cell size (by flow cytometry) and alkaline phosphatase activity of CRF and control chondrocyte cultures were not different. Growth responses of CRF chondrocytes were reduced (P < 0.01) compared with control chondrocytes when grown in 10% FCS and 10% normal rat serum. Under serum free conditions, growth responses of CRF chondrocytes were reduced to GH and IGF-I at concentrations of 10, 30 and 100 ng/ml, and to insulin at 100, 300 and 1,000 ng/ml compared with controls cells (P < 0.01). To show that this resistance is specific for the GH/IGF system, growth responses to fibroblast growth factor and transforming growth factor beta 1 were studied and showed no difference between CRF and control cells. Thus, the present study provides direct evidence of specific end-organ resistance to GH, IGF-I in CRF chondrocytes in the absence of circulating factors.