tbuckley/cabot-search huggingface dataset:
The pathogenesis of miliaria rubra.
Authors: ERHARD HOLZLE, ALBERT M. KLIGMAN
Journal: British Journal of Dermatology (1978)

Anhidrosis was induced in volunteers by covering the skin with an impermeable plastic film. The degree of sweat suppression and miliaria after a thermal stimulus was directly proportional to the increase in the density of resident aerobic bacteria, notably cocci. No anhidrosis resulted when antibacterial substances were used to prevent the expansion of the microflora. Histological study showed a PAS-positive diastase resistant amorphous mass deep within the acrosyringium after 2 days of occlusion, accompanied by a periductal dermal infiltration of leukocytes. After another 2 days the duct became clogged by an amalgam of degenerating leukocytes. This impaction sloughed after about 3 weeks as a result of epidermal renewal. Colonies of bacteria were never found within the ducts. It is postulated that cocci secrete a toxin which injures luminal cells and precipitates a cast within the lumen. Infiltration by leukocytes creates an impaction which completely obstructs the passage of sweat for several weeks.
Monetary value of lost productivity over a five year follow up in early rheumatoid arthritis estimated on the basis of official register data on patients' sickness absence and gross income: experience from the FIN-RACo trial
Authors: K Puolakka
Journal: Annals of the Rheumatic Diseases (2005)

To explore the monetary value of rheumatoid arthritis related loss of productivity in patients with early active disease.In a prospective cohort substudy of the FIN-RACo Trial, 162 patients with recent onset rheumatoid arthritis, aged 18 to 65 years and available to the workforce, were followed up for five years. Loss of work productivity in euros 2002 was estimated by data on absence for sickness and on income (human capital approach) from official databases. Treatment responses were evaluated by area under the curve (AUC) of the ACR-N measure and by increase in number of erosions in radiographs of hands and feet. The health assessment questionnaire (HAQ) at six months was linked to the International Classification of Functioning, Disability and Health (ICF).In all, 120 (75%) patients, women more often (82%) than men (61%) (p=0.002), lost work days. The mean lost productivity per patient-year was euro7217 (95% confidence interval (CI), 5561 to 9148): for women, euro6477 (4858 to 8536) and for men, euro8443 (5389 to 12,898). There was an inverse correlation with improvement: euro1101 (323 to 2156) and euro14 952 (10,662 to 19,852) for the highest and lowest quartiles of AUC of ARC-N, respectively. Lost productivity was associated with increase in the number of erosions and with disability in "changing and maintaining body position" subcategory of the ICF.Despite remission targeted treatment with disease modifying antirheumatic drugs, early rheumatoid arthritis results in substantial loss of productivity. A good improvement in the disease reduces the loss markedly.
P241 ‘CURE-CAP’: A Comprehensive Admission &amp; Discharge Pneumonia Care Bundle
Authors: P Cunningham, J Burke, L McCulloch, R Varia
Journal: Thorax (2013)

<h3>Introduction</h3> The annual incidence of Community acquired pneumonia (CAP) is 5–11/1000. Between 22% and 42% require admission to hospital. Wide variation exists in the management of CAP despite guidelines issued by the British Thoracic Society (BTS). Care bundles have been shown to improve outcomes through standardisation of care in other diseases as well as in CAP. A BTS/NHS Improvement initiative is due to launch a pneumonia admission bundle. However, it does not address the issue of standards around comprehensive discharge care. <h3>Objectives</h3> To design and implement a care bundle for the management of CAP, that incorporates admission and discharge standards and to assess improvements post-implementation. <h3>Methods</h3> We formulated a CAP bundle including a triage tool, with the acronym ‘CURE-CAP’, focussing on seven key standards (Fig. 1). Data was collected retrospectively on consecutive patients admitted to our GP Assessment Unit with a primary diagnosis of CAP with a 3-month period of implementation in between. Compliance to standards before and after implementation of the bundle was then measured. <h3>Results</h3> The pre-implementation cohort had 43 patients (17 (40%) male; median (range) age 74 (36 –101)) and post–implementation cohort had 30 (8 (27%) male; median (range) age 82 (36–93)). Chest x-ray was performed within 4 hrs in 30/43 (70%) in the pre-implementation cohort, increasing to 30/30 (100%) post-implementation. Time from admission to x-ray improved as well (median (range) 2:49 (0:30–18:27) to 1:00 (0:21–2:42). Urgent oxygen assessment was performed in 100% cases in both cohorts. Recording of the CURB-65 severity score improved from 35/43 (81%) to 28/30 (93%). Early antibiotic administration (within 4 hrs) increased from 12/43 (28%) to 20/30 (68%) with appropriate (severity based) antibiotics selection improving from 29/43 (67%) to 28/30 (93%). The bundle led to total compliance with all discharge standards including appropriate smoking cessation counselling (5/7 (71%) to 4/4 (100%)), patient information leaflet provision (0% to 100%) and appropriate follow-up arranged (16/43 (37%) to 30/30 (100%)). <h3>Conclusions</h3> We have successfully designed a CAP admission and discharge care bundle and shown improvements across all measured standards post implementation. A further study is planned to measure effects on direct patient outcomes.
Significance of Axillary Lymph Node Metastasis in Primary Breast Cancer
Authors: Ismail Jatoi, Susan G. Hilsenbeck, Gary M. Clark, C. Kent Osborne
Journal: Journal of Clinical Oncology (1999)

PURPOSE: Axillary lymph node status is the single most important prognostic variable in the management of patients with primary breast cancer. Yet, it is not known whether metastasis to the axillary nodes is simply a time-dependent variable or also a marker for a more aggressive tumor phenotype. The purpose of this study was to determine whether nodal status at initial diagnosis predicts outcome after relapse and therefore also serves as a marker of breast cancer phenotype. PATIENTS AND METHODS: Survival experience after first relapse in 1,696 primary breast cancer cases was analyzed using Cox proportional hazards regression. The following explanatory variables and their first-order interactions were considered: number of axillary lymph nodes involved (zero v one to three v four or more), hormone receptor status (any estrogen receptor [ER] negativity v ER negativity/progesterone receptor positivity v other ER positivity), primary tumor size (&lt; 2 cm v 2 to 5 cm v &gt; 5 cm), site of relapse (locoregional v distant), disease-free interval (&lt; 1.5 years v 1.5 to 3 years v &gt; 3 years), adjuvant endocrine therapy (none v any), adjuvant chemotherapy (none v any), and menopausal status (pre-, peri-, or postmenopausal). RESULTS: Axillary lymph node status, site of relapse, and hormone receptor status were all highly significant as main effects in the model. After adjustment for other variables, disease-free interval alone was only modestly significant but interacted with nodal status. After disease-free interval, hormone receptor status, and site of relapse were accounted for, survival after relapse was poorer in node-positive cases, when compared with node-negative cases. The hazard ratios for patients with one to three and four or more involved nodes were 1.2 (95% confidence interval [CI], 0.8 to 1.9) and 2.5 (95% CI, 1.8 to 3.4), respectively. CONCLUSION: Patients with four or more involved nodes at initial diagnosis have a significantly worse outcome after relapse than node-negative cases, regardless of the duration of the disease-free interval. We conclude that nodal metastasis is not only a marker of diagnosis at a later point in the natural history of breast cancer but also a marker of an aggressive phenotype.
Number of exacerbations in COPD patients treated with nasal high flow heated and humidified oxygen
Authors: Line Margrethe Storgaard, M. Frystyk, H. Hockey, Ulla Møller Weinreich
Journal: European Respiratory Journal (2014)

Introduction:  This randomized, placebo-controlled one-year study of 200 patients is to evaluate the effect of the AIRVO device delivering nasal high flow (NHF) warmed and humidified oxygen-enriched air between 20 to 30 L per minute to COPD patients in need of long term oxygen therapy (LTOT). An interim analysis at six months has evaluated the treatment effect on the number of exacerbations of COPD(AECOPD).   Method : In this prospective study, 86 COPD patients, treated with LTOT, who were randomized to NHF or placebo between March 2012 and July 2013, are included in an interim analysis of AECOPD. Any patients who have discontinued prior to six months are included. The two groups are compared for baseline and demographic characteristics.   Results : Patients to date are equally divided between the NHF (43) and the control (43) groups. The 86 patients are 69% (59/86) female with average age 71 years (range 47-86). The two groups are comparable in age, gender, smoking status, pack years, BMI, mMRC-score, FEV1%, 6 minutes walking test and number of exacerbations 12 months prior to study start. Twenty subjects have not completed to six months for various reasons, including death; 12 in the NHF group (2 deaths) and 8 in the treatment group (3 deaths). There are 71 cases of AECOPD in the NHF group and 119 in the control group, giving a significant difference (p l 0.01) when modeled as Poisson data.   Conclusion : Preliminary analysis results show a significant treatment effect in favor of NHF reducing AECOPD in COPD patients in need of LTOT.
Pediatrics I. Respiratory
Authors: L. Storme, Y. Riou, F. Leclerc, N. Kacet, J. P. Dubos, S. Rousseau, P. Lequien, M. Durand, S. Sardesai, C. McEvoy, M. Alvarado, L. Bindl, U. Herberq, S. Buderus, U. Bode, M. Lentze, V. Varnholt, P. Lasch, G. Suske, W. Kachel, H. Wirth, J. Pfenninger, Th. Kolobow, W. Lindner
Journal: Intensive Care Medicine (1992)
Increased Aortic Intima-Media Thickness
Authors: Mikko J. Järvisalo, Laura Jartti, Kirsti Näntö-Salonen, Kerttu Irjala, Tapani Rönnemaa, Jaakko J. Hartiala, David S. Celermajer, Olli T. Raitakari
Journal: Circulation (2001)

Background — Autopsy studies in children have shown that atherosclerotic lesions begin to develop first in the intima of the aorta. Recent developments in ultrasound techniques have made it possible to visualize the intima-medial thickness of the abdominal aorta directly (aIMT). Therefore, we examined the feasibility of measuring aIMT in children and studied its value in distinguishing high-risk children from healthy controls compared with a more established marker of subclinical atherosclerosis, the common carotid artery intima-medial thickness (cIMT). Methods and Results — IMTs were measured using high-resolution (13 MHz) ultrasound in 88 children (aged 11±2 years); 16 had hypercholesterolemia (LDL cholesterol, 5.1±1.2 mmol/L), 44 had type 1 diabetes (mean duration, 4.4±3.1 years; LDL cholesterol, 2.3±0.7 mmol/L), and 28 were healthy (controls; LDL cholesterol, 2.5±0.8 mmol/L). High-risk children had significantly increased aIMTs and cIMTs (both P &lt;0.001) compared with controls. In controls, aIMT was similar to cIMT ( P =NS), but aIMT was higher than cIMT in the children with hypercholesterolemia and diabetes (both P &lt;0.01). Both markers showed excellent and approximately equal between-observer (&lt;4%) and between-subject variation (&lt;5%). Conclusions — Children with hypercholesterolemia and diabetes show increased IMTs compared with healthy controls, with a relatively greater increase in the aIMT than in the cIMT. Because atherosclerosis begins first in the intima of the aorta, these data suggest that the aIMT might provide the best currently available noninvasive marker of preclinical atherosclerosis in children.
Role of the indoor environment in determining the severity of asthma
Authors: A. Woodcock, A. Custovic
Journal: Thorax (1998)

Allergen exposure can confound the management of asthma. To understand the potential mechanisms by which allergens increase the steroid requirements in atopic asthmatics, we examined the effects of allergens on glucocorticoid receptor (GCR) binding affinity and glucocorticoid (GC) responsiveness of peripheral blood mononuclear cells (PBMC) from atopic asthmatics. A significant reduction (p &lt; 0.001) in the GCR binding affinity (Kd) was observed in ragweed-allergic asthmatics during ragweed pollen season compared with PBMC obtained before and after ragweed season. In vitro effects of allergen on PBMC GCR Kd were also examined by incubating PBMC from atopic asthmatics with allergen (ragweed and cat) versus Candida albicans. GCR binding affinity was significantly reduced after incubation with ragweed (p &lt; 0.001) or cat allergen (p &lt; 0.001) compared with baseline or C. albicans stimulation. This effect was limited to atopic asthmatics in that in vitro cat allergen incubation for 48 h failed to significantly alter GCR binding affinity in nonasthmatic, atopic individuals. These allergen-induced reductions in GCR binding affinity also rendered the PBMC less sensitive to the inhibitory effects of hydrocortisone and dexamethasone on allergen-induced proliferation (p &lt; 0.01). To test the hypothesis that allergen-induced alterations in GCR binding affinity were cytokine- induced, we examined the effects of interleukin-2 (IL-2) and IL-4 neutralization using anticytokine antibodies. Addition of both anti-IL- 2 and anti-IL-4 antibodies resulted in a significant (p &lt; 0.001) inhibition of allergen-induced alterations in GCR binding affinity. Furthermore incubation with cat allergen induced significantly higher concentrations of IL-2 (p = 0.03) and IL-4 (p = 0.02) by PBMC from atopic as compared with nonatopic subjects. Our current observations suggest that allergen exposure may contribute to poor asthma control by reducing GCR binding affinity in mononuclear cells. This appears to be mediated through IL-2 and IL-4. These findings may have important implications for novel approaches to the treatment of poorly controlled asthma.
Short-Term Single-Blind Fluvoxamine Treatment of Pathological Gambling
Authors: Eric Hollander, Concetta M. DeCaria, Eduardo Mari, Cheryl M. Wong, Serge Mosovich, Robert Grossman, Tomer Begaz
Journal: American Journal of Psychiatry (1998)

The authors' goal was to assess the efficacy and tolerability of the selective serotonin reuptake inhibitor fluvoxamine in the treatment of pathological gambling.Sixteen patients with pathological gambling entered an 8-week placebo lead-in phase, and 10 of these patients completed an 8-week single-blind fluvoxamine trial.Seven of the 10 patients who completed the fluvoxamine trial were judged treatment responders at the end of the study: 1) they had greater than 25% decreases in their gambling behavior scores on the pathological gambling modification of the Yale-Brown Obsessive Compulsive Scale, and 2) their clinician-rated Clinical Global Impression scores for gambling severity were very much improved or much improved. Fluvoxamine treatment resulted in gambling abstinence in seven of the 10 patients.Findings from this preliminary study suggest that fluvoxamine may be effective in reducing the urge to gamble. Randomized placebo-controlled and maintenance trials are required to confirm these findings and to determine whether improvement persists.
Phase I Dose Escalation and Pharmacokinetic Study of Lapatinib in Combination With Trastuzumab in Patients With Advanced ErbB2-Positive Breast Cancer
Authors: Anna Maria Storniolo, Mark D. Pegram, Beth Overmoyer, Paula Silverman, Nancy W. Peacock, Suzanne F. Jones, Jill Loftiss, Nikita Arya, Kevin M. Koch, Elaine Paul, Lini Pandite, Ronald A. Fleming, Peter F. Lebowitz, Peter T.C. Ho, Howard A. Burris
Journal: Journal of Clinical Oncology (2008)

The combination of lapatinib and trastuzumab has been observed to have a synergistic, antiproliferative effect against ErbB2-positive breast cancer cells in vitro. This phase I study assessed the safety, clinical feasibility, optimally tolerated regimen (OTR), pharmacokinetics (PK), and preliminary clinical activity of this combination in patients with ErbB2-positive advanced breast cancer.Cohorts of three patients with ErbB2-positive advanced breast cancer were treated with escalating doses of lapatinib (750 to 1,500 mg) administered once daily (continuous) in combination with trastuzumab (4 mg/kg loading dose then 2 mg/kg weekly) to determine the OTR. Once the OTR was determined, additional patients were enrolled to provide the PK profile of both agents alone and in combination.A total of 54 patients were treated: 27 in the dose-escalation group and 27 in the PK group. Overall, adverse events were mild to moderate in severity, with no drug-related grade 4 events. The most frequent drug-related grade 3 events included diarrhea (17%), fatigue (11%), and rash (6%). The OTR was 1,000 mg lapatinib with standard weekly trastuzumab. One patient had a complete response and seven patients had partial responses. The PK parameters (maximum concentration in plasma and area under the curve) of lapatinib and trastuzumab in combination were not significantly different than when either was administered alone.The OTR of the lapatinib/trastuzumab combination was lapatinib 1,000 mg per day with standard weekly trastuzumab. At these doses, the regimen was well tolerated and clinically active in this heavily pretreated ErbB2-positive breast cancer population.
African AIDS Vaccine Programme for a Coordinated and Collaborative Vaccine Development Effort on the Continent
Authors: Pontiano Kaleebu, Alash'le Abimiku, Shenaaz El-Halabi, Sinata Koulla-Shiro, Nicole Mamotte, Souleymane Mboup, Roy Mugerwa, John Nkengasong, Coumba Toure-Kane, Tim Tucker, Douglas Wassenaar, Carolyn Williamson, Dawit Wolday
Journal: PLoS Medicine (2008)

Nearly 30 years after the first cases of AIDS were reported [1] and HIV identified as the causative agent, Africa today bears a disproportionate burden of the disease. Sub-Saharan Africa has just over 10% of the world's population but is home to more than 65% of the 33 million people in the world estimated to be living with HIV/AIDS. The annual rate of new infections continues to rise, with an estimated 2.5 million people newly infected in 2007 [2].

Although newer initiatives aimed at providing universal access to antiretroviral therapy in Africa are ongoing, most Africans receive neither treatment nor adequate care [3]. Relatively few HIV-infected patients in sub-Saharan Africa (about 1 million) are currently receiving antiretroviral treatment [4], and many more new cases are occurring each year [2]. It is thus evident that treatment alone will not control the spread of the disease and that a vaccine is our best hope of halting this pandemic.

In the history of infectious diseases, effective vaccines are critical public health tools to control and prevent diseases. Developing an effective HIV vaccine is proving to be one of the greatest challenges in biomedical research. The need for a simple, safe, effective, affordable, and equitably distributed preventive HIV vaccine to complement existing HIV/AIDS prevention, treatment, and care programs is greater than ever. It is probable that vaccines will form part of future innovative interventions including microbicides and circumcision, used in conjunction with other more traditional prevention interventions.

Summary Points

The AIDS pandemic continues to be the most serious public health challenge facing the world today, and Africa bears an overwhelming proportion of infections, with unprecedented medical and socioeconomic consequences.


The best hope to end the AIDS pandemic remains the development of an effective HIV vaccine, and its distribution to all communities.


The African AIDS Vaccine Programme (AAVP), formed in 2000, is a network of African HIV vaccine stakeholders, led by Africans across the continent, with a vision of an African continent without AIDS.


AAVP supports and represents the diverse African communities involved in HIV vaccine research and development (R&D), and is an important unified voice for African stakeholders.


This paper describes what AAVP is, what it does, and its impact, successes, and challenges. Finally, we discuss where AAVP is heading to harmonize with the Global HIV Vaccine Enterprise and the dynamic HIV vaccine research field.
p8 Is a New Target of Gemcitabine in Pancreatic Cancer Cells
Authors: Valentin Giroux, Cédric Malicet, Marc Barthet, Meritxell Gironella, Cendrine Archange, Jean-Charles Dagorn, Sophie Vasseur, Juan L. Iovanna
Journal: Clinical Cancer Research (2006)

Gemcitabine is the only available chemotherapeutic treatment of pancreatic cancers. It is, however, moderately effective, showing a tumor response rate of only 12%. The aim of this work was to identify new pathways involved in the resistance of pancreatic cancer cells to gemcitabine, in the hope of developing new adjuvant strategies to enhance its therapeutic efficacy. Comparison of gene expression patterns of five human pancreatic cancer cell lines showing different degrees of resistance to gemcitabine revealed specific overexpression of several genes in the most resistant. One of them encoded the antiapoptotic p8 protein. We found that (a) knocking down p8 expression in gemcitabine-resistant cells promoted cell death and increased caspase-3 activity; (b) forced overexpression of p8 in gemcitabine-sensitive cells increased their resistance to gemcitabine-induced apoptosis; and (c) gemcitabine down-regulated p8 mRNA expression. These results suggest that, in pancreatic cancer cells, a large part of gemcitabine-induced apoptosis results from the inhibition of the constitutive antiapoptotic activity of p8. Hence, targeting the p8-associated pathway could be a new adjuvant therapy improving the response of patients with pancreatic cancer to gemcitabine treatment.
Homing in on consciousness in the nervous system: An action-based synthesis
Authors: Ezequiel Morsella, Christine A. Godwin, Tiffany K. Jantz, Stephen C. Krieger, Adam Gazzaley
Journal: Behavioral and Brain Sciences (2015)

What is the primary function of consciousness in the nervous system? The answer to this question remains enigmatic, not so much because of a lack of relevant data, but because of the lack of a conceptual framework with which to interpret the data. To this end, we have developed Passive Frame Theory, an internally coherent framework that, from an action-based perspective, synthesizes empirically supported hypotheses from diverse fields of investigation. The theory proposes that the primary function of consciousness is well-circumscribed, serving the somatic nervous system. For this system, consciousness serves as a frame that constrains and directs skeletal muscle output, thereby yielding adaptive behavior. The mechanism by which consciousness achieves this is more counterintuitive, passive, and "low level" than the kinds of functions that theorists have previously attributed to consciousness. Passive frame theory begins to illuminate (a) what consciousness contributes to nervous function, (b) how consciousness achieves this function, and (c) the neuroanatomical substrates of conscious processes. Our untraditional, action-based perspective focuses on olfaction instead of on vision and is descriptive (describing the products of nature as they evolved to be) rather than normative (construing processes in terms of how they should function). Passive frame theory begins to isolate the neuroanatomical, cognitive-mechanistic, and representational (e.g., conscious contents) processes associated with consciousness.