tbuckley/cabot-search huggingface dataset:
Older Breast Cancer Survivors: Geriatric Assessment Domains Are Associated With Poor Tolerance of Treatment Adverse Effects and Predict Mortality Over 7 Years of Follow-Up
Authors: Kerri M. Clough-Gorr, Andreas E. Stuck, Soe Soe Thwin, Rebecca A. Silliman
Journal: Journal of Clinical Oncology (2009)

Purpose To evaluate geriatric assessment (GA) domains in relation to clinically important outcomes in older breast cancer survivors. Methods Six hundred sixty women diagnosed with primary breast cancer in four US geographic regions (Los Angeles, CA; Minnesota; North Carolina; and Rhode Island) were selected with disease stage I to IIIA, age ≥ 65 years at date of diagnosis, and permission from attending physician to contact. Data were collected over 7 years of follow-up from consenting patients' medical records, telephone interviews, physician questionnaires, and the National Death Index. Outcomes included self-reported treatment tolerance and all-cause mortality. Four GA domains were described by six individual measures, as follows: sociodemographic by adequate finances; clinical by Charlson comorbidity index (CCI) and body mass index; function by number of physical function limitations; and psychosocial by the five-item Mental Health Index (MHI5) and Medical Outcomes Study Social Support Survey (MOS-SSS). Associations were evaluated using t tests, χ 2 tests, and regression analyses. Results In multivariable regression including age and stage, three measures from two domains (clinical and psychosocial) were associated with poor treatment tolerance; these were CCI ≥ 1 (odds ratio [OR] = 2.49; 95% CI, 1.18 to 5.25), MHI5 score less than 80 (OR = 2.36; 95% CI, 1.15 to 4.86), and MOS-SSS score less than 80 (OR = 3.32; 95% CI, 1.44 to 7.66). Four measures representing all four GA domains predicted mortality; these were inadequate finances (hazard ratio [HR] = 1.89; 95% CI, 1.24 to 2.88; CCI ≥ 1 (HR = 1.38; 95% CI, 1.01 to 1.88), functional limitation (HR = 1.40; 95% CI, 1.01 to 1.93), and MHI5 score less than 80 (HR = 1.34; 95% CI, 1.01 to 1.85). In addition, the proportion of women with these outcomes incrementally increased as the number of GA deficits increased. Conclusion This study provides longitudinal evidence that GA domains are associated with poor treatment tolerance and predict mortality at 7 years of follow-up, independent of age and stage of disease.
The Impact of the Demographic Transition on Dengue in Thailand: Insights from a Statistical Analysis and Mathematical Modeling
Authors: Derek A. T. Cummings, Sopon Iamsirithaworn, Justin T. Lessler, Aidan McDermott, Rungnapa Prasanthong, Ananda Nisalak, Richard G. Jarman, Donald S. Burke, Robert V. Gibbons
Journal: PLoS Medicine (2009)

Background An increase in the average age of dengue hemorrhagic fever (DHF) cases has been reported in Thailand. The cause of this increase is not known. Possible explanations include a reduction in transmission due to declining mosquito populations, declining contact between human and mosquito, and changes in reporting. We propose that a demographic shift toward lower birth and death rates has reduced dengue transmission and lengthened the interval between large epidemics. Methods and Findings Using data from each of the 72 provinces of Thailand, we looked for associations between force of infection (a measure of hazard, defined as the rate per capita at which susceptible individuals become infected) and demographic and climactic variables. We estimated the force of infection from the age distribution of cases from 1985 to 2005. We find that the force of infection has declined by 2% each year since a peak in the late 1970s and early 1980s. Contrary to recent findings suggesting that the incidence of DHF has increased in Thailand, we find a small but statistically significant decline in DHF incidence since 1985 in a majority of provinces. The strongest predictor of the change in force of infection and the mean force of infection is the median age of the population. Using mathematical simulations of dengue transmission we show that a reduced birth rate and a shift in the population's age structure can explain the shift in the age distribution of cases, reduction of the force of infection, and increase in the periodicity of multiannual oscillations of DHF incidence in the absence of other changes. Conclusions Lower birth and death rates decrease the flow of susceptible individuals into the population and increase the longevity of immune individuals. The increase in the proportion of the population that is immune increases the likelihood that an infectious mosquito will feed on an immune individual, reducing the force of infection. Though the force of infection has decreased by half, we find that the critical vaccination fraction has not changed significantly, declining from an average of 85% to 80%. Clinical guidelines should consider the impact of continued increases in the age of dengue cases in Thailand. Countries in the region lagging behind Thailand in the demographic transition may experience the same increase as their population ages. The impact of demographic changes on the force of infection has been hypothesized for other diseases, but, to our knowledge, this is the first observation of this phenomenon. Please see later in the article for the Editors' Summary
Acute decrease in left ventricular diastolic chamber distensibility during simulated angina in isolated hearts.
Authors: S Isoyama, C S Apstein, L F Wexler, W N Grice, B H Lorell
Journal: Circulation Research (1987)

It is not clear what factors contribute to the prompt and reversible decrease in left ventricular diastolic chamber distensibility during angina pectoris that is induced by an increase in myocardial energy demand due to exercise or pacing tachycardia. To simulate the demand ischemia that occurs clinically during pacing-induced angina, we used isolated, blood-perfused rabbit hearts with restricted coronary flow and increased myocardial energy demand. A constant left ventricular balloon volume model was used to measure left ventricular diastolic chamber distensibility during 6 minutes of low-flow global ischemia, induced by a reduction in coronary perfusion pressure from 100 to 20 mm Hg. To investigate the influence of different levels of myocardial energy demand, the effects of two different heart rates were studied during low-flow global ischemia; pacing tachycardia (6.4 +/- 0.2 Hz, n = 7) was compared with the rabbit's baseline heart rate of 4 Hz (n = 7). Low-flow ischemia caused a marked decrease in contractile function relative to the baseline preischemic state. In the pacing-tachycardia group, myocardial energy demand, as estimated by the rate X systolic pressure product, was significantly greater than in the constant heart-rate group. When tachycardia was imposed during low-flow global ischemia, there was a transient and reversible increase in isovolumic left ventricular end-diastolic pressure from 14 +/- 1 to 25 +/- 4 mm Hg (measured during long diastoles obtained with transient cessation of pacing) in the pacing-tachycardia group, but there was no increase in left ventricular end-diastolic pressure during low flow ischemia in the constant heart-rate group with lower energy demand (p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)
Associations of Frequency and Duration of Patient-Doctor Contact in Hemodialysis Facilities with Mortality
Authors: Takehiko Kawaguchi, Angelo Karaboyas, Bruce M. Robinson, Yun Li, Shunichi Fukuhara, Brian A. Bieber, Hugh C. Rayner, Vittorio E. Andreucci, Ronald L. Pisoni, Friedrich K. Port, Hal Morgenstern, Tadao Akizawa, Rajiv Saran
Journal: Journal of the American Society of Nephrology (2013)

It is unknown whether regular patient-doctor contact (PDC) contributes to better outcomes for patients undergoing hemodialysis. Here, we analyzed the associations between frequency and duration of PDC during hemodialysis treatments with clinical outcomes among 24,498 patients from 778 facilities in the international Dialysis Outcomes and Practice Patterns Study (DOPPS). The typical facility PDC frequency, estimated by facility personnel, was high (more than once per week) for 55% of facilities, intermediate (once per week) for 24%, and low (less than once per week) for 21%. The mean ± SD estimated duration of a typical interaction between patient and physician was 7.7 ± 5.6 minutes. PDC frequency and duration varied across DOPPS phases and countries; the proportion of facilities with high PDC frequency was 17% in the United States and 73% across the other countries. Compared with high PDC frequency, the adjusted hazard ratio (HR) for all-cause mortality was 1.06 (95% confidence interval [CI], 0.96 to 1.17) for intermediate PDC frequency and 1.11 (95% CI, 1.01 to 1.23) for low PDC frequency (P=0.03 for trend). Furthermore, each 5-minutes-shorter duration of PDC was associated with a 5% higher risk for death, on average (HR, 1.05; 95% CI, 1.01 to 1.09), adjusted for PDC frequency and other covariates. Multivariable analyses also suggested modest inverse associations between both PDC frequency and duration with hospitalization but not with kidney transplantation. Taken together, these results suggest that policies supporting more frequent and longer duration of PDC may improve patient outcomes in hemodialysis.
The immune suppressive effect of dexamethasone in rheumatoid arthritis is accompanied by upregulation of interleukin 10 and by differential changes in interferon gamma and interleukin 4 production
Authors: C. M Verhoef, J. A G van Roon, M. E Vianen, F. P J G Lafeber, J. W J Bijlsma
Journal: Annals of the Rheumatic Diseases (1999)

The influence of dexamethasone on interleukin 10 (IL10) production and the type 1 (T1)/type 2 (T2) T cell balance found in rheumatoid arthritis (RA) was studied.Peripheral blood mononuclear cells (PB MNC) were isolated from 14 RA patients both before and 7 and 42 days after high dose dexamethasone pulse therapy. The ex vivo production of IL10, interferon gamma (IFN gamma) (T1 cell), and IL4 (T2 cell) by PB MNCs was assessed, along with parameters of disease activity (erythrocyte sedimentation rate, C reactive protein, Visual Analogue Scale, Thompson joint score). In addition, the in vitro effect of dexamethasone (0.02, 0.2, and 2 microM) on PB MNC IL10, IFN gamma, and IL4 production was studied.Dexamethasone pulse therapy resulted in a rapid and sustained decrease in RA disease activity. IL10 production increased after dexamethasone treatment and this was sustained for at least six weeks. A transient strong decrease in IFN gamma was seen shortly after corticosteroid treatment, while IL4 only decreased slightly. This led to an increased IL-4/IFN gamma ratio. In vitro, IL10 production was not detectable, IFN gamma and IL4 decreased, but the effect was more pronounced for IFN gamma than for IL4, which again resulted in an increased IL4/IFN gamma ratio.Dexamethasone therapy in RA patients leads to a rapid, clinically beneficial effect. The upregulation of IL10 production may be involved in the prolonged clinical benefit. The strong immunosuppressive effect is most evident in the decrease in IFN gamma, and is therefore accompanied by a relative shift towards T2 cell activity. In vitro evaluation showed that this shift in T cell balance was a direct effect of dexamethasone and thus independent of the hypothalamic-pituitary-adrenal axis.
Eye Defects of Mentally Handicapped Children
Authors: J. L. K. Bankes
Journal: BMJ (1974)

Among 171 children who received routine ophthalmic and orthoptic examinations as part of their evaluation for suspected or known developmental handicap it was found that there was an unusually high incidence of ocular defects. Especially prevalent were high refractive errors (52%) and squints (40%), but there were also a number of other serious eye defects ranging from nystagmus and cataracts to microphthalmos. Because of this high incidence of eye defects it was considered essential that ophthalmic and orthoptic examinations should be part of the routine evaluation of developmentally handicapped children by the team of workers in an assessment centre.
S25 Arterial Stiffness and Airway Infection and Inflammation During COPD Exacerbations
Authors: ARC Patel, BS Kowlessar, R Sapsford, SN George, DS Garcha, GC Donaldson, AJ Mackay, R Singh, JA Wedzicha, JR Hurst
Journal: Thorax (2012)

<h3>Introduction</h3> Cardiovascular risk is elevated following COPD exacerbations requiring systemic therapy (Donaldson <i>et al</i>, Chest 2010:137; 1091–7). We have recently shown that a potential mechanism is increased arterial stiffness during COPD exacerbations compared to the stable state (Patel <i>et al</i>, AJRCCM 2012:185; A5853). We hypothesised that arterial stiffness may be mediated by airway infection and inflammation during COPD exacerbations. <h3>Methods</h3> We used aortic pulse wave velocity (aPWV) as a non-invasive validated measure of arterial stiffness using Vicorder apparatus (Skidmore Medical, UK) in outpatients from the London COPD cohort when they presented within seven days of exacerbation symptom onset and prior to any systemic therapy. These events were defined using our usual symptomatic criteria (Seemungal <i>et al</i>, AJRCCM 1998:157; 1418–22). We collected spontaneous sputum at the same clinic visit to identify typical bacterial (<i>S pneumoniae, H influenzae</i> and<i> M catarrhalis</i>) and rhinovirus infection using PCR. We also measured IL-6 and IL-8 in sputum supernatant using commercial ELISA kits (R&amp;D Systems, USA). <h3>Results</h3> 32 exacerbating COPD patients produced a spontaneous sputum sample during the same clinic visit as an aPWV measurement. Their stable clinical characteristics were: 69% male; 25% current smokers; median (IQR) 39 (21.74) pack year smoking history; mean±SD age 72.4±8.1 years; FEV1 1.18±0.41L and 46.8±18.0%predicted; FEV1/FVC ratio 0.44±0.15 and BMI 25.4±3.8 kg/m2. Arterial stiffness was higher in patients with airway infection at exacerbation presentation (mean ±SD aPWV 12.3±2.3 (n=19) vs 10.8±1.8 (n=13) m/s, p=0.030) (Figure 1A). Arterial stiffness was strongly correlated with sputum IL-6 at exacerbation (n=32, rho=0.495, p=0.003) (Figure 1B) but not IL-8 (n=31, rho=0.100, p=0.591). <h3>Conclusions</h3> Arterial stiffness is related to airway infection and inflammation during COPD exacerbations. Interventions to prevent and reduce airway infection and inflammation may lower cardiovascular risk during COPD exacerbations.
Stem Cells and Chronic Lung Disease
Authors: Brigitte N. Gomperts, Robert M. Strieter
Journal: Annual Review of Medicine (2006)

Stem cells have been shown to contribute to the repair and regeneration of injured lungs. These stem cells are resident in specific protected niches in the lung, or they can be mobilized from the bone marrow and recruited from the circulation in the setting of severe injury. Normal repair of the airway involves regeneration of the airway epithelium by stem cells in both the proximal airway and distal airspace, whereas aberrant repair of the lung may result from stem cells that lead to fibrosis. The stem cell niche in the lung is probably critical in determining whether “good” or “bad” stem cells are involved in local repair, and therefore whether fibrosis predominates. There is much excitement about the possibility of harnessing stem cells for repair and regeneration of the lungs. This review highlights current knowledge of this area and identifies gaps in our understanding of this complicated process.
Toward an Understanding of Disengagement from HIV Treatment and Care in Sub-Saharan Africa: A Qualitative Study
Authors: Norma C. Ware, Monique A. Wyatt, Elvin H. Geng, Sylvia F. Kaaya, Oche O. Agbaji, Winnie R. Muyindike, Guerino Chalamilla, Patricia A. Agaba
Journal: PLoS Medicine (2013)

Background The rollout of antiretroviral therapy in sub-Saharan Africa has brought lifesaving treatment to millions of HIV-infected individuals. Treatment is lifelong, however, and to continue to benefit, patients must remain in care. Despite this, systematic investigations of retention have repeatedly documented high rates of loss to follow-up from HIV treatment programs. This paper introduces an explanation for missed clinic visits and subsequent disengagement among patients enrolled in HIV treatment and care programs in Africa. Methods and Findings Eight-hundred-ninety patients enrolled in HIV treatment programs in Jos, Nigeria; Dar es Salaam, Tanzania; and Mbarara, Uganda who had extended absences from care were tracked for qualitative research interviews. Two-hundred-eighty-seven were located, and 91 took part in the study. Interview data were inductively analyzed to identify reasons for missed visits and to assemble them into a broader explanation of how missed visits may develop into disengagement. Findings reveal unintentional and intentional reasons for missing, along with reluctance to return to care following an absence. Disengagement is interpreted as a process through which missed visits and ensuing reluctance to return over time erode patients' subjective sense of connectedness to care. Conclusions Missed visits are inevitable over a lifelong course of HIV care. Efforts to prevent missed clinic visits combined with moves to minimize barriers to re-entry into care are more likely than either approach alone to keep missed visits from turning into long-term disengagement. Please see later in the article for the Editors' Summary
Smoking cessation improves both direct and indirect airway hyperresponsiveness in COPD
Authors: B.W.M. Willemse
Journal: European Respiratory Journal (2004)

Smoking induces chronic obstructive pulmonary disease (COPD) and is associated with airway inflammation and airway hyperresponsiveness (AHR). It has not been studied in COPD whether direct (methacholine) and indirect (adenosine-59-monophosphate (AMP)) stimuli are associated with airway inflammation and neither whether smoking cessation improves these features. The current authors cross-sectionally investigated the relationship of AHR to methacholine and AMP with lung function and inflammatory cells in the sputum of 33 smokers with COPD. In addition, changes in these parameters were prospectively assessed in 14 smokers who successfully quit smoking for 1 yr. The presence of AHR to both methacholine and AMP was associated with lower lung function, but not with sputum inflammation. AHR to methacholine and AMP improved significantly after a 1-yr smoking cessation, yet this was unrelated to changes in sputum cell counts. The numbers of neutrophils and epithelial cells significantly increased with smoking cessation. Both direct and indirect airway hyperresponsiveness are associated with lower lung function, but not with sputum inflammation in chronic obstructive pulmonary disease. Interestingly, 1-yr smoking cessation improved both direct and indirect airway hyperresponsiveness, yet without a significant association with changes in lung function or sputum inflammation. Thus, other factors are likely to induce these improvements, <i>e.g.</i> a reduction in stimulation of irritant receptors, airway wall changes or mucus hypersecretion.
Comparison of Nasal and Oral Inhalation during Exhaled Breath Condensate Collection
Authors: Géza Vass, Éva Huszár, Erzsébet Barát, Márta Valyon, Domonkos Kiss, István Pénzes, Mónika Augusztinovicz, Ildikó Horváth
Journal: American Journal of Respiratory and Critical Care Medicine (2003)

Analysis of exhaled breath condensate is a method for noninvasive assessment of the lung. Condensate can be collected with a nose clip (subjects inhale and exhale via the mouth) or without it (subjects inhale via the nose and exhale via the mouth), but the mode of inhalation may influence condensate volume and mediator levels. We compared condensate volume and adenosine, ammonia, and thromboxane B2 levels in young healthy volunteers (n = 25) in samples collected for 10 minutes from subjects with or without a nose clip. Patients with allergic rhinitis (n = 8) were also studied to assess the effect of upper airway inflammation on mediator levels. Adenosine, ammonia, and thromboxane B2 levels were determined by HPLC, spectrophotometry, and radioimmunoassay, respectively. Volume of condensate was significantly higher without nose clip than that with nose clip (mean +/- SD, 2321 +/- 736 microl and 1746 +/- 400 microl, respectively; p = 0.0001). We found no significant difference in any mediator levels between these two collection modes in healthy volunteers, but adenosine showed a tendency to differ between oral and nasal inhalation in patients with allergic rhinitis. Our data indicate that whereas a greater volume of condensate can be obtained when subjects inhale through their noses, the mode of inhalation does not influence mediator levels in young healthy volunteers, but may affect these levels in patients with allergic rhinitis.
Immunological Aspects of Renal Tubular and Interstitial Diseases
Authors: R T McCluskey, R B Colvin
Journal: Annual Review of Medicine (1978)

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the cause of coronavirus disease 2019 (COVID-19), emerged in China in December 2019 and quickly spread around the globe, killing more than 4 million people and causing a severe economic crisis. ...Read More
Extrahepatic bile duct growth in mice repeatedly injected with human normal serum, IgA-deficient serum or purified secretory IgA
Authors: Pierre M. E. Solbreux, Paul Maldague, Jean Pierre Vaerman
Journal: Hepatology (1991)

Another group of researchers has reported that seven intraperitoneal injections into mice of purified human serum IgA or normal human serum--but not IgA-deficient serum, mouse serum or saline--induced considerable growth of the extrahepatic bile duct epithelium. They stated that heterologous IgA was principally responsible for this effect. We have quantitated this growth by another method: enumeration of total and radiolabeled nuclei of the lumenal and glandular epithelium in transverse duct sections after tritiated thymidine injection and autoradiography. Our data show maximal incorporation between 18 and 24 hr after the last injection, with the highest labeling index in the lumenal epithelium after only three injections and before any duct enlargement. After four to seven injections, thymidine incorporation continued in juxtalumenal glands, together with massive glandular proliferation into the thickening wall and obvious inflammation. These changes were more pronounced in the liver-proximal part of the duct without affecting intrahepatic duct and gallbladder epithelia. Subcutaneous serum injections were less active. We confirm the inactivity of buffered saline, but, unlike previous authors, demonstrate strong activity in purified human milk secretory IgA and in IgA-deficient serum. We suggest that this different approach of quantitating epithelial proliferation will allow comparison of the bile duct growth effects of different, well-characterized human and animal IgA preparations.