tbuckley/cabot-search huggingface dataset:
Zoledronic acid reduces knee pain and bone marrow lesions over 1 year: a randomised controlled trial
Authors: Laura Louise Laslett, Dawn A Doré, Stephen J Quinn, Philippa Boon, Emma Ryan, Tania Maree Winzenberg, Graeme Jones
Journal: Annals of the Rheumatic Diseases (2012)

To compare the effect of a single infusion of zoledronic acid (ZA) with placebo on knee pain and bone marrow lesions (BMLs).Adults aged 50-80 years (n=59) with clinical knee osteoarthritis and knee BMLs were randomised to receive either ZA (5 mg/100 ml) or placebo. BMLs were determined using proton density-weighted fat saturation MR images at baseline, 6 and 12 months. Pain and function were measured using a visual analogue scale (VAS) and the knee injury and osteoarthritis outcome score (KOOS) scale.At baseline, mean VAS score was 54 mm and mean total BML area was 468 mm(2). VAS pain scores were significantly reduced in the ZA group compared with placebo after 6 months (-14.5 mm, 95% CI -28.1 to -0.9) but not after 3 or 12 months. Changes on the KOOS scales were not significant at any time point. Reduction in total BML area was greater in the ZA group compared with placebo after 6 months (-175.7 mm(2), 95% CI -327.2 to -24.3) with a trend after 12 months (-146.5 mm(2), 95% CI -307.5 to +14.5). A greater proportion of those in the ZA group achieved a clinically significant reduction in BML size at 6 months (39% vs 18%, p=0.044). Toxicity was as expected apart from a high rate of acute phase reactions in treatment and placebo arms.ZA reduces knee pain and areal BML size and increases the proportion improving over 6 months. Treatment of osteoarthritis may benefit from a lesion specific therapeutic approach.ACTRN 12609000399291.
Effects of Emphysema on Diaphragm Microvascular Oxygen Pressure
Authors: DAVID C. POOLE, CASEY A. KINDIG, BRAD J. BEHNKE
Journal: American Journal of Respiratory and Critical Care Medicine (2001)

Pulmonary emphysema impairs lung and respiratory muscle function leading to restricted physical capacity and accelerated morbidity and mortality consequent to respiratory muscle failure. In the absence of direct evidence, an O2 supply–demand imbalance within the diaphragm and other respiratory muscles in emphysema has been considered the most likely explanation for this failure. To test this hypothesis, we utilized phosphorescence quenching techniques to measure mean microvascular Po 2 (Po 2m) within the medial costal diaphragm of control (C, n = 10) and emphysematous (E, elastase instilled, n = 7) hamsters. Po 2m and mean arterial pressure (MAP) were measured in the spontaneously breathing anesthetized hamster at inspired O2 percentages of 10, 21, and 100, and across a range of mean MAPs from 40 to 115 mm Hg. At each inspired O2, diaphragm Po 2m was significantly (p < 0.05) lower in E animals (10%: C, 19 ± 3; E, 9 ± 2; 21%: C, 32 ± 2; E, 21 ± 2; 100%: C, 60 ± 8; E, 36 ± 9 mm Hg). At 21% inspired O2, the Po 2m decrease was correlated with reduced MAP in both C (r = 0.968) and E (r = 0.976) animals. We conclude that diaphragmatic Po 2m (and therefore microvascular O2 content) is decreased in emphysematous hamsters reflecting a greater diaphragmatic O2 utilization at rest and a lower O2 extraction reserve. According to Fick's law, this lower Po 2m will mandate an exaggerated fall in intramyocyte Po 2, which is expected to accelerate muscle glycogen depletion and consequently fatigue. This provides empirical evidence in support of one possible mechanism for respiratory muscle failure in emphysema.
House‐dust mite exposure reduction in specially designed, mechanically ventilated “healthy” homes
Authors: H. Harving, J. Korsgaard, R. Dahl
Journal: Allergy (1994)

Exposure to house‐dust mites ( Dermatophagoides spp.) was investigated in 30 asthmatic patients before and after moving to homes with mechanical ventilation systems. Median house‐dust mite concentration was 110 mites per gram of mattress dust at the initial investigation and 20 mites per gram at the first follow‐up after a mean of 4.7 months in the new homes. This was lower ( P &lt; 0.05) than counts in a control group of 23 asthmatic patients that had unchanged counts. At a second follow‐up, after 15.0 months, mite counts in the study group were further reduced ( P &lt; 0.01) from initial values. Among 16 patients, with initial mite counts above the recommended threshold limit value (TLV) of 100 mites per gram of dust, the mite counts fell, in most cases, below this TLV. Air‐exchange rates increased ( P &lt; 0.001) from a median value of 0.40 air changes per hour (ach) to 1.52 ach at the second follow‐up investigation. Furthermore, a reduction ( P &lt; 0.01) was found in indoor absolute air humidity, with a median value of 5.6 g of water/kg. No such changes were found in the control group. The present study indicates that reduction of air humidity through an increased supply of fresh air may significantly diminish and, in some cases, even eliminate house‐dust mites in homes.
Receptor activities for low-density lipoprotein and acetylated low-density lipoprotein in a mouse macrophage cell line (IC21) and in human monocyte-derived macrophages.
Authors: M G Traber, V Defendi, H J Kayden
Journal: The Journal of Experimental Medicine (1981)

IC21 macrophages, a permanent culture of a line of cells derived from a single colony of mouse peritoneal macrophages transformed with simian virus 40, demonstrate most of the characteristics of lipoprotein metabolism that have been described for primary cultures of rodent or canine peritoneal macrophages. IC21 macrophages have low but demonstrable low-density lipoprotein (LDL) receptor activity. They actively degrade acetylated LDL (AcLDL), which has a negative charge and is not recognized by the LDL receptor. Incubation of IC21 macrophages with human lipoprotein-depleted serum leads to a marked increase in cholesterol synthesis, as measured by incorporation of labeled acetate into sterols. Sterol synthesis is inhibited by further incubation with AcLDL; incubation with LDL also decreases cholesterol synthesis with an accumulation of radioactivity from acetate in sterol intermediates, which indicates that some uptake of LDL occurs. Incubation with AcLDL but not LDL leads to a marked stimulation of cholesterol esterification, as measured by labeled oleic acid incorporation into cholesteryl esters, and a concomitant increase in cellular cholesteryl ester content. IC21 macrophages as compared with human monocyte-derived macrophages are shown to have marked difference in their abilities to degrade native LDL and AcLDL. Human monocyte-derived macrophages degrade LDL at low concentrations at a rate sevenfold greater than do IC21 macrophages. The rate of cholesteryl ester synthesis after LDL receptor induction and incubation with LDL increases linearly with LDL concentration in HMD macrophages, but no increase was found in similarly incubated IC21 macrophages. IC21 macrophages degrade AcLDL at a rate two- to fourfold greater than do human monocyte-derived macrophages.
Patient-Empowerment Interactive Technologies
Authors: Carol S. Bruggers, Roger A. Altizer, Robert R. Kessler, Craig B. Caldwell, Kurt Coppersmith, Laura Warner, Brandon Davies, Wade Paterson, Jordan Wilcken, Troy A. D’Ambrosio, Massiell L. German, Glen R. Hanson, Lynn A. Gershan, Julie R. Korenberg, Grzegorz Bulaj
Journal: Science Translational Medicine (2012)

Video games capture the rapt attention of an individual player's mind and body, providing new opportunities for personalized health care. An example of therapeutic interactive technologies is an incentive-based video game that translates physical exercise into mental empowerment via motivational metaphoric visualization in order to help patients psychologically overcome cancer. Such nonpharmacological interventions may enhance patients' resilience toward various chronic disorders via neuronal mechanisms that activate positive emotions and the reward system.
Continuous Glucose Monitoring–Guided Insulin Adjustment in Children and Adolescents on Near-Physiological Insulin Regimens
Authors: Kylie Yates, Abul Hasnat Milton, Keith Dear, Geoffrey Ambler
Journal: Diabetes Care (2006)

This randomized controlled trial assesses the effect on glycemic control of continuous glucose monitoring system (CGMS)-guided insulin therapy adjustment in young people with type 1 diabetes on intensive diabetes treatment regimens with continuous subcutaneous insulin infusion (CSII) or glargine.Pediatric subjects were recruited if they had an HbA(1c) (A1C) <10% and had been on CSII or glargine for at least 3 months. Thirty-six subjects were randomized to insulin adjustment on the basis of 72 h of CGMS every 3 weeks or intermittent self-monitoring of blood glucose (SMBG) for 3 months. A1C and fructosamine were measured at baseline and 6 and 12 weeks. Follow-up A1C was measured at 6 months. Mean baseline A1C was 8.2% (n = 19) in the CGMS group and 7.9% (n = 17) in the control group.There was a significant improvement in A1C from baseline values in both groups, but there was no difference in the degree of improvement in A1C at 12 weeks between the CGMS (-0.4% [95% CI -0.7 to -0.1]) and the control group (-0.4% [-0.8 to 0.2]). In the CGMS group, improved A1C was at the cost of increased duration of hypoglycemia.CGMS is no more useful than intermittent fingerstick SMBG and frequent review in improving diabetes control in reasonably well-controlled patients on near-physiological insulin regimens when used in an outpatient clinic setting.
Granulocyte macrophage colony-stimulating factor is the main cytokine enhancing survival of eosinophils in asthmatic airways
Authors: CS Park, YS Choi, SY Ki, SH Moon, SW Jeong, ST Uh, YH Kim
Journal: European Respiratory Journal (1998)

Interleukin (IL)-3, IL-5 and granulocyte macrophage colony-stimulating factor (GM-CSF) prolong the survival of eosinophils, which are conspicuous in asthmatic airways, but it is still controversial which one plays a major role in enhancing the survival of eosinophils in asthmatic airways. The role of these cytokines in airway eosinophilia was investigated using bronchoalveolar lavage (BAL) fluids from 11 symptomatic and nine asymptomatic patients with asthma and eight normal subjects. Eosinophil survival-enhancing activity (ESEA) was measured by a numerical change in viable eosinophils isolated from the peripheral blood of atopic patients and cultured with BAL fluids. ESEA was characterized by neutralization with antibodies to IL-3, IL-5 and/or GM-CSF. The differential count of BAL cells was achieved using Diff-Quik stain. T-cell subsets and activated T-cells were analysed by flow cytometry with dual stain using monoclonal antibodies to CD3, CD4, CD8 and CD25. ESEA was detected in eight of 11 BAL fluids of symptomatic asthma, but not in those of normal controls or asymptomatic asthmatics. In six symptomatic asthmatics, the mean percentage of inhibition in ESEA by anti-GM-CSF was higher than that of anti-IL-5 as well as anti-IL-3 (p<0.05). A mixture of antibodies to IL-3, IL-5 and GM-CSF totally inhibited the ESEA in four cases. The ESEA correlated with the percentage of eosinophils (p<0.05) and that of CD25(+)CD4 lymphocytes (p<0.05) of BAL cells. In conclusion, granulocyte macrophage colony-stimulating factor, rather than interleukin-3 or -5, is associated with eosinophil survival-enhancing activity inside the airways of symptomatic asthmatics. The activation of CD4 lymphocytes is related to the elevation of such activity.
Small-Molecule CFTR Inhibitors Slow Cyst Growth in Polycystic Kidney Disease
Authors: Baoxue Yang, Nitin D. Sonawane, Dan Zhao, Stefan Somlo, A. S. Verkman
Journal: Journal of the American Society of Nephrology (2008)

Cyst expansion in polycystic kidney disease (PKD) involves progressive fluid accumulation, which is believed to require chloride transport by the cystic fibrosis transmembrane conductance regulator (CFTR) protein. Herein is reported that small-molecule CFTR inhibitors of the thiazolidinone and glycine hydrazide classes slow cyst expansion in in vitro and in vivo models of PKD. More than 30 CFTR inhibitor analogs were screened in an MDCK cell model, and near-complete suppression of cyst growth was found by tetrazolo-CFTR(inh)-172, a tetrazolo-derived thiazolidinone, and Ph-GlyH-101, a phenyl-derived glycine hydrazide, without an effect on cell proliferation. These compounds also inhibited cyst number and growth by >80% in an embryonic kidney cyst model involving 4-d organ culture of embryonic day 13.5 mouse kidneys in 8-Br-cAMP-containing medium. Subcutaneous delivery of tetrazolo-CFTR(inh)-172 and Ph-GlyH-101 to neonatal, kidney-specific PKD1 knockout mice produced stable, therapeutic inhibitor concentrations of >3 microM in urine and kidney tissue. Treatment of mice for up to 7 d remarkably slowed kidney enlargement and cyst expansion and preserved renal function. These results implicate CFTR in renal cyst growth and suggest that CFTR inhibitors may hold therapeutic potential to reduce cyst growth in PKD.
Does taking probiotics routinely with antibiotics prevent antibiotic associated diarrhoea?
Authors: C. C. Butler, D. Duncan, K. Hood
Journal: BMJ (2012)

Diarrhoea develops in association with antibiotic treatment in 1% to 44%1 2 of cases, and ranges from mild episodes that resolve when antibiotics are stopped to serious complications such as toxic megacolon, bowel perforation, and death. Risk is increased with extremes of age, co-morbidity, oral broad spectrum antibiotics (particularly clindamycin, β-lactams, and third generation cephalosporins), prolonged antibiotic duration, previous antibiotic associated diarrhoea, and hospitalisation. Probiotics—live microorganisms that, when administered in adequate amounts, confer a health benefit on the host—are present in products available in shops as foodstuffs, and in formulations used for specific therapeutic purposes. Probiotics are thought to combat antibiotic associated diarrhoea through restoring resistance to colonisation by pathogenic bacteria after the normal colonic microflora have been damaged by antibiotics, by breaking down non-absorbable compounds into absorbable products, by interfering with pathogenic toxins, and by enhancing immunity. Effects of probiotics vary by strain owing to differing resistance to gastric acid and bile, ability to colonise mucosa, and susceptibility to antibiotics.3

Probiotics carry theoretical risks, including infection beyond the gut and transfer of antibiotic resistant genes. However, so far, there have been no reports of bacteraemia or fungaemia attributable to the probiotics in trials included in published systematic reviews.4 5 6 7 8 9 10

Lactobacillus bacteraemia is rare and has a low mortality rate.11 Cancer, diabetes, broad spectrum antibiotic therapy, organ transplantation, and abscess may be risk factors for lactobacillus bacteraemia. Twelve cases of lactobacillus bacteraemia have been reported in patients taking a probiotic and 24 cases of fungaemia associated with the probiotic Saccharomyces boulardii. However, many lactobacillus strains are human …
Endocrine mechanisms for the formation of sex-related differences in hepatic estrogen receptor content and their significance for the realization of an estrogen effect on angiotensinogen blood level in rats
Authors: Lidia L. Ignatenko, Guranda D. Mataradze, Victor B. Rozen
Journal: Hepatology (1992)

The use of a modified, adequate method of quantification of estrogen receptors has permitted us to prove the existence of sex-specific peculiarities in rat liver estrogen reception and their significance for the realization of sex-dependent changes in angiotensinogen plasma level after estrogenization. Endocrine mechanisms for the formation of sex-related differences in hepatic estrogen receptor content in rats were investigated in detail. The investigation shows that androgens have negative regulatory influence on the hepatic estrogen receptor level in rats. Estrogens and adrenal and thyroid hormones do not take part in the regulation of hepatic estrogen receptor content in rats. It has been proven that the decisive role in keeping up a certain estrogen receptor concentration in hepatocytes belongs to pituitary growth hormone. It was shown for the first time that androgens are able to inhibit the stimulatory effect of growth hormone on hepatic estrogen receptors.
Personal exposure to nitrogen dioxide and risk of airflow obstruction in asthmatic children with upper respiratory infection
Authors: C H Linaker
Journal: Thorax (2000)

Several studies have linked air pollution by nitrogen dioxide (NO(2)) with increased hospital admissions for asthma in children. Exacerbations of asthma in children are often precipitated by upper respiratory infections. It is therefore possible that NO(2) increases the risk of airways obstruction when asthmatic children develop upper respiratory infections.To test this hypothesis a sample of 114 asthmatic children aged 7-12 years were followed for a total of up to 13 months. Probable upper respiratory infections were identified by consensus review of daily symptom diaries, and episodes of airways obstruction from serial records of peak expiratory flow (PEF). Personal exposures to NO(2) were measured with Palmes tubes that were changed weekly. Generalised estimating equations were used to assess the relative risk (RR) of an asthmatic exacerbation starting within seven days of an upper respiratory infection according to estimated NO(2) exposure during the one week period from two days before to four days after the onset of the infection.The children were followed for an average of 34 weeks during which 318 upper respiratory infections and 224 episodes of reduced PEF were diagnosed. PEF episodes were much more likely to occur in the seven days following the onset of an upper respiratory infection than at other times. Estimated exposures to NO(2) at the time of infections were generally low (geometric mean 10.6 microg/m(3)). Compared with exposures of < or = 8 microg/m(3), exposures of >28 microg/m(3) were associated with a RR of 1.9 (95% confidence interval 1.1 to 3.4) for the development of an asthmatic episode within seven days of an infection.The findings give some support to the hypothesis that NO(2) increases the risk of asthmatic exacerbations following respiratory infections, even at relatively low levels of exposure. Further studies in populations with higher exposures would be useful.
Clinical, Angiographic, and Procedural Predictors of Angiographic Restenosis After Sirolimus-Eluting Stent Implantation in Complex Patients
Authors: Pedro A. Lemos, Angela Hoye, Dick Goedhart, Chourmouzios A. Arampatzis, Francesco Saia, Willem J. van der Giessen, Eugene McFadden, Georgios Sianos, Pieter C. Smits, Sjoerd H. Hofma, Pim J. de Feyter, Ron T. van Domburg, Patrick W. Serruys
Journal: Circulation (2004)

Background— The factors associated with the occurrence of restenosis after sirolimus-eluting stent (SES) implantation in complex cases are currently unknown. Methods and Results— A cohort of consecutive complex patients treated with SES implantation was selected according to the following criteria: (1) treatment of acute myocardial infarction, (2) treatment of in-stent restenosis, (3) 2.25-mm diameter SES, (4) left main coronary stenting, (5) chronic total occlusion, (6) stented segment &gt;36 mm, and (7) bifurcation stenting. The present study population was composed of 238 patients (441 lesions) for whom 6-month angiographic follow-up data were obtained (70% of eligible patients). Significant clinical, angiographic, and procedural predictors of post-SES restenosis were evaluated. Binary in-segment restenosis was diagnosed in 7.9% of lesions (6.3% in-stent, 0.9% at the proximal edge, 0.7% at the distal edge). The following characteristics were identified as independent multivariate predictors: treatment of in-stent restenosis (OR 4.16, 95% CI 1.63 to 11.01; P &lt;0.01), ostial location (OR 4.84, 95% CI 1.81 to 12.07; P &lt;0.01), diabetes (OR 2.63, 95% CI 1.14 to 6.31; P =0.02), total stented length (per 10-mm increase; OR 1.42, 95% CI 1.21 to 1.68; P &lt;0.01), reference diameter (per 1.0-mm increase; OR 0.46, 95% CI 0.24 to 0.87; P =0.03), and left anterior descending artery (OR 0.30, 95% CI 0.10 to 0.69; P &lt;0.01). Conclusions— Angiographic restenosis after SES implantation in complex patients is an infrequent event, occurring mainly in association with lesion-based characteristics and diabetes mellitus.
Characteristics of bone mineral density at the time of diagnosis in postmenopausal breast cancer patients
Authors: H. J. Kim, E. Park, W. Lim, J. Sei, B. Koh, B. Son, S. Ahn
Journal: Journal of Clinical Oncology (2009)

e22187 Background: Bone mass has been proposed as a marker of cumulative exposure to estrogen in women. We have studied the association between bone mass and breast cancer in postmenopausal women. Methods: We investigated the association between bone mineral density(BMD), as measured at the lumbar spine and femoral neck and the breast cancer in women age 50 or older, who were received an initial diagnosis of stage 0-III breast cancer, confirmed by pathologic assessment of breast tissue. We recruited 718 women with newly diagnosed breast cancer in a Asan Medical Center from 1, Jun. 2006 to 31, Dec. 2007. BMD was measured by lunar EXPERT-XL for breast cancer patients Results: Median age at diagnosis was 58 (range 47–82). Patients with higher BMD at lumbar spine were found to have low grade disease (p&lt;0.005). The patients with hormone receptor positive breast tumor showed higher BMD at lumbar spine and lower serum 25(OH)D than hormone receptor negative tumor. Serum estradiol level did not show a relation to BMD. There were no significant differences between breast cancer stage and serum 25(OH)D and BMD. Conclusions: The patients who have hormone receptor positive breast cancer had higher Lumbar spine BMD and lower 25(OH)D than hormone receptor negative patients. No significant financial relationships to disclose.
Epidemiology, diagnosis and management of hirsutism: a consensus statement by the Androgen Excess and Polycystic Ovary Syndrome Society
Authors: H.F. Escobar-Morreale, E. Carmina, D. Dewailly, A. Gambineri, F. Kelestimur, P. Moghetti, M. Pugeat, J. Qiao, C.N. Wijeyaratne, S.F. Witchel, R.J. Norman
Journal: Human Reproduction Update (2011)

Hirsutism, defined by the presence of excessive terminal hair in androgen-sensitive areas of the female body, is one of the most common disorders in women during reproductive age. We conducted a systematic review and critical assessment of the available evidence pertaining to the epidemiology, pathophysiology, diagnosis and management of hirsutism. The prevalence of hirsutism is ∼10% in most populations, with the important exception of Far-East Asian women who present hirsutism less frequently. Although usually caused by relatively benign functional conditions, with the polycystic ovary syndrome leading the list of the most frequent etiologies, hirsutism may be the presenting symptom of a life-threatening tumor requiring immediate intervention. Following evidence-based diagnostic and treatment strategies that address not only the amelioration of hirsutism but also the treatment of the underlying etiology is essential for the proper management of affected women, especially considering that hirsutism is, in most cases, a chronic disorder needing long-term follow-up. Accordingly, we provide evidence-based guidelines for the etiological diagnosis and for the management of this frequent medical complaint.
Primary Ovarian Insufficiency
Authors: Lawrence M. Nelson
Journal: New England Journal of Medicine (2009)

A 30-year-old woman presents with a history of no menses since she stopped taking oral contraceptives 6 months ago in order to conceive. She had undergone normal puberty, with menarche at the age of 12. She reports stress at work. Her weight is 59 kg, and her height 1.66 m; her body-mass index (the weight in kilograms divided by the square of the height in meters) is 21.3. The pelvic examination is normal, a pregnancy test is negative, the prolactin level is normal, and the follicle-stimulating hormone level is in the menopausal range. How should she be evaluated and treated?