tbuckley/cabot-search huggingface dataset:
Cost evaluation of the medical management of neurofibromatosis 1: a prospective study on 201 patients
Authors: P. Wolkenstein, I. Durand-Zaleski, J.C. Moreno, J. Zeller, F. Hemery, J. Revuz
Journal: British Journal of Dermatology (2000)

Abstract Neurofibromatosis 1 (NF1) is associated with many internal complications as well as skin manifestations, and patients may require a variety of medical and surgical interventions. We aimed to assess the medical needs of NF1 patients, and to evaluate the financial cost of the resources used for them in relation to the severity of the disease. We conducted a prospective analysis on a cohort of 201 patients in our referral centre for adults. Severity of the disease was assessed. Therapeutic management was considered as multidisciplinary if it required more than three different specialists. Plastic and dermatological surgery procedures performed were recorded. Hospital costs were computed over a 3-year period and included all hospitalization days, clinic visits and procedures performed in all departments where the patients were admitted. One hundred and thirty-seven patients had at least one out-patient procedure or one hospitalization during the follow-up period. The mean cost per patient per year was £810 (median 240; range 0–13,860). Multidisciplinary procedures were more frequent in moderately and severely affected NF1 patients than in milder cases (P &amp;lt; 0·0001); hence, the costs for moderate and severe cases were higher than for less severe groups (P = 0·005). Plastic and/or dermatological surgery was performed with the same frequency in the different severity groups (71%). Regardless of the presence of serious intractable complications, the patients’ priority is for treatment of the disfigurement due to the disease. The management of these patients can be considered relatively inexpensive from the viewpoint of the healthcare system.
Development of a metabolite profile for colorectal cancer detection.
Authors: Haiwei Gu, Jin Dai, Fausto Carnevale Neto, Danijel Djukovic, Jiangjiang Zhu, Daniel Raftery
Journal: Journal of Clinical Oncology (2014)

422 Background: While carcinogenesis of colorectal cancer (CRC) is a complex process involving genetic abnormalities, metabolomics, which aims to establish metabolic responses of living systems to external or internal perturbations, has great potential to develop a metabolite profile specific to CRC for both early detection and treatment monitoring purposes. In this pilot study, we examined the colon cancer-induced alterations of amino acids and their distribution in the three domains of free amino acids (FAAs), free amino acids and soluble peptide amino acids (FAASPAAs), and proteome amino acids (PAAs). Methods: 56 serum samples were collected from 28 colon cancer patients and 28 healthy controls. FAAs were extracted after protein precipitation. FAASPAAs and PAAs were obtained using traditional acid hydrolysis. We utilized LC-MS/MS to make the amino acid measurements, and performed penalized logistic regression analysis on the amino acid signals in the three domains, both individually and in combination. Results: There were 10, 9, and 14 amino acids with low P-values (&lt;0.05) in FAAs, FAASPAAs, and PAAs, respectively, when comparing the two groups. The penalized logistic regression model based on amino acids from the three domains had a sensitivity of 65% when the specificity was 95%. An area under the receiver operator curve (AUROC) of 0.91 was achieved for the combined statistical model. Significant amino acids in statistical modeling included aspartic acid, glutamic acid, glutamine/lysine, and histidine from FAAs, lysine from FAASPAAs, and arginine, serine, and tyrosine from PAAs. Conclusions: To the best of our knowledge, this is the first study to perform a combined analysis of amino acids in the three domains and derive a multivariate statistical model for detecting colon cancer. It was discovered that amino acid concentrations in all three domains are changed significantly in colon cancer and their relative distributions are also altered. The combined analysis helped improve the statistical model for detecting colon cancer. Since this study aims to investigate amino acids that directly connect the metabolome and proteome, it potentially brings new insights to the diagnosis of and mechanism involved in colon cancer development.
Textbook of Pulmonary Diseases
Authors: Gerald L. Baum, Emanuel Wolinsky
Journal: Annals of Internal Medicine (1989)

The normal lung diagnostic methods differential diagnosis pulmonary pharmacology inflammatory and interstitial diseases infectious diseases environmental lung disease obstructive lung disease respiratory insufficiency pulmonary manifestations of systemic diseases pulmonary vascular diseases neoplastic diseases congenital, developmental and genetic diseases of the lung pleural diseases.
Abstract 1134: Active Adaptation of the Tethered Mitral Valve: Insights into a Compensatory Mechanism for Ischemic Mitral Regurgitation
Authors: Jacob P Dal-Bianco, Elena Aikawa, Joyce Bischoff, J L Guerrero, Mark D Handschumacher, Suzanne Sullivan, Benjamin Johnson, James S Titus, Yoshiko Iwamoto, Jill Wylie-Sears, Alain Carpentier, Robert A Levine
Journal: Circulation (2008)

Background: In patients with myocardial infarction (MI) or left ventricular (LV) dilatation, mitral regurgitation (MR) is frequently induced by leaflet tethering imposed by displaced papillary muscles (PMs), and doubles mortality. Despite this, little is known about mitral valve (MV) tissue biology and its potential to compensate for LV remodeling, which has not yet been studied prospectively. We tested the hypothesis that MV area increases over time with mechanical stretch induced by PM displacement, and as a consequence of cell activation and matrix production as opposed to passive stretching. Methods: Under cardiopulmonary bypass, the PM tips in 6 adult sheep were retracted apically short of producing MR to replicate tethering without confounding MI or turbulence. Diastolic MV leaflet area (without systolic stretch) was quantified by a new validated 3D echo algorithm at baseline and after 61±6 days, and MV tissue collected for histology (H&amp;E, Masson) and fluorescent cell sorting at sacrifice. Data were compared with 6 unstretched sheep MVs. Results: Total diastolic MV leaflet area increased by 2.4±1.3cm2 (17±10%) from 14.3±1.9cm2 to 16.7±1.9cm2 (p&lt;0.01) with maintained stretch, without significant change in unstretched valves despite sham open-heart surgery. Stretched MVs were 2.8 times thicker than normal (1.18±0.43 vs 0.42±0.14mm, p&lt;0.01) due to increased spongiosa layer. Endothelial cells (CD31+) also expressing alpha-smooth muscle actin (α-SMA) were significantly more common by cell sorting in tethered versus normal leaflets (41±19% vs 9±5%, p=0.02), indicating endothelial-mesenchymal transdifferentiation (EMT); α-SMA+ positive cells indicating activation/EMT appeared in the high-stress atrial layer, penetrating into the valve interstitium, with increased collagen deposition, all absent normally. Conclusion: Mechanical stresses imposed by PM tethering increase MV leaflet area and matrix thickness, with cellular changes suggestive of reactivated embryonic valve development pathways. These findings support the concept of an actively adapting MV; understanding adaptive mechanisms can potentially provide therapeutic opportunities to augment MV area and reduce ischemic MR.
Association between comorbidities, disease severity and body mass index in COPD patients
Authors: Marli Knorst, Juliana Nunes, Lucas Ries, Jorge Valentini, Leandro Rech
Journal: European Respiratory Journal (2011)

Background:  COPD patients are often afflicted by multiple comorbidities.   Objectives:  To assess the nature and prevalence of comorbid diseases in a COPD population and to study the association between comorbidities and COPD severity and nutritional status.   Methods:  We studied 470 patients who met GOLD spirometric criteria for COPD (post-bronchodilator FEV 1 /FVC  25 30; n=95). Data are presented as mean (SD); Spearman test Kruskal-Wallis test were used.   Results:  Of the patients studied, 281 were men (59.8%), with mean age of 64.9 (10.3) years, FEV1 of 1.31 (0.3) l and BMI of 25.3 (5.7) kg/m 2 ). The average number of comorbidities per patient was 3.1 (1.9). In 105 patients (22.3%) five or more comorbidities were identified. The most frequent comorbidities found were hypertension (44.9%), cardiac disease (20%), diabetes (14.7%), osteoporosis (13.6%) and dyslipidemia (13%). There was no correlation between COPD severity and number of comorbidities (p>0.05). There was a significant correlation between BMI and number of comorbidities (r = 0.323; p    Conclusions:  We found that comorbidities are frequent in COPD and are associated with increase of BMI. Therefore, COPD patients should be encouraged to maintain their weight in the normal range.  Supported by FIPE/HCPA and FAPERGS.
Elevation of fasting serum lipids in patients treated with low-dose cyclosporine for severe plaque-type psoriasis
Authors: Matthew J. Stiller, Grace H. Pak, Clare Kenny, Lorrie Jondreau, Ira Davis, Seth Wachsman, Jerome L. Shupack
Journal: Journal of the American Academy of Dermatology (1992)

Elevation of fasting serum lipids in patients treatedwith low-dose cyclosporine for severe plaque-type .
Abstract 2011: ETV4 promotes pancreatic cancer progression and metastasis
Authors: Nikhil Tyagi, Sanjeev K. Srivastava, Arun Bhardwaj, Sumit Arora, William E. Grizzle, Laurie B. Owen, Ajay P. Singh, Seema Singh
Journal: Cancer Research (2014)

Abstract Pancreatic cancer is a highly metastatic disease with a 5 year survival rate of ∼6.0% after diagnosis. The poor outcome of pancreatic cancer is largely due to its highly aggressive nature and lack of effective therapies against metastatic disease. Therefore, it is imperative to identify novel molecular targets driving metastatic progression of pancreatic cancer. ETV4, proto-oncogenic transcription factor, has been shown to be expressed aberrantly in various cancers types and to play important roles in pathobiology; however, its roles in pancreatic cancer have not been defined. We investigated the pathological significance of ETV4 in pancreatic cancer by its silencing in two highly metastatic pancreatic cancer cell lines, Colo357 and ASPC1, and by forced overexpression in weakly tumorigenic BXPC3 cells. Silencing of ETV4 led to decreases in growth, clonogenicity, motility and invasiveness of pancreatic cancer cells, whereas its overexpression had opposite effects. Furthermore, our data demonstrate a correlation with changes in the expression of mesenchymal (N-cadherin, Vimentin, Slug and Snail) and epithelial (E-cadherin) markers upon ETV4 modulation, indicating its role in epithelial to mesenchymal transition (EMT). More importantly, our in vivo studies in an orthotopic mouse model of pancreatic cancer demonstrated a direct association of ETV4 overexpression with tumorigenicity and metastatic potential of pancreatic cancer cells. In summary, our studies establish a functional role of ETV4 in pancreatic cancer pathogenesis. Citation Format: Nikhil Tyagi, Sanjeev K. Srivastava, Arun Bhardwaj, Sumit Arora, William E. Grizzle, Laurie B. Owen, Ajay P. Singh, Seema Singh. ETV4 promotes pancreatic cancer progression and metastasis. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2011. doi:10.1158/1538-7445.AM2014-2011
Epidermal growth factor (EGF) and its receptors (ERBBs) in smokers with and without COPD: An index of epithelial repair imbalance?
Authors: Aristotelis Anagnostis, Eirini Neofytou, Nikolaos Soulitzis, Maria Avgousti, Charalampos Stroumpos, Ioannis Drositis, Nikolaos Siafakas, Eleni Tzortzaki
Journal: European Respiratory Journal (2012)

Background: The EGF and its receptors are expressed in the lung and orchestrate the epithelial repair process. We hypothesized that EGF pathways are involved in COPD pathogenesis.  Aim: To study EGF and ERBB receptors mRNA expression in lung tissue of smokers with or without COPD and control non-smokers.  Methods: Lung tissue specimens from 45 male subjects were studied: A) 10 patients with mild COPD (GOLD stage I), B) 10 patients with moderate COPD (GOLD stage II), C) 15 non-COPD smokers with normal lung function, and D) 10 non-smokers, serving as the control group. Quantitative Real-Time PCR experiments were carried out for EGF and receptors ERBB1, ERBB2, ERBB3, ERBB4, using beta-actin housekeeping gene as internal control.  Results: All study groups were matched for age. Moderate COPD patients had higher ERBB1 (EGFR), ERBB2 and ERBB3 mRNA levels compared to the other three groups. On the contrary, while moderate-COPD ERBB4 mRNA levels were statistically increased when compared to non-smokers (P=0.041), they did not differ when compared to mild-COPD patients (P=0.19) or to non-COPD smokers (P=0.18). Finally, EGF expression was at least 2-fold increased in moderate- and mild-COPD patients and non-COPD smokers, when compared to non-smokers, a finding which was statistically significant only between moderate-COPD patients and non-smokers (P=0.010).  Conclusions: EGF was over-expressed in all three smoking9 study groups. However, its receptors (especially ERBB1-3), were elevated only in moderate-COPD patients. This could reflect the epithelial “repair” or “remodeling” process exerting by the EGF signaling pathway as COPD progresses.
IgA nephropathy, the most common cause of glomerulonephritis, is linked to 6q22–23
Authors: Ali G. Gharavi, Yan Yan, Francesco Scolari, F. Paolo Schena, Giovanni M. Frasca, Gian Marco Ghiggeri, Kerry Cooper, Antonio Amoroso, Battista Fabio Viola, Graziana Battini, Gianluca Caridi, Cristina Canova, Anita Farhi, Vairavan Subramanian, Carol Nelson-Williams, Sue Woodford, Bruce A. Julian, Robert J. Wyatt, Richard P. Lifton
Journal: Nature Genetics (2000)
Abstract 20674: Genetic CETP Deficiency Associated With Higher eGFR and Lower Coronary Stenosis Index in Dyslipdemic Patients in Japan
Authors: Atsushi Nohara, Akihiro Inazu, Satoko Okazaki, Mie Yoshida, Mika Mori, Chiaki Nakanishi, Hayato Tada, Masa-aki Kawashiri, Kunimasa Yagi, Masakazu Yamagishi, Hiroshi Mabuchi
Journal: Circulation (2014)

Background: It is still controversial whether lower CETP is anti-atherogenic or not. Genetic deficiency should have greater impact on clinical course because its lifetime long effect. We evaluated impact of CETP deficiency on coronary atherosclerosis among dyslipidemic patients with non-familial hypercholesterolemia (non-FH) and with FH in Japanese population that include approximately 10% of heterozygous CETP deficiency. Methods: 374 non-FH dyslipidemic patients (170 males, mean age of 58 ± 14) including 201 subjects coronary angiography (CAG) assessed, and 235 genetically confirmed FH heterozygotes (121 males, mean age of 47 ± 17) including 61 CAG assessed were enrolled. Two common CETP variant, intron 14 G(+1)-to-A transition and D442G missense mutation in exon 15, were genotyped. Fasting lipid profiles without lipid drugs were analysed. Subgroup with LDL-C ≥140mg/dL (52% of non-FH) was defined as “hyper-LDL” in this study. Estimated Glomerular Filtration Rate (eGFR) and other conventional coronary risk factors were also analyzed. Results: Heterozygotes of CETP mutations were identified in 12% in non-FH group, and 8% in FH group. There were no differences in age or sex. In non-FH group, CETP mutations showed higher HDL-C (56 ± 22 vs. 50 ± 15 mg/dL, p &lt;0.05), lower non-HDL-C (172 ± 39 vs. 188 ± 48 mg/dL, p &lt;0.05), lower plasma CETP (2.1 ± 0.8 vs. 2.5 ± 0.7 μg/mL, p &lt;0.05), higher eGFR (83.6 ± 18 vs. 78.1 ± 21 ml/min/1.73m 2 , p &lt;0.05), and lower coronary stenosis index (CSI) (7.0 ± 7 vs. 11.1 ± 11, p &lt;0.05) in CAG. Plasma CETP showed strong positive correlation with LDL-C ( p &lt;0.0001, R 2 13%). In non-FH subgroup, CETP mutation showed lower CSI in hyper-LDL group (5.7 ± 8 vs. 12.6 ± 11, p &lt;0.05), but no difference in normal-LDL group (8.0 ± 7 vs. 10.2 ± 11, ns ). In FH group, CETP mutations showed higher HDL-C (58 ± 19 vs. 48 ± 14 mg/dL, p &lt;0.005), tendency of lower LDL-C (258 ± 51 vs. 275 ± 102 mg/dL, ns ) and higher eGFR (92.4 ± 27 vs. 83.1 ± 21 ml/min/1.73m 2 , ns ), but no difference in CSI (16.2 ± 15 vs. 19.2 ± 11, ns ). High HDL may have favorable effect also on kidney function, but further study will be required for the mechanism. Conclusion: CETP deficiency carriers showed favourable lipid profiles, eGFR, and CSI in non-FH dyslipidemic group especially with high LDL-C.
Abstract 2373: The Effects of Statin Therapy on MMP Families in Patients with Acute Heart Failure
Authors: Akihiro Shirakabe, Kunuya Asai, Noritake Hata, Shinya Yokoyama, Koichi Akutsu, Takuro Shinada, Nobuaki Kobayashi, Katsuhiro Kanemaru, Kyoichi Mizuno
Journal: Circulation (2008)

Introduction: It is known that increased matrix metalloprotease (MMP) accelerated cardiac remodeling in chronic heart failure (HF). Although roles of MMPs in acute HF have not been well clarified, we also found that MMPs increased in acute HF and decreased in the improvement of HF with conventional therapy. Pharmacological modification of MMPs may be beneficial for a treatment of acute HF. Therefore we assessed the hypothesis that a statin decreased MMPs in acute HF. Methods: Serum levels of MMP-2,-3, and -9 were measured on admission (Day 1), Day 3, and Day 14 in 38 acute HF patients. The patients were randomized to either atorvastatin group (n = 20) or control group (n = 18). Atorvastatin (10 –20mg per day) was started within 12 hours after their admission and continued for two weeks. There was no limitation in HF treatment and the treatment was not different between the two groups except atorvastatin. Patient characteristics including an etiology of HF and cardiac function were also not different between the groups. Results: There were no differences in serum levels of MMP-2, -3, and-9 on Day 1 between atorvastain group (1435.3 ± 292.6 ng/ml, 72.2 ± 40.4 ng/ml, 132.9 ± 85.5 ng/ml, respectively) and control group(1284.5 ± 399.6 ng/ml, 142.0 ± 139.7 ng/ml, 88.4 ± 51.2 ng/ml, respectively). MMP-2 significantly decreased in both atorvastatin and control group on Day 3 and Day 14. But, decreases of MMP-2 on Day 3 and Day 14 from Day 1 were significantly greater in atorvastatin group (− 581.3 ± 237.3 ng/ml and − 447.7 ± 228.3 ng/ml, respectively) than in control group (− 321.3 ± 257.8 ng/ml and − 275.0 ± 179.4 ng/ml, respectively). MMP-9 significantly decreased in atorvastatin group on Day 3 and Day 14 (132.9 ± 85.5 ng/ml on Day1, 71.4 ± 48.6 ng/ml on Day 3, 53.0 ± 28.5 ng/ml on Day 14; p &lt; 0.05), but did not change significantly in control group. MMP-3 did not significantly change in both groups. Conclusion: MMP-2 decreased with conventional HF treatment, but MMP-3 and -9 did not. Interestingly, early start of statin treatment significantly decreased both MMP-2 and -9, but not MMP-3 in acute HF. This is the first report demonstrating the effects of statin on MMPs in acute HF.
Angiosarcoma arising in a chronically lymphoedematous leg
Authors: None Sinclair, None Sviland, None Natarajan
Journal: British Journal of Dermatology (1998)

Cutaneous angiosarcoma is a rare aggressive tumour of capillary and lymphatic endothelial cell origin. It presents as multiple purple and red papules and nodules on the head and neck or the extremities. We report an 86-year-old woman with angiosarcoma arising on her chronically lymphoedematous right leg. The lymphoedema, secondary to chronic immobility, had developed gradually over 40 years. No other family members had lymphoedema. The patient presented with a plaque of friable tumour tissue on the lower right leg and dorsum of the foot, and satellite lesions on the knee and groin which initially appeared to be petechial haemorrhages. The satellite lesions in the groin grew into tumour nodules. There was no evidence of a preceding malignancy, nor any operative intervention to the affected limb or abdomen. Histological examination of all tumour specimens revealed moderately to poorly differentiated angiosarcoma. She died within 5 months of the first appearance of the skin nodules.
Metabolic Acidosis Suppresses 25-Hydroxyvitamin D3-1α-Hydroxylase in the Rat Kidney
Authors: Hiroyuki Kawashima, Jeffrey A. Kraut, Kiyoshi Kurokawa
Journal: Journal of Clinical Investigation (1982)

Effect of metabolic acidosis on two distinct 25-hydroxyvitamin D3-1α-hydroxylase (1α-hydroxylase) systems was studied in the kidneys of vitamin D-deficient rats; one is localized in the proximal convoluted tubule (PCT), is activated in vitamin D deficiency, and is regulated primarily by parathyroid hormone (PTH) via cyclic AMP; the other is localized in the proximal straight tubule (PST), is latent in vitamin D deficiency, and is selectively stimulated by calcitonin via a cyclic AMP-independent mechanism. The 1α-hydroxylase activities were measured in the PCT and PST microdissected from the kidney of vitamin D-deficient rats with or without metabolic acidosis of varying duration. The 1α-hydroxylase activity decreased in the PCT from 0.74±0.07 fmol/mm per h to 0.24±0.02 at day 3 of metabolic acidosis without a further decline at day 7. Neither metabolic acidosis of 16 h duration nor reduction of the incubation medium pH from 7.4 to 7.0 affected the enzyme activity in the PCT. To examine the underlying mechanism for the suppression of 1α-hydroxylase activity, PTH, cyclic AMP, or calcitonin was given to rats with metabolic acidosis of 3 d duration. Although PTH failed to augment the suppressed 1α-hydroxylase activity in the PCT, cyclic AMP restored it to the level of control rats. The 1α-hydroxylase activity in the PST remained undetectable in control rats and in acidotic rats with or without PTH or cyclic AMP treatments. However, calcitonin stimulated the 1α-hydroxylase activity in the PST equally from undetectable to 0.75±0.09 fmol/mm per h in control and to 0.78±0.10 in acidotic rats. The data suggests that metabolic acidosis suppresses 1α-hydroxylase only in the PCT by inhibiting PTH-dependent adenylate cyclase, and that cellular events beyond cyclic AMP in the PCT and the events responsive to calcitonin in the PST are unaffected. The results show the definite advantage of using defined single nephron segments to study the hormonal and ionic control of the 1α-hydroxylase system in the kidney.
Review: Acetaminophen reduces pain in hip or knee osteoarthritis by a small amount, but not low back pain
Authors: Roger Chou
Journal: Annals of Internal Medicine (2015)

Source Citation Machado GC, Maher CG, Ferreira PH, et al. Efficacy and safety of paracetamol for spinal pain and osteoarthritis: systematic review and meta-analysis of randomised placebo controlled trials. BMJ. 2015;350:h1225. 25828856
Continuation of Low-Dose Aspirin Therapy in Peptic Ulcer Bleeding
Authors: Joseph J.Y. Sung, James Y.W. Lau, Jessica Y.L. Ching, Justin C.Y. Wu, Yuk T. Lee, Philip W.Y. Chiu, Vincent K.S. Leung, Vincent W.S. Wong, Francis K.L. Chan
Journal: Annals of Internal Medicine (2020)

Sung and colleagues tested the idea that continuing aspirin therapy with proton-pump inhibitors after endoscopic control of peptic ulcer bleeding was not inferior to stopping aspirin therapy in adu...