tbuckley/cabot-search huggingface dataset:
FODMAPs alter symptoms and the metabolome of patients with IBS: a randomised controlled trial
Authors: Keith McIntosh, David E Reed, Theresa Schneider, Frances Dang, Ammar H Keshteli, Giada De Palma, Karen Madsen, Premysl Bercik, Stephen Vanner
Journal: Gut (2016)

Objective To gain mechanistic insights, we compared effects of low fermentable oligosaccharides, disaccharides and monosaccharides and polyols (FODMAP) and high FODMAP diets on symptoms, the metabolome and the microbiome of patients with IBS. Design We performed a controlled, single blind study of patients with IBS (Rome III criteria) randomised to a low (n=20) or high (n=20) FODMAP diet for 3 weeks. Symptoms were assessed using the IBS symptom severity scoring (IBS-SSS). The metabolome was evaluated using the lactulose breath test (LBT) and metabolic profiling in urine using mass spectrometry. Stool microbiota composition was analysed by 16S rRNA gene profiling. Results Thirty-seven patients (19 low FODMAP; 18 high FODMAP) completed the 3-week diet. The IBS-SSS was reduced in the low FODMAP diet group (p&lt;0.001) but not the high FODMAP group. LBTs showed a minor decrease in H 2 production in the low FODMAP compared with the high FODMAP group. Metabolic profiling of urine showed groups of patients with IBS differed significantly after the diet (p&lt;0.01), with three metabolites (histamine, p-hydroxybenzoic acid, azelaic acid) being primarily responsible for discrimination between the two groups. Histamine, a measure of immune activation, was reduced eightfold in the low FODMAP group (p&lt;0.05). Low FODMAP diet increased Actinobacteria richness and diversity, and high FODMAP diet decreased the relative abundance of bacteria involved in gas consumption. Conclusions IBS symptoms are linked to FODMAP content and associated with alterations in the metabolome. In subsets of patients, FODMAPs modulate histamine levels and the microbiota, both of which could alter symptoms. Trial registration number NCT01829932.
Few eligible patients currently receive treatment
Authors: S. Tuominen, P. Romppanen, A. Rosenvall
Journal: BMJ (1995)

in better paediatric care, education, or social environment, which are more likely than in vitro fertilisation to maximise utility.When resources for health care are scarce we need to consider the opportunity costs of any investment.While infertility can cause psychological distress, a better use of resources may be to offer counselling to allow couples to accept their condition, or to attempt to alter the expectations of relatives and friends.
Dramatic Response to Combination Erlotinib and Crizotinib in a Patient with Advanced, EGFR -Mutant Lung Cancer Harboring De Novo MET Amplification
Authors: Justin F. Gainor, Matthew J. Niederst, Jochen K. Lennerz, Ibiayi Dagogo-Jack, Sara Stevens, Alice T. Shaw, Lecia V. Sequist, Jeffrey A. Engelman
Journal: Journal of Thoracic Oncology (2016)
Vancouver data supports a weak association between tendon pathology and serum lipid profiles
Authors: Elise Huisman, Pierre Guy, Alex Scott
Journal: British Journal of Sports Medicine (2016)

We read with great interest Tilley et al 1 meta-analysis which demonstrates the strong association between tendon pathology and serum lipid profiles. This paper included 17 studies involving 2612 participants who were either controls, or who had verified pathology of the Achilles or rotator cuff tendons. The authors conclude that individuals with abnormal lipid profile are much more likely to develop tendon problems. This paper would seem to respond with a resounding ‘Yes!’ to the question posed in 2010, in the pages of BJSM , by Longo et al 2—‘Triglycerides and total serum cholesterol in rotator cuff tears: do they matter?’ Tilley's data suggest that triglycerides and total serum cholesterol matter in Achilles tendinopathy and rupture as well.

The results of …
The clinicopathologic characteristics and outcome of atypical anti-glomerular basement membrane nephritis
Authors: Samih H. Nasr, A. Bernard Collins, Mariam Priya Alexander, Daniel F. Schraith, Loren Herrera Hernandez, Mary E. Fidler, Sanjeev Sethi, Nelson Leung, Fernando C. Fervenza, Lynn D. Cornell
Journal: Kidney International (2016)

Classic anti-glomerular basement membrane (GBM) disease presents with rapidly progressive glomerulonephritis (GN) with or without pulmonary hemorrhage. On biopsy typical disease displays bright polytypic linear GBM staining for IgG by immunofluorescence and diffuse crescentic/necrotizing GN on light microscopy. Here, we studied 20 patients with atypical anti-GBM nephritis typified by bright linear GBM staining for immunoglobulins but without a diffuse crescentic phenotype. Patients had hematuria, proteinuria, and mild renal insufficiency, without pulmonary hemorrhage. Light microscopy showed endocapillary proliferative GN in 9 patients, mesangial proliferative GN in 6, membranoproliferative GN in 3, and focal segmental glomerulosclerosis with mesangial hypercellularity in 2. Eight of the 20 showed features of microangiopathy. Crescents/necrosis were absent in 12 and were focal in 8 patients. Bright linear GBM staining for IgG was seen in 17 patients, IgM in 2, and IgA in 1 patient, which was polytypic in 10 patients and monotypic in 10 patients. No circulating α3NC1 antibodies were detected by commercial ELISA. The 1-year patient and renal survival rates were 93% and 85%, respectively. Thus, atypical anti-GBM nephritis is a rare variant of anti-GBM disease characterized clinically by an indolent course, no pulmonary involvement, and undetectable circulating α3NC1 antibodies. Further studies are needed to characterize the molecular architecture of GBM autoantigens in these patients and establish optimal therapy.
Prolonged response without prolonged chemotherapy: A lesson from PCV chemotherapy in low-grade gliomas.
Authors: M. Peyre, S. Cartalat-Carel, D. Meyronet, M. Sunyach, E. Jouanneau, J. Guyotat, A. Jouvet, D. Frappaz, J. Honnorat, F. Ducray
Journal: Journal of Clinical Oncology (2010)

e12519 Background: Previous studies with temozolomide suggest that a prolonged duration of chemotherapy is important for treating low-grade gliomas (LGGs). The objective of this retrospective study was to evaluate the impact of first-line PCV chemotherapy on LGGs growth. Methods: For this purpose, the mean tumor diameter (MTD) of 21 LGGs was evaluated on serial magnetic resonance images before (n = 13), during and after PCV onset (= 21). Results: During PCV, a decrease of the MTD was observed in all patients. After the end of PCV, though at a slower rate, a continuing decrease of the MTD was observed in 20 out of 21 patients. Median duration of this persistent decrease was 2.7 years (0-7 years). According to MacDonald's criteria, the rates of partial and minor responses were 44% at the end of PCV (6% partial and 38% minor responses) but 75 % at the time of maximal tumor response, after a median of 3.4 years following PCV onset (43% partial and 32% minor responses). A persistent and prolonged decrease of LGGs volume (> 2 years) was observed in 60% of the patients despite no more chemotherapy was administered. Conclusions: These results challenge the current view that in LGGs a prolonged chemotherapy treatment is necessary in order to achieve a prolonged response and raise also the issue of the mechanisms involved in the persistent tumor decrease once chemotherapy is stopped. No significant financial relationships to disclose.
Targeted delivery of let-7b to reprogramme tumor-associated macrophages and tumor infiltrating dendritic cells for tumor rejection
Authors: Zhen Huang, Jingjing Gan, Ziyan Long, Guangxing Guo, Xiafei Shi, Chunming Wang, Yuhui Zang, Zhi Ding, Jiangning Chen, Junfeng Zhang, Lei Dong
Journal: Biomaterials (2016)
Abstract 18918: Distinct Gene Expression Profiles of the Mitral Valve Leaflets in Barlow’s Disease and Fibroelastic Defficiency
Authors: Tarek S Absi, Cristi L Galindo, Michael Petracek, Daniel Lenihan, Marzia Leacche, Dougals B Sawyer, John Byrne, Yan Ru Su
Journal: Circulation (2013)

OBJECTIVES: The mitral valve (MV) leaflets in severe MR undergo structural remodeling associated with multiple degenerative and adaptive changes. We hypothesized that the gene expression profiles of the posterior MV leaflets from patients with bileaflet prolapse (Barlow’s valves) are distinct from those with only posterior leaflet degeneration (fibroelastic deficiency or MMR), reflecting different underlying pathophysiologic processes. Methods: MVs were obtained from 12 Barlow’s patients (9 m, 3 f; age= 59.8±12.2 y, LVEF=60.4±5.8%) and 17 MMR patients (10 m, 7 f, age= 54.2±6.6 y, LVEF=59.7±5.1%) undergoing surgery for severe MR. Normal MV were obtained from 6 unmatched donor hearts (4 m, 2 f, age= 41.5±10.7 y, LVEF=57.5±8.8%). RNA was extracted and cDNA microarray was carried on the Affymetrix Gene Chip 1.1. Normalization and two-way ANOVA analysis were performed. Only genes that resulted in &gt;1.5 fold difference and p &lt;0.05 were considered significantly altered. RESULTS: Of ~29,000 genes examined, 973 (3.3%) were differentially expressed between the two disease groups. Principal component analysis and Hierarchical clustering of the normalized fluorescence signal values for these genes successfully differentiated all the Barlow’s from the MMR samples (Figure 1). Based on functional analysis, selected statistically significant enriched biological processes are listed in (table1). Conclusions: MV leaflets in Barlow’s and MMR exhibit distinct gene expression patterns, suggesting different pathophysiologic mechanisms are involved in the leaflet remodeling processes. Understanding such adaptive mechanisms can potentially provide therapeutic opportunities.
Clinical impact of early absolute lymphocyte count after allogeneic stem cell transplantation
Authors: D. H. Kim, J. G. Kim, J. H. Baek, S. K. Sohn, J. S. Suh, K. S. Lee, K. B. Lee
Journal: Journal of Clinical Oncology (2004)

6632 Background: The role of repopulating lymphocytes after allogeneic SCT (stem cell transplantation) can include the prevention of serious infections and attacking of residual tumor cells in the early post-transplant phase. Therefore, the current study analyzes the role of the absolute lymphocyte count (ALC) on day 21 after SCT in predicting transplant outcomes in terms of the risk of opportunistic infections and recurrence of original diseases. Methods: Eighty-four patients (41 AML, 17 CML, 9 AA, 5 ALL, 6 MDS, 2 NHL, 2 MM, and 2 others) receiving allogeneic SCT were enrolled. The median dose of CD34+, CD3+, and mononuclear cells infused was 6.89×106/kg, 2.38×108/kg, and 9.98×108/kg, respectively. Patients were stratified into two risk groups based on the ALC checked on day 21 (high ALC; ≥350/uL, low ALC; <350/uL). Results: The high ALC group was associated with the use of PBSCs, matched sibling donors, and higher cell doses of MNC, CD3+, and CD4+ cells. The incidence of severe acute GVHD was lower in the high ALC group than in the low ALC group, yet the overall incidence of acute GVHD or chronic GVHD was similar between the two groups. The high ALC group also exhibited a better overall survival (OS) (55.9% vs 17.7%, p=0.0010) and disease-free survival (DFS) (50.4% vs 15.9%, p=0.0012) after 3 years, and lower cumulative incidence of relapse (27.2% vs 77.9%, p=0.0089) and lower incidence of fungal infections (3.0% vs 19.5%, p=0.0132) after 1 year. Furthermore, the cumulative incidence of CMV antigenemia was lower in the high ALC group (50.0% vs 73.7%, p=0.0224). Conclusions: Accordingly, identifying the ALC on day 21 would appear to be a useful and simple measurement that can predict patient groups with a high risk of opportunistic infections and high risk of relapse after allogeneic SCT. No significant financial relationships to disclose.
Organic Mercurial Preparations in Skin Diseases
Authors: E. A. J. Byrne
Journal: BMJ (1947)

MEDICAL JOURNALonly a small proportion of the total attendance for that disease, but these records, mostly of Ganda patients, were chosen for their relative completeness.In 173 of these 190 cases (all young adult males) the serum Kahn was positive or spiro- chaetes were found.In 7 the serum Kahn was negative.Penile sores were present in 60 cases; 41* admitted and 6 denied having had any penile lesions.Among these 190 cases the following frequency of lesions was recorded: condylo- mata, 91; " secondary rashes," 21; macules, 20; papules, 14; maculo-papules, 9; circinate lesions on scrotum, 8; buccal mucous membrane lesions, 8; papulo-squamous, 3; squam- ous, 2; circinate, 2. The condylomata were described as scrotal, perineal, and anal.No mention was made of any framboesiforni lesions.At Lira the atypical secondary yaws lesions, and genital lesions, in the absence of typical lesions were infrequent.Loewenthal (1939) reported syphilitic aortitis and aneurysm, meningo-vascular lesions, choroiditis, and gum- matous iritis in patients at Mulago, but stated that visceral gummata were rare.Such lesions were not seen among the Lango.Serological Surveys Sera collected in January, 1939, from 100 consecutive male Lango prisoners, aged 18 to 35 years, in the Erute (Lira) Gaol gave the following Kahn reactions: + + + +, 46; ++ 21; + +, 14; +, 2; ±, 7; and -, 10.If reactions of +, ±, andare regarded as negative, then 81 were positive.The ages of these subjects were: 18-20 years, 32; 21-25, 36; 26-30, 23 ; 31-35, 9. Other findings in this group and in 130 station labourers are given in Table VI.TABLE VI.-Clinical Findings in Two Groups of Adult Lango Males at Lira 100 Prisoners 130 Station Labourers History of having had yaws 94 90 Scars of previous secondary yaws 78 79 Enlarged epitrochlear glands 72 69 Bone changes 68 62 Palmar changes 51 60 Plantar changes 61 73 Bone pain 49 41One case each of dorsal ganglion of the wrist, Dupuytren- like contractures of the fingers, and aortic systolic murmur was seen among prisoners under 30 years of age; the sera from these were Kahn + + + +.Among the labourers were 4 cases with ganglion and 12 with Dupuytren-like contractures.Bone changes consisted mainly of bowing, thickening, or irregularity of tibiae.Palmar and plantar changes comprised thickening, localized or generalized erosion, fissuring, pitting, and laminar desquamation.Among the prisoners no statistical association was found between any of the items in Table VI and the reaction of the serum Kahn.The six prisoners who denied having had yaws were under 25 years of age; the serum from two was Kahn + + + +, from another two it was Kahn + + +, and from the remaining two Kahn -.The last two subjects were 20 years
Snk/Plk2 CpG methylation in patients with multiple myeloma
Authors: A. Dasoula, E. Hatzimichael, G. Dranitsaris, L. Benetatos, N. Syed, A. Vassou, J. Stebbing, T. Crook, K. Bourantas
Journal: Journal of Clinical Oncology (2009)

e19532 Background: We previously showed that polo like kinase 2 (Snk/Plk2) is subject to methylation-dependent transcriptional silencing in a very high frequency in Burkitt lymphomas. Here, we have examined CpG methylation in Snk/Plk2 in a well-characterized series of multiple myeloma (MM) patients. Methods: Bone marrow samples from individuals with MM were obtained at diagnosis and in 5 cases at disease progression as well. Genomic DNA was isolated and bisulphite modification was performed using commercially available kits. The methylation-specific polymerase chain reaction (MSP) was employed to study its methylation status. Control methylated and unmethylated genomic DNAs were included in each experiment. Ten bone marrow samples from individuals proven to have no haematological malignancy, served as negative controls. Logistic regression analyses were used to measure the association between gene methylation and the development of advanced disease (DS≥II), extramedullary disease, bone disease, anemia (Hb 10 mg/dl), serum albumin and beta 2 microglobulin levels. Results: We analyzed the methylation of Snk/Plk2 in 45 cases of MM (24 male, 21 female, mean age 66.4 years ±12.4). Classical cytogenetic analysis was available in 30/45 patients and none of them was found to have chromosome 13 abnormalities. No sample from the control population was found methylated. The Snk/Plk2 promoter was found to be methylated in 27/45 patients (60%). Median survival of patients in whom the Snk/Plk2 CpG island was methylated was 7.1 years compared to a median survival of 8.8 years for unmethylated. However Snk/Plk2 methylation was not a predictor of excess mortality (HR=0.6, p=0.5), bone lytic lesions (OR=0.56, p=0.3), anemia (OR=0.5, p=0.3) or advanced stage as defined above (OR=0.8, p=0.7). Conclusions: Snk/Plk2 DNA Methylation is a frequent event in patients with multiple myeloma. There was no association between the methylation status of the gene and relevant clinical parameters. Further evaluation in a larger sample of patients is needed in order to better define the prognostic and clinical value if any of Snk/Plk2 methylation in MM. No significant financial relationships to disclose.
MicroRNA <i>MIR21</i> (miR-21) and PTGS2 Expression in Colorectal Cancer and Patient Survival
Authors: Kosuke Mima, Reiko Nishihara, Juhong Yang, Ruoxu Dou, Yohei Masugi, Yan Shi, Annacarolina da Silva, Yin Cao, Mingyang Song, Jonathan Nowak, Mancang Gu, Wanwan Li, Teppei Morikawa, Xuehong Zhang, Kana Wu, Hideo Baba, Edward L. Giovannucci, Jeffrey A. Meyerhardt, Andrew T. Chan, Charles S. Fuchs, Zhi Rong Qian, Shuji Ogino
Journal: Clinical Cancer Research (2016)

Prostaglandin-endoperoxide synthase 2 (PTGS2, cyclooxygenase-2; a target of aspirin) produces inflammatory mediator prostaglandin E2 (PGE2), and contributes to colorectal neoplasia development. PTGS2-driven inflammatory responses can induce tumor expression of microRNA MIR21 (miR-21) that can increase local PGE2 level by downregulating PGE2-metabolizing enzymes. We hypothesized that the prognostic association of tumor MIR21 expression level in colorectal carcinoma might depend on inflammatory tumor microenvironment and be stronger in tumors expressing high-level PTGS2.Utilizing 765 rectal and colon cancer specimens in the Nurses' Health Study and the Health Professionals Follow-up Study, we measured MIR21 expression by quantitative reverse transcription PCR, and PTGS2 expression by immunohistochemistry. Cox proportional hazards regression model was used to assess statistical interaction between MIR21 and PTGS2 in colorectal cancer-specific survival analysis, controlling for potential confounders including microsatellite instability, CpG island methylator phenotype, LINE-1 methylation level, and KRAS, BRAF, and PIK3CA mutations.Tumor MIR21 expression level was associated with higher colorectal cancer-specific mortality (Ptrend = 0.029), and there was a statistically significant interaction between MIR21 and PTGS2 (Pinteraction = 0.0004). The association between MIR21 expression and colorectal cancer-specific mortality was statistically significant in PTGS2-high cancers (multivariable hazard ratio of the highest vs. lowest quartile of MIR21, 2.28; 95% confidence interval, 1.42-3.67; Ptrend = 0.0004) but not in PTGS2-absent/low cancers (Ptrend = 0.22).MIR21 expression level in colorectal carcinoma is associated with worse clinical outcome, and this association is stronger in carcinomas expressing high-level PTGS2, suggesting complex roles of immunity and inflammation in tumor progression. Clin Cancer Res; 22(15); 3841-8. ©2016 AACR.
Paracetamol does not reduce pain or improve function in osteoarthritis, study shows
Authors: Susan Mayor
Journal: BMJ (2016)

Paracetamol had virtually no effect on pain or function in patients with osteoarthritis, shows a large meta-analysis that found the non-steroidal anti-inflammatory drug (NSAID) diclofenac to be more effective.1

Paracetamol and NSAIDs are commonly used to treat pain associated with osteoarthritis. But the wide range of different preparations and dosages complicates prescribing decisions, and systematic reviews have previously reported their effects on reducing pain when compared with placebo, so this has not allowed for comparisons between different agents.

To compare different …
Double-pigtail stent migration invading the spleen: rare potentially fatal complication of endoscopic internal drainage for sleeve gastrectomy leak
Authors: Gianfranco Donatelli, Gheorghe Airinei, Eric Poupardin, Thierry Tuszynski, Philippe Wind, Robert Benamouzig, Bruno Meduri
Journal: Endoscopy (2016)

Endoscopic internal drainage (EID) by means of a double-pigtail stent is increasingly used as an effective approach to management of leak and fistula following gastrointestinal (GI) surgery, particularly surgery for obesity [1] [2] [3]. Complications related to this technique include GI ulceration at the tip of the double-pigtail stent, migration into the abdominal cavity, and bleeding.
Regulatory considerations for early clinical studies of anti-cancer drugs in healthy volunteers
Authors: R. N. Dagher, L. A. Rosario, D. E. Morse, R. Pazdur
Journal: Journal of Clinical Oncology (2005)

3101 Background: Most phase 1 trials designed to evaluate anticancer agents enroll patients with refractory malignancies. Availability of non-cytotoxic drugs permits conduct of studies in healthy volunteers (HV). Reasons to conduct phase 1 trials in HV may include exploration of bioavailability, reduction of patient exposure to relatively low/ineffective drug doses, and relatively rapid study accrual. Pre-clinical and clinical considerations must be addressed in study design. Methods: We reviewed proposals for phase 1 trials of anti-cancer drugs to be conducted in HV under US INDs from 2003–2004. Although genotoxicity study requirements are generally waived for cytotoxic drugs evaluated in cancer patients, studies in HV require completion of the in vitro portion of the genotoxicity battery and completion of the in vivo portion is highly encouraged. In contrast to the cytotoxic paradigm of starting dose defined as 1/10 of the severely toxic dose (STD10) in rodents, studies in HV generally require a starting dose 1/10 of the rodent no-adverse-event-level (NOAEL) and safe passage in a non-rodent species. Clinical considerations include the need to limit drug exposure to 1 or 2 doses in most cases and to employ a conservative dosing schema with cessation when any grade 2 toxicity is encountered. Results: Design elements for 8 HV studies of anti-cancer drugs are as follows: Studies included signaling agents (2) receptor modulators (3) growth factors (2) and one chemoprevention agent. Genotoxicity battery results included full batteries that were negative in 7 cases and one case where in vitro studies were negative. In 3 studies the starting dose was ≤ 1/10 the rodent NOAEL and in 5 studies the starting dose was based on clinical data. In 6 studies, a single drug dose was proposed. In one study, two doses were proposed per patient, and one study employed a daily x 5 dosing scheme x 1 based on clinical data. Conclusions: Pre-clinical and clinical considerations involving evaluation of genotoxicity, estimation of starting dose, limitation of clinical exposure, and attention to a conservative dose escalation plan must be addressed in designing early clinical trials of anti-cancer drugs in HV. No significant financial relationships to disclose.