tbuckley/cabot-search huggingface dataset:
Neuropsychiatric Disorders Caused by Cobalamin Deficiency in the Absence of Anemia or Macrocytosis
Authors: John Lindenbaum, Edward B. Healton, David G. Savage, John C.M. Brust, Thomas J. Garrett, Elaine R. Podell, Paul D. Margell, Sally P. Stabler, Robert H. Allen
Journal: New England Journal of Medicine (1988)

Among 141 consecutive patients with neuropsychiatric abnormalities due to cobalamin deficiency, we found that 40 (28 percent) had no anemia or macrocytosis. The hematocrit was normal in 34, the mean cell volume was normal in 25, and both tests were normal in 19. Characteristic features in such patients included paresthesia, sensory loss, ataxia, dementia, and psychiatric disorders; long-standing neurologic symptoms without anemia; normal white-cell and platelet counts and serum bilirubin and lactate dehydrogenase levels; and markedly elevated serum concentrations of methylmalonic acid and total homocysteine. Serum cobalamin levels were above 150 pmol per liter (200 pg per milliliter) in 2 patients, between 75 and 150 pmol per liter (100 and 200 pg per milliliter) in 16, and below 75 pmol per liter (100 pg per milliliter) in only 22. Except for one patient who died during the first week of treatment, every patient in this group benefited from cobalamin therapy. Responses included improvement in neuropsychiatric abnormalities (39 of 39), improvement (often within the normal range) in one or more hematologic findings (36 of 39), and a decrease of more than 50 percent in levels of serum methylmalonic acid, total homocysteine, or both (31 of 31). We conclude that neuropsychiatric disorders due to cobalamin deficiency occur commonly in the absence of anemia or an elevated mean cell volume and that measurements of serum methylmalonic acid and total homocysteine both before and after treatment are useful in the diagnosis of these patients. (N Engl J Med 1988; 318:1720–8.)
Advancing the Treatment for Chagas' Disease
Authors: Pedro Albajar-Viñas, João Carlos P. Dias
Journal: New England Journal of Medicine (2014)

It is estimated that 8 million people are infected with Trypanosoma cruzi worldwide, with the majority of cases occurring in the Latin American countries in which the parasite is endemic. However, cases of Chagas' disease have been increasingly detected in the United States, Canada, many European countries, and some Western Pacific countries, owing primarily to an increase in population movements between Latin America and other continents. Moreover, some countries in which the parasite is not endemic have higher estimated numbers of cases than many endemic countries in Latin America (e.g., >300,000 cases in the United States and >50,000 in Spain). . . .
Cholecysto-duodenal fistula as the source of upper gastrointestinal bleeding
Authors: N. Mohammed, E. Godfrey, V. Subramanian
Journal: Endoscopy (2013)

A 44-year-old woman was admitted with recurrent hematemesis. She had a history of intermittent upper abdominal pain, which was investigated by computed tomography (CT) scan 1 year prior to the presentation ([Fig. 1]). She was taking aspirin for ischemic heart disease.
Mechanisms of Chronic Muscle Wasting and Dysfunction after an Intensive Care Unit Stay. A Pilot Study
Authors: Claudia dos Santos, Sabah N. A. Hussain, Sunita Mathur, Martin Picard, Margaret Herridge, Judy Correa, Alexandra Bain, Yeting Guo, Andrew Advani, Suzanne L. Advani, George Tomlinson, Hans Katzberg, Catherine J. Streutker, Jill I. Cameron, Annemie Schols, Harry R. Gosker, Jane Batt
Journal: American Journal of Respiratory and Critical Care Medicine (2016)

Critical illness survivors often experience permanent functional disability due to intensive care unit (ICU)-acquired weakness. The mechanisms responsible for long-term weakness persistence versus resolution are unknown.To delineate cellular mechanisms underlying long-term weakness persistence in ICU survivors.We conducted a nested, prospective study of critically ill patients mechanically ventilated for 7 days or longer. The patients were recruited from the RECOVER program and serially assessed over 6 months after ICU discharge. Twenty-seven of 82 patients consented to participate; 15 and 11 patients were assessed at 7 days and 6 months after ICU discharge, respectively.We assessed motor functional capacity, quadriceps size, strength, and voluntary contractile capacity and performed electromyography, nerve conduction studies, and vastus lateralis biopsies for histologic, cellular, and molecular analyses. Strength and quadriceps cross-sectional areas were decreased 7 days after ICU discharge. Weakness persisted to 6 months and correlated with decreased function. Quadriceps atrophy resolved in 27% patients at 6 months. Muscle mass reconstitution did not correlate with resolution of weakness, owing to persistent impaired voluntary contractile capacity. Compared with Day 7, increased ubiquitin-proteasome system-mediated muscle proteolysis, inflammation, and decreased mitochondrial content all normalized at 6 months. Autophagy markers were normal at 6 months. Patients with sustained atrophy had decreased muscle progenitor (satellite) cell content.Long-term weakness in ICU survivors results from heterogeneous muscle pathophysiology with variable combinations of muscle atrophy and impaired contractile capacity. These findings are not explained by ongoing muscle proteolysis, inflammation, or diminished mitochondrial content. Sustained muscle atrophy is associated with decreased satellite cell content and compromised muscle regrowth, suggesting impaired regenerative capacity.
Abstract 429: Damage-induced apoptosis in primary human lymphocytes is a genetic program modified by gender and age.
Authors: Mark A. Applebaum, Andrew Skol, Gareth Bond, Kenan Onel
Journal: Cancer Research (2013)

Abstract Apoptosis is a core pathway deregulated in hematologic and other cancers. Although there are considerable functional and genetic data on the regulation of apoptosis in vitro and in model organisms, little is known about how these pathways are modified in primary cells freshly isolated from people, who are continually subjected to a variety of different and often unquantified environmental stimuli. We hypothesize that these exposures may have important and as yet unappreciated modifying effects on apoptosis that may have implications for cancer risk or response to therapy. To test this, we isolated peripheral blood mononuclear cells (PBMCs) from 90 normal healthy individuals and treated them with 5 Gy ionizing radiation (IR). Damage-induced apoptosis was measured at 24 hours after IR by TUNEL. We observed surprising heterogeneity in apoptosis among individuals, ranging from 21-65 percent. To determine whether this diversity in response was programmed or stochastic, we repeated the experiment 3 times in 10 individuals spanning the entire IR-induced apoptotic range and found results to be completely reproducible within individuals, suggesting that it resulted from a genetic program. We then assessed the association with individual characteristics. Whereas neither race nor age was associated with IR-induced apoptosis, gender was significantly associated (Mean: 44.8% vs 32.9%; p = 1.02 x 10-8). Moreover, when stratified by gender, age was significantly associated with IR-induced apoptosis in males (p = 0.026) but not females (p = 0.94). Thus, we conclude that IR-induced apoptosis in freshly isolated human PBMCs results from an intrinsic genetic program modified by age, but only within males. Genetic models to explain this will be discussed. Citation Format: Mark A. Applebaum, Andrew Skol, Gareth Bond, Kenan Onel. Damage-induced apoptosis in primary human lymphocytes is a genetic program modified by gender and age. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 429. doi:10.1158/1538-7445.AM2013-429
NC-15 * RELATIONSHIPS BETWEEN NEUROCOGNITIVE FUNCTIONING AND IDH1 GENETIC MUTATION STATUS IN MALIGNANT ASTROCYTOMA
Authors: J. Wefel, K. Noll, G. Rao, D. Cahill
Journal: Neuro-Oncology (2014)

BACKGROUND: Patients with malignant astrocytoma in similar brain regions present with variation in neurocognitive function (NCF). One potential contributor to this variation is the rate at which the tumor progresses or "lesion momentum". IDH1-wild type (IDH1-WT) tumors are more rapidly progressive than IDH1-mutant (IDH1-M) tumors. We hypothesized that patients with IDH1-WT tumors would exhibit worse NCF than patients with IDH1-M tumors. METHODS: The IDH1 status of 119 patients with malignant astrocytoma was determined with immunohistochemistry and genetic sequencing. Patients completed NCF testing prior to surgical resection [WAIS-III: Block Design, Similarities, Digit Span (DS), Digit Symbol; Hopkins Verbal Learning Test-Revised; Confrontation Naming; Controlled Oral Word Association (COWA); Token Test; Trail Making Test (TMT); Grooved Pegboard]. Raw NCF test scores were converted to age-adjusted z-scores. Lesion volume was calculated from preoperative T2/FLAIR MRI. RESULTS: Patients with IDH1-WT tumors (n = 66; mean age = 54.40) were significantly older than those with IDH1-M tumors (n = 53; mean age = 37.74; p < .001). No between group differences were found in years of education, gender, race, lesion location, or lesion volume. IDH1-WT patients performed worse than IDH1-M patients on all NCF tests with statistically significantly lower (p= .025 to .001) performances on HVLT-R Total Recall, HVLT-R Delayed Recall, TMTA, TMTB, COWA, Digit Symbol, Token, and Grooved Pegboard. For IDH1-WT patients, FLAIR volume was significantly associated with 12 of 14 NCF tests (r = -0.33 to -0.51, p < .009 for all). For IDH1-M patients, FLAIR volume was only significantly associated with Naming [r = -0.48, p = .001]. CONCLUSION: Patients with IDH1-WT malignant astrocytoma exhibit worse NCF than those with IDH1-M tumors. FLAIR lesion volume is inversely associated with NCF for patients with IDH1-WT but not IDH1-M tumors. These findings are consistent with the hypothesis that patients with IDH1-WT tumors present with greater NCF dysfunction secondary to greater lesion momentum that may preclude compensatory neuroplasticity and brain reorganization.
OP0247 Reduction of radiographic spinal progression in patients with ankylosing spondylitis treated with non-steroidal anti-inflammatory drugs is most evident in the presence of syndesmophytes and active systemic inflammation
Authors: D. Poddubnyy, H. Haibel, J. Listing, E. Märker-Hermann, H. Zeidler, J. Braun, M. Rudwaleit, J. Sieper
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Non-steroidal anti-inflammatory drugs (NSAIDs) are clinically effective and considered as a first line therapy in patients with ankylosing spondylitis (AS). NSAIDs might also have disease-modifying activities retarding radiographic spinal progression in AS. However, it is not clear whether the radiographic response to NSAIDs depends on the presence or absence of risk factors of radiographic spinal progression. <h3>Objectives</h3> The objective of the study was to investigate the effect of NSAIDs intake on the radiographic spinal progression in patients with AS in the presence and absence of risk factors for such a progression. <h3>Methods</h3> In total, 88 patients with AS according to the modified New York criteria from the German Spondyloarthritis Inception Cohort (GESPIC) have been selected for this analysis based on availability of spinal radiographs at baseline and after 2 years of follow-up and of the data on NSAIDs intake during this period of time. None of the patients included in this analysis received anti-TNF therapy. Radiographs of the cervical and lumbar spine were scored according to the mSASSS independently by two trained readers, who were blinded for time point and all clinical data. Data on NSAIDs intake were collected at baseline and every 6 months thereafter during 2 years of follow-up. An ASAS index of the NSAIDs counting both dose and duration of drug intake was calculated. High NSAIDs intake was defined as a mean NSAID intake index over 2 years of ≥50, low NSAIDs intake – as a mean NSAID intake index &lt;50. <h3>Results</h3> Patients with AS and high NSAIDs intake (n=24 or 27%), in comparison to patients with low NSAIDs intake (n=64 or 73%), had a lower rate of radiographic spinal progression as assessed by the change of mSASSS score over 2 years (0.02±1.38 vs. 0.96±2.78 mSASSS units). However, the positive effect of the NSAIDs intake was nearly exclusively evident in patients who were at high risk for radiographic progression due to the presence of syndesmophytes and persistent systemic inflammation. In patients with both, syndesmophytes and elevated (&gt;6 mg/l) time-averaged C-reactive protein (CRP), the mSASSS progression over two years was 4.36±4.53 vs 0.14±1.80 in the groups with low and high NSAIDs intake, respectively (p=0.02), while there was nearly no progression in patients without both risk factors: 0.35±1.07 vs 0.07±1.06, respectively (p=0.48) – figure. <h3>Conclusions</h3> Retardation of radiographic spinal progression in AS under NSAID therapy is most prominent in patients who are at high risk for progression. This might have an implication on the choice of the optimal NSAIDs regimen in individual patients in the clinical practice. <h3>Disclosure of Interest</h3> None Declared
A Surgical Approach to the Treatment of Fetal Hydrocephalus
Authors: William H. Clewell, Michael L. Johnson, Paul R. Meier, John B. Newkirk, Sheldon L. Zide, Robert W. Hendee, Watson A. Bowes, Frederick Hecht, Daniel O'Keeffe, George P. Henry, Robert H. Shikes
Journal: New England Journal of Medicine (1982)

Untreated fetal hydrocephalus results in gross cranial and facial abnormalities and profound brain damage. In an attempt to prevent both, a ventriculoamniotic shunt was implanted in a fetus with probable X-linked aqueductal stenosis and hydrocephalus. Performed at 24 weeks' gestation, the procedure used techniques similar to those used for intrauterine transfusion. After shunt placement, the fetal head size grew normally until after the 32d week, when the shunt failed. A cesarean delivery was performed at 34 weeks' gestation. The infant received a standard ventriculoperitoneal shunt after delivery, and his neonatal course has been evaluated through the first three months of life. In selected cases, the ventriculoamniotic shunt may be an acceptable treatment for fetal hydrocephalus.
Abstract 3079: Akt interacts and phosphorylates PHF20, a transcription factor binding to and inducing p53
Authors: Donghwa Kim, Sungman Park, Fei Yan, Lili He, Jin Q. Cheng
Journal: Cancer Research (2012)

Abstract Akt regulates a diverse arrays of cellular function, including apoptosis, cellular proliferation, differentiation, and metabolism. While a number of molecules have been identified as upstream regulators or downstream targets, the mechanism by which Akt regulates these cellular processes remains elusive. Here, we identified a novel transcription factor, PHF20, which binds to Akt and p53. PHF20 is an evolutionarily conserved protein. We showed that PHF20 is a transcriptional factor and transactivates p53. Furthermore, the interaction of PHF20 and p53 led to stabilize p53. Akt phosphorylates PHF20 in vitro and in vivo, which resulted in change of PHF20 nuclear localization and disassociation of p53 from PHF20 as well as decrease of p53 expression at mRNA and protein levels. In addition, knockdown of PHF20 reduces whereas ectopic expression of PHF20 increases p53 expression. These data suggest that PHF20 is a novel substrate of Akt and plays an important role in maintaining normal p53 function. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 3079. doi:1538-7445.AM2012-3079
Bone Imaging in Advanced Gastric Cancer
Authors: N Watanabe, M Haida, I Mikuni, M Shimizu, A Nakajima, H Seto
Journal: Clinical Nuclear Medicine (1998)

Tc-99m MDP bone scintigraphy is widely used to detect bone metastases. Besides, bone scintigraphy showed gastric uptake in various conditions, including stomach artifact, gastric calcification, and vitamin D toxification. The authors reported that Tc-99m MDP bone scintigraphy demonstrated increased gastric uptake in a patient with advanced gastric cancer.
Urinary Diastase in Mumps
Authors: Martin M. Nothman
Journal: New England Journal of Medicine (1951)

ELEVATION of serum diastase has been found in the great majority of adult patients with mumps.1 2 3 4 5 6 The increased levels may assist in establishing the diagnosis in doubtful cases. Most of the studies were performed on soldiers in epidemics of parotitis during the war. Examinations of the serum diastase in children have been rare. Applebaum1 included 3 cases in his series of 60, and Murphy, Bozalis and Bieri6 4 in a series of 35.Since an elevated level of diastase in the serum brings about an increase in the urinary excretion of the enzyme it was to be expected that the . . .
A Clinical, Epidemiologic and Laboratory Investigation of Aseptic Meningitis during the Four-Year Period, 1955–1958
Authors: Martha L. Lepow, David H. Carver, Harry T. Wright, Wilna A. Woods, Frederick C. Robbins
Journal: New England Journal of Medicine (1962)

ASEPTIC meningitis1 is a clinical syndrome encompassing a group of illnesses that includes and is clinically indistinguishable from nonparalytic poliomyelitis. The principal features are fever and signs of meningeal irritation, with cerebrospinal-fluid findings of pleocytosis, increased protein, normal sugar and absence of bacteria. Among infectious agents, viruses have been most frequently associated with this syndrome. In recent years the relation of some of the newly recognized members of the enterovirus group2 to the aseptic-meningitis syndrome has been established by isolation in tissue culture of viruses from patients with these illnesses. This group of viruses has epidemiologic and laboratory attributes closely . . .
MDS1/EVI1 enhances TGF-β1 signaling and strengthens its growth-inhibitory effect, but the leukemia-associated fusion protein AML1/MDS1/EVI1, product of the t(3;21), abrogates growth-inhibition in response to TGF-β1
Authors: R Sood, A Talwar-Trikha, SR Chakrabarti, G Nucifora
Journal: Leukemia (1999)
Abstract P4-04-01: Combination of intratumoral CpG with systemic anti-OX40 and anti-CTLA4 mAbs eradicates established triple negative breast tumors in mice
Authors: J Li, V Tandon, R Levy, L Esserman, M Campbell
Journal: Cancer Research (2012)

Abstract Background: Evidence is mounting across diverse datasets and scientific techniques implicating immune dysregulation in poor outcomes of high grade and/or triple negative breast cancers. A multimodal strategy to stimulate the immune system could be an effective therapeutic approach for breast cancer. CpG oligodeoxynucleotides are single-stranded DNA that stimulate dendritic cells and B cells by binding to Toll-like receptor 9 (TLR9). OX40 (CD134) is predominantly expressed on activated T cells and the binding of OX40 with an agonistic antibody (anti-OX40) leads to the proliferation and survival of T cells. Agonistic anti-OX40 antibodies can also reverse the suppressive effects of Treg cells. A third avenue is to target Cytotoxic T lymphocyte associated antigen (CTLA4), which plays a negative regulatory role in T cell activation and is also constitutively expressed on Treg cells. Blocking CTLA4 with an antagonistic antibody (anti-CTLA4) has been shown to enhance anti-tumor responses. In this study, we tested the combination of intratumoral (IT) CpG with systemic anti-OX40 plus anti-CTLA4 in a mouse model of triple negative breast cancer. Methods: 4T1, an aggressive, triple-negative mammary carcinoma, was implanted orthotopically into syngeneic BALB/C mice. Treatment was initiated when tumors were ∼0.5 cm in the largest dimension. Mice were divided into 8 groups. Various combinations of PBS control, CpG, taxol, and anti-OX40+anti-CTLA4 mAbs were tested (Tables 1 and 2). CpG, 100 µg, was injected IT for 5 consecutive days (days 1–5); Taxol, 16 mg/kg, was administered IP on day 1; anti-OX40 (400 µg) and anti-CTLA4 (100 µg) were given IP on days 1 and 5. Mice were sacrificed once tumors became ulcerated or reached a diameter &amp;gt;2 cm. Results: As shown in Table 1, CpG alone, taxol alone, or the anti-OX40 + anti-CTLA4 combination each delayed the growth of established 4T1 tumors when compared to the untreated control group. However, the majority of the mice (except one in CpG treated group) died from tumor progression. The combination of CpG + anti-OX40 + anti-CTLA4 had the best anti-tumor effects, with 4 out of 5 mice having demonstrated complete regression of their tumors (Table 2). The addition of taxol to the combination of CpG + anti-OX40 + anti-CTLA4 did not improve the anti-tumor effect, and while there was a substantial delay in growth, only one animal achieved a complete regression. Conclusion: Our study demonstrated that the combination of IT CpG with systemic anti-OX40 + anti-CTLA4 mAbs can cure mice with established triple negative breast tumors, supporting the possibilities of applying immune modulation approach in human triple negative tumors. Studies are on-going to further dissect the immunological mechanisms involved. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P4-04-01.
SAT0301 A comparative analysis of PSA spondylitis patients with PSA and AS 12 months after initiation of TNFI therapy
Authors: J. Madruga Dias, E. Balogh, L. Harty, E. Flynn, A. Grier, M. Molloy, P. Minnock, E. Molloy, O. Fitzgerald, D.J. Veale
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Spondyloarthropathies (SpA) are a family of disorders with common characteristics. This study compares baseline data and clinical outcomes 12 months post-TNFi therapy in patients with PsA plus spondylitis (PsAs), psoriatic arthritis without spondylitis (PsA) and ankylosing spondylitis (AS). <h3>Methods</h3> 77 SpA patients (n=23, PsAs; n=26, PsA; n=28, AS) were recruited, prior to TNFi therapy, and followed prospectively for 12 months. PsA was defined by the CASPAR criteria, PsAs plus inflammatory back pain and AS by the ASAS criteria. Demographic, radiographic, clinical and serological data were collected. Kruskal Wallis and Mann Whitney U tests were used to compare non parametric data between categories. Spearman’s Rho was used to test significance of correlations between baseline statistics and longitudinal outcomes. Results are presented as the mean and/or percentages. Statistical analysis was performed using SPSS 18. <h3>Results</h3> The PsAs group were significantly younger than the AS and the PsA group (43yrs&lt;47yrs&lt;53yrs; p=0.021). PsAs were more frequently male than AS and PsA (65% v 61% v 54%). 79% of AS patients were using NSAIDs compared to 52% of PsAs and 13% PsA. 64% PsAs patients were on Etanercept, 23% on Adalimumab, 9% on Infliximab and 4% Golimumab. PsAs patients had significantly higher DAS28 scores at baseline (5.2 v 4.1, p=0.006) yet lower 1yr DAS28 scores (1.5 v 2.6, p=0.003) compared to PsA. The ESR (2 v 16 v 13, p&lt;0.01) and CRP (3 v 7 v 6, p=0.03) were significantly lower in PsAs compared to both AS and PsA pt’s at 1yr, respectively. <h3>Conclusions</h3> The PsAs group appear to be younger, more males and have higher DAS28 scores at baseline compared to PsA without spondylitis or AS patients. <h3>Disclosure of Interest</h3> None Declared