tbuckley/cabot-search huggingface dataset:
<i>Bacillus anthracis</i>Meningitis
Authors: A G Garcia, R R Jimenez
Journal: New England Journal of Medicine (1999)

Figure 1 A 49-year-old sheep farmer came to us with a necrotic lesion on his chin, with surrounding gelatinous edema (arrow in Panel A), and a three-day history of obtundation. On examination, he had a temperature of 39°C, a stiff neck, Kernig's sign, generalized hyperreflexia, and bilateral Babinski signs. His left pupil was fixed and dilated. A specimen of cerebrospinal fluid was grossly bloody, and microscopical examination revealed chains of gram-positive bacilli (arrow in Panel B). Cultures of blood and cerebrospinal fluid yielded Bacillus anthracis. Treatment was begun with 24 million U of penicillin G per day. One week later, seizures developed, followed by hemiplegia of the right side. Multisystem failure occurred, and the patient died. Autopsy revealed a left frontal and parietal hematoma and congested leptomeninges (Panel C), with hemorrhagic infiltration by lymphocytes, polymorphonuclear leukocytes, and aggregates of gram-positive bacilli. The walls of the blood vessels were thickened, with areas of necrosis. The lungs showed marked congestion of both lower lobes, with gram-positive bacilli in the exudate. Figure 1 A 49-year-old sheep farmer came to us with a necrotic lesion on his chin, with surrounding gelatinous edema (arrow in Panel A), and a three-day history of obtundation. On examination, he had a temperature of 39°C, a stiff neck, Kernig's sign, generalized hyperreflexia, and bilateral Babinski signs. His left pupil was fixed and dilated. A specimen of cerebrospinal fluid was grossly bloody, and microscopical examination revealed chains of gram-positive bacilli (arrow in Panel B). Cultures of blood and cerebrospinal fluid yielded Bacillus anthracis. Treatment was begun with 24 million U of penicillin G per day. One week later, seizures developed, followed by hemiplegia of the right side. Multisystem failure occurred, and the patient died. Autopsy revealed a left frontal and parietal hematoma and congested leptomeninges (Panel C), with hemorrhagic infiltration by lymphocytes, polymorphonuclear leukocytes, and aggregates of gram-positive bacilli. The walls of the blood vessels were thickened, with areas of necrosis. The lungs showed marked congestion of both lower lobes, with gram-positive bacilli in the exudate. Ascension Gonzalez Garcia, M.D.Rafael Rodriguez Jimenez, M.D.Hospital Universitario Virgen Macarena, 41071 Seville, Spain
HPV16 Sublineage Associations With Histology-Specific Cancer Risk Using HPV Whole-Genome Sequences in 3200 Women
Authors: Lisa Mirabello, Meredith Yeager, Michael Cullen, Joseph F Boland, Zigui Chen, Nicolas Wentzensen, Xijun Zhang, Kai Yu, Qi Yang, Jason Mitchell, David Roberson, Sara Bass, Yanzi Xiao, Laurie Burdett, Tina Raine-Bennett, Thomas Lorey, Philip E Castle, Robert D Burk, Mark Schiffman
Journal: JNCI Journal of the National Cancer Institute (2016)

Background: HPV16 is a common sexually transmitted infection although few infections lead to cervical precancer/cancer; we cannot distinguish nor mechanistically explain why only certain infections progress. HPV16 can be classified into four main evolutionary-derived variant lineages (A, B, C, D) that have been previously suggested to have varying disease risks.
Environmental Chemicals in Urine and Blood: Improving Methods for Creatinine and Lipid Adjustment
Authors: Katie M. O’Brien, Kristen Upson, Nancy R. Cook, Clarice R. Weinberg
Journal: Environmental Health Perspectives (2015)

Investigators measuring exposure biomarkers in urine typically adjust for creatinine to account for dilution-dependent sample variation in urine concentrations. Similarly, it is standard to adjust for serum lipids when measuring lipophilic chemicals in serum. However, there is controversy regarding the best approach, and existing methods may not effectively correct for measurement error.We compared adjustment methods, including novel approaches, using simulated case-control data.Using a directed acyclic graph framework, we defined six causal scenarios for epidemiologic studies of environmental chemicals measured in urine or serum. The scenarios include variables known to influence creatinine (e.g., age and hydration) or serum lipid levels (e.g., body mass index and recent fat intake). Over a range of true effect sizes, we analyzed each scenario using seven adjustment approaches and estimated the corresponding bias and confidence interval coverage across 1,000 simulated studies.For urinary biomarker measurements, our novel method, which incorporates both covariate-adjusted standardization and the inclusion of creatinine as a covariate in the regression model, had low bias and possessed 95% confidence interval coverage of nearly 95% for most simulated scenarios. For serum biomarker measurements, a similar approach involving standardization plus serum lipid level adjustment generally performed well.To control measurement error bias caused by variations in serum lipids or by urinary diluteness, we recommend improved methods for standardizing exposure concentrations across individuals.
Case 13-2016
Authors: Lee H. Schwamm, Michael R. Jaff, K. Sophia Dyer, R. Gilberto Gonzalez, Amelia E. Huck
Journal: New England Journal of Medicine (2016)

A 49-year-old woman was brought to the ED 2 hours after the onset of hemiplegia and aphasia during a transatlantic flight. Examination revealed evidence of acute ischemic stroke. Additional diagnostic studies were performed.
Phase II trial of capecitabine, oxaliplatin plus bevacizumab followed by bevacizumab plus erlotinib: XELOBER trial
Authors: A. Muñoz, A. Salut, C. Pericay, C. García, J. Roca, R. Dueñas, F. Rivera, V. Alonso, M. Alonso, E. Falcó
Journal: Journal of Clinical Oncology (2008)

15078 Background: Bevacizumab (Bev) is being commonly used as first line treatment for metastatic colorectal cancer (mCRC). At the present time lots of trials have already been published in wich Bev has been combined with many different chemotherapy regimens based on Irinotecan or oxaliplatin (Ox). In most of these trials treatment with all the drugs of the combination should be maintained until disease progression or unaceptable toxicity but there are no clear data regarding the optimal duration of the treatment. In this trial we will try to determine the efficacy of a treatment in wich XELOX is stopped after 6 cycles to continue with Bev plus Erlotinib (E) as maintenance therapy until disease progression. Methods: This is a phase II, multicenter, non-randomized trial, in wich 88 pts diagnosed with mCRC will receive XELOX (capecitabine 1,000 mg/m2 bid vo days 1–14 and oxaliplatin 130 mg/m2 d1) plus Bev (7.5 mg/kg dy 1) all of them every 3 wks, for 6 cycles and then will continue with a maintenance treatment of Bev (7.5 mg/d1 q3w) plus E (150 mg daily vo) until disease progression or unaceptable toxicity. The primary end point is PFS. Secondary end points are: OS, ORR and toxicity. Elegibility criteria: Measurable, non resectable and untreated mCRC, age ≥18 yrs, ECOG 0–1 and adequate organ function. Results: So far 31 pts have been recruited. Toxicity data are available on 27 pts. Baseline characteristics: median age 62 yrs (46–75), male/female 81%/20%, ECOG 0/1 68/32%. Most common toxicities reported are: asthenia in 63% pts (G1 11.2% G2 44.4% and G3 7.4%), diarrhea in 40.74% pts (G1 22%,G2 7.4%, G3 11%) and hand-foot-syndrome in 33.3% pts (G1 22.2% and G2 11%). Specific AE‘s related to Bev were very uncommon: hypertension, rectorrhage and epistaxis were reported in 1 pts each (all grade 1). No other Bev related toxicities have been reported yet. Conclusions: The combination of Bev with XELOX seems to be well tolerated. Results will be updated during the congress Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Roche
Incidence, characteristics, and associations of oxaliplatin-induced peripheral neuropathy in colorectal cancer patients: Results of a prospective, multicenter, international study.
Authors: Andreas Argyriou, Paola Alberti, Chiara Briani, Roser Velasco, Jordi Bruna, Marta Campagnolo, Marina Elena Cazzaniga, Francesca Bergamo, Diego Luigi Cortinovis, Cristina Santos, Konstantinos Papadimitriou, Guido Cavaletti, Haralabos Kalofonos
Journal: Journal of Clinical Oncology (2012)

9090 Background: We sought to trace the incidence and severity of oxaliplatin-induced peripheral neuropathy (OXLIPN) and to determine its clinical pattern. Among other associations, we also specifically aimed at testing whether the degree of acute neuropathy is clinically related to the development and severity of chronic OXLIPN. Methods: 170 patients (mean age 64y), scheduled to be treated with either FOLFOX or XELOX for metastatic colorectal cancer were studied. Patients were prospectively monitored at baseline and followed-up during chemotherapy in four European sites. The motor/neurosensory NCI-CTCv3 criteria and the clinical version of the Total Neuropathy Score were applied to clinically grade the severity of OXLIPN. Nerve conduction studies were also longitudinally performed. Results: Evidence of acute OXLIPN was disclosed in 146/170 patients (85.9%). The vast majority of patients manifested cold-induced perioral (95.2%) or pharyngolaryngeal dysesthesias (91.8%). Other uncommon symptoms, such as jaw spasm were also present. Severe acute OXLIPN, requiring prolongation of OXL infusion from 2 to 4-6 hours was evident in 32/146 patients (21.9%). Overall, 123/170 patients (72.4%) experienced chronic OXLIPN. Severities were grade I: 39 (22.9%); grade II: 52 (30.6%); grade III: 33 patients (19.4%). Worst severities were related to cumulative oxaliplatin dose (r:0.269;p&lt;0.001). Follow-up assessments revealed significant decrease in all sensory action potentials examined. The severity of the acute OXLIPN was significantly correlated with both the development (r:0.450;p&lt;0.001) and degree of the chronic form (r:0.703;p&lt;0.001). Conclusions: Most patients treated with oxaliplatin-based chemotherapy would manifest OXLIPN, mainly of moderate degree. The severity of the acute syndrome appears to clinically correlate with the degree of the chronic form of OXLIPN. Our data suggest that acute phenomena, related to axonal hyperexcitability, could contribute to the development of peripheral neuropathy; thus it could be advisable to test agents against acute OXLIPN in order to verify their effects on the chronic form.
Prognostic impact of primary surgical outcome on survival after recurrence in patients with advanced ovarian cancer: Analysis of prospective randomized phase III trials.
Authors: S. Mahner, A. Reuss, E. Pujade-Lauraine, P. Harter, I. Ray-Coquard, J. Pfisterer, A. Du Bois
Journal: Journal of Clinical Oncology (2010)

5100 Background: The prognostic role of complete debulking is well established at initial diagnosis of advanced ovarian cancer. Whether the result of primary surgery also has an impact on the clinical outcome after recurrence is not clear. Methods: Individual patient data meta-analysis of three prospective randomized AGO-OVAR/GINECO trials (AGO OVAR 3, 5 and 7) conducted between 1995 and 2002 to investigate platinum-taxane based chemotherapy regimens in advanced ovarian cancer. Results: A total of 3126 patients were analyzed. Approximately one third each had complete resection (microscopic residuals), small residual tumor (1-10 mm), or gross residual disease (> 10 mm) after primary surgery. There was no significant effect of the surgical outcome on further course of disease in patients developing progression within 12 months after primary therapy. However, patients experiencing recurrence later than 12 months after primary therapy showed a significantly different progression- free survival (PFS) and overall survival (OS) depending on initial surgical outcome. Median PFS after progression in the subgroups with microscopic residuals, 1-10 mm, or > 10 mm was 14.3, 12.6, and 12.0 months (logrank p = 0.0265) and the corresponding median OS was 28.1, 22.7, and 20.2 months, respectively (logrank p = 0.0079). This difference remained significant after adjustment for time-to-recurrence as continuous variable to rule out the effect of different time intervals before relapse (Cox model). Conclusions: Our analysis represents the first study investigating the relevance of primary surgical outcome for survival after recurrence in ovarian cancer. Complete surgical debulking significantly improves prognosis in advanced ovarian cancer not only at primary diagnosis but also after disease recurrence. No significant financial relationships to disclose.
Comparison of Therapeutic Effect of Total Laryngectomy Vs Larynx-Preservation Approach for T4A Larynx Cancer: a Multicenter Retrospective Study
Authors: Y.S. Choi, S. Park, E. Song, S. Cho, M. Park, K.U. Park, K.H. Lee, H.J. Yun
Journal: Annals of Oncology (2014)
Treatment of hind limb ischemia using angiogenic peptide nanofibers
Authors: Vivek A. Kumar, Qi Liu, Navindee C. Wickremasinghe, Siyu Shi, Toya T. Cornwright, Yuxiao Deng, Alon Azares, Amanda N. Moore, Amanda M. Acevedo-Jake, Noel R. Agudo, Su Pan, Darren G. Woodside, Peter Vanderslice, James T. Willerson, Richard A. Dixon, Jeffrey D. Hartgerink
Journal: Biomaterials (2016)
Careful prescribing is beneficial
Authors: P. Shvartzman
Journal: BMJ (1994)

The annual incidence of sore throat in general practice has been estimated at 100 per 1000 people per year.1 Some doctors prescribe antibiotics for every patient presenting with a sore throat. Others use clinical scoring systems to establish the probability of group A s haemolytic streptococcal infection. They use the score result together with a knowledge of the prevalence of streptococci in the community to derive a treatment strategy.2 Thus the management of sore throat, although essentially simple, illustrates Osler's dictum that medicine is a science of uncertainty and an art of probability.3

Bacteria can be isolated from 40-50% of patients with sore throat who present to general practitioners, although up to 30% of those with positive cultures may be carriers.4 Group A s haemolytic streptococci are the most common bacterial pathogens, with Corynebacterium diphtheriae, and group C and group G streptococci much rarer. An increasing number of cases may be due to synergistic infection with Staphylococcus aureus, Moraxella catarrhalis, Haemophilus influenzae, or anaerobic organisms. Recently, evidence has emerged that some cases of non-streptococcal pharyngitis may be associated with mycoplasma and chlamydial infections.4

A large study of patients with acute tonsillitis in 17 European countries found that 90% were treated with antibiotics.5 Since up to half of patients with sore throats have positive bacterial cultures, it is natural to consider such treatment for every patient. This policy is supported by a recent analysis of strategies for dealing with sore throat in which the likelihood of rheumatic fever after untreated streptococcal infection was assumed to be 37.5 times …
Case 45-1991
Authors: Richard C. Cabot, Robert E. Scully, Eugene J. Mark, William F. McNeely, Betty U. McNeely, R.F. Polisson, A.E. Rosenberg
Journal: New England Journal of Medicine (1991)

Presentation of CaseAn 84-year-old man was admitted to the hospital because of a mass in the left leg.The patient was in stable health until three years earlier, when he became aware of a mass in the left popliteal space. A physician aspirated the mass 21/2 years before admission and made a diagnosis of a cyst, but the mass later increased in size. Several months thereafter the mass was again aspirated and was called a "cyst" but continued to enlarge during the next six months. Seven months before entry the patient consulted an orthopedic surgeon, who advised that no . . .
HER2-negative metastatic breast cancer patients receiving first-line docetaxel: Survival data and prognostic factors
Authors: M. Deblock, B. Esterni, C. Tarpin, E. Charaffe-Jauffret, J. M. Extra, P. Viens, A. Goncalves
Journal: Journal of Clinical Oncology (2007)

1105 Background: Modern management of metastatic breast cancer (MBC) patients (pts) is currently based on molecular stratification according to HER2 status and first-line taxanes. We sought to examine outcome data and prognostic factors in a prospectively characterized cohort of HER2 negative MBC pts receiving first-line docetaxel in a routine setting. Methods: Medical records from 162 HER2-, MBC pts treated at the Institut Paoli-Calmettes with first-line docetaxel-based regimen between 1997 and 2005 were reviewed. These patients had been treated with docetaxel single-agent or in combination according to standard institutional protocols. Univariate and multivariate analysis according Cox regression model were employed to identify prognostic factors for progression-free survival (PFS) and overall survival (OS). Results: Pt characteristics were the following: median age (ys), 51 (24 -75); Histological type (ductal/lobular/other, %) 81/15/4; Grade (1/2/3, %); Hormonal Receptivity (HR) (yes/no, %) 83/17; Adjuvant chemotherapy (CT) (yes/no; %) 66/34; Disease-free interval (DFI) (&lt;24 months/&gt;24 months, %) 47/53; visceral disease (yes/no, %) 46/54; number of metastatic sites (&lt;3/&gt;3,%) 78/22; liver metastasis (yes/no, %) 31/67; bone metastasis (yes/no, %) 65/35. After a median follow-up of 33 months, median PFS and OS were 11.7 months (95%CI , 9.7 -14.8) and 35 months (95%CI, 28.1–52.1), respectively. By univariate analysis, HR- (p=7.9 e-06), visceral disease (p=0.015), shorter DFI (p=0.027) and previous adjuvant CT (p=0.0038) were negatively associated with PFS, while HR- (p=6.3e-07), visceral disease (p=0.0094) and shorter DFI (p=0.01) were also negatively associated to OS. 14. These parameters retained independent prognostic significance by multivariate analysis, the strongest being HR-(p=2.4e-5) for OS. HR- pts had a PFS of 6.87 months [95%CI, 4.27 - 11.0] Vs 14 months [95%CI, 11.84 - 18.5] in HR+ pts (log-rank test p= 3.16e-06). 2-year OS were 38% [95%CI, 21.9–65] and 76%[95%CI, 68.7–84.4] (p = 6.52e-08) in HR- and HR+ pts, respectively. Conclusions: In the taxane era, median OS of HER2- MBC pts is nearly 3 yrs. Triple negative pts (HER2-, HR-) are a very poor-risk group requiring innovative therapeutic strategies. No significant financial relationships to disclose.
Genetic testing in pulmonary hypertension: how should our clinical practice reflect recent advances?
Authors: Mark Toshner
Journal: European Respiratory Journal (2016)

In this issue of the European Respiratory Journal , Girerd et al. [1] summarise their experience to date with genetic testing for reported mutations in cohorts of patients with familial pulmonary arterial hypertension (PAH), idiopathic PAH, pulmonary veno-occlusive disease (PVOD) and pulmonary capillary haemangiomatosis (PCH). This collective work from the French Referral Centre of Pulmonary Hypertension represents a current state of the art in a fast moving and complex area from a group with considerable experience. In the last decade, we have moved from a simple and unequivocal association of one gene; heterozygous germline mutations in the bone morphogenetic protein receptor type 2 (BMPR2) [2, 3], to multiple hits in the BMPR2 signalling pathway [4–8], to additional genes in non-canonical BMP pathways of uncertain clinical significance or definitively agreed frequencies [9–11]. How to test, what to test and how to counsel is already a potential minefield. It is only likely to become more complicated in the immediate future given the technological advances and rapidly decreasing costs involved in large-scale genetic studies. So for now, we have a well-delineated step-wise model set out, in which patients are first tested for BMPR2 and, if negative, a sub-selected population proceeded to activin receptor-like kinase (ALK)1 and endoglin testing. EIF2AK4 (eukaryotic translation initiation factor 2 alpha kinase 4) was only screened in patients suspected of having PVOD/PCH. This is not dissimilar to the recent change to guidelines where it is now recommend that genetic testing should be offered in PVOD/PCH, familial and sporadic PAH, but largely leave the specifics of this to local guidelines and regulations. If BMPR2 testing is negative, it is suggested that endoglin/ALK1 should be considered for patients aged under 40 years or with a history (or family history) of hereditary haemorrhagic telangiectasia (HHT) [12]. In a French cohort, those with a familial history were also tested for SMAD9, KCNK3 and CAV-1of PAH if negative for BMPR2/ALK1/endoglin. The largest genetic screen to date shows that some pulmonary hypertension patients should be offered genetic testing <http://ow.ly/WE1vG>
Cytoskeleton Alterations in Cells of Rat Hepatomas Induced by 4-Dimethylaminoazobenzene&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: Normand Brière
Journal: JNCI Journal of the National Cancer Institute (1972)

Preneoplastic foci and hepatomas were induced in livers of rate given a low profein diet containing the azo dye 4-dimethylamino-azobenzene. Cytoplasmic RNA in these cell populations stained intensely with toluidine blue, and this phenomenon was used to identify them. The staining technique [tannic acid-phosphomolybdic acid-amido black (TPA)] that permits observation with the light microscope of cell web, terminal bars, and desmosomes was used to determine whether the hyperbasophilic cells were characterized by any modifications in cell web elements and other TPA-positive components. In normal hepatocytes and those surrounding the hyperbasophilic areas, the cell web was complete, extending all around the cells, and desmosomes were always present near the bile canaliculi. But, in preneoplastic and tumor cells, cytoskeleton and desmosomes were much reduced, absent, or too scanty to be observed. Moreover, cyfoplasmic background (probably proteins) in surrounding tissue stained intensely with TPA, whereas hyperbasophilic cells were negative or weakly positive. RNA extraction by ribonuclease did not alter significantly protein stainabilify, a suggestion that those proteins were not masked by RNA responsible for hyperbasophilia, but present in small concentrations or absent from cancer cells. The results indicate that important alterations in TPA-positive materials, especially cytoskeleton and cellular attachment sites, are associated with the phenomenon of hyperbasophilia and the neoplastic transformation.
Uptake of Fibrinogen and Fibrinolytic Enzymes by Neoplastic Tissue&lt;xref ref-type="fn" rid="FN1"&gt;2&lt;/xref&gt;&lt;xref ref-type="fn" rid="FN2"&gt;3&lt;/xref&gt;
Authors: N. Back, R. R. Shields, G. DeWitt, R. H. Branshaw, C. M. Ambrus
Journal: JNCI Journal of the National Cancer Institute (1966)

With the aid of radioisotopic and indirect immunofluorescence techniques, human fibrinogen and urokinase-activated human plasmin were found to localize in transplanted Murphy-Sturm lymphosarcoma of rats. The maximal uptake of both fibrinogen and plasmin appeared to occur 6 to 12 hours after intravenous administration. The degree of plasmin uptake appeared to correlate well with fibrinogen (or fibrin) concentration in the tumor, as revealed by paired-labeling (I131-I125) experiments. The possible pathophysiologic role of fibrin and plasmin in tumors is discussed.
Oncogenicity of Murine Mammary Tumor Virus Produced in Tissue Culture: Brief Communication2
Authors: Larry O. Arthur, Donald L. Fine, Peter Bentvelzen
Journal: JNCI Journal of the National Cancer Institute (1978)

Murine mammary tumor virus (MuMTV), produced from a glucocorticoid-stimulated C3H mouse mammary adenocarcinoma cell line, was free of murine leukemia virus and oncogenic for weanling BALB/c mice. Adenocarcinomas were induced by MuMTV as early as 136 days post inoculation and with as low as 5 X 10(3) virus particles/mouse. Tumor incidence did not correlate directly with virus dose; rather, it was low at higher MuMTV concentrations (1.2 X 10(8) particles/mouse), reached and optimum at 1.3 X 10(5) particles/mouse, and decreased with virus dilution.