tbuckley/cabot-search huggingface dataset:
Case 11-1986
Authors: Richard C. Cabot, Robert E. Scully, Eugene J. Mark, Betty U. McNeely, Edward C. Tarlov, Edward P. Richardson
Journal: New England Journal of Medicine (1986)

Presentation of CaseA 34-year-old woman was admitted to the hospital because of episodic right facial numbness.She was well until one year earlier, when she experienced the first of three episodes of numbness that affected the right upper and lower teeth, the buccal mucosa, and the lower portion of the face and subsided in less than one minute without residual symptoms. Three weeks before admission a fourth bout of facial numbness developed, lasted about five minutes, and was associated with numbness and stiffness of the right hand, a heavy feeling in the tongue, and dysarthria. She came to this . . .
Enzyme replacement with PEGylated cystathionine β-synthase ameliorates homocystinuria in murine model
Authors: Erez M. Bublil, Tomas Majtan, Insun Park, Richard S. Carrillo, Helena Hůlková, Jakub Krijt, Viktor Kožich, Jan P. Kraus
Journal: Journal of Clinical Investigation (2016)

Homocystinuria, which typically results from cystathionine β-synthase (CBS) deficiency, is the most common defect of sulfur amino acid metabolism. CBS condenses homocysteine and serine to cystathionine that is then converted to cysteine. Individuals with homocystinuria have markedly elevated plasma levels of homocysteine and methionine and reduced concentrations of cystathionine and cysteine. Clinical disease manifestations include thromboembolism and neuropsychiatric, ocular, and skeletal complications. Here, we have shown that administration of PEGylated CBS into the circulation of homocystinuria model mice alters the extra- and intracellular equilibrium of sulfur amino acids, resulting in a decrease of approximately 75% in plasma total homocysteine (tHcy) and normalization of cysteine concentrations. Moreover, the decrease in homocysteine and the normalization of cysteine in PEGylated CBS-treated model mice were accompanied by improvement of histopathological liver symptoms and increased survival. Together, these data suggest that CBS enzyme replacement therapy (ERT) is a promising approach for the treatment of homocystinuria and that ERT for metabolic diseases may not necessitate introduction of the deficient enzyme into its natural intracellular compartment.
<i>Clostridium difficile</i> Infection
Authors: Ciarán P. Kelly, J. Thomas LaMont
Journal: Annual Review of Medicine (1998)

Clostridium difficile infection is associated with broad-spectrum antibiotic therapy and is the most common cause of infectious diarrhea in hospital patients. Pathogenic strains of C. difficile produce two protein exotoxins, toxin A and toxin B, which cause colonic mucosal injury and inflammation. Infection may be asymptomatic, cause mild diarrhea, or result in severe pseudomembranous colitis. Diagnosis depends on the demonstration of C. difficile toxins in the stool. The first step in management is to discontinue the antibiotic that caused diarrhea. If diarrhea and colitis are severe or persistent, oral metronidazole is the treatment of choice. Oral vancomycin is also effective, but it is more expensive than metronidazole and its widespread use may encourage the proliferation of vancomycin-resistant nosocomial bacteria. Diarrhea and colitis usually improve within three days after a patient starts taking metronidazole or vancomycin, but 20% suffer a relapse of diarrhea when these agents are discontinued.
Efficacy and safety of radiotherapy (RT) plus temozolomide (TMZ) in elderly patients (EP) with glioblastoma (GBM).
Authors: Giuseppe Lombardi, Luisa Bellu, Franco Berti, Patrizia Farina, Sara Galuppo, Fable Zustovich, Alessandro Della Puppa, Carla Carollo, Roberta Bertorelle, Domenico D'Avella, Vittorina Zagonel
Journal: Journal of Clinical Oncology (2013)

2043 Background: the optimal management of EP with GBM remains controversial. The role of RT with TMZ for EP is unclear, and EP are often treated with RT alone, TMZ alone or palliative approaches. We describe our experience of combining RT with concurrent TMZ for treatment of EP with GBM Methods: medical records of patients ≥65 years old with newly GBM, histologically confirmed at Veneto Institute of Oncology – Padua, and treated with RT plus TMZ, were reviewed. Concomitant TMZ was 75mg/m2/die. The adjuvant treatment consisted of TMZ 150-200mg/m2/die for six cycles. Median progression-free survival(PFS) and overall survival(OS) were estimated with Kaplan-Meier method. Toxicity was scored according to CTCAE 4.0 Results: we analyzed 60 patients(PTS), 34 males and 26 females; the average age was 70 (range 65-82); ECOG PS was 0-1 in 35 PTS and 2 in 25 PTS; complete surgery was performed in 35 PTS, partial surgery in 25 PTS. 40 and 20 PTS received RT within 6 or more weeks (range 7-9) from surgery. MGMT and IDH1 were analyzed in 43 PTS: MGMT methylated in 20 PTS (46%), all PTS had wild-type IDH1. 34 PTS were treated with RT 40Gy in 15 fractions, 26 PTS with RT 60Gy in 30 fractions with no significant difference in ECOG PS, MGMT and type of surgery between the two subgroups. For all PTS, PFS and OS were 9.5 and 12.7 ms, respectively. OS was 13.7 and 12.4 ms (p=0.9) in PTS receiving RT within 6 or more weeks from surgery, respectively. 13% of PTS showed grade 3-4 haematological toxicity, 12% grade 3-4 asthenia, 3% nausea/vomiting. MGMT methylated and complete surgery was associated with a longer survival. PFS was 9 vs 10 months (p=0.4) and OS was 11.7 vs 13.7 ms (p=0.1), for PTS treated with 40Gy and 60Gy, respectively. Regarding toxicity: grade 3-4 haematological toxicity was 9% vs 23%, severe asthenia was 9% vs 15%, nausea/vomiting was 3% vs 4% of PTS receiving RT 40Gy and 60Gy, respectively. Conclusions: RT plus TMZ is effective and safe in EP with GBM and good ECOG PS. PFS and OS was not statistically different between PTS receiving RT 40Gy or 60Gy, although we showed a trend for longer OS with RT 60Gy; in contrast, severe toxicity was higher in PTS with RT 60Gy. OS was similar between PTS receiving RT within 6 or more weeks (7-9ws) from surgery.
Abstract 1637: Radiation Dose Measurements on Subjects Undergoing Combined CT Perfusion and CT Angiography Imaging with a Prototype 256-row MDCT Scanner
Authors: Richard George, Joao Lima, Mahadevappa Mahesh
Journal: Circulation (2007)

Introduction: The purpose of this study was to directly measure the radiation dose on subjects undergoing combined CT Perfusion (CTP) and CT Angiography (CTA) imaging on a 256-row MDCT scanner. Methods: Fifteen patients underwent combined CTP and CTA imaging on a prototype 256 row MDCT scanner (Toshiba, Nasu, Japan). The prototype 256-row MDCT scanner consists of 256 rows of 0.5 mm size detectors with the capability to scan 12.8 cm length in the axial plane per CT gantry rotation in 0.5 secs. The protocol included a scout scan and test bolus scan followed by adenosine stress CTP (120 kVp, 200 mA, gantry rotation speed of 0.5 secs for 3 rotations, 128x1.0 mm) and rest CTA (120 kVp, 350 mA, gantry rotation speed of 0.5 secs for 3 rotations, 256x0.5 mm) in an axial scan mode. Direct dose measurements were performed using a custom vest worn by the patient fitted with 15–25 thermoluminiscent dosimeters (TLDs) (Landauer, IL) placed in AP and lateral locations. An anthropomorphic phantom was also scanned with the same protocol with TLDs positioned on the surface and inside the phantom at various organ locations. Effective doses were estimated based on the maximum surface dose according to previously validated methodology. Results: The effective dose from TLD measurements ranged from 22 to 32 mSv for the entire protocol. This is based on direct dose measured on subjects and not based on dose derived from phantom measurements as done routinely. Conclusions: The doses reported in this study are comparable to similarly measured doses from 64-slice MDCT coronary angiography alone. This prototype scanner uses 3 gantry rotations and a 1.5 second exposure time in it current configuration. Since, 256-row MDCT can cover the entire heart in a single rotation, it eliminates the need for tissue overlap from low pitch values. Efforts are currently underway to develop a prospective ECG-gated protocol that can limit radiation exposure to a single rotation for both stress and rest CTA scans. With a single rotation, the effective dose can be reduced to nearly one-third of the dose measured with this prototype, or approximately 7–11 mSv for a combined CTP and CTA imaging.
Phase I study of GS-5745 alone and in combination with chemotherapy in patients with advanced solid tumors.
Authors: Johanna C. Bendell, Alexander Starodub, Manish A. Shah, Sunil Sharma, Zev A. Wainberg, Dung Luong Thai
Journal: Journal of Clinical Oncology (2015)

4030 Background: GS-5745 is a monoclonal antibody that inhibits matrix metalloproteinase 9 (MMP9), an extracellular enzyme involved in matrix remodeling, tumor growth, and metastasis. Inhibiting MMP9 is expected to block paracrine signaling and metastasis and to alter the immune environment within the tumor. Methods: The safety, pharmacokinetics (PK), and efficacy of GS-5745 alone and in combination with chemotherapy are being evaluated in a phase I dose escalation and expansion study in patients (pts) with advanced solid tumors. Dose escalation occurred at doses up to 1800 mg of GS-5745 IV every 2 weeks followed by a dose expansion at 800 mg IV every 2 weeks in pts with pancreatic adenocarcinoma combined with gemcitabine/nab-paclitaxel and pts with esophagogastric adenocarcinoma combined with mFOLFOX6. All pts continued until disease progression or unacceptable toxicity. Results: As of January 13, 2015, 88 pts were treated. Treatment-emergent AEs (TEAEs) in > 30% of pts included nausea (38%), dyspnea (31%), and fatigue (31%). No DLTs were observed after monotherapy treatment. Non-linear PK, suggestive of target-mediated disposition, was observed with a mean half-life of ~8 days at doses of 600 and 1800 mg. When combined with chemotherapy, the most common TEAEs were diarrhea (59%), fatigue (47%), and nausea (38%). There were no observed responses in the monotherapy escalation phase. In the expansion phase, objective response rates in pts with measurable target lesions were 64% (7/11 esophagogastric) and 41% (7/17 pancreatic) based on investigator evaluation. Two complete responses in the esophagogastric cohort were noted by central radiology review. Conclusions: Preliminary safety data demonstrate a manageable safety profile for GS-5745 alone and in combination with chemotherapy. The study has been expanded to enroll additional subjects with pancreatic and esophagogastric cancer to identify potential pharmacodynamic and predictive biomarkers of response.
Abstract 322: A Crucial Role of Rho/Rho-kinase Pathway in Constriction and Closure of Human and Rabbit Ductus Arteriosus: Redox Activation Mediates Calcium Sensitization
Authors: Hidemi Kajimoto, Kyoko Hashimoto, Sandra Bonnet, Alois Haromy, Rohit Moudgil, Ivan Rebeyka, Stephen L Archer
Journal: Circulation (2006)
PTH-093 One year mortality outcomes of patients with liver cirrhosis admitted to a teaching hospital intensive care unit: Abstract PTH-093 Table 1
Authors: D Tai, H Lewis, Y Derwa, A Lillis, T Reynolds, K Maitland, D Hall, W Alazawi, GR Foster, JS Hadley
Journal: Gut (2015)

<h3>Introduction</h3> Cirrhotic patients admitted to the intensive care unit (ICU) are reported to have poor outcomes with published one year mortality rates of up to 81%.<sup>1</sup>ICU mortality in cirrhotic patients has improved over recent years, but there is no recent data on one year outcomes. The aim of this study was to examine one year mortality, assess organ and liver scoring systems predictive value for one year mortality and to compare outcomes in patients with alcohol and non-alcohol related cirrhosis admitted to the ICU of a non-transplant tertiary Hepatology centre. <h3>Method</h3> This was a retrospective analysis of prospectively collected data on outcomes of consecutively admitted patients with liver cirrhosis to the Royal London Hospital, from Intensive Care National Audit and Research Centre records. <h3>Results</h3> Between 01/01/2006 and 31/12/2013, 253 cirrhotic patients were admitted to ICU. The most common reasons for admission were sepsis (33%), GI bleed (24%) and hepatic encephalopathy (11%). Aetiologies of cirrhosis included alcohol (68%), viral hepatitis (17%) and NASH (4%). There were significant differences in median age (53 vs 57), ethnicity (White/Black/Asian – 87/5/8% vs 56/13/31%) and admissions for sepsis (38% vs 21%) between those with alcohol and non-alcohol related aetiologies. One year, hospital and ICU mortality were 66%, 57% and 39% overall, 66%, 58% and 40% in alcohol, and 66%, 54% and 38% in non-alcohol aetiologies of cirrhosis respectively (p=ns.). 1 year mortality in patients requiring 1, 2, 3 and 4 organ support was 49%, 68%, 95% and 88%. Patients requiring renal replacement therapy (RRT) had more organs failing (3 vs 1 p &lt; 0.0001) and a higher MELD score (19 vs 15 p &lt; 0.005) compared to those not requiring RRT. ICU, hospital and one-year mortality was 70%, 86% and 89% in this group. The SAPS II score was a better predictor of one-year mortality than other organ failure scores. <h3>Conclusion</h3> One-year mortality in our series compares favourably with the 81% previously reported in a UK transplant centre,<sup>1</sup>and most patients who survive hospital admission will survive to one year. Patients with alcohol and non-alcohol aetiologies of cirrhosis have similar outcomes. The requirement for RRT bestows a poor prognosis. Organ failure scores, particularly the SAPS II, are better at predicting one year mortality than the MELD score, but their discriminatory power was relatively poor. <h3>Disclosure of interest</h3> None Declared. <h3>Reference</h3> Mackle IJ <i>et al</i>. One year outcome of intensive care patients with decompensated alcoholic liver disease. Critical Care 2006;97:49–8
Abstract 1915: ApoE derived lipopeptide containing Gadolinium mixed Micelles for Macrophage Imaging in ApoE ko Mice
Authors: Esad Vucic, Karen C Briley-Saboe, Eik Leupold, Juan Gilberto Aguinaldo, Vardan Amirbekian, Edward A Fisher, Margitta Dathe, Zahi A Fayad
Journal: Circulation (2007)
Authors’ reply to Braillon and Bewley
Authors: Simone N Vigod, Claire A Wilson, Louise M Howard
Journal: BMJ (2016)

Firstly, we agree with Braillon and Bewley that more is needed to support education in this area at the point of care,1 2 and our teams have been working on developing an online patient decision aid that aims to help women make decisions about drugs during pregnancy in collaboration with their providers.3 This tool is currently being evaluated, and one main advantage is that its electronic nature will enable timely updating when new evidence emerges and broad access. Because of the rapidly changing literature, with the harms and benefits of antidepressant use in pregnancy being inconsistently reported, we would also argue that printed …
Adefovir Dipivoxil for the Treatment of Hepatitis B e Antigen–Positive Chronic Hepatitis B
Authors: Patrick Marcellin, Ting-Tsung Chang, Seng Gee Lim, Myron J. Tong, William Sievert, Mitchell L. Shiffman, Lennox Jeffers, Zachary Goodman, Michael S. Wulfsohn, Shelly Xiong, John Fry, Carol L. Brosgart
Journal: New England Journal of Medicine (2003)

In preclinical and phase 2 studies, adefovir dipivoxil demonstrated potent activity against hepatitis B virus (HBV), including lamivudine-resistant strains.We randomly assigned 515 patients with chronic hepatitis B who were positive for hepatitis B e antigen (HBeAg) to receive 10 mg of adefovir dipivoxil (172 patients), 30 mg of adefovir dipivoxil (173), or placebo (170) daily for 48 weeks. The primary end point was histologic improvement in the 10-mg group as compared with the placebo group.After 48 weeks of treatment, significantly more patients who received 10 mg or 30 mg of adefovir dipivoxil per day than who received placebo had histologic improvement (53 percent [P<0.001], 59 percent [P<0.001], and 25 percent, respectively), a reduction in serum HBV DNA levels (by a median of 3.52 [P<0.001], 4.76 [P<0.001], and 0.55 log copies per milliliter, respectively), undetectable levels (fewer than 400 copies per milliliter) of serum HBV DNA (21 percent [P<0.001], 39 percent [P<0.001], and 0 percent, respectively), normalization of alanine aminotransferase levels (48 percent [P<0.001], 55 percent [P<0.001], and 16 percent, respectively), and HBeAg seroconversion (12 percent [P=0.049], 14 percent [P=0.01], and 6 percent, respectively). No adefovir-associated resistance mutations were identified in the HBV DNA polymerase gene. The safety profile of the 10-mg dose of adefovir dipivoxil was similar to that of placebo; however, there was a higher frequency of adverse events and renal laboratory abnormalities in the group given 30 mg of adefovir dipivoxil per day.In patients with HBeAg-positive chronic hepatitis B, 48 weeks of 10 mg or 30 mg of adefovir dipivoxil per day resulted in histologic liver improvement, reduced serum HBV DNA and alanine aminotransferase levels, and increased the rates of HBeAg seroconversion. The 10-mg dose has a favorable risk-benefit profile for long-term treatment. No adefovir-associated resistance mutations were identified in the HBV DNA polymerase gene.
Oral Contraceptives and the Risk of Myocardial Infarction
Authors: Bea C. Tanis, Maurice A.A.J. van den Bosch, Jeanet M. Kemmeren, Volkert Manger Cats, Frans M. Helmerhorst, Ale Algra, Yolanda van der Graaf, Frits R. Rosendaal
Journal: New England Journal of Medicine (2001)

An association between the use of oral contraceptives and the risk of myocardial infarction has been found in some, but not all, studies. We investigated this association, according to the type of progestagen included in third-generation (i.e., desogestrel or gestodene) and second-generation (i.e., levonorgestrel) oral contraceptives, the dose of estrogen, and the presence or absence of prothrombotic mutations.
Abortion incidence between 1990 and 2014: global, regional, and subregional levels and trends
Authors: Gilda Sedgh, Jonathan Bearak, Susheela Singh, Akinrinola Bankole, Anna Popinchalk, Bela Ganatra, Clémentine Rossier, Caitlin Gerdts, Özge Tunçalp, Brooke Ronald Johnson, Heidi Bart Johnston, Leontine Alkema
Journal: The Lancet (2016)
Anatomic location does not impact survival in soft tissue sarcoma of the extremity
Authors: C. K. Chang, I. A. Jacobs, G. I. Salti
Journal: Journal of Clinical Oncology (2004)

9056 Background: Various prognostic factors are known to influence outcome of soft tissue sarcomas. Although anatomic location of extremity sarcoma as a prognostic factor is debatable, several studies suggest lower extremity sarcoma have a worse outcome than upper extremity sarcoma. The aims of the current study were to evaluate overall survival (OS) and disease-free survival (DFS) of soft tissue sarcomas located in the extremity, and test the prognostic value of a series of clinicopathological parameters. Methods: A Retrospective review was undertaken to identify patients with sarcoma located in the extremities. All patients received their primary surgical treatment in our department between January 1991 and December 2001. Univariate and multivariate analyses of potential predictive factors were evaluated with the log-rank test and Cox regression. Results: Of the 134 patients identified, 99 patients had lower extremity sarcoma and 35 patients had upper extremity sarcoma. No differences in size, stage or adjuvant therapy were identified between upper and lower extremity sarcomas (p=.11, p=.22 and p=.24, respectively). Mean age was 50 years. Median follow-up was 27 months (range 1–116 months). By univariate analysis, stage, size, and adjuvant therapy of the primary tumor were associated with a decreased in both OS (p<.05) and DFS (p<.05). Age 50 years or greater influenced OS (p<.001) but not DFS (p=.21). Histology of the primary tumor did not effect OS (p=.21) but tended to effect DFS (p<.001). Anatomic location and gender did not significantly influence OS or DFS. By multivariate Cox regression, only adjuvant therapy effected DFS (p=.002). Age, gender, histology, size, stage, and adjuvant therapy did not significantly influence DFS. Overall-survival was influenced by age, histology, stage, and adjuvant therapy. Anatomic location did not have an effect on OS (p=.17) or DFS (p=.99). Conclusion: Location of the primary site of extremity sarcoma does not influence overall survival and disease-free survival. Patients with upper extremity sarcoma do not have a worse outcome than patients with lower extremity sarcoma. No significant financial relationships to disclose.
Case 16-1970
Authors: Richard C. Cabot, Benjamin Castleman, Betty U. McNeely, John M. Craig, Benjamin Castleman
Journal: New England Journal of Medicine (1970)

PRESENTATION OF CASEA forty-one-year-old woman was admitted to the hospital because of a mass in the vulva.For the past year she had had a malodorous, yellow vaginal discharge and vulvar pruritus. During the eight months before entry there had been episodes of intermenstrual spotting. The menstrual periods were normal in frequency, amount and duration. She was referred to this hospital because of a vulvar mass found at another hospital four months previously.Fifteen years before admission a diagnosis of mild diabetes insipidus was made, and she was treated with vasopressin for several years. She continued to experience urinary . . .
The prostaglandin transporter (PGT) as a potential mediator of ovulation
Authors: Gil M. Yerushalmi, Svetlana Markman, Yuval Yung, Ettie Maman, Sarit Aviel-Ronen, Raoul Orvieto, Eli Y. Adashi, Ariel Hourvitz
Journal: Science Translational Medicine (2016)

The prostaglandin transporter is a mediator of ovulation, and inhibiting it blocks ovulation in mice.
Political interference derails Punjab Medical Council’s investigation into “ghost faculty”
Authors: Priyanka Pulla
Journal: BMJ (2016)

An investigation into allegations that around 400 doctors are falsely claiming to be employees of medical colleges has been derailed by a Punjabi state minister, the president of the Punjab Medical Council has alleged.

Gurinder Singh Grewal, the council president, has accused Anil Joshi, Punjab state minister of medical education and research, of undue interference into the investigation of so …
Role of Circulating Tumor Cells (Ctc) in Stage III Colorectal Cancer (Crc)
Authors: M. Sotelo Lezama, J. Sastre, S. Veganzones, V.La De Orden, J.M. Viéitez, V. Alonso, C. Grávalos, P. Escudero, R. Vera, E. Aranda, P. García Alfonso, J. Gallego Plazas, C. López, C. Pericay, A. Arrivi, M.P. Vicente Lazcano, P. Ballesteros, E. Elez, A. López-Ladrón, E. Díaz-Rubio
Journal: Annals of Oncology (2014)