tbuckley/cabot-search huggingface dataset:
Selective Deficiency of Hepatic Triglyceride Lipase in Uremic Patients
Authors: Rubino Mordasini, Felix Frey, Walter Flury, Gerald Klose, Heiner Greten
Journal: New England Journal of Medicine (1977)

To investigate the pathogenesis of hypertriglyceridemia in patients with renal disease we measured plasma lipoprotein composition as well as hepatic triglyceride lipase and lipoprotein lipase in post-heparin plasma. Three groups with renal disease were studied: conservatively treated chronic uremia; patients undergoing maintenance hemodialysis; and renal-allograft recipients. A selective decrease of hepatic triglyceride lipase with normal lipoprotein lipase was found in conservatively treated uremia and in patients undergoing hemodialysis. Elevated levels of very-low-density lipoproteins and increased triglycerides in low-density lipoproteins occurred in these patients. In contrast, hepatic triglyceride lipase and lipoprotein lipase were both normal in patients after renal transplantation who had Type II hyperlipoproteinemia as a common lipoprotein pattern with increased low-density-lipoprotein cholesterol and decreased high-density-lipoprotein cholesterol concentrations. The accumulation of a triglyceride-rich low-density lipoprotein in the majority of patients with renal disease may be the consequence of low hepatic triglyceride lipase.
Safety and efficacy of AMG 655 plus modified FOLFOX6 (mFOLFOX6) and bevacizumab (B) for the first-line treatment of patients (pts) with metastatic colorectal cancer (mCRC)
Authors: L. Saltz, J. Infante, L. Schwartzberg, J. Stephenson, C. Rocha-Lima, F. Galimi, K. Dillingham, M. Hsu, J. Wiezorek, C. Fuchs
Journal: Journal of Clinical Oncology (2009)

4079 Background: AMG 655 is an investigational fully human monoclonal antibody (IgG1) agonist of human death receptor 5 (DR5). AMG 655 activates caspases and induces apoptosis in sensitive tumor cells. The primary objective of this phase 1b study was to determine the maximum tolerated dose (up to a target dose of 10 mg/kg IV every 2 weeks) of AMG 655 that can be safely administered in combination with mFOLFOX6-B to mCRC pts. Methods: Eligible pts were ≥ 18 years old with previously untreated mCRC, ECOG PS of 0 or 1, and adequate hematologic, hepatic, and renal function. Pts were enrolled into sequential cohorts of 3- or 10-mg/kg AMG 655 + mFOLFOX6-B administered on day 1 of each 14-day cycle. Study endpoints included incidence of dose-limiting toxicities (DLT), adverse events (AE), pharmacokinetic (PK) parameters of AMG 655, and objective response rate (by modified RECIST). Results: As of 09/08, 12 pts (6 per cohort) were enrolled and received ≥ 1 cycle of treatment; 8 were female. Median (range) age was 54 (37–75), median (range) time on AMG 655 treatment was 6.9 (1.6 to 11.4+) months; 8 pts continue on study treatment. There were no DLTs in the first 28 days of treatment. Eight pts had grade 3–4 AE; the most common were diarrhea, febrile neutropenia, peripheral neuropathy, neutropenia, DVT, and pulmonary embolism (2 pts each). Post baseline laboratory parameters grade ≥ 3: no ALT and AST; 1 grade 3 bilirubin (due to disease progression), and 3 grade 3 lipase (asymptomatic). No anti-AMG 655 antibodies were detected. AMG 655 PK values (C max , C min ) were similar to those observed with single-agent AMG 655 (LoRusso JCO 2007; 25: abstract 3534). AMG 655 did not appear to affect PK of oxaliplatin or bevacizumab. Best overall tumor response: 5 partial responses (2 unconfirmed, both underwent resection); 6 stable disease; 1 pt had non-measurable disease at baseline. Time to disease progression (3 patients): 8, 42, and 44 weeks. Conclusions: The addition of AMG 655 does not appear to substantially alter the safety profile of mFOLFOX6-B. The randomized phase 2 part of the trial (mFOLFOX6-B ± AMG 655) is in progress. [Table: see text]
Adductor-Canal Thrombosis
Authors: George R. Dunlop, Rodriguez Santos
Journal: New England Journal of Medicine (1957)

THE routine use of arteriography in the study of arterial insufficiency of the lower extremities has made a most significant contribution to the management of this problem. Today, we are in a position to state the exact level and extent of the obstruction, the degree of associated sclerosis, the quality of the "run-off" distal to the obstruction, the adequacy of the collateral circulation and which of the many surgical procedures available is best suited for the individual case.Lumbar sympathectomy has proved to be of value over the years in patients with a vasospastic component. The effect on claudication has . . .
Cisplatin chemotherapy in the treatment of BRCA1-positive metastatic breast cancer (MBC)
Authors: T. Byrski, M. Foszczynska-Kloda, T. Huzarski, R. Dent, J. Gronwald, C. Cybulski, T. Debniak, B. Gorski, J. Lubinski, S. Narod
Journal: Journal of Clinical Oncology (2009)

1099 Background: Preclinical data suggest that women with BRCA1 related breast cancers may be particularly sensitive to chemotherapeutic agents that cause DNA damage such as cisplatin chemotherapy. This study was conducted to assess the efficacy and safety of cisplatin chemotherapy in patients with BRCA1 positive MBC. Methods: This was a multicenter, open label, single arm study of cisplatin 75 mg/m 2 given intravenously every three weeks until disease progression or toxicity. The primary objective was to assess antitumour activity of cisplatin, as measured by clinical benefit response (CR, PR, or SD ≥ 6 months). Eligible patients had locally recurrent or MBC, had 0–2 prior chemotherapy regimens in the metastatic setting, and had received prior therapy with an anthracycline. Patients were restaged every eight weeks. The study protocol was approved by the institutional review boards of participating institutions. Results: A total of 15 patients were enrolled. Mean age was 48.1 years (range: 32 to 70). ECOG performance status scores were 0 (6 pts), 1 (5 pts), 2 (4 pts). All patients had a confirmed BRCA1 mutation (7 with C61G mutation, 7 with 5382 insC, 1 with 4153delA). Five patients (33%) were ER or PR + and none were HER-2+. Prior history of MBC chemotherapy included 1 regimen (4 pts) and 2 regimens (7 pts). Seven (46%) and 4 (26%) patients had complete and partial responses by Response Evaluation Criteria in Solid Tumors (RECIST) criteria, for an overall response rate of 72%. Median duration of response has not yet been reached. In general, cisplatin was well tolerated. Neutropenia was the commonest toxicity with 33% grade 2 (6,7% and 0%, grades 3 and 4 neutropenia). No patients developed febrile neutropenia. Conclusions: Significant activity and favorable toxicity profile provides a basis for considering cisplatin for further evaluation in phase III trials for women with BRCA1 positive MBC. No significant financial relationships to disclose.
Tumor Necrosis Factor and the Jarisch–Herxheimer Reaction
Authors: Bruce Beutler, Robert S. Munford
Journal: New England Journal of Medicine (1996)

In certain infectious diseases, the first dose of an effective antimicrobial drug can trigger an inflammatory host response. Within an hour or two after receiving the drug, the patient abruptly experiences chills, followed by fever and sweating and worsening of preexisting symptoms and lesions. Hyperventilation and tachycardia are accompanied by hypertension, and then by a drop in blood pressure due to vasodilation and declining peripheral resistance. Usually, the reaction resolves over a period of 6 to 12 hours.The identification of this distressing and sometimes fatal phenomenon is usually credited to Jarisch and Herxheimer, each of whom described components of . . .
A Follow-up Study of Vascular Disease in Growth-Hormone-Deficient Dwarfs with Diabetes
Authors: Thomas J. Merimee
Journal: New England Journal of Medicine (1978)

Thirty - one growth - hormone - deficient dwarfs were re-examined after a period of 10 to 12 years. These subjects had initially shown glucose intolerance, insulinopenia and hyperlipidemia comparable to those of diabetic patients matched for age and sex, but vascular complications were not present in dwarfs. After 10 years glucose tolerance became progressively more abnormal in dwarfs than could be accounted for by expected deterioration with age, and hyperglycemia after mixed meals remained greater than in control subjects. Serum lipid and serum lipoprotein concentrations were abnormal in over one third of the dwarfs. Despite the metabolic similarity to the diabetic patients, clinical complications of diabetes were absent in dwarfs: retinopathy did not occur, and the prevalence of hypertension and arteriosclerosis was considerably lower in dwarfs than in the diabetic subjects in both study periods. The follow-up data support the hypothesis that growth hormone has at least a supportive role in the pathogenesis of vascular disease in the diabetic state. (N Engl J Med 298:1217–1222, 1978)
Vaginal Ring Provides Modest Protection Against HIV
Authors: M. J. Friedrich
Journal: JAMA (2016)

A vaginal ring containing the experimental antiretroviral drug dapivirine modestly reduced the risk of HIV infection among African women, according to a study by an international team of investigators (Baeten JM et al. N Engl J Med. doi:10.1056/NEJMoa1506110 [published online February 22, 2016]).
Case 35-2001
Authors: Steven K. Grinspoon, E. Tessa Hedley-White
Journal: New England Journal of Medicine (2001)

Presentation of CaseAn 81-year-old man was transferred to the hospital because of bradycardia, hypothermia, and increasing confusion.A platelet count of 85,000 per cubic millimeter had been discovered five years before admission, but no cause had been determined. The patient also had a history of coronary artery disease with a reduced ejection fraction as well as chronic obstructive pulmonary disease and chronic cough.Fourteen months before admission, the chronic cough worsened, and a thoracic radiograph revealed a mass in the left lung. A computed tomographic (CT) scan of the chest showed a pleura-based mass, 2.5 cm in diameter, in . . .
Prediction of the long-term outcomes associated with body mass index and advanced gastric cancer.
Authors: Jae Gyu Kim, Beom Jin Kim, Kyong-Choun Chi, Jung Min Park, Mi Kyoung Kim, In Kyu Hwang
Journal: Journal of Clinical Oncology (2016)

82 Background: Radical gastrectomy followed by adjuvant chemotherapy for advanced gastric cancer brings about serious nutritional impairment. Recent studies have shown an association between body mass index (BMI) and perioperative outcomes of gastric cancer. However, little is known about the association between BMI and long-term outcomes of advanced gastric cancer. Our study evaluated the clinical impact of BMI on the long-term outcomes of gastric cancer staged at II and III, treated by radical gastrectomy followed by adjuvant chemotherapy. Methods: We analysed a total of 211 cases of advanced gastric cancer stage II and III between January 2005 and December 2010 at Chung-Ang University Hospital. The patients were divided into 4 groups according to BMI; underweight, normal, overweight, and obese. In addition, they were divided into two groups (BMI-High vs BMI-Low). We assessed age, sex, tumor location, lymph node involvement, operation method, initial cancer stage, recurrence, and survival (overall survival and disease free survival) between two groups. Results: We classified them into 4 groups according to BMI; underweight, normal, overweight, and obese. There was no difference in overall survival between normal, overweight, and obese group. However, there was significant difference between underweight group and the other groups. As for disease free survival, similar findings were observed. Among 211 patients, 154 patients (72.9%) were included in BMI-L (body mass index &lt; 25), whereas 57 patients (27.1%) in BMI-H (body mass index ≥ 25). There was no difference in age, sex, tumor location, stage, lymph node involvement, operation method, recurrence, and cancer-related death between two groups. When classified into 4 groups as stage II in BMI-H, stage II in BMI-L, stage III in BMI-H, and stage III in BMI-L, overall survival showed significant difference in stage, however, no difference between BMI-H and BMI-L. Disease free survival showed no significant difference in stage and BMI, especially, no significant difference between stage II in BMI-L and stage III in BMI –H. Conclusions: Our findings suggest that preoperative BMI may predict the long term outcomes of advanced gastric cancer after radical surgery and chemotherapy.
Organ‐Mounted Electronics: An Universal and Easy‐to‐Use Model for the Pressure of Arbitrary‐Shape 3D Multifunctional Integumentary Cardiac Membranes (Adv. Healthcare Mater. 8/2016)
Authors: Yewang Su, Zhuangjian Liu, Lizhi Xu
Journal: Advanced Healthcare Materials (2016)

Recently developed concepts for 3D, organ-mounted electronics for cardiac applications require an universal and easy-to-use mechanical model to calculate the average pressure associated with operation of the device, which is crucial for evaluation of design efficacy and optimization. A simple, accurate, easy-to-use, and universal model to quantify the average pressure for arbitrarily shaped organs is proposed by Y. Su and colleagues on page 889. Cover designed by Zhenhai Li.
Reduction in Venous Thromboembolism by Agents Affecting Platelet Function
Authors: Edwin W. Salzman, William H. Harris, Roman W. DeSanctis
Journal: New England Journal of Medicine (1971)

The protection against venous thrombosis and pulmonary embolism afforded by three drugs affecting platelet function was assessed in a controlled study of 169 patients undergoing vitallium-mold arthroplasty of the hip. The prophylactic administration of dipyridamole, aspirin and dextran was compared with the effects of warfarin. Thromboembolic complications occurred in six of 43 patients who received warfarin, nine of 34 receiving dipyridamole, six of 43 receiving aspirin and six of 49 receiving dextran. These results with aspirin, dextran and warfarin, but not dipyridamole, are better than those in an untreated group previously reported (26 thromboembolic complications in 67 patients). The frequency of bleeding complications did not differ in the four groups.
Multiple-Balloon Kymographic Recording of the Comparative Action of Demerol, Morphine and Placebos on the Motility of the Upper Small Intestine in Man
Authors: William P. Chapman, Eirwyn N. Rowlands, Chester M. Jones
Journal: New England Journal of Medicine (1950)

NUMEROUS claims have been made that Demerol, in addition to its analgesic properties, has a spasmolytic or relaxing action on the motility of the intestinal tract. Eisleb and Schaumann,1 who in 1939 synthesized Demerol, and Duguid and Heathcote2 were among the first to report that this drug exerted an antispasmodic effect on smooth muscle of the intestine in animals. In 1942 Batterman,3 using the balloon intubation method, observed an antispasmodic action of the drug on the gastrointestinal tract in man. In a later publication he claimed that with 50 to 100 mg. of Demerol administered intramuscularly an antispasmodic action was . . .
Familial Occurrence of Inflammatory Bowel Disease
Authors: Marianne Orholm, Pia Munkholm, Ebbe Langholz, Ole Haagen Nielsen, Thorkild I.A. Sørensen, Vibeke Binder
Journal: New England Journal of Medicine (1991)

We assessed the familial occurrence of inflammatory bowel disease in Copenhagen County, where there has been a long-term interest in the epidemiology of such disorders. In 1987 we interviewed 662 patients in whom inflammatory bowel disease had been diagnosed before 1979, asking whether their first- and second-degree relatives had this disorder. Ninety-six percent of the patients (504 with ulcerative colitis and 133 with Crohn's disease) provided adequate information.As compared with the general population, the first-degree relatives of the 637 patients with ulcerative colitis or Crohn's disease had a 10-fold increase in the risk of having the same disease as the patients, after standardization for age and sex. The risk of having the other of the two diseases was also increased, but less so, and the increase in the risk of having Crohn's disease was not significant in the relatives of patients with ulcerative colitis. The risk of ulcerative colitis in first-degree relatives of patients with ulcerative colitis appeared to be virtually independent of the generation to which the first-degree relative belonged and of the sex of the patient and the relative. The risk of ulcerative colitis in first-degree relatives tended to be higher if the disease had been diagnosed in the patient before the age of 50, but the risk seemed to be independent of the current age of the relatives. The prevalence of the same disease as that of the patient (either ulcerative colitis or Crohn's disease) among second-degree relatives was increased; the prevalence of the other disease was not increased.The 10-fold increase in the familial risk of ulcerative colitis and Crohn's disease strongly suggests that these disorders have a genetic cause.
Elevated factor VIII activity is common in patients with newly diagnosed high-grade gliomas
Authors: M. B. Streiff, S. A. Grossman, X. Ye, T. S. Kickler, G. J. Lesser, T. T. Batchelor, J. T. Jani, S. Desideri
Journal: Journal of Clinical Oncology (2008)

2035 Background: Patients with malignant gliomas are at high risk for venous thromboembolism (VTE). The reason for this association is unclear. We sought to identify clinical and laboratory risk factors for VTE in adult patients with high-grade gliomas. Methods: The NABTT CNS Consortium prospectively enrolled patients with newly-diagnosed grade 3 or 4 malignant glioma prior to antineoplastic therapy. Patients with a previous history of VTE, antineoplastic therapy or on chronic anticoagulation were excluded. At enrollment, we collected demographic and clinical information (age, gender, ethnicity, tumor histopathology and grade, KPS, ABO blood group) and blood samples for measurement of factor VIII activity, fibrinogen, quantitative D dimer, thrombin generation and C reactive protein using standard laboratory assays. Results: 65 patients (47% male) with a median age 57 years (range 29–85) were enrolled between 6/05 and 12/07. Sixty-five percent had glioblastoma and the remainder had other high grade gliomas. Median Karnofsky performance status at enrollment was 90. The distribution of ABO blood group in patients was: Blood group O (53%), A (26%), B (14%), and AB (7%) similar to the distribution in US general population: Blood group O (45%), A (40%), B (11%), AB (4%). The mean factor VIII activity in patients and 40 normal controls was 164±13% and 79±24%. The mean fibrinogen in patients and normal controls was 366±33 mg/dL and 287±86 mg/dL while the mean D dimer level in patients and normal controls was 1.8±0.3 mg/L and 1.4±0.5 mg/L, respectively. Conclusions: Elevated factor VIII activity is an established risk factor for initial and recurrent VTE. Our results suggest that elevated factor VIII activity independent of ABO blood group status contributes to the increased risk of VTE associated with high-grade gliomas. Future reports will include measurements of thrombin generation and C reactive protein and a correlation of these results with symptomatic episodes of VTE in this prospective study of more than 100 patients that is nearing its accrual goal. No significant financial relationships to disclose.
Chromosome Studies in Leukemia
Authors: Leonard E. Reisman, Muneo Mitani, Wolf W. Zuelzer
Journal: New England Journal of Medicine (1964)

THE idea that a malignant process might be related to a breakdown of mitotic control, leading to aberrant chromosomal constitution of neoplastic cells, was suggested by Boveri1 in his classic studies on sea-urchin eggs in 1914. The accumulation of cytogenetic data needed to test this concept had to await the development of modern cytogenetic methods in the second half of the century. Leukemia is especially suitable for chromosome analysis because, unlike solid neoplasms, which require prolonged culturing under conditions conducive to in vitro alterations of karyotypes, the affected system consists of free cells that can be readily studied by direct . . .
Good standard of care is associated with good leadership, finds regulator
Authors: Gareth Iacobucci
Journal: BMJ (2015)

The Care Quality Commission has praised the standard of care being delivered by most health and social care services in England but has pledged to remain focused on tackling a “significant variation in quality” across all the sectors it regulates.

In its annual state of care report,1 the first to be published since it introduced a tougher inspection regime and a ratings system for acute, primary, and adult social care services in England, the health and care regulator rated most services as “good” and some “outstanding,” indicating that most people are receiving safe and effective care.

But although it acknowledged the “increasingly challenging circumstances” in which healthcare providers were operating, the CQC said that it remained concerned about variations in quality, particularly …
P122 Combination therapy with inhaled salmeterol plus fluticasone propionate is more effective than salmeterol alone in reducing the risk of clinically important deterioration in COPD: A post-hoc analysis of the TORCH trial: Abstract P122 Table 1
Authors: I Naya, L Tombs, P Jones
Journal: Thorax (2015)

<h3>Background</h3> Most COPD patients will deteriorate over time, so a key aim of COPD management is to minimise this risk. We developed a composite endpoint of three aspects of worsening: COPD exacerbations, clinically important deteriorations (CID) in lung function and health status. This method was applied in a <i>post hoc</i> analysis of TORCH, a 3-year, double-blind, placebo-controlled trial in moderate/severe COPD that compared salmeterol 50 mcg/fluticasone proprionate 500 mcg combination (SFC) with placebo (PBO), salmeterol 50 mcg (SAL) alone and fluticasone 500 mcg alone. In this analysis, SFC was compared with SAL to test whether the addition of inhaled corticosteroids (ICS) reduced the risk of a CID beyond their known effect on exacerbations. <h3>Method</h3> The overall analysis was performed in 6112 patients, 3054 treated with SFC and SAL. A CID was defined as a decrease ≥100 mL in post-bronchodilator FEV<sub>1</sub>, an increase (worsening) in St George’s Respiratory Questionnaire (SGRQ) total score of ≥4 units, or an on-treatment moderate/severe exacerbation. The time to the first deterioration of each component and the composite endpoint was analysed using a Cox’s proportional hazards model with covariates of: treatment, smoking status and geographical region; baseline values for FEV<sub>1 and </sub>SGRQ score were included for those individual component endpoints. The analysis was performed on the intention-to-treat (ITT) population and in patient categorised into GOLD grades I/II and III/IV. <h3>Results</h3> A similar percentage of patients in both treatment groups eventually experienced ≥1 category of deterioration during the 3-year trial. The Hazard Ratios (HR) show that compared to SAL, SFC significantly reduced the time to first worsening of FEV<sub>1</sub> and SGRQ (Table 1). The benefit of SFC over SAL was seen with the composite endpoint in the ITT population and both GOLD subgroups. <h3>Conclusion</h3> This <i>post hoc</i> analysis showed that, although most patients eventually experienced one of the three measures of deterioration, SFC significantly reduced the risk of a first composite CID compared to SAL. This added benefit of ICS was equally present in patients with mild/moderate or severe/very severe COPD.