tbuckley/cabot-search huggingface dataset:
Use of Surgery Among Elderly Patients With Stage IV Colorectal Cancer
Authors: Larissa K.F. Temple, Lillian Hsieh, W. Douglas Wong, Leonard Saltz, Deborah Schrag
Journal: Journal of Clinical Oncology (2004)

The role of surgery to remove the primary tumor among patients with stage IV colorectal cancer (CRC) is controversial. The purpose of this study was to evaluate surgical practice patterns for patients > or = 65 years of age with stage IV CRC in a US population-based cohort.We used the Surveillance, Epidemiology, and End Results-Medicare-linked database to evaluate the patterns of cancer treatment for 9,011 Medicare beneficiaries presenting with stage IV CRC from 1991 to 1999. Patients were categorized according to whether they had primary-cancer-directed surgery (CDS) or no CDS within 4 months of diagnosis. The use of other treatment modalities, including metastasectomy, chemotherapy, and radiation, was evaluated in relationship to whether patients belonged to the CDS or no CDS group.Seventy-two percent (6,469 of 9,011) of patients received CDS, and their 30-day postoperative mortality was 10%. Patients with left-sided or rectal lesions, patients older than age 75 years, blacks, and those of lower socioeconomic status were less likely to undergo CDS; but even among those older than age 75, the CDS rate was 69% (3,378 of 4,909). In contrast, chemotherapy use was less common (47% for patients who had CDS and 31% for those who did not). Metastasectomy was rare; only 3.9% of patients underwent these operations at any point from diagnosis to death.Palliative resection of the primary tumor is often performed for elderly US patients with stage IV colorectal cancer. This practice pattern merits re-evaluation, given the improvement in the efficacy of systemic chemotherapy.
Adjuvant therapy for intracoronary stents. Investigations in atherosclerotic swine.
Authors: G P Rodgers, S T Minor, K Robinson, D Cromeens, S C Woolbert, L C Stephens, J R Guyton, K Wright, G S Roubin, A E Raizner
Journal: Circulation (1990)

Early thrombosis has complicated human stent implantation in several trials. To determine the best anticoagulation/antiplatelet therapy to maintain stent patency after percutaneous transluminal coronary angioplasty, we implanted the flexible balloon-expandable coil stent into the left anterior descending coronary artery of 28 atherosclerotic 8-month-old Hanford miniature swine. Animals were randomly assigned to one of three treatment groups: group A, aspirin (1 mg/kg/day) and dipyridamole (1 mg/kg three times a day); group B, aspirin and dipyridamole (same doses) plus Coumadin (dose required to prolong prothrombin time 1.3-1.5-fold that of normal); and group C, control. Adjuvant therapy was begun 3 days before stenting. Two pigs (one from group A and one from group B) died during implantation, both without thrombosis. Twenty-six animals survived until follow-up angiography and sacrifice at 1 month. No occlusive thrombosis of the stent occurred in survivors. Reduction of the stent lumen diameter was observed in every case at follow-up. Percent lumen reduction was 19% in group A, 26% in group B, and 24% in group C. Marked smooth muscle cell hyperplasia was seen by light and transmission electron microscopy at stent struts. Scanning electron microscopy of the luminal surface showed a variable morphology consisting of normal endothelium, adherent leukocytes, stellate periluminal cells, and occasional fibrin strands and red blood cells. Luminal narrowing was not affected by anticoagulation therapy, antiplatelet drugs, cholesterol level, or stent sizing. We conclude that occlusive thrombosis does not complicate stent implantation in this model but that substantial luminal narrowing due in part to smooth muscle hyperplasia does occur. The significance of luminal narrowing at the stent site requires further study.
Upregulation of hepatic angiotensin-converting enzyme 2 (ACE2) and angiotensin-(1–7) levels in experimental biliary fibrosis
Authors: Chandana B. Herath, Fiona J. Warner, John S. Lubel, Rachael G. Dean, Zhiyuan Jia, Rebecca A. Lew, A. Ian Smith, Louise M. Burrell, Peter W. Angus
Journal: Journal of Hepatology (2007)

Angiotensin-converting enzyme 2 (ACE2), its product, angiotensin-(1-7) and its receptor, Mas, may moderate the adverse effects of angiotensin II in liver disease. We examined the expression of these novel components of the renin angiotensin system (RAS) and the production and vasoactive effects of angiotensin-(1-7) in the bile duct ligated (BDL) rat.BDL or sham-operated rats were sacrificed at 1, 2, 3 and 4 weeks. Tissue and blood were collected for gene expression, enzyme activity and peptide measurements. In situ perfused livers were used to assess angiotensin peptide production and their effects on portal resistance.Hepatic ACE2 gene and activity (P<0.0005), plasma angiotensin-(1-7) (P<0.0005) and Mas receptor expression (P<0.01) were increased following BDL compared to shams. Perfusion experiments confirmed that BDL livers produced increased angiotensin-(1-7) (P<0.05) from angiotensin II and this was augmented (P<0.01) by ACE inhibition. Whilst angiotensin II increased vasoconstriction in cirrhotic livers, angiotensin-(1-7) had no effect on portal resistance.RAS activation in chronic liver injury is associated with upregulation of ACE2, Mas and hepatic conversion of angiotensin II to angiotensin-(1-7) leading to increased circulating angiotensin-(1-7). These results support the presence of an ACE2-angiotensin-(1-7)-Mas axis in liver injury which may counteract the effects of angiotensin II.
Loss of the proapoptotic protein, Bim, breaks B cell anergy
Authors: Paula M. Oliver, Tibor Vass, John Kappler, Philippa Marrack
Journal: The Journal of Experimental Medicine (2006)

Although B cells that respond with high avidity to self-antigen are eliminated early in their development, many autoreactive B cells escape elimination and are tolerized later in their lives via anergy. Anergic B cells are unresponsive to antigen and die prematurely. It has been suggested that the proapoptotic protein, Bim, controls the fate of anergic B cells. To test this idea, mice lacking Bim were crossed with mice that express soluble hen egg lysozyme and whose B cells bear receptors specific for the protein. In Bim+/+ mice these B cells are anergic and die rapidly. If the mice lack Bim, however, the B cells live longer, are more mature, respond to antigen, and secrete anti–hen egg lysozyme antibodies. This break of tolerance is not due to expression of endogenous B cell receptors, nor is it dependent on T cells. Rather, it appears to be due to a reduced requirement for the cytokine BAFF. Normal B cells require BAFF both for differentiation and survival. Bim−/− B cells, on the other hand, require BAFF only for differentiation. Therefore, autoreactive B cells are allowed to survive if they lack Bim and thus accumulate sufficient signals from differentiating factors to drive their maturation and production of autoantibodies.
Morbidity and mortality of car occupants: comparative survey over 24 months.
Authors: M S Christian
Journal: BMJ (1984)

The severity of injuries sustained by 2577 car occupants in road traffic accidents in the catchment area of one district accident service during February 1982 to January 1984 inclusive was assessed using the injury severity score system. In the first 12 months the mean injury severity score for front seat occupants injured in a road traffic accident was 4.94 and in the second 12 month period, after the implementation of the seat belt law, the mean injury severity score of all injured front seat occupants was 2.80. These figures indicated a reduction in injury severity of front seat occupants of 53.4% on the previous 12 month figures. The severity of injury sustained by unbelted front seat occupants and back seat passengers showed no significant change over the two years. The number of front seat occupants killed or sustaining serious injuries (injury severity score greater than 12) showed a reduction of 54% in the 12 months beginning February 1983. Front seat occupants requiring admission for injuries sustained showed a decline of 42% in the 12 months after the introduction of the seat belt law, and deaths among front seat occupants fell by 27% compared with the previous 12 months. After the implementation of seat belt legislation those front seat occupants killed or sustaining serious injuries included a significantly higher proportion of victims who were not wearing their seat belts or showed positive evidence of alcohol intake at the time of the accident. This series suggests that the incidence of serious injury or deaths among front seat occupants of cars has decreased substantially since the seat belt law became effective on 31 January 1983.
Two-protein signature of novel serological markers apolipoprotein-A2 and serum amyloid alpha predicts prognosis in patients with metastatic renal cell cancer and improves the currently used prognostic survival models
Authors: J S Vermaat, I van der Tweel, N Mehra, S Sleijfer, J B Haanen, J M Roodhart, J Y Engwegen, C M Korse, M H Langenberg, W Kruit, G Groenewegen, R H Giles, J H Schellens, J H Beijnen, E E Voest
Journal: Annals of Oncology (2009)
Jury is still out on National Blood Service
Authors: P J Bowell
Journal: BMJ (1996)

EDITOR,—E Angela E Robinson criticises Ann Oakley's editorial about blood donation for being based on a catalogue of false premises.1 2 The rosy picture of the English blood transfusion service that Robinson paints, however, does not match my experience. Staff morale, an indicator of the wellbeing of any organisation, is at an all time low as the proposals to rationalise the service are forced through. The departure of so many skilled and experienced staff is also …
Pharmacometabonomic Profiling as a Predictor of Toxicity in Patients with Inoperable Colorectal Cancer Treated with Capecitabine
Authors: Alexandra Backshall, Rohini Sharma, Stephen J. Clarke, Hector C. Keun
Journal: Clinical Cancer Research (2011)

Endogenous metabolic profiles have been shown to predict the fate and toxicity of drugs such as acetaminophen in healthy individuals. However, the clinical utility of metabonomics in oncology remains to be defined. We aimed to evaluate the effect of pretreatment serum metabolic profiles generated by (1)H NMR spectroscopy on toxicity in patients with inoperable colorectal cancer receiving single agent capecitabine.Serum was collected from 54 patients with a diagnosis of locally advanced or metastatic colorectal cancer prior to treatment with single agent capecitabine. (1)H NMR spectroscopy was used to generate metabolic profile data for each patient. Toxicities were graded according to National Cancer Institute Common Toxicity Criteria version 2.0.Higher levels of low-density lipoprotein-derived lipids, including polyunsaturated fatty acids and choline phospholipids predicted for higher grade toxicity over the treatment period. Statistical analyses revealed a "pharmacometabonomic" lipid profile that correlated with severity of toxicity.This study suggests that metabolic profiles can delineate subpopulations susceptible to adverse events and have a potential role in the assessment of treatment viability for cancer patients prior to commencing chemotherapy.
Regulating Viral Myocarditis: Allografted Regulatory T Cells Decrease Immune Infiltration and Viral Load
Authors: David J. Marchant, Bruce M. McManus
Journal: Circulation (2010)

4][5][6] Many other viruses have since been shown to cause myocarditis and its long-term sequelae, arrhythmias, dilated cardiomyopathy, and heart failure.By example, adenovirus, herpesviruses, and influenza can cause myocarditis in humans and models of heart failure.Because immune cell infiltration is an easily seen feature of myocarditis, it is perhaps not surprising that the inflammatory response would be posited as a major cause of tissue injury during viral myocarditis.However, the virus itself has lytic and destructive potential, and a range of data indicate both viral and immune contributions to cardiomyocyte and interstitial damage during myocarditis.The question is often posed: Is damage primarily virus-mediated or more so the product of an overzealous immune response and autoimmunity?Perhaps the greatest error in the discussion has been approaching these 2 facets of the disease process in a mutually exclusive manner.Shi et al 7 now show in this issue of Circulation that virus replication and the immune response are exquisitely intertwined in myocarditis pathogenesis.
Individuals with inherited chromosomally integrated human herpes virus 6 (ciHHV-6) have functionally active HHV-6 specific T-cell immunity
Authors: V. Strenger, S. Kayser, K.-E. Witte, D. Lassner, W. Schwinger, G. Jahn, C. Urban, T. Feuchtinger
Journal: Clinical Microbiology and Infection (2015)
Angiotensin II–Nitric Oxide Interaction on Sympathetic Outflow in Conscious Rabbits
Authors: Jun-Li Liu, Hiroshi Murakami, Irving H. Zucker
Journal: Circulation Research (1998)

Abstract —Increasing evidence suggests that endogenous NO inhibits sympathetic outflow in anesthetized animals. However, in a recent study from this laboratory, we were unable to find any evidence of increased renal sympathetic nerve activity (RSNA) in response to blockade of NO synthesis in conscious rabbits. Because angiotensin II (Ang II) increases sympathetic outflow, one factor for this discrepancy may be the difference in the resting level of Ang II, which may be lower in well-trained conscious animals. In the present study, the effects of blockade of NO synthesis with N ω -nitro- l -arginine methyl ester (L-NAME, 30 mg/kg IV) on resting RSNA with and without a background intravenous infusion of Ang II (10 ng · kg −1 · min −1 ) was investigated in conscious rabbits. Intravenous administration of L-NAME (30 mg/kg) caused an increase in mean arterial blood pressure (MAP, from 80.4±2.9 to 92.8±2.5; P =.0001) and a decrease in RSNA (from 100±0% to 53.4±8.6%, P =.0016). When the elevated blood pressure was returned to control by infusion of hydralazine (0.01 to 0.06 mg · kg −1 · min −1 ), RSNA returned to the level before L-NAME administration. During a sustained infusion of Ang II (10 ng · kg −1 · min −1 ), L-NAME increased MAP from 89.2±2.9 to 109.0±4.3 mm Hg ( P =.0101) and decreased RSNA from 100.0±0% to 53.7±7.5% ( P =.0013). Under this circumstance, however, when the MAP was returned to the level that existed before the administration of L-NAME, RSNA increased significantly above the level that existed before the administration of L-NAME (164.5±17.7% versus 100±0%, P =.0151). The enhancement of the sympathetic response by Ang II was completely blocked by the AT 1 receptor antagonist, losartan. In contrast, during a background infusion of phenylephrine, which increased MAP to the same level as produced by Ang II, L-NAME had no effect on RSNA when MAP was returned to the control level. N ω -Nitro- d -arginine methyl ester had no effect on MAP and RSNA. Intravenous infusion of Ang II alone for 75 minutes had no effect on RSNA when MAP was returned to control levels. These data suggest that an elevated level of Ang II is critical for the inhibitory effect of NO on sympathetic outflow in conscious rabbits and imply that these two substances have a major impact on the regulation of sympathetic outflow.
Treatment of Refractory Pityriasis Rubra Pilaris With Novel Phosphodiesterase 4 (PDE4) Inhibitor Apremilast
Authors: Ifat Zerin Krase, Kevin Cavanaugh, Clara Curiel-Lewandrowski
Journal: JAMA Dermatology (2015)

Discussion | Acrodermatitis continua of Hallopeau, also known as acrodermatitis perstans and dermatitis repens, is a rare inflammatory pustular dermatosis of the distal fingers and toes.It is considered a variant of pustular psoriasis or, less commonly, its own pustular psoriasis-like independent entity. 1 Precise pathophysiology and incidence are unknown.Case literature suggests predominance in women, but the disease affects both sexes and, rarely, children. 2 Acrodermatitis continua of Hallopeau initially presents as erythema overlying the distal digits that evolves into pustules. 2The nail bed is often involved, with paronychial and subungual involvement and atrophic skin changes. 3ost patients experience a chronic, relapsing course involving the proximal digit as the condition worsens. 4Acrodermatitis continua of Hallopeau has been reported to both evolve into and stem from generalized plaque or pustular psoriasis. 3The present patient was noted to have plaque psoriasis lesions nearly 1 year after the onset of her disease.Psoriatic arthritis is a rare complication, 3 but distal phalanx osteolysis is an important comorbidity. 1he differential diagnosis includes infectious paronychia of viral, fungal, or bacterial etiology, infected contact dermatitis, and dyshidrotic eczema. 4Gram stain, potassium hydroxide mount, culture, and microscopy may be useful in diagnosis.Histopathologically, ACH is characterized by neutrophil-rich spongiform pustules within the epidermis, dermal edema, and lymphohistiocytosis. 4 As in pustular psoriasis, biopsy from the nail bed often reveals acanthosis and spongiform pustules. 3reatment with topical corticosteroids, tacrolimus, fluorouracil, calcipotriol, methotrexate, acitretin, cyclosporine, and phototherapy have produced inconsistent responses.Successful treatment with tumor necrosis factor inhibitors and the IL-1 inhibitor anakinra 5 have been reported.However, these agents are not always efficacious and may even have the potential to incite pustular psoriasis. 6 Two cases of ACH treated with concomitant ustekinumab and acitretin have been reported, one successfully, 1 the other unsuccessfully. 5The present case is the first to our knowledge to be successfully treated with ustekinumab as monotherapy.Given that the literature supports ustekinumab as monotherapy and concomitant therapy for pustular psoriasis, ustekinumab was a reasonable choice for our patient and succeeded when other agents had failed.
ADAMTS13 and von Willebrand Factor in Thrombotic Thrombocytopenic Purpura
Authors: X. Long Zheng
Journal: Annual Review of Medicine (2015)

Pathogenesis of thrombotic thrombocytopenic purpura (TTP) was a mystery for over half a century until the discovery of ADAMTS13. ADAMTS13 is primarily synthesized in the liver, and its main function is to cleave von Willebrand factor (VWF) anchored on the endothelial surface, in circulation, and at the sites of vascular injury. Deficiency of plasma ADAMTS13 activity (&lt;10%) resulting from mutations of the ADAMTS13 gene or autoantibodies against ADAMTS13 causes hereditary or acquired (idiopathic) TTP. ADAMTS13 activity is usually normal or modestly reduced (&gt;20%) in other forms of thrombotic microangiopathy secondary to hematopoietic progenitor cell transplantation, infection, and disseminated malignancy or in hemolytic uremic syndrome. Plasma infusion or exchange remains the initial treatment of choice to date, but novel therapeutics such as recombinant ADAMTS13 and gene therapy are under development. Moreover, ADAMTS13 deficiency has been shown to be a risk factor for the development of myocardial infarction, stroke, cerebral malaria, and preeclampsia.
Apolipoprotein E phenotypes in patients with gout: relation with hypertriglyceridaemia.
Authors: Y Moriwaki, T Yamamoto, S Takahashi, Z Tsutsumi, K Higashino
Journal: Annals of the Rheumatic Diseases (1995)

OBJECTIVE--To elucidate the relationship, if any, between lipid abnormalities and apolipoprotein E (apo E) polymorphism, by investigating apo E phenotype and allele frequency. METHODS--Fasting blood samples were taken for determination of apo E phenotype and serum lipids in 221 male patients with gout and 141 control male subjects. Apo E phenotype was determined by one dimensional flat gel isoelectric focusing. RESULTS--Frequencies of apo E phenotypes in gout were apo E3/3 67.9%, E4/3 18.1%, E4/4 2.3%, E4/2 1.8%, E3/2 9.5%, and E2/2 0.5%; those in control male subjects were 74.5%, 15.6%, 0%, 1.4%, 7.1%, and 1.4%, respectively. Frequencies of the e2, e3, and e4 alleles in gout were 0.061, 0.817 and 0.122, compared with the corresponding control frequencies of 0.057, 0.858 and 0.085. These differences in apo E phenotype and allele frequencies between gout and control subjects were not significant. The frequency of apo e4 allele in hyperlipidaemic gout subjects was significantly greater than that in normolipidaemic gout subjects; in contrast, its frequency was not different between hyperlipidaemic and normolipidaemic control subjects. Serum triglyceride, total cholesterol, apo B and E concentrations were significantly greater in gouty patients with the apo E4/3 phenotype than in those with gout having the apo E3/3 phenotype. CONCLUSIONS--These data suggest that gout subjects with hyperlipidaemia (hypertriglyceridaemia, hypercholesterolaemia or both) possess the apo e4 allele with higher frequency than those with normolipidaemia. They also suggest that apo e4 may induce some susceptibility to the development of hyperlipidaemia in gout in addition to that induced by obesity or excessive alcohol consumption, and may contribute to the high prevalence of atherosclerotic diseases in gout patients.
Prognosis After Ipsilateral Breast Tumor Recurrence and Locoregional Recurrences in Patients Treated by Breast-Conserving Therapy in Five National Surgical Adjuvant Breast and Bowel Project Protocols of Node-Negative Breast Cancer
Authors: Stewart J. Anderson, Irene Wapnir, James J. Dignam, Bernard Fisher, Eleftherios P. Mamounas, Jong-Hyeon Jeong, Charles E. Geyer, D. Lawrence Wickerham, Joseph P. Costantino, Norman Wolmark
Journal: Journal of Clinical Oncology (2009)

Purpose Locoregional failure (LRF) after breast-conserving therapy (BCT) is associated with increased risk of distant disease and death. The magnitude of this risk has not been adequately characterized in patients with lymph node-negative disease. Patients and Methods Our study population included 3,799 women randomly assigned to five National Surgical Adjuvant Breast and Bowel Project protocols of node-negative disease (ie, B-13, B-14, B-19, B-20, and B-23) who underwent lumpectomy and whole breast irradiation with or without adjuvant systemic therapy. Cumulative incidences of ipsilateral breast tumor recurrence (IBTR) and other locoregional recurrence (oLRR) were calculated, along with distant-disease–free interval (DDFI) and overall survival (OS) after these events. Cox models were employed to model mortality by using clinical and pathologic factors jointly with these events. Results Four hundred nineteen patients (11.0%) experienced LRF: 342 (9.0%) experienced IBTR, and 77 (2.0%) experienced oLRR. The 12-year cumulative incidences of IBTR and oLRR in patients treated with adjuvant systemic therapy were 6.6% and 1.8%, respectively. Overall, 37.1% of IBTRs and 72.7% of oLRRs occurred within 5 years of diagnosis. Older age, black race, higher body mass index (BMI), larger tumors, and occurrence of IBTR or oLRR were significantly associated with increased mortality. The 5-year OS after IBTR and oLRR were 76.6% and 34.9%, respectively. Adjusted hazard ratios for mortality associated with IBTR and oLRR were significantly higher in estrogen receptor (ER)–negative patients than in ER-positive patients (P = .002 and P &lt; .0001, respectively). Patients with early LRF had worse OS and DDFI than those with later-occurring LRF. Conclusion Although LRF is uncommon in patients with node-negative breast cancer who are treated with lumpectomy, radiation, and adjuvant systemic therapy, those who do develop LRF have substantially worse OS and DDFI.