tbuckley/cabot-search huggingface dataset:
Recombinant alfa interferon in renal cell carcinoma: a randomized trial of two routes of administration.
Authors: H B Muss, J J Costanzi, R Leavitt, R D Williams, R A Kempf, R Pollard, H Ozer, P J Zekan, S M Grunberg, M S Mitchell
Journal: Journal of Clinical Oncology (1987)

Ninety-seven patients with recurrent or metastatic renal cell carcinoma were randomized to receive recombinant interferon (IFN) alfa-2b (Intron A; Schering-Plough, Kenilworth, NJ) by either the subcutaneous (SC) or intravenous (IV) route. The SC dosage was 2 X 10(6) IU/m2 three times weekly, and the IV dose 30 X 10(6) IU/m2 for five consecutive days every 3 weeks. Dose escalation to a maximum of 10 X 10(6) IU/m2 SC and 50 X 10(6) IU/m2 IV was allowed for patients with minimal or absent toxicity. Five of 51 of the SC-treated patients (10%) and three of 46 of the IV-treated patients (7%) had a partial response (PR) or complete response (CR). Patients with prior nephrectomy, no prior treatment, and lack of bone metastases were most likely to respond, and a retrospective analysis of this subgroup revealed a 23% response rate. Achievement of response took from 3 weeks to 11 months, while response duration lasted from 3 to 31+ months. All responders had prior nephrectomy; six of eight had no prior chemotherapy or hormonal therapy; five had lung metastases, and none had bone metastases. Regardless of route, almost all patients developed a flu-like syndrome; however, grade 3 or greater toxicity was much more common for IV-treated patients. This trial demonstrates modest, but definite antitumor activity for recombinant interferon in advanced renal cell carcinoma. SC administration with lower dose and toxicity is as effective as treatment administered IV.
Effect of a Low-Fat Diet on Hormone Levels in Women With Cystic Breast Disease. I. Serum Steroids and Gonadotropins&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: D P Rose, A P Boyar, C Cohen, L E Strong
Journal: JNCI Journal of the National Cancer Institute (1987)

For examination of the effect of a low-fat diet on serum estrogen, progesterone, and gonadotropin levels, 16 patients with cystic breast disease and cyclic mastalgia were studied before dietary intervention and at 2 and 3 months thereafter. Four-day food diaries indicated that total fat intake was reduced from a prediet average of 69 g (35% of total kilocalories/day) to an average of 32 g (21% of total kilocalories) after 3 months. Highly significant reductions (P less than .001) occurred in dietary cholesterol and less changes occurred in protein and total kilocalorie consumption (P less than .05); fiber intakes were not affected. After 3 months on this low-fat diet, there were significant reductions in luteal-phase serum total estrogens (P less than .001), estrone (P less than .005), and estradiol (P less than .01); progesterone, luteinizing hormone, and follicle-stimulating hormone levels were unchanged. Two of the 16 patients were excluded from the hormone statistical analyses because the serum progesterone levels were not consistent with sampling in the luteal phase of the menstrual cycle. It is concluded that a reduction of dietary fat intake to 20% of the total kilocalories will result in significant decreases in circulating estrogens in benign breast disease patients and that this effect is achievable without increasing dietary fiber consumption. Absence of changes in serum progesterone and gonadotropins during the dietary intervention is consistent with altered enterohepatic circulation of estrogens rather than with effects on the pituitary-ovarian axis.
Baseline hemodynamic predictors of treatment response in pulmonary arterial hypertension
Authors: Christian Gerges, Mario Gerges, Yi Zhou, Lixia Zhang, Marie Lang, Irene Lang
Journal: European Respiratory Journal (2013)

PURPOSE: Pulmonary arterial hypertension (PAH) is a progressive disease characterized by an increase in pulmonary vascular resistance (PVR), by right ventricular dysfunction, and ultimately, right heart failure and death. Although PVR can be reduced by vasodilator treatment, PVR remains elevated above normal in the vast majority of patients, and prognosis remains poor. The purpose of this study was to identify baseline hemodynamic predictors of treatment response in patients with PAH.  METHODS: A retrospective data set of 3107 patients undergoing right heart catheterization was analyzed. 1094 patients were classified as post-capillary and 137 as pre-capillary PH. Of these, 23 patients had idiopathic PAH (iPAH). Hemodynamic cut-offs for the discrimination between iPAH and post-capillary PH were determined by ROC curves. A prospective data set of 541 PAH patients receiving treprostinil or placebo was utilized for the validation of hemodynamic cut-offs.  RESULTS: ROC analysis identified mPCWP of 12mmHg (area under the curve [AUC] 0.99) and diastolic pressure gradient (DPG) of 20mmHg (AUC 0.97) as the best hemodynamic values for the differentiation between iPAH and post-capillary PH. Patients with mPCWP  20mmHg or a combination of both had a significant improvement in hemodynamics under treprostinil compared to corresponding placebo groups, with a decrease in PVR of 3.1WU [1.3, 4.9], 2.9WU [1.0, 4.7] and 3.6WU [1.5, 5.8], respectively. By contrast, hemodynamics did not improve in patients with mPCWP ≥12mmHg or DPG ≤20mmHg, or both.  CONCLUSION: An mPCWP of less than 12 and a DPG of over 20mmHg identify PAH patients who are likely to have a significant benefit under vasodilator treatment.
XmAb5574: In vitro and in vivo efficacy of an Fc-engineered anti-CD19 monoclonal antibody against lymphoma and leukemia and its effect on B cells in non-human primates
Authors: E. Zhukovsky, H. Horton, C. E. Lawrence, S. Chu, E. Pong, J. Richards, M. Peipp, R. Repp, J. Desjarlais
Journal: Journal of Clinical Oncology (2008)

3078 Background: CD19 is a pan-B cell surface receptor expressed from early stages of pre-B cell development through terminal differentiation into plasma cells. It is an attractive target for cancers of lymphoid origin since it is expressed on the vast majority of Non- Hodgkin Lymphoma (NHL) and leukemia cells. The majority of NHL patients relapse after the current treatment regimen of chemotherapy combined with rituximab (CHOP-R), thus salvage regimens with non-cross resistant antibody therapies are warranted. We present the characterization of a novel humanized Fc-engineered anti-CD19 antibody (XmAb5574). Methods: We applied XmAb technology to a chimeric CD19 antibody to humanize it, increase its affinity for Fc gamma receptors, improve its effector function, and thus significantly increase its antitumor potency. This approach yielded a pre-clinical candidate (XmAb5574) that was tested in a series of in vitro cytotoxicity assays and in mouse xenograft models of NHL. We also tested the depletion of B cells in peripheral blood, lymph nodes, bone marrow and spleen of cynomolgus monkeys. Results: XmAb5574 is a novel anti-CD19 antibody that is highly cytotoxic against a panel of lymphoma and leukemia cell lines. This antibody does not appreciably internalize, and in vitro it mediates ADCC (EC50 ∼ 1 - 0.03 ng/ml) and phagocytosis (EC50 ∼ 3 - 0.1 ng/ml) superior to that of rituximab and alemtuzumab. XmAb5574-mediated ADCC is also significantly increased relative to rituximab in patient-derived ALL, CLL and MCL cells. XmAb5574 exhibits in vitro apoptotic activity that is significantly more potent than that of rituximab. Xenograft mouse models, Ramos and Raji sc and iv, show that XmAb5574 has robust protection in both protocols. Finally, we observed sustained depletion of peripheral and lymphoid B cells in cynomolgus monkeys dosed with XmAb5574. Conclusions: The main features of XmAb5574 are: i) improved in vitro cytotoxicity in tumor cells, ii) robust antitumor activity in mouse xenograft models, and iii) B cell depletion in cynomolgus monkeys. Thus XmAb5574, our anti-CD19 Fc variant antibody engineered for increased effector function, is a promising next-generation immunotherapeutic for leukemias and lymphomas. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Xencor Xencor
Performance indicators and the public reporting of healthcare-associated infection rates
Authors: H Humphreys, R Cunney
Journal: Clinical Microbiology and Infection (2008)

Surveillance of healthcare-associated infections (HCAIs) makes evident the importance of the quality of patient care, and the increasing demand for public reporting of HCAI surveillance data and related quality indicators is thus not surprising. However, there is little evidence that public reporting results in improved patient care. Debate continues about which HCAI-related indicators are the best measures of performance and thus the most appropriate for public reporting. Suitable indicators should allow improvements leading to better patient outcomes, and should be comparable among hospitals and countries. Appropriate examples include central vascular catheter infections, surgical prophylaxis and surgical site infections.
Hospital at home for patients with acute exacerbations of chronic obstructive pulmonary disease; will it be an effective home care model?
Authors: Dicle Kaymaz, Pinar Ergün, Ersin Günay, Selma Aktas, Nilgün Mendil, Saliha Battal, Ezgi Utku, Pervin Demir
Journal: European Respiratory Journal (2011)

The current acute care model for COPD is, in general, insufficient for optimal management of the disease.Coordination of services is especially important at the time of the COPD exacerbation,which is characterised by high morbidity,high healthcare utilisation and even worse fragmentation of care.Home care services can offer a great potential for this aim.Hospital-at-home (HAH) care model is feasible, safe,and efficacious for certain patients with selected acute medical illnesses who require acute hospital-level care.   Aim:  The aim of the present study was to analyze the effectiveness of HAH for patients with COPD exacerbation.   Methods:  Two hundered and six patients who were admitted to our institution via the emergency department with the diagnosis of COPD exacerbation were included to HAH. Patients were followed up during the year after HAH practise. Hospitalization rates,emergency department,out patient clinic admissions,and hospitalisation days when needed were evaluated before and after one year period of HAH.   Results:  After one year follow up period of HAH practise hospitalisation rates,emergency department and out patient clinic addmitions, length of hospital stay were decreased.Respectively 40.29% 21.18%, 54.94% and 46.35%. The decreases for all parametres were found statistical significant (p   Conclusion:  We conclude that integrated care services including home care using the HAH modalities are strongly needed to enhance both health and managerial outcomes. Clinicians should consider this form of management, especially as there is increasing pressure for inpatient beds in Turkey.
Effect of Tumor Cells on Pre-Existing Collagen and on Collagen Production by Normal Cells Grown in Diffusion Chambers
Authors: Emma Shelton
Journal: JNCI Journal of the National Cancer Institute (1964)

Experiments were designed to test the effect of tumors on collagen production and on pre-existing collagen of normal tissues. Both mouse and rat tumors and normal tissues were used. The cells of mouse lymphomas L#1 and L#2 and of a mouse tumor derived from liver, Hepatoma 129(P), were freed of “contaminating” normal stroma by rapid transplantation in diffusion chambers. The tumor cells were then recombined in diffusion chambers with normal mouse peritoneal cells and normal mouse connective tissue. Control chambers containing normal cells alone were also prepared. After 4 weeks of growth, the total collagen in the chambers was estimated by the determination of total hydroxyproline. To test the effect of tumor tissue growing outside the chamber on tissue growing within the chamber, rat connective tissue and Novikoff hepatoma were placed in diffusion chambers implanted subcutaneously in the rat. Some chambers were dipped in a slurry of the Novikoff hepatoma or the Walker carcinosarcoma 256 before subcutaneous implantation so that the chambers were quickly surrounded by the tumor mass. After 3 weeks, the chambers containing connective tissue were analyzed for hydroxyproline (as an estimate of total collagen), while those containing the Novikoff hepatoma were analyzed for deoxyribonucleic acid (as an estimate of total cell number). The results showed that the mouse tumors did not have the capacity to destroy pre-existing collagen. However, the total collagen found in the chambers was usually decreased in the presence of the tumor cells. This decrease appeared to be due to an inhibition of the proliferation of collagen-producing cells rather than to the suppression of collagen synthesis.
Clinical investigation of idiopathic pleuroparenchymal fibroelastosis cases diagnosed by radiologic findings and fibroelastosis obtained by TBLB
Authors: Ryota Sato, Shinobu Akagawa, Nobuharu Ohshima, Keita Takeda, Takahiro Ando, Kazuya Koyama, Ken-ichi Okuda, Masahiro Shimada, Masahiro Kawashima, Kimihiko Masuda, Hirotoshi Matsui, Akira Hebisawa, Ken Ohta
Journal: European Respiratory Journal (2014)

Background :Idiopathic pleuroparenchymal fibroelastosis (IPPFE) was newly included in ATS/ERS classification as a rare IIP, and fibroelastosis (FE) is one of the fundamental histological findings. Because performing VATS is often difficult, the clinical diagnosis remained unconfirmed.   Objectives :We aimed to clarify the clinical features of IPPFE cases which were diagnosed by radiologic findings and histological FE in upper lobes obtained by TBLB.   Methods :We selected cases with FE proven by TBLB in our hospital from 2003 to 2012. PPFE was diagnosed based on pleuroparenchymal thickening and volume loss of upper lobes as well as upper lobe dominant radiological abnormalities.   Results :Among 27 cases with FE detected by TBLB, clinical diagnoses suspected before TBLB were PPFE in 11 cases, pulmonary aspergillosis in 6, non-tuberculous mycobacteriosis (NTM) in 3, and others in 7. Finally, 14 cases were diagnosed as PPFE, including two cases of suspected association with collagen vascular diseases. In 12 IPPFE cases (9 male, 3 female, average age 66.8), 6 had thinness (BMI   Conclusions : Clinical features of IPPFE cases diagnosed by radiologic findings and histological FE by TBLB are similar to those of IPPFE cases diagnosed by VATS reported previously. Comprehensive approach including radiograph is important to diagnose IPPFE.
Monitoring of liver function in patients with pulmonary hypertension treated with endothelin receptor antagonists: The value of a novel monitoring system
Authors: Charlotte Blewett, Eleanor Lunn, David Kiely, Lisa Martin, Judith Hurdman, Neil Hamilton, Iain Armstrong, Paul Septon, Jane Wilkinson, Robin Condliffe, Charlie Elliott
Journal: European Respiratory Journal (2011)

Background:  Endothelin receptor antagonists are used for treatment of pulmonary arterial hypertension (PAH). However, these drugs have been associated with liver injury and patients require regular monitoring of liver function (LFT). We introduced a postal system whereby patients receiving these therapies had blood taken by their local practitioner and sent pre packaged boxes to our centre for analysis and monitoring on a monthly basis.   Aim:  We audited effectiveness of this system with respect to frequency of blood sampling and compliance with accepted guidelines for monitoring of LFT derangements.   Results:  Data on 181 patients aged mean 61.6 was collected with mean duration of therapy of 1.81 years representing a total of 327.61 patient years. Over this period, 2181 LFT9s were performed representing an mean 6.66 samples per patient year. Of 181 patients 32.0% had ≥10 samples per year, 59.1% ≥ 8 samples per year, 72.9% ≥ 6 samples per year and 82.3% ≥ 4 samples per year. All patients had LFT9s performed prior to commencing ERA therapy. Over this period 21 (11.6%) had LFT > 3 ULN and 10 (5.5%) ≥ 8 ULN. Of these patients 48.4% of patients with > 3 ULN had their ERA stopped and 19.4% of patients were re-challenged. Of 10 (5.5%) of patients with LFT> 8 ULN 3 (30%) were re-challenged with ERA. During follow up 87 patients died, of which 2 had LFT > 3 ULN. Data for LFT9s was not available for 6 patients who died.   Conclusion:  A novel system using pre-packaged boxes with prescribing centre laboratory monitoring and supervision by specialist nursing staff is capable of providing an acceptable level of compliance with recommended LFT monitoring.
Fever Control Using External Cooling in Septic Shock
Authors: Frédérique Schortgen, Karine Clabault, Sandrine Katsahian, Jerome Devaquet, Alain Mercat, Nicolas Deye, Jean Dellamonica, Lila Bouadma, Fabrice Cook, Olfa Beji, Christian Brun-Buisson, François Lemaire, Laurent Brochard
Journal: American Journal of Respiratory and Critical Care Medicine (2012)

Rationale: Fever control may improve vascular tone and decrease oxygen consumption, but fever may contribute to combat infection.Objectives: To determine whether fever control by external cooling diminishes vasopressor requirements in septic shock.Methods: In a multicenter randomized controlled trial, febrile patients with septic shock requiring vasopressors, mechanical ventilation, and sedation were allocated to external cooling (n = 101) to achieve normothermia (36.5–37°C) for 48 hours or no external cooling (n = 99). Vasopressors were tapered to maintain the same blood pressure target in the two groups. The primary endpoint was the number of patients with a 50% decrease in baseline vasopressor dose after 48 hours.Measurements and Main Results: Body temperature was significantly lower in the cooling group after 2 hours of treatment (36.8 ± 0.7 vs. 38.4 ± 1.1°C; P < 0.01). A 50% vasopressor dose decrease was significantly more common with external cooling from 12 hours of treatment (54 vs. 20%; absolute difference, 34%; 95% confidence interval [95% CI], −46 to −21; P < 0.001) but not at 48 hours (72 vs. 61%; absolute difference, 11%; 95% CI, −23 to 2). Shock reversal during the intensive care unit stay was significantly more common with cooling (86 vs. 73%; absolute difference, 13%; 95% CI, 2 to 25; P = 0.021). Day-14 mortality was significantly lower in the cooling group (19 vs. 34%; absolute difference, –16%; 95% CI, −28 to −4; P = 0.013).Conclusions: In this study, fever control using external cooling was safe and decreased vasopressor requirements and early mortality in septic shock.
Pattern, Severity and Aetiology of Injuries in Victims of Assault
Authors: J P Shepherd, M Shapland, N X Pearce, C Scully
Journal: Journal of the Royal Society of Medicine (1990)

Although the incidence of assault and other violent crime is increasing in the UK, the cause and overall pattern of injury, and the need for admission have not been defined in adult victims who attend hospital. In a prospective study, all 539 adult victims of assault attending a major city centre Accident & Emergency department in 1986 were therefore interviewed and examined. Facial injury was extremely common: 83% of all fractures, 66% of all lacerations and 53% of all haematomas were facial. The upper limb was the next most common site of injury (14% of all injuries). Twenty-six per cent of victims sustained at least one fracture and nasal fractures were the most frequently observed skeletal injuries (27%) followed by zygomatic fractures (22%) and mandibular body (12%), angle (12%) and condyle (9%) fractures. Seventeen per cent of victims required hospital admission. Overall, the type of injury observed correlated with the alleged weapon used (P = less than 0.001) though 20% of victims who reported attacks with sharp weapons sustained only haematomas or fractures. Injury most often resulted from punching (72% of assaults) or kicking (42% of assaults). Only 6% of victims reported injury with knives but 11% were injured by broken drinking glasses. Those who were kicked were most likely to need hospital admission.
Antigenic Loss in a Transplantable, Chemically Induced Leukemia of C57BL/6 Mice
Authors: Daniel J. Rubin, Harvey R. Colten, Tibor Borsos, Herbert J. Rapp
Journal: JNCI Journal of the National Cancer Institute (1970)

The C1− fixation and transfer test, a method for the quantitative determination of cell surface antigens, was applied to the study of murine leukemias. With this test we demonstrated by repeated absorptions of a heterologous antiserum that EL4 cells lack at least one antigen present on the cell surfaces of normal lymphoid cells and on the cells of two virus-induced murine leukemias of C57BL/6 mice. This lack of “normal” antigen on EL4 cells precludes the use of these cells as “normal” controls in immunologic analysis of tumor-specific membrane antigens of C57BL/6 mice.
Association of thymic stromal lymphopoietin gene polymorphisms with atopic status, pulmonary function and airway hyperresponsiveness in a Japanese adult asthmatic population
Authors: Satoshi Moriguchi, Yu Utsumi, Takayuki Miyamoto, Kenshi Sekimura, Nobuhito Sasaki, Masahiro Yamashita, Yuataka Nakamura, Hitoshi Kobayashi, Kohei Yamauchi
Journal: European Respiratory Journal (2013)

Background: Single-nucleotide polymorphism (SNP: rs2289276, rs3806933) of thymic stromal lymphopoietin (TSLP) has been reported to have susceptibility to bronchial asthma (Harada et al.AJRCMB, 2011). Association of polymorphisms of TSLP gene with atopic status, pulmonary function (PF) and airway hyperresponsiveness (AHR) in asthmatics with or without smoking has not been precisely elucidated.  Objectives: We analyzed the relationship between SNP of TSLP (rs2289276, rs3806933) and atopic status, PF and AHR in asthmatics.  Methods: We recruited 280 asthmatics to the current study who visited Iwate Medical University Hospital from 2006 to 2011. Subjects were genotyped using rs2289276 and rs3806933 by 7500 Fast Real-Time PCR System, (Applied Biosystems USA). PF was evaluated by spirometer. AHR to methacholine was measured by Astograph; Jupitor 21 (Chest, Japan). AHR was expressed as D min. This study was approved by the ethics committee of Iwate Medical University.  Results: Genotyping of rs3806933 showed that 165 C/C, 115 C/T and 19 T/T. Atopic status between C/C and C/T+T/T was significantly different (Chi-square analysis). Neither PF or D min of the 3 genotypes was not significantly different. However there was a significant difference of FEV1 %predicted between C/C and C/T+T/T in never smoker with asthma (p=0.015, Mann-Whitney U-test)  Conclusion: SNP (rs3806933) in TSLP was associated with atopic status and FEV1 %predicted in the never smoker of the current asthmatic population, suggesting that TSLP was involved in immune response induced by allergens and modification of immune reaction by smoking.
Associations between measurements of health related quality of life (HRQoL) and physical activity (PA) in patients with interstitial lung disease (ILD)
Authors: Veronica Barbier, Silvia Perez-Bogerd, Miek Hornikx, Daniel Langer, Chris Burtin, Hans Vanremoortel, Heleen Demeyer, Marc Decramer, Wim Janssens, Wim Wuyts, Thierry Troosters
Journal: European Respiratory Journal (2012)

PURPOSE:   PA is not well studied in patients with ILD. It is unknown to what extent PA relates to HRQoL in these patients. The aim of this study was to investigate associations between HRQoL and PA.   METHODS:   We studied 54 patients with ILD (Age: 64 ± 11 years; FVC: 81 ± 23%; DLCO: 45 ± 13%). HRQoL was assessed by the Chronic Respiratory Disease Questionnaire (CRDQ) and the Saint Georges Respiratory Questionnaire (SGRQ). The SenseWear Armband was used to assess PA. Mean steps (STEPS) and moderate intense activity (MOD PA) were calculated over 7 consecutive days.   RESULTS:   Baseline characteristics are presented in Table 1.  Spearman Correlation Coefficients were used to examine relationships between HRQoL questionnaires and PA (Table 2). The SGRQ and CRDQ correlated modestly to each other (r=-0.57; p   CONCLUSION:   The SGRQ and CRDQ are measuring similar concepts but HRQoL is unrelated to PA levels in patients with ILD.