tbuckley/cabot-search huggingface dataset:
The immunostimulant OK-432 enhances liver regeneration after 90% hepatectomy in rats
Authors: Kazuya Kato, Minoru Matsuda, Mitsuo Kusano, Kazuhiko Onodera, Junji Kato, Shinichi Kasai, Michio Mito, John W.B. Hodgson
Journal: Hepatology (1994)

The effect of reticuloendothelial system activation on liver regeneration after 90% hepatectomy was investigated. OK-432, a killed streptococcal preparation that increases reticuloendothelial system activity, was administered to rats before 90% partial hepatectomy. Pretreated rats showed marked improvement in long-term survival: 87% (18 of 23) survived beyond 42 hr, compared with only 44.2% (24 of 52) of controls (p < 0.05). Survival was determined by means of life-table analysis and regeneration response by means of bromodeoxyuridine labeling index of hepatic DNA. OK-432 pretreatment had significantly increased bromodeoxyuridine labeling index 18, 24, and 42 hr after partial hepatectomy (p < 0.05). The results indicate that reticuloendothelial system activation by OK-432 before 90% partial hepatectomy enhances liver regeneration and improves survival, but these factors may not be related. The improved survival may be because of less infection in macrophage-stimulated animals or more rapid clearance of hypotension-causing vasoactive compounds.
Pulmonary function studies in healthy Pakistani adults.
Authors: D E Williams, R D Miller, W F Taylor
Journal: Thorax (1978)

Predicted normal spirometric values have been shown to have significant geographical and ethnic variation. These variations are of epidemiological significance in determining the prevalence of disease and of clinical importance in measuring the effects on pulmonary function of various diseases. A total of 599 men were chosen from employees of a package manufacturer, a general hospital in Lahore, and a village in northern Pakistan; 94 students and staff of a women's college in Lahore were also studied. The forced vital capacity (FVC) was recorded from three satisfactory efforts, and the FVC, one second forced expiratory volume (FEV1), and maximal midexpiratory flow (MMF, or FEF25-75%) were calculated from the best FVC effort. The FVC and FEV1 in men were found to be similar to those of a group of emigrant Pakistanis and a north-western Indian population (Delhi) but higher than populations in south and eastern India. Pakistani women had values similar to those of women in northern India. None of the women smoked and, among Pakistani men, the smokers (285) averaged 6.7 pack years. While the FVC and FEV1 values did not differ between smokers and non-smokers, there was a significant difference in MMF (FEF25-75%) in the two groups. This latter finding corroborates studies on North American populations in which smokers generally have had a higher lifelong cigarette consumption. This confirms the MMF (FEF25-75%) to be a more sensitive test of subtle, asymptomatic changes in pulmonary function than the more widely used FVC and FEV1.
Oxaliplatin With Weekly Bolus Fluorouracil and Low-Dose Leucovorin as First-Line Therapy for Patients With Colorectal Cancer
Authors: Howard Hochster, Abraham Chachoua, James Speyer, Juliette Escalon, Anne Zeleniuch-Jacquotte, Franco Muggia
Journal: Journal of Clinical Oncology (2003)

To determine the activity of biweekly oxaliplatin, combined with weekly bolus fluorouracil (FU) and low-dose leucovorin (LV) chemotherapy (bFOL), as first-line therapy for patients with metastatic colorectal cancer.Patients with measurable metastatic colorectal cancer; no previous therapy for advanced disease (adjuvant therapy allowed if >6 months since completion); and performance status 0, 1, or 2 were eligible and were treated with oxaliplatin 85 mg/m2 days 1 and 15 plus LV 20 mg/m2 over 10 to 20 minutes, followed by a 500 mg/m2 bolus dose of FU on days 1, 8, and 15 every 28 days. Patients underwent response evaluation by computed tomographic scan every 2 months.Forty-two patients were entered, and 41 patients were treated, including 20 men and 22 women, nine with previous adjuvant chemotherapy and four with radiation therapy. Three patients achieved complete response, and 23 patients achieved partial response, for a response rate of 63% (95% CI, 49% to 78%). Major toxicities included cumulative neuropathy grade 2 (24%) and grade 3 (12%; requiring discontinuation of oxaliplatin), diarrhea grade 3 to 4 (29%) and grade 3 to 4 hematologic toxicity (10%). Median time to progression was 9.0 months (95% confidence interval, 7.1 to 10.8 months) with median survival of 15.9 months (95% confidence interval, 11.4 to 19.7 months).The bFOL regimen seems to have activity comparable to be infusional programs of FU combined with oxaliplatin. Prospective trials are warranted to determine the relative merits of this schedule compared with the currently indicated schedules.
131 HEPATIC STELLATE CELL ACTIVATION: AN IMPORTANT CONTRIBUTOR TO PERSISTENT HEPATIC RESISTANCE IN SMALL-FOR-SIZE LIVERS AFTER EXTENDED PARTIAL HEPATECTOMY IN THE RAT
Authors: Y.-D. Fan, E. Vanheule, D. Meester, J. Van Huysse, K. Olievier, M. Praet, I. Colle, B. de Hemptinne
Journal: Journal of Hepatology (2010)
Antidrug antibodies to tumour necrosis factor specific neutralising agents in chronic inflammatory diseases: a real issue, a clinical perspective; comment on the article by Vincent <i>et al</i>
Authors: Alfons A den Broeder, Aatke van der Maas, Bart J F van den Bemt
Journal: Annals of the Rheumatic Diseases (2013)

Vincent et al present a thorough review of available clinical research on antidrug antibodies to tumour necrosis factor (TNF) blocking agents.1 We agree to a large extent with their interpretation of the data with regard to pathophysiology, assay characteristics and variation in drug and antidrug antibody serum levels. However, the conclusion that measurement of (anti)drug levels should therefore be used for clinical decision making in non-responding biological patients with inflammatory diseases to save costs, prevent adverse events and improve disease activity, including their proposed algorithm, seems flawed and is thus far insufficiently supported by evidence. In our comment we will focus on rheumatoid arthritis (RA), but for other inflammatory disease the same comments can be made.

First, we would argue that the most promising application for therapeutic drug monitoring (TDM) to save costs or adverse events is not to predict response to the next treatment option in non-responding patients, but rather to predict successful dose reduction and stopping in patients who are doing well. All treatment alternatives in non-responding patients employ either another biological or a higher dose of the same biological, so even optimal channelling of patients can only lead to better disease control, not to saved costs or prevented adverse events. In patients doing well however, it could …
A Contemporary Appraisal of the Heart Failure Epidemic in Olmsted County, Minnesota, 2000 to 2010
Authors: Yariv Gerber, Susan A. Weston, Margaret M. Redfield, Alanna M. Chamberlain, Sheila M. Manemann, Ruoxiang Jiang, Jill M. Killian, Véronique L. Roger
Journal: JAMA Internal Medicine (2015)

IMPORTANCE Heart failure (HF) is commonly referred to as an epidemic, posing major clinical and public health challenges.Yet, contemporary data on its magnitude and implications are scarce.OBJECTIVE To evaluate recent trends in HF incidence and outcomes overall and by preserved ejection fraction (HFpEF) or reduced ejection fraction (HFrEF).
Hypoxemia After Thoracentesis
Authors: Robert D. Brandstetter
Journal: JAMA (1979)

Hypoxemia was observed at 20 minutes and two hours postprocedure in 15 patients who had a thoracentesis. The hypoxemia resolved after 24 hours. No effect on pH, Paco<sub>2</sub>, or bicarbonate ion was observed. The degree of hypoxemia was correlated directly with the volume of fluid removed. Oxygen therapy was found to reverse this effect. Hypoxemia that follows thoracentesis may be caused by several factors, the most important being frank pulmonary edema. (<i>JAMA</i>242:1060-1061, 1979)
Provocative gene therapy strategy for the treatment of hepatocellular carcinoma
Authors: Frederick Askari, James Wilson
Journal: Hepatology (1992)

An approach involving retroviral-mediated gene therapy for the treatment of neoplastic disease is described. This therapeutic approach is called “virus-directed enzyme/prodrug therapy” (VDEPT). The VDEPT approach exploits the transcriptional differences between normal and neoplastic cells to achieve selective killing of neoplastic cells. We now describe development of the VDEPT approach for the treatment of hepatocellular carcinoma. Replication-defective, amphotrophic retroviruses were constructed containing a chimeric varicella-zoster virus thymidine kinase (VZV TK) gene that is transcriptionally regulated by either the hepatoma-associated α-fetoprotein or liver-associated albumin transcriptional regulatory sequences. Subsequent to retroviral infection, expression of VZV TK was limited to either α-fetoprotein or albumin-positive cells, respectively. VZV TK metabolically activated the nontoxic prodrug 6-methoxypurine arabinonucleoside (araM), ultimately leading to the formation of the cytotoxic anabolite adenine arabinonucleoside triphosphate (araATP). Cells that selectively expressed VZV TK became selectively sensitive to araM due to the VZV TK-dependent anabolism of araM to araATP. Hence, these retroviral-delivered chimeric genes generated tissue-specific expression of VZV TK, tissue-specific anabolism of araM to araATP, and tissue-specific cytotoxicity due to araM exposure. By utilizing such retroviral vectors, araM was anabolized to araATP in hepatoma cells, producing a selective cytotoxic effect.
NFAT regulates the expression of AIF-1 and IRT-1: yin and yang splice variants of neointima formation and atherosclerosis
Authors: Lisa M. Berglund, Olga Kotova, Peter Osmark, Helena Grufman, Chen Xing, Marie-Louise Lydrup, Isabel Goncalves, Michael V. Autieri, Maria F. Gomez
Journal: Cardiovascular Research (2011)

Alternative transcription and splicing of the allograft inflammatory factor-1 (AIF-1) gene results in the expression of two different proteins: AIF-1 and interferon responsive transcript-1 (IRT-1). Here, we explore the impact of AIF-1 and IRT-1 on vascular smooth muscle cell (VSMC) activation and neointima formation, the mechanisms underlying their alternative splicing, and associations of AIF-1 and IRT-1 mRNA with parameters defining human atherosclerotic plaque phenotype.Translation of AIF-1 and IRT-1 results in different products with contrasting cellular distribution and functions. Overexpression of AIF-1 stimulates migration and proliferation of human VSMCs, whereas IRT-1 exerts opposite effects. Adenoviral infection of angioplasty-injured rat carotid arteries with AdAIF-1 exacerbates intima hyperplasia, whereas infection with AdIRT-1 reduces neointima. Expression of these variants is modulated by changes in nuclear factor of activated T-cells (NFAT) activity. Pharmacological inhibition of NFAT or targeting of NFATc3 with small interfering RNA (siRNA) lowers the AIF-1/IRT-1 ratio and favours an anti-proliferative outcome. NFAT acts as a repressor on the IRT-1 transcriptional start site, which is also sensitive to interferon-γ stimulation. Expression of AIF-1 mRNA in human carotid plaques associates with less extracellular matrix and a more pro-inflammatory plaque and plasma profile, features that may predispose to plaque rupture. In contrast, expression of IRT-1 mRNA associates with a less aggressive phenotype and less VSMCs at the most stenotic region of the plaque.Inhibition of NFAT signalling, by shifting the AIF-1/IRT-1 ratio, may be an attractive target to regulate the VSMC response to injury and manipulate plaque stability in atherosclerosis.
Abstract 1340: Examination of in vivo mutagenicity and carcinogenicity in the gpt delta rat with Dammar resin
Authors: Masaki Tajiri, Min Wei, Yumi Obo, Naomi Ishii, Shotaro Yamano, Hideki Wanibuchi
Journal: Cancer Research (2011)

Abstract Dammar resin is a food additive as a thickening agent. The purposes of this study are to evaluate carcinogenicity and in vivo mutagenicity of Dammar resin in gpt delta rats. 6 week-old male gpt delta rats were divided into 5 groups. Groups 1-3 were treated with five carcinogen (DMBDD) during the first 4 weeks of experiment as follows: diethylnitrosamine (100 mg/kg b.w. i.p.), N-methyl-N-nitrosourea (20mg/kg b.w. i.p.), 1,2-dimethylhydrazine (40 mg/kg b.w. s.c.), 0.05% N-butyl-N-(4-hydroxypropyl) nitrosamine in the drinking water from week 1 to 2, and 0.1% dihydroxybutyl-di-N-propylnitrosamine in the drinking water from week 3 to 4. Groups 4-5 were given vehicle. From experimental week 5, groups 1-3 were treated with Dammar resin in diet at doses of 0, 0.03, and 2% for 13 weeks. Groups 4-5 were treated with Dammar resin in diet at doses of 0, and 2%, respectively. At 18 weeks after starting the experiment, quantitative analysis of glutathione S-transferase placental form (GST-P) positive foci, which are preneoplastic lesions in the rat liver and mutation assays (gpt and Spi- mutation assays) were performed. Both numbers and area of GST-P positive foci were significantly increased in rats administered DMBDD with 2% Dammar resin (group 3) compared to rats administered DMBDD alone (group 1). 0.03% Dammar resin (group 2) had no effects on the development of GST-P positive foci. There were no significant differences in mutant frequencies of gpt and red/gam genes in the livers between rats administered basal diet (group 4) and 2% Dammar resin (group 5). These findings indicated that Dammar resin exerts promotion effect on liver carcinogenesis but lack of in vivo mutagenicity in the livers of gpt delta rats. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 1340. doi:10.1158/1538-7445.AM2011-1340
Postoperative shivering: the influence of body temperature
Authors: A. W A Crossley
Journal: BMJ (1995)

May be related more to peripheral than core temperature and can be reduced by space blankets

Postoperative shivering is common.1 During recovery from anaesthesia increased muscular activity increases oxygen consumption as much as fivefold. Hypoxaemia, lactic acidosis, and hypercarbia may then complicate recovery from anaesthesia,2 at a time when the patient is at risk of hypoxaemia from other causes. Even without these complications patients find shivering uncomfortable, and preventing the syndrome is clearly desirable.

Why do patients shiver postoperatively? It is tempting to assume that heat loss is contributory, exacerbated by peripheral vasodilatation that in turn is induced by …
Recent Advances in Active Immunization
Authors: G. Bousfield
Journal: BMJ (1952)

Inhaled diesel exhaust particles (DEP) exert proinflammatory effects in the respiratory tract. This effect is related to the particle content of redox cycling chemicals and is involved in the adjuvant effects of DEP in atopic sensitization. We demonstrate that organic chemicals extracted from DEP induce oxidative stress in normal and transformed bronchial epithelial cells, leading to the expression of heme oxygenase 1, activation of the c-Jun N-terminal kinase cascade, IL-8 production, as well as induction of cytotoxicity. Among these effects, heme oxygenase 1 expression is the most sensitive marker for oxidative stress, while c-Jun N-terminal kinase activation and induction of apoptosis-necrosis require incremental amounts of the organic chemicals and increased levels of oxidative stress. While a macrophage cell line (THP-1) responded in similar fashion, epithelial cells produced more superoxide radicals and were more susceptible to cytotoxic effects than macrophages. Cytotoxicity is the result of mitochondrial damage, which manifests as ultramicroscopic changes in organelle morphology, a decrease in the mitochondrial membrane potential, superoxide production, and ATP depletion. Epithelial cells also differ from macrophages in not being protected by a thiol antioxidant, <i>N</i>-acetylcysteine, which effectively protects macrophages against cytotoxic DEP chemicals. These findings show that epithelial cells exhibit a hierarchical oxidative stress response that differs from that of macrophages by more rapid transition from cytoprotective to cytotoxic responses. Moreover, epithelial cells are not able to convert <i>N</i>-acetylcysteine to cytoprotective glutathione.
Short-term effects of uninephrectomy on electrical properties of the cortical collecting duct from rabbit remnant kidneys.
Authors: S Muto, S Ebata, Y Asano
Journal: Journal of Clinical Investigation (1994)

Microelectrode techniques were used to determine the Na+ and K+ transport properties of the collecting duct cell in the isolated cortical collecting duct (CCD) from rabbits 14 d after uninephrectomy (UNX); results were compared with those from sham-operated rabbits (control). UNX had no effects on plasma aldosterone levels. The CCDs from UNX rabbits exhibited structural hypertrophy. The lumen negative transepithelial voltage and the basolateral membrane voltage (VB) were elevated in the UNX group. Although the transepithelial conductance (GT) and the fractional apical membrane resistance (fRA) were not different between the two groups, the conductances of the apical and the basolateral membranes were increased, and the tight junction conductance was decreased in the UNX group. The amiloride-sensitive changes in apical membrane voltage (VA), fRA, and GT were greater in the UNX group. The changes in VA upon raising the perfusate K+ concentration and the changes in VA and GT upon addition of Ba2+ to the perfusate were elevated in the UNX group. Upon raising K+ in the bath, a large depolarization of VB was observed in the UNX group. Lowering the bath Cl- resulted in a small depolarization of VB in the UNX group. Addition of Ba2+ to the bath in the UNX group caused the VB to hyperpolarize in parallel with decreases in GT and fRA whereas in the control group it had no effect on VB. Addition of ouabain to the bath resulted in a large depolarization of VB in the UNX group. We conclude that (a) UNX stimulates conductances of Na+ and K+ in the apical membrane, active Na(+)-K+ pump activity, and K+ conductance in the basolateral membrane, independently of plasma aldosterone; (b) The basolateral membrane in the tubules of UNX rabbits is more selective to K+; and (c) the hyperpolarization of VB upon UNX may increase passive K+ entry into the cell across the basolateral membrane.
Esophageal Ulcers Associated With Tetracycline Therapy
Authors: Thomas D. Crowson
Journal: JAMA (1976)

Esophageal ulceration has rarely been reported secondary to medicinal agents. We have treated three patients with esophageal ulceration associated with the ingestion of tetracycline or its derivative doxycycline. In light of the strong temporal relationship between taking the capsules and the onset of the esophageal ulceration, we believe that the capsules were the cause of the ulcers. We therefore recommend an alternative agent to tetracycline or doxycycline, if possible, for patients with any esophageal obstructive element. We also recommend that patients be cautioned not to take these drugs within one hour of going to bed. (<i>JAMA</i>235:2747-2748, 1976)
Selected Treatment Strategies for Septic Shock Based on Proposed Mechanisms of Pathogenesis
Authors: Charles Natanson
Journal: Annals of Internal Medicine (1994)

Purpose: To review selected new therapies for septic shock designed to inhibit bacterial toxins or endogenous mediators of inflammation. Data Sources: Scientific journals, scientific meeting proceedings, and Food and Drug Administration advisory committee proceedings. Study Selection and Extraction: Preclinical and clinical data from trials using core-directed antiendotoxin antibodies and anticytokine therapies for sepsis and studies in animal models of sepsis from our laboratory. Results of Data Synthesis: Ten clinical trials using core-directed antiendotoxin antibodies produced inconsistent results and did not conclusively establish the safety or benefit of this approach. Both anti-interleukin-1 and anti-tumor necrosis factor (TNF) therapies have been beneficial in some animal models of sepsis but did not clearly improve survival in initial human trials, and one anti-TNF therapy actually produced harm. Neutrophils, another target for therapeutic intervention, protect the host from infection but may also contribute to the development of tissue injury during sepsis. In a canine model of septic shock, granulocyte colony-stimulating factor increased the number of circulating neutrophils and improved survival, but an anti-integrin (CD11/18) antibody that inhibits neutrophil function worsened outcome. Nitric oxide, a vasodilator produced by the host, causes hypotension during septic shock but may also protect the endothelium and maintain organ blood flow. In dogs challenged with endotoxin, the inhibition of nitric oxide production decreased cardiac index and did not improve survival. Conclusions: No new therapy for sepsis has shown clinical efficacy. Perhaps more accurate clinical and laboratory predictors are needed to identify patients who may benefit from a given treatment strategy. On the other hand, the therapeutic premises may be flawed. Targeting a single microbial toxin such as endotoxin may not represent a viable strategy for treating a complex inflammatory response to diverse gram-negative bacteria. Similarly, the strategy of inhibiting the host inflammatory response may not be beneficial because immune cells and cytokines play both pathogenic and protective roles. Finally, our scientific knowledge of the complex timing of mediator release and balance during sepsis may be insufficient to develop successful therapeutic interventions for this syndrome.