tbuckley/cabot-search huggingface dataset:
Changes in specific airways conductance and forced expiratory volume in one second after a bronchodilator in normal subjects and patients with airways obstruction
Authors: C. Skinner, K. N. V. Palmer
Journal: Thorax (1974)

<b>Skinner, C. and Palmer, K.N.V. (1974).</b><i>Thorax</i>, <b>29,</b> 574-577. <b>Changes in specific airways conductance and forced expiratory volume in one second after a bronchodilator in normal subjects and patients with airways obstruction.</b> Specific conductance (SGaw) and the forced expiratory volume in one second (FEV<sub>1</sub>) were measured in 10 normal, 10 asthmatic, and 10 obstructive bronchitic subjects before and after aerosol salbutamol. Mean SGaw increased by 37% in normals, by 109% in asthmatics, and by 38% in obstructive bronchitics. Mean FEV<sub>1</sub> increased by 2% in normals, by 32% in asthmatics, and by 12% in obstructive bronchitics. SGaw appears to be a more sensitive indicator than FEV<sub>1</sub> of changes in airways calibre following a bronchodilator drug in normal subjects, but FEV<sub>1</sub> is as good an indicator of these changes as SGaw in patients with airways obstruction.
Insulin-Induced Decreases in Aortic Wave Reflection and Central Systolic Pressure Are Impaired in Type 2 Diabetes
Authors: Marjo Tamminen, Jukka Westerbacka, Satu Vehkavaara, Hannele Yki-Järvinen
Journal: Diabetes Care (2002)

To determine whether large arteries are resistant to insulin.Insulin normally acutely decreases central systolic pressure by decreasing wave reflection in vivo. This effect occurs before any changes in peripheral vascular resistance or heart rate under normoglycemic conditions. We determined whether the ability of insulin to decrease central aortic pressure is altered in uncomplicated type 2 diabetes. The study subjects consisted of 16 type 2 diabetic patients (age 54 +/- 2 years, BMI 29 +/- 1 kg/m(2)) and 19 matched nondiabetic individuals (51 +/- 2 years, 29 +/- 1 kg/m(2)) studied under normoglycemic-hyperinsulinemic conditions. Central aortic pressure waveforms were synthesized from those recorded in the periphery using applanation tonometry and a validated reverse transfer function to construct the central aortic pressure waveform every 30 min. This method allowed determination of aortic augmentation (the pressure difference between the first and second central systolic pressure waves) and the augmentation index (augmentation divided by pulse pressure).Whole-body insulin sensitivity was 31% lower (P < 0.05) in the type 2 diabetic patients than in the normal subjects. Basally, before the insulin infusion, augmentation averaged 8.9 +/- 1.3 and 11.1 +/- 1.2 mmHg (NS) and the augmentation index averaged 23.1 +/- 2.1 and 27.5 +/- 2.1% (NS) in the normal subjects and diabetic patients, respectively. After 30 min of hyperinsulinemia, augmentation decreased significantly to 6.1 +/- 1.1 mmHg (P < 0.001) in the normal subjects but remained unchanged at 9.1 +/- 1.1 mmHg (NS) in type 2 diabetic patients. At 30 min, the augmentation index had decreased significantly (30 +/- 7% decrease) to 17.9 +/- 2.6% in the normal subjects but remained at 24.4 +/- 2.4% in the diabetic patients (13 +/- 4% decrease, P < 0.05 for change vs. normal subjects). Central systolic pressure decreased significantly by 30 min in the normal subjects but only after 120 min in the type 2 diabetic patients. There were no significant changes in heart rate, pulse pressure, or forearm blood flow during the first 120 min of the insulin infusion.Insulin resistance in type 2 diabetes involves a delay in the ability of insulin to decrease central aortic pressure. This defect could predispose these patients to develop systolic hypertension.
Impaired Hepatic Extraction and Increased Splanchnic Production Contribute to Lactic Acidosis in Canine Sepsis
Authors: CARLA CHRUSCH, COLIN BANDS, DEEPAK BOSE, XING LI, HANS JACOBS, KRIKA DUKE, EDGAR BAUTISTA, GREGG ESCHUN, R. BRUCE LIGHT, STEVEN N. MINK
Journal: American Journal of Respiratory and Critical Care Medicine (2000)

In septic shock, the extent to which lactic acidosis (LA) is a consequence of splanchnic lactate overproduction (SLP) or impaired hepatic lactate extraction (HLE) is not clear. We examined SLP and HLE in E. coli sepsis in dogs. We further determined the effects of vasopressor treatments, which included phenylephrine, dopamine, norepinephrine, and a combination of dobutamine and norepinephrine treatment, on SLP and HLE in respective groups. The animals were studied while anesthetized and ventilated. During sepsis, SLP increased as compared with presepsis ( − 0.017 versus 0.07 mmol/min, p < 0.05), but this increase could not be explained by reduced splanchnic oxygen delivery (SOD). During sepsis, HLE increased as compared with baseline (0.8 versus 8%, p < 0.05), but was significantly lower than that found during lactic acid loading in nonseptic dogs. None of the vasopressor treatments had a detrimental effect on SLP. These results indicate that LA in sepsis occurs secondary to an increase in splanchnic lactate production that is not related to reduced splanchnic oxygen delivery, as well as to a decrease in hepatic lactate extraction. Effects of different vasoactive agents did not alter either splanchnic lactate production or hepatic lactate extraction in this sepsis model. Chrusch C, Bands C, Bose D, Li X, Jacobs H, Duke K, Bautista E, Eschun G, Light RB, Mink SN. Impaired hepatic extraction and increased splanchnic production contribute to lactic acidosis in canine sepsis.
Adjuvant Endocrine Therapy for Postmenopausal Women with Early Breast Cancer
Authors: James N. Ingle
Journal: Clinical Cancer Research (2006)

Abstract Results from multiple clinical trials involving aromatase inhibitors have added to the knowledge base relating to endocrine therapy of postmenopausal women with hormone receptor–positive early breast cancer. In the extended adjuvant setting, data from the Austrian Breast and Colorectal Cancer Study Group 6a trial showed an advantage for anastrozole following 5 years of tamoxifen treatment, consistent with the more robust MA.17 trial that examined letrozole versus placebo following 5 years of tamoxifen treatment. The combined analysis of the Austrian Breast and Colorectal Cancer Study Group 8 trial and the German Arimidex Nolvadex 95 trial, plus the Italian Tamoxifen Anastrozole trial, have shown the advantage of switching to anastrozole over continuing the tamoxifen to complete the full 5 years of adjuvant therapy. These trials support the previously reported larger and double-blind Intergroup Exemestane Study. The Arimidex, Tamoxifen, Alone or in Combination trial now has data out to 68 months of median follow-up showing the maintenance of a significant advantage of anastrozole over tamoxifen for disease-free survival. In this initial treatment setting, the Breast International Group 1-98 trial recently showed a significant advantage for letrozole over tamoxifen. The current debate is centered on whether the optimal strategy is to give an aromatase inhibitor initially or after several years of tamoxifen treatment. Multiple important questions remain, including the predictive value of molecular markers such as progesterone receptor, the optimal duration of aromatase inhibitor therapy, the long-term adverse effects, and the relative efficacy and toxicity of the different aromatase inhibitors.
Guidelines for resection of colorectal cancer liver metastases
Authors: O J Garden
Journal: Gut (2006)

There has been increasing recognition of the potential benefits of liver resection for colorectal metastases in the UK although this treatment has been established more widely in other Western countries. There are no randomised studies assessing outcome following resection compared with no treatment or other therapeutic modalities in patients with known resectable liver metastases as it is generally considered unethical not to offer surgery for resectable disease. There has been increased interest in more aggressive chemotherapy regimens that have been reported to not only control metastatic disease but also to render some advanced liver metastases resectable.1–4 Furthermore, other new modalities have become available that allow safe ablation of liver metastases without the need for surgical intervention. There is therefore a need to produce clear guidelines on the appropriate management of patients with colorectal cancer who have been shown to have hepatic metastases.

These guidelines are intended to address a number of issues:



1.  the principles under which patients with hepatic metastases should be managed;

2.  which patients who have undergone attempted curative resection of the primary colorectal tumour should be offered surveillance;

3.  what investigations are required to determine appropriate management; and

4.  which treatment modality is most appropriate in a given clinical context.



The process of formulating any clinical guidelines requires a guideline development group, a search strategy with review of the relevant literature, synthesis of evidence (and consensus methods for topics when evidence is lacking), followed by external review. A multidisciplinary meeting with representation from a number of interested bodies involving surgeons, gastroenterologists, oncologists, diagnostic and interventional radiologists, pathologists, general practitioners, clinical nurse specialists, nurse practitioners, and patients was held in the Pelican Centre in Basingstoke on 2–4 October 2003 (see appendix 1). The Appraisal of Guidelines Research and Evaluation (AGREE) instrument was used to provide a framework for assessing …
On the Treatment of Pleuritic Effusion
Authors: T. C. Allbutt
Journal: BMJ (1877)

IN the paper I am to read before this Section, I can scarcely hope to say much that is new, but I may hope to put the old before you strengthened by the results of a maturer experience.My own views of ihe treatment of pleuritic effusion have been laid repeatedly before the profession, and have contributed to the formation of a bolder habit of procedure in the matter.It is, therefore, neither needful nor possible in the time before me to enter into anly full or minute discussion of the -uhole of our subject, but rather to set forth as pointedly as possible my views on the more difficult or disputed points.Under such circumstances, I must ask your forgiveness for any apparent abruptness or dogmatism.It appears to me that our first duty is so to divide pleurisies into classes as to enable us to know more clearly what we have to deal with, and thus to avoid much of that controversy which gathers about ill-defi,td propositions as parasites gather about ill-nourished tissues.Althbogh no hard lines can be drawn around them, yet the following divisions are fairly recognisable if we disregard transitional cases.t. Dry pleurisies, in which the tubercular may be included.2. Acute effusive pleurisies, in which the rheumatic are included.3. Quiet effusive pleurisies in the serous stage.4 Empyemata. Pleuritic dropsy.Of Class i, I have now nothing to say.The tubercular pleurisies are at times effusive, but the exigencies of individual cases are too vat ous to be here considered.Class ii.Acute effusive pleurisies are those of an actively inflam- n-.ory kind, which make themselves sharply felt from the beginning by * Read in the Section of Medicine at the Annual Meeting of the British Medical A sociation in Manchester, August I877.* I mean here aspirations as the chest refills.On the other hand, the more receut proposal to aspirate every other day, or at very short intervals, is, in my opinion, well deserving of careful trial.
Evaluation of Plasma Chemokines and Cytokines in the Setting of Egg Oral Immunotherapy (OIT)
Authors: Stephanie Albin, Kezhen Fei, Robert A. Wood, David M. Fleischer, Scott H. Sicherer, Robert W. Lindblad, Brian P. Vickery, Andrew H. Liu, Amy M. Scurlock, A. Wesley Burks, Stacie M. Jones, Hugh A. Sampson, Cecilia Berin
Journal: Journal of Allergy and Clinical Immunology (2015)
Antiestrogenic Glyceollins Suppress Human Breast and Ovarian Carcinoma Tumorigenesis
Authors: Virgilo A. Salvo, Stephen M. Boué, Juan P. Fonseca, Steven Elliott, Cynthia Corbitt, Bridgette M. Collins-Burow, Tyler J. Curiel, Sudesh K. Srivastav, Betty Y. Shih, Carol Carter-Wientjes, Charles E. Wood, Paul W. Erhardt, Barbara S. Beckman, John A. McLachlan, Thomas E. Cleveland, Matthew E. Burow
Journal: Clinical Cancer Research (2006)

Abstract Purpose: We have identified the phytoalexin compounds glyceollins I, II, and III, which exhibit marked antiestrogenic effects on estrogen receptor function and estrogen-dependent tumor growth in vivo. The purpose of this study was to investigate the interactions among the induced soy phytoalexins glyceollins I, II, and III on the growth of estrogen-dependent MCF-7 breast cancer and BG-1 ovarian cancer cells implanted in ovariectomized athymic mice. Experimental Design: Four treatment groups for each cell line were used: vehicle control, 20 mg/kg/mouse/d glyceollin mixture injection, 0.72 mg estradiol (E2) implant, and E2 implant + 20 mg/kg/mouse/d glyceollin injection. Results: Treatment with glyceollin suppressed E2-stimulated tumor growth of MCF-7 cells (−53.4%) and BG-1 cells (−73.1%) in ovariectomized athymic mice. These tumor-inhibiting effects corresponded with significantly lower E2-induced progesterone receptor expression in the tumors. In contrast to tamoxifen, the glyceollins had no estrogen-agonist effects on uterine morphology and partially antagonized the uterotropic effects of estrogen. Conclusions: These findings identify glyceollins as antiestrogenic agents that may be useful in the prevention or treatment of breast and ovarian carcinoma.
Influenza virus hemagglutinin-specific cytotoxic T cell response induced by polypeptide produced in Escherichia coli.
Authors: A Yamada, M R Ziese, J F Young, Y K Yamada, F A Ennis
Journal: The Journal of Experimental Medicine (1985)

We have tested the abilities of various polypeptides of A/PR/8/34 (H1N1) virus, constructed by recombinant DNA techniques, to induce influenza virus-specific secondary cytotoxic T lymphocyte (CTL) responses. A hybrid protein (c13 protein), consisting of the first 81 amino acids of viral nonstructural protein (NS1) and the HA2 subunit of viral hemagglutinin (HA), induced H-2-restricted, influenza virus subtype-specific secondary CTL in vitro, although other peptides did not. Using a recombinant virus, the viral determinant responsible for recognition was mapped to the HA2 portion of c13 protein. Immunization of mice with c13 protein induced the generation of memory CTL in vivo. The CTL precursor frequencies of A/PR/8/34 virus- and c13 protein-immune mice were estimated as one in 8,047 and 50,312, respectively. These results indicate that c13 protein primed recipient mice, even though the level of precursor frequency was below that observed in virus-immune mice.
Antigen recognition. V. Requirement for histocompatibility between antigen-presenting cell and B cell in the response to a thymus-dependent antigen, and lack of allogeneic restriction between T and B cells.
Authors: E Nisbet-Brown, B Singh, E Diener
Journal: The Journal of Experimental Medicine (1981)

The restrictions imposed by the major histocompatibility complex on T-B-antigen-presenting cell (APC) interactions were studied with an in vivo adoptive transfer system, using mutually tolerant T and B cells taken from one-way fetal liver chimeras. It was found that the B cells and adoptive recipient (which provides APC function) have to share determinants encoded by the left-hand end of the H-2 complex for cooperation, whereas there is apparently no such requirement for T-B cell syngeneicity. Suppression arising from allogeneic effects between the host and the transferred T or B cells was excluded by the use of tolerant as well as normal adoptive recipients; both were functionally equivalent. We conclude that under experimental conditions, unrestricted helper T cell function and concurrent APC-B cell genetic restriction can be demonstrated in vivo.
Clinical effectiveness of health visitor training in psychologically informed approaches for depression in postnatal women: pragmatic cluster randomised trial in primary care
Authors: C J. Morrell, P. Slade, R. Warner, G. Paley, S. Dixon, S. J Walters, T. Brugha, M. Barkham, G. J Parry, J. Nicholl
Journal: BMJ (2009)

<b>Objective</b> To evaluate benefits for postnatal women of two psychologically informed interventions by health visitors. <b>Design</b> Prospective cluster trial randomised by general practice, with 18 month follow-up. <b>Setting</b> 101 general practices in Trent, England. <b>Participants</b> 2749 women allocated to intervention, 1335 to control. <b>Intervention</b> Health visitors (n=89 63 clusters) were trained to identify depressive symptoms at six to eight weeks postnatally using the Edinburgh postnatal depression scale (EPDS) and clinical assessment and also trained in providing psychologically informed sessions based on cognitive behavioural or person centred principles for an hour a week for eight weeks. Health visitors in the control group (n=49 38 clusters) provided usual care. <b>Main outcome measures</b> Score ≥12 on the Edinburgh postnatal depression scale at six months. Secondary outcomes were mean Edinburgh postnatal depression scale, clinical outcomes in routine evaluation-outcome measure (CORE-OM), state-trait anxiety inventory (STAI), SF-12, and parenting stress index short form (PSI-SF) scores at six, 12, 18 months. <b>Results</b> 4084 eligible women consented and 595 women had a six week EPDS score ≥12. Of these, 418 had EPDS scores available at six weeks and six months. At six months, 34% women (93/271) in the intervention group and 46% (67/147) in the control group had an EPDS score ≥12. The odds ratio for score ≥12 at six months was 0.62 (95% confidence interval 0.40 to 0.97, P=0.036) for women in the intervention group compared with women in the control group. After adjustment for covariates, the odds ratio was 0.60 (0.38 to 0.95, P=0.028). At six months, 12.4% (234/1880) of all women in the intervention group and 16.7% (166/995) of all women in the control group had scores ≥12 (0.67, 0.51 to 0.87, P=0.003). Benefit for women in the intervention group with a six week EPDS score ≥12 and for all women was maintained at 12 months postnatally. There was no differential benefit for either psychological approach over the other. <b>Conclusion</b> Training health visitors to assess women, identify symptoms of postnatal depression, and deliver psychologically informed sessions was clinically effective at six and 12 months postnatally compared with usual care. <b>Trial registration</b>ISRCTN92195776.
Phase II Trial of Infusional Fluorouracil, Leucovorin, Mitomycin, and Dipyridamole in Locally Advanced Unresectable Pancreatic Adenocarcinoma: SWOG S9700
Authors: William H. Isacoff, Jacqueline K. Bendetti, John J. Barstis, Abdul-Rahman Jazieh, John S. Macdonald, Philip A. Philip
Journal: Journal of Clinical Oncology (2007)

To test the hypothesis that dual biochemical modulation of fluorouracil (FU) in combination with mitomycin improves the survival of patients with pancreas cancer.Eligibility included stage II or III unresectable adenocarcinoma of the pancreas, performance status of 0 to 2, and adequate organ function. Treatment included FU 200 mg/m2/d via continuous intravenous infusion for 4 weeks followed by 1 week of rest; leucovorin 30 mg/m2 administered via intravenous bolus infusion on days 1, 8, 15, and 22, followed by 1 week rest; mitomycin 10 mg/m2 intravenous bolus infusion every 6 weeks for a total of four doses. Dipyridamole 75 mg was administered orally three times daily during the FU administration.Fifty patients (median age, 61 years; 23 males, 27 females) with localized unresectable pancreatic cancer were eligible for this trial. Twenty-seven patients survived past 1 year for a 1-year survival probability of 54% (95% CI, 40% to 68%). Overall, the objective response rate was 26% (confirmed and unconfirmed) in the 47 patients with measurable disease, with two complete responders. Six of the responding patients underwent curative successful resection of the tumor. The most common toxicity to treatment was stomatitis. Three patients had reversible hemolytic uremic syndrome. Five patients experienced grade 4 toxicity. There were no treatment-related deaths.Potential improvement in survival and resectability of localized unresectable pancreatic cancer may be attained without radiation. The strategy of dual biochemical modulation of FU warrants additional investigation in a randomized fashion.
Cardiac Toxicity of Sunitinib and Sorafenib in Patients With Metastatic Renal Cell Carcinoma
Authors: Manuela Schmidinger, Christoph C. Zielinski, Ursula M. Vogl, Andja Bojic, Marija Bojic, Christoph Schukro, Marquerite Ruhsam, Michael Hejna, Herwig Schmidinger
Journal: Journal of Clinical Oncology (2008)

Sunitinib and sorafenib are tyrosine kinase inhibitors (TKIs) that have considerable efficacy in metastatic renal cell carcinoma. TKI-associated cardiotoxicity was reported in approximately 10% of the patients. Detailed cardiovascular monitoring during TKI treatment may reveal early signs of myocardial damage.In this observational, single-center study, all patients intended for TKI treatment were analyzed for coronary artery disease (CAD) risk factors, history or evidence of CAD, hypertension, rhythm disturbances, and heart failure. Monitoring included assessment of symptoms, ECGs, and biochemical markers (ie, creatine kinase-MB, troponin T). Echocardiography was performed at baseline in selected patients and in all patients who experienced a cardiac event. A cardiac event was defined as the occurrence of increased enzymes if normal at baseline, symptomatic arrhythmia that required treatment, new left ventricular dysfunction, or acute coronary syndrome.A total of 86 patients were treated with either sunitinib or sorafenib. Among 74 eligible patients, 33.8% experienced a cardiac event, 40.5% had ECG changes, and 18% were symptomatic. Seven patients (9.4%) were seriously compromised and required intermediate care and/or intensive care admission. All patients recovered after cardiovascular management (ie, medication, coronary angiography, pacemaker implantation, heart surgery) and were considered eligible for TKI continuation. Statistically, there was no significant survival difference between patients who experienced a cardiac event and those who did not experience a cardiac event.Our observations indicate that cardiac damage from TKI treatment is a largely underestimated phenomenon but is manageable if patients have careful cardiovascular monitoring and cardiac treatment at the first signs of myocardial damage.