tbuckley/cabot-search huggingface dataset:
Cardiopulmonary Effects of Pulmonary Venous Hypertension with Special Reference to Pulmonary Lymphatic Flow
Authors: ERWIN R. RABIN, EDWARD C. MEYER
Journal: Circulation Research (1960)

Acute elevation of left atrial pressure could be precisely controlled at any desired level up to a mean of 60 mm. Hg in dogs with an intact thorax. The following observations were made in a series of 15 dogs. Right lymphatic duct flow did not increase at acutely elevated left atrial mean pressure below 25 mm. Hg, whereas flow increased 3- to 4-fold at mean pressure above 25 mm. Hg. The total amount of lymph at maximum flow, however, was only 0.3 ml./min. Lymph flow remained elevated for as long as 1 hour after left atrial pressure was restored to normal. Elevation of left atrial pressure did not affect lymph flow in the thoracic duct. Pulmonary edema did not occur readily at left atrial mean pressure elevated only slightly above plasma oncotic pressure. The production of pulmonary edema was observed only after a considerable elevation of left atrial pressure above plasma oncotic pressure was maintained for a period of one half hour or more in an otherwise normal dog. The hematocrit increased significantly after a 10-minute period of high left atrial pressure. Pulmonary vascular resistance decreased sharply as left atrial mean pressure was raised from 0 to 15 mm. Hg. The resistance gradually rose as left atrial pressure was raised to between 15 and 30 mm. Hg. Pulmonary arterial pressure uniformly rose and cardiac output uniformly declined with increasing left atrial pressure. Chronic elevation of left atrial pressure was achieved in 15 dogs. Left atrial mean pressure varied from 10 to 23 mm. Hg. These dogs were followed up to 10 months and the following observations were made. Right lymphatic duct flow did not increase at chronically elevated left atrial mean pressure below 25 mm. Hg. Flow was not studied at higher pressures since we were unable to sustain left atrial mean pressure above 25 mm. Hg in any dog in our chronic group. The animals that were brought to left atrial mean pressure between 30 and 40 mm. Hg and in whom these high levels were presumably maintained were found dead in their cages with pulmonary edema 1 to 2 days after tightening the snare. Many of the usual functional and structural changes often found in lungs of patients with mitral stenosis, except for hemosiderosis, were not observed in our experimental animals although the extent of the supravalvular stenosis produced was marked. Pulmonary arterial pressure rose slightly and cardiac output declined slightly. No change was noted in pulmonary vascular resistance. Ascites and other signs of right sided failure were not encountered.
Inhibition of sodium transport by prostaglandin E2 across the isolated, perfused rabbit collecting tubule.
Authors: J B Stokes, J P Kokko
Journal: Journal of Clinical Investigation (1977)

This study was designed to examine whether prostaglandin E2 can directly affect sodium transport across isolated perfused rabbit renal collecting tubules. Changes in transepithelial potential and isotopic sodium fluxes in response to peritubular prostaglandin E2 were measured. In addition, changes in transepithelial potential of the outer medullary collecting tubule in response to prostaglandin E2 were also measured. With few exceptions, all rabbits received 5 mg/day desoxycorticosterone acetate for 4-11 days before experimentation. The results of the experiments show that: (a) prostaglandin E2 inhibits the negative transepithelial potential in the cortical collecting tubule as well as the outer medullary collecting tubule; (b) prostaglandin E2 inhibits net sodium transport out of the lumen by inhibiting efflux while backflux is unaffected; (c) prostaglandin E2 produces this inhibition within 15 min, and the effects are dose dependent and reversible. These results suggest that prostaglandin E2 may modulate sodium transport in vivo and may contribute to the final regulation of sodium excretion.
Managing perineal trauma after childbirth
Authors: S. Webb, M. Sherburn, K. M. K. Ismail
Journal: BMJ (2014)

#### The bottom line

Every year millions of women worldwide sustain trauma to the perineum when giving birth. Around 6% of these women will have short term wound complications such as infection and dehiscence.1 Some are also at risk of long term problems such as dyspareunia, pain, urinary and faecal incontinence, pelvic organ prolapse, and psychosocial problems. Correct assessment and repair of this trauma is therefore essential to help reduce long term complications. In this review we focus on the management of childbirth related perineal trauma that does not involve injury to the anal sphincter complex (this has been dealt with previously2)—that is, first and second degree perineal trauma. We provide healthcare professionals caring for women during childbirth and the postnatal period with an overview of the current best evidence for the assessment, repair, and postnatal management of perineal trauma to reduce the incidence of complications in the short and long term.

#### Sources and selection criteria

We searched Medline and Embase from 1980 to date, limited to publications in English and to studies in women. Our search strategy used a combination of MeSH, textwords, and appropriate word variants of “perineal” or “trauma” and “obstetric” or “labour”. We supplemented these …
Interactions between metals and microbial communities in New Bedford Harbor, Massachusetts.
Authors: T Ford, J Sorci, R Ika, J Shine
Journal: Environmental Health Perspectives (1998)

The fate of toxic metals in marine sediments depends on a combination of the physical, chemical, and biologic conditions encountered in any given environment. These conditions may vary dramatically, both spatially and temporally, in response to factors ranging from seasonal changes and storm events to human activities such as dredging or remediation efforts. This paper describes a program designed to evaluate the interrelationships between the microbial community and pollutants in the New Bedford Harbor, Massachusetts, area, a U.S. Environmental Protection Agency designated Superfund site. Research has focused on establishing distributional relationships between contaminant metals, fluxes of metals between sediments and the overlying water, changes in microbial diversity in response to metals, and potential use of the microbial community as a biomarker of contaminant availability. This research has shown that a significant flux of metals to the water column is mediated by benthic biologic activity, and that microbial communities may be a responsive marker of contaminant stress. A combination of biogeochemical studies and the use of molecular tools can be used to improve our understanding of the fate and effect of heavy metals released to aquatic systems.
Short-Course Montelukast for Intermittent Asthma in Children
Authors: Colin F. Robertson, David Price, Richard Henry, Craig Mellis, Nicholas Glasgow, Dominic Fitzgerald, Amanda J. Lee, Jane Turner, Melissa Sant
Journal: American Journal of Respiratory and Critical Care Medicine (2006)

Rationale: In children, intermittent asthma is the most common pattern and is responsible for the majority of exacerbations. Montelukast has a rapid onset of action and may be effective if used intermittently.Objectives: To determine whether a short course of montelukast in children with intermittent asthma would modify the severity of an asthma episode.Methods: Children, aged 2–14 years with intermittent asthma participated in this multicenter, randomized, double-blind, placebo-controlled clinical trial over a 12-month period. Treatment with montelukast or placebo was initiated by parents at the onset of each upper respiratory tract infection or asthma symptoms and continued for a minimum of 7 days or until symptoms had resolved for 48 hours.Measurements and Main Results: A total of 220 children were randomized, 107 to montelukast and 113 to placebo. There were 681 treated episodes (345 montelukast, 336 placebo) provided by 202 patients. The montelukast group had 163 unscheduled health care resource utilizations for asthma compared with 228 in the placebo group (odds ratio, 0.65; 95% confidence interval, 0.47–0.89). There was a nonsignificant reduction in specialist attendances and hospitalizations, duration of episode, and β-agonist and prednisolone use. Symptoms were reduced by 14% and nights awakened by 8.6% (p = 0.043), and days off from school or childcare by 37% and parent time off from work by 33% (p < 0.0001 for both).Conclusions: A short course of montelukast, introduced at the first signs of an asthma episode, results in a modest reduction in acute health care resource utilization, symptoms, time off from school, and parental time off from work in children with intermittent asthma.
Prognostic Significance of Fascin Overexpression in Human Esophageal Squamous Cell Carcinoma
Authors: Yosuke Hashimoto, Tetsuo Ito, Harutaka Inoue, Tomoyuki Okumura, Eiji Tanaka, Shigeru Tsunoda, Motoshige Higashiyama, Go Watanabe, Masayuki Imamura, Yutaka Shimada
Journal: Clinical Cancer Research (2005)

Abstract Purpose: Fascin, an actin bundling protein, induces membrane protrusions and increased cell motility in various transformed cells. The expression of fascin in epithelial neoplasms has been described only recently, and the role of fascin in esophageal squamous cell carcinoma (ESCC) is still unknown. Experimental Design: Paraffin sections of 200 patients with ESCC were immunohistochemically investigated. The expression levels of fascin mRNA in 20 ESCC tissues were compared with that in corresponding normal esophageal epithelium by semiquantitative reverse transcription-PCR. We also examined fascin protein expression in 33 ESCC cell lines. The role of fascin in cell motility and invasiveness in ESCC cells was assessed by the vector-based small interfering RNA. Results: In immunohistochemical study, the intensity of fascin expression was usually increased in the tumor compared with that in normal epithelium. Fascin overexpression was significantly associated with a poor prognosis (immunoreactive rate, P = 0.033; immunoreactive intensity, P = 0.031). The fascin immunoreactive rate was associated with extent of the tumor (P = 0.002) and lymph node metastasis (P = 0.003). Multivariate analysis showed that fascin expression intensity was an independent prognostic factor, but the immunoreactive rate was not. In addition, up-regulation of fascin mRNA was found in 60% (12 of 20) of patients. In vitro study revealed that all 33 ESCC cell lines expressed fascin protein at a certain level. KYSE170, one of the fascin-overexpressed cells, decreased its motile and invasive properties after down-regulation of fascin expression. Conclusion: Our findings suggest that fascin overexpression may play an important role in the progression of ESCC.
THE INFLUENCE OF LECITHIN AND CHOLESTERIN UPON THE GROWTH OF TUMORS
Authors: T. Brailsford Robertson, Theodore C. Burnett
Journal: The Journal of Experimental Medicine (1913)

1. Cholesterin, whether suspended in dilute alcohol or in sodium oleate solution, when injected directly into tumors causes a marked acceleration both of the primary and of the metastatic growth. 2. The acceleration of the growth of the primary tumor by cholesterin is most evident in the premetastatic stage. 3. Lecithin, when injected in the form of an aqueous emulsion directly into tumors, diminishes the tendency to form metastases, retards the metastatic growth when it does occur, and in some instances also retards the primary growth. 4. The retardation due to lecithin is most evident in the metastatic stage. 5. Simultaneous injection of M/6 strontium chloride solution into the tumors does not appreciably affect the action of the lecithin.
Gene Immunotherapy of Chronic Lymphocytic Leukemia: A Phase I Study of Intranodally Injected Adenovirus Expressing a Chimeric CD154 Molecule
Authors: Januario E. Castro, Johanna Melo-Cardenas, Mauricio Urquiza, Juan S. Barajas-Gamboa, Ramin S. Pakbaz, Thomas J. Kipps
Journal: Cancer Research (2012)

Abstract New therapies for chronic lymphocytic leukemia (CLL) are needed, particularly those that can eradicate residual disease and elicit anti-CLL immune responses. CD40 ligation on CLL cells, which can be achieved using adenovirus encoding chimeric CD154 (Ad-ISF35), enhances their ability to function as antigen-presenting cells and increases their sensitivity to clearance by immune-effector mechanisms. In this study, we report the results of a first-in-man phase I trial of intranodal direct injection (IDI) of Ad-ISF35 in patients with CLL to evaluate toxicity, safety, and tolerability. Fifteen patients received a single IDI of 1 × 1010 to 33 × 1010 Ad-ISF35 viral particles (vp), with a defined maximum tolerated dose as 1 × 1011 vp. Although the most common adverse events were transient grade 1 to 2 pain at the injection site and flu-like symptoms following IDI, some patients receiving the highest dose had transient, asymptomatic grade 3 to 4 hypophosphatemia, neutropenia, or transaminitis. Increased expression of death receptor, immune costimulatory molecules, and Ad-ISF35 vector DNA was detected in circulating CLL cells. Notably, we also observed preliminary clinical responses, including reductions in leukemia cell counts, lymphadenopathy, and splenomegaly. Six patients did not require additional therapy for more than 6 months, and three achieved a partial remission. In conclusion, Ad-ISF35 IDI was safely delivered in patients with CLLs and induced systemic biologic and clinical responses. These results provide the rationale for phase II studies in CLLs, lymphomas, and CD40-expressing solid tumors. Cancer Res; 72(12); 2937–48. ©2012 AACR.
The serum levels of sE-selectin are increased in patients with bullous pemphigoid or pemphigus vulgaris. Correlation with the number of skin lesions and recovery after corsticosteroid therapy
Authors: L. D'AURIA, P.CORDIALI FEI, M. PIETRAVALLE, C. FERRARO, A. MASTROIANNI, C. BONIFATI, B. GIACALONE, F. AMEGLIO
Journal: British Journal of Dermatology (1997)

Soluble E (sE)-selectin represents the soluble isoform of cellular E-selectin, an adhesion molecule synthesized only by endothelial cells. As a consequence, it may be considered a marker of endothelial activity. The aim of this study was therefore to evaluate the serum levels of sE-selectin in nine patients affected with pemphigus vulgaris (PV) and in 15 patients with bullous pemphigold (BP). Higher amounts of sE-selectin, median 40.3 ng/mL, range 30-109.6 were found in the patients when compared with 20 healthy individuals, median 28.5 ng/mL, range 6.4-48; P < 0.01, matched for sex and age. These levels were also significantly correlated with the number of detectable lesions (r = 0.63, P < 0.001) when the patient data were considered at the time of the first observation. Thirteen subjects were followed over time for a maximum of 3 months (from three to seven observations). During therapy, the number of lesions and the serum sE-selectin values decreased concomitantly. Differently from sE-selectin, the serum soluble intercellular adhesion molecule-1 (sICAM-1) values were not significantly different in the patients from the controls and showed no correlation with the serum sE-selectin concentrations or with the number of lesions. The data presented point to the possible use of sE-selectin determinations as a non-specific follow-up marker, suitable to gauge disease intensity over time and emphasize that endothelial activation is present in BP as well as in PV.
Positron Emission Tomography in Combination With Sentinel Node Biopsy Reduces the Rate of Elective Neck Dissections in the Treatment of Oral and Oropharyngeal Cancer
Authors: Adorján F. Kovács, Natascha Döbert, Jochen Gaa, Christian Menzel, Klaus Bitter
Journal: Journal of Clinical Oncology (2004)

To assess the impact of a diagnostic ladder including [(18)F]fluorodeoxyglucose positron emission tomography (PET) and lymphoscintigraphy guided sentinel node biopsy (LS/SNB) on neck treatment in patients with oral and oropharyngeal squamous cell carcinoma (OOSCC).Prospectively, 62 patients with resectable T1-3 OOSCC underwent computed tomography (CT) and PET. Patients without neck uptake in PET were defined as cN0 and were accrued for LS/SNB. Results were correlated with histopathology. The traditional guidelines according to CT findings were compared to the actual regimen and the outcome.Sensitivity, specificity, validity, and positive and negative predictive value of PET versus CT were 72% v 89%, 82% v 77%, 79% v 80.5%, 62% v 61.5%, and 88% v 94.5% (not significant). Thirty-eight PET negative patients underwent LS/SNB. Sentinel lymph nodes were found in all 38 patients. Five patients had positive nodes (PET false-negatives) and underwent neck dissection (ND). Fifty-one neck sides in 36 patients who were CT-negative would have been treated with selective ND according to the guidelines, and at least 45 neck sides would have had to undergo extensive ND because of positive CT findings (96 of 124 neck sides). In contrast, PET in combination with LS/SNB spared 59 neck sides, and 41 of 124 neck sides actually underwent ND as a result of PET staging, LS/SNB, and intraoperative decision. After a median follow-up of 35 months, two patients (both cN+ve and pN+ve) suffered from neck relapses.Diagnostics using PET in combination with LS/SNB considerably reduced the number of extensive ND in OOSCC as compared to CT without locoregional hazard.
Induction of Early Post-Transplant Graft-versus-Leukemia Effects Using Intentionally Mismatched Donor Lymphocytes and Elimination of Alloantigen-Primed Donor Lymphocytes for Prevention of Graft-versus-Host Disease
Authors: Iris Yung, Lola Weiss, Ali Abdul-Hai, Judith Kasir, Shoshana Reich, Shimon Slavin
Journal: Cancer Research (2005)

Graft-versus-leukemia (GVL) effects can be induced in tolerant mixed chimeras prepared with nonmyeloablative conditioning. GVL effects can be amplified by post-grafting donor lymphocyte infusion (DLI). Unfortunately, DLI is frequently associated with graft-versus-host disease (GVHD). We investigated the feasibility of induction of potent GVL effects by DLI using intentionally mismatched lymphocytes followed by elimination of alloreactive donor T cells by cyclophosphamide for prevention of lethal GVHD following induction of very short yet most potent GVL effects. Mice inoculated with B-cell leukemia (BCL1) and mismatched donor lymphocytes were treated 2 weeks later with low-dose or high-dose cyclophosphamide. All mice receiving cyclophosphamide 2 weeks after DLI survived GVHD, and no residual disease was detected by PCR; all control mice receiving DLI alone died of GVHD. Analysis of host (female) and donor (male) DNA showed that cyclophosphamide treatment eradicated most alloreactive donor cells, yet mixed chimerism was converted to full donor chimerism following transient self-limited GVHD. Our working hypothesis suggests that short-term yet effective and safe adoptive immunotherapy of leukemia may be accomplished early post-transplantation using alloreactive donor lymphocytes, with prevention of GVHD by elimination of GVL effector cells.
Identification and characterization of VEGF-A–responsive neutrophils expressing CD49d, VEGFR1, and CXCR4 in mice and humans
Authors: Sara Massena, Gustaf Christoffersson, Evelina Vågesjö, Cédric Seignez, Karin Gustafsson, François Binet, Carmen Herrera Hidalgo, Antoine Giraud, Jalal Lomei, Simone Weström, Masabumi Shibuya, Lena Claesson-Welsh, Pär Gerwins, Michael Welsh, Johan Kreuger, Mia Phillipson
Journal: Blood (2015)
Koebnerizing sclerodermatous graft-versus-host disease caused by donor lymphocyte infusion and interferon-<i>α</i>
Authors: J.M.L. White, S. Devereux, A. Pagliuca, J.R. Salisbury, A.W.P. Du Vivier, D. Creamer
Journal: British Journal of Dermatology (2006)

Graft-versus-host disease (GvHD) is a common sequel to allogeneic bone marrow transplants, which may be accompanied by desirable graft-versus-tumour effects. Sclerodermatous GvHD is a rare subtype that is very difficult to treat. We report the first case of sclerodermatous GvHD as part of the Koebner phenomenon. We propose that donor lymphocyte infusion and interferon-alpha were involved in the pathogenesis of this case.
Phase I Trial of Polifeprosan 20 With Carmustine Implant Plus Continuous Infusion of Intravenous <i>O</i><sup>6</sup>-Benzylguanine in Adults With Recurrent Malignant Glioma: New Approaches to Brain Tumor Therapy CNS Consortium Trial
Authors: Jon Weingart, Stuart A. Grossman, Kathryn A. Carson, Joy D. Fisher, Shannon M. Delaney, Mark L. Rosenblum, Alessandro Olivi, Kevin Judy, Stephen B. Tatter, M. Eileen Dolan
Journal: Journal of Clinical Oncology (2007)

Purpose This phase I trial was designed to (1) establish the dose of O 6 -benzylguanine (O 6 -BG) administered intravenously as a continuous infusion that suppresses O 6 -alkylguanine-DNA alkyltransferase (AGT) levels in brain tumors, (2) evaluate the safety of extending continuous-infusion O 6 -BG at the optimal dose with intracranially implanted carmustine wafers, and (3) measure the pharmacokinetics of O 6 -BG and its metabolite. Patients and Methods The first patient cohort (group A) received 120 mg/m 2 of O 6 -BG over 1 hour followed by a continuous infusion for 2 days at escalating doses presurgery. Tumor samples were evaluated for AGT levels. The continuous-infusion dose that resulted in undetectable AGT levels in 11 or more of 14 patients was used in the second patient cohort. Group B received the optimal dose of O 6 -BG for 2, 4, 7, or 14 days after surgical implantation of the carmustine wafers. The study end point was dose-limiting toxicity (DLT). Results Thirty-eight patients were accrued. In group A, 12 of 13 patients had AGT activity levels of less than 10 fmol/mg protein with a continuous-infusion O 6 -BG dose of 30 mg/m 2 /d. Group B patients were enrolled onto 2-, 4-, 7-, and 14-day continuous-infusion cohorts. One DLT of grade 3 elevation in ALT was seen. Other non-DLTs included ataxia and headache. For up to 14 days, steady-state levels of O 6 -BG were 0.1 to 0.4 μmol/L, and levels for O 6 -benzyl-8-oxoguanine were 0.7 to 1.3 μmol/L. Conclusion Systemically administered O 6 -BG can be coadministered with intracranially implanted carmustine wafers, without added toxicity. Future trials are required to determine if the inhibition of tumor AGT levels results in increased efficacy.
IVERMECTIN AND PROTHROMBIN TIME
Authors: FrankO. Richards, MaryseB. Mcneeley, RalphT. Bryan, MarkL. Eberhard, DavidF. Mcneeley, PatrickJ. Lammie, HarrisonC. Spencer, MichelC. Pacque, Beatriz Munoz, AlbertT. White, P.N. Williams, BruceM. Greene, HughR. Taylor
Journal: The Lancet (1989)