tbuckley/cabot-search huggingface dataset:
Bromodeoxyuridine Alternating With Radiation for Advanced Uterine Cervix Cancer: A Phase I and Drug Incorporation Study
Authors: Avraham Eisbruch, John M. Robertson, Carolyn M. Johnston, Joseph Tworek, Kevin R. Reynolds, James A. Roberts, Theodore S. Lawrence
Journal: Journal of Clinical Oncology (1999)

Preclinical studies show a significant increase in the ratio of the radiosensitizer bromodeoxyuridine (BUdR) in tumors versus the intestinal mucosa during the drug elimination period, compared with the ratio during drug infusion. We constructed a phase I study in patients with locally advanced cervix cancer, using alternating cycles of BUdR and radiation therapy (RT).Eighteen patients with stage IIB to IVA cervix cancer participated. A treatment cycle consisted of a 4-day BUdR infusion followed by a week of pelvic RT, 15 Gy twice daily in 1.5-Gy fractions. After three cycles, additional BUdR was infused, followed by brachytherapy. The fraction of thymidine replaced by BUdR and the fraction of cells incorporating BUdR were determined in rectal mucosa and tumor biopsies at the end of the first BUdR infusion (day 5), at the middle of the first RT week (day 10), and at the time of brachytherapy.Dose-limiting toxicity was observed in one of 16 patients receiving 1,000 mg/m2/d x 4 days and in both patients receiving 1,333 mg/m2/d x 4 days each cycle. After a median follow-up of 39 months, 12 patients (66%) were free of pelvic disease and nine (50%) were alive and disease free. The ratio of tumor to rectum BUdR incorporation averaged 1.5 to 1.8 and did not differ significantly between day 5 and day 10. A trend toward reduced ratio was observed at brachytherapy. Drug-containing cells in rectal biopsies migrated from the crypts to the mucosal surface.In this schedule, 1,000 mg/m2/d is the maximum-tolerated dose of BUdR. BUdR incorporation levels in tumors were consistent with clinically significant radiosensitization. The migration of BUdR-containing rectal mucosa cells from the crypts to the surface at the time of RT suggests that this regimen may offer a relative sparing of the mucosa from radiosensitization.
Pulmonary hypertension in a district general hospital
Authors: Yan-Pin Lin, Dominic Davenport, Natasha Shrikrishna, Abigail Cole, Harpreet Ranu
Journal: European Respiratory Journal (2012)

Introduction  There is an increasing awareness to identify patients with pulmonary hypertension (PH). Classification of the underlying cause defines further management and referral to specialist centres.   Aim  To assess the burden of PH at St Richard9s Hospital, which serves a population of 2309000.   Methods  All departmental transthoracic echocardiographs (TTEs) between 1st January 2009 and 30th June 2009 were reviewed using ERS suggested criteria to identify patients with possible PH and likely PH. Further investigations were reviewed to identify the underlying aetiology in those with likely PH.   Results   A total of 2038 TTEs were reviewed. 93 (5%) had likely PH with a pulmonary artery systolic pressure (PASP) of >50mmHg. 624 (31%) had possible PH with either the presence of additional echocardiographic variables suggestive of PH or a PASP 37-50mmHg.  Of those with likely PH, 48% were male and 52% were female. The median age was 85 years (range 52-98). The overall mortality rate was 39% at 1 year and 58% at 2 years. Only 13% had right heart catheterisation locally.   Conclusions  PH is associated with a poor prognosis. The most common cause in our population was LH disease. However in patients without LH disease, less than a quarter had further investigations to exclude potentially curable CTEPH.
Respiratory status of the female workers engaged in the manual brick manufacturing industries of the unorganized sectors of India
Authors: Moumita Sett, Subhashis Sahu
Journal: European Respiratory Journal (2013)

Introduction:  Manual brick making units of the unorganized sectors of India employ workers from low socio-economic class and are engaged for a period of eight months (except the monsoons) on contract basis. The key occupational health hazards are associated with dust, from mud, sand, coal dust (used as fuel to bake the bricks) and chimney smoke.   Aims and Objective:  The aim is to investigate the respiratory status of the female brick field workers exposed to the field dust for the working period.  Methods:  Forced Vital Capacity (FVC), Forced Expiratory Volume in one second (FEV 1 ) and as a percentage of FVC (FEV 1 %); forced expiratory flows of four intervals (FEF 25% ,  50% ,  75%;   25-75% ) and maximum voluntary ventilation (MVV) were recorded using a computerized Spirometer (Maestros Mediline Systems Limited, India) and Peak Expiratory Flow Rate (PEFR) by Wright’s peak flow meter (Medicare Equipments, India). The test group and the control group consisted of 216 female workers engaged in manual brick making units and 209 female students of the same age group respectively.   Results:  Pulmonary Function values significantly differed (p Conclusion:  All the subjects were young at age, so alteration in the pulmonary functions in the test group could be attributed to the irritation of the upper respiratory mucosa causing hypertrophy of mucosal cells and formation of mucous plugs resulting in obstruction of exhaled air, caused due to exposure of the dusty environment.
Dynamic changes of serum sTREM-1 and its gene polymorphisms associated with sepsis prognosis
Authors: Longxiang Su, Lixin Xie, Zhaoxu Jiang, Xin Zhang, Dan Feng
Journal: European Respiratory Journal (2012)

Introduction: More and more studies have confirmed that sepsis is an acquired genetic disease.  Objectives :To explore how sepsis prognosis is associated with the dynamic changes of serum sTREM-1, as well as with gene polymorphisms.  Methods : 80 subjects were selected from inpatients in the RICU,SICU,and EICU. 80 healthy volunteers acted as control. To detect the dynamic changes of serum sTREM-1 over a 14-day observation, ELISA was performed. Four exons of TREM-1 gene were sequenced on ABI3730.  Results : The nonsurvivors9sTREM-1 levels remain significantly higher than the survivors9 over period of 14 days( P ). The curves show that the nonsurvivors register higher sTREM-1 levels at the initial stage, which steadily go up with the passage of time. In contrast, the survivors9sTREM-1 levels are on the decline all the time. Three TREM-1 SNPs (rs144672509,rs2234237 and rs2234246) are detected from four exons. In three inherited models, rs2234237 is clearly related to sepsis prognosis( P ). The log-rank test shows that patients with the rs2234237 genetic variation stand a greater probability of a 28-day death( P ). However, no relationship is spotted between TREM-1 gene polymorphism and the dynamic concentrations of serum sTREM-1. Logistic regression analysis shows that sTREM-1,APACHE II score,and TREM-1 rs2234237 genetic variation are risk factors affecting the prognosis.  Conclusions : Dynamic changes in serum sTREM-1 may be more accurate and valuable for sepsis monitoring and for dynamic assessments of prognosis. It is proved that TREM-1 rs2234237 polymorphism is associated with high 28-day mortality among sepsis patients, constituting a risk factor affecting prognosis.
A Parallel Analysis of Cancer Mortality Among Atomic Bomb Survivors and Patients With Ankylosing Spondylitis Given X-Ray Therapy&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: S C Darby, E Nakashima, H Kato
Journal: JNCI Journal of the National Cancer Institute (1985)

Radiation-induced cancer mortality rates among atomic bomb survivors with doses of at least 100 rad and patients with ankylosing spondylitis given X-ray therapy have been compared for the first time. The estimated average mean bone marrow dose for the spondylitics is more than twice that for atomic bomb survivors, and yet spondylitics experienced only half the risk of radiation-induced leukemia of atomic bomb survivors. For sites that were heavily irradiated in the spondylitics, provisional estimates indicate comparable doses in the two studies, and similar levels of cancer risk were observed. For these sites, when information from the studies was combined, there were statistically significant excesses for cancers of the esophagus, stomach, lung, and ovaries, multiple myeloma, other lymphomas, and tumors of the spinal cord and nerves. Very high relative risks (RR's) for tumors of the spinal cord and nerves were observed in both studies. For sites that were lightly irradiated in the spondylitics, in addition to previously documented sites, there was a statistically significant excess of cancers of the liver and gallbladder among atomic bomb survivors. A previous subdivision of cancer sites into radiosensitive and other tissues was not supported by the atomic bomb survivor data. Changes in the rates of radiation-induced cancers with age at exposure and time since exposure were studied and compared with the use of generalized linear modeling of the RR's and also by examination of the excess mortality rates. The level of agreement between the two studies was high; provided it is accepted that the reduced level of leukemia risk in the spondylitics is due to cell sterilization, no inconsistencies were found. For a group of solid tumors selected from heavily irradiated sites in the spondylitics, excess risk increased with both age at exposure and time since exposure and RR decreased with age at exposure, but it did not vary with time since exposure between about 5 and at least 30 years following exposure. The finding of a constant RR with time since exposure did not extend to all remaining neoplasms other than leukemia, because the RR for these neoplasms increased with time since exposure in atomic bomb survivors.
High-dose ifosfamide with mesna uroprotection: a phase I study.
Authors: A D Elias, J P Eder, T Shea, C B Begg, E Frei, K H Antman
Journal: Journal of Clinical Oncology (1990)

Phase II trials of ifosfamide have been performed with standard doses of 5 to 8 g/m2/course. In this phase I study, 29 patients were treated with a 4-day continuous infusion ifosfamide to determine the maximum-tolerated dose and the nonhematologic dose-limiting toxicity. Autologous bone marrow support was to have been used for the subsequent dose level if granulocytes were more than 500/microL for more than 14 days in two of two to five patients at a given dose level. Doses were escalated from 8 to 18 g/m2 ifosfamide. Mesna was given at an equivalent dose by continuous infusion for 5 days. At the 18 g/m2 dose level, dose-limiting renal insufficiency and a median of 11 days (range, 8 to 18 days) of granulocytopenia (less than 500/microL) were observed. Thus, autologous bone marrow reinfusion ws not used. The duration of myelosuppression, the frequency and severity of mucositis, and renal tubular acidosis were all dose-dependent. Mild to moderate CNS toxicity also appeared to be related to dose; however, severe CNS toxicity (transient confusion, hallucinations, and somnolence) was observed sporadically at both low- and high-dose levels. Transient hematuria (greater than 50 red blood cells [RBCs]/high power field) occurred once but did not affect treatment. There were nine responses (two complete) in 27 heavily pretreated assessable patients including seven responses in 20 patients with advanced refractory sarcoma. Ifosfamide with mesna uroprotection can undergo considerable dose escalation over the usual prescribed doses before nonhematologic dose-limiting toxicity is encountered. Ifosfamide has broad cytotoxicity against solid tumors and may prove to be an important addition to high-dose combination chemotherapy regimens.
Four DNA methylation biomarkers in biliary brush samples accurately identify the presence of cholangiocarcinoma
Authors: Kim Andresen, Kirsten Muri Boberg, Hege Marie Vedeld, Hilde Honne, Peter Jebsen, Merete Hektoen, Christopher A. Wadsworth, Ole Petter Clausen, Knut E.A. Lundin, Vemund Paulsen, Aksel Foss, Øystein Mathisen, Lars Aabakken, Erik Schrumpf, Ragnhild A. Lothe, Guro E. Lind
Journal: Hepatology (2015)

Early detection of the highly aggressive malignancy cholangiocarcinoma (CCA) remains a challenge but has the potential to render the tumor curable by surgical removal. This study evaluates a biomarker panel for the diagnosis of CCA by DNA methylation analyses of biliary brush samples. The methylation status of 13 candidate genes ( CDO1 , CNRIP1 , DCLK1 , FBN1 , INA , MAL , SEPT9 , SFRP1 , SNCA , SPG20 , TMEFF2 , VIM , and ZSCAN18 ) was investigated in 93 tissue samples (39 CCAs and 54 nonmalignant controls) using quantitative methylation‐specific polymerase chain reaction. The 13 genes were further analyzed in a test series of biliary brush samples (15 CCAs and 20 nonmalignant primary sclerosing cholangitis controls), and the methylation status of the four best performing markers was validated (34 CCAs and 34 primary sclerosing cholangitis controls). Receiver operating characteristic curve analyses were used to evaluate the performance of individual biomarkers and the combination of biomarkers. The 13 candidate genes displayed a methylation frequency of 26%‐82% in tissue samples. The four best‐performing genes ( CDO1 , CNRIP1 , SEPT9 , and VIM ) displayed individual methylation frequencies of 45%‐77% in biliary brushes from CCA patients. Across the test and validation biliary brush series, this four‐gene biomarker panel achieved a sensitivity of 85% and a specificity of 98%, with an area under the receiver operating characteristic curve of 0.944. Conclusion : We report a straightforward biomarker assay with high sensitivity and specificity for CCA, outperforming standard brush cytology, and suggest that the biomarker panel, potentially in combination with cytological evaluation, may improve CCA detection, particularly among primary sclerosing cholangitis patients. (H epatology 2015;61:1651–1659)
Rash on the arms and legs:
Authors: Melvyn Jones, Paul de Keyser
Journal: BMJ (2015)

An 11 year old girl presented to her general practitioner with painful skin lesions on her arms (fig A⇓) and legs (fig B). She had a three week history of an upper respiratory illness and had been started on amoxicillin for presumed lower respiratory tract infection. Three days after starting treatment, she re-attended with a rash on her arms and legs; her parents were worried that it was caused by a drug allergy. Apart …
Psychiatry and the Law: Changing the System Through Changing the Training
Authors: JACK ZUSMAN, WILLIAM A. CARNAHAN
Journal: American Journal of Psychiatry (1974)

The development of a more useful relationship between psychiatry and the law depends upon mutual understanding and solution of common problems. Present training in law for psychiatrists emphasizes acceptance of the status quo. The authors propose a new training approach involving both disciplines that would emphasize interactional problems and practical methods for bringing about change, thus improving the present system.
Immunosuppression in Mice After Inoculation With 334C, a Murine Lymphatic Leukemia-Inducing Virus 2
Authors: Paul J. Schenk, Rita F. Buffett
Journal: JNCI Journal of the National Cancer Institute (1977)

334C murine leukemia virus, which induces a high incidence of lymphatic leukemias (80-90%) in susceptible mice following a long latency period, was found to cause a severe in vivo suppression of direct plaque-forming cells from the spleen, following antigenic stimulation with sheep red blood cells. Neonatally infected inbred BALB/c and outbred Ha/ICR Swiss mice, which develop a sustained viremia, were highly susceptible to the immunosuppressive effect of this virus as early as 1 week after virus infection, long before any detectable histologic evidence of leukemia development. Ha/ICR Swiss mice, which are highly resistant to the leukemogenic potential of this virus following infection in adult life, were highly resistant to its immunosuppressive action; only a moderate and transient suppression, without viremia, occurred 2 weeks after virus infection. In marked contrast, BALB/c mice were highly susceptible to the immunosuppressive action of 334C murine leukemia virus following infection in adult life; a severe and sustained suppression was observed as early as 1 week after virus infection and was followed by a sustained viremia, beginning at 2 weeks, with a 55-60% incidence of leukemia observed over a period of 1 year. Infectious virus was essential to produce theimmunosuppressive effect; heat-inactivated (56 degrees C/30 min) and attenuated (4 degrees C/4 1/2 mo) virus preparations were ineffective. The plaque-forming response of spleen cells from lethally irradiated syngeneic adult BALB/c mice was markedly suppressed following reconstitution with thymus-dependent (T) or thymus-independent (B) cells from the thymus and bone marrow, respectively, of virus-infected mice, in combination with each other, or with the appropriate cell populations from normal mice.
Mouse Strain GR: A Comparative Study of Its Naturally Occurring Mammary Tumor Virus
Authors: George Vlahakis
Journal: JNCI Journal of the National Cancer Institute (1977)

Journal Article Mouse Strain GR: A Comparative Study of Its Naturally Occurring Mammary Tumor Virus Get access George Vlahakis George Vlahakis Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 59, Issue 2, August 1977, Pages 447–449, https://doi.org/10.1093/jnci/59.2.447 Published: 01 August 1977 Article history Received: 20 December 1976 Accepted: 11 March 1977 Published: 01 August 1977
Doxorubicin and Paclitaxel Versus Fluorouracil, Doxorubicin, and Cyclophosphamide as First-Line Therapy for Women With Metastatic Breast Cancer: Final Results of a Randomized Phase III Multicenter Trial
Authors: Jacek Jassem, Tadeusz Pieńkowski, Anna Płuzańska, Svetislav Jelic, Vera Gorbunova, Zrinka Mrsic-Krmpotic, Juris Berzins, Tomas Nagykalnai, Nelly Wigler, Josette Renard, Stephane Munier, Catherine Weil
Journal: Journal of Clinical Oncology (2001)

PURPOSE: This phase III trial compared the efficacy and safety of doxorubicin and paclitaxel (AT) to 5-fluorouracil, doxorubicin, and cyclophosphamide (FAC) as first-line therapy for women with metastatic breast cancer. PATIENTS AND METHODS: A total of 267 women with metastatic breast cancer were randomized to receive either AT (doxorubicin 50 mg/m 2 followed 24 hours later by paclitaxel 220 mg/m 2 ) or FAC (5-fluorouracil 500 mg/m 2 , doxorubicin 50 mg/m 2 , cyclophosphamide 500 mg/m 2 ), each administered every 3 weeks for up to eight cycles. Patients had to have measurable disease and an Eastern Cooperative Oncology Group performance status of 0 to 2. Only one prior non–anthracycline, nontaxane-containing adjuvant chemotherapy regimen was allowed. RESULTS: Overall response rates for patients randomized to AT and FAC were 68% and 55%, respectively (P = .032). Median time to progression and overall survival were significantly longer for AT compared with FAC (time to progression 8.3 months v 6.2 months [P = .034]; overall survival 23.3 months v 18.3 months [P = .013]). Therapy was generally well-tolerated (median of eight cycles delivered in each arm). Grade 3 or 4 neutropenia was more common with AT than with FAC (89% v 65%; P &lt; .001); however, the incidence of fever and infection was low. Grade 3 or 4 arthralgia and myalgia, peripheral neuropathy, and diarrhea were more common with AT, whereas nausea and vomiting were more common with FAC. The incidence of cardiotoxicity was low in both arms. CONCLUSION: AT conferred a significant advantage in response rate, time to progression, and overall survival compared with FAC. Treatment was well-tolerated with no unexpected toxicities.
Sonoclot coagulation analysis of in-vitro haemodilution with resuscitation solutions
Authors: E V Brazil, T J Coats
Journal: Journal of the Royal Society of Medicine (2000)

The colloid and crystalloid solutions used for resuscitation should preferably be free from effects on coagulation. In 10 volunteers, the effects of haemodilution with various concentrations of 0.9% sodium chloride and 4% succinylated gelatin were assessed by Sonoclot analysis, which describes the whole coagulation process. Small and moderate haemodilution (up to 40%) with 0.9% sodium chloride promoted coagulation. Similar haemodilution with 4% succinylated gelatin impaired coagulation, and at 60% haemodilution coagulation was very poor. These findings need to be confirmed in vivo and their clinical relevance determined.
Dual inhibition of CDK4/Rb and PI3K/AKT/mTOR pathways by ON123300 induces synthetic lethality in mantle cell lymphomas
Authors: S K A Divakar, M V Ramana Reddy, S C Cosenza, S J Baker, D Perumal, A C Antonelli, J Brody, B Akula, S Parekh, E Premkumar Reddy
Journal: Leukemia (2015)
REPRODUCTION IN VITRO OF ENTAMŒBA TETRAGENA AND ENTAMŒBA COLI FROM THEIR CYSTS
Authors: Kazuyoshi Yoshida
Journal: The Journal of Experimental Medicine (1920)

1. The vegetative forms of amebae may be developed in vitro from the cysts. 2. The cysts of Entamoeba tetragena and Entamoeba coli each produce only a single vegetative individual. It has not been observed in vitro that a number of daughter amebae, corresponding to the number of nuclei present in the cyst, emerge from the mother cyst, as claimed by Casagrandi and Barbagallo, Schaudinn, and a number of other investigators. 3. The daughter nuclei in the cystic stage correspond to the gamete nuclei of other protozoa. The syngamic nuclear union in the case of these two amebae does not take place in the tetranuclear stage of the cyst, as claimed by Schaudinn and Wenyon, but during reproduction. 4. The process of autogamy of both amebae is not restricted to two nuclei; it may involve more than two, which unite to form a syncaryon. In the case of all other protozoa, autogamy is restricted to two nuclei. 5. In order to distinguish the two types of autogamy, one has been termed simple autogamy and the other polynuclear autogamy. The latter may again be classified according to the number of nuclei involved, as trinuclear and tetranuclear autogamy. 6. The majority of cysts treated for 5 minutes in a 2 per cent solution of hydrochloric acid survives. 7. It was possible to demonstrate in vitro the developmental cycle of Entamoeba tetragena. 8. No evidence of heterogamy has been observed in vitro in Entamoeba tetragena or Entamoeba coli. 9. The vegetative form of Entamoeba tetragena, at a certain stage of its life cycle in vitro, shortly after its formation, has not only one or two, but may have as many as three or four nuclei.
Abstract 17079: Tetrahydrobiopterin (NOS Cofactor) Treatment Improves Atrial Electrophysiology in Chronic Heart Failure.
Authors: Yoshinori Nishijima, Arun Sridhar, Ingrid M Bonilla, Murugesan Velayutham, Pedro Vargas-Pinto, Jay L Zweier, Sandor Gyorke, Arturo J Cardounel, Cynthia A Carnes
Journal: Circulation (2010)

Heart failure (HF) is a common antecedent to atrial fibrillation (AF). Atrial oxidative stress is known to contribute to the substrate for AF. We examined whether manipulating NOS activity by administration of NOS substrate (Arginine-ARG) and cofactor (tetrahydrobiopterin, BH4) altered HF-induced abnormalities in atrial electrophysiology.   Methods:  We used a 4 month model of tachypacing induced canine HF (n=12) to evaluate NOS (NOS) function in the left atrium, relative to a matched ARG-BH4 treated HF group (n=9, 6 week treatment), and a control group. Left atrial appendage myocytes were studied using perforated patch whole cell techniques to elicit action potentials (T=36 ± 0.5°C).   Results:  Final LV fractional shortening was 37 ± 0.8% in controls, 15.0 ± 1.9% in HF, and 17.7 ± 1.7% in ARG-BH 4  treated HF. HF reduced atrial [BH 4 ] (p 2 • − . EPR spectroscopy indicated that ARG-BH4 reduced HF-induced atrial oxidative stress (p   Conclusion:  These data suggest that modulation of atrial [BH4] and NOS activity may be antiarrhythmic during chronic heart failure.