tbuckley/cabot-search huggingface dataset:
Increased Levels of the FoxM1 Transcription Factor Accelerate Development and Progression of Prostate Carcinomas in both TRAMP and LADY Transgenic Mice
Authors: Tanya V. Kalin, I-Ching Wang, Timothy J. Ackerson, Michael L. Major, Carol J. Detrisac, Vladimir V. Kalinichenko, Alexander Lyubimov, Robert H. Costa
Journal: Cancer Research (2006)

Abstract The proliferation-specific Forkhead Box M1 (FoxM1 or FoxM1b) transcription factor is overexpressed in a number of aggressive human carcinomas. Mouse hepatocytes deficient in FoxM1 fail to proliferate and are highly resistant to developing carcinogen-induced liver tumors. We previously developed a transgenic (TG) mouse line in which the ubiquitous Rosa26 promoter was used to drive expression of the human FoxM1b cDNA transgene in all mouse cell types. To investigate the role of FoxM1b in prostate cancer progression, we bred Rosa26-FoxM1b mice with both TRAMP and LADY TG mouse models of prostate cancer. We show that increased expression of FoxM1b accelerated development, proliferation, and growth of prostatic tumors in both TRAMP and LADY double TG mice. Furthermore, development of prostate carcinomas in TRAMP/Rosa26-FoxM1b double TG mice required high levels of FoxM1 protein to overcome sustained expression of the alternative reading frame tumor suppressor, a potent inhibitor of FoxM1 transcriptional activity. Depletion of FoxM1 levels in prostate cancer cell lines PC-3, LNCaP, or DU-145 by small interfering RNA transfection caused significant reduction in proliferation and anchorage-independent growth on soft agar. This phenotype was associated with increased nuclear levels of the cyclin-dependent kinase inhibitor protein p27Kip1 and diminished expression of S-phase promoting cyclin A2 and M-phase promoting cyclin B1 proteins. Finally, we show that elevated levels of FoxM1 protein correlate with high proliferation rates in human prostate adenocarcinomas. Our results suggest that the FoxM1 transcription factor regulates development and proliferation of prostate tumors, and that FoxM1 is a novel target for prostate cancer treatment. Cancer Res 2006; 66(3): 1712-20
Pediatric Phase I Trials in Oncology: An Analysis of Study Conduct Efficiency
Authors: Debra P. Lee, Jeffrey M. Skolnik, Peter C. Adamson
Journal: Journal of Clinical Oncology (2005)

Purpose To determine the efficacy and safety of pediatric phase I oncology trials in the era of dose-intensive chemotherapy and to analyze how efficiently these trials are conducted. Methods Phase I pediatric oncology trials published from 1990 to 2004 and their corresponding adult phase I trials were reviewed. Dose escalation schemes using fixed 30% dose increments were studied to theoretically determine whether trials could be completed utilizing fewer patients and dose levels. Results Sixty-nine pediatric phase I oncology trials enrolling 1,973 patients were identified. The pediatric maximum-tolerated dose (MTD) was strongly correlated with the adult MTD (r = 0.97). For three-fourths of the trials, the pediatric and adult MTD differed by no more than 30%, and for more than 85% of the trials, the pediatric MTD was less than or equal to 1.6 times the adult MTD. The median number of dose levels studied was four (range, two to 13). The overall objective response rate was 9.6%, the likelihood of experiencing a dose-limiting toxicity was 24%, and toxic death rate was 0.5%. Conclusion Despite the strong correlation between the adult and pediatric MTDs, more than four dose levels were studied in 40% of trials. There appeared to be little value in exploring dose levels greater than 1.6 times the adult MTD. Limiting pediatric phase I trials to a maximum of four doses levels would significantly shorten the timeline for study conduct without compromising safety.
Antitumor effects of anti-CD40/CpG immunotherapy combined with gemcitabine or 5- fluorouracil chemotherapy in the B16 melanoma model
Authors: Alexander Rakhmilevich, Xiaoyi Qu, Mildred Felder, Zulmarie Perez Horta, Paul Sondel
Journal: Journal for ImmunoTherapy of Cancer (2013)

Meeting abstracts Our previous studies demonstrated that anti-CD40 mAb (anti-CD40) can synergize with CpG oligodeoxynucleotides (CpG) to mediate antitumor effects by activating myeloid cells, such as macrophages in tumor-bearing mice. Separate teams have shown that chemotherapy with gemcitabine (
A Double-Blind Comparison of Clonidine and Methyldopa in Hypertensive Patients.
Authors: William J. Mroczek
Journal: Annals of Internal Medicine (1972)

Meeting Abstracts1 May 1972A Double-Blind Comparison of Clonidine and Methyldopa in Hypertensive Patients.William J. Mroczek, M.D., Michael Davidov, M.D., Frank A. Finnerty Jr., M.D.William J. Mroczek, M.D.Search for more papers by this author, Michael Davidov, M.D.Search for more papers by this author, Frank A. Finnerty Jr., M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-76-5-875_2 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptThe relative efficacy of Clonidine and methyldopa, each combined with a diuretic, was studied in 41 outpatients with moderately severe or severe hypertension. The antihypertensive effect of each combination was compared with that of the diuretic alone. After a control period, all patients received chlorthalidone for 3 weeks. An antihypertensive drug was then added in a double-blind, randomized, crossover fashion. Either Clonidine hydrochloride, 0.45 mg, or methyldopa, 750 mg, was given daily in three divided oral doses. After 12 weeks, patients received the alternate antihypertensive for a similar period. Compared to base-line, all three treatments reduced the blood pressure to... This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Washington, D.C. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 May 1972Volume 76, Issue 5Page: 875-875KeywordsBlood pressureDiureticsDrugsHypertensionOutpatients Issue Published: 1 May 1972 PDF DownloadLoading ...
Potassium deficiency during treatment with Brinaldix K.
Authors: R T Taylor, M J Peaston
Journal: BMJ (1973)

fication on this point would be welcome, as well as how the actual trial tablets com- pare with the commercially available.Since comparative trials of different drugs are now more conmnon it seems important to report not only the relative merits of various drugs tested but also the absolute merits in terms of the variables used, as well as to pay close attention to all aspects of methodology.-Iam, etc.
Drug misusers in Lothian: changes in injecting habits 1988-90.
Authors: S Griffin, A Peters, M Reid
Journal: BMJ (1993)

sometimes unaware of the difficulties that general practitioners may face in obtaining the information required.Marinker et al have recommended the development of protocols for referral between general practitioners and consultants.5Some departments of child psychiatry now use standardised referral forms with specific questions on the attitude of the family to referral and involvement of other agencies.This study has shown that child psychiatrists have some special requirements for referral letters, but they are unlikely to obtain the desired information unless they educate general practi- tioners.I am indebted to Maurice Place for his support and advice at every stage of this project.
EFFECTIVENESS OF AGGRESSIVE HEART FAILURE MANAGEMENT DESPITE CARDIORENAL SYNDROME IN THE OUTPATIENT SETTING: SYMPTOM IMPROVEMENT AND PREVENTION OF READMISSION
Authors: Mridula Rai, Faisal Zaeem, Dalia Giedrimiene, Lynn O’Bara, Daniel Madison, Joseph Radojevic, Detlef Wencker
Journal: Journal of the American College of Cardiology (2010)
Clot retraction is mediated by factor XIII-dependent fibrin-αIIbβ3-myosin axis in platelet sphingomyelin-rich membrane rafts
Authors: Kohji Kasahara, Mizuho Kaneda, Toshiaki Miki, Kazuko Iida, Naoko Sekino-Suzuki, Ikuo Kawashima, Hidenori Suzuki, Motoyuki Shimonaka, Morio Arai, Yoshiko Ohno-Iwashita, Soichi Kojima, Mitsuhiro Abe, Toshihide Kobayashi, Toshiro Okazaki, Masayoshi Souri, Akitada Ichinose, Naomasa Yamamoto
Journal: Blood (2013)
"Would you like to see the wound?"
Authors: Gillian Stowell
Journal: BMJ (2008)

Patients have often asked me as a general practitioner whether I’d like to see their wound. I usually decline, believing that there is little need to see wounds unless they cause problems. But have I been missing the point?

Until January this year I had no visible scars—a pristine body with nothing added or taken away. I have always had an aversion to body piercings, tattoos, and cosmetic surgery and struggle to comprehend how some people seem to welcome surgical invasion of their bodies.

On learning I would need major abdominal surgery and a temporary stoma to treat bowel cancer I was horrified by many things, not least of them the certainty of huge scars. I became acutely aware of how my identity was embodied by a trim figure, a flat belly (even after three pregnancies), and freedom to wear whatever I liked. My passions in life relied on a healthy physique. I did not want to surrender this body to the knife.

There were of course more serious fears: premature …
Effect of Puberty on the Pharmacodynamic and Pharmacokinetic Properties of Insulin Pump Therapy in Youth With Type 1 Diabetes
Authors: Karena L. Swan, Stuart A. Weinzimer, James D. Dziura, Garry M. Steil, Gayane R. Voskanyan, Amy T. Steffen, Melody L. Martin, William V. Tamborlane
Journal: Diabetes Care (2007)

Development of biosynthetic techniques for production of human insulin enabled the pharmaceutical industry to produce rapid-acting insulin analogs that are more rapidly absorbed following subcutaneous injection than regular insulin (1–5). These analogs may be especially useful in treating adolescents with type 1 diabetes who require large premeal bolus doses due to the peripheral insulin resistance of puberty (6). When used in large doses, the peak action of regular insulin is delayed (to 3–4 h) and the duration markedly prolonged (to 8 h or more) (7). The pharmacokinetic and pharmacodynamic properties of the rapid-acting insulin analogs have not been well studied in pediatric patients or when administered by continuous subcutaneous insulin infusion. This study was undertaken to examine the effect of puberty on the pharmacokinetics and -dynamics of aspart insulin in pump-treated patients.

A total of 21 healthy nonobese subjects with type 1 diabetes ranging in age from 8 to 17 years were studied. All were receiving continuous subcutaneous insulin infusion therapy and had A1C levels between 6.5 and 8.9%. The Yale Human Investigation Committee approved the study; written informed consent was obtained from the parents and assent from the subjects. Subjects were divided into two groups: prepubertal (Tanner stage I, n = 9) and pubertal (Tanner stages II–V, n = 12). The two groups did not differ significantly in A1C levels, duration of diabetes, and BMI percentiles. Daily insulin doses were available in …
Scintigraphic Detection of Pulmonary Embolization of Esophageal Variceal Sclerosant
Authors: E. G. DePuey, W. O. Richards, W. J. Millikan, J. M. Henderson
Journal: Endoscopy (1988)

Intravariceal injection of a sodium morrhuate sclerosant solution, an effective therapy for bleeding esophageal varices, is complicated occasionally by fever and pneumonia. To determine if embolization of sclerosant to or through the pulmonary circulation occurs, chest scintigrams were performed following intravariceal injection of 1-3 mCi 99m-Tc-MAA mixed with 5-20cc of sclerosant in 18 patients undergoing a total of 25 sclerotherapy sessions. Sclerosant embolization was documented in 15/25 procedures (60%). Tracer localization in esophageal veins cephalad to the injection site (gastroesophageal junction) occurred in 2 studies. Atelactasis, effusion, or infiltrate on chest x-ray occurred after 6/25 procedures. Post-sclerosis fever (greater than 99.5 degrees F) occurred in 5/15 (33%) with embolization and in 1/10 (10%) without. However, neither x-ray abnormalities nor fever were positively correlated with sclerosant embolization. We conclude that embolization of sclerosant to the pulmonary arterial circulation occurs frequently. Chest radiographs may be negative despite significant embolization. We conclude that embolization of sclerosant to the pulmonary arterial circulation occurs frequently. Chest radiographs may be negative despite significant embolization.
Early rise in exhaled nitric oxide and mast cell activation in repeated low-dose allergen challenge
Authors: E. Ihre
Journal: European Respiratory Journal (2006)

Repeated low-dose allergen inhalation challenge mimics natural allergen exposure, providing a model for early mechanisms in the triggering of asthma. The current authors performed a controlled study to evaluate the time course of changes in exhaled nitric oxide fraction (<i>F</i><sub>e,NO</sub>) and urinary biomarkers of airway inflammation. Eight subjects with mild allergic asthma completed two 7-day repeated low-dose challenge periods, with diluent and allergen, respectively. Subjects were symptom free at inclusion and were investigated when not exposed to specific allergen. Pulmonary function and symptoms were followed, and <i>F</i><sub>e,NO</sub> and urinary mediators were correlated to changes in airway responsiveness to histamine and adenosine. Despite no change in pulmonary function (forced expiratory volume in one second mean±sem fall 0.3±0.7 <i>versus</i> 0.6±1.0%, for diluent and allergen, respectively) and no asthma symptoms, repeated allergen exposure, in contrast to diluent, caused significant increases in histamine responsiveness (2.3 doubling doses), an early and gradual increase in <i>F</i><sub>e,NO</sub> (up to a doubling from baseline) and a small increase in the mast cell marker 9α11β-prostaglandin F<sub>2</sub> after adenosine challenge. In conclusion, serial measurements of exhaled nitric oxide fraction have the potential to provide a very sensitive strategy for early detection of emerging airway inflammation and subsequent changes in airway hyperresponsiveness to histamine.
Mechanism of Digitalis Action on the Heart
Authors: Jan Koch-Weser
Journal: New England Journal of Medicine (1967)

FOR almost two hundred years digitalis has been so essential and effective in cardiac therapy that it has been called the most useful drug of all times. Despite widespread and skillful clinical use its primary circulatory actions have become fully established only during the last two decades, and the underlying cellular mechanisms remain uncertain to this day. Few questions in biology have been the subject of such intensive research effort, but many findings are still controversial or conflicting. The following is a brief summary of current thinking in this field. More extensive discussions and pertinent references are included in several . . .
A silanized hydroxypropyl methylcellulose hydrogel for the three-dimensional culture of chondrocytes
Authors: C. Vinatier, D. Magne, P. Weiss, C. Trojani, N. Rochet, G.F. Carle, C. Vignes-Colombeix, C. Chadjichristos, P. Galera, G. Daculsi, J. Guicheux
Journal: Biomaterials (2005)
Some Operative and Postoperative Hazards of Legal Termination of Pregnancy
Authors: S. V. Sood
Journal: BMJ (1971)

Analysis of 1,317 patients admitted for N.H.S. abortion showed an overall morbidity of 16·8% excluding urinary tract infection. Genital infection, chest infection, reevacuation or perforation of the uterus, and haemorrhage were the more common complications. There was one maternal death.
Influence of a boosting in the recognition and specificity of IgE antibodies in patients with immediate allergic reaction to betalactams
Authors: G. Canto, J.L. Rodriguez-Bada, C. Mayorga, M.J. Torres, R. R-Pena, C. Antunez, J.A. Cornejo-Garcia, T. Fernandez, M. Blanca
Journal: Journal of Allergy and Clinical Immunology (2005)
Bronchobiliary Fistula as a Complication of Liver Metastases: Diagnosis by HIDA Scan
Authors: Lina Andalkar, Terence K. Trow, Betty Motroni, Douglas S. Katz
Journal: Clinical Nuclear Medicine (2004)

Bronchobiliary fistulas are rare, may result from infection with Echinococcus or Amebiasis, trauma, or hepatic malignancy, and present with biliptysis, the expectoration of bile. The authors present a 49-year-old woman who presented with frank biliptysis as a result of previously treated metastatic colon cancer to the liver. A hepatobiliary scan is the noninvasive diagnostic imaging test of choice for demonstration of such fistulas, and was useful in confirming the diagnosis in our patient.
Large Doses of Procainamide for Paroxysmal Ventricular Tachycardia
Authors: Robert D. Patton
Journal: JAMA (1969)

Although recurrent ventricular tachycardia can be controlled in many patients with standard doses of procainamide hydrochloride or quinidine sulfate, the occasional patient with a condition refractory to this therapy has been treated with beta- adrenergic blocking agents, cardiac sympathectomy, or pacemakers. In four patients with refractory ventricular tachycardia, 7.5 to 10.5 gm procainamide hydrochloride successfully controlled the arrhythmia without adverse sequelae. Physicians should consider large doses of procainamide before they utilize more radical therapy.
Increased high-density lipoprotein-3 binding to leukocytes following weight loss and improved glycemic control in type 2 diabetic patients
Authors: J.A. Paniagua, J. López-Miranda, S. Jansen, J.L. Zambrana, F. López Segura, J.A. Jiménez Perepérez, F. Pérez-Jiménez
Journal: Metabolism (2000)
GidB mutation as a phylogenetic marker for Q1 cluster Mycobacterium tuberculosis isolates and intermediate-level streptomycin resistance determinant in Lisbon, Portugal
Authors: J. Perdigão, R. Macedo, D. Machado, C. Silva, L. Jordão, I. Couto, M. Viveiros, I. Portugal
Journal: Clinical Microbiology and Infection (2013)
Malodorous Tumors and Metronidazole
Authors: DONALD C. DOLL
Journal: Annals of Internal Medicine (1981)

Letters1 January 1981Malodorous Tumors and MetronidazoleDONALD C. DOLL, M.D., KINDER J. DOLL, M.D.DONALD C. DOLL, M.D.Search for more papers by this author, KINDER J. DOLL, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-94-1-139_2 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the editor: Dr. Finegold has written an excellent review of the therapeutic uses and indications for metronidazole (1). We wish to add another potential use for this drug: the treatment of malodorous tumors.We have recently seen two patients with ulcerating breast cancer with a strong, foul odor. This odor was most distressing to the patients as well as to the hospital personnel who attended them. Because this offensive smell was reminiscent of anaerobic infection metronidazole was given, at 250 mg orally, three times a day for 10 days. Both patients had complete amelioration of their odor. Other authors...References1. FINEGOLD S. Metronidazole. Ann Intern Med. 1980; 93:585-7. LinkGoogle Scholar2. ASHFORDPLANTMAHEN RGJ. Metronidazole in smelly tumors. Lancet. 1980; 1:874-5. Letter. CrossrefMedlineGoogle Scholar3. SPARROWMONTONRUBENSSIMMONSAUBREY GMRNC. Metronidazole in smelly tumors. Lancet. 1980; 1:1185. Letter. CrossrefMedlineGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Maricopa County Hospital Phoenix AZ 85008 PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited ByMalodorous fungating wounds: uncertain concepts underlying the management of social isolationThe use of metronidazole in the treatment of malodorous woundsManagement of cutaneous symptomsMetronidazole Use in Malodorous Skin LesionsEsophageal cancer: Treatment and nursing interventionsTHE USE OF SMELL IN DIFFERENTIAL DIAGNOSIS 1 January 1981Volume 94, Issue 1Page: 139-140KeywordsBreast cancerDrugsSmellUlcers Issue Published: 1 January 1981 PDF DownloadLoading ...
The Marmara earthquake: Epidemiological analysis of the victims with nephrological problems
Authors: Mehmet Şükrü Sever, Ekrem Erek, Raymond Vanholder, Emel Akoğlu, Mahmut Yavuz, Hülya Ergin, Mustafa Tekçe, Didem Korular, M. Yaşar Tülbek, Kenan Keven, Bruno Van Vlem, Norbert Lameire, None for the Marmara Earthquake Study Group
Journal: Kidney International (2001)
Misplacement of the Elderly in Hospital
Authors: C. B. Kidd
Journal: BMJ (1962)

patients.No matter how thoroughly a new drug has been tested in experimental animals, possible species differences must never be forgotten in assessing its precise effect in man.As Mr. Hanbury, of the British Pharmaceutical Industry, has recently said, " there are innumerable examples of drugs of the utmost value, even penicillin itself, which have brought life and health to millions of people but serious trouble to the few.Vaccination against smallpox involves a grave risk to a tiny minority, considered worth taking for the good of the majority.Even the use of the homely aspirin is by no means devoid of danger.Those who say that nothing short of complete safety will suffice are crying for the moon, and if their clamour were taken at its face value stagnation would be the sequel.The public which demands therapeutic progress must be prepared to accept some risk, though its degree and extent can be minimized by intelligent safeguards."
Abnormal vitamin D metabolism in cirrhosis.
Authors: R T Jung, M Davie, J O Hunter, T M Chalmers, D E Lawson
Journal: Gut (1978)

Vitamin D metabolism was investigated in 10 patients with cirrhosis. Mean plasma 25 hydroxycholecalciferol (25 OHD) centration in alcoholic cirrhosis was lower than in controls but the difference was not significant. In three patients restudied after the summer, plasma 25 OHD had risen. In contrast to the finding in normal subjects, the half-life of intravenously administered 3H cholecalciferol was short in cirrhotics and showed no correlation with plasma 25 OHD. Furthermore, the appearance of 3H 25 OHD from 3H cholecalciferol was reduced compared to the control group four hours after injection. Increased rate of metabolism of cholecalciferol and deficient production of 25 ohd contribute to vitamin D deficiency in liver disease.
Gumboots at the Christmas party
Authors: D. Curr
Journal: BMJ (1993)

Off we went again, to the People's Republic of Tanzania, which was at that time a true socialist state.There I met racial prejudice for the first time.Many young Tanzanians had been taught that a white man was wicked, colonialist, and never to be trusted.It was at first depressing and then infuriating, having to carry this awful stigna.My feelings then seemed very similar to those of some of my coloured colleagues in Britain.It did not make for a happy life.So what did I learn from my travels?As T H Lawrence says in the Seven Pilars of Wisdom, "just because you can't cope in your own society, there's no reason to believe that by escaping to another you will solve those problems.The problem lies with you, not with your society."I learnt that I could not be an Albert Schweitzer and, without religion, working in the Third World is pretty useless, apart from the learning experience for you.That in itself is important, but don't think that you are going to the Third World to help the Third World.: you are going to try to help yourself.I leamt that the highly praised skills of the Westem world are largely irrelevant to the other 90% of the world's population.I also tasted the bitter pill of being on the receiving end ofracial prejudice.Would I do it again?Yes, of course I would.I would try to do it differently, but I don't suppose I would succeed.Should you do it?Yes, of course you should.You should go fufll of opimism and determination to try and do some good and have a good time.You won't succeed, but you'll learn a lot in the trying.