tbuckley/cabot-search huggingface dataset:
Macroscopic appearance of intestinal angiodysplasias under antiangiogenic treatment with thalidomide
Authors: J. Bauditz, H. Lochs, W. Voderholzer
Journal: Endoscopy (2006)

Background and study aims: Angiodysplasias are the main cause of bleeding from the small intestine. Single lesions may be treated by endoscopic coagulation or surgical resection. However, multiple disseminated angiodysplasias are frequently present, making local therapy an unfavorable choice or impossible. Currently there is no established medical treatment available for these patients. Thalidomide is a potent inhibitor of angiogenesis in experimental models. As angiodysplasias are a result of unregulated vessel growth, antiangiogenic treatment may inhibit growth of angiodysplasias. Patients and methods: We studied the effect of thalidomide on the macroscopic appearance of angiodysplasias in three patients with bleeding due to multiple angiodysplasias of the small intestine. During the previous 12 months patients had experienced 3 - 7 bleeding episodes and had received a mean of 16.7 blood units. Results: After start of treatment with thalidomide at a dose of 100 mg daily, no further bleeding episodes occurred. Although thalidomide was stopped after 3 months, bleeding did not recur and hemoglobin reached and maintained normal levels without further transfusions for the whole observation period (mean follow-up 34 months). Repeat wireless capsule endoscopy after 3 months' thalidomide demonstrated substantial reductions in the number, size, and color intensity of angiodysplasias. Conclusion: Thalidomide seems to inhibit growth of intestinal angiodysplasias and may be useful for treatment of patients with bleeding related to angiodysplasias. Wireless capsule endoscopy allows monitoring of the macroscopic effects of antiangiogenic therapy.
Clinical Observation
Authors: George L. Engel
Journal: JAMA (1965)

In  current era  medicine, medical students are led to believe that what derives from  laboratory is by definition more  than what derives from clinical observation. In fact,  preclinical disciplines are generally called the  sciences, as if they alone are  approaches truly  to medicine.  Basic means of or pertaining to  base or essence; fundamental, a relative term, specifying those data or concepts which are necessary before any particular scientific question can be posed or examined. As currently used in medicine, basic predominantly reflects  reductionistic view  biology, which states that all biological events can be explained by  fundamental laws governing spatial arrangements and interaction  molecules and their component parts. 1 Such a perspective demands an a priori faith that living things are nothing but physical-chemical machines. While great scientific advances have accrued from such an assumption,  fact that
Activated Lymphocyte Recruitment Into the Tumor Microenvironment Following Preoperative Sipuleucel-T for Localized Prostate Cancer
Authors: Lawrence Fong, Peter Carroll, Vivian Weinberg, Stephen Chan, Jera Lewis, John Corman, Christopher L. Amling, Robert A. Stephenson, Jeffrey Simko, Nadeem A. Sheikh, Robert B. Sims, Mark W. Frohlich, Eric J. Small
Journal: JNCI Journal of the National Cancer Institute (2014)

Sipuleucel-T is a US Food and Drug Administration-approved immunotherapy for asymptomatic or minimally symptomatic metastatic castration-resistant prostate cancer (mCRPC). Its mechanism of action is not fully understood. This prospective trial evaluated the direct immune effects of systemically administered sipuleucel-T on prostatic cancer tissue in the preoperative setting.Patients with untreated localized prostate cancer were treated on an open-label Phase II study of sipuleucel-T prior to planned radical prostatectomy (RP). Immune infiltrates in RP specimens (posttreatment) and in paired pretreatment biopsies were evaluated by immunohistochemistry (IHC). Correlations between circulating immune response and IHC were assessed using Spearman rank order.Of the 42 enrolled patients, 37 were evaluable. Adverse events were primarily transient, mild-to-moderate and infusion related. Patients developed T cell proliferation and interferon-γ responses detectable in the blood following treatment. Furthermore, a greater-than-three-fold increase in infiltrating CD3(+), CD4(+) FOXP3(-), and CD8(+) T cells was observed in the RP tissues compared with the pretreatment biopsy (binomial proportions: all P < .001). This level of T cell infiltration was observed at the tumor interface, and was not seen in a control group consisting of 12 concurrent patients who did not receive any neoadjuvant treatment prior to RP. The majority of infiltrating T cells were PD-1(+) and Ki-67(+), consistent with activated T cells. Importantly, the magnitude of the circulating immune response did not directly correlate with T cell infiltration within the prostate based upon Spearman's rank order correlation.This study is the first to demonstrate a local immune effect from the administration of sipuleucel-T. Neoadjuvant sipuleucel-T elicits both a systemic antigen-specific T cell response and the recruitment of activated effector T cells into the prostate tumor microenvironment.
Inducible heme oxygenase in the kidney: a model for the homeostatic control of hemoglobin catabolism
Authors: Neville R. Pimstone, Peter Engel, Raimo Tenhunen, Paul T. Seitz, Harvey S. Marver, Rudi Schmid
Journal: Journal of Clinical Investigation (1971)

We have recently identified and characterized NADPH-dependent microsomal heme oxygenase as the major enzymatic mechanism for the conversion of hemoglobin-heme to bilirubin-IXalpha in vivo. Enzyme activity is highest in tissues normally involved in red cell breakdown, that is, spleen, liver, and bone marrow, but it usually is negligible in the kidney. However, renal heme oxygenase activity may be transiently increased 30- to 100-fold following hemoglobinemia that exceeded the plasma haptoglobin-binding capacity and consequently resulted in hemoglobinuria. Maximal stimulation of enzyme activity in rats is reached 6-16 hr following a single intravenous injection of 30 mg of hemoglobin per 100 g body weight; activity returns to basal levels after about 48 hr. At peak level, total enzyme activity in the kidneys exceeds that of the spleen or liver. Cyclohexamide, puromycin, or actinomycin D, given just before, or within a few hours after, a single intravenous injection of hemoglobin minimizes or prevents the rise in renal enzyme activity; this suggests that the increase in enzyme activity is dependent on continued synthesis of ribonucleic acid and protein. The apparent biological half-life of renal heme oxygenase is about 6 hr. These observations indicate that functional adaptation of renal heme oxygenase activity reflects enzyme induction either directly or indirectly by the substrate, hemoglobin. Filtered rather than plasma hemoglobin appears to regulate renal heme oxygenase activity. Thus, stabilization of plasma hemoglobin in its tetrameric form with bis (N-maleimidomethyl) ether, which diminishes its glomerular filtration and retards it plasma clearance, results in reduced enzyme stimulation in the kidney, but enhances its activity in the liver. These findings suggest that the enzyme is localized in the tubular epithelial cells rather than in the glomeruli and is activated by luminal hemoglobin. Direct support for this concept was obtained by the demonstration of heme oxygenase activity in renal tubules isolated from rabbits that had been injected with hemoglobin.
Colonic and small intestinal response to intravenous prostaglandin F2 alpha and E2 in man.
Authors: G J Milton-Thompson, J H Cummings, A Newman, J A Billings, J J Misiewicz
Journal: Gut (1975)

The effects of intravenous infusions of prostaglandins (PGs) F2 alpha(0-4 or 0-8 mug kg-1 min-1) or E2 (0-08 or 0-1 mug kg-1 min equals1) on net colonic movement of water and electrolytes and on ileal flow were measured in eight healthy males by simultaneous ileal and colonic perfusion. Ileal flow was increased by PGF2 alpha (six subjects) from a mean of 1-69 ml min-1 to 4-63 ml min-1 (P smaller than 0-01); it also increased in the two subjects given PGE2. Colonic absorptive function was not significantly diminished by either prostaglandin. These results suggest that diarrhoea due to prostaglandins originates in the small intestine.
Challenges in managing profound hypokalaemia
Authors: W. Welfare
Journal: BMJ (2002)

benefit from iloprost.Administered to four patients suffering from multiple cholesterol emboli, iloprost caused the disappearance of most cyanotic lesions, with a dramatic relief of pain, and, in at least one patient, stabilised and subsequently improved renal function.These cases suggest that the drug should be initiated early to stabilise, and even reverse, the clinical syndrome, but only randomised controlled trials can provide firm evidence of a beneficial effect of iloprost in this syndrome.In cholesterol emboli syndrome cholesterol crystals obstruct small arterioles, causing local ischaemia and end organ damage.Iloprost, a prostacyclin stable analogue used for treating critical leg ischaemia, Raynaud's syndrome, and pulmonary hypertension, 3 is a potent vasodilator and antiplatelet aggregant, which stabilises endothelial integrity and has cytoprotective properties.This might explain our clinical observations in these four patients.
Urinary Excretion of IGF-I and Growth Hormone in Children With IDDM
Authors: Teresa Quattrin, Christine H Albini, Edward O Reiter, Barbara J Mills, Margaret H MacGillivray
Journal: Diabetes Care (1992)

Objective To compare the urinary output of insulinlike growth factor I (IGF-I) and growth hormone (GH) in prepubertal and pubertal children with insulin-dependent diabetes mellitus (IDDM) versus nondiabetic subjects and to analyze the relationship between the urinary excretion of these peptides and degree of metabolic control. Research Design and Methods Group 1 included 30 IDDM patients who had had diabetes for 4.9 ± 0.7 yr and had normal renal function (mean age 11.6 ± 0.9 yr); group 2 consisted of 31 control subjects (mean age 9.2 ± 0.6 yr). Sensitive radioimmunoassays were used to measure IGF-I and GH in urine aliquots from 12-h timed overnight collections that had been dialyzed, concentrated 50-fold, and lyophilized. Results Significantly lower IGF-I and GH outputs per kilogram body weight per 12 h were observed in IDDM subjects compared with control subjects. When data were expressed per kilogram of body weight, no difference was observed between the urinary output of IGF-I and GH between prepubertal and pubertal subjects within group 1 or group 2. The prepubertal children had significantly lower HbA1 than the pubertal population; however, no correlation was found between urinary output of IGF-I or GH and HbA1. A positive correlation was observed between urinary IGF-I and GH (r = 0.85, P &amp;lt; .001). Conclusions Patients with long-standing IDDM excrete significantly lower urinary levels of IGF-I and GH compared with normal subjects. Serial measurements of these peptides from onset of IDDM are needed to define whether the changes observed are present at diagnosis or are secondary to duration of disease.
Don't beam me up just yet
Authors: T. Jackson
Journal: BMJ (2012)

Proton beam therapy might once have seemed like the magic bullet to zap cancer, the state of the art treatment we have all been waiting for. The technology is big and expensive—the world’s “most costly and complicated medical devices,” according to one description cited by Keith Epstein in this week’s cover article (doi:10.1136/bmj.e2488)—and looks and sounds as if a Star Trek scriptwriter might have dreamt it up. As Epstein writes, “by accelerating subatomic particles towards the speed of light and concentrating them in a beam, proton treatment is thought to target cancerous tissue more precisely.”

England’s health secretary, Andrew Lansley, clearly believes it represents the future of cancer services—his …
Trends in Use of Oral Hypoglycemic Agents 1964–1986
Authors: Dianne L Kennedy, Joyce M Piper, Carlene Baum
Journal: Diabetes Care (1988)

Oral hypoglycemic (OH) agents have been available in the United States for the treatment of non-insulin-dependent diabetes mellitus (NIDDM) for almost 30 yr. During this time they have been subject to considerable controversy. In this article, we present pharmaceutical marketing research data that provide a review of several facets of OH use. The number of OH prescriptions dispensed peaked in 1973, decreased through 1980, and has been increasing since that year. In 1986, OH agents accounted for 21.5 million prescriptions: 1% of all prescriptions dispensed that year. Chlorpropamide is currently the most frequently ingested OH agent; it is used by 33% of the market. The two OH agents introduced in 1984, glyburide and glipizide, had acquired 41% of the OH market by the end of 1986. The rate of OH use per 1000 diabetes mellitus visits increases with patient's age. Patients aged 60 yr and older received OH prescriptions at a rate of 478 per 1000 diabetes mellitus visits in 1986. Data estimating both the number of patients diagnosed with diabetes and the number of diabetic patients taking OH agents indicate that the percentage receiving OH treatment has increased over the past 5 yr, with approximately 35% of all diabetic patients taking OH agents in 1986.
Physiological Genomics of Human Arteries
Authors: Séverine Durier, Céline Fassot, Stéphane Laurent, Pierre Boutouyrie, Jean-Paul Couetil, Erika Fine, Patrick Lacolley, Victor J. Dzau, Richard E. Pratt
Journal: Circulation (2003)

Previous genomic studies with human tissues have compared differential gene expression between 2 conditions (ie, normal versus diseased) to identify altered gene expression in a binary manner; however, a potentially more informative approach is to correlate the levels of gene expression with quantitative physiological parameters.In this study, we have used this approach to examine genes whose expression correlates with arterial stiffness in human aortic specimens. Our data identify 2 distinct groups of genes, those associated with cell signaling and those associated with the mechanical regulation of vascular structure (cytoskeletal-cell membrane-extracellular matrix). Although previous studies have concentrated on the contribution of the latter group toward arterial stiffness, our data suggest that changes in expression of signaling molecules play an equally important role. Alterations in the profiles of signaling molecules could be involved in the regulation of cell cytoskeletal organization, cell-matrix interactions, or the contractile state of the cell.Although the influence of smooth muscle contraction/relaxation on arterial stiffness could be controversial, our provocative data would suggest that further studies on this subject are indicated.
Dr William W. Duke: Pioneer in Platelet Research
Authors: Thomas Stephen Kickler
Journal: JAMA (2009)

The purpose of this article is to report 3 cases and experiments that furnish additional evidence showing that blood platelets play a part in stopping hemorrhagic disease. In addition, a method for studying hemorrhage called the bleeding time, and a simple method for determining the coagulation time are described.See PDF for full text of the original JAMA article.
Randomized Trial of Intravitreal Bevacizumab Alone or Combined with Triamcinolone versus Macular Photocoagulation in Diabetic Macular Edema
Authors: Masoud Soheilian, Alireza Ramezani, Arash Obudi, Bijan Bijanzadeh, Masoud Salehipour, Mehdi Yaseri, Hamid Ahmadieh, Mohammad H. Dehghan, Mohsen Azarmina, Siamak Moradian, Gholam A. Peyman
Journal: Ophthalmology (2009)
Abstract 1568: Evaluate the efficacy of new therapeutics using advanced metastatic mouse models.
Authors: Juan Zhang, Sheng Guo, Jie Cai, Yanmei Sun, Guanping Mao, Zhun Wang, Lan Zhang, Ying Jin, Qian Shi, Taiping Chen
Journal: Cancer Research (2013)

Abstract Metastasis, the spread and growth of tumor cells to distant organs, is usually a final and fatal step in the progression of solid malignancies. Preclinical test of the new anti-cancer therapies that could mimic the disease present in most clinical trials asks for robust metastatic models than just the subcutaneous models. We sought to establish and validate a panel of experimental (i.v. inoculation) and spontaneous (orthotopic inoculation) mouse models with high metastatic potential and varied tissue tropism in different types of cancer models, covering colorectal, liver, prostate, breast, pancreatic cancer and melanoma. The responsiveness of metastasis to several therapies that are proved to be clinically effective or ineffective was investigated. A higher predictive power of the metastatic models was demonstrated compared with the corresponding subcutaneous models. By means of the transcriptomic analysis of the paired primary tumor population and the distant lung metastasis population in 5 orthotopic tumor models, we identified the gene signatures that differentiate the two populations in different tumor types. Our signature was also compared with the clinical relevant gene signatures correlated with lung metastasis risk. Several genes are concordantly expressed in both signatures and are biologically meaningful. Overall, given the higher predictive power and the clinical relevance, the use of the metastatic mouse models constitutes an effective and important strategy to preclinically evaluate the efficacy of new therapeutic regimens. Citation Format: Juan Zhang, Sheng Guo, Jie Cai, Yanmei Sun, Guanping Mao, Zhun Wang, Lan Zhang, Ying Jin, Qian Shi, Taiping Chen. Evaluate the efficacy of new therapeutics using advanced metastatic mouse models. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1568. doi:10.1158/1538-7445.AM2013-1568
Effect of essential hypertension on cardiac autonomic function in type 2 diabetic patients
Authors: Naohiko Takahashi, Mikiko Nakagawa, Tetsunori Saikawa, Tatsuhiko Ooie, Kunio Yufu, Sakuji Shigematsu, Masahide Hara, Hiroshi Sakino, Isao Katsuragi, Toshimitsu Okeda, Hironobu Yoshimatsu, Toshiie Sakata
Journal: Journal of the American College of Cardiology (2001)
Cluster Analysis of p53 and Ki67 Expression, Apoptosis, Alpha-Fetoprotein, and Human Chorionic Gonadotrophin Indicates a Favorable Prognostic Subgroup Within the Embryonal Carcinoma Germ Cell Tumor
Authors: Madhu Mazumdar, Jennifer Bacik, Satish K. Tickoo, Deborah Dobrzynski, Alessia Donadio, Dean Bajorin, Robert Motzer, Victor Reuter, George J. Bosl
Journal: Journal of Clinical Oncology (2003)

The prognostic information provided by alpha-fetoprotein and human chorionic gonadotrophin in the management of germ cell tumor (GCT) patients is a biochemical reflection of tumor differentiation. Ki67, p53, and apoptosis have been found to be related to proliferation (Ki67), cell death (p53, apoptosis), and possibly differentiation chemoresistance (p53). We sought to determine whether simultaneous expression of one or more of these markers could identify clinically relevant subgroups of patients with nonseminomatous GCT (NSGCT).These five marker values were obtained for 95 previously untreated patients with embryonal carcinoma with or without other germ cell components. A multivariate cluster analysis was performed to identify patients with similar marker patterns.One prominent cluster (n = 37; 36 testis retroperitoneum), consisting of 26 (70%) good-risk (GR), nine (24%) intermediate-risk (IR), and two (6%) poor-risk (PR) patients, as defined by the International Germ Cell Consensus Cancer Group (IGCCCG), was observed. The 5-year survival of the prominent cluster (with 30% IR/PR patients) was 94% (95% confidence interval [CI], 86% to 100%), which is comparable to the 91% (95% CI, 89% to 93%) 5-year survival of the IGCCCG GR patients. IGCCCG risk status (P =.005) and cluster affiliation (P =.04) were independent predictors of outcome with hazard ratios of 5.0 (95% CI, 1.6 to 15.4) and 4.6 (95% CI, 1.04 to 20.1), respectively.These results suggest that there is a subgroup of NSGCT patients with embryonal carcinoma (with or without other histologies) with a specific tumor biology profile (high Ki67, low apoptosis, and low p53) whose survival is better than that of the overall patient group. The unexpectedly good outcome for the prominent cluster and independent-risk status suggest that subgroups of GCT reflecting different abilities to respond to treatment exist within IGCCCG prognostic categories.
Snobbery with violence
Authors: T. Dalrymple
Journal: BMJ (2011)

Two whole generations, I suppose, may now have grown up without any knowledge of hat pins, not even that they once existed. I was raised just as they were disappearing along with the hats that they kept attached to ladies’ heads. My grandmother’s hat pin fascinated me almost as much as her smell of mothballs, and her fox fur stole that ended in fox heads with beady glass eyes. Her hat pin was by far the largest pin that I had ever seen, and had a sphere of jet at its end (all her hats were black). Even at the age of eight, I saw it as a potentially lethal weapon, and wondered what would happen if you stuck such …
Medical Prospect — Nurses' Pay and Nurses' Dress — Sherlock Holmes Returns
Authors: John Lister
Journal: New England Journal of Medicine (1968)

THE old-fashioned general practitioner or family doctor has probably been more symbolic of the pattern of medical care in this country than any other type of doctor, although the flamboyant surgeon and the fashionable Harley Street consultant have often been the subjects of caricature.Before the days of the National Health Service it was usual for many general practitioners to have hospital bed privileges, particularly in provincial hospitals, where orthodoxly trained consultants were few and far between. One of the major achievements of the Service has been the upgrading of these provincial hospitals, which are now staffed by well trained . . .
Sex Chromosome Disorders
Authors: Park S. Gerald
Journal: New England Journal of Medicine (1976)

The sex chromosome abnormalities are one of the most common types of chromosome disorders, occurring once among every 1100 females and once among every 380 males. Their effect upon the clinical appearance or phenotype of the patient varies from the subtle to the markedly overt. In general, the phenotypic changes are chronic rather than acute and affect the patient's occupational and procreative capacities instead of the life-span. The varied nature of the patients' complaints causes them to seek help from a wide variety of physicians, from the generalist to the specialist. The remarks to follow represent a core of information . . .
Soluble intercellular adhesion molecule-1 levels of patients with acute myeloid leukemia after allogeneic bone marrow transplantation
Authors: Yasuhiro Maeda, Junichi Chihara, Yoshiyasu Sumimoto, Hidekazu Yamada, Jun-ichi Miyatake, Mitsuhiro Matsuda, Fusanari Horiuchi, Kiyohiro Irimajiri, Atsushi Horiuchi
Journal: Journal of Allergy and Clinical Immunology (1997)
Benefits of trastuzumab outweigh its harms, says Cochrane review
Authors: J. Wise
Journal: BMJ (2014)

The benefits of trastuzumab (marketed as Herceptin) outweigh the increased risk of heart problems in women with metastatic breast cancer, a systematic review has concluded.1

The monoclonal antibody reduces overall mortality from breast cancer by one fifth after two years of follow-up, but the risk of heart toxicity is between three and four times more likely than in regimens that did not include the drug, concludes the review published in the Cochrane Library.

Overexpression or amplification of HER2 receptors is seen in about a fifth of women with breast cancer, …
829 EFFECTIVENESS OF HEPATITIS C VIRUS TREATMENT IN REAL-LIFE PRACTICE: A PROSPECTIVE OBSERVATIONAL MULTICENTER STUDY IN ITALY (PROBE)
Authors: M. Rizzetto, M. Colombo, A. Ascione, F. Piccinino, A. Craxi, A. Alberti, T. Stroffolini, C. Iannacone, M. Sarracino
Journal: Journal of Hepatology (2008)