tbuckley/cabot-search huggingface dataset:
Parathyroid hormone suppression by intravenous 1,25-dihydroxyvitamin D. A role for increased sensitivity to calcium.
Authors: J A Delmez, C Tindira, P Grooms, A Dusso, D W Windus, E Slatopolsky
Journal: Journal of Clinical Investigation (1989)

Numerous in vitro studies in experimental animals have demonstrated a direct suppressive effect of 1,25-dihydroxyvitamin D (1,25(OH)2D) on parathyroid hormone (PTH) synthesis. We therefore sought to determine whether such an effect could be demonstrated in uremic patients undergoing maneuvers designed to avoid changes in serum calcium concentrations. In addition, the response of the parathyroid gland in patients undergoing hypercalcemic suppression (protocol I) and hypocalcemic stimulation (protocol II) before and after 2 wk of intravenous 1,25(OH)2D was evaluated. In those enlisted in protocol I, PTH values fell from 375 +/- 66 to 294 +/- 50 pg (P less than 0.01) after 1,25(OH)2D administration. During hypercalcemic suppression, the "set point" (PTH max + PTH min/2) for PTH suppression by calcium fell from 5.24 +/- 0.14 to 5.06 +/- 0.15 mg/dl (P less than 0.05) with 1,25(OH)2D. A similar decline in PTH levels after giving intravenous 1,25(OH)2D was noted in protocol II patients. During hypocalcemic stimulation, the parathyroid response was attenuated by 1,25(OH)2D. We conclude that intravenous 1,25(OH)2D directly suppresses PTH secretion in uremic patients. This suppression, in part, appears to be due to increased sensitivity of the gland to ambient calcium levels.
Romidepsin for Cutaneous T-cell Lymphoma
Authors: H. Miles Prince, Michael Dickinson
Journal: Clinical Cancer Research (2012)

Cutaneous T-cell lymphomas (CTCL) are relatively rare lymphomas with an annual incidence of approximately 0.2 to 0.8/100,000 and comprise a variety of clinical entities; mycosis fungoides or its leukemic variant Sezary syndrome account for the majority of cases. Advanced-stage disease is typically treated with bexarotene (a retinoid), interferon, or conventional chemotherapeutic agents, but relapses are inevitable. Histone deacetylase inhibitors, which modify the epigenome, are an attractive addition to the armamentarium. On the basis of 2 large phase II studies, the U.S. Food and Drug Administration approved intravenous romidepsin for patients with relapsed and/or refractory CTCL. Romidepsin provides a subset of patients with an opportunity for prolonged clinical responses with a tolerable side effect profile.
Phase I to II Study of Pleurectomy/Decortication and Intraoperative Intracavitary Hyperthermic Cisplatin Lavage for Mesothelioma
Authors: William G. Richards, Lambros Zellos, Raphael Bueno, Michael T. Jaklitsch, Pasi A. Jänne, Lucian R. Chirieac, Beow Y. Yeap, Rene J. Dekkers, Phillip M. Hartigan, Leah Capalbo, David J. Sugarbaker
Journal: Journal of Clinical Oncology (2006)

Purpose To evaluate morbidity, mortality, maximum-tolerated dose (MTD), and outcome of intraoperative intracavitary hyperthermic cisplatin lavage in patients undergoing pleurectomy for malignant pleural mesothelioma (MPM). Patients and Methods Sixty-one patients were prospectively registered. Forty-four resectable patients with MPM underwent pleurectomy, followed by a 1-hour lavage of the resection cavity with dose-escalated cisplatin (50, 100, 150, 175, 200, 225, and 250 mg/m 2 ) at 42°C and then intravenous sodium thiosulfate (16 g/m 2 over 6 hours). Survival estimates were compared using the log-rank test and proportional hazards regression. Results Median age was 71 years (range, 50 to 82 years). Twenty-four patients had epithelial tumors, and 20 had sarcomatous or mixed histology. Postoperative mortality was 11% (five of 44 patients). Dose-limiting renal toxicity occurred at 250 mg/m 2 , establishing the MTD at 225 mg/m 2 . Other morbidity included atrial fibrillation (14 of 44 patients, 32%) and deep venous thrombosis (four of 44 patients, 9%). Median survival time of all registered patients was 9 months, and the median survival time of resected patients was 13 months. Survival estimates differed significantly for resectable patients exposed to low doses (50 to 150 mg/m 2 ; n = 9; median, 6 months) versus high doses (175 to 250 mg/m 2 ; n = 35; median, 18 months) of hyperthermic cisplatin (P = .0019); recurrence-free interval also differed significantly (4 v 9 months, respectively; P &lt; .0001). Low dose level (relative risk = 3.418) and nonepithelial histology (relative risk = 2.336) were independent risk factors for poor survival. Twenty patients with epithelial tumors who underwent high-dose cisplatin lavage had a 26-month median survival time. Conclusion Pleurectomy and high-dose intraoperative intracavitary hyperthermic cisplatin lavage is feasible in this patient population with restricted surgical options. An apparent dose-related survival benefit warrants further study.
Next generation sequencing and a new era of medicine
Authors: Graham Casey, David Conti, Robert Haile, David Duggan
Journal: Gut (2012)

The 10th anniversary of the publication of the first draft sequence of the human genome was celebrated recently, following the launch of the Human Genome Project in 1990.1 Now, 10 years later, a human genome can be sequenced in less than 10 days and soon will be sequenced routinely within a day. This remarkable progress is due to significant advances in DNA sequencing technologies from Sanger sequencing that has been dominant for nearly 30 years to next generation sequencing (NGS, also termed massively parallel sequencing). The ability to rapidly sequence human genomes and to generate genetic, transcriptomic, epigenetic data and other genome-wide data for a relatively small cost opens up numerous opportunities for translation into the clinic over the next few years. Can the knowledge gained through NGS advances lead to personalized medicine for cancer patients? In this review we provide an overview of NGS technologies and the challenges associated with handling massive amounts of data, data integration, visualization and analysis, followed by a discussion of the biological information that obtained through NGS within the context of colorectal cancer. Finally we will discuss the remaining challenges for NGS to change clinical management of disease.

The first draft of the human genome was generated using Sanger sequencing (considered first generation sequencing technology), a very successful but labour-intensive approach that required gel electrophoresis to size-separate dideoxy-terminated, PCR amplification products (originally radio-labelled nucleotides were used, but the change to fluorescent dye-labelled nucleotides greatly accelerated the application of this technology). While other sequencing methods existed (such as Maxam–Gilbert sequencing), Sanger sequencing was the mainstay sequencing method used worldwide for nearly 3 decades and has yielded many promising findings in cancer that have already entered the clinic.2 First generation sequencing approaches such as Sanger sequencing relied on sequencing PCR …
The cytokine interleukin 21: a new player in coeliac disease?
Authors: B. Meresse, J. Verdier, N. Cerf-Bensussan
Journal: Gut (2008)

In this issue of Gut ,1 Fina et al demonstrate that interleukin 21 (IL21) expression is increased in the intestinal mucosa of patients with active coeliac disease (CD) but not that of treated patients ( see page 887 ). The authors show that IL21 is produced by CD4+ lamina propria T cells, a finding consistent with previous work indicating that this cytokine is exclusively produced by CD4+ T cells. Using a neutralising anti-IL21 antibody, they observed that blocking IL21 activity reduced the increase in interferon γ mRNA induced by gliadin digests in intestinal organ cultures from treated CD patients. Since the anti-IL21 antibody also reduced the induction of mRNA for T-bet, the transcription factor that controls the differentiation of interferon γ-producing CD4+ T lymphocytes (so-called T helper cell type 1 or Th1 lymphocytes), the authors conclude that IL21 is an important contributor to the mucosal Th1 proinflammatory response.1 The mucosal Th1 response in CD is generally ascribed to lamina propria CD4+ T cells that recognise gluten peptides presented by the human leucocyte antigen (HLA)-DQ2/8 molecules at the surface of mucosal dendritic cells. This response accounts for the interplay between the major genetic risk factor, the MHC (major histocompatibility complex) class II genes encoding the HLA-DQ2/8 molecules, and the triggering environmental factor gluten, and is considered instrumental in the pathogenesis of CD enteropathy.2

These results are of particular interest following the first genome-wide association study recently carried out in CD by van Heel et al .3 The latter study has indeed provided convincing evidence that the chromosomal 4q27 region harbouring the genes encoding the IL2 and IL21 cytokines might be involved in CD. In this study based on the use of single-nucleotide polymorphisms (SNPs), several variants were highly significant when analysed in three distinct populations of UK, Dutch and …
The Role of Agrin in Synapse Formation
Authors: M A Bowe, J R Fallon
Journal: Annual Review of Neuroscience (1995)

The brain's default mode network consists of discrete, bilateral and symmetrical cortical areas, in the medial and lateral parietal, medial prefrontal, and medial and lateral temporal cortices of the human, nonhuman primate, cat, and rodent brains. Its ...Read More
Homing and invasiveness of MLL/ENL leukemic cells is regulated by MEF2C
Authors: Maike Schwieger, Andrea Schüler, Martin Forster, Afra Engelmann, Michael A. Arnold, Ruud Delwel, Peter J. Valk, Jürgen Löhler, Robert K. Slany, Eric N. Olson, Carol Stocking
Journal: Blood (2009)
THE TREATMENT OF SEPTIC HAEMOTHORAX AND EMPYEMA
Authors: J. Campbell
Journal: BMJ (1918)

TREATMENT OF SEPTIC HAEMOTHORAX, El BJouMu& Iog +.-_}iuu1ysis (,.r 17tcil acic C'ases Operated cui (Riccoreries ouly).-(Continted.'itweentietlh day;-Case 21 on the nineteenth ; Case 22 oni the fifteenth; Case 23 on the tlhirtieth; andl Case 24 on the tiventy-first.Case 2;-.-Traumatopnoea with hole in lug; admi-iitting two fingers.Complete operation.Aspirated.Got up onl the thirty-fifth dav.Case 996.-Traunmatopnoea with lhole in lng; admitting two finigers.Complete operation.Aspirated, but leaked pus (staphylococcus) from localized emi-pyeiima.W'as otut of bed on the sixty-fourth (lay.Case ?, .-Traumnatopuoea.with missile lodged in mediastinium.Complete operation ; missile removed from miie(liastinuLrln.Aspirated.Grot up on the fiftietlh (lay.Case .28.-Traumatopnoea (hole into chest admitting two fingers`and laceration of lung.Complete operationl.Aspirated; leaked pus (stap,hylococcus) from localized empyema; close(d completely andl spontaneously.Patient wvas ouit of bed on the ninietv-gixth day.C;ase 29.-Traumatopnoea (adlmitting three fingers); lacera- tion 6f lung, pericarrdium perforated.Complete operation; small missile nlot removed.Aspirated.Got up oln the twentieth day.Case 30.-Penetration of chest and mediastiinum; laceration of lung.Comiplete operationi; missile removed from medias- tinum.Aspirated; lealked pus (staphylococcus) from medias- tinum; closed completely anld spolntanieously.Got up on the twenty-eightlh day.Case 31.-Penptration of chest; laceration of lung; multiple wounds.Complete oiperation; muiltiple wounds excisedt.Aspirated.Got uip on the forty-first day.Case 3?.-Penetration of chest; multiple wounds.Complete operation; multiple wournds excised; ampuitation of left arm.Aspirated.Evacuated on the thiirty-fifth (lay.Cases 33 to 36.-Penetration of chiest; laceration of lung.Complete operation; missile removed, except in Case 36.Aspirate(l.Case 33 got up oni the fortietlh day; Case 34 oni the forty-fifth *andCase35 onthesixty--fifth.Case 35 was evacuated on the twenity-first day.Case 3,.-Penetration of clest (through-and-through): lacera- tion of luing.Complete operationi oni the ninthi day, because of 1).pertr iuyeuls infection.Infected lhaemothorax (1.per:frineslels and streptococcuis) ; operationlate.Developed empyemna af ter operation;: aspirated fouir times (cflttures uneliangedi.Recover- wsithout drainage.W^as out of bed on the fortieth day.Case 38.
Radioimmunoassay of carcinoembryonic antigen in serum of normal subjects and patients with colonic carcinoma
Authors: M. S. Kleinman, M. D. Turner
Journal: Gut (1972)

Sera from 14 normal subjects and 43 patients with colonic carcinoma were evaluated for the presence of carcinoembryonic antigen (CEA). Inhibiting material which behaved in the assay in a similar manner to CEA was found in normal serum at concentrations below 2.8 ng/ml. Its nature has not so far been established. Thirty-eight of the 43 patients with colonic carcinoma showed levels of serum CEA in excess of 2.8 ng/ml. The concentration of CEA in serum was correlated with the extent of the disease as classified by a staging procedure similar to that of Dukes (1932). Examination of a small number of specimens of colonic carcinoma and normal colonic mucosa suggested that the concentration of CEA in different adenocarcinomata may vary, and that traces of cross-reacting material may be found in some normal mucosae.
Effect of propranolol on hepatic and systemic hemodynamics in dogs with chronic bile duct ligation
Authors: Bernard Willems, Jean-Pierre Villeneuve, P.-Michel Huet
Journal: Hepatology (1986)

Propranolol has been reported to reduce portal and wedged hepatic vein pressures in man and may be useful for the prevention of variceal bleeding. However, its mechanism of action remains unclear. We have examined the effect of propranolol on the systemic and hepatic circulations in dogs with chronic bile duct ligation and secondary biliary cirrhosis. Underanesthesia, eight dogs received four increasing doses of propranolol as an i.v. bolus followed by continuous infusion. Systemic and hepatic hemodynamic parameters were measured in basal conditions and after a 30 min infusion for each dose. Portal vein and hepatic artery blood flows were measured with electromagnetic flow meters. All dogs had portal hypertension(portal venous pressure 15.3 ± 0.8 mm Hg), a hyperdynamic circulation and severe liver disease resulting in a marked decrease of propranolol systemic clearance (8.75 ml per min per kg) and extraction (40%). The first dose of propranolol induced a decrease in heart rate (-27%) and in cardiac index(-21%), and an increase in systemic vascular resistance (+20%). With increasing doses, the systemic vascular resistance decreased with an increase in the cardiac index. Propranolol was not associated with significant modifications of hepatic hemodynamics: portal, wedged and free hepatic venous pressures and hepatic artery blood flow were stable, and portal blood flow decreased slightly at very high propranolol levels. In seven dogs studied without dissection of the hepatic vessels, there was a small decrease in portal pressure, but not in wedged and free hepatic venous pressures with increasing doses of propranolol. Thus, in dogs with intrahepatic portal hypertension, propranolol has significant effects on systemic hemodynamics, but only minimal effects on the hepatic circulation.
Randomized Controlled Trial of Intensity-Modulated Radiotherapy for Early Breast Cancer: 5-Year Results Confirm Superior Overall Cosmesis
Authors: Mukesh B. Mukesh, Gillian C. Barnett, Jennifer S. Wilkinson, Anne M. Moody, Charles Wilson, Leila Dorling, Charleen Chan Wah Hak, Wendi Qian, Nicola Twyman, Neil G. Burnet, Gordon C. Wishart, Charlotte E. Coles
Journal: Journal of Clinical Oncology (2013)

There are few randomized controlled trial data to confirm that improved homogeneity with simple intensity-modulated radiotherapy (IMRT) decreases late breast tissue toxicity. The Cambridge Breast IMRT trial investigated this hypothesis, and the 5-year results are reported.Standard tangential plans of 1,145 trial patients were analyzed; 815 patients had inhomogeneous plans (≥ 2 cm(3) receiving 107% of prescribed dose: 40 Gy in 15 fractions over 3 weeks) and were randomly assigned to standard radiotherapy (RT) or replanned with simple IMRT; 330 patients with satisfactory dose homogeneity were treated with standard RT and underwent the same follow-up as the randomly assigned patients. Breast tissue toxicities were assessed at 5 years using validated methods: photographic assessment (overall cosmesis and breast shrinkage compared with baseline pre-RT photographs) and clinical assessment (telangiectasia, induration, edema, and pigmentation). Comparisons between different groups were analyzed using polychotomous logistic regression.On univariate analysis, compared with standard RT, fewer patients in the simple IMRT group developed suboptimal overall cosmesis (odds ratio [OR], 0.68; 95% CI, 0.48 to 0.96; P = .027) and skin telangiectasia (OR, 0.58; 95% CI, 0.36 to 0.92; P = .021). No evidence of difference was seen for breast shrinkage, breast edema, tumor bed induration, or pigmentation. The benefit of IMRT was maintained on multivariate analysis for both overall cosmesis (P = .038) and skin telangiectasia (P = .031).Improved dose homogeneity with simple IMRT translates into superior overall cosmesis and reduces the risk of skin telangiectasia. These results are practice changing and should encourage centers still using two-dimensional RT to implement simple breast IMRT.
Xenobiotic metabolising enzyme expression in colonic neoplasia.
Authors: J A McKay, G I Murray, R J Weaver, S W Ewen, W T Melvin, M D Burke
Journal: Gut (1993)

The cytochrome P450, epoxide hydrolase, and glutathione S-transferase enzyme families play an important part in the metabolism of many carcinogens and anti-cancer drugs. The expression of two forms of cytochrome P450 (P450 1A and P450 3A), epoxide hydrolase and of the alpha, mu, and pi forms of glutathione S-transferase in normal colon, colonic adenomas, and adenocarcinoma of the colon were studied by immunohistochemistry. This allowed the precise cellular site and distribution of each enzyme to be determined. Expression of all the xenobiotic metabolising enzymes studied was almost wholly confined to the epithelial cells, whether in normal, adenoma or carcinoma samples, except that cytochrome P450 3A was also identified in mast cells and glutathione S-transferase pi was also present in chronic inflammatory cells. Cytochrome P450 was present in only a small proportion of normal colon samples, whereas epoxide hydrolase and glutathione S-transferase mu were identified in about half, and glutathione S-transferase alpha and pi in most normal samples. By contrast all the enzyme forms studied were expressed in virtually all adenomas and in over half the carcinomas. These results suggest that cytochrome P450 1A and cytochrome P450 3A are more specific markers of colonic neoplasia than epoxide hydrolase or glutathione S-transferases alpha, mu, and pi.
Treatment-Related Myelodysplastic Syndrome and Acute Myelogenous Leukemia in Patients Treated With Ibritumomab Tiuxetan Radioimmunotherapy
Authors: Myron S. Czuczman, Christos Emmanouilides, Mohamed Darif, Thomas E. Witzig, Leo I. Gordon, Stephen Revell, Katie Vo, Arturo Molina
Journal: Journal of Clinical Oncology (2007)

To investigate the incidence of treatment-related myelodysplastic syndrome (t-MDS) and treatment-related acute myelogenous leukemia (t-AML) after treatment with ibritumomab tiuxetan radioimmunotherapy.Analysis of the incidence of t-MDS and t-AML in 746 patients with non-Hodgkin's lymphoma (NHL) treated with the ibritumomab tiuxetan regimen in registration and compassionate-use trials between 1996 and 2002.Nineteen patients (2.5%) developed t-MDS or t-AML at a median follow-up of 4.4 years (range, 0 to 9.3). These malignancies were diagnosed at a median of 5.6 years (range, 1.4 to 13.9) after the diagnosis of NHL and 1.9 years (range, 0.4 to 6.3) after radioimmunotherapy. The annualized rates were 0.3% per year after the diagnosis of NHL and 0.7% per year after treatment. Most patients with t-MDS or t-AML had multiple cytogenetic aberrations, commonly on chromosomes 5 and 7, suggesting an association with previous exposure to chemotherapy.Analysis of data from patients in registration and compassionate-use trials suggests that the annualized incidences of t-MDS and t-AML are consistent with that expected in patients with NHL who have had extensive previous chemotherapy treatment and do not appear to be increased after treatment with the ibritumomab tiuxetan regimen. Cytogenetic testing before treatment with radioimmunotherapy may identify existing chromosomal abnormalities in previously treated patients, particularly those who have been treated with alkylating agents and purine nucleoside analogs and would be at higher risk for t-MDS or t-AML.
The Volume-Quality Relationship of Mental Health Care: Does Practice Make Perfect?
Authors: Benjamin G. Druss, Carolyn Levinson Miller, Harold Alan Pincus, Sarah Shih
Journal: American Journal of Psychiatry (2004)

OBJECTIVE: An extensive literature has demonstrated a relationship between hospital volume and outcomes for surgical care and other medical procedures. The authors examined whether an analogous association exists between the volume of mental health delivery and the quality of mental health care. METHOD: The study used data for the 384 health maintenance organizations participating in the Health Employer Data and Information Set (HEDIS), covering 73 million enrollees nationwide. Analyses examined the association between three measures of mental health volume (total annual ambulatory visits, inpatient discharges, and inpatient days) and the five HEDIS measures of mental health performance (two measures of follow-up after psychiatric hospitalization and three measures of outpatient antidepressant management), with adjustment for plan and enrollee characteristics. RESULTS: Plans in the lowest quartile of outpatient and inpatient mental health volume had an 8.45 (95% CI [confidence interval]=4.97–14.37) to 21.09 (95% CI=11.32–39.28) times increase in odds of poor 7- and 30-day follow-up after discharge from inpatient psychiatric hospitalization. Low-volume plans had a 3.49 (95% CI=2.15–5.67) to 5.42 (95% CI=3.21–9.15) times increase in odds of poor performance on the acute, continuation, and provider measures of antidepressant treatment. CONCLUSIONS: The large and consistent association between mental health volume and performance suggests parallels with the medical and surgical literature. As with that previous literature, further work is needed to better understand the mechanisms underlying this association and the potential implications for using volume as a criterion in plan choice.