tbuckley/cabot-search huggingface dataset:
Abstract C61: The use of beta blockers improve cancer-specific survival in prostate cancer patients receiving androgen deprivation therapy
Authors: Helene Hartvedt Grytli, Lise Lund Håheim, Kristin Austlid Taskén
Journal: Cancer Research (2012)

Abstract Objective: To examine the potential effects of beta blocker use on clinical prognostic factors present at the time of prostate cancer diagnosis and on prostate cancer specific survival. Experimental procedures: The present study is a prospective study of men who participated both in the Oslo study of 1972/73 and in a follow-up health screening in 2000 (n=6515). Self-administrated questionnaires provided information about use of beta blockers during the past four weeks before the survey in 2000 (n=776; 11.9%). Data from the 2000 survey were coupled with clinical and prognostic information from the Norwegian Cancer Registry to identify those men diagnosed with prostate cancer. Mortality data was obtained from the Norwegian Causes of Death Registry. All men diagnosed with prostate cancer that did not report the use of a beta blocker were considered the control group. Results: Out of the 6515 men participating in the Oslo II study, a total of 655 men (10.1%) were diagnosed with prostate cancer. There was no significant differences between beta blocker users (n=80) and non users (n=575) regarding PSA, clinical T-stage, Gleason score, metastasis, or age at diagnosis. There were also no effects on prostate cancer specific survival in the group as a whole, analyzed by competing risk regression modeling (adjusted subdistribution hazard ratio (SHR) 0.69, 95% confidence interval (CI) 0.36-1.30, p = 0.252). When stratifying patients according to androgen deprivation therapy (ADT) from time of diagnosis, there was an association between beta blocker use and improved prostate cancer specific survival for men in the ADT- treated group (n=263), with an adjusted SHR of 0.18 (95% CI 0.03–0.96, p = 0.044). For patients not treated with ADT from the time of diagnosis (n=227), no difference on prostate cancer specific survival was seen (adjusted SHR 1.19, 95% CI 0.20-6.99, p = 0.844). Adjustment was made for metastasis, age at diagnosis and level of education as recorded in the 2000 screening. Conclusion: The use of beta blockers was associated with an increased prostate cancer specific survival in men treated with ADT. Citation Format: Helene Hartvedt Grytli, Lise Lund Håheim, Kristin Austlid Taskén. The use of beta blockers improve cancer-specific survival in prostate cancer patients receiving androgen deprivation therapy [abstract]. In: Proceedings of the AACR Special Conference on Advances in Prostate Cancer Research; 2012 Feb 6-9; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2012;72(4 Suppl):Abstract nr C61.
Activation of hepatic Nrf2in vivo by acetaminophen in CD-1 mice
Authors: Christopher E. P. Goldring, Neil R. Kitteringham, Robert Elsby, Laura E. Randle, Yuri N. Clement, Dominic P. Williams, Michael McMahon, John D. Hayes, Ken Itoh, Masayuki Yamamoto, Kevin B. Park
Journal: Hepatology (2004)

The transcription factor NF-E2-related factor 2 (Nrf2) plays an essential role in the mammalian response to chemical and oxidative stress through induction of hepatic phase II detoxification enzymes and regulation of glutathione (GSH). Enhanced liver damage in Nrf2-deficient mice treated with acetaminophen suggests a critical role for Nrf2; however, direct evidence for Nrf2 activation following acetaminophen exposure was previously lacking. We show that acetaminophen can initiate nuclear translocation of Nrf2 in vivo, with maximum levels reached after 1 hour, in a dose dependent manner, at doses below those causing overt liver damage. Furthermore, Nrf2 was shown to be functionally active, as assessed by the induction of epoxide hydrolase, heme oxygenase-1, and glutamate cysteine ligase gene expression. Increased nuclear Nrf2 was found to be associated with depletion of hepatic GSH. Activation of Nrf2 is considered to involve dissociation from a cytoplasmic inhibitor, Kelch-like ECH-associated protein 1 (Keap1), through a redox-sensitive mechanism involving either GSH depletion or direct chemical interaction through Michael addition. To investigate acetaminophen-induced Nrf2 activation we compared the actions of 2 other GSH depleters, diethyl maleate (DEM) and buthionine sulphoximine (BSO), only 1 of which (DEM) can function as a Michael acceptor. For each compound, greater than 60% depletion of GSH was achieved; however, in the case of BSO, this depletion did not cause nuclear translocation of Nrf2. In conclusion, GSH depletion alone is insufficient for Nrf2 activation: a more direct interaction is required, possibly involving chemical modification of Nrf2 or Keap1, which is facilitated by the prior loss of GSH. (Hepatology 2004;39:1267-1276.)
Immunogenetic analysis of bone marrow aspirates in patients with non‐hodgkin lymphomas
Authors: Douglas J. Ellison, Eddie Hu, Dan Zovich, Lauren Pinter‐Brown, Paul K. Pattengale
Journal: American Journal of Hematology (1990)

The immunogenetic analysis (IGA) on the staging bone marrow aspirates in 15 patients with non-Hodgkin lymphoma (NHL) is reported. We found the sensitivity of IGA and morphologic examination in detecting bone marrow involvement by malignant lymphoma to be 91% and 82%, respectively. In 11 cases there was agreement between the morphologic findings and IGA. In 8 of these 11 cases, IGA confirmed the morphologic involvement of the bone marrow by demonstrating clonal rearrangement of either the immunoglobulin heavy- and/or light-chain or the T-cell receptor beta chain (TCR) genes. In 3 of these 11 cases, morphology showed no involvement and IGA showed germline configurations for both the immunoglobulin heavy- and light-chain or the TCR genes. In 2 additional cases the techniques proved to be complementary, as involvement was detected by only 1 of the 2 procedures. In 1 of these 2 cases, IGA showed gene rearrangement while morphologic examination was negative for involvement by NHL, while in the other case, morphologic examination showed involvement by NHL, but IGA did not show gene rearrangement. IGA was also useful in determining the clonality of solitary lymphoid nodules in the 2 remaining cases when morphologic interpretation was equivocal. In the 12 cases with bone marrow involvement, the immunophenotype and immunogenotype agreed in 11 cases. In the one case in which there was a discordance between the immunophenotype and immunogenotype, the immunophenotype was incorrectly interpreted as B-cell lineage, while the immunogenotype demonstrated a T-cell lineage. IGA also demonstrated a clonal population in 1 case of T-chronic lymphocytic leukemia where other techniques could not demonstrate the clonality of the pathologic process. IGA analysis may detect bone marrow involvement in NHL which may not be detected by morphologic examination because of patchy distribution.
Captopril in primary pulmonary hypertension.
Authors: C V Leier, D Bambach, S Nelson, J B Hermiller, P Huss, R D Magorien, D V Unverferth
Journal: Circulation (1983)

Seven women with primary pulmonary hypertension underwent hemodynamic evaluation, at rest and during exercise, before and after the oral administration of captopril. Dose-response curves were generated for the 25-, 50- and 100-mg doses. Captopril significantly reduced systemic blood pressure and systemic vascular resistance; these effects persisted at submaximal levels of exercise. Captopril did not alter pulmonary artery pressure or resistance, cardiac output or stroke volume at rest or during exercise. Exercise tolerance did not improve. Four of the patients also received captopril chronically for 12 weeks at doses of 75 and 100 mg every 8 hours. Resting and exercise hemodynamic evaluation was repeated at the end of the 12-week period. Except for a persistent reduction in mean systemic blood pressure at rest, chronic captopril administration did not elicit hemodynamic changes. Measured exercise duration did not change during continuous captopril treatment, although one patient reported mild subjective improvement in activity tolerance. In primary pulmonary hypertension, captopril exerts its major effect on systemic vasculature, with little or no effect on the pulmonary circuit. While an occasional patient may experience some clinical improvement with captopril therapy, the majority of adult patients with severe primary pulmonary hypertension will not benefit from its chronic administration.
Histamine induces proliferation in keratinocytes from patients with atopic dermatitis through the histamine 4 receptor
Authors: Franziska Glatzer, Maria Gschwandtner, Sarah Ehling, Kristine Rossbach, Katrin Janik, Andreas Klos, Wolfgang Bäumer, Manfred Kietzmann, Thomas Werfel, Ralf Gutzmer
Journal: Journal of Allergy and Clinical Immunology (2013)
Mechanistic considerations in benzene physiological model development.
Authors: M A Medinsky, E M Kenyon, M J Seaton, P M Schlosser
Journal: Environmental Health Perspectives (1996)

Benzene, an important industrial solvent, is also present in unleaded gasoline and cigarette smoke. The hematotoxic effects of benzene in humans are well documented and include aplastic anemia, pancytopenia, and acute myelogenous leukemia. However, the risks of leukemia at low exposure concentrations have not been established. A combination of metabolites (hydroquinone and phenol, for example) may be necessary to duplicate the hematotoxic effect of benzene, perhaps due in part to the synergistic effect of phenol on myeloperoxidase-mediated oxidation of hydroquinone to the reactive metabolite benzoquinone. Because benzene and its hydroxylated metabolites (phenol, hydroquinone, and catechol) are substrates for the same cytochrome P450 enzymes, competitive interactions among the metabolites are possible. In vivo data on metabolite formation by mice exposed to various benzene concentrations are consistent with competitive inhibition of phenol oxidation by benzene. In vitro studies of the metabolic oxidation of benzene, phenol, and hydroquinone are consistent with the mechanism of competitive interaction among the metabolites. The dosimetry of benzene and its metabolites in the target tissue, bone marrow, depends on the balance of activation processes such as enzymatic oxidation and deactivation processes such as conjugation and excretion. Phenol, the primary benzene metabolite, can undergo both oxidation and conjugation. Thus the potential exists for competition among various enzymes for phenol. Zonal localization of phase I and phase II enzymes in various regions of the liver acinus also impacts this competition. Biologically based dosimetry models that incorporate the important determinants of benzene flux, including interactions with other chemicals, will enable prediction of target tissue doses of benzene and metabolites at low exposure concentrations relevant for humans.
Induction of Interferon Pathways Mediates In Vivo Resistance to Oncolytic Adenovirus
Authors: Ilkka Liikanen, Vladia Monsurrò, Laura Ahtiainen, Mari Raki, Tanja Hakkarainen, Iulia Diaconu, Sophie Escutenaire, Otto Hemminki, João D Dias, Vincenzo Cerullo, Anna Kanerva, Sari Pesonen, Daniela Marzioni, Marco Colombatti, Akseli Hemminki
Journal: Molecular Therapy (2011)

Oncolytic adenoviruses are an emerging experimental approach for treatment of tumors refractory to available modalities. Although preclinical results have been promising, and clinical safety has been excellent, it is also apparent that tumors can become virus resistant. The resistance mechanisms acquired by advanced tumors against conventional therapies are increasingly well understood, which has allowed development of countermeasures. To study this in the context of oncolytic adenovirus, we developed two in vivo models of acquired resistance, where initially sensitive tumors eventually gain resistance and relapse. These models were used to investigate the phenomenon on RNA and protein levels using two types of analysis of microarray data, quantitative reverse transcriptase-polymerase chain reaction and immunohistochemistry. Interferon (IFN) signaling pathways were found upregulated and Myxovirus resistance protein A (MxA) expression was identified as a marker correlating with resistance, while transplantation experiments suggested a role for tumor stroma in maintaining resistance. Furthermore, pathway analysis suggested potential therapeutic targets in oncolytic adenovirus-resistant cells. Improved understanding of the antiviral phenotype causing tumor recurrence is of key importance in order to improve treatment of advanced tumors with oncolytic adenoviruses. Given the similarities between mechanisms of action, this finding might be relevant for other oncolytic viruses as well.
A CASE OF BRAIN SYPHILIS
Authors: Nathan B. Eddy
Journal: JAMA (1913)

The course of the case of brain syphilis previously reported by me<sup>1</sup>has been interesting and for correctness a further report is necessary. <h3>Previous History.</h3> —The previous report stated that the patient, F. M., aged 34, married, a laborer, having a positive syphilitic history, was admitted to the hospital Dec. 28, 1912, in coma with convulsions and a transient left-sided hemiplegia. He had a strongly positive Wassermann and was treated by repeated injections of salvarsan, neosalvarsan and mercury salicylate. For the time being his recovery was complete and on Feb. 8, 1913, he was discharged from the hospital, apparently in perfect health. During February and the first part of March the patient returned weekly for intramuscular injections of mercury salicylate, one grain being injected each time. About the first of March he went to work in an iron foundry. <h3>Second Attack.</h3> —April 14, 1913, while at work, be suddenly
Antidepressant Drugs as a Cause of Death
Authors: Martin B. Keller
Journal: JAMA (1983)

<h3>To the Editor.—</h3> We heartily concur with Dr Lundberg's call for caution and data concerning the risk of depressive patients using antidepressants as suicidal agents (1982; 248:1879). The development of safer and more effective antidepressant drugs should help in reducing this risk. Meanwhile, we echo Dr Lundberg's warning that the currently available antidepressants are potent toxins when taken in overdose, and we strongly agree that patients who are at active risk of suicide must be treated carefully. Rather than be handed a "bottle of poison," patients who are actively suicidal should almost always be hospitalized and have any potentially lethal medication dispensed in safe dosages. We agree that no study has quantified the decrease in self-destructive attempts related to the efficacy of antidepressants. However, we think it is reasonable to infer from the studies that demonstrate the efficacy of these drugs in alleviating depression that a sizable proportion of untreated
Vaginal Birth after Cesarean Revisited
Authors: Michael F. Greene
Journal: New England Journal of Medicine (2004)

The U.S. total cesarean delivery rate has risen from 4 percent of deliveries in 1950 to 26 percent in 2002.1 Concerned about the rising rate of cesarean deliveries, and noting that 98 percent of women with a prior cesarean section delivered by repeated cesarean section, a National Institutes of Health Consensus Development Task Force in 1980 recommended that "properly selected" women should be encouraged to labor and deliver vaginally after a prior cesarean delivery.2 U.S. obstetricians and their patients were slow to respond to this call, but by the end of the 1980s, the rate of vaginal birth after prior . . .
England's largest hospital trust is put into special measures after catalogue of failings
Authors: M. Limb
Journal: BMJ (2015)

The head of England’s largest NHS hospital trust has apologised for care failings after a damning report by the healthcare inspector found that poor leadership, a culture of bullying, and low staffing levels had put patient safety at risk.1

Barts Health NHS Trust was placed in special measures after the Care Quality Commission (CQC) judged care standards “inadequate” at London’s Whipps Cross University Hospital, one of the trust’s six hospital sites.

Mike Richards, chief inspector of hospitals, said that some staff were reluctant to speak to inspectors and that some feared “repercussions” if their views were recorded. He said that many of the failings found in a previous inspection were still not resolved and that a “damaging” decision in 2013 to remove 220 posts across the trust and to “down-band” several hundred more nursing staff was still being felt. “The trust must get a grip on what is happening here and on the low staff morale,” Richards said.

The CQC also criticised high …
Making the dilemma of universal health checks clear to patients
Authors: S. L. Wookey
Journal: BMJ (2013)

Our practice is paid to provide health checks, which are both popular and appreciated.1

If the Cochrane review’s conclusions are correct,2 these checks do not benefit our patients.

I see four options: (1) continue; (2) continue but report myself to the General Medical Council for promoting an intervention from which I profit and which I …
Mental handicap and the family
Authors: L. C. Hall
Journal: BMJ (1967)

methohexitone methods' no immediate or late complications occurred, and in 2,000 of these the treatment lasted for one to two and even more hours.The technique is described in a film.8A Scottish dental school has recently proposed a diploma course in dental anaesthesia.While one must deplore the creation of too many " splinter " diplomas, the suggestion in this case is worth serious consideration, particularly if the course provides adequate training in the newer intravenous techniques.-I am, ete.,
Pyloric Channel Ulcer
Authors: Arno W. Sommer
Journal: JAMA (1960)

Seventy-eight patients with a roentgenologic diagnosis of an ulcer crater in the pyloric channel were studied (1) to determine if there is a symptom complex characteristic of pyloric channel ulcer, (2) to evaluate the accuracy of roentgen diagnosis, and (3) to survey the results of treatment. From the standpoint of symptoms alone, pyloric channel ulcer could not be distinguished from uncomplicated gastric or duodenal ulcer. Fifty-seven patients responded favorably to medical management, and complete healing of the ulcer crater was demonstrated roentgenologically and clinically in 30 of these patients. The roentgenologic diagnosis was confirmed in 16 of the 21 patients who had surgical treatment. Pyloric channel ulcer probably can be diagnosed more accurately by roentgenologic than by any other method including exploratory laparotomy.
Acute renal failure with selective medullary injury in the rat.
Authors: S N Heyman, M Brezis, C A Reubinoff, Z Greenfeld, C Lechene, F H Epstein, S Rosen
Journal: Journal of Clinical Investigation (1988)

Since human acute renal failure (ARF) is frequently the result of multiple rather than single insults, we used a combination of treatments to induce ARF in rats. Uninephrectomized, salt-depleted rats injected with indomethacin developed ARF after administration of radiocontrast. After 24 h, the plasma creatine rose from 103 +/- 3 to 211 +/- 22 mumol/liter (mean +/- SE) and the creatinine clearance dropped from 0.7 +/- 0.1 to 0.2 +/- 0.04 ml/min (P less than 0.001). Severe injury was confined to the outer medulla and comprised necrosis of medullary thick ascending limbs (mTALs), tubular collapse, and casts. Other nephron segments were free of damage except for the proximal convoluted tubules which showed vacuole formation originating from lateral limiting membranes that resembled changes reported in human contrast nephropathy. Cell damage to mTALs included mitochondrial swelling, nuclear pyknosis, and cytoplasmic disruption with superimposed calcification; these changes were most severe in the deepest areas of the outer medulla, away from vasa recta in zones remote from oxygen supply. The fraction of mTALs with severe damage was 30 +/- 7% (range 2-68) and the extent of injury was correlated with a rise in plasma creatinine (r = 0.8, P less than 0.001). Thus, the nature of mTAL injury was similar to the selective lesions observed in isolated kidneys perfused with cell-free medium and was shown to derive from an imbalance between high oxygen demand by actively transporting mTALs and the meager oxygen supply to the renal medulla. Combined multiple renal insults in the rat produce ARF that resembles the clinical syndrome of contrast nephropathy and is characterized by selective mTAL injury conditioned by medullary hypoxia.
701 PHARMACOKINETICS, EFFICACY AND SAFETY OF INTRAMUSCOLARE AND INTRAVENOUS OF HEPATITIS B IMMUNOGLOBULINS COMBINED WITH NUCLEOSIDE ANALOGUES IN PROPHYLAXIS OF HEPATITIS B AFTER LIVER TRANSPLANTPHARMACOKINETICS, EFFICACY AND SAFETY OF INTRAMUSCULAR AND INTRA
Authors: A. Marzano, P. Andreone, R. Volpes, D. Canova, C. Cursaro, A. Riili, B. Fiorentino, M. Bacci, S. Guazzini, P. Burra
Journal: Journal of Hepatology (2008)
Inhalation of Crack Cocaine Can Mimic Pulmonary Embolism
Authors: Siva Ramachandaran, Asad U. Khan, Simin Dadaparvar, Michael S. Sherman
Journal: Clinical Nuclear Medicine (2004)

Inhaled cocaine has been associated with a number of pulmonary manifestations including pulmonary edema, hypersensitivity pneumonitis, bronchospasm, obliterative bronchiolitis, alveolar hemorrhage, and pneumomediastinum. However, the effects of cocaine on pulmonary vasculature have been poorly described. The authors report a patient with a history of cocaine inhalation presenting with high clinical suspicion for pulmonary embolism and a high probability ventilation-perfusion lung scan. A pulmonary angiogram revealed no pulmonary embolism. The authors believe this syndrome was caused by intense pulmonary artery vasospasm secondary to cocaine inhalation. A pulmonary angiogram may be required to establish the correct diagnosis and avoid unnecessary anticoagulation in such patients.
Migraine doctor is suspended for serious breach of professional standards
Authors: C. Dyer
Journal: BMJ (2015)

Andrew Dowson, a leading migraine specialist, has been suspended from the UK medical register for four months for a “serious breach of professional standards” in the conduct of a clinical trial.

Dowson, director of headache services at King’s College Hospital in London, was co-principal investigator with Peter Wilmshurst, a cardiologist, in the Migraine Intervention with STARFlex Technology (MIST) trial to test whether a new device for closing patent foramen ovale could cure migraine.1

After casting doubt on the accuracy of the trial’s results Wilmshurst was sued by the device’s US based manufacturer, NMT Medical, in a notable libel case, which was eventually abandoned when the company went into liquidation and which helped to bring about reforms to English defamation law.

A panel of the Medical Practitioners Tribunal Service found that …
Reversible Hypertension
Authors: Manfred Blum
Journal: JAMA (1977)

Reversible hypertension occurred in a patient during episodes of hypercalcemia caused by hyperparathyroidism, vitamin D toxicity, and an infusion of calcium during an 11-year period of observation. It is suggested that normal renal function may be required for the hypertension of hyperparathyroidism to be reversible and that the hypertension may be directly related to the hypercalcemia in some patients. Early surgery is suggested for otherwise asymptomatic, mildly hypercalcemia hyperparathyroidism that is accompanied by hypertension. (<i>JAMA</i>237:262-263, 1977)