tbuckley/cabot-search huggingface dataset:
All doctors great and small.
Authors: E Lowes, J H McCoy
Journal: BMJ (1978)

IgE, T cells and transfer factor in mycosis fungoides SIR,-We have studied with great interest the article of Dr P L Amlot and Mr L A Green (11 February, p 327) on atopy and IgE concentrations in Hodgkin's disease (HD) and other lymphomas.The authors state that with one exception no valid study so far has shown any differences in serum IgE concentrations between people with malignant diseases and those without, the one exception being HD.We should like to point out that Tan et all in 1974 found an elevated serum IgE in patients with mycosis fungoides (MF), another malignant lymphoma.We would also like to add that we in 1975,2 although we were not able to confirm an increased mean IgE value for our patients with MF, found highly elevated values in 4 out of 22 cases.None of these 4 patients were atopic.This clearly indicates that high serum IgE values may also be found in other types of lymphoma.The distribution of B cells in the peripheral blood of our patients was normal, while the mean percentage of T cells was significantly lower than in controls.We have recently completed a preliminary investigation on transfer factor (TF) as an additional thera- peutic agent in MF.Twelve patients in a state of progressive disease were investigated.All but one had previously been in remission induced by topical whole-body treatment with nitrogen mustard.All continued their previous treatment in unchanged dosages but also received monthly injections of TF.Following this combined treatment seven patients improved significantly and two of these went into complete remission.Treatment was followed by an increase in T lymphocytes and a decrease in serum IgE.This decrease in IgE had no relationship to atopy.The differences between the original and latest values were significant (P < 0 05).We believe that the reverse relation between T cells and serum IgE following therapy adds support to the idea of a deficiency of suppressor T cells accounting for the increased IgE levels in some lymphomas, a suggestion dismissed by Dr Amlot and Mr Green.This, however, cannot be proved until an evaluation of the distribution of the various subpopulations of T lymphocytes has been performed.We believe that our own as well as Dr Amlot and Mr Green's findings may have a bearing on treatment.
Acute effects of an endothelin-1 receptor antagonist bosentan at different stages of heart failure in conscious dogs
Authors: R Choussat
Journal: Cardiovascular Research (1998)

Objective: Inhibition by endothelin antagonist is a potential therapy in heart failure. However, the effect of endothelin inhibition during the development of heart failure has not been evaluated. The goal of our study was to examine the acute hemodynamic effects of the mixed endothelin receptor antagonist bosentan in the control state and at different stages of heart failure induced by right ventricular pacing (250 bpm) in conscious dogs. Methods: Nine dogs were chronically instrumented for the measurements of left ventricular pressure and its first derivative (dP/dt), cardiac output, left ventricular regional wall thickness and aortic pressure. Bosentan (3 mg/kg, i.v. bolus) and placebo were given at control, at 1 week of pacing (stage of left ventricular dysfunction with perserved cardiac output) and at 3 weeks of pacing (phase of heart failure with low cardiac output). Results: With the development of heart failure, baseline plasma endothelin level increased progressively. Placebo did not induce hemodynamic and plasma endothelin changes during the 30 min recording at any stage. At control, bosentan did not change hemodynamics. At 1 and 3 weeks of pacing, bosentan did not modify left ventricular myocardial function indices but reduced mean arterial pressure (by 7±2 and 8±1 mm Hg respectively, p<0.005). Bosentan increased stroke volume at 3 weeks of pacing only. Conclusions: Endothelin inhibition by endothelin antagonist bosentan, decreases aortic pressure in both early left ventricular dysfunction and in heart failure in contrast with the control state. In the phase of heart failure with low cardiac output, bosentan increases stroke volume. In the early left ventricular dysfunction, bosentan, by reducing arterial pressure, may limit the deterioration of cardiac function through a reduction of the workload imposed on the heart.
Disposition of oral metronidazole in hepatic cirrhosis and in hepatosplenic schistosomiasis.
Authors: T K Daneshmend, M Homeida, C M Kaye, A A Elamin, C J Roberts
Journal: Gut (1982)

The pharmacokinetics of metronidazole 500 mg orally were determined in patients with hepatosplenic schistosomiasis and normal controls in the Sudan, and in cirrhotics and normal controls in Bristol. Plasma metronidazole levels were above the minimum inhibitory concentration of most susceptible anaerobic bacteria for four to six hours post-dose in all groups. Liver disease did not markedly influence the disposition of single oral doses of metronidazole. Cirrhotics showed some prolongation of metronidazole half-life, and somewhat greater metronidazole concentrations 24 hours after the dose. Concentrations of the oxidative metabolite of metronidazole were lower in Sudanese patients and normal controls than in normal British subjects. In chronic liver disease adjustment of metronidazole dosage is probably not required provided renal function is unimpaired.
Rupture of Abdominal Aortic Aneurysm Demonstrated on Tc-99m RBC Gastrointestinal Bleeding Study
Authors: C ROBERT DeARMAS, HARRY S. GILBERT
Journal: Clinical Nuclear Medicine (1995)

A 72-year-old woman with respiratory failure and chronic obstructive lung disease had abdominal pain and gastrointestinal bleeding. An ultrasound demonstrated an abdominal aortic aneurysm and during performance of a Tc-99m RBC gastrointestinal bleeding study, rupture of the aneurysm was observed. She was taken to the operating room where a large, contained retroperitoneal hematoma was found in association with a ruptured abdominal aortic aneurysm. This was repaired with a graft and the patient underwent colectomy for Ischemic bowel as well. The patient died the next day.
Induction of insulitis by glutamic acid decarboxylase peptide-specific and HLA-DQ8-restricted CD4(+) T cells from human DQ transgenic mice.
Authors: L Wen, F S Wong, L Burkly, M Altieri, C Mamalaki, D Kioussis, R A Flavell, R S Sherwin
Journal: Journal of Clinical Investigation (1998)

Insulin-dependent diabetes mellitus in humans is linked with specific HLA class II genes, e.g., HLA-DQA1*0301/ DQB1*0302 (DQ8). To investigate the roles of HLA-DQ8 molecules and glutamic acid decarboxylase (GAD) in disease development, we generated DQ8(+)/I-Abo transgenic mice expressing functional HLA-DQ8 molecules and devoid of endogenous mouse class II. DQ8(+)/I-Abo mice produced antigen-specific antibodies and formed germinal centers after immunization with GAD65 peptides. Two GAD peptide-specific (247-266 and 509-528), DQ8 restricted Th1 CD4(+) T cell lines, were generated from immunized DQ8(+)/I-Abo mice. They induced severe insulitis after adoptive transfer into transgene positive (but not negative) mice who were treated with a very low dose of streptozotocin that alone caused no apparent islet pathology. In addition to CD4, islet mRNA from these mice also showed expression of CD8, IFNgamma, TNFalpha, Fas, and Fas ligand. Our data suggest that a mild islet insult in the presence of HLA-DQ8 bearing antigen-presenting cells promotes infiltration of GAD peptide reactive T cells into the islet.
Control of Heparin Therapy With Activated Partial Thromboplastin Times
Authors: I. Spector, M. Corn
Journal: JAMA (1967)

In vitro and in vivo studies were carried out to determine whether a standardized laboratory procedure, the activated (kaolin) partial thromboplastin time (PTT), could be used to regulate heparin therapy. In vitro, increasing heparin concentrations caused progressive prolongation of both the Lee-White (L-W) coagulation time and the activated PTT. Comparison of the activated PTT with the L-W coagulation time in 78 patients revealed an approximate linear correlation between the two tests, with corresponding prolonged values for each test found in almost all heparinized patients. Our observations suggest that the activated PTT test procedure can be used to regulate heparin anticoagulation. The major advantage of this test is that it can be performed in the laboratory by trained technicians and completed within a few minutes.
Public concern about complaints against doctors is widespread
Authors: A. Savage
Journal: BMJ (1998)

EDITOR—In your review of the Dispatches television programme that attacked the General Medical Council you made several pertinent points about public disquiet.1 I have now been working as a volunteer for the Patients' Association for over two years, answering letters and calls on the helpline, and I have found that concern about the complaints procedures in place at the local level is widespread. How widespread I cannot say as we only hear from the …
Studies of Carbohydrate and Lipid Metabolism in Women Developing Hypertension on Oral Contraceptives
Authors: B. Mason, N. Oakley, V. Wynn
Journal: BMJ (1973)

Metabolic studies in 100 women developing hypertension on combined oestrogen-progestogen oral contraceptives have been compared with similar studies in normotensive women on oral contraceptives, matched for age and duration of contraceptive use, and in women not taking contraceptives.The metabolic changes known to be induced by oral contraceptives-impaired glucose tolerance, elevated blood pyruvate levels, and raised serum lipid concentrations-were found to be exaggerated in the matched hypertensive group, largely due to pronounced abnormalities in 33 subjects with diastolic blood pressures over 110 mm Hg.Women developing severe hypertension were older, more obese, and of higher parity than those with mild hypertension and there was a high incidence of previous toxaemia of pregnancy in the hypertensive group.The results show that in women on oral contraceptives changes in blood pressure and in metabolic functions tend to be correlated with one another, and are consistent with the hypothesis that oral contraception induces a primary biochemical effect whose expression in the individual is determined by intrinsic factors including genetic constitution, age, weight, and parity.
Multiple Biomarker Expression in Circulating Tumor Cells (CTCs) from Metastatic Breast Cancer (MBC) Patients (Pts).
Authors: G. Somlo, H. Hsieh, D. Curry, P. Frankel, R. Krivacic, S. Lau, N. Lazarus, N. Baker, S. Swain-Cabriales, R. Bruce
Journal: Cancer Research (2009)

Abstract Background: Numeration of CTCs from MBC pts is predictive of outcome. Quantitative changes in CTC-s are currently tested for their potential to monitor therapy (Rx). Biomarker characterization of CTCs may be a useful adjunctive guide for Rx selection. Method: At the COHCC between 5/1/2008 and 4/31/09, consecutively treated pts with newly diagnosed/or progressing MBC were accrued. Blood samples (10-40 ml) were procured prior to or during systemic Rx, and were sent to PARC for analysis. A novel high-speed scanning instrument located CTCs from cytokeratin (CK) labeling enabling high resolution images to be selectively acquired using digital microscopy. From these images, CTCs were identified by CK, DAPI (nuclear marker) and CD45, and protein expression levels were determined for HER2, ER, ERCC1 and EGFR. Cell lines with expression of each marker were used for normalization of the cell intensities, and a scoring system was used to account for relative number and expression levels of markers on the CTCs. Results: Of 21pts tested 81% were found to have detectable CTCs. CTCs were further analyzed from 13 such pts, some of whom had multiple specimens. Expression of EGFR and ERCC1 were detected in 77% and 92% of specimens tested. Expression of HER2 was detected in 47% and ER in 91% in samples tested. Discordance rates for the expression of the above 4 markers on the primary tumors vs. CTC were measured either before, during systemic treatment, or at progression on therapy. We observed significant discordance rates for all markers tested:ER 36%; ERCC1:20%; EGFR:60%; and HER2: 50%, respectively. Conclusions: Multiplex tumor marker testing of CTCs from pts with MBC is feasible. Following additional validation of expression patterns and the high discordance rates observed between CTCs and primary or metastatic tumor sites, prospective trials incorporating CTC expression into personalized treatment strategies may be justified. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 3007.
Methsuximide Overdose
Authors: Steven B. Karch
Journal: JAMA (1973)

To my knowledge, this is the third reported case of methsuximide overdosage. The resulting disorder is biphasic in nature, an apparently benign phase preceding deep coma by a variable number of hours. This sequence, unless anticipated, may lead to potentially lethal results in what otherwise should be a benign condition. The plasma half-life of methsuximide is less than three hours, but a metabolite, 2-methyl-2-phenyl-succinimide, was detected at high levels in the blood of our patient 60 hours postingestion, while the patient was still deeply comatose. The deep coma produced by overdose with methsuximide may be due to the continuing presence of its metabolite, and not to the drug itself. Similar arguments may apply to the antiseizure activity as well.
The impact of prophylactic fresh-frozen plasma and cryoprecipitate on the incidence of central nervous system thrombosis and hemorrhage in children with acute lymphoblastic leukemia receiving asparaginase
Authors: Lesleigh S. Abbott, Mariana Deevska, Conrad V. Fernandez, David Dix, Victoria E. Price, Hao Wang, Louise Parker, Margaret Yhap, Colleen Fitzgerald, Dorothy R. Barnard, Jason N. Berman
Journal: Blood (2009)
Psychiatry in Mainland China: History and Recent Status
Authors: LORRIN M. KORAN
Journal: American Journal of Psychiatry (1972)

The author summarizes the English language literature on ancient, modern, and recent Chinese psychiatry for psychiatrists traveling to mainland China and others interested in cross-cultural psychiatry. Practices and beliefs regarding the etiology, diagnosis, and treatment of mental illness are described, together with manpower and facilities, professional publications, and research directions. The article concludes with a suggested outline for data gathering by psychiatric travelers to mainland China.
Autocrine activation of the MET receptor tyrosine kinase in acute myeloid leukemia
Authors: Alex Kentsis, Casie Reed, Kim L Rice, Takaomi Sanda, Scott J Rodig, Eleni Tholouli, Amanda Christie, Peter J M Valk, Ruud Delwel, Vu Ngo, Jeffery L Kutok, Suzanne E Dahlberg, Lisa A Moreau, Richard J Byers, James G Christensen, George Vande Woude, Jonathan D Licht, Andrew L Kung, Louis M Staudt, A Thomas Look
Journal: Nature Medicine (2012)
Androgen deprivation treatment in prostate cancer
Authors: B. C. Thomas, D. E. Neal
Journal: BMJ (2013)

A 65 year old man presents with lower back pain and acute urinary retention. He has tenderness over his lumbar spine, a palpable urinary bladder, and a firm, irregularly enlarged prostate on digital rectal examination. His prostate specific antigen (PSA) level was 75 ng/mL (75 µg/L) (normal range <4.0 ng/mL). A transrectal ultrasound guided biopsy of the prostate confirms prostate cancer. A bone scan shows increased uptake in the pelvis and lumbar spine suggestive of metastases. His urinary retention is treated. After discussion of the diagnosis and treatment options with the patient, a decision is made to start androgen deprivation treatment.

Androgen deprivation treatment refers to treatments that act by reducing the effects of testosterone and other androgens, thus inhibiting the progression of prostate cancer.1 Surgical castration was the first form of such treatment, but the main treatments now are luteinising hormone releasing hormone (LHRH) agonists and anti-androgens.

### LHRH agonists

LHRH agonists such as goserelin, leuprorelin, and triptorelin induce castrate levels of testosterone by binding to their associated receptors in the anterior pituitary. This results in down regulation of the receptors, reducing luteinising hormone release from the pituitary and decreasing testosterone production by testicular Leydig cells. The initial stimulation of the receptors may lead to an initial flare-up of testosterone level, lasting up to 10 days. Castrate levels of testosterone (<1.74 nmol/L (< 50 ng/dL)) are reached within four weeks.

### Anti-androgens

This is a broad category of drugs that act mainly by inhibiting signalling through the androgen receptor, sometimes by competing with testosterone and dihydrotestosterone for receptor binding. Diminished signalling through the androgen receptor leads to apoptosis and inhibition of prostate cancer growth. There are two classes of anti-androgens: steroidal (cyproterone acetate) and non-steroidal (bicalutamide, nilutamide, and flutamide).

### Newer drugs

Other forms of androgen deprivation treatment include LHRH antagonists, such as degarelix, which binds …
Abstract 137: Targeting IAPs: NF-κB signaling pathways play a critical role in IAP antagonist induced apoptosis
Authors: Eugene Varfolomeev, Tatiana Goncharov, Domagoj Vucic
Journal: Cancer Research (2010)

Abstract Inhibition of apoptosis enhances the survival of cancer cells and facilitates their escape from immune surveillance and cytotoxic therapies. Inhibitor of apoptosis (IAP) proteins are anti-apoptotic regulators that block cell death in response to diverse stimuli. Because these proteins play an active role in promoting tumor maintenance, they are attractive targets for developing a novel class of cancer therapeutics. Through TRAF2 interactions, c-IAP1 and c-IAP2 are recruited to tumor necrosis factor receptor 1 (TNFR1)-associated protein complexes where they regulate receptor-mediated signaling. The ubiquitin E3 ligase activity of c-IAP1/2 regulates canonical and noncanonical NF-κB pathways by promoting ubiquitination of RIP1 and NIK. We have designed small-molecule IAP antagonists that bind with high affinities to select baculovirus IAP repeat (BIR) domains of IAPs resulting in a dramatic induction of c-IAP auto-ubiquitination and rapid proteasomal degradation. Neutralization of c-IAPs through knockdown or small-molecule IAP antagonists blunts TNF stimulated NF-κB activation and greatly sensitizes cells to TNF induced cell death. Investigation of death receptor signaling complexes revealed that FLIP plays an important role in IAP antagonist stimulated apoptotic pathways and that down-regulation of FLIP sensitizes otherwise resistant cells to IAP antagonist induced cell death. In addition, regulation of NF-kB signaling pathways by cellular IAPs represents a pivotal point in IAP antagonists induced cell death. The interplay between pro-survival and pro-apoptotic signaling involves multiple levels of coordination and the regulation of these processes can determine the fate of treated cells. Finally, our IAP antagonists inhibit tumor growth in vivo as single agents and in combination with a number of standard of care anti-tumor agents including death receptor agonists. Interestingly, while single-agent activity of IAP antagonists relies on TNF signaling, the synergistic activity of IAP antagonists with FasL or anti-DR5 antibody does not depend on TNF signaling but on XIAP antagonism. Understanding the significance of protein stability and death receptors mediated pathways for inhibition of apoptosis by IAP proteins is important for the design of potent IAP-directed compounds. These compounds can be used in the treatment of malignancies in which IAP expression contributes to tumor progression and resistance to conventional chemotherapeutic agents. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 137.
Effect of intravenous infusion of insulin in diabetics with acute myocardial infarction.
Authors: R S Clark, M English, G P McNeill, R W Newton
Journal: BMJ (1985)

Diabetes mellitus is associated with a high mortality after myocardial infarction. To see whether this may be decreased by improved diabetic control the effect of an insulin infusion regimen was studied in patients with acute myocardial infarction. From April 1982 to April 1983, 33 diabetics were admitted with acute myocardial infarction. Those being treated with diet alone or oral hypoglycaemic drugs continued with this unless control was poor, when they were changed to a "sliding scale" regimen of subcutaneous insulin injections thrice daily. Those already receiving insulin were maintained on thrice daily subcutaneous injections. From April 1983 to April 1984, 29 diabetics had acute myocardial infarction. Those receiving treatment with oral hypoglycaemic drugs or insulin were changed to continuous intravenous infusion of insulin, the aim being to maintain the blood glucose concentration at 4-7 mmol/I (72-126 mg/100 ml). Those being treated with diet alone continued with this if blood glucose concentrations were acceptable. Total mortality fell from 42% in the first year to 17% in the second (p less than 0.05). Over the same period mortality among non-diabetic patients with myocardial infarction did not change significantly. There was a significant fall in cardiac arrhythmias (expressed as the percentage of patients in whom arrhythmias were recorded) from 42% to 17% (p less than 0.05). The most significant fall in the incidence of complications occurred in those who had been receiving oral hypoglycaemic drugs on entry to the study (87% to 50%, p less than 0.05).
Reducing Injuries from Falls
Authors: Lesley M. Day, Caroline F. Finch, Leonie Segal
Journal: New England Journal of Medicine (2008)

To the Editor: Evaluating systemwide fall-prevention programs is crucial for translating the now substantial trial-based evidence of the efficacy of certain fall-prevention measures. Tinetti et al. (July 17 issue)1 report a 9% reduction in serious fall-related injuries after a U.S. community-wide intervention that encouraged clinicians to implement a range of evidence-based fall-prevention strategies. This finding is consistent with the results of our own recent research in Australia. Using population-level epidemiologic modeling, we have predicted reductions in national rates of fall-related hospital admissions for people 65 years of age or older that range from 0.4 to 4.6% in a 12-month period . . .
Editorial: A different drummer
Authors: S. Vaisrub
Journal: JAMA (1974)

Hemoglobinuria, occurring—albeit infrequently—after a long march or run, was originally attributed to exertion and thus labeled "exertional." Later, when it was observed that the exertion always entailed prolonged locomotion, this syndrome was renamed "march hemoglobinuria." Only after Davidson<sup>1</sup>had provided convincing evidence that trauma to the capillary bed of the soles was responsible for the fragmentation of erythrocytes, did the traumatic nature of this pigmenturia become apparent. The traumatic etiology became even more obvious when Streeton<sup>2</sup>reported a variant of "march" hemoglobinuria occurring not after marching, but after karate exercises. The trauma was brought about not by the impact of the sole but by that of the fist and ulnar aspect of the hand on concrete and wooden surfaces. Just as in the case of the stomping marcher, it could be prevented by the interposition of foam rubber at the areas of impact. Another variant of "traumatic"—the term