tbuckley/cabot-search huggingface dataset:
Referrals between consultants: System has potential for error
Authors: Peter Gooderham
Journal: BMJ (2006)

Case reports of suspected adverse drug reactions Case reports were dismissed too quicklyEditor-The main difference between the replications by Loke et al of Venning's studies from the 1980s and the original is the evidence that is accepted as further follow-up. 1 Loke et al mention that 56 of 63 case reports on adverse reactions were cited at least once but accept only nine instances as valid follow-up: attempts at proof of mechanisms or controlled studies.However, unexpected adverse effects are by definition due to an unknown mechanism, and many established adverse effects still escape elucidation after years.Moreover, further accumulation of anecdotal reports can be sufficient evidence.A 10 year tally of 22 drugs that were withdrawn from the market showed that 18 were prompted by case reports and only four by a controlled study; for at least 13 the case reports proved sufficient reason for withdrawal. 2 A highly unusual event that is repeatedly reported in a recently marketed drug, in the absence of publicity, points to an exceedingly high relative risk, a good argument for cause and effect. 3 Moreover, these risks will be picked up spontaneously. 4 5 Apart from the nine instances of follow-up that were accepted by Loke et al, 15 datasheets were amended and seven BNP drug monographs changed.So, even with some overlap, close to half of the case reports were somehow sufficiently noteworthy to have had consequences.Given the small sample size, this is not far from Venning's original.It is a pity that Loke et al do not make all follow-up more explicit for all 56 instances that followed the 63 reports.Their overall conclusion that lack of follow-up means that case reports are of limited value is a non-sequitur.It shows that a more consistent scheme of hypothesistesting studies by industry, government, or third parties is needed instead of the current haphazard approach to drug safety.Such publications may alert and help clinicians in recognising potential adverse events in their patients.Often there is no other way of discovering something unusual.The record of systematic-that is, controlledpostmarketing surveillance in detecting unexpected adverse effects remains surprisingly poor.
The Near-Death Experience
Authors: Michael B. Sabom
Journal: JAMA (1980)

To the Editor.—  In a recent COMMENTARY (242:2291, 1979), Richard S. Blacher, MD, points out that the  after   of the dying patient tells us nothing of the final state of death itself. Furthermore, he urges that misinterpretation of this  could be avoided with a closer examination of the phenomenon.  I have recently conducted a systematic investigation of these experiences in 107 persons known to have survived an episode of unconsciousness and near death (ie, cardiac arrest and coma). 1 Using standardized interview techniques, the social, religious, and demographic backgrounds of each person were evaluated along with the details of each medical crisis event and any possible recollections from the period of unconsciousness. Like Blacher, I have concluded that these experiences are not by themselves prima facie evidence of life after death. Thus, near-death experience (NDE) becomes an appropriate label. Furthermore, I concur that a closer examination
Effect of the long-term administration of corticotropin-releasing factor on the pituitary-adrenal and pituitary-gonadal axis in the male rat.
Authors: C Rivier, W Vale
Journal: Journal of Clinical Investigation (1985)

The effect of the continuous exposure to ovine corticotropin-releasing factor (oCRF) was measured in adult male rats. The intravenous infusion of 0.75 nmol oCRF/h to intact rats over a 24-h period was accompanied by a peak of ACTH and corticosterone secretion that occurred during the first 90 min of administration of the releasing factor, followed by a decrease to lower, but still above control, values. Additionally, corticotropin-releasing factor (CRF)-treated rats had decreased plasma testosterone levels. The subcutaneous administration of 0.075 or 0.75 nmol oCRF/h to intact rats for 7 d also resulted in elevations of both plasma ACTH and corticosterone levels comparable to those measured after a 24-h exposure to the releasing factor, as well as dose-related hypertrophy of the adrenals and increases in pituitary ACTH content. In these animals, CRF markedly inhibited luteinizing hormone (LH) (but not follicle-stimulating hormone [FSH] ), testosterone, and PRL secretion and decreased seminal vesicle weights. All the effects of CRF were mimicked by exogenously administered ACTH. By contrast, with the exception of FSH secretion, which was slightly elevated by CRF, neither CRF nor ACTH were able to significantly modify reproductive parameters in adrenalectomized animals, which suggests that the elevation of circulating levels of adrenal steroids induced by peripherally administered CRF represents major mediators of CRF-induced inhibition of fertility. These results indicate that in the rat, the continuous stimulation of the pituitary-adrenal axis by peripherally administered CRF causes some degree of desensitization of the pituitary-adrenal axis, but is still accompanied by persistent elevations of the circulating levels of both ACTH and corticosteroids. The increased secretion of adrenal steroids by CRF-treated rats is believed to participate in the disruption of reproductive parameters observed in these rats.
Recurrence After Curative Excision of Carcinoma of the Large Bowel
Authors: E.S.R. Hughes, A.M. Cuthbertson
Journal: JAMA (1962)

A major difference is noted between the recurrences of carcinoma of the rectum as compared with carcinoma of the colon; as for example, in the first three years following surgery, 6% of patients with carcinoma of the rectum showed systemic metastasis compared with 1% of those with carcinoma of the colon. The most likely avenues for spread are the middle and inferior hemorrhoidal veins. Accordingly, the authors recommend that ligation of the inferior mesenteric vascular pedicle be undertaken following mobilization of the rectum.
Membrane type 1–matrix metalloproteinase is involved in migration of human monocytes and is regulated through their interaction with fibronectin or endothelium
Authors: Salomón Matías-Román, Beatriz G. Gálvez, Laura Genís, María Yáñez-Mó, Gonzalo de la Rosa, Paloma Sánchez-Mateos, Francisco Sánchez-Madrid, Alicia G. Arroyo
Journal: Blood (2005)
CURIOUS FACTS YOU FIND IN GENERAL SURGERY.
Authors: LUCIEN LOFTON
Journal: JAMA (1900)

<h3>INJURY TO NEGRO'S HEAD.</h3> Not many months ago I was called into the country to see a negro who had been chopped in the head with an ax "during a friendly" bout. I found a seemingly inanimate form, lying prone on the ground, and oozing leisurely from a long wound on the side of the head and face were several streams of blood. The man had received the cut three hours before and nothing had been done to check the flow of blood. Negroes are a peculiar people. Under no circumstances would one have helped this poor fellow, from the fear of getting "mixed" up with the courts, although they were perfectly willing to look on and speculate on the final outcome of everything connected with the case. Upon a closer examination I found that the external temporal and the transverse facial arteries had been entirely severed, besides a number
DIFFERENTIATION BETWEEN ANXIETY AND DEPRESSION BY THE PHOTICALLY ACTIVATED ELECTROENCEPHALOGRAM
Authors: CHARLES SHAGASS
Journal: American Journal of Psychiatry (1955)

1. To determine whether the EEG response to intermittent photic stimulation was quantitatively different in different emotional states, 134 psychiatric patients and 20 control subjects were studied. The amount of photic driving at flash rates of 10 and 15 per sec. was measured and the 15:10 response ratio determined. 2. There were significant differences in driving response between the sexes, females showing a greater response at all frequencies. 3. Response ratios were significantly higher in anxiety states than in depressions, with control subjects and paranoid schizophrenics intermediate. 4. Serial studies in a control subject showed that the driving response was labile and fluctuated in relation to feeling state. The direction of these fluctuations was as expected from the group differences demonstrated between anxiety and depression. 5. Results supported the hypothesis that the photically activated EEG is quantitatively different in different emotional states and that further research along present lines is indicated.
Recanalized Umbilical Vein in a Patient with a Hepatoma
Authors: GARY M. LEVINE, JAMES D. SLAVIN, NEAL F. EPSTEIN, RICHARD P. SPENCER
Journal: Clinical Nuclear Medicine (1992)

CT and ultrasound showed a mass in the right hepatic lobe of a man with a history of ethanol abuse. Biopsy revealed a hepatoma. A Tc-99m red blood cell study done previously showed a large vessel on the arterial phase running from the liver to the umbilicus, with an inferior continuation to the iliac vessels. At surgery, the upper pathway proved to be a hepatic artery fistula feeding into a patent umbilical vein. The fistula and the umbilical vein were ligated before chemoembolization of the intrahepatic tumor.
Evaluation of the free α‐hemoglobin pool in red blood cells: A new test providing a scale of β‐thalassemia severity
Authors: Corinne Vasseur, Serge Pissard, Elisa Domingues‐Hamdi, Michael C. Marden, Frédéric Galactéros, Véronique Baudin‐Creuza
Journal: American Journal of Hematology (2010)

β-Thalassemias are characterized by an imbalance of globin chains with an excess of α-chains which precipitates in erythroid precursors and red blood cells (RBCs) leading to inefficient erythropoiesis. The severity of the disease correlates with the amount of unpaired α-chains.Our goal was to develop a simple test for evaluation of the free α-hemoglobin pool present in RBC lysates. Alpha-Hemoglobin Stabilizing Protein (AHSP), the chaperone of α-Hb, was used to trap excess a-Hb. A recombinant GST-AHSP fusion protein was bound to an affinity micro-column and then incubated with hemolysates of patients. After washing, the α-Hb was quantified by spectrophotometry in the elution fraction. This assay was applied to 54 patients: 28 without apparent Hb disorder, 20 β-thalassemic and 6 α-thalassemic. The average value of free α-Hb pool was 93 ± 21 ppm (ng of free α-Hb per mg of Hb subunits)in patients without Hb disorder, while it varies from 119 to 1,756 ppm, in β-thalassemic patients and correlated with genotype. In contrast,the value of the free α-Hb pool was decreased in α-thalassemic patients (65 ± 26 ppm). This assay may help to characterize β-thalassemia phenotypes and to follow the evolution of the globin chain imbalance(α/β+γ ratio) in response to treatment.
HLA-A31- and HLA-Aw68-restricted cytotoxic T cell responses to a single hepatitis B virus nucleocapsid epitope during acute viral hepatitis.
Authors: G Missale, A Redeker, J Person, P Fowler, S Guilhot, H J Schlicht, C Ferrari, F V Chisari
Journal: The Journal of Experimental Medicine (1993)

We have recently developed the technology to identify and characterize the human histocompatibility leukocyte antigen (HLA) class I-restricted, CD8+ cytotoxic T lymphocyte (CTL) response to hepatitis B virus (HBV)-encoded antigens in patients with acute viral hepatitis. CTL are expanded in vitro by stimulation with HBV-derived synthetic peptides and selected by restimulation with a panel of HLA-matched stable transfectants that express the corresponding HBV protein. We have recently reported the existence of an HLA-A2-restricted, CD8+ CTL response to an epitope located between residues 18 and 27 of the HBV nucleocapsid core antigen (HBcAg). We now report the discovery of a CTL epitope located between HBcAg residues 141 and 151 that completely overlaps a critical domain in the viral nucleocapsid protein that is essential for its nuclear localization and genome packaging functions as well as processing of the precore protein. The CTL response to this epitope is dually restricted by the HLA-A31 and HLA-Aw68 alleles, which, unexpectedly, appear to use a common binding motif based on the results of alanine substitution and competition analysis, and the binding properties of these two alleles predicted from their known primary sequence, and from the three-dimensional structure of HLA-Aw68. We have also demonstrated that the HBV-specific CTL response to this epitope is polyclonal during acute viral hepatitis, since these two restriction elements can present the HBcAg 141-151 epitope to independent CTL clones derived from a single patient; and that the CTL response is multispecific, since HLA-A2-restricted and HLA-Aw68-restricted CTL responses to HBcAg 18-27 and HBcAg 141-151, respectively, have been identified to coexist in another patient. The foregoing argue against the emergence of CTL escape mutants as a significant problem during HBV infection, especially at this locus, where mutations might be incompatible with viral replication. Finally, our data suggest an association between the HBV-specific CTL response and viral clearance, and they have implications for the design of immunotherapeutic strategies to terminate HBV infection in chronically infected patients.
Telomere Length and Recurrence Risk after Curative Resection in Patients with Early-Stage Non–Small-Cell Lung Cancer: A Prospective Cohort Study
Authors: Eric S. Kim, Yuanqing Ye, Ara A. Vaporciyan, Jinliang Xing, Maosheng Huang, Jian Gu, Jack A. Roth, Scott M. Lippman, Xifeng Wu
Journal: Journal of Thoracic Oncology (2014)
Am I my father's keeper?
Authors: Jim Young
Journal: BMJ (2004)

My 84 year old dad was in a nursing home and had pretty lousy short term memory. He also had a chronic and painful diabetic ulcer on the great toe of his right foot, and intermittent spasm of the calf muscles caused him to wince in time with an incessant and involuntary knees-up.

The vascular surgeon recommended a below knee amputation. After explaining this to my …
TCT-888 Patients With Aortic Stenosis Referred For Transcatheter Aortic Valve Implantation: Treatment Decision, In-hospital Outcome And Determinants Of Survival
Authors: Rutger-Jan Nuis, Antonio Dager, Robert M.A. Van Der Boon, Marisol Jaimes, Bernardo Caicedo, Jaimes Fonseca, Nicolas van Mieghem, Luis Benitez, Juan Pablo Umana, William O'Neill, Eduardo de Marchena, Peter De Jaegere
Journal: Journal of the American College of Cardiology (2012)
THE EFFECTS OF VENOUS OBSTRUCTION UPON INTERSTITIAL PRESSURE IN ANIMAL AND HUMAN SKIN
Authors: Philip D. McMaster
Journal: The Journal of Experimental Medicine (1946)

The changes of intracutaneous pressure in the limbs of mice and human beings have been followed during and after periods of venous obstruction with almost unhindered arterial flow. During the first 30 minutes of obstruction the interstitial pressure in the tense skin of the lower legs of mice, a pressure which is slightly higher than that in the loose skin of the ears, backs, and thighs (21), rose from 2.6 to 4.6 cm. of water to about 32 cm., thereafter remaining constant. It would appear that the escape of fluid from the capillaries is checked at this pressure. In the skin of the arm and leg of man the interstitial pressure rose from 2.5-3.7 cm. of water to 15.0-23.0, within 15 to 27 minutes after venous obstruction had been produced, mounting no higher during the period of observation. When venous obstruction had existed for about 20 minutes or more the subjects sometimes experienced sensations of relief from congestion as if some tissue adjustment or the opening of some venous by-pass in the marrow had occurred, preventing a further rise of pressure. However this may be, the pressures still appeared to be great enough to prevent further escape of fluid from the capillaries, at least for the time being.
THE HOUR-GLASS DUODENUM.A PLEA FOR A MORE EXTENDED USE OF PLASTIC SURGERY TO PRESERVE THE DUODENAL ROUTE.
Authors: KENNETH A. J. MACKENZIE
Journal: JAMA (1906)

Only the most casual reference is made in literature to the deformities of the duodenum, and when the pyloric end of the stomach is the seat of intrinsic obstructive disorders the pylorus is almost invariably referred to as the seat of the obstructing cause. In these later days of gastric surgery there is evident a growing sense of appreciation of the important rôle played by the duodenal ulcer in causing obstructive disorders of the stomach, and more critical analysis of the distribution of the so-called peptic ulcer tends to demonstrate an increasing ratio of duodenal ulcers. The tardy discovery of this fact is easily explained by the vaguely defined symptom-complex of the duodenal ulcer. During the last eight years I have operated on four cases of the so-called acute abdomen and discovered perforated duodenal ulcers. In all these cases but one, the most careful canvass of the personal history failed
Interpretation of male rat renal tubule tumors.
Authors: I S Rodgers, K P Baetcke
Journal: Environmental Health Perspectives (1993)

Based on an analysis of recent scientific studies, a Technical Panel of the U.S. Environmental Protection Agency's (EPA) Risk Assessment Forum recently advised EPA risk assessors against using information on certain male rat renal tubule tumors to assess human risk under conditions specified in a new Forum report. Risk assessment approaches generally assume that chemicals producing tumors in laboratory animals are a potential cancer hazard to humans. For most chemicals, including classical rodent kidney carcinogens such as N-ethyl-N-hydroxyethylnitrosamine, this extrapolation remains appropriate. Some chemicals, however, induce accumulation of alpha 2u-globulin (alpha 2u-g), a low molecular weight protein, in the male rat kidney. The alpha 2u-g accumulation initiates a sequence of events that appears to lead to renal tubule tumor formation. Female rats and other laboratory mammals administered the same chemicals do not accumulate low molecular weight protein in the kidney, and they do not develop renal tubule tumors. Because humans appear to be more like other laboratory animals than like the male rat, in this special situation, the male rat is not a good model for assessing human risk. The Forum report stresses the need for full scrutiny of a substantial set of data to determine when it is reasonable to presume that renal tumors in male rats are linked to a process involving alpha 2u-g accumulation and to select appropriate procedures for estimating human risks under such circumstances.
QUANTIFICATON OF IMPROVED CEREBRAL PERFUSION FOLLOWING CAROTID ENDARTERECTOMY USING SPECT IMP IMAGING AND A NEW REPERFUSION INDEX
Authors: W A Morgan, J A Siegel, A J Comerota, R A Vitti, A H Maurer
Journal: Clinical Nuclear Medicine (1989)

Morgan, W. A.; Siegal, J. A.; Comerota, A. J.; Vitti, R. A.; Maurer, A. H. Author Information
DNA Damage Disrupts the p14ARF-B23(Nucleophosmin) Interaction and Triggers a Transient Subnuclear Redistribution of p14ARF
Authors: Casey Lee, Brian A. Smith, Keya Bandyopadhyay, Ruth A. Gjerset
Journal: Cancer Research (2005)

Abstract The p14 alternate reading frame (ARF) tumor suppressor plays a central role in cancer by binding to mdm2 (Hdm2 in humans) and enhancing p53-mediated apoptosis following DNA damage and oncogene activation. It is unclear, however, how ARF initiates its involvement in the p53/mdm2 pathway, as p53 and mdm2 are located in the nucleoplasm, whereas ARF is largely nucleolar in tumor cells. We have used immunofluorescence and coimmunoprecipitation to examine how the subnuclear distribution and protein-protein interactions of ARF change immediately after DNA damage and over the time course of the DNA damage response in human tumor cells. We find that DNA damage disrupts the interaction of ARF with the nucleolar protein B23(nucleophosmin) and promotes a transient p53-independent translocation of ARF to the nucleoplasm, resulting in a masking of the ARF NH2 terminus that correlates with the appearance of ARF-Hdm2 complexes. The translocation also results in an unmasking of the ARF COOH terminus, suggesting that redistribution disrupts a nucleolar interaction of ARF involving this region. By 24 hours after irradiation, DNA repair has ceased and the pretreatment immunofluorescence patterns and complexes of ARF have been restored. Although the redistribution of ARF is independent of p53 and likely to be regulated by interactions other than Hdm2, ARF does not promote UV sensitization unless p53 is expressed. The results implicate the nucleolus and nucleolar interactions of the ARF, including potentially novel interactions involving its COOH terminus as sites for early DNA damage and stress-mediated cellular events.
Randomised clinical trials in general practice.
Authors: M. Aylett, P. Creighton, S. Jachuck
Journal: BMJ (1992)

<b><i>Article abstract</i></b> Creatine monohydrate has been shown to increase strength in studies of young healthy subjects and in a few studies with patients. Creatine monohydrate (10 g daily for 5 days to 5 g daily for 5 days) was administered to patients with neuromuscular disease in a pilot study (Study 1; n = 81), followed by a single-blinded study (Study 2; n = 21). Body weight, handgrip, dorsiflexion, and knee extensor strength were measured before and after treatment. Creatine administration increased all measured indices in both studies. Short-term creatine monohydrate increased high-intensity strength significantly in patients with neuromuscular disease.
STUDIES ON THE PRECIPITABLE SUBSTANCES OF BACILLI OF THE SALMONELLA GROUP
Authors: J. Furth, K. Landsteiner
Journal: The Journal of Experimental Medicine (1929)

Specific precipitable substances rich in carbohydrates, containing very little protein and small amounts of a material apparently of fatty nature, have been prepared from the main serological types of the typhoid-paratyphoid groups. The preparations in their present state of purity do not exhibit very pronounced chemical differences in spite of serological dissimilarity. In this respect the results differ from those observed with the polysaccharides of pneumococci. The specificity of the precipitin reactions of these substances parallels in a general way the so called small flaking agglutination. Attempts to separate different fractions from the active substance serologically by means of precipitation with antibody solutions were on the whole unsuccessful. The differences in resistance to the action of acid and alkali were found to be characteristic for various specific carbohydrates.
Intracranial Tumor Due to Traumatism.
Authors: W. W. Keen
Journal: JAMA (1907)

Florence, Italy, Nov. 1, 1907.  To the Editor:  —I was much interested in the case of cerebral tumor resulting from trauma, reported inThe Journal, Oct. 19, 1907, page 1361, by Dr. Leszynsky and commented on editorially in the same issue. The report reminded me of the first case of cerebral surgery in which I ever operated. The cause of the tumor—in my case, a fibroma—was the same, viz., trauma from a small splinter of bone from the inner table of the skull—a very rare fracture. In Dr. Leszynsky's case only two years elapsed between the accident and death; in my own over twenty years elapsed between the accident and the operation. The bone splinter was found at operation, adhering to the dura from which the fibroma arose. The operation was done in the autumn of 1887 and was reported in the American Journal of the Medical Sciences in, I