tbuckley/cabot-search huggingface dataset:
Effect of Penicillin on the Adherence of Streptococcus sanguis In Vitro and in the Rabbit Model of Endocarditis
Authors: Franklin D. Lowy, Daniel S. Chang, Ellen G. Neuhaus, Diane S. Horne, Alexander Tomasz, Neal H. Steigbigel
Journal: Journal of Clinical Investigation (1983)

The effect of penicillin treatment of Streptococcus sanguis in vitro, on subsequent bacterial density in the bloodstream and on cardiac valves in the rabbit model of endocarditis was studied. As experimental tools for this study, isogenic pairs of S. sanguis differing in resistance to streptomycin or rifampin were prepared by genetic transformation. Rabbits with traumatized heart valves received an intravenous inoculation of penicillin treated (1 μg/ml) and untreated S. sanguis, each marked by resistance to either streptomycin or rifampin. The number of penicillin-treated and untreated bacteria attached to the valvular surfaces was determined by differential counting on streptomycin or rifampin containing media. Penicillin pretreatment reduced cardiac valve colonization 5 min after inoculation ("adherence ratio" × 108 was 4.11 for the control and 3.66 for the penicillin-treated bacteria, P < 0.001). The results were not due to differences in serum killing or bacterial densities in the bloodstream. There was no difference in valvular bacterial densities 24 h after bacterial inoculation (adherence ratio × 108, 7.26 untreated vs. 6.34 penicillin-pretreated, P > 0.10).
The prince and the professor: Heretics unite
Authors: Lesley J Fallowfield
Journal: BMJ (2004)

Editor—Well done Michael Baum, you deserve a knighthood at the very least for putting your head on the block yet again and having the courage to say what most of us believe, but usually feel too cowardly to express in the presence of the Royals.1 See you in the Tower.

From your fellow heretic.
Acute Coronary Thrombosis in Boston Marathon Runners
Authors: Alfred J. Albano, Paul D. Thompson, Navin K. Kapur
Journal: New England Journal of Medicine (2012)

Acute Coronary Thrombosis in Boston Marathon RunnersTo the Editor: Regular exercise reduces the incidence of coronary atherosclerotic disease and decreases mortality after myocardial infarction, 1 but vigorous activity increases the risk of myocardial infarction and sudden death among patients with occult and diagnosed coronary artery disease. 2,3We describe three male athletes in good condition without diagnosed coronary artery disease who presented with acute coronary thrombosis immediately after completing the 2011 Boston Marathon (Fig. 1).The first patient was a 45-year-old man in whom chest pressure developed 15 minutes after he completed the marathon, leading to the diagnosis of an anterior ST-segment elevation myocardial infarction (STEMI).Coronary angiography (Fig. 1A and1B) showed a proximal 70% stenosis of the left anterior descending artery with a heavy thrombus burden.After successful aspiration thrombectomy, intravascular ultrasonographic examination confirmed a ruptured plaque, which required a single stent.
Trephine needle bone marrow biopsy in the initial staging of Hodgkin disease: Sensitivity and specificity of the ann arbor staging procedure criteria
Authors: Mark E. Ellis, Louis F. Diehl, Elder Granger, Edward Elson
Journal: American Journal of Hematology (1989)

Abstract The purpose of this study was to test the value of the Ann Arbor staging procedures committee criteria in defining a group of newly diagnosed patients with Hodgkin disease who do not have involvement of the bone marrow and do not need this procedure performed. One hundred sixty‐six bilateral and 16 unilateral trephine bone marrow biopsies were performed in a consecutive series of 182 patients undergoing initial staging for Hodgkin disease. Bone marrow involvement was found in 13 patients. Advanced stage, defined as stage III or IV, occurring in 92%, anemia occurring in 100%, and “B” symptoms present in 100% were found to be the most sensitive indicators for bone marrow involvement. Osseous disease (99%), platelet count &lt; 150,000/mm 3 (98%), and WBC &lt; 4,800/mm 3 (94%) were the most specific parameters. The known association of bone marrow involvement with older patients, lymphocyte depleted histology, lower blood cell counts, anemia, advanced stage, and poorer survival is verified. The Ann Arbor staging procedures committee criteria for performing a bone marrow biopsy were shown to be 100% sensitive and 40% specific. Use of these criteria would have found all 13 patients with bone marrow involvement. Of the 73 patients who did not meet the criteria, no patient had bone marrow involvement. Use of the Ann Arbor staging procedures committee criteria is recommended.
Acetylator phenotype in diabetic neuropathy.
Authors: E H McLaren, A C Burden, P J Moorhead
Journal: BMJ (1977)

The proportions of slow and fast acetylators in a group of diabetics with symptomatic peripheral neuropathy were compared with those in a group of diabetics who had had the disease for at least 10 years without developing neuropathy. There was a significantly higher proportion of fast acetylators in the group of diabetics without neuropathy than in those with neuropathy or in the normal population. Hence genetic factors separate from the diabetic diathesis may determine the development of neuropathy in any particular diabetic.
Cimetidine, Cigarette Smoking, and Recurrence of Duodenal Ulcer
Authors: Stephen Sontag, David Y. Graham, Alphonso Belsito, Jerome Weiss, Alain Farley, Richard Grunt, Norman Cohen, Douglas Kinnear, William Davis, Andre Archambault, James Achord, Walter Thayer, Richard Gillies, Joseph Sidorov, Seymour M. Sabesin, Walter Dyck, Bertram Fleshler, Iain Cleator, Julius Wenger, Antone Opekun
Journal: New England Journal of Medicine (1984)

Three hundred seventy patients with recently healed duodenal ulcer entered into a one-year, double-blind, randomized multicenter trial comparing placebo with three different dose schedules of cimetidine (200 mg twice a day, 300 mg twice a day, and 400 mg at bedtime) for the prevention of recurrent duodenal ulcer. By the end of one year, the cumulative symptomatic recurrence rate as demonstrated by endoscopy was similar for the patients receiving the three dosages of cimetidine (19 per cent, 15 per cent, and 13 per cent, respectively; not significant), whereas the placebo-treated group had a 34.7 per cent symptomatic recurrence rate (P less than 0.01 as compared with each cimetidine group). Cigarette smoking was found to be an important variable; among the placebo recipients ulcer recurrence was significantly more likely in smokers (72 per cent) than in nonsmokers (21 per cent, P less than 0.001). The frequency of ulcer recurrence in smokers was significantly reduced by treatment with cimetidine (from 72 per cent to 34 per cent, P less than 0.). Smokers who received cimetidine were at least as likely to have a recurrence as were nonsmokers who received placebo (34 per cent vs. 21 per cent, not significant). Thus, smoking appears to be a major factor in recurrence of duodenal ulcer, and in smokers, giving up smoking may be more important in the prevention of ulcer recurrences than administration of cimetidine.
The art of being human
Authors: C. Martin
Journal: BMJ (2011)

Extremes in presynaptic differentiation can be studied at the crayfish leg extensor muscle where, on the same muscle fiber, one motoneuron makes “phasic” depressing synapses that have a high probability of neurotransmitter release and another motoneuron makes “tonic,” low-probability, facilitating synapses. The large motor axons permit intracellular access to presynaptic sites. We examined the role of phosphorylation during low-frequency depression (LFD) in the relatively little studied phasic synapses. LFD occurs with stimulation at 0.2 Hz and develops with time constants of 4 and 105 min to reach &gt;50% depression of transmitter release in 60 min similar to long-term depression in mammals. LFD is not associated with changes in postsynaptic sensitivity to transmitter and thus is a presynaptic event, although it is not accompanied by changes in the presynaptic action potential. Blockade of protein kinases accelerated the slow phase of LFD, but stimulation of kinases reduced depression. Blockade of protein phosphatases 1A/2A reversed the slow phase. When calcineurin was inhibited, both phases of LFD were abolished, and facilitation occurred instead. Immunostaining showed calcineurin-like immunoreactivity in synaptic terminals. Recovery from LFD occurred in ∼1 h if stimulation frequency was reduced to 0.0016 Hz. Recovery was blocked by kinase inhibition. This study shows that phosphorylation-dependent mechanisms are involved in LFD and suggests that exocytosis is controlled by conditions that shift the balance between phosphorylated and unphosphorylated substrates. The shift can occur by alteration in the relative activities of protein kinases and phosphatases.
Right Subhepatic Abscesses Detected by Technetium Liver Scans
Authors: JOSEPH F. NORFRAY, LAWRENCE SCHLACHTER, WILLIAM J. HEISER, ANTONIO RAMOS, MARSHALL S. SPARBERG
Journal: Clinical Nuclear Medicine (1978)

A focal defect at the inferior margin of the right lobe of the liver was found in two patients with subhepatic abscesses. This defect must be differentiated from the porta hepatis and the gallbladder fossa. When technetium liver scans are obtained in patients with suspect abdominal abscesses, the inferior margin of the right lobe of the liver should be carefully scrutinized so that right subhepatic abscesses will not be overlooked.
In Vivo Delivery of Recombinant Viruses to the Fetal Murine Cochlea: Transduction Characteristics and Long-Term Effects on Auditory Function
Authors: Jeffrey C. Bedrosian, Michael Anne Gratton, John V. Brigande, Waixing Tang, Jessica Landau, Jean Bennett
Journal: Molecular Therapy (2006)

Congenital hearing deficits can be caused by a variety of genetic and acquired conditions. Complete reversal of deficits in the peripheral auditory system may require delivery of corrective genes to cochlear progenitor cells. We tested delivery of lentivirus and an array of recombinant adeno-associated viral (AAV) serotypes for efficiency and cellular specificity of transgene expression after in utero delivery to the developing mouse otocyst. Stability of expression and safety with respect to auditory function were then tested in those vectors that had the most favorable in utero cochlear transduction characteristics (AAV2/1, AAV2/8, and lentivirus). AAV2/1 was found to be the optimal vector for in utero cochlear gene transfer. It efficiently transduced progenitors giving rise to both inner and outer hair cells and supporting cells and had no adverse effect on cochlear cell differentiation. Further, it had no pathological effect on differentiated hair cells or the integrity of the auditory nerve or brain-stem nuclei as measured by auditory brain-stem response testing. AAV2/1 promises to be useful in further studies evaluating differentiation pathways of cochlear cells in health and disease and for developing gene-based therapies for congenital and acquired forms of peripheral hearing loss.
SOME INTRA-ABDOMINAL COMPLICATIONS FOLLOWING LAPAROTOMIES
Authors: ARTHUR E. BENJAMIN
Journal: JAMA (1913)

Some of the questions that a patient who is suffering from abdominal disease considers before an operation is consented to are: Has a proper diagnosis been made in his individual case? Will the operation cure him of his trouble? Will it leave him in a worse condition? Will it leave a different train of symptoms with an equal amount of suffering? Is the disease of such importance that he is warranted in taking the risk of an operation? For a number of years I have been investigating the cause of postoperative intra-abdominal disturbances in my own as well as other surgeons' cases that have come to my attention, and have tried to determine the underlying factors in the production of the various symptoms that patients complain of after laparotomy. Intra-abdominal pain is usually due to some interference with the function of the alimentary canal, and
Effect of vagotomy on gastric acid secretion stimulated by pentagastrin and histamine.
Authors: R A Payne, A G Cox, J Spencer, F C Cheng
Journal: BMJ (1967)

JOURNAWith the peanut preparation evaluated in the present double- blind trial on 92 haemophiliacs no favourable effect on bleeding could be observed.Based on these findings we would propose to refrain from recommending peanuts or their extracts as a haemostatic agent to haemophilic patients until definite proof of the beneficial effect of a given peanut preparation to the control of haemophilic bleeding is presented. SummaryThe haemostatic value of an aqueous extract of raw ground and hexane-defatted peanut kernels was evaluated in 92 severely affected haemophilic patients during a six-months double-blind trial.With the criteria selected, no statistical proved benefit ,on the bleeding incidence could be demonstrated during the -"-active" treatment.
Etiology-dependent molecular mechanisms in human hepatocarcinogenesis
Authors: Christof Schlaeger, Thomas Longerich, Claudia Schiller, Peter Bewerunge, Arianeb Mehrabi, Grischa Toedt, Jörg Kleeff, Volker Ehemann, Roland Eils, Peter Lichter, Peter Schirmacher, Bernhard Radlwimmer
Journal: Hepatology (2007)

Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide and is characterized by aggressive tumor behavior coupled with poor prognosis. Various etiologies have been linked to HCC development, most prominently chronic hepatitis B and C virus infections as well as chronic alcohol consumption. In approximately 10% of HCCs, the etiology remains cryptic; however, recent epidemiological data suggest that most of these cryptogenic HCCs develop due to nonalcoholic steatohepatitis. To identify etiology-dependent DNA copy number aberrations and genes relevant to hepatocarcinogenesis, we performed array-based comparative genomic hybridization of 63 HCCs of well-defined etiology and 4 HCC cell lines followed by gene expression profiling and functional analyses of candidate genes. For a 10-megabase chromosome region on 8q24, we observed etiology-dependent copy number gains and MYC overexpression in viral and alcohol-related HCCs, resulting in up-regulation of MYC target genes. Cryptogenic HCCs showed neither 8q24 gains, nor MYC overexpression, nor target gene activation, suggesting that tumors of this etiology develop by way of a distinct MYC-independent pathomechanism. Furthermore, we detected several etiology-independent small chromosome aberrations, including amplification of MDM4 on 1q32.1 and frequent gains of EEF1A2 on 20q13.33. Both genes were overexpressed in approximately half the HCCs examined, and gene silencing reduced cell viability as well as proliferation and increased apoptosis rates in HCC cell lines.Our findings suggest that MDM4 and EEF1A2 act as etiology-independent oncogenes in a significant percentage of HCCs.
On the Nature and Ethics of Phase I Clinical Trials of Cancer Chemotherapies
Authors: Mortimer B. Lipsett
Journal: JAMA (1982)

PHYSICIANS and members of the public understand that each new drug must, at some point, be given to humans for the first time without confident knowledge of its effects and toxic potential. Although the ethics and constraints necessary for this testing have been discussed widely, there has been little attention given specifically to the first trials of new cancer chemotherapeutic agents (phase I trials). However, new cancer chemotherapeutic agents cannot be treated simply as new drugs; their toxic effects are often so much greater than those of other drugs that the clinical investigator must weigh many conflicting arguments to justify the trial. Referring physicians, in their role as advisors, are often called on to explain the trials and to counsel patients who may enter them. Thus, they should have full appreciation of the nature and ethics of such trials. A phase I clinical trial in patients with cancer does not
Detailed molecular characterisation of acute myeloid leukaemia with a normal karyotype using targeted DNA capture
Authors: N Conte, I Varela, C Grove, N Manes, K Yusa, T Moreno, A Segonds-Pichon, A Bench, E Gudgin, B Herman, N Bolli, P Ellis, D Haddad, P Costeas, R Rad, M Scott, B Huntly, A Bradley, G S Vassiliou
Journal: Leukemia (2013)

Advances in sequencing technologies are giving unprecedented insights into the spectrum of somatic mutations underlying acute myeloid leukaemia with a normal karyotype (AML–NK). It is clear that the prognosis of individual patients is strongly influenced by the combination of mutations in their leukaemia and that many leukaemias are composed of multiple subclones, with differential susceptibilities to treatment. Here, we describe a method, employing targeted capture coupled with next-generation sequencing and tailored bioinformatic analysis, for the simultaneous study of 24 genes recurrently mutated in AML–NK. Mutational analysis was performed using open source software and an in-house script (Mutation Identification and Analysis Software), which identified dominant clone mutations with 100% specificity. In each of seven cases of AML–NK studied, we identified and verified mutations in 2–4 genes in the main leukaemic clone. Additionally, high sequencing depth enabled us to identify putative subclonal mutations and detect leukaemia-specific mutations in DNA from remission marrow. Finally, we used normalised read depths to detect copy number changes and identified and subsequently verified a tandem duplication of exons 2–9 of MLL and at least one deletion involving PTEN. This methodology reliably detects sequence and copy number mutations, and can thus greatly facilitate the classification, clinical research, diagnosis and management of AML–NK.
Solvents for ear wax.
Authors: P. G. Harris
Journal: BMJ (1968)

Adrenocortical scintigraphy was examined as an indicator of therapeutic success in aldosteronomas treated by transcatheter arterial embolization (TAE) with absolute ethanol (AE). <b>Methods:</b> Adrenocortical scintigraphy was performed 7 days after intravenous injection of 37 MBq <sup>131</sup>I-6-β-iodomethy1-19-norcholesterol before and after TAE. Complete or incomplete therapeutic success was determined by periodic measurements of the levels of plasma aldosterone and correlated with the scintigraphic results. <b>Results:</b> The aldosteronoma was visualized as a hot nodule in nine patients and a warm nodule in one patient before TAE. Scintigraphy showed a hot, residual hot or warm nodule on seven occasions (six occasions after the first TAE and one occasion after the second TAE) when the techniques were incompletely successful and disappearance on seven occasions when success was achieved (three occasions after the first TAE and one occasion after the second TAE). Of the seven occasions when TAE was unsuccessful, four patients received the second or third TAE to result in complete destruction of the aldosteronoma; three patients underwent unilateral adrenalectomy. <b>Conclusion:</b> Adrenocortical scintigraphy can correctly predict the effect of TAE on aldosteronomas and is a valuable indicator for decisions on the necessity of repeated TAE or adrenalectomy.
Transferrin receptors on human reticulocytes: Variation in site number in hematologic disorders
Authors: Kenneth H. Shumak, Rose A. Rachkewich
Journal: American Journal of Hematology (1984)

Abstract Assays of binding of 125 iodine‐labeled ( 125 I) human transferrin were used to study transferrin receptor sites on reticulocytes from 15 normal subjects and from 66 patients with various hematologic disorders. In normal subjects, few or no transferrin receptors were detected whereas the average number of receptors per reticulocyte varied greatly from patient to patient, ranging from 0 to 67,700 in samples, from 35 patients, on which Scatchard analysis of binding of [ 125 I]‐transferrin was done. Marked heterogeneity in the number of reticulocyte transferrin receptors in different hematologic disorders was also found in assays with [ 125 I]‐OKT9 (monoclonal antibody to the human transferrin receptor). The number of receptors was not correlated with either the reticulocyte count or the hemoglobin.
Production of interleukin-6, tumor necrosis factor α and interleukin-10 in vitro correlates with the clinical immune defect in chronic hemodialysis patients
Authors: Matthias Girndt, Hans Köhler, Erika Schiedhelm-Weick, Jörg F. Schlaak, Karl-Hermann Meyer zum Büschenfelde, Bernhard Fleischer
Journal: Kidney International (1995)
867-5 Rosiglitazone modulates angiogenic progenitor cell differentiation and attenuates intimal hyperplasia after vascular intervention
Authors: Chao-Hung Wang, Shu-Hong Li, Richard D Weisel, Paul E Szmitko, Cristina Fayet, Ren-Ke Li, William Stanford, Subodh Verma
Journal: Journal of the American College of Cardiology (2004)
Scavenger receptor-specific allergen delivery elicits IFN-γ-dominated immunity and directs established TH2-dominated responses to a nonallergic phenotype
Authors: Sumeena Bhatia, Sangita Mukhopadhyay, Elizabeth Jarman, Gillian Hall, Anna George, Sandip K. Basu, Satyajit Rath, Jonathan R. Lamb, Vineeta Bal
Journal: Journal of Allergy and Clinical Immunology (2002)
Hemophilic pseudotumor: Multicenter experience over 25‐year period
Authors: M. Magallón, J. Monteagudo, C. Altisent, A. Ibáñez, A. Rodriguez‐Pérez, J. Riba, J. Tusell, J. Martin‐Villar
Journal: American Journal of Hematology (1994)

Abstract Pseudotumor is an infrequent manifestation of bleeding diathesis seen in hemophiliacs, the management of which is still controversial. To ascertain the effectiveness of the main therapies of choice, we have reviewed 1,831 patients affected by hemophillas A (1,108) and B (172), von Willebrand's disease (329), and other miscellaneous coagulopathles (222) diagnosed between 1965 and 1990 in a multicentric, retrospective study. Pseudotumor was proven in 21 patients. Replacement therapy was given in 15 cases as the first therapeutic approach, with complete success attained in only two, whereas surgery, which was carried out in 14 patients, completely resolved the process in eight ( P = 0.017). Patients over 40 years of age demonstrated worse prognosis than younger patients ( P = 0.02), but no other clinical parameters were shown to have influenced the patients' evolution. Surgical management was the most effective treatment for pseudotumor, although more conservative therapies cannot be overlooked in selected cases. © 1994 Wiley‐Liss, Inc.
Screening for Chlamydia trachomatis
Authors: B. Andersen, F. Olesen
Journal: BMJ (2012)

Screening may not be the best next step

Population based screening for asymptomatic Chlamydia trachomatis infection has been postulated since the introduction of nucleic amplification techniques that enable testing on non-invasive samples.1 Screening also seems logical because the infection is common and curable, and asymptomatic, and symptomatic infections are thought to be important causes of pelvic inflammatory disease and other complications of the female reproductive system.2

In the linked cluster randomised trial with a stepped wedge design (doi:10.1136/bmj.e4316), van den Broek and colleagues report on the effectiveness of screening in more than 300 000 Dutch men and women.3 The study provides important new information on the feasibility of screening. The results are disappointing and suggest that the strategy should be reconsidered. Over the course of three rounds of screening the participation rate fell from 16.1% to 9.5%. In addition, 4.2% of participants were C trachomatis positive at the first invitation and there was only …