tbuckley/cabot-search huggingface dataset:
Acadesine lowers temporal threshold for the myocardial infarct size limiting effect of preconditioning
Authors: A. Tsuchida, G. S Liu, K. Mullane, J. M Downey
Journal: Cardiovascular Research (1993)

Journal Article Acadesine lowers temporal threshold for the myocardial infarct size limiting effect of preconditioning Get access Akihito Tsuchida, Akihito Tsuchida Department of Physiology, College of Medicine, University of South Alabama, Mobile, AL 36688, USA: A Tsuchida, G S Liu, J M Downey; Gensia Pharmaceuticals, San Diego, California, USA: K Mullane. Correspondence to Dr Downey. Search for other works by this author on: Oxford Academic PubMed Google Scholar Guang S Liu, Guang S Liu Department of Physiology, College of Medicine, University of South Alabama, Mobile, AL 36688, USA: A Tsuchida, G S Liu, J M Downey; Gensia Pharmaceuticals, San Diego, California, USA: K Mullane. Correspondence to Dr Downey. Search for other works by this author on: Oxford Academic PubMed Google Scholar Kevin Mullane, Kevin Mullane Department of Physiology, College of Medicine, University of South Alabama, Mobile, AL 36688, USA: A Tsuchida, G S Liu, J M Downey; Gensia Pharmaceuticals, San Diego, California, USA: K Mullane. Correspondence to Dr Downey. Search for other works by this author on: Oxford Academic PubMed Google Scholar James M Downey James M Downey Department of Physiology, College of Medicine, University of South Alabama, Mobile, AL 36688, USA: A Tsuchida, G S Liu, J M Downey; Gensia Pharmaceuticals, San Diego, California, USA: K Mullane. Correspondence to Dr Downey. Search for other works by this author on: Oxford Academic PubMed Google Scholar Cardiovascular Research, Volume 27, Issue 1, January 1993, Pages 116–120, https://doi.org/10.1093/cvr/27.1.116 Published: 01 January 1993 Article history Received: 01 May 1992 Accepted: 27 August 1992 Published: 01 January 1993
A review of clinical and histological parameters associated with contralateral neck metastases in oral squamous cell carcinoma
Authors: Song Fan, Qiong‐lan Tang, Ying‐jin Lin, Wei‐liang Chen, Jin‐song Li, Zhi‐quan Huang, Zhao‐hui Yang, You‐yuan Wang, Da‐ming Zhang, Hui‐jing Wang, Eduardo Dias‐Ribeiro, Qiang Cai, Lei Wang
Journal: International Journal of Oral Science (2011)

Oral squamous cell carcinoma (OSCC) has a high incidence of cervical micrometastases and sometimes metastasizes contralaterally because of the rich lymphatic intercommunications relative to submucosal plexus of oral cavity that freely communicate across the midline, and it can facilitate the spread of neoplastic cells to any area of the neck consequently. Clinical and histopathologic factors continue to provide predictive information to contralateral neck metastases (CLNM) in OSCC, which determine prophylactic and adjuvant treatments for an individual patient. This review describes the predictive value of clinical‐histopathologic factors, which relate to primary tumor and cervical lymph nodes, and surgical dissection and adjuvant treatments. In addition, the indications for elective contralateral neck dissection and adjuvant radiotherapy (aRT) and strategies for follow‐up are offered, which is strongly focused by clinicians to prevent later CLNM and poor prognosis subsequently.
Prevention of diabetes in the BB rat by essential fatty acid deficiency. Relationship between physiological and biochemical changes.
Authors: J Lefkowith, G Schreiner, J Cormier, E S Handler, H K Driscoll, D Greiner, J P Mordes, A A Rossini
Journal: The Journal of Experimental Medicine (1990)

Essential fatty acid (EFA) deficiency exerts a striking protective effect in several animal models of autoimmune disease. We now report that EFA deprivation prevents diabetes in the BB rat, an animal model of human insulin-dependent diabetes mellitus. In diabetes-prone (DP)-BB rats, the incidences of spontaneous diabetes and insulitis (the pathological substrate of autoimmune diabetes) were greatly reduced by EFA deficiency. This beneficial effect of the deficiency state was also seen in diabetes-resistant (DR)-BB rats that, after treatment with antibody to eliminate RT6+ T cells, would otherwise have become diabetic. The susceptibility of EFA-deprived DP-BB rats to spontaneous diabetes was restored when they were given dietary supplements of linoleate at 70 d of age (during the usual period of susceptibility), but not when they were repleted beginning at 120 d (after the peak incidence of diabetes). EFA deficiency did lead to growth retardation, but calorically restricted control rats demonstrated that the protective effect of the deficiency state was not a function of decreased weight. To examine the relationship between the biochemical changes of EFA deficiency and its physiological effects in this system, we compared the fatty acid changes that occurred in EFA-deficient animals that did and did not develop diabetes. Nondiabetic animals had significantly lower levels of (n-6) fatty acids (i.e., linoleate and arachidonate) and higher levels of oleate, an (n-9) fatty acid, than did diabetic animals. Levels of 20:3(n-9), the fatty acid that uniquely characterizes EFA deficiency, were similar in both groups, however. Among diabetic EFA-deficient rats, the age at onset of diabetes was found to correlate inversely with the level of (n-6) fatty acids, the least depleted animals becoming diabetic earliest, whereas there was no correlation with levels of 20:3(n-9). Among animals repleted with linoleate beginning at 70 d, restoration of susceptibility to diabetes correlated with normalization of the level of arachidonate. In summary, EFA deprivation reduced the frequency of diabetes in both DP and RT6-depleted DR-BB rats. This protective effect was strongly associated with depletion of (n-6) fatty acids, particularly arachidonate, but not with accumulation of the abnormal 20:3(n-9). Conjecturally, arachidonate and/or a metabolite may play a key role in mediating inflammatory injury in this animal model of autoimmune diabetes.
The OECD program to validate the rat uterotrophic bioassay. Phase 2: dose-response studies.
Authors: Jun Kanno, Lesley Onyon, Shyamal Peddada, John Ashby, Elard Jacob, William Owens
Journal: Environmental Health Perspectives (2003)

The Organisation for Economic Co-operation and Development has completed phase 2 of an international validation program for the rodent uterotrophic bioassay. The purpose of the validation program was to demonstrate the performance of two versions of the uterotrophic bioassay, the immature female rat and the adult ovariectomized rat, in four standardized protocols. This article reports the dose-response studies of the validation program; the coded single-dose studies are reported in an accompanying paper. The dose-response study design used five selected weak estrogen agonists, bisphenol A, genistein, methoxychlor, nonylphenol, and o,p -DDT. These weak agonists were administered in a prescribed series of doses to measure the performance and reproducibility of the protocols among the participating laboratories. All protocols successfully detected increases in uterine weights when the weak agonists were administered. Within each protocol, there was good agreement and reproducibility of the dose response among laboratories with each substance. Substance-specific variations were observed in the influence of the route of administration on the uterine response, the potency as related to the dose producing the first statistically significant increase in uterine weights, and the maximum increase in uterine weight. Substantive performance differences were not observed between the uterotrophic bioassay versions or among the standardized protocols, and these were judged to be qualitatively equivalent. It is noteworthy that these results were reproducible under a variety of different experimental conditions (e.g., animal strain, diet, housing, bedding, vehicle, animal age), indicating that the bioassay's performance as a screen is robust. In conclusion, both the intact, immature, and adult OVX versions, and all protocols appear to be reproducible and transferable across laboratories and are able to detect weak estrogen agonists.
QUANTITATIVE STUDIES OF PROSTATIC SECRETION
Authors: Charles Huggins, John Lambert Sommer
Journal: The Journal of Experimental Medicine (1953)

The prostate of the dog was relocated permanently in the perineum where its size could be measured and correlated with the output of prostatic secretion during many months. The secretion of a submaxillary gland obtained through a fistula was utilized as an internal biologic standard of the effects of pilocarpine, the secretory stimulus employed, because the amount and route of administration of the alkaloid are critical factors in inducing secretion. Prostatic secretion was found to be profoundly affected by androgenic and estrogenic compounds, in contrast to salivation. The curves of the secretory response of the prostate and submaxillary glands to pilocarpine proved to be similar and a mathematical formula has been constructed to represent them. When testosterone propionate was administered in increasing quantities for periods of weeks at each level, the volume of the prostate increased in a series of flattened curves. This volume, under the conditions mentioned, was found to stand in a simple arithmetic relationship to the amount of testosterone propionate administered. Moderate quantities of testosterone propionate masked the effects of small amounts of stilbestrol on the prostate. The reverse was also true and the critical amounts of these compounds were defined. The amounts of stilbestrol were determined which lowered the quantity of prostatic secretion resulting from the simultaneous administration of moderate amounts of testosterone propionate in castrate dogs, the result being a level and flat secretory curve which was maintained for many weeks. We designate this effect the plateau phenomenon. When this amount of estrogen was continued, and the dosage of testosterone propionate greatly augmented, the prostatic secretion did not increase in volume. Very slight increases above the critical amount of stilbestrol, however, caused the secretory curve to fall to new and still lower levels though the secretion was never completely suppressed. The acid phosphatase content of the prostatic secretion in the regions of secretory plateaus was similar to that of castrate dogs injected with androgen alone. The plateau phenomenon is due to simultaneous physiologic action of androgenic and estrogenic compounds on the prostatic cells. The depression of prostatic secretion resulting in the plateau phenomenon is due to both functional and structural changes in the prostatic epithelium. They are best explained on the assumption that differences in steroid threshold exist in groups of cells within the prostate, those of the anterior rim of the gland being least susceptible to estrogenic activity.
Metformin versus Insulin for the Treatment of Gestational Diabetes
Authors: Janet A. Rowan, William M. Hague, Wanzhen Gao, Malcolm R. Battin, M. Peter Moore
Journal: New England Journal of Medicine (2008)

Metformin is a logical treatment for women with gestational diabetes mellitus, but randomized trials to assess the efficacy and safety of its use for this condition are lacking.
Molecular Analysis of a Binding Site for Quinidine in a Human Cardiac Delayed Rectifier K <sup>+</sup> Channel
Authors: Sarita W. Yeola, Tom C. Rich, Vic N. Uebele, Michael M. Tamkun, Dirk J. Snyders
Journal: Circulation Research (1996)

Abstract The antiarrhythmic agent quinidine blocks the human cardiac hKv1.5 channel expressed in mammalian cells at therapeutically relevant concentrations (EC 50 , 6.2 μmol/L). Mechanistic analysis has suggested that quinidine acts as a cationic open-channel blocker at a site in the internal mouth of the ionic pore and that binding is stabilized by hydrophobic interactions. We tested these hypotheses using site-directed mutagenesis of residues proposed to line the internal mouth of the channel or of nearby residues. Amino acid substitutions in the midsection of S6 (T505I, T505V, T505S, and V512A) reduced the dissociation rate for quinidine, increased the affinity (0.7, 1.5, 3.4, and 1.4 μmol/L, respectively), and preserved both the voltage-dependent open channel–block mechanism and the electrical binding distance (0.19 to 0.22). In contrast, smaller or nonsignificant effects were observed for: deletion of the intracellular C-terminal domain, charge neutralizations in the region immediately C-terminal to S6, elimination of aromatic residues in S6, and mutations at the putative internal turn of the P loop, at the external entrance of the pore, and at sites in the S4S5 linker. The ≈10-fold increase in affinity with T505I and the reduction of the dissociation rate constant with the mutations that increased affinity are consistent with a hydrophobic stabilization of binding. Moreover, the T505 and V512 residues align on the same side of the putative α-helical S6 segment. Taken together, these results localize the hydrophobic binding site for this antiarrhythmic drug in the internal mouth of this human K + channel and provide molecular support for the open channel–block model and the role of S6 in contributing to the inner pore.
National Security, Budget Trimming and Medical Science
Authors: F. J. Ingelfinger
Journal: New England Journal of Medicine (1973)

More eloquently than words, Dr. Craige's cartoon expresses the reaction of medical academe to the phasing out of the training and fellowship programs of the National Institutes of Health. No matter how sincere or logical, however, the arguments of Dr. Craige and his professorial colleagues will be discounted by the budget trimmers as self-seeking efforts to keep alive overstuffed and useless — well, hayburners. Budget trimmers, moreover, are not impressed by impractical abstractions such as research and education. But perhaps their stony hearts might respond to numbers prefixed by dollar signs, to priorities realistically arranged on a cost-benefit scale, and . . .
Emergency doctor is struck off over "catalogue of failures"
Authors: C. Dyer
Journal: BMJ (2014)

Background: Recent investigations have shown that on average patients hospitalized with coronavirus disease 2019 (COVID-19) have a poorer post-discharge prognosis than those hospitalized without COVID-19, but this impact remains unclear among dialysis patients with end-stage kidney disease (ESKD). Methods: Leveraging a national ESKD patient claims database administered by the United States Centers for Medicare &amp; Medicaid Services, we conducted a retrospective cohort study, which characterized the effects of in-hospital COVID-19 on all-cause unplanned readmission and death within 30 days of discharge for dialysis patients. Included in this study were 436,745 live acute-care hospital discharges of 222,154 Medicare beneficiaries on dialysis from 7,871 Medicare-certified dialysis facilities between January 1, 2020 and October 31, 2020. Adjusting for patient demographics, clinical characteristics, and prevalent comorbidities, we fit facility-stratified Cox cause-specific hazard models with two interval-specific (1-7 and 8-30 days after hospital discharge) effects of in-hospital COVID-19 as well as effects of pre-hospitalization COVID-19. Results: The hazard ratios due to in-hospital COVID-19 over the first 7 days following discharge were 1.59 for readmission and 1.53 for death, both with P&lt;0.001. For the remaining 23 days, the hazard ratios were 0.92 and 0.96 with P&lt;0.001 and P=0.50, respectively. Effects of pre-hospitalization COVID-19 were mostly nonsignificant. Conclusions: In-hospital COVID-19 had an adverse effect on both post-discharge readmission and death over the first week. With the surviving COVID-19 patients substantially selected from those hospitalized, in-hospital COVID-19 was associated with lower rates of readmission and death starting from the second week.
SOME RECENT EXPERIENCES WITH CHRONIC SUPPURATIONS OF THE EAR.
Authors: PHILIP HAMMOND
Journal: JAMA (1904)

Discharge from the ear is regarded by most patients as disagreeable, but few recognize the fact that it is a distinct menace to life. After the acute symptoms of abscess formation have subsided, the absence of pain may lead to the neglect of the discharge, or the secretion may be so slight in quantity as to escape observation, and in this way become chronic. With any long-continued suppuration there is very apt to be some invasion of bone tissue and consequent necrosis. In the ear, around which center so many important structures, this is an especially dangerous condition, the more so as the erosion of the bone is insidious, the patient experiencing no discomfort whatever. This carious process usually attacks the ossicles first, and is often limited to them, but later spreads to the main bone. The bone separating the ear cavity from the brain and the large blood vessels
Mammalian Target of Rapamycin Is the Key Effector of Phosphatidylinositol-3-OH–Initiated Proliferative Signals in the Thyroid Follicular Epithelium
Authors: Nicole Yeager, Charlene Brewer, Kathy Qi Cai, Xiang-Xi Xu, Antonio Di Cristofano
Journal: Cancer Research (2008)

Abstract Activation of the phosphatidylinositol-3-OH kinase (PI3K) signaling cascade is becoming increasingly recognized as a common feature of thyroid follicular neoplasms. We have recently shown that conditional loss of Pten in the mouse thyroid follicular cells is sufficient to stimulate continuous autonomous growth, leading to a homogeneously hyperplastic gland and to the development of follicular adenomas. Because the PI3K/AKT cascade can activate a plethora of different signaling pathways, it is still unclear which of these may represent the key mitogenic output of PI3K-initiated signaling. Here, we show that the in vivo proliferative response to chronic PI3K activation profoundly relies on the activation of the mammalian target of rapamycin (mTOR)/S6K1 axis, and that mTOR inhibition in Pten mutant mice and cells restores virtually normal proliferation rates, despite the presence of still elevated Akt activity, at least in part by down-regulating cyclins D1 and D3, and without affecting cell survival. [Cancer Res 2008;68(2):444–9]
Cytokine and chemokine profiles in autologous graft-versus-host disease (GVHD): interleukin 10 and interferon γ may be critical mediators for the development of autologous GVHD
Authors: Yuji Miura, Christopher J. Thoburn, Emilie C. Bright, Weiran Chen, Shinji Nakao, Allan D. Hess
Journal: Blood (2002)
POSTMORTEM RECORDS OF HOSPITALS
Authors: Paul Keller
Journal: JAMA (1926)

<h3>To the Editor:</h3> —We have read with a great deal of interest the article by Christian (The Journal, May 15) entitled "Selecting a Hospital for Internship." At the outset, we wish to subscribe heartily to the statements as to the importance of necropsies and their value as a teaching medium, both for the staff and for the interns. The Newark Beth Israel Hospital, with an active 125 bed general service, of which about 60 per cent are ward beds, is supported by the Jewish Community but is nonsectarian in its policies, treating about 45 per cent of non-Jewish patients. During the year 1925 there were 182 deaths in the hospital, in thirty-eight of which, or 20.9 per cent of all deaths (both private and ward), necropsies were held. Realizing the importance of necropsies and desirous of getting a greater percentage of our deaths to the postmortem room, we undertook a
Trigger factors and HL-A antigens in chronic active hepatitis
Authors: J. Lindberg, A. Lindholm, P. Lundin, S. Iwarson
Journal: BMJ (1975)

Forty-six patients with histologically verified chronic active hepatitis (CAH) were divided into three groups according to whether the CAH was virus-induced, drug-induced, or cryptogenic. The frequency of the HL-A antigens 1 and 8 was increased in the cryptogenic group while the other groups did not differ significantly from healthy controls. Autoantibodies were often found in high titres in the drug-induced and cryptogenic groups but were infrequent in the virus-induced group.
Report on the Bacteriological Examination of the Water Supplied to the Dublin Military Barracks: With Observations on the Biology of Coliform Organisms
Authors: E. J. McWeeney
Journal: BMJ (1896)

DURING the late autumn of last year the press, both lay and medical, contained frequent allusions to the prevalence of typhoid fever at several of the Dublin barracks.It will, of course, be within the recollection of many of your readers that some few years ago the heavy incidence of this disease at the Royal Barracks Dublin, was a matter of common knowledge, and that several young officers contracted the disease whilst stationed there.After the sanitary condition of the barracks had been thoroughly overhauled and many grave defects set right, the number of typhoid cases underwent a great diminution.Towards the autumn of last year the disease began to crop up again in the Dublin garrison, but this time it was not the Royal Barracks which was to suffer most heavily-it was the Richmond, and above all Island Bridge Barracks which had to bear the brunt of the attack.So serious did the state of health of the last-named barracks become, that early in the year it had to be evacuated by the troops.Under these circumstances the writer was re- quested to undertake the bacteriological examination of the drinking water supplied to the Dublin Barracks generally,
What is the target?
Authors: M Lemyze, S Salomon, D Brown, P Detouche, F Collet
Journal: BMJ (2009)

A 44 year old man was brought to the emergency department with a two day history of fever, skin rash, and a rapidly progressive shortness of breath. On examination, notable observations included an extensive rash, cyanosis, a fast respiratory rate (40 breaths/min), bilateral crackles on lung auscultation, and a temperature that reached a maximum of 40.4°C. Arterial blood gas levels showed severe hypoxemia (PaO2, 48 mmHg; fraction of inspired oxygen [FiO2], 21%). Chest radiography showed bilateral consolidation of the air spaces, mainly in the lower lung fields, which confirmed the clinically suspected diagnosis of community acquired pneumonia (fig 1).⇓



Fig 1 Skin rash in a patient with community acquired pneumonia 





### Short answers

### Long answers

#### 1 Diagnosis of the skin rash

The term “erythema multiforme” is used to describe a special category of maculopapular rash that encompasses a wide range of different morphologic types (including plaques, vesicles, and bullae), which can occur concurrently. Rashes of this nature occur as a reaction to an infection or to medication (box 1);1 …