tbuckley/cabot-search huggingface dataset:
Epigastric pain and elevated pancreatic enzymes
Authors: M Khreiss, K M Musallam, A Soweid, G Zaatari, A S Yakan, F R Jamali
Journal: Gut (2009)

Innovation is often regarded as uniformly positive. This paper shows that the role of innovation in quality improvement is more complicated. The authors identify three known paradoxes of innovation in healthcare. First, some innovations diffuse rapidly, yet are of unproven value or limited value, or pose risks, while other innovations that could potentially deliver benefits to patients remain slow to achieve uptake. Second, participatory, cooperative approaches may be the best way of achieving sustainable, positive innovation, yet relying solely on such approaches may disrupt positive innovation. Third, improvement clearly depends upon change, but change always generates new challenges. Quality improvement systems may struggle to keep up with the pace of innovation, yet evaluation of innovation is often too narrowly focused for the system-wide effects of new practices or technologies to be understood. A new recognition of the problems of innovation is proposed and it is argued that new approaches to addressing them are needed.
REMARKS ON SPINAL SURGERY, WITH ILLUSTRATIVE CASES.
Authors: ANDREW J. McCOSH
Journal: JAMA (1901)

The spinal canal has for many centuries been considered legitimate ground for operative procedures. As early as the 7th century the advisability of operation for fractured spine was urged by Paul d'Egine<sup>1</sup>and others. In the 16th century and since that time, various surgeons have advised operative interference for the relief of this condition, but it was probably not until the beginning of the 19th century that a definite operation was performed for a fractured spine. Since then the subject has constantly thrust itself into prominence and has been much debated and often with considerable heat and vigor. This was especially true of a discussion which took place in the Royal Society of Surgery of London in 1820. About the same time (1823), A. Cooper wrote: "If you could save one life in ten, aye, one in a hundred, by such an operation, it is your duty to attempt
Serum Gastrin Levels before and after Vagotomy and Pyloroplasty or Vagotomy and Antrectomy
Authors: J. E. McGuigan, W. L. Trudeau
Journal: New England Journal of Medicine (1972)

Fasting serum gastrin concentrations and rates of basal and maximum gastric acid secretion were measured in patients with duodenal ulcer before and at least six months after either antrectomy with vagotomy or pyloroplasty with vagotomy. The mean serum gastrin level after antrectomy and vagotomy was substantially and significantly (p less than 0.001) reduced; this decrease was accompanied by more than 90 per cent reduction in both basal and stimulated acid secretion. In sharp contrast, although gastric acid secretion was reduced, no fall in fasting serum gastrin concentrations was observed after pyloroplasty with vagotomy. These results indicate that reductions in gastric acid secretion after vagal transaction, with pyloroplasty, cannot be interpreted as consequences of reductions in vagally stimulated gastrin release; more probable mechanisms include modification of the sensitivity of the parietal-cell mass to gastrin or interruption of more direct vagal effects on acid-secreting cells.
Arrested Mental Development Induced by Lead-poisoning
Authors: J. W. G. Gibb, J. F. MacMahon
Journal: BMJ (1955)

<h3>Abstract</h3> Respiratory syncytial virus has evolved a unique strategy to evade host immune response by coding for two non-structural proteins NS1 and NS2. Recently it was shown that in infected cells, nuclear NS1 could be involved in transcription regulation of host genes linked to innate immune response, via an interaction with chromatin and the Mediator complex. Here we identified the MED25 Mediator subunit as an NS1 interactor in a yeast two-hybrid screen. We demonstrate that NS1 directly interacts with MED25 <i>in vitro</i> and <i>in cellula</i>, and that this interaction involves the C-terminal α3 helix of NS1 and the MED25 ACID domain. More specifically we showed by NMR that the NS1 α3 sequence primarily binds to the MED25 ACID H2 face, which is a transactivation domain (TAD) binding site for transcription regulators such as ATF6α, a master regulator of ER stress response activated upon viral infection. Moreover, we found out that the NS1 α3 helix could compete with ATF6α TAD binding to MED25. This finding points to a mechanism of NS1 interfering with innate immune response by impairing recruitment by cellular TADs of the Mediator via MED25 and hence transcription of specific genes by RNA polymerase II. <h3>Importance</h3> Human RSV is the leading cause of infantile bronchiolitis in the world and one of the major causes of childhood deaths in resource-poor settings. It is a major unmet target for vaccines and anti-viral drugs. RSV non-structural protein NS1 is known to antagonize the cellular immune response and was recently shown to be involved in transcription regulation of infected cells. However, the exact mechanism of this regulation is not well defined. Here we show that nuclear NS1 interacts directly with the Mediator subunit MED25 and is able to compete with a cellular transcription activator, which is activated during viral infection. We hypothesize that this interaction may underlie regulation of the expression of genes involved in the innate immune response.
Pathogens in popular food
Authors: B Dixon
Journal: BMJ (1994)

<h3>Abstract</h3> An intracellular microsporidian parasite was first observed within oocytes of <i>Maculaura alaskensis</i>, a small pilidiophoran nemertean, commonly found on sandflats along the Pacific coast of North America. Infected oocytes have large vesicles containing dozens to hundreds of diplokaryotic, ellipsoid spores measuring 1.3 by 2.3 μm. A partial small subunit nuclear ribosomal 18S gene sequence isolated from the microsporidian does not match any known microsporidian sequences in the public databases. Phylogenetic analysis groups it with <i>Hepatospora eriocheir</i> in a sister clade to the Enterocytozoonidae. All the known life stages of this parasite are contained within a membranous envelope. This microsporidian was identified in <i>M. alaskensis, Maculaura aquilonia, Maculaura oregonensis</i>, and <i>Maculaura cerebrosa</i> in Coos Bay, Oregon, in <i>M. alaskensis</i> from Newport, Oregon, and in <i>M. aquilonia</i> collected in Juneau, Alaska. This is, to our knowledge, the first species of microsporidia found to directly infect nemertean host cells. <h3>Graphical abstract</h3>
ERYTHROCYTE SEDIMENTATION RATE IN DISEASE
Authors: H. A. Reimann
Journal: JAMA (1933)

<h3>To the Editor:</h3> —In an editorial inThe Journal, March 11, entitled "The Erythrocyte Sedimentation Rate in Disease," it is stated that, in spite of many studies, the theory behind variations in the sedimentation rate remains clouded. There is, however, a general agreement among many observers, e. g., Fåhraeus (<i>Physiol. Rev.</i><b>9</b>:241 [April] 1929), Starlinger (<i>Biochem. Ztschr.</i><b>114</b>: 129, 1921), Westergren (<i>Ztschr. f. d. ges. exper. Med.</i><b>75</b>: 668, 1931) and Gram (<i>Arch. Int. Med.</i><b>28</b>:312 [Sept.] 1921), that an increase in the sedimentation rate is chiefly due to an increase in the fibrinogen or globulins of the blood. Although other factors also play a rôle, such as hydremia, anemia, erythrocytosis and color index (Rourke and Plass:<i>J. Clin. Investigation</i><b>7</b>:365 (Aug.) 1929. Rourke and Ernstene,<i>ibid.</i><b>8</b>:545 [June] 1930. Bendien and Snapper:<i>Biochem. Ztschr.</i><b>235</b>: 14, 1931. Ohno:<i>Ztschr. f. d. ges. exper. Med.</i><b>52</b>
Descriptive Clinicopathologic Study of 17 Patients With Endometrial Cancer During or After Adjuvant Tamoxifen in Early Breast Cancer
Authors: T. Fornander, A.-C. Hellstrom, B. Moberger
Journal: JNCI Journal of the National Cancer Institute (1993)

Background : Studies have shown that patients with early-stage endometrial cancer who have previously used endogenous estrogen (oral contraceptives or estrogen replacement therapy) have a favorable prognosis. This has not yet been demonstrated for patients with early-stage endometrial cancer who have received tamoxifen. In addition, studies have raised the question of whether women receiving tamoxifen are at increased risk of endometrial cancer. Purpose : Our aim was to determine whether the prognosis is favorable for patients with diagnosis of endometrial cancer after adjuvant treatment with tamoxifen for breast cancer. Methods : We matched 931 patients from the Stockholm Adjuvant Tamoxifen Trial in early breast cancer against the Swedish Cancer Registry and identified 17 who subsequently had endometrial cancer. These patients had been randomly assigned to receive 40 mg/d tamoxifen orally for 2 years beginning 4, Weeks after surgery for breast cancer. Histologic specimens, patient records, and death certificates were reviewed to verify treatment and causes of death. Results : Thirteen of the 17 patients diagnosed with endometrial cancer were alive; for three of the four who had died, the cause of death was endometrial can cause of death was endometrial cancer. All 16 evaluable tumors except one were world Health Organisation (WHO) histologic grades I-II. Only one patient had advanced disease (stage IV); the remaining tumor was a mixed mesodermal malignant tumor that could not be classified under the WHO grading system. Median time for adjuvant tamoxifen use was 24 monoths (range, 6–60 months) with a median cumulative tamoxifen dose of 29 g (range, 7–72 g). Median time from initiation of adjuvant tamoxifen to diagnosis to diagnosis of endometrial cancer was 32 months (range, 6–130 months). Ten-year actuarial survival after diagnosis of endometrial cancer for the 17 patients treated with tamoxifen was 73%. Conclusion : Because of the small number of patients, our results do not rule out the possibility of a favourable prognosis for patients with a diagnosis of endometrial cancer following tamoxifen treatment. Implications : The incidence of secondary endometrial cancer reported in this study following treatment of breast cancer patients with tamoxifen at doses of 40 mg/d in a large clinical trial is higher than that reported for previous large trials of tamoxifen at doses of 20 mg/d. Thus, tamoxifen dosage may be a critical factor in the subsequent occurence of endometrial cancer. Our results also suggest two important considerations for improved follow-up in long-term tamoxifen trials: careful registration of second cancers registration of second cancers and routine gynecologic examinations of ensure early detection of endometrial cancer. [J Natl Cancer Inst 85:1850–1885, 1993]
Glossopharyngeal neuralgia with cardiac arrhythmia: a rare but treatable cause of syncope.
Authors: R R Jacobson, R W Russell
Journal: BMJ (1979)

with intensive eye toilet, as described above, using 1",, kanamycin eye drops.Follow-up smear cultures on days 3, 7, and 14 of kanamycin treatment were negative for Ngonorrhoeae.Both mother and child have since been well.
Vitamin C improves endothelium-dependent vasodilation in patients with non-insulin-dependent diabetes mellitus.
Authors: H H Ting, F K Timimi, K S Boles, S J Creager, P Ganz, M A Creager
Journal: Journal of Clinical Investigation (1996)

Endothelium-dependent vasodilation is impaired in humans with diabetes mellitus. Inactivation of endothelium-derived nitric oxide by oxygen-derived free radicals contributes to abnormal vascular reactivity in experimental models of diabetes. To determine whether this observation is relevant to humans, we tested the hypothesis that the antioxidant, vitamin C, could improve endothelium-dependent vasodilation in forearm resistance vessels of patients with non-insulin-dependent diabetes mellitus. We studied 10 diabetic subjects and 10 age-matched, nondiabetic control subjects. Forearm blood flow was determined by venous occlusion plethysmography. Endothelium-dependent vasodilation was assessed by intraarterial infusion of methacholine (0.3-10 micrograms/min). Endothelium-independent vasodilation was measured by intraarterial infusion of nitroprusside (0.3-10 micrograms/min) and verapamil (10-300 micrograms/min). Forearm blood flow dose-response curves were determined for each drug before and during concomitant intraarterial administration of vitamin C (24 mg/min). In diabetic subjects, endothelium-dependent vasodilation to methacholine was augmented by simultaneous infusion of vitamin C (P = 0.002); in contrast, endothelium-independent vasodilation to nitroprusside and to verapamil were not affected by concomitant infusion of vitamin C (P = 0.9 and P = 0.4, respectively). In nondiabetic subjects, vitamin C administration did not alter endothelium-dependent vasodilation (P = 0.8). We conclude that endothelial dysfunction in forearm resistance vessels of patients with non-insulin-dependent diabetes mellitus can be improved by administration of the antioxidant, vitamin C. These findings support the hypothesis that nitric oxide inactivation by oxygen-derived free radicals contributes to abnormal vascular reactivity in diabetes.
Oakley's case for using randomised controlled trials is misleading
Authors: D. Nutbeam
Journal: BMJ (1999)

EDITOR—Oakley examines lessons in the history of the use of randomised controlled trials to evaluate social interventions.1 Her examination provides a misleading assessment of their usefulness in the evaluation of contemporary health promotion interventions. She suggests that randomised controlled trials are “ignored or regarded with suspicion” by the discipline of health promotion and that “experts … have resisted the notion that rigorous evaluation of their …
Racial Hygiene: Medicine Under the Nazis
Authors: Burton C. Einspruch
Journal: JAMA (1989)

The circumstances surrounding Drew's death after an automobile accident and the multiple efforts to disseminate the truth surrounding this event are tenaciously confirmed by the author after interviewing innumerable witnesses and participants. Drew's untimely death occurred after World War II when black martyrs were needed. Despite detailed confirmation by those in attendance who unsuccessfully managed Drew's multiple fatal injuries, the myth [that he was denied proper treatment because of his race] lingers. Finally, the humanist side of Charles Drew, who exerted a magnetic effect on those who interfaced with him at multiple professional and social levels, is graphically portrayed in his letters to his wife, Lenore. His love of Lenore provided the opportunity in his moments of loneliness at Columbia to bare his soul to her. The penetrating and descriptive nature of the man is reflected in these letters as compassionate and visionary. The letters made me (as a surgeon)
Studies of Cardiopulmonary Blood Volume
Authors: GILBERT E. LEVINSON, MARTIN J. FRANK, MANOUCHEHR NADIMI, MILTON BRAUNSTEIN
Journal: Circulation (1967)

The measurement of ventricular end-diastolic volume from washout of an indicator requiring blood sampling was studied in a heart model and in dogs and applied to the left ventricle in 34 human subjects. The model, under the ideal conditions of constant ejection fraction, uniform cycle length, and complete or nearly complete mixing, demonstrated that dye dilution accurately measures chamber volumes if the distorting effects of catheter sampling are obviated by clearance of the sampling system at least once per two cardiac cycles. The studies in dogs and in human beings demonstrated that the required sampling conditions are achievable. In 11 normal human subjects, left ventricular end-diastolic volume ranged from 72 to 99 with a mean of 82 ± 12 ml/m, 2 end-systolic volume, from 22 to 60 with a mean of 37 ± 11 ml/m, 2 and ejection fraction, from 0.39 to 0.71 with a mean of 0.55 ± 0.08. These measurements are in substantial agreement with results by radiocardiography and thermal dilution and are systematically, but only slightly, higher than results by quantitative angiocardiography. In six considerably older patients with chronic pulmonary disease, cardiac output was normal for the age group but ejection from a ventricle of normal size was reduced. In 12 subjects with pure mitral stenosis and in five with atrial septal defect, end-diastolic volume and ejection fraction were significantly reduced. End-diastolic volume correlated with stroke volume in all groups and in the series as a whole, but a correlation between end-diastolic volume and cardiac output was demonstrated only in the patients with mitral stenosis or atrial septal defect. This suggests that chronic restriction to ventricular filling results in decreased end-diastolic volume. The absence of a significant correlation between end-diastolic volume and end-diastolic pressure indicates that variation in ventricular compliance precludes reliance on end-diastolic pressure as a valid index of end-diastolic fiber length.
Progression From Conduct Disorder to Antisocial Personality Disorder Following Treatment for Adolescent Substance Abuse
Authors: Mark G. Myers, David G. Stewart, Sandra A. Brown
Journal: American Journal of Psychiatry (1998)

This study investigated the progression from conduct disorder to antisocial personality disorder among individuals treated for adolescent substance abuse. This issue is important because of the poor outcomes observed among individuals with antisocial pathology after treatment for alcohol and drug problems. The utility of factors assessed at the time of treatment in predicting progression to adult antisocial personality disorder was evaluated in the context of developmental models of antisocial behavior.This was a prospective longitudinal study of 137 substance-abusing adolescents (53 female and 84 male), whose average age was 15.9 years and who met the DSM-III-R criteria for conduct disorder. Consecutively admitted patients were recruited from two adolescent inpatient alcohol and drug treatment facilities. Participants were interviewed again 4 years after treatment.Four years after treatment, 61% of the study group met the DSM-III-R criteria for antisocial personality disorder. Results of a logistic regression analysis indicated that onset of deviant behavior at or before age 10, a greater diversity of deviant behavior, and more extensive pre-treatment drug use best predicted progression to antisocial personality disorder. At 4-year follow-up, the subjects with an antisocial personality disorder diagnosis exhibited more involvement with alcohol and drugs and poorer functioning across important life domains than the subjects without antisocial personality disorder.This study found a high rate of progression to antisocial personality disorder among substance-abusing adolescents and identified factors predictive of this progression. Careful assessment of conduct disorder history at the time of treatment may be valuable for treatment planning and intervention.
Syndromes of Hyperviscosity
Authors: Roe Wells
Journal: New England Journal of Medicine (1970)

THE use of syndromes to describe complex lists of symptoms and signs represents a convenient economy of scientific expression. The state of serum hyperviscosity, which involves spontaneous bleeding with neurologic and ocular disorders, has, as a further economy of expression, correctly been called a hyperviscosity syndrome.1 But there are other disorders in which blood is equally hyperviscous, and they are not rare. Hyperviscosity of blood may be due not only to elevated serum viscosity but also to increased numbers of cells (polycythemia or leukemia) or to increased resistance of cells to deformation (sicklemia or spherocytosis). The clinical manifestations of any . . .
Guide to Drug Usage in Adult Patients With Impaired Renal Function
Authors: William M. Bennett
Journal: JAMA (1973)

Four previously published tables describing maintenance dosage intervals for common drugs used in patients with renal disease are supplemented and updated. Emphasis is given to the use of biological half-life and creatinine clearance for modification of the usual dose schedules. Toxic effects and adjustments required by patients undergoing dialysis are also noted.
Philadelphia-positive patients who already harbor imatinib-resistant Bcr-Abl kinase domain mutations have a higher likelihood of developing additional mutations associated with resistance to second- or third-line tyrosine kinase inhibitors
Authors: Simona Soverini, Alessandra Gnani, Sabrina Colarossi, Fausto Castagnetti, Elisabetta Abruzzese, Stefania Paolini, Serena Merante, Ester Orlandi, Silvia de Matteis, Antonella Gozzini, Ilaria Iacobucci, Francesca Palandri, Gabriele Gugliotta, Cristina Papayannidis, Angela Poerio, Marilina Amabile, Daniela Cilloni, Gianantonio Rosti, Michele Baccarani, Giovanni Martinelli
Journal: Blood (2009)
PYOGENIC INFECTIONS TREATED WITH NEOMYCIN
Authors: Clarence S. Livingood
Journal: JAMA (1952)

Neomycin, discovered by Waksman and Lechevalier 1 in 1949, is an antibiotic which is produced by a strain of Streptomycetes closely related to Streptomyces fradiae. It is a basic compound, heat stable, and freely soluble in water. It does not lose its potency in watery solution or, indeed, in any type of vehicle, which is in striking contrast to many other antibiotics which are available for the topical treatment of cutaneous pyogenic infections.  The laboratory work of Waksman and Lechevalier 1 and that of other investigators 2 indicated that neomycin is bactericidal in vitro against an unusually wide variety of both gram-negative and gram-positive organisms. Furthermore, in their original article on neomycin, Waksman and Lechevalier 1 reported that bacterial organisms did not appear to become resistant to the antibiotic, as often happens with streptomycin in particular.  Waisbren and Spink, 3 Carr and Brown, 4 Duncan and others, 5 Wolgamot and
Impaired kisspeptin signaling decreases metabolism and promotes glucose intolerance and obesity
Authors: Kristen P Tolson, Christian Garcia, Stephanie Yen, Stephanie E Simonds, Aneta Stefanidis, Alison R Lawrence, Jeremy Troy Smith, Alexander Sasha Kauffman
Journal: Journal of Clinical Investigation (2014)

The neuropeptide kisspeptin regulates reproduction by stimulating gonadotropin-releasing hormone (GnRH) neurons via the kisspeptin receptor KISS1R. In addition to GnRH neurons, KISS1R is expressed in other brain areas and peripheral tissues, which suggests that kisspeptin has additional functions beyond reproduction. Here, we studied the energetic and metabolic phenotype in mice lacking kisspeptin signaling (Kiss1r KO mice). Compared with WT littermates, adult Kiss1r KO females displayed dramatically higher BW, leptin levels, and adiposity, along with strikingly impaired glucose tolerance. Conversely, male Kiss1r KO mice had normal BW and glucose regulation. Surprisingly, despite their obesity, Kiss1r KO females ate less than WT females; however, Kiss1r KO females displayed markedly reduced locomotor activity, respiratory rate, and energy expenditure, which were not due to impaired thyroid hormone secretion. The BW and metabolic phenotype in Kiss1r KO females was not solely reflective of absent gonadal estrogen, as chronically ovariectomized Kiss1r KO females developed obesity, hyperleptinemia, reduced metabolism, and glucose intolerance compared with ovariectomized WT females. Our findings demonstrate that in addition to reproduction, kisspeptin signaling influences BW, energy expenditure, and glucose homeostasis in a sexually dimorphic and partially sex steroid–independent manner; therefore, alterations in kisspeptin signaling might contribute, directly or indirectly, to some facets of human obesity, diabetes, or metabolic dysfunction.