tbuckley/cabot-search huggingface dataset:
Morituri Te Salutamus!
Authors: Leon Goldman
Journal: JAMA (1975)

<h3>To the Editor.—</h3> An occasional antiquated remnant of the pre-Flexner era is still present on the current medical scene. This vestige of an ancient time represents a true liaison between the now worried Gown and the all too busy Town. This Ancient One is the volunteer who, through various interests, goals, persuasions, and threats (re: hospitalization of his patients in a university medical center) used to work in academia while he struggled in<i>practica</i>. In the old days, this was a necessary tolerance for the practitioner because of the inadequate funding of a department in which he was interested. In brief, at the present time, such a creature is needed to bring realism and clinical teaching for the misguided medical students wandering through now "leaning ivory towers." Many of these students are going into private practice, not academia. Too frequently, the complete teaching of medical students is done by nonclinical
Hepatitis C and Progression of HIV Disease
Authors: Mark S. Sulkowski
Journal: JAMA (2002)

OFtransmission, an estimated 15% to 30% of human immunodeficiency virus (HIV)infectedpersonsarecoinfectedwithhepatitis C virus (HCV) in the United States and Europe. 1,2][5][6][7][8][9] However, there are conflicting reports regarding the effect of HCV on the natural history of HIV disease.Prior to the availability of highly active antiretroviral therapy (HAART), increased rates of progression of HIV disease were detected in some studies 5,10,11 but not others. 12-17Recently, Greub et al 18 reported that, in a study involving HIV-infected patients in Switzerland, among patients receiving HAART,HCV-coinfectedpatientshaddecreased survival rates, increased risk of progressiontoacquiredimmunodeficiency syndrome (AIDS), and impaired CD4 cell recovery.The objective of this study was to assess the effect of HCV coinfection on clinical and immunologic progression of HIV-1 disease and immunologic response to HAART in a large, urban US patient cohort observed before and during the advent of HAART.
Abstract 4480: Combination of a PI3K/mTOR inhibitor and a MEK inhibitor at suboptimal dose significantly inhibits growth of lung adenocarcinoma tumors in KrasG12D-LSL mice
Authors: Farbod Shojaei, Brett H. Simmons, Joseph H. Lee, Anthony Wong, Gerrit Los, Julie Kan, James G. Christensen
Journal: Cancer Research (2011)

Abstract The KrasG12D-LSL conditional GEMMs (genetically engineered mouse models) are a valuable tool in translational research to study tumor progression and to investigate efficacy of anti-tumor compounds in a variety of cancer types. Here, intranasal delivery of adeno-Cre resulted in the expression of mutant Kras leading to development of tumor lesions in the lungs including adenomatous hyperplasia, large adenoma and adenocarcinoma. Treatment of tumor bearing mice at adenocarcinoma stage (at 14 weeks post adeno-cre inhalation) with suboptimal dose of PF-04691502 (PI3Ka/mTOR inhibitor; 7.5 mg/kg; SID) and PD-0325901 (MEK inhibitor, 1.5 mg/kg; SID) reduced tumor lesions in mice treated with single agents and significantly inhibited tumor growth in mice treated with combination of both compounds. In addition, immunohistochemistry showed inhibition of pS6 in the treated animals particularly in the combination group providing a proof of mechanism for the tumor growth inhibition. Similar response was observed when mice bearing H460 (carry Kras and PIK3CA mutations) orthotopic lung tumors were treated with the combination regimen. These observations provide some clue to further pursue efficacy of PF-04691502 plus PD-0325901 in the clinical settings and also in more invasive models such as KrasG12D-LSLp53flox/flox mice. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 4480. doi:10.1158/1538-7445.AM2011-4480
Walcheren 1809: a medical catastrophe
Authors: M. R Howard
Journal: BMJ (1999)

In July 1809 the largest British expeditionary force ever assembled weighed anchor off the Kent coast and sailed for the island of Walcheren in the Scheldt estuary. 1 2 French naval activity at Antwerp had made the Dutch coast “a pistol held at the head of England,” and the government was keen to strike a decisive blow at Napoleon's ambitions. In the event, the preparation of the expedition was ponderous and its strategic aim was redundant before its execution. Napoleon had consolidated his grip on the continent by defeating the Austrians at Wagram earlier in the month.

The potential success of the venture was also compromised by the appointment of senior military and naval staff who appear, almost 200 years later, like characters from a pantomime. The overall commander, Lord Chatham, was elder brother to the late Mr Pitt and was himself nicknamed “the late earl” because of his difficulty in rising from bed in the morning. He was accompanied to Walcheren by his pet turtles. Commodore Sir Home Popham was described by a fellow officer, perhaps unfairly, as being like a hippopotamus—“an amfiberous hanimal, wot cannot live on the land, and wot dies in the water.” His immediate naval superior, Rear-Admiral Sir Richard Strachan, was somewhat more competent but also out of his depth in the shallow waters of the Scheldt.3

#### Summary points

In July 1809 the largest British expeditionary force ever assembled departed for the island of Walcheren in the Scheldt estuary

The military objectives were soon overshadowed by an epidemic of disease that largely destroyed the army

Review of contemporary sources suggests that Walcheren fever was due to a lethal combination of malaria, typhus, typhoid, and dysentery

The conduct of the army's senior medical officers was severely criticised in a parliamentary inquiry

Whatever the military bungling, an account …
BORACIC ACID AND MASSAGE IN PANNUS.Read in the Section of Ophthalmology at the Forty-first Annual Meeting of the American Medical Association, held at Nashville, Tenn., May, 1890.
Authors: C. R. HOLMES
Journal: JAMA (1891)

The treatment of a limited number of affections of the eye and its appendages by massage is, as is well known, not new, and to Donders belongs the honor of having first proposed it, at the Ophthalmological Congress in London in 1872. Massage has been practiced with or without the addition of ointment; but Landolt was, so far as I know, the first to systematically use boracic acid and massage in granular affections of the conjunctiva and cornea. Acting on this suggestion, I began last year to make observations on a number of cases, and present herewith the results. New methods and remedies are too often lauded far above their real worth, but after nearly a year's trial, I am satisfied that in the treatment of pannus, whether acute or chronic, it is most valuable, especially when used in connection with one or more of the standard remedies directed toward
EOSINOPENIC RESPONSE TO EPINEPHRINE
Authors: Robert M. Kark
Journal: JAMA (1952)

To the Editor:—  It is unfortunate that so many investigators, such as Drs. Charles W. Dowden and James T. Bradbury (Eosinophil Response to Epinephrine and Corticotropin: Studies in Alcoholics and Nonalcoholics,J. A. M. A.149:725-728 [June 21] 1952) continue to use subnormal eosinopenic response to injection of epinephrine as a means of testing pituitary-adrenal function.  In 1950, on the basis of animal investigations, Thorn and his associates (Recant, Hume, Forsham, and Thorn: Studies on the Effect of Epinephrine on the Pituitary-Adrenocortical System,J. Clin. Endocrinol.10:187, 1950) postulated that the hypothalamus, pituitary, and adrenal cortex are successively stimulated to produce epinephrine eosinopenia. Thorn and Forsham wrote that ... a fall of 50% or more in circulating eosinophils (after injection of epinephrine) excludes the presence of serious pituitary A.C.T.H. or adrenal cortical insufficiency, (Thorn and Forsham: Clinical Tests for Adrenal Cortical Reserve, in Progress in Clinical Endocrinology, Soskin, S.,
How can a large gallstone give rise to chronic diarrhoea?
Authors: F Parente, A Colli, M Costa, S Bargiggia, S Greco
Journal: Gut (2008)

<h3>Abstract</h3> <h3>Rationale &amp; Objectives</h3> High dose influenza vaccine provides better protection against influenza infection in older adults than standard dose vaccine. We compared vaccine seroresponse among hemodialysis patients over 4 months after high dose inactivated (HD-IIV3), standard dose inactivated (SD-IIV4) or recombinant (RIV4) influenza vaccine. <h3>Study Design</h3> Prospective observational study. <h3>Setting &amp; Participants</h3> Patients at four hemodialysis clinics who received influenza vaccination. Hemagglutination inhibition titers were measured at baseline and at 1, 2, 3 and 4 months following vaccination with HD-IIV3, SD-IIV4 or RIV4 influenza vaccine. <h3>Outcome</h3> The primary outcome was seroprotection rates at ≥1:40 and ≥1:160 (which correspond to antibody levels providing protection from infection in about 50% and 95% immunocompetent individuals, respectively) at 1, 3 and 4 months after vaccination. <h3>Analytical approach</h3> We determined GMT and seroprotection and seroconversion rates. Chi-square or Fisher exact tests were used for categorical data; continuous values were analyzed using Wilcoxon rank-sum tests. Generalized estimating equation was used to determine association between GMT and age. <h3>Results</h3> 254 HD patients received HD-IIV3 (n=141), SD-IIV4 (n=36) or RIV4 (n=77) vaccine. A robust initial seroresponse to influenza A strains was observed after all 3 vaccines, with no difference in seroprotection rates at either the ≥1:40 or ≥1:160 titer at 1 and 2 months. Seroresponses to RIV4 and SD-IIV4 waned thereafter, such that by month 3 and 4, seroprotection by HD-IIV3 was significantly higher. Seroprotection rates were lower to the B strains across all three vaccines. Results trended similarly across patients aged below 65 years. <h3>Limitations</h3> Due to use of observational data, bias by unmeasured confounders may exist. Some of the subgroups by age were low in number. <h3>Conclusions</h3> Hemodialysis patients achieved high seroprotection rates after all 3 vaccines. The seroresponse waned more slowly with HD-IIV3 as compared to SD-IIV4 or RIV4 vaccine.
The Alpha Particle or Proton Beam in Radiosurgery of the Pituitary Gland for Cushing's Disease
Authors: John A. Linfoot, John H. Lawrence, James L. Born, Cornelius A. Tobias
Journal: New England Journal of Medicine (1963)

IN the early days of the modern nuclear era, one of the first studies carried out as a means of assessing the danger from some of the radiations from the nuclear age was on the biologic effects of neutron rays. These neutral heavy particles, having the approximate weight of a proton, are approximately two thousand times as heavy as electrons and are called heavy for this reason. The early workers around the cyclotron were being constantly bombarded by these particles in addition to gamma rays, and they asked themselves, "What would be the safe daily dose?" For this reason it . . .
Acute Generalized Exanthematous Pustulosis Caused by Dihydrocodeine Phosphate in a Patient With Psoriasis Vulgaris and a Heterozygous<i>IL36RN</i>Mutation
Authors: Noriaki Nakai, Kazumitsu Sugiura, Masashi Akiyama, Norito Katoh
Journal: JAMA Dermatology (2014)

Acute generalized exanthematous pustulosis (AGEP) is a rare and severe type of drug eruption. Dihydrocodeine phosphate is a semisynthetic opioid analgesic. Recently, recessive mutations in IL36RN have been identified in generalized pustular psoriasis (GPP). To date, 4 cases of AGEP and IL36RN mutation without previous history of psoriasis vulgaris (PV) have been reported.A woman in her 60s with PV presented with diffuse erythema, nonfollicular pustules, and fever. She had been treated with dextromethorphan hydrobromide hydrate, amoxicillin hydrate, clarithromycin, dihydrocodeine phosphate, tipepidine hibenzate, and tulobuterol tape for a cough and common cold. Based on histopathologic results and a positive result in a drug provocation test with dihydrocodeine phosphate, she was diagnosed with AGEP. A heterozygous IL36RN mutation c.28C>T (p.Arg10X) was also confirmed by mutation analysis.This is the first report of dihydrocodeine phosphate-induced AGEP. In this case, helper T cells, type 17, might have been activated because of morphine and underlying PV, followed by increased production of interleukin (IL) 36. However, because of the IL36RN mutation, IL-36 signaling was uncontrolled, which might have resulted in the occurrence of AGEP. An IL36RN mutation might underlie several different pustular skin eruptions, including AGEP and GPP, and further accumulation of patient data is required.
Serum Hepatitis B Surface Antigen Quantitation Can Reflect Hepatitis B Virus in the Liver and Predict Treatment Response
Authors: Henry Lik–Yuen Chan, Vincent Wai–Sun Wong, Ada Mei–Ling Tse, Chi–Hang Tse, Angel Mei–Ling Chim, Hoi–Yun Chan, Grace Lai–Hung Wong, Joseph Jao–Yiu Sung
Journal: Clinical Gastroenterology and Hepatology (2007)
BLOOD MICROCIRCULATION IN THE LYMPH NODE DURING THE PRIMARY IMMUNE RESPONSE
Authors: Peter G. Herman, Itaru Yamamoto, Harry Z. Mellins
Journal: The Journal of Experimental Medicine (1972)

Microangiography performed after total blood replacement with contrast material provided complete visualization of the vascular structures of the lymph node. Starting of the 2nd day, there is capillary redistribution throughout the cortex of the lymph node. The previously rather avascular nodules dissolve, and the cortical lymphoid tissue becomes uniformly vascular. Beginning on the 2nd day and reaching its peak on the 5th day, there is a significant increase in diameter and density of the subcapsular and medullary cord capillaries. 15 days after the antigenic stimulus, the appearance of the microvasculature returns to normal. The postcapillary venules (the microvascular structures which follow the capillaries) are widely distributed throughout. Histologically, only a fraction of these venules have a high endothelial lining (HE venules). Therefore, it is suggested that among the postcapillary venules, those with high endothelial lining should be specifically denoted. Great individual variation in the number of HE venules was observed, and no correlation with the timing of the immune response could be established. Whether the microvascular changes described lead to cellular change or are mere expressions of it cannot definitely be stated. However, the significant hypervascularity along the intranodal lymph pathways and the diffuse, even redistribution of the capillaries and postcapillary structures could greatly facilitate the humoral and cellular exchange between the circulating blood, the circulating lymph, and the tissues of the lymph node.
Survey of hepatitis B surface variant infection in children 15 years after a nationwide vaccination programme in Taiwan
Authors: H-Y Hsu
Journal: Gut (2004)

It is not known whether hepatitis B virus (HBV) with mutations in the a determinant (amino acids (aa) 121-149) of the hepatitis B surface antigen (HBsAg) affect vaccination efficacy.To investigate the prevalence and clinical significance of these mutants in children, 15 years after universal vaccination in Taiwan.Nucleotide sequences encoding the a determinant region (aa 110-160) of HBsAg were analysed in all HBV-DNA positive sera from 1357 children and 219 adolescents serosurveyed in 1999. We then compared the prevalence and changes in the mutants in these children with our previous surveys in the same area conducted in 1984 (just before vaccination), 1989, and 1994.The prevalence of a determinant mutants in HBV-DNA positive children was 7.8% (8/103) in 1984, which significantly increased to 19.6% (10/51) in 1989, peaked at 28.1% (9/32) in 1994, and remained at 23.1% ((3/13) (T131I, G145R, G145R)) in 1999; it was higher in those fully vaccinated compared with those not vaccinated (15/46 v 15/153; p<0.001). However, the number of mutant infected children in each survey was stable in the first 5-10 year period but decreased 10-15 years post vaccination. Increased amino acid variation in the a determinant region occurred in carrier children in the post vaccination survey. Mutated residues tended to occur more frequently in the region with greater local hydrophilicity (residues 140-149) in those vaccinated than in unvaccinated children with variant infection (12/15 v 6/15; p = 0.062). More HBsAg positive a determinant mutants emerged in children fully vaccinated with plasma derived vaccine than those given recombinant vaccine (10/2399 (0.46%) v 0/503; p = 0.122).We found that a determinant variants have an advantage in infecting immunised children but do not threaten current HBV vaccination strategies in Taiwan.
Multicentre studies should be cited by study name
Authors: M.-L. Newell
Journal: BMJ (1995)

lead to nationally agreed terms and conditions of work and much enhanced status.We still urge all women who can to work as principals, but we recognise the need for officially recognised, short term, part time posts in general practice.Vocationally trained doctors who cannot take on the commitment that a post as a principal entails have no such option at present, and the alternatives available-assistantships, locum work, and the retainer scheme-tend to be poorly rewarded and poorly regarded.We regret the Department of Health's refusal to upgrade the retainer scheme, despite the evident need for this, and will continue to collect evidence on the scheme's use from all those interested.We would welcome correspondence on this as well as the other issues mentioned.The need for more flexible working patterns extends throughout medicine as more women enter medicine and more men seek a better way to combine their home and working lives.Flexible working patterns and changes in ways of providing cover for out of hours services would help to maintain the health and morale of
The fractalkine receptor CX3CR1 protects against liver fibrosis by controlling differentiation and survival of infiltrating hepatic monocytes
Authors: Karlin Raja Karlmark, Henning W. Zimmermann, Christoph Roderburg, Nikolaus Gassler, Hermann E. Wasmuth, Tom Luedde, Christian Trautwein, Frank Tacke
Journal: Hepatology (2010)

Chemokines modulate inflammatory responses that are prerequisites for organ fibrosis upon liver injury. Monocyte-derived hepatic macrophages are critical for the development, maintenance, and resolution of hepatic fibrosis. The specific role of monocyte-associated chemokine (C-X3-C motif) receptor 1 (CX3CR1) and its cognate ligand fractalkine [chemokine (C-X3-C motif) ligand 1)] in liver inflammation and fibrosis is currently unknown. We examined 169 patients with chronic liver diseases and 84 healthy controls; we found that CX3CL1 is significantly up-regulated in the circulation upon disease progression, whereas CX3CR1 is down-regulated intrahepatically in patients with advanced liver fibrosis or cirrhosis. To analyze the functional relevance of this pathway, two models of experimental liver fibrosis were applied to wild-type (WT) and CX3CR1-deficient mice. Fractalkine expression was induced upon liver injury in mice, primarily in hepatocytes and hepatic stellate cells. CX3CR1−/− animals developed greater hepatic fibrosis than WT animals with carbon tetrachloride–induced and bile duct ligation–induced fibrosis. CX3CR1−/− mice displayed significantly increased numbers of monocyte-derived macrophages within the injured liver. Chimeric animals that underwent bone marrow transplantation revealed that CX3CR1 restricts hepatic fibrosis progression and monocyte accumulation through mechanisms exerted by infiltrating immune cells. In the absence of CX3CR1, intrahepatic monocytes develop preferentially into proinflammatory tumor necrosis factor–producing and inducible nitric oxide synthase–producing macrophages. CX3CR1 represents an essential survival signal for hepatic monocyte–derived macrophages by activating antiapoptotic bcl2 expression. Monocytes/macrophages lacking CX3CR1 undergo increased cell death after liver injury, which then perpetuates inflammation, promotes prolonged inflammatory monocyte infiltration into the liver, and results in enhanced liver fibrosis. Conclusion: CX3CR1 limits liver fibrosis in vivo by controlling the differentiation and survival of intrahepatic monocytes. The opposing regulation of CX3CR1 and fractalkine in patients suggests that pharmacological augmentation of this pathway may represent a possible therapeutic antifibrotic strategy. (Hepatology 2010;52:1769-1782)
Major Hemorrhage and Tolerability of Warfarin in the First Year of Therapy Among Elderly Patients With Atrial Fibrillation
Authors: Elaine M. Hylek, Carmella Evans-Molina, Carol Shea, Lori E. Henault, Susan Regan
Journal: Circulation (2007)

Background— Warfarin is effective in the prevention of stroke in atrial fibrillation but is under used in clinical care. Concerns exist that published rates of hemorrhage may not reflect real-world practice. Few patients ≥80 years of age were enrolled in trials, and studies of prevalent use largely reflect a warfarin-tolerant subset. We sought to define the tolerability of warfarin among an elderly inception cohort with atrial fibrillation. Methods and Results— Consecutive patients who started warfarin were identified from January 2001 to June 2003 and followed for 1 year. Patients had to be ≥65 years of age, have established care at the study institution, and have their warfarin managed on-site. Outcomes included major hemorrhage, time to termination of warfarin, and reason for discontinuation. Of 472 patients, 32% were ≥80 years of age, and 91% had ≥1 stroke risk factor. The cumulative incidence of major hemorrhage for patients ≥80 years of age was 13.1 per 100 person-years and 4.7 for those &lt;80 years of age ( P =0.009). The first 90 days of warfarin, age ≥80 years, and international normalized ratio (INR) ≥4.0 were associated with increased risk despite trial-level anticoagulation control. Within the first year, 26% of patients ≥80 years of age stopped taking warfarin. Perceived safety issues accounted for 81% of them. Rates of major hemorrhage and warfarin termination were highest among patients with CHADS 2 scores (an acronym for congestive heart failure, hypertension, age ≥75, diabetes mellitus, and prior stroke or transient ischemic attack) of ≥3. Conclusions— Rates of hemorrhage derived from younger noninception cohorts underestimate the bleeding that occurs in practice. This finding coupled with the short-term tolerability of warfarin likely contributes to its underutilization. Stroke prevention among elderly patients with atrial fibrillation remains a challenging and pressing health concern.
Metrizamide in venography.
Authors: M L Thomas, H L Walters
Journal: BMJ (1979)

in psychopathology, which worsened after a three-day washout period and became similar to that seen before metoclopramide treatment.The patient was then treated with the classical neuroleptic haloperidol.At a dose of 45 mg/day the same extrapyramidal syndrome re-emerged and was completely responsive to trihexyphenidyl 2 mg by mouth three times daily.After haloperidol dosage was increased to 100 mg'day the tremor emerged in a milder form.Psychopathology at this dosage was partially improved, but some disorganisation of thought, delusions, and hallucinations persisted.His state at this time (10th day of haloperidol treatment) was comparable to that noted after metoclopramide 1 g/day.