tbuckley/cabot-search huggingface dataset:
Activation of the mammalian target of rapamycin signaling pathway in hepatocellular carcinoma
Authors: Ishwaria M. Subbiah, Robert E. Brown, Michael B. Fallon
Journal: Hepatology (2010)

We have read with great interest the article entitled "Sirolimus-Based Immunosuppression Is Associated with Increased Survival After Liver Transplantation for Hepatocellular Carcinoma" by Toso et al.1 The prospect of a dual role for inhibitors of mammalian target of rapamycin (mTOR), the so-called rapalogs, in both immunosuppression and chemotherapy will shape future therapy for hepatocellular carcinoma (HCC). We are writing now to draw attention to our institutional data reported by Li et al.,2 who evaluated mTOR expression in patients with HCC versus its expression in the cirrhotic liver and in normal liver tissue. These data show significantly elevated expression of p-mTOR in the sinusoidal endothelial cells of HCC tissue samples in comparison with non-HCC tissue (i.e., hepatic adenoma, cirrhotic nodules, and normal liver tissue), suggesting that this pathway plays a plausible role in HCC progression. With several mTOR inhibitors in the clinic [sirolimus (rapamycin), everolimus (RAD001), and temsirolimus (CCI-779)], this immunohistological confirmation of elevated mTOR expression in HCC forms the rational foundation for signaling cascade activation–based targeted therapy with mTOR inhibitors. Moreover, a feedback loop pathway stemming from the use of mTOR, which leads to activation of the mitogen-activated protein kinase pathway, can be targeted by sorafenib3 (which is already in use and remains the only novel targeted drug demonstrating a survival benefit for patients with HCC). mTOR inhibitors have also shown promise in combination with other agents such as transarterial chemoembolization, adriamycin, and bevacizumab (Avastin)4, 5 in experimental preclinical models of HCC. We hope that novel "omics-based" techniques will unravel the mysteries of all the cell signaling pathways of each HCC with respect to the targeted therapy. We await with anticipation the outcomes of several ongoing phase 1 trials combining the next generation of mTOR, multikinase, and angiogenesis inhibitors (both small molecules and antibodies) for patients with HCC. Ishwaria M. Mohan M.D., M.S.* , Robert E. Brown M.D. , Michael B. Fallon M.D. , * Divisions of Internal Medicine, University of Texas at Houston, Houston, TX, Divisions of Pathology, University of Texas at Houston, Houston, TX, Divisions of Gastroenterology, Hepatology, and Nutrition, University of Texas at Houston, Houston, TX.
Genetic epidemiology of β‐thalassemia in sicily: Do sequences 5′ to the <sup>G</sup>γ gene and 5′ to the β gene interact to enhance HbF expression in β‐thalassemia?
Authors: Angela Ragusa, Mario Lombardo, Cherif Beldjord, Concetta Ruberto, Turi Lombardo, Jacques Elion, Ronald L. Nagel, Rajagopal Krishnamoorthy
Journal: American Journal of Hematology (1992)

Abstract The present epidemiological study of the molecular characteristics of β‐thalassemia in Sicily was prompted by the disparate phenotypic expression (in clinical status and absolute HbF level) observed in two β‐thalassemic homozygotes who were also homozygous for the β‐like globin gene cluster haplotype III. We suspected that polymorphisms within haplotype III could be the cause for the discrepancy. Based on the association of particular conformations of the (AT) x T y motif (‐540 5′ to the β gene) with milder forms of thalassemia and sickle cell anemia, 38 homozygous β‐thalassemia patients were studied to define their haplotypes, the −158 site 5′ to the G γ gene (linked to haplotype III) and the structure of the (AT) x T y motif. We found that the patient who was phenotypically mild and homozygous for β‐thalassemia, haplotype III, and the −158 C→T mutation was homozygous for the rare (AT) 9 T 5 motif. In contrast, the patient homozygous for β‐thalassemia, haplotype III, and the —158 mutation, but exhibiting a severe clinical course, was homozygous for the (AT) 7 T 7 configuration. Others have suggested that (AT) 9 T 5 is a negative regulatory protein binding sequence, and it is a silent carrier state for β‐thalassemia. The usual configuration (AT) 7 T 7 , has considerably less affinity for regulatory protein binding, and it is the most common configuration in Sicilian β‐thalassemics (67 of the 78 chromosomes studied). Within the 38 patients studied, seven were informative because they had various combinations of the (AT) 9 T 5 and (AT) 7 T 7 motif, and the −158 C→T mutation. The results in these patients suggest that only the co ‐presence of the (AT) 9 T 5 configuration and a C→T change at −158.5′ to the G γ gene is associated with high HbF expression and a mild clinical phenotype. We postulate that these two regions of the β‐like globin gene cluster interact, when endowed with the proper sequences, to enhance the expression of HbF secondary to anemia. © 1992 Wiley‐Liss, Inc.
OSTEOMYELITIS OF CREST OF RIGHT PUBIC BONE
Authors: A. Belcham Keyes
Journal: JAMA (1923)

The infrequency of pubic osteomyelitis, both as a spontaneous disease, and as secondary to the rare anterior pelvic (parametric) abscess that may later involve the bone, makes a report of this case of especial interest.  History.  —Mrs. R. W., white, aged 24, with one boy, living and robust, aged 3, was brought to my office, April 7, 1920. With theexception of children's diseases she had always had good health. The heredity was good, and the patient stated that there had been no venereal disease, attempts to induce abortion, or pelvic treatment or examination of any kind.  In the autumn of 1918, she had influenza and pneumonia, being sick about four weeks, with very violent spells of coughing, occasionally lasting as long as fifteen minutes, and often accompanied by bleeding from the mouth and ears.  Some weeks after recovery, though still quite weak, she went to work in a stationery store.
Iron removal therapy in porphyria cutanea tarda: phlebotomy versus slow subcutaneous desferrioxamine infusion
Authors: E. ROCCHI, P. GIBERTINI, M. CASSANELLI, A. PIETRANGELO, A. BORGHI, M. PANTALEONI, J. JENSEN, E. VENTURA
Journal: British Journal of Dermatology (1986)

Twenty-five patients with overt clinical and biochemical findings of porphyria cutanea tarda took part in a study comparing intensive phlebotomy with slow subcutaneous desferrioxamine treatment. Fifteen male patients (Group A) had intensive venesection therapy. Ten patients (Group B) with associated diseases(minor thalassemia, cardiovascular impairment, pulmonary tuberculosis or severe liver cirrhosis) received 1.5 g of desferrioxamine by slow subcutaneous infusion using and automatic syringe pump 5 days a week. No patient complained of appreciable side effects. Serum iron, ferritin and uroporphyrins were normalized in all subjects by the end of treatment. The mean time necessary for complete recovery was 13.8 months (range 9–19) and 11.2 months (range 6–14) in Groups A and B, respectively. Liver fucntion significantly improved during and after the treatments in both groups. We conclude that recover from porphyria cutanea tarda can be achieved equally well using phlebotomy or desferrioxamine subcutaneous infusion. Phlebotomey is easily performed and remains the treatment of choice; slow subcutaneous desferrioxamine treatment, although expensive, is recommended when severe associated diseases contra-indicate venesection.
Endoscopic Discovery and Capture of Necator americanus in the Stomach
Authors: A. Dumont, V. Seferian, P. Barbier
Journal: Endoscopy (1983)

We report a case of the endoscopic discovery and removal of a specimen of Necator americanus hooked into the gastric mucosa of a black woman from Zaire. We extracted the parasite by means of biopsy forceps. Signs of previous bites were seen in the antrum. This exceptional localization might be due to a jejuno-duodeno-gastric reflux.
Solitary sclerotic fibroma of the lip
Authors: F. Ide, K. Mishima, I. Saito
Journal: British Journal of Dermatology (2003)

Sir, Sclerotic fibroma (SF) is a rare peculiar type of dermal fibroma. SF was first described to be associated with Cowden's disease by Weary et al.1 and is now considered to be a cutaneous hallmark of this cancer‐prone genodermatosis only when it is multiple.2, 3 Consequently, the occurrence of a solitary SF may not allow the dermatologists to suggest the diagnosis of Cowden's disease. Although oral manifestations are common in Cowden's disease, multiple mucosal papules and nodules typically are simple fibroepithelial hyperplasia4 and SF is a very rare complication.1 To our knowledge, none of the cases of sporadic SF described in the British literature involved the oral mucosa. We observed a solitary mucosal tumour of the lip that fulfilled the diagnostic criteria of SF in a patient without Cowden's disease. A 64‐year‐old woman had a painless, slowly enlarging mass on the lower lip of 1‐year duration. There were no signs of Cowden's disease in the patient and her family members. On examination, a solitary, 7 × 6 × 5 mm, firm, mobile nodule was found (Fig. 1a). At operation, three small lobules of salivary glands were attached to the tumour. There was no evidence of recurrence or a new lesion. Histological examination showed a rounded, sharply demarcated fibrocollagenous tumour in the submucosa (Fig. 1b). A dense proliferation of hypocellular hyalinized bands of collagen with prominent empty clefts were arranged in a peculiar whorled or plywood pattern (Fig. 1c). A few spindle‐shaped tumour cells were entrapped among the thick bundles, but the major part of the lesion was acellular. These cells were immunoreactive with vimentin, factor XIIIa and CD34 (Fig. 1d). Bcl‐2, factor VIII‐related antigen, smooth muscle actin, S‐100 protein and Ki‐67 were uniformly negative in tumour cells.
STUDIES ON HOST FACTORS IN PNEUMOCOCCUS INFECTIONS
Authors: Kenneth Goodner
Journal: The Journal of Experimental Medicine (1934)

In the experimental disease brought about by infecting rabbits intradermally with Type I Pneumococcus the use of relatively small or subeffective amounts of specific antipneumococcus serum leads to the survival of some individuals and the death of others. It has been shown that both the severity of the infection and the white blood cell count are factors in the determination of the outcome of the disease but that there remain other host factors which have to do with the utilization or functioning of the specific antisera.
A CASE OF FRACTURE OF THE THYROID CARTILAGE WITH PROMPT RECOVERY
Authors: A. C. MATTHEWS
Journal: JAMA (1910)

big the most momentous are those relating to the up-keep of fie body by alimentation.It is food that supplies the mate¬ rial for that perpetual ' series of transformations in which ¡ife consists, and it, must be adequate in quantity and suitable i» quality, if these transformations are to proceed with that
Experimental Epicrisis of Some Late Researches on Liver-Sugar
Authors: J. L. W. Thudichum
Journal: BMJ (1860)

ORIGINAL COMMUNICATION& S.O 17, 18G.section of these lectures, and in whom an orgaised conetion existed in the left heart, is the second ease of this kind to which I would refer.This lady had sufered certainly from symptoms which had been referred to the heart, but not of an intensity sufficient, as it seemed, to endanger life.Suddenly, after some tritling exertion, she fell and died almost instantly, the globular concretion being carried by the blood-stream into the aorta, and occluding it as effectually as a tight ligature around the vessel.Lastly, the deposit of fibrine in the heart, in cases of old stand- ing heart-disease, may give rise to peculiarities of symptom re- flecting on those of simple cardiac disorder on the one hand, and on those of concretion on the other.In the instance of a girl who had suffered for some years with hypertrophy of the heart and mitral induration, an acute but slight rheumatic attack led to deposition, and to the most extensive deposition I have perbaps ever witnessed.In the course of this case, about four days before denth, the mitral murmnur disappeared altogether; the pulse at the samie time becoming Most irregular, and so quick that it was barely to be counted.Without any marked general irndications of obstruction from clot, this patient, while sitting up in bed taking drink, exclaimed "Oh dear, how weak I am!"t and died instantly from syncope.Now, in this case, the disappearance of the mitral murmur was accounted for fully at the poot mortem examination.It was found that the indurated mitral valve was held back by a fibrinous band; wbile the absence of the special signs of con.cretion was accounted for by the great size and dilatation of
Methylmercury neurotoxicity in Amazonian children downstream from gold mining.
Authors: P Grandjean, R F White, A Nielsen, D Cleary, E C de Oliveira Santos
Journal: Environmental Health Perspectives (1999)

In widespread informal gold mining in the Amazon Basin, mercury is used to capture the gold particles as amalgam. Releases of mercury to the environment have resulted in the contamination of freshwater fish with methylmercury. In four comparable Amazonian communities, we examined 351 of 420 eligible children between 7 and 12 years of age. In three Tapajós villages with the highest exposures, more than 80% of 246 children had hair-mercury concentrations above 10 microg/g, a limit above which adverse effects on brain development are likely to occur. Neuropsychological tests of motor function, attention, and visuospatial performance showed decrements associated with the hair-mercury concentrations. Especially on the Santa Ana form board and the Stanford-Binet copying tests, similar associations were also apparent in the 105 children from the village with the lowest exposures, where all but two children had hair-mercury concentrations below 10 microg/g. Although average exposure levels may not have changed during recent years, prenatal exposure levels are unknown, and exact dose relationships cannot be generated from this cross-sectional study. However, the current mercury pollution seems sufficiently severe to cause adverse effects on brain development.
High dose rate brachytherapy for the local control of endobronchial carcinoma following external irradiation.
Authors: P Hernandez, A Gursahaney, T Roman, K Schwartzman, D Donath, M G Cosio, R D Levy
Journal: Thorax (1996)

External irradiation is an established palliative treatment for patients with inoperable lung cancer. However, persistent or recurrent symptoms due to local disase are common following external irradiation. The impact of high dose rate (HDR) brachytherapy in the palliative management of patients with local sequelae of residual or recurrent endobronchial lung carcinoma following external irradiation was investigated.A prospective cohort of 29 patients (19 men, mean age 65 years) underwent HDR brachytherapy for inoperable lung cancer. All patients had completed external irradiation at least one month before entry into the study (mean (SD) dose 4400 (1481) cGy, completed 12.9 (21.3) months previously). Patients underwent outpatient bronchoscopic placement of 1-3 HDR brachytherapy catheters for delivery of 750-1000 cGy of intraluminal irradiation every two weeks on 1-3 occasions. Prospective evaluation before and four weeks after completion of HDR brachytherapy included assessment of indices of level of function, symptoms, extent of atelectasis (chest radiography), and bronchoscopic determination of degree of endobronchial obstruction.One hundred and eighteen catheters were placed in 81 treatments. Eleven of the 26 patients who underwent repeat bronchoscopy showed a reduction in the degree of endobronchial obstruction; five of 18 patients had radiographic improvement in the extent of atelectasis. Positive response rates ranged from 25% for signs and symptoms related to pneumonitis to 69% for haemoptysis. Performance status improved in 24% of patients. Two patients died before completion of the study protocol. Short term complications included one episode of non-fatal, massive haemoptysis, five of minor haemoptysis, and one pneumothorax.HDR brachytherapy may improve the degree of endobronchial obstruction, atelectasis, symptoms, and level of function with minimal short term complications in patients with recurrent or residual symptomatic disease following external irradiation.
The Labeling of Specimens as Infectious-Reply
Authors: H. Hunter Handsfield
Journal: JAMA (1988)

<h3>In Reply.</h3> —We stand by the results of our study. There is an apparent conflict between Dr Godfrey's agreement that "all specimens should... be handled with appropriate precautions" and his statement that laboratory workers should "protect themselves with increased caution" when handling specimens labeled as infectious. What additional measures does he recommend? Whatever they are, our study shows that they should apply to unlabeled specimens as well as to labeled ones. As Dr Godfrey points out, this recommendation has the support of the Public Health Service<sup>1</sup>and the American Hospital Association, as well as the Association for Practitioners in Infection Control.<sup>2</sup>These organizations did not develop their guidelines in a vacuum; each received substantial input from representatives of laboratories, nurses, and others that routinely handle specimens. Of course, HIV and hepatitis B virus are not the only concerns. Specimens likely to harbor cytomegalovirus, Epstein-Barr virus, the human T-cell
Clarification of a clarification
Authors: G. Shaw
Journal: BMJ (2009)

<h3>Objective</h3> To investigate the relationship between matrix metalloproteinase-9, high sensitive C-reactive protein and carotid intima-media thickness. <h3>Methods</h3> 180 patients were selected. High-resolution ultrasound was used to scan carotid, brachial arteries of all patients in order to check and measure carotid intima-media thickness (CIMT), plaques of carotid arteries and diameter of brachial arteries at rest. Patients were divided into four groups: the normal carotid intima group, the difficuse proliferative carotid intima group, the stable plaque group and the unstable plaque group. Serum levels of MMP-9, hsCRP were determined with immunological method. The relationship between the results measured by ultrasound instrument and the concentrations of MMP-9, and hsCRP was analysed. <h3>Results</h3> The serum levels of MMP-9 and hsCRP in the proliferative carotid intima group were higher than in the normal carotid intima group (p&lt;0.01). The serum levels of MMP-9 and hsCRP in the unstable plaque group and in the stable plaque group were higher than in difficuse proliferative carotid intima group (p&lt;0.05). The serum levels MMP-9 and hsCRP in the unstable plaque group were higher than in the stable plaque group (p&lt;0.05). <h3>Conclusion</h3> The increased concentrations of MMP-9 and hsCRP were closely correlated with the increment of carotid intima-media thickness, the unsteady of plaque.
SV40 as a causative agent in mesothelioma: a new twist to the story
Authors: Y C G Lee
Journal: Thorax (2004)

<h3>Objective</h3> This work aims to explore whether Toll-like receptor 9 (TLR9) −1486T/C and 2848G/A polymorphisms are associated with cervical cancer risk. <h3>Methods</h3> A comprehensive electronic search of studies published from January 1999 to October 2014 was conducted in Medline (Ovid), Embase, PubMed, Wanfang, Weipu, and CNKI. The algorithm included “TLR,” “Toll-like receptor,” “polymorphism,” “variant,” “mutation,” and “cervical cancer.” Seven articles, including 9 studies, were pooled using Revman 5.2 (Cochrane Collaboration, Copenhagen, Denmark). Odds ratio (OR) was used to explore the involvement of minor allele C (C vs T and CC + CT vs TT) of TLR9 (−1486T/C, rs187084) and minor allele A (A vs G and AA + AG vs GG) of TLR9 (2848G/A, rs352140) in cervical cancer risk. <h3>Results</h3> Toll-like receptor 9 (−1486T/C, rs187084) polymorphisms were associated with an elevated risk of cervical cancer (C vs T: OR, 1.15; 95% confidence interval [CI], 1.03–1.29; CC + CT vs TT: OR, 1.30; 95% CI, 1.11–1.53). We found no significant association between TLR9 (2848G/A, rs352140) polymorphisms and cervical cancer risk (A vs G: OR, 1.15; 95% CI, 0.87–1.54; AA + AG vs GG: OR, 1.27; 95% CI, 0.75–2.17). <h3>Conclusions</h3> This meta-analysis indicates that TLR9 (−1486T/C, rs187084)—but not TLR9 (2848G/A, rs352140)—may be a risk factor for cervical cancer.
Taming the monster
Authors: F. Godlee
Journal: BMJ (2013)

Imagine for a moment that you could redesign your job. What would it look like if there were no bean counters? So asks David Loxterkamp in his BMJ Essay this week (doi:10.1136/bmj.f5539). Loxtercamp was an early adopter of the electronic health record. As a family physician in America, he revelled in how much it simplified and organised his practice. Thirteen years on, the benefits are still clear to him: fewer prescribing errors, closer adherence to evidence based guidelines. But he also now …
SERIAL ANGIOGRAPHIC OUTCOMES &amp;gt; 2 YEARS AFTER SIROLIMUS-ELUTING STENT IMPLANTATION: CONTEMPORARY PRACTICE IN REAL WORLD POPULATION
Authors: Euihong Ko, Nasu Kenya, Tsuyoshi Itoh, Maoto Habara, Tairo Kurita, Yoshihisa Kinoshita, Etsuo Tsuchikane, Yasushi Asakura, Takahiko Suzuki
Journal: Journal of the American College of Cardiology (2012)
Sarcomatoid carcinoma of the liver with skin and pleural metastases
Authors: W. Nishie, M. Iitoyo, T. Koshiyama, T. Kusama
Journal: British Journal of Dermatology (2003)

Journal Article Sarcomatoid carcinoma of the liver with skin and pleural metastases Get access W. Nishie, W. Nishie Departments of Dermatology and Search for other works by this author on: Oxford Academic Google Scholar M. Iitoyo, M. Iitoyo Departments of Dermatology and Search for other works by this author on: Oxford Academic Google Scholar T. Koshiyama, T. Koshiyama Internal Medicine, Kin‐ikyo Sapporo Hospital, Kikusui 4‐1‐9‐22, Shiroishi‐ku, Sapporo 003‐8510, Japan, and Search for other works by this author on: Oxford Academic Google Scholar T. Kusama T. Kusama Department of Internal Medicine, Kin‐ikyo Central Hospital, Sapporo, Japan. E‐mail: wataru@seagreen.ocn.ne.jp Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 148, Issue 5, 1 May 2003, Pages 1069–1071, https://doi.org/10.1046/j.1365-2133.2003.05320.x Published: 01 May 2003
An 11 month old girl with bilateral wrist swelling
Authors: R Hodgkinson, D S Urquhart, L Thia, S Padley, A Bush, A. Gupta
Journal: BMJ (2008)

An 11 month old girl presented to the paediatric department with a lower respiratory tract infection. She also had failure to thrive and mild motor developmental delay. On examination, she had swollen wrists bilaterally. A radiograph of her right arm is shown below (fig 1)⇓. Her blood results were urea 4.3 mmol/l, creatinine 29 μmol/l, corrected calcium 2.47 mmol/l, alkaline phosphatase 3340 U/l, and phosphate 1.88 mmol/l. Fig 1 Wrist radiograph of an 11 month old girl with bilateral wrist swelling Fig 2 Wrist radiograph showing splaying, cupping, and widespread demineralisation Fig 3 Chest radiograph showing prominent costochondral joints (rachitic rosary)
The FDA, Politics, and the Public
Authors: Louis Lasagna
Journal: JAMA (1975)

SINCE it was begun in 1907, the Food and Drug Administration (FDA) has often been the center of controversy. Recent scandals in the executive branch of the government have reminded us that public officials are not above either the law or the public they are supposed to serve. It is therefore appropriate that the FDA be responsive to public concerns, and be held accountable when criticism erupts, be it from consumerists, the medical profession, the drug industry, or the Congress. Still, it is also crucial that a regulatory agency not become so embroiled in defensive maneuvers that it loses its ability to serve the public properly. During the last decade, the FDA has been accused both of overregulation and underregulation. Such a situation is not as paradoxical as it might seem. On the one hand, the FDA might be considered culpable if it fails to police drug manufacturers and allows