tbuckley/cabot-search huggingface dataset:
TREATMENT OF HYPERPIESIA
Authors: W. Edgecombe
Journal: BMJ (1932)

What is the cause of this arteriolar contraction?Diathesis, psychic factors, overwork, sedentary.occupa- tions, obesity, endocrine changes, circulating pressor bases, have all had their advocates.Their very number is a confession of our ignorance.There is no doubt that high blood pressure is often familial.Lord Dawson found a percentage of school children had pressures above the normal,2 but it is as yet too early to say whether any of them will eventually develop true hyperpiesia.Nervous causes and overwork certainly raise the pressure, but many men overwork and never suffer from hyperpiesia, and neurotic people often have low pressures.Sedentary occupations are blamed for many things: hyperpiesia is only one of them.Hyperpiesia and overweight may coexist, but it is doubtful whether the majority of obese persons have high pressures.There is no reason why circulating pressor bases should not be eliminated, since it is known that the kidneys remain normal until their arterioles become affected with those of the rest of the body.Hvperpiesia will probably be found to be a deficiency disease.As noted by IsmailP it has something in common
A biological staging model for operable non-small cell lung cancer
Authors: G Cox
Journal: Thorax (2001)

Background-Currently the best prognostic index for operable non-small cell lung cancer (NSCLC) is the TNM staging system.Molecular biology holds the promise of predicting outcome for the individual patient and identifying novel therapeutic targets.Angiogenesis, matrix metalloproteinases (MMP)-2 and -9, and the erb/HER type I tyrosine kinase receptors are all implicated in the pathogenesis of NSCLC.Methods-A retrospective analysis of 167 patients with resected stage I-IIIa NSCLC and >60 days postoperative survival with a minimum follow up of 2 years was undertaken.Immunohistochemical analysis was performed on paraYn embedded sections for the microvessel marker CD34, MMP-2 and MMP-9, EGFR, and c-erbB-2 to evaluate the relationships between and impact on survival of these molecular markers.Results-Tumour cell MMP-9 (HR 1.91 (1.23-2.97)), a high microvessel count (HR 1.97 (1.28-3.03)),and stage (stage II HR 1.44 (0.87-2.40), stage IIIa HR 2.21 (1.31-3.74))were independent prognostic factors.Patients with a high microvessel count and tumour cell MMP-9 expression had a worse outcome than cases with only one (HR 1.68 (1.04-2.73))or neither (HR 4.43 (2.29-8.57)) of these markers.EGFR expression correlated with tumour cell MMP-9 expression (p<0.001).Immunoreactivity for both of these factors within the same tumour was associated with a poor prognosis (HR 2.22 (1.45-3.41)).Conclusion-Angiogenesis, EGFR, and MMP-9 expression provide prognostic information independent of TNM stage, allowing a more accurate outcome prediction for the individual patient.The development of novel anti-angiogenic agents, EGFR targeted therapies, and MMP inhibitors suggests that target specific adjuvant treatments may become a therapeutic option in patients with resected NSCLC.
We can learn from disciplines outside medicine
Authors: L. Polak
Journal: BMJ (2012)

Moynihan and colleagues have omitted three issues from their article on preventing overdiagnosis.1

Firstly, who decides where the balance of harms and benefits tips into overdiagnosis? For taxpayers, some screening and preventive treatments may be the most cost effective use of NHS resources. For patients, preference depends on the values they ascribe—for example, to reducing risk of fractures versus risk …
IRON METABOLISM. IRON STORES IN MAN AS MEASURED BY PHLEBOTOMY 1
Authors: Donald Haskins, Alexander R. Stevens, Stuart Finch, Clement A. Finch
Journal: Journal of Clinical Investigation (1952)

Hemosiderin and ferritin represent storage iron, available for hemoglobin synthesis when need arises.Previous observations (1, 2) have indi- cated that these stores must be depleted before iron deficiency becomes manifest in the circulating red cell mass.The depletion of iron stores associ- ated with normal hematological measurements may therefore be regarded as the "preclinical " phase of iron deficiency.Interest in the pathogenesis of iron deficiency anemia has led us to further methods of evaluating iron stores.A rough estimate of iron reserves may be obtained by examination of sternal mar- row for hemosiderin (2).A more quantitative measurement may be made by determination of iron mobilized for red cell production following phlebotomy.Data obtained by the latter technique are presented to define the size of the iron storage compartment in order to determine its availability and rate of replenishment in normal adult males and in subjects with abnormalities of iron metabo- lism. METHODSVolunteers were repeatedly phlebotomized as previously described (3).A balance sheet was kept on each subject recording the amount of iron removed by phle- botomy and the weekly change in red cell mass expressed in mg. of iron.Repeated blood volumes were performed in each subject, in some individuals weekly over a period of two months.Despite the development of anemia the total blood volume showed no change thought to be sig-
Penetration of amoxycillin/clavulanic acid into bronchial mucosa with different dosing regimens.
Authors: I M Gould, G Harvey, D Golder, T M Reid, S J Watt, J A Friend, J S Legge, J G Douglas
Journal: Thorax (1994)

BACKGROUND--The efficacy of an antibiotic is related to its concentration at the site of infection. Previous studies of the concentrations of amoxycillin and clavulanic acid (co-amoxiclav) in respiratory secretions or whole lung tissue have suffered from methodological problems. The concentration of amoxycillin and clavulanic acid was determined in bronchial mucosal biopsy samples obtained at bronchoscopy following five different dosing regimens. METHODS--Bronchial biopsy and serum samples were obtained from 50 patients undergoing diagnostic bronchoscopy. Ten patients each received 375 mg, 625 mg, 750 mg, and 3.25 g oral, and 1.2 g intravenous co-amoxiclav 1-3 hours before bronchoscopy. The concentrations of clavulanic acid and amoxycillin were determined by high performance liquid chromatography using a microbore column, solid phase extraction, and preconcentration to improve sensitivity tenfold over previous methods. RESULTS--Concentrations of both clavulanic acid and amoxycillin in bronchial mucosa were dose related and were well above the MIC90 of co-amoxiclav for the common bacterial respiratory pathogens including Haemophilus influenzae, Micrococcus catarrhalis and Streptococcus pneumoniae for all dosing regimens. Mean mucosal levels were 200% and 118% of the corresponding serum levels for amoxycillin and clavulanic acid respectively. CONCLUSIONS--Amoxycillin and clavulanic acid are concentrated in bronchial mucosa and, even at the lowest dose of 375 mg orally, are likely to produce tissue levels in the lung sufficient to inhibit all the common community acquired respiratory pathogens.
Prognoses of patients with acute-on-chronic hepatitis B liver failure are closely associated with altered SOCS1 mRNA expression and cytokine production following glucocorticoid treatment
Authors: Jian-Jun Zhang, Yu-Chen Fan, Ze-Hua Zhao, Yang Yang, Cheng-Yun Dou, Shuai Gao, Kai Wang
Journal: Cellular and Molecular Immunology (2014)
Liprin β1 is highly expressed in lymphatic vasculature and is important for lymphatic vessel integrity
Authors: Camilla Norrmén, Wouter Vandevelde, Annelii Ny, Pipsa Saharinen, Massimiliano Gentile, Guttorm Haraldsen, Pauli Puolakkainen, Eugene Lukanidin, Mieke Dewerchin, Kari Alitalo, Tatiana V. Petrova
Journal: Blood (2009)
Dermatofibrosarcoma Protuberans of the Toe Findings on Multiple Imaging Modalities
Authors: GHADA S. ASSASSA, MICHAEL E. SIEGEL, DAVID C. CHEN, AZIZULLAH N. ANSARI
Journal: Clinical Nuclear Medicine (1993)

Dermatofibrosarcoma protuberans occurs early in life, is an unusual soft tissue tumor, and is uncommonly seen distal to knees. The authors present a rare case of dermatofibrosarcoma protuberans of the toe with different imaging modalities.
Improved Tumor Immunity Using Anti-Tyrosinase Related Protein-1 Monoclonal Antibody Combined with DNA Vaccines in Murine Melanoma
Authors: Yvonne M. Saenger, Yanyun Li, Karoline C. Chiou, Brian Chan, Gabrielle Rizzuto, Stephanie L. Terzulli, Taha Merghoub, Alan N. Houghton, Jedd D. Wolchok
Journal: Cancer Research (2008)

Abstract Passive immunization with monoclonal antibody TA99 targeting melanoma differentiation antigen tyrosinase-related protein-1 (Tyrp1; gp75) and active immunization with plasmid DNA encoding altered Tyrp1 both mediate tumor immunity in the B16 murine melanoma model. We report here that TA99 enhances Tyrp1 DNA vaccination in the treatment of B16 lung metastases, an effect mediated by immunologic mechanisms as Tyrp1 has no known role in regulating tumor growth. TA99 is shown to increase induction of anti-Tyrp1 CD8+T-cell responses to DNA vaccination against Tyrp1 as assessed by IFN-γ ELISPOT assays. Immunohistochemistry studies reveal that TA99 localizes rapidly and specifically to B16 lung nodules. Augmentation of T-cell responses is dependent on the presence of tumor as well as on activating Fc receptors. Furthermore, TA99 enhances DNA vaccination against a distinct melanoma antigen, gp100(pmel17/silver locus), improving antitumor efficacy, augmenting systemic CD8+ T-cell responses to gp100, and increasing CD8+ T-cell infiltration at the tumor site. Epitope spreading was observed, with CD8+ T-cell responses generated to Tyrp1 peptide in mice receiving gp100 DNA vaccination in the presence of TA99. Finally, we show that TA99 improves therapeutic efficacy of DNA vaccination combined with adoptive T-cell transfer in treatment of established subcutaneous B16 melanoma. In conclusion, TA99 enhances DNA vaccination against both the target antigen Tyrp1 and a distinct melanoma antigen gp100 in an Fc receptor–dependent mechanism, consistent with enhanced cross-presentation of tumor-derived antigen. Monoclonal antibodies should be tested as vaccine adjuvants in the treatment of cancer. [Cancer Res 2008;68(23):9884–91]
1101-66 Intimal hyperplasia thickness is independent of stent size in paclitaxel-coated stents: A serial intravascular ultrasound analysis from the Asian paclitaxel-eluting stent clinical trial
Authors: Esteban Escolar, Gary S Mintz, Myeong-Ki Hong, Cheol Whan Lee, Jae-Joong Kim, Neal E Fearnot, Seong-Wook Park, Seung-Jung Park, Neil J Weissman
Journal: Journal of the American College of Cardiology (2004)
Erythropoietic protoporphyria. A clinical and genetic study
Authors: W. B. Reed
Journal: JAMA (1970)

A genetic and clinical study was conducted on nine families. There were 16 clinically affected individuals and 43 carriers. A predominance of males in our study and from the literature was noted. Two families showed transmission of the trait from a carrier to an affected individual to a carrier through several generations. Carriers were detected by increased fluorescing erythrocytes because fecal and erythrocyte protoporphyrin levels are often normal. Erythrocytic protoporphyrins are probably not important for photosensitivity, though protoporphyrins from the liver may well be. The disorder should be called erythrohepatic protoporphyria in order to emphasize the complete metabolic defect. The disorder is transmitted as an autosomal dominant with many carriers and few clinically involved individuals.
Acute and Chronic Cardiovascular Effects of 6-Hydroxydopamine in Dogs
Authors: Pierre Gauthier, Réginald Nadeau, Jacques de Champlain
Journal: Circulation Research (1972)

Acute and chronic cardiovascular effects of repeated injections of 6-hydroxydopamine were studied in unanesthetized dogs. The acute response to initial injections of small doses of 6-hydroxydopamine consisted of an intense sympathomimetic effect characterized by a marked increase in blood pressure and a reflex bradycardia. Three days after the administration of a total dose of 50 mg/kg of 6-hydroxydopamine, significant decreases in heart rate, blood pressure, and total peripheral resistance were observed, but cardiac output remained unchanged. The absence of a response to intravenously injected tyramine, to electrical stimulation of the right stellate ganglion, and to bilateral carotid occlusion was consistent with a state of complete peripheral sympathectomy. Along with the functional impairment of transmission at the sympathetic nerve endings, marked endogenous norepinephrine depletion was observed in the heart, carotid sinus, and spleen. In contrast, endogenous norepinephrine was increased in the stellate ganglion. The response to electrical stimulation of the distal end of the right vagus was not altered by treatment with 6-hydroxydopamine. In anesthetized dogs treated with 6-hydroxydopamine, clamping of the hilar vessels of the adrenal glands for 10 minutes caused hypotension, but the same procedure in normal dogs did not affect blood pressure, demonstrating the importance of the compensatory role of the adrenal medulla in sympathectomized animals. It is concluded that 6-hydroxydopamine can be used effectively to obtain a generalized chemical sympathectomy in unanesthetized dogs and provides a useful means for studying the role of the autonomic nervous system in the regulation of cardiovascular functions.
Intraepithelial Carcinoma of the Cervix Uteri in Women Aged under 35 Years
Authors: S. W. Davies, R. M. Kelly
Journal: BMJ (1971)

The number of cases of intraepithelial carcinoma of the cervix among women of different age groups has been related to the number of cervical smears from women of the same age groups. Among women aged 25 to 34 years the incidence of intraepithelial carcinoma was 0·67% and among those aged 35 to 44 years it was 0·75%. The overall rate of intraepithelial carcinoma in women under 35 years was 0·55% compared with an overall rate of 0·59% in women over 35 years. If screening of women for cervical cancer is to play any part in preventive medicine it is suggested that the national campaign for the early detection of cervical cancer should be expanded to encourage practitioners to take cervical smears from younger women, particularly from those under 35 years.
Complement Lysis Activity in Autologous Plasma Is Associated with Lower Viral Loads during the Acute Phase of HIV-1 Infection
Authors: Michael Huber, Marek Fischer, Benjamin Misselwitz, Amapola Manrique, Herbert Kuster, Barbara Niederöst, Rainer Weber, Viktor von Wyl, Huldrych F Günthard, Alexandra Trkola
Journal: PLoS Medicine (2006)

Background To explore the possibility that antibody-mediated complement lysis contributes to viremia control in HIV-1 infection, we measured the activity of patient plasma in mediating complement lysis of autologous primary virus. Methods and Findings Sera from two groups of patients—25 with acute HIV-1 infection and 31 with chronic infection—were used in this study. We developed a novel real-time PCR-based assay strategy that allows reliable and sensitive quantification of virus lysis by complement. Plasma derived at the time of virus isolation induced complement lysis of the autologous virus isolate in the majority of patients. Overall lysis activity against the autologous virus and the heterologous primary virus strain JR-FL was higher at chronic disease stages than during the acute phase. Most strikingly, we found that plasma virus load levels during the acute but not the chronic infection phase correlated inversely with the autologous complement lysis activity. Antibody reactivity to the envelope (Env) proteins gp120 and gp41 were positively correlated with the lysis activity against JR-FL, indicating that anti-Env responses mediated complement lysis. Neutralization and complement lysis activity against autologous viruses were not associated, suggesting that complement lysis is predominantly caused by non-neutralizing antibodies. Conclusions Collectively our data provide evidence that antibody-mediated complement virion lysis develops rapidly and is effective early in the course of infection; thus it should be considered a parameter that, in concert with other immune functions, steers viremia control in vivo.
TCT-509 Low Overall Rates of Angiographically Visible Distal Embolization in INFUSE-AMI: Possible Explanation for Lack of Efficacy of Manual Aspiration Thrombectomy
Authors: Magdi El-Omar, Sorin Brener, Akiko Maehara, Thomas Scott, Roxana Mehran, Wim Aengevaeren, Dariusz Dudek, Martin Fahy, C. Michael Gibson, Gregg Stone
Journal: Journal of the American College of Cardiology (2012)
Delayed Neuropathy and Myelopathy after Organophosphate Intoxication
Authors: Chia Chang Chuang, Thy Sheng Lin, Ming Che Tsai
Journal: New England Journal of Medicine (2002)

To the Editor: Massive organophosphorus-compound intoxication is relatively common. Although uncommon, delayed neurotoxicity may also occur in humans.1 Persons with organophosphorus-compound poisoning have acute toxic effects, with a cholinergic crisis due to inhibition of acetylcholinesterase. Some persons subsequently have organophosphate-induced delayed neuropathy, which may be related to the inhibition of neurotoxic esterase.2 Organophosphate-induced delayed neuropathy results in damage to both the peripheral and the central nervous systems.3 The exact sequence of lesions in these systems remains controversial, and few reports have discussed central nervous system neuropathological changes in humans. We describe a patient who had a classic acute cholinergic crisis . . .
Effects of hormone replacement therapy in rheumatoid arthritis: a double blind placebo-controlled study.
Authors: A G MacDonald, E A Murphy, H A Capell, U Z Bankowska, S H Ralston
Journal: Annals of the Rheumatic Diseases (1994)

AIMS--To study the effects of ovarian hormone replacement therapy (HRT) on bone mineral density and disease activity in postmenopausal women with rheumatoid arthritis (RA). METHOD--A placebo controlled double-blind study was carried out on 62 patients with RA, 22 on placebo and 40 on HRT (transdermal oestradiol patches twice weekly for 48 weeks plus norithisterone tablets when clinically indicated). Bone mineral density of spine, hip and wrist was measured at 0 and 48 weeks and clinical and laboratory measures of general well-being and disease activity at 0, 12, 24 and 48 weeks. RESULTS--Thirteen of 22 (59%) of placebo and 31 of 40 (78%) of the HRT group completed 48 weeks in the study. At entry, bone mineral density (BMD) values in the lumbar spine and femoral neck were similar to those in age and sex matched controls in both treatment groups, whereas at the distal radius, BMD was significantly reduced to approximately 50% of control values (both p &lt; 0.001 from controls). In the HRT group, spine BMD increased significantly by a median of +0.94% at 48 weeks (p = 0.024), but did not change significantly in the placebo group. BMD at the femoral neck and distal radius did not change in either group. In the HRT group, there was significant improvement in well being as assessed by the Nottingham Health Care Profile (p &lt; 0.01) and in the articular index (p &lt; 0.05). There were no significant changes in ESR or CRP in either group. CONCLUSION--Transdermal HRT was well tolerated, increased well being, reduced articular index and increased lumbar spine bone density over a one year period in postmenopausal women with RA. Although no laboratory evidence was found of a disease modifying effect, the symptomatic benefits and improvements in bone density indicate that HRT may be a valuable adjunct to conventional antirheumatic therapy in RA.
Double-Balloon Enteroscopy and Capsule Endoscopy Have Comparable Diagnostic Yield in Small-Bowel Disease: A Meta-Analysis
Authors: Shabana F. Pasha, Jonathan A. Leighton, Ananya Das, M. Edwyn Harrison, G. Anton Decker, David E. Fleischer, Virender K. Sharma
Journal: Clinical Gastroenterology and Hepatology (2008)
A CASE OF DIAPHRAGMATIC HERNIA
Authors: G. J. Langley
Journal: BMJ (1922)

A schoolgirl, aged 10 years, was brought to hospital, having had a cough ancd cold for two wveeks. There were eight other children in the family, all healthiy and vell. The mother had had one mis carriage, and onie chlild h:id died at the age of 12 moniths from zvnyotic eiiteritis. The patient LbAd never been robust, but the only serious illness cecurred whenl, at 2' years of agle, she developed morbili followed by pneumonia. Thle child( had been to hospital on three or more previous occasions for trivial ailments, but in spite of this had lost very little time from Fchcol. The oiily present complaint was of cough and cold. At no time had there been anly reason to suppose tlhat 'the gastro-intestinal tract was other than normal.
The inhibition of the potassium channel TASK-1 in rat cardiac muscle by endothelin-1 is mediated by phospholipase C
Authors: Julia Schiekel, Moritz Lindner, Andrea Hetzel, Konstantin Wemhöner, Vijay Renigunta, Günter Schlichthörl, Niels Decher, Dominik Oliver, Jürgen Daut
Journal: Cardiovascular Research (2012)

The two-pore-domain potassium channel TASK-1 is robustly inhibited by the activation of receptors coupled to the Gαq subgroup of G-proteins, but the signal transduction pathway is still unclear. We have studied the mechanisms by which endothelin receptors inhibit the current carried by TASK-1 channels (ITASK) in cardiomyocytes. Patch-clamp measurements were carried out in isolated rat cardiomyocytes. ITASK was identified by extracellular acidification to pH 6.0 and by the application of the TASK-1 blockers A293 and A1899. Endothelin-1 completely inhibited ITASK with an EC50 of <10 nM; this effect was mainly mediated by endothelin-A receptors. Application of 20 nM endothelin-1 caused a significant increase in action potential duration under control conditions; this was significantly reduced after pre-incubation of the cardiomyocytes with 200 nM A1899. The inhibition of ITASK by endothelin-1 was not affected by inhibitors of protein kinase C or rho kinase, but was strongly reduced by U73122, an inhibitor of phospholipase C (PLC). The ability of endothelin-1 to activate PLC-mediated signalling pathways was examined in mammalian cells transfected with TASK-1 and the endothelin-A receptor using patch-clamp measurements and total internal reflection microscopy. U73122 prevented the inhibition of ITASK by endothelin-1 and blocked PLC-mediated signalling, as verified with a fluorescent probe for phosphatidylinositol-(4,5)-bisphosphate hydrolysis. Our results show that ITASK in rat cardiomyocytes is controlled by endothelin-1 and suggest that the inhibition of TASK-1 via endothelin receptors is mediated by the activation of PLC. The prolongation of the action potential observed with 20 nM endothelin-1 was mainly due to the inhibition of ITASK.
Bile Acid Regulation of Gene Expression: Roles of Nuclear Hormone Receptors
Authors: John Y. L. Chiang
Journal: Endocrine Reviews (2002)

Bile acids derived from cholesterol and oxysterols derived from cholesterol and bile acid synthesis pathways are signaling molecules that regulate cholesterol homeostasis in mammals. Many nuclear receptors play pivotal roles in the regulation of bile acid and cholesterol metabolism. Bile acids activate the farnesoid X receptor (FXR) to inhibit transcription of the gene for cholesterol 7alpha-hydroxylase, and stimulate excretion and transport of bile acids. Therefore, FXR is a bile acid sensor that protects liver from accumulation of toxic bile acids and xenobiotics. Oxysterols activate the liver orphan receptors (LXR) to induce cholesterol 7alpha-hydroxylase and ATP-binding cassette family of transporters and thus promote reverse cholesterol transport from the peripheral tissues to the liver for degradation to bile acids. LXR also induces the sterol response element binding protein-1c that regulates lipogenesis. Therefore, FXR and LXR play critical roles in coordinate control of bile acid, cholesterol, and triglyceride metabolism to maintain lipid homeostasis. Nuclear receptors and bile acid/oxysterol-regulated genes are potential targets for developing drug therapies for lowering serum cholesterol and triglycerides and treating cardiovascular and liver diseases.