tbuckley/cabot-search huggingface dataset:
Stiffness and Impaired Blood Flow in Lower-Leg Arteries Are Associated With Severity of Coronary Artery Calcification Among Asymptomatic Type 2 Diabetic Patients
Authors: Masanobu Tsuchiya, Eiji Suzuki, Katsuya Egawa, Yoshihiko Nishio, Hiroshi Maegawa, Shinji Inoue, Kenichi Mitsunami, Shigehiro Morikawa, Toshiro Inubushi, Atsunori Kashiwagi
Journal: Diabetes Care (2004)

OBJECTIVE—To clarify whether stiffness and impaired blood flow in lower-leg arteries are associated with severity of coronary artery calcification among asymptomatic diabetic patients. RESEARCH DESIGN AND METHODS—We enrolled 102 asymptomatic type 2 diabetic patients with no history of cardiovascular complications consecutively admitted to our hospital. Agatston coronary artery calcium (CAC) score, as a marker of coronary artery calcification, was obtained using electron-beam computed tomography. Total flow volume and resistive index, as an index of vascular resistance, at the popliteal artery were evaluated using gated two-dimensional cine-mode phase-contrast magnetic resonance imaging. Brachial-ankle pulse-wave velocity (PWV), as an index of distensibility in the lower-extremity arteries, was also measured using an automatic device. RESULTS—When the patients were grouped according to CAC scores of 0–10 (n = 54), 11–100 (n = 25), and &amp;gt;100 (n = 23), those with the highest scores, which is considered to show possible coronary artery disease, showed the highest brachial-ankle PWV (P &amp;lt; 0.001) and resistive index (P &amp;lt; 0.001) and the lowest total flow volume (P &amp;lt; 0.001) among the groups. Simple linear regression analyses showed that both brachial-ankle PWV (r = 0.508, P &amp;lt; 0.001) and resistive index (r = 0.500, P &amp;lt; 0.001) were positively correlated and total flow volume (r = −0.528, P &amp;lt; 0.001) was negatively correlated with the log-transformed CAC score. Receiver operator characteristic curve analyses indicated that 1,800 cm/s for brachial-ankle PWV, 1.03 for resistive index, and 70 ml/min for total flow volume were diagnostic values for identifying patients with the highest scores. CONCLUSIONS—Quantitatively assessed stiffness and impaired blood flow in lower-leg arteries may help identify diabetic patients with possible coronary artery disease.
Cardiac secretion of adrenomedullin in human heart failure.
Authors: M Jougasaki, R J Rodeheffer, M M Redfield, K Yamamoto, C M Wei, L J McKinley, J C Burnett
Journal: Journal of Clinical Investigation (1996)

Adrenomedullin (ADM) is a newly discovered endogenous vasorelaxing and natriuretic peptide. Recently, we have reported that plasma ADM is increased in severe congestive heart failure (CHF) in humans and that increased immunohistochemical staining is observed in the failing human ventricular myocardium. The present study was designed to test the hypothesis that the failing human ventricle secretes ADM and that circulating ADM progressively increases with the severity of clinical CHF. Plasma ADM was significantly increased in human CHF (39.8 +/- 3.6 pg/ml, P < 0.001 vs. normal) as compared with normal subjects (14.4 +/- 2.7 pg/ml). Plasma ADM was increased in mild CHF (NYHA class II, 30.1 +/- 3.4 pg/ml, P < 0.01 vs. normal), moderate CHF (NYHA class III, 31.5 +/- 3.0 pg/ml, P < 0.01 vs. normal), and severe CHF (NYHA class IV, 66.1 +/- 9.4 pg/ml, P < 0.001 vs. normal). In 13 patients with CHF in whom plasma samples were obtained from aorta (AO), coronary sinus (CS) and anterior interventricular vein (AIV), there was a significant step-up in plasma ADM between AO and AIV (50.6 +/- 9.3 pg/ml and 62.1 +/- 11.1 pg/ml, respectively, P < 0.01) and between AO and CS (50.6 +/- 9.3 pg/ml and 58.6 +/- 11.4 pg/ml, respectively, P < 0.05). The current study demonstrates that the failing human heart secretes ADM in human CHF suggesting contribution to the increase in plasma ADM, and indicates for the first time an additional endocrine system of cardiac origin which is activated in human CHF and may function in cardiorenal regulation.
Lymphoblastoid interferon in controlled trials of chronic hepatitis B virus infection
Authors: Stephanos J. Hadziyannis
Journal: Hepatology (1988)

A controlled trial of lymphoblastoid interferon versus no therapy in patients positive for HBsAg, HBeAg and DNA polymerase activity with separate randomisation for sexual preference and histology is underway. Thirty-two patients have been followed for a minimum period of 6 months of whom 15 have been randomised to receive interferon thrice weekly for 6 months after a 5-day induction phase. Five treated patients developed an hepatitis-like illness during the 3rd month of therapy concurrent with an abrupt and complete loss of DNA polymerase activity from serum. In 3 this was permanent and anti-HBe subsequently developed; 2 of these have also lost HBsAg. In the other 2 patients inhibition of viral replication was transient. In 5 further treated patients DNA polymerase activity was completely inhibited throughout treatment only to return as soon as interferon was withdrawn. In this group serum aminotransferase became normal during treatment. In the remaining 5 treated patients, inhibition of DNA polymerase activity was never complete and serum amino-transferases were unaffected. All the control patients remain seropositive for HBsAg, HBeAg and DNA polymerase activity. The low seroconversion rate in treated patients and the absence of seroconversion in the control group are probably a reflection of the exclusion of patients with marked elevation of serum aminotransferases. The occurrence of an hepatitis-like illness in the 3rd month of therapy in a third of the patients and the loss of HBsAg in 2 of 3 who eventually sero-converted are likely to be a consequence of therapy rather than spontaneous events. If these data prove representative of the completed trial, the results will indicate a small but real benefit from interferon therapy in patients with stable disease. Thirty male patients (27 homosexual) with biopsy proven chronic active hepatitis B were randomised to receive lymphoblastoid interferon (Wellferon) or no treatment. All patients were HBeAg positive and had continuing viral replication. Patients receiving treatment were given a single daily intramuscular injection of interferon for 28 days at a starting dose of 2.5 MU/m 2 increasing to a maximum of 7.5 MU/m 2 /day. Transient side effects of malaise and influenza like symptoms occurred in all patients and resolved rapidly after treatment. Hepatitis B viral replication was suppressed during interferon treatment in all patients but the effect was limited to the period of therapy. After one year there was not appreciable difference in viral markers between the two groups of patients and this treatment schedule appears less effective than the thrice weekly, three month regimes recently reported from other centres.
Diet and Heartburn
Authors: Bart Chernow
Journal: JAMA (1979)

SYMPTOMATIC gastroesophageal reflux (heartburn) is a ubiquitous postprandial complaint. Although usually a recurring complaint, it can be transient (as in the third trimester of pregnancy) or persistent and progressive (as in progressive systemic sclerosis). Regardless of frequency, gastroesophageal reflux produces annoying symptoms for which medical attention is sought. A characteristic feature of heartburn is its relation to food ingestion. Thus, medical advice concerning antireflux dietary adjustments is appropriate. Although no specific smooth muscle sphincter is demonstrable anatomically at the esophagogastric junction, a physiological high-pressure zone exists in this region to prevent regurgitation of acid-peptic stomach contents into the esophagus. In the normal human esophagus, this lower esophageal sphincter (LES) exerts a squeezing pressure of approximately 15 to 20 mm Hg greater than that within the stomach. Failure to maintain this normal pressure barrier results in sphincter incompetence and creates the potential for gastroesophageal reflux.<sup>1</sup> <h3>Effects of Foods on the</h3>
Acromegaly After Pituitary Apoplexy-Reply
Authors: Renato Candrina
Journal: JAMA (1987)

<h3>In Reply.—</h3> We thank Dr Sadun for his favorable comments on our recent article about a case of acromegaly developing after an episode of pituitary apoplexy and strongly agree with him on the necessity of having a transnasal decompression of sellar content performed as soon as there is evidence of this ominous complication. However, this position is probably biased by the clinical experience gained in our centers, which serve as third-level referral facilities and thus care for the most severely ill patients. In fact, the spectrum of clinical presentation of pituitary apoplexy ranges from lifethreatening events to mild or even asymptomatic illnesses.<sup>1,2</sup>This clinical heterogeneity probably depends on prior extrasellar extension of the tumor.<sup>2</sup>As the existence of this complication becomes more widely known, more and more cases of minor apoplectic attacks are diagnosed before operation and successfully managed conservatively with careful evaluation of hormonal and metabolic status
Deficiency of 3-methylglutaconyl-coenzyme A hydratase in two siblings with 3-methylglutaconic aciduria.
Authors: K Narisawa, K M Gibson, L Sweetman, W L Nyhan, M Duran, S K Wadman
Journal: Journal of Clinical Investigation (1986)

We studied two patients with 3-methylglutaconic aciduria in order to determine the molecular defect. A new assay for 3-methylglutaconyl-coenzyme A (CoA) hydratase has been developed in which the substrate, [5-14C]3-methylglutaconyl-CoA, was synthesized using 3-methylcrotonyl-CoA carboxylase purified from bovine kidney. In this assay the products of the reaction are isolated by reverse-phase high performance liquid chromatography and the rates of conversion from substrate are measured. The Michaelis constant for 3-methylglutaconyl-CoA in normal fibroblasts was 6.9 mumol/liter. The mean activity of 3-methylglutaconyl-CoA hydratase in control fibroblasts was 495 pmol/min per mg protein. In the two patients the values were 11 and 17 pmol/min per mg protein, or 2-3% of normal.
Imaging investigation of postmenopausal bleeding
Authors: A. Sahdev
Journal: BMJ (2009)

A 72 year old woman presented with a two month history of postmenopausal vaginal bleeding. Relevant medical history included insulin dependent diabetes, hypertension, and recent breast cancer. She had been taking tamoxifen for three years.⇓





### Short answers



Fig 1 Transvaginal ultrasound shows endometrial thickening measuring 1 cm.



### Long answer

#### 1 Investigations

Postmenopausal bleeding represents 5% of all gynaecology outpatient attendances.1 Transvaginal ultrasound is a …
Mast cell–derived angiopoietin-1 plays a critical role in the growth of plasma cell tumors
Authors: Takayuki Nakayama, Lei Yao, Giovanna Tosato
Journal: Journal of Clinical Investigation (2004)

Multiple myeloma in humans is frequently associated with mast cell infiltration and neovascularization, which correlate directly with disease severity, but the mechanisms underlying this relationship remain unclear. Here, we report that primary murine mast cells express angiopoietin-1 (Ang-1) and low levels of VEGF-A but not Ang-2 and that 2 established murine plasmacytoma cell lines express high levels of VEGF-A but little or no Ang-1 or Ang-2. An in vivo angiogenesis assay using extracellular matrix components shows that mast cells and plasmacytoma cells, together, promote marked neovascularization composed of dilated vessels, which is prevented by neutralization of VEGF-A and Ang-1 but is only partially reduced by neutralization of either VEGF-A or Ang-1. Mast cells within extracellular matrix components express Ang-1, and recombinant Ang-1 together with plasmacytoma cells promotes extracellular matrix neovascularization similar to that induced by mast cells. A transplantation assay shows that primary mast cells accelerate tumor growth by established plasmacytoma cell lines and that neutralization of Ang-1 alone or with VEGF-A reduces significantly the growth of plasmacytomas containing mast cells. These results demonstrate that mast cell–derived Ang-1 promotes the growth of plasmacytomas by stimulating neovascularization and provide further evidence supporting a causal relationship between inflammation and tumor growth.
BACTERIOLOGICAL STUDIES ON AN EPIZOOTIC OF INTESTINAL DISEASE IN SUCKLING AND NEWLY WEANED MICE
Authors: Jerome T. Syverton, Peter K. Olitsky
Journal: The Journal of Experimental Medicine (1934)

It is now quite generally conceded that the presence in animals of bacteria of Salmonella type is indicative of an active, or potentially active, pathogenic agent (26). In the present instance bacteriological studies of the organs of acutely ill infant mice revealed the presence of one of the Salmonella group. It showed itself to be such by an absence of fermentation of lactose and saccharose, by other cultural reactions, and by cross-agglutination with certain members of the Salmonella group in very low dilutions of their antisera.(6) However, the bacterium cannot be included in any of the known species of the group because of its indol-forming properties, differences in carbohydrate reactions, and specific serological reactions. Its presence in affected mice, growth on artificial media, ability to cause the disease following enteral and parenteral inoculations, and the fact that it can be recovered from artificially infected mice fulfill the postulates of Koch. Furthermore, agglutinins are present in the blood of recovered mice and not in that of normal animals, and recovery of mice from natural infection evokes an apparent resistance against the special recovered Salmonella bacterium. The organism would appear to fall in the Asiaticusdivision of the genus, as designated by Castellani and Chalmers (27).
Concerted action of sulfiredoxin and peroxiredoxin I protects against alcohol-induced oxidative injury in mouse liver
Authors: Soo Han Bae, Su Haeng Sung, Eun Jung Cho, Se Kyoung Lee, Hye Eun Lee, Hyun Ae Woo, Dae-Yeul Yu, In Sup Kil, Sue Goo Rhee
Journal: Hepatology (2010)

Abstract Peroxiredoxins (Prxs) are peroxidases that catalyze the reduction of reactive oxygen species (ROS). The active site cysteine residue of members of the 2-Cys Prx subgroup (Prx I to IV) of Prxs is hyperoxidized to cysteine sulfinic acid (Cys-SO2) during catalysis with concomitant loss of peroxidase activity. Reactivation of the hyperoxidized Prx is catalyzed by sulfiredoxin (Srx). Ethanol consumption induces the accumulation of cytochrome P450 2E1 (CYP2E1), a major contributor to ethanol-induced ROS production in the liver. We now show that chronic ethanol feeding markedly increased the expression of Srx in the liver of mice in a largely Nrf2-dependent manner. Among Prx I to IV, only Prx I was found to be hyperoxidized in the liver of ethanol-fed wildtype mice, and the level of Prx I-SO2 increased to ≈30% to 50% of total Prx I in the liver of ethanol-fed Srx−/− mice. This result suggests that Prx I is the most active 2-Cys Prx in elimination of ROS from the liver of ethanol-fed mice and that, despite the up-regulation of Srx expression by ethanol, the capacity of Srx is not sufficient to counteract the hyperoxidation of Prx I that occurs during ROS reduction. A protease protection assay revealed that a large fraction of Prx I is located together with CYP2E1 at the cytosolic side of the endoplasmic reticulum membrane. The selective role of Prx I in ROS removal is thus likely attributable to the proximity of Prx I and CYP2E1. Conclusion: The pivotal functions of Srx and Prx I in protection of the liver in ethanol-fed mice was evident from the severe oxidative damage observed in mice lacking either Srx or Prx I. (Hepatology 2011)
Inhaled IFN- for persistent nontuberculous mycobacterial pulmonary disease due to functional IFN- deficiency
Authors: T.S. Hallstrand, H.D. Ochs, Q. Zhu, W.C. Liles
Journal: European Respiratory Journal (2004)

Pulmonary infection with nontuberculous mycobacteria (NTM) in previously healthy human immunodeficiency virus-seronegative individuals is difficult to treat. Recently, functional interferon (IFN)-γ deficiency has been identified in individuals susceptible to this disease. Treatment with inhaled IFN-γ for NTM pulmonary disease associated with functional IFN-γ deficiency has not been previously described. In this study, the IFN-γ pathway was characterised in an individual who had progressive NTM pulmonary infection, despite appropriate multidrug antibiotic therapy, and 10 healthy controls. Levels of IFN-γ and tumour necrosis factor-α in whole blood were assessed before and after incubation with lipopolysaccharide, heat-killed Escherichia coli , heat-killed Staphylococcus aureus and phorbol myristate acetate/ionomycin. The coding regions of interleukin (IL)-12, IL-18 and the IL-12 receptor were sequenced using nested primers. IFN-γ1b (100 µg·dose −1 ) was administered to the affected individual by ultrasonic nebuliser 3 days·week −1 for 3 months. In vitro whole blood production of IFN-γ with and without physiological stimuli was consistent with functional IFN-γ deficiency in the affected individual. There was no evidence of mutation in the coding regions of IL-12p35, IL-12p40, IL-12Rβ1 and IL-18 in the affected individual. Treatment with inhaled IFN-γ resulted in rapid and sustained clearance of the organism from the airways and stabilisation of lung function. In conclusion, inhaled interferon-γ can be effective for the treatment of nontuberculous mycobacteria pulmonary disease associated with functional interferon-γ deficiency.
Staged Repair of Extensive Aortic Aneurysms
Authors: Hazim J. Safi, Charles C. Miller, Anthony L. Estrera, Tam T.T. Huynh, Forrest S. Rubenstein, Mahesh H. Subramaniam, L. Maximilian Buja
Journal: Circulation (2001)

Background — Extensive aortic aneurysms (ascending aorta, aortic arch, and descending or thoracoabdominal aorta) require innovative surgical techniques. Some surgeons advocate a single procedure with long periods of profound hypothermia, whereas others use a staged approach. We adopted a two-staged procedure (elephant trunk technique) in 1991 for elective repair of extensive aortic aneurysms. Methods and Results — Between February 1991 and May 2000, we performed a total of 1146 aortic aneurysm operations. Of these, 182 (15.9%) operations were first- or second-stage elephant trunk procedures, performed in a total of 117 patients. Stage 1 was completed in all 117 patients. Stage 2 was completed in 65 (55.6%) of 117 patients. Thirty-day mortality rate for the first stage was 5.1% (6 of 117). Mortality rate during the interval between operations was 3.6% (4 of 111), of which 75% (3of 4) were the result of aneurysm rupture. Thirty-day mortality rate for the second stage was 6.2% (4 of 65). A total of 43 patients did not return for second-stage repair. Among these patients, within an average period of 3.4 years (range, 1.5 months to 4.9 years), 13 of 43 (30.2%) died, 4 of 13 (30.8%) as the result of rupture. Two of 117 (1.7%) first-stage patients had postoperative stroke. No spinal cord dysfunction occurred in second-stage patients. Conclusions — Extensive aortic aneurysms can be repaired with acceptable morbidity and mortality rates through the use of the elephant trunk technique. Death was most commonly the result of rupture, both in interval patients awaiting scheduled second-stage repair and in patients who did not return. After the first stage, prompt treatment of the remaining segment is crucial to the success of staged repair.
Neuroendocrine tumor of the extrahepatic bile duct: a tumor in an unusual site visualized by cholangioscopy
Authors: L. De Luca, S. Tommasoni, A. de Leone, M. Bianchi, M. de Nictolis, D. Baroncini
Journal: Endoscopy (2013)

A 78-year-old man who had previously undergone a cholecystectomy was admitted with symptoms of obstructive jaundice and cholangitis. The endoscopic ultrasound (EUS) showed a hypoechoic mass in the distal common bile duct (CBD) with no signs of vascular invasion or metastatic nodes ([Fig. 1]). The patient underwent endoscopic retrograde cholangiopancreatography (ERCP), which revealed a filling defect of approximately 1.5 cm ([Fig. 2]) with severe obstruction at the mid CBD and upstream biliary dilatation. Cholangioscopy with SpyGlass (Boston Scientific, Natick, Massachusetts, USA) showed a superficially ulcerated exophytic mass arising from the bile duct mucosa with a CBD stricture ([Fig. 3]; [Video 1]). Endoluminal biopsies performed with SpyBite (Boston Scientific) showed inflammatory changes of the epithelium with necrotic material. A stent was inserted through the stricture. He underwent pancreaticoduodenectomy.
Degree of diversity of hepatitis C virus quasispecies and progression of liver disease
Authors: Masao Honda, Shuichi Kaneko, Akito Sakai, Masashi Unoura, Seishi Murakami, Kenichi Kobayashi
Journal: Hepatology (1994)

We examined the quasispecies of the hepatitis C virus genome in 28 patients with liver disease of varying severity. Nucleotide sequences of the hepatitis C virus genome spanning the region from the core to envelope were used to calculate the nucleotide diversity: 0.58% +/- 0.88% in 5 patients with acute hepatitis, 0.85% +/- 0.62% in 5 patients with chronic persistent hepatitis, 1.79% +/- 0.92% in 11 patients with chronic active hepatitis, 3.05% +/- 1.26% in 4 patients with cirrhosis and 2.71% +/- 1.47% in 3 patients with cirrhosis complicated by hepatocellular carcinoma. Thus the intrapatient variation in nucleotides increased significantly with severity of liver disease (p < 0.01), except in those cases of cirrhosis complicated by hepatocellular carcinoma. Multivariate analysis including the histology, duration of infection, age, sex, history of blood transfusion and serum level of ALT at diagnosis as variables showed that the histological finding was the strongest independent factor of the nucleotide diversity (p = 0.003). Serial analysis of the genome in three patients demonstrated that the intra-patient variation in nucleotides increased with the progression of liver disease. The magnitude of the intrapatient variation in nucleotides deduced from the observed changes in the patients was correlated with the mean serum levels of ALT. These findings suggest that the degree of diversity of HCV quasispecies is related to the progression of liver disease.
Lower abdominal pain in women after binge drinking
Authors: M D Dooldeniya, R Khafagy, H Mashaly, A J Browning, S K Sundaram, C S Biyani
Journal: BMJ (2007)

Alcohol misuse is costing the NHS up to £3bn (€4.4bn; $5.9bn) a year—with over 28 000 hospital admissions caused by alcohol dependence or poisoning.1 This is small compared with the annual cost to employers, which is estimated at £6.4bn, but it excludes the hidden costs in terms of alcohol related crime and social problems. The resulting use of hospital facilities places a considerable financial burden on the NHS; inpatient costs alone accounting for 2-12% of total NHS expenditure on hospitals.1 In terms of pathology it is estimated that there are 22 000 premature deaths each year caused by problems related to alcohol. The heaviest burden is on accident and emergency departments. Around 40% of such admissions are alcohol related, and this increases to 70% after midnight.2

Women have now caught up with men in their alcohol consumption, with 86% of women compared with 91% of men consuming alcohol regularly.3 Health concerns that were initially raised about drinking habits in men now seem to affect women as well.