tbuckley/cabot-search huggingface dataset:
Immunoglobulin light chain amyloidosis: 2014 update on diagnosis, prognosis, and treatment
Authors: Morie A. Gertz
Journal: American Journal of Hematology (2014)

Disease Overview: Immunoglobulin light chain amyloidosis is a clonal, nonproliferative plasma cell disorder in which fragments of immunoglobulin light chain are deposited in tissues. Clinical features depend on organs involved but can include restrictive cardiomyopathy, nephrotic syndrome, hepatic failure, peripheral/autonomic neuropathy, and atypical multiple myeloma. Diagnosis : Tissue biopsy stained with Congo red demonstrating amyloid deposits with apple‐green birefringence is required for diagnosis. Invasive organ biopsy is not required because amyloid deposits can be found in bone marrow biopsy or subcutaneous fat aspirate in 85% of patients. Verification that amyloid is composed of immunoglobulin light chains is mandatory. Prognosis : N‐terminal pro‐brain natriuretic peptide (NT‐proBNP), serum troponin T, and difference between involved and uninvolved immunoglobulin free light chain values are used to classify patients into four groups of similar size; median survivals are 94.1, 40.3, 14.0, and 5.8 months. Therapy : All patients with a systemic amyloid syndrome require therapy to prevent deposition of amyloid in other organs and prevent progressive organ failure of involved sites. Stem cell transplant (SCT) is preferred, but only 20% of patients are eligible. Requirements for safe SCT include NT‐proBNP &lt;5,000 ng/mL, troponin T &lt;0.06 ng/mL, age &lt;70 years, &lt;3 organs involved, and serum creatinine ≤1.7 mg/dL. Nontransplant candidates can be offered melphalan–dexamethasone or cyclophosphamide–bortezomib–dexamethasone. Other combinations of chemotherapy with agents such as cyclophosphamide–thalidomide (or lenalidomide)–dexamethasone, bortezomib–dexamethasone, and melphalan–prednisone–lenalidomide have documented activity. Future Challenges : Late diagnosis remains a major obstacle to initiating effective therapy. Recognizing the presenting syndromes is necessary for improving survival.Am. J. Hematol. 89:1133–1140, 2014. © 2014 Wiley Periodicals, Inc.
Epilepsy Surgery for Pharmacoresistant Temporal Lobe Epilepsy
Authors: Hyunmi Choi, Randall L. Sell, Leslie Lenert, Peter Muennig, Robert R. Goodman, Frank G. Gilliam, John B. Wong
Journal: JAMA (2008)

Patients with pharmacoresistant epilepsy have increased mortality compared with the general population, but patients with pharmacoresistant temporal lobe epilepsy who meet criteria for surgery and who become seizure-free after anterior temporal lobe resection have reduced excess mortality vs those with persistent seizures.To quantify the potential survival benefit of anterior temporal lobe resection for patients with pharmacoresistant temporal lobe epilepsy vs continued medical management.Monte Carlo simulation model that incorporates possible surgical complications and seizure status, with 10,000 runs. The model was populated with health-related quality-of-life data obtained directly from patients and data from the medical literature. Insufficient data were available to assess gamma-knife radiosurgery or vagal nerve stimulation.Life expectancy and quality-adjusted life expectancy.Compared with medical management, anterior temporal lobe resection for a 35-year-old patient with an epileptogenic zone identified in the anterior temporal lobe would increase survival by 5.0 years (95% CI, 2.1-9.2) with surgery preferred in 100% of the simulations. Anterior temporal lobe resection would increase quality-adjusted life expectancy by 7.5 quality-adjusted life-years (95%, CI, -0.8 to 17.4) with surgery preferred in 96.5% of the simulations, primarily due to increased years spent without disabling seizures, thereby reducing seizure-related excess mortality and improving quality of life. The results were robust to sensitivity analyses.The decision analysis model suggests that on average anterior temporal lobe resection should provide substantial gains in life expectancy and quality-adjusted life expectancy for surgically eligible patients with pharmacoresistant temporal lobe epilepsy compared with medical management.
CHARACTERISTICS OF RENAL BICARBONATE REABSORPTION IN MAN*
Authors: Donald W. Seldin, Richard M. Portwood, Floyd C. Rector, Robert Cade
Journal: Journal of Clinical Investigation (1959)

The reabsorption of filtered HCO3by the kid- ney is thought to result not from the active reab- sorption of HCO3ions but rather from the secre- tion of cellular H+ in exchange for tubular Na+ (1, 2).The secreted H+ reacts with filtered HCO3to form H2C03 which then decomposes to CO, and H20, thereby effecting the reabsorption of NaHCO3.The enzyme carbonic anhydrase, the inhibition of which blocks HCO3-reabsorption, is thought to maintain an adequate supply of H+ for secretion by accelerating the hydration of CO2 within the renal cells.In support of this theory is the fact that HCO:reabsorption varies linearly with plasma pCO2 (3-3).Recently Schwartz.Falbriard and Relman (6) have suggested an alternative role for carbonic anhvdrase.By a kinetic analysis of the effects of partial inhibition of carbonic anhydrase on HC03reabsorption during severe metabolic acidosis they found that at a given dose of Diamox®& the recipro- cals of HCO3reabsorption and of plasma HCO3- concentration were linearly related.As carbonic anhydrase was progressively inhibited with in- creasing doses of Diamox®9 a family of lines typi- cal of stubstrate-enzyme-inhibitor kinetics was obtained.From these relationships it was suggested that HC03was reabsorbed by some mechanism in which cellular carbonic anhydrase was the en- zyme and filtered HC03-(or some intermediate derived from it) was the substrate for the enzyme.
PI(3)K/PTEN/AKT pathway
Authors: Anne-Christine Piguet, Jean-François Dufour
Journal: Journal of Hepatology (2010)

Cancer and metabolic disorders are associated with an aberrant activity of the PI(3)K/PTEN/AKT pathway. In liver tumours, this pathway is activated by loss of function of PTEN [1] or gains of function of receptor tyrosine kinases and PI(3)K [2].
The Chief Complaint-Reply
Authors: Joseph Hardison
Journal: JAMA (1981)

<h3>In Reply.—</h3> I agree that patients are admitted to hospitals for predetermined reasons and particular problems. My concern is that a reason for admission is sought rather than a complaint. It is not necessary that all complaints be followed by voluminous histories, physicals, and laboratory tests. I do believe that the better a physician knows his patient, the better the care he can provide.
Administration of a Decoy Against the Activator Protein-1 Binding Site Suppresses Neointimal Thickening in Rabbit Balloon-Injured Arteries
Authors: Masazumi Kume, Kimihiro Komori, Takuya Matsumoto, Toshihiro Onohara, Kensuke Takeuchi, Yoshikazu Yonemitsu, Keizo Sugimachi
Journal: Circulation (2002)

Transcription factor activator protein-1 (AP-1) is activated and upregulated in injured arterial smooth muscle cells in vivo, yet the exact role of the AP-1--related pathway in vascular disease in vivo has remained unclear. We examined the role of the transfer of synthetic double-stranded cis-element decoy oligodeoxynucleotides (ODNs) in balloon-injured rabbit carotid arteries and the effects of these ODNs on neointimal thickening.Transfection of fluorescein isothiocyanate--labeled ODNs using the hemagglutinating virus of Japan liposome method resulted in widespread distribution of fluorescent nuclear signals over the entire medial layer in injured arteries. Gel mobility shift assay revealed that AP-1 DNA binding was activated and that the AP-1 decoy reduced AP-1 DNA binding activity as a result of specific binding affinity to AP-1 in vivo. In morphometric analyses, AP-1 decoy led to a significant reduction in the neointimal area and a significant reduction in cell number and transforming growth factor-beta(1) production of human aortic smooth muscle cells under conditions of platelet-derived growth factor stimulation.Because AP-1 decoy transfection in vivo dramatically prevented neointimal thickening in balloon-injured arteries, AP-1 may be a useful molecular target for gene therapy to reduce restenosis.
Preliminary progression free survival and SPARC tumor correlatives from a phase II neoadjuvant trial of gemcitabine, epirubicin, and nab paclitaxel.
Authors: DA Yardley, R Inhorn, B Daniel, D Daniel, Y Naot, J Zubkus, S Hanson, V Trieu, D Knauer, N Desai, HA Burris
Journal: Cancer Research (2009)

Abstract Abstract #5116 Background: Neoadjuvant combinations of gemcitabine (G), anthracyclines and taxanes have demonstrated significant activity with pCR rates of 20-25% albeit with significant myelosuppression. Secreted protein acidic rich in cysteine (SPARC) is an albumin binding protein that mediates intratumoral accumulation of nab-paclitaxel (nab-P) via a SPARC-albumin specific binding activity. This study was designed to evaluate a biweekly schedule of neoadjuvant nab paclitaxel (nab-P) with gemcitabine and epirubicin (E). SPARC tumor assessments were performed in consenting patients (pts) with subsequent pathologic and survival correlatives.&amp;#x2028; Methods: Eligibility: Clinical T1c-T4d and/or N0-3, M0 breast cancer (T1N0M0 excluded), ECOG PS 0-2, normal LVEF. ER/PR/HER2 obtained for all pts. Treatment: 6 cycles neoadjuvant G 2000 mg/m2, E 50 mg/m2, and nab-P 175 mg/m2 q14 days followed by surgery. Post operative therapy: 4 cycles G 2000 mg/m2 and nab-P 220 mg/m2 q14 days. Myeloid growth factors were mandated with all cycles. 2 antibody reagents were used to probe for SPARC expressions. For this study, level 3 immunohistochemical (IHC) SPARC staining was considered positive. Results: 123 pts have enrolled with pathologic responses available for 106. 82 pts consented to SPARC testing. Median age 51 (29-72). Median tumor size 4.5 cm. Histology: 81% ductal, 10% lobular, 9% other. 42% ER and PR negative. 55% clinical T3/T4 and 66% lymph node positive at presentation. G3/4 toxicity present in &amp;gt;5% of pts: neutropenia 16% (febrile neutropenia 1 pt), thrombocytopenia 9% with arthralgias 11%, fatigue 10%, and infection 7%. 20 pts did not complete study treatment for the following reasons: disease progression 7, toxicity 3, pt/MD request 5, and other 5. pCR was noted in 23 pts (22%) with PRs in 76 pts (71%), and 6 SD. SPARC IHC staining was available for 76 tumors. SPARC level 3 IHC staining was noted in 65 tumors (86%); 65% were associated with a PR or pCR. Median PFS was 23 months and overall survival at 24 months is 77%. Pts who relapsed ≤16 months from diagnosis were more likely to be triple negative (p = 0.04), or ER negative (p = 0.001), or PR negative (p = 0.0006). Conclusions: Neoadjuvant dose dense GEA is active and better tolerated than other gemcitabine/anthracycline/taxane combinations. The pCR rate of 22% compares favorably with other comparable neoadjuvant regimens albeit with minimal toxicity. Pts with early relapse defined as ≤16 months from diagnosis were more likely to demonstrate a triple negative phenotype or demonstrate estrogen or progesterone receptor negativity. SPARC tumor correlatives with progression free and overall survival are on ongoing and will be presented. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 5116.
Regulation of gastric acid secretion by neurotensin in man. Evidence against a hormonal role.
Authors: M H Mogard, V Maxwell, B Sytnik, J H Walsh
Journal: Journal of Clinical Investigation (1987)

The present study was designed to evaluate neurotensin as a hormonal regulator of gastric acid secretion in man. After a fat-rich meal, the strongest known stimulus of neurotensin release, plasma neurotensin-like immunoreactivity (NTLI) was elevated from 7.6 +/- 1.9 to 15.5 +/- 2.5 pM. Plasma NTLI was measured with antiserum L170, which requires the biologically active carboxyl-terminal hexapeptide of the neurotensin molecule for recognition and does not crossreact significantly with any known natural catabolite in human plasma. Intravenous infusion of neurotensin at 25 pmol X kg-1 h-1 resulted in a plasma level of 14.7 +/- 2.1 pM, similar to the maximal physiological level observed after the fat-rich meal. Intravenous infusion of neurotensin at 25 pmol X kg-1 h-1 during 2 h, however, failed to significantly inhibit peptone meal-stimulated gastric acid secretion measured by intragastric titration. The 2-h acid output to peptone was 40.8 +/- 6.2 and 41.3 +/- 6.9 mmol during the vehicle and the neurotensin infusion, respectively. Intravenous infusion of neurotensin at 100 or 400 pmol X kg-1 h-1 did not affect acid output, whereas at 1,600 pmol X kg-1 h-1, which resulted in a plasma neurotensin concentration of 725 +/- 80 pM, significantly reduced peptone meal-stimulated gastric acid secretion. The neurotensin-induced inhibition of acid output was independent of the hormone gastrin. The present results provide evidence against a hormonal role for neurotensin in the regulation of meal-stimulated gastric acid secretion in man.
Acute Hemorrhage from Peptic Ulcer
Authors: Austin B. Chinn, Arthur S. Littell, George F. Badger, Argyle J. Beams
Journal: New England Journal of Medicine (1956)

ACUTE hemorrhage is an important and dramatic complication of peptic ulcer. Although there is an extensive bibliography concerning individual bleeding episodes, only a few studies have been reported on the part played by acute hemorrhage in the natural history of the disease.1 2 3 4 5 Those which have been made have been follow-back or historical in character and with nonuniform methods of study. The value of these studies as an aid in prognosticating the future of such patients is questionable.Because of this scarcity of information, it was decided to follow a group of patients who were known to have had at . . .
Differentiation of glucose toxicity from beta cell exhaustion during the evolution of defective insulin gene expression in the pancreatic islet cell line, HIT-T15.
Authors: A Moran, H J Zhang, L K Olson, J S Harmon, V Poitout, R P Robertson
Journal: Journal of Clinical Investigation (1997)

Chronic exposure of HIT-T15 cells to supraphysiologic glucose concentration diminishes insulin gene expression and decreased binding of two critical insulin gene transcription factors, STF-1 and RIPE-3b1 activator. To distinguish whether these changes are caused by glucose toxicity or beta cell exhaustion, HIT-T15 cells grown from passage 75 through 99 in media containing 11.1 mM glucose were switched to 0.8 mM glucose at passage 100. They regained binding of STF-1 and RIPE-3b1 activator and had a partial but minimal return of insulin mRNA expression. In a second study, inclusion of somatostatin in the media-containing 11.1 mM glucose inhibited insulin secretion; however, despite this protection against beta cell exhaustion, dramatic decreases in insulin gene expression, STF-1 and RIPE-3b1 binding, and insulin gene promoter activity still occurred. These data indicate that the glucotoxic effects caused by chronic exposure to supraphysiologic concentration of glucose are only minimally reversible and that they are not due simply to beta cell exhaustion. These observations carry with them the clinical implication that Type II diabetic patients who remain hyperglycemic for prolonged periods may have secondary glucose toxic effects on the beta cell that could lead to defective insulin gene expression and worsening of hyperglycemia.
Percutaneous Transhepatic Cholangiography
Authors: M. Atkinson, M. G. Happey, F. G. Smiddy
Journal: Gut (1960)

This is an evaluation of percutaneous transhepatic cholangiography, a technique of over eight years' standing, previously considered by many authorities as both unrewarding and dangerous. The value and risks of the procedure have been examined in 20 patients with obstructive jaundice of uncertain origin and in one further patient with a post-cholecystectomy syndrome. The presence and the nature of extrahepatic obstructive lesions was correctly diagnosed in 10 of 11 patients shown to have this cause for jaundice. The failure to obtain cholangiograms in the remaining 10 patients was correctly correlated with the presence of intrahepatic obstructive disease due to hepatitis or primary biliary cirrhosis. The risks of percutaneous cholangiography seem over-rated, biliary peritonitis occurring in under 5% of patients submitted to the procedure.
The vascularity of internal fistulae in Crohn's disease: an in vivo power Doppler ultrasonography assessment
Authors: G Maconi
Journal: Gut (2002)

Aim: To evaluate the efficacy of power Doppler sonography (US) in depicting internal fistulae and their vascularity, and to study the characteristics of blood flow within the fistula wall. Patients and methods: The study involved 45 consecutive patients with Crohn9s disease and suspected internal fistulae detected by grey scale US. The fistulae were subsequently evaluated using power Doppler US to reveal any areas of increased vascularity, and the results were compared with radiographic, endoscopic, or intraoperative findings. Whenever feasible, we also performed spectral analysis of blood flow revealed by power Doppler US, calculated its resistance index (RI), and analysed its characteristics, reproducibility, and relationship with biochemical and clinical variables (Crohn9s disease activity index, disease duration, location, and abdominal complications). Results: Power Doppler US revealed vascularity in all of the internal fistulae that where subsequently confirmed by diagnostic procedures. In the case of intra-abdominal abscesses in the vicinity of the fistula, vascular signals were detected mostly around and not within the lesions. The intensity and distribution of the signals differed within the fistulae tracks and had only slight day to day reproducibility; furthermore, there was no significant correlation with clinical or biochemical variables. Spectral analyses of blood flow within the fistulae revealed arterial flow in 96.7% of patients (median RI 0.715). RI was a more reproducible parameter and significantly correlated with clinical (<i>r</i>= 0.54) and biochemical activity (<i>r</i>= 0.56) of CD. It was also higher in fistulae complicated by abscesses. Conclusion: Power Doppler US can reveal the presence of vasculature within the wall of internal fistulae and therefore enhance grey scale US performance. The RI characteristics of blood flow within the fistulae are reproducible and correlate with biochemical and clinical disease activity.
A Prospective Study Identifying Risk Factors for Discontinuance of Insulin Pump Therapy
Authors: John C Floyd, Richard G Cornell, Scott J Jacober, Lauren E Griffith, Martha M Funnell, Leora L Wolf, Fredric M Wolf
Journal: Diabetes Care (1993)

OBJECTIVE To identify characteristics of adult patients at baseline associated with duration of subsequent, continuous, subcutaneous infusion of insulin treatment (pump therapy) of type I diabetes. RESEARCH DESIGN AND METHODS For 6 wk, patients followed a standardized conventional therapy and kept a record of insulin dosages, capillary blood glucose concentrations, and symptomatic hypoglycemia. They were then hospitalized. Additional baseline data were obtained and pump therapy was started. Survival analysis was used to determine the relationship between baseline independent variables or risk factors and duration of pump therapy, which is the dependent variable. RESULTS Of the 68 participants, 33 (49%) terminated pump therapy after an average of 9.9 mo of treatment. Two models (each P &amp;lt; 0.00005) were developed that exhibited a high degree of consistency. Of the 6 variables, 5 were common to both models (HbA1 autonomic neuropathy, mean amplitude of glycemic excursions, frequency of symptoms of hypoglycemia when blood glucose was &amp;lt; 70 mg/dl, and erythema at injection sites). The sixth variable in model 1 (insulin dosage) was replaced in model 2 by a variable, Adult Self-Efficacy for Diabetes, which was obtained on the 33 more recently enrolled patients; this variable related to patient perceptions of self-care behaviors. CONCLUSIONS We found that, at baseline, the presence of a high concentration of HbAx and a low estimation by the patient of their ability to treat the disease portend failure of insulin pump therapy as evidenced by its discontinuation. This effect is accentuated when clinical evidence of autonomic neuropathy is observed. These findings offer guidance in selecting patients with type I diabetes for insulin pump therapy.
Foreign Medical Graduates and Physician Assistants
Authors: James F. Cawley
Journal: JAMA (1982)

<h3>To the Editor.—</h3> Louis J. Goodman, PhD, and Lorna E. Wunderman, MPH, report a decline in the flow of foreign medical graduates (FMGs) into US graduate medical education programs (1981;246:854). The authors attribute this decline to certain provisions of the 1976 Health Professions Educational Assistance Act (PL 94-484) and point out that, despite offsetting increases in US medical graduates and US citizen FMGs, residency positions in certain urban hospitals will go unfilled. They recommend waiver of sections of PL 94-484 as a means of providing these facilities with a continuing supply of health manpower in the form of FMGs. This analysis fails to take into consideration that many of these hospitals have already discovered an alternative solution to resident shortages brought about by FMG restrictions. Physician assistants (PAs) are commonly replacing FMG house staff in many institutions. Over the past several years a number of hospitals that were previously dependent
211 INDOCYANINE GREEN CLEARANCE (ICG) AS A PREDICTOR OF 2-YEARS CLINICAL DECOMPENSATION AND MORTALITY IN PATIENTS WITH COMPENSATED LIVER CIRRHOSIS
Authors: A. Lisotti, F. Azzaroli, F. Buonfiglioli, P. Cecinato, M. Montagnani, R. Arena, C. Calvanese, P. Simoni, S. Belvisi, A. Porro, A. Cucchetti, A. Colecchia, D. Festi, R. Golfieri, G. Mazzella
Journal: Journal of Hepatology (2013)