tbuckley/cabot-search huggingface dataset:
The Effect of High-Dose Saquinavir on Viral Load and CD4+ T-Cell Counts in HIV-Infected Patients
Authors: Jonathan M. Schapiro
Journal: Annals of Internal Medicine (1996)

Objective: To evaluate the efficacy and safety of high-dose therapy with the human immunodeficiency virus (HIV) protease inhibitor saquinavir and to establish the duration of the effect of this therapy. Design: Open-label study. Setting: Clinical research referral center. Patients: 40 adults with human immunodeficiency virus type 1 (HIV-1) infection and CD4+ T-cell counts of 200 to 500 cells/mm3. Intervention: Monotherapy with 3600 mg or 7200 mg of saquinavir per day, in six divided doses, for 24 weeks. Measurements: Patients were monitored for adverse events and were evaluated monthly for CD4+ T-cell count, HIV-1 viral load (as measured by reverse transcriptase polymerase chain reaction [PCR] for plasma HIV RNA levels), immune-complex-disassociated p24 antigen levels, peripheral blood mononuclear cell viral DNA levels (as measured by PCR), and resistance mutations to saquinavir. Quantitative peripheral blood mononuclear cell cultures were also done every 2 months. Results: The low-dose saquinavir regimen (3600 mg/d) resulted in a maximal mean decrease in plasma HIV RNA levels of 1.06 log RNA copies/mL of plasma and a mean maximal increase in CD4 counts of 72 cells/mm3. At week 24, the plasma HIV RNA level remained 0.48 log RNA copies/mL of plasma lower than baseline (P < 0.001) and the CD4 count remained 31 cells/mm3 higher than baseline (P = 0.165). The high-dose saquinavir regimen (7200 mg/d) produced a mean maximal decrease in the plasma HIV RNA level of 1.34 log RNA copies/mL of plasma and a mean maximal increase in CD4 count of 121 cells/mm3. At week 24, the plasma HIV RNA level remained 0.85 log RNA copies/mL of plasma lower than baseline (P < 0.001) and the CD4 count remained 82 cells/mm3 higher than baseline (P = 0.002). The high-dose regimen produced a greater reduction in plasma HIV RNA level (P = 0.08), a greater reduction in peripheral blood mononuclear cell cultures (P = 0.008), and a greater increase in CD4 count (P = 0.002) than did the low-dose regimen. Higher plasma drug concentrations in individual patients correlated with greater reductions in plasma HIV RNA levels over the two doses. Nine patients receiving the low-dose regimen and four patients receiving the high-dose regimen developed key saquinavir resistance mutations. Adverse reactions, most commonly gastrointestinal problems and elevated serum aminotransferase levels, were more common in patients receiving the high-dose regimen, but most adverse events were mild and all were reversible. Conclusion: Saquinavir is a potent antiviral agent that has a favorable toxicity profile at high doses. Higher doses produce a greater and more durable suppression of viral load and elevation in CD4+ T-cell counts and may delay the development of resistance mutations. Therapy with high-dose saquinavir alone or in combination with other antiretroviral agents should be investigated further.
Book Review Intestinal Failure: Diagnosis, Management, and Transplantation Edited by Alan N. Langnas, Olivier Goulet, Eamonn M.M. Quigley, and Kelly A. Tappenden. 390 pp., illustrated. Malden, MA, Blackwell, 2008. $149.95. 978-1-4051-4637-1
Authors: Susan Hill
Journal: New England Journal of Medicine (2008)
THE RISE AND PROGRESS OF DERMATOLOGY.
Authors: MALCOLM MORRIS
Journal: JAMA (1897)

As embryology furnishes the key to the riddles of anatomy, so the history of the evolution of any branch of science throws light on many points that would otherwise be dark, explains the origin of terms and theories, rescues from oblivion truths overlooked or forgotten, and, showing the pitfalls which hindered those who have gone before, teaches us to walk more warily. Dermatology, although its victories have perhaps been less showy than those won in some other special departments, has not lagged behind in the onward march of medicine. The centenary of the birth of scientific dermatology is not long past. In 1790 the Medical Society of London awarded the Fothergillian gold medal to Robert Willan, who had some time before submitted to it the outline of his plan for the arrangement and description of cutaneous diseases. Willan may justly be called the creator of dermatology. Before him the skin
256 BASELINE CHARACTERISTICS AND ON-TREATMENT PREDICTORS OF RESPONSES FROM REAL-WORLD PATIENT COHORTS: INTERIM RESULTS OF THE MULTINATIONAL PROPHESYS COHORTS
Authors: P. Ferenci, M.L. Shiffman, M. Puoti, A. Orlandini, F.A. Caruntu, D. Ouzan, M. Bozic, M. Bourliere, G.F. Silva, J. Schuller, J.-P. Mulkay, A. Horban, D. Messinger, A. Tietz, A. Mangia
Journal: Journal of Hepatology (2010)
Relationships between the cytotoxicity of tiazofurin and its metabolism by cultured human lung cancer cells.
Authors: D N Carney, G S Ahluwalia, H N Jayaram, D A Cooney, D G Johns
Journal: Journal of Clinical Investigation (1985)

The antitumor activity of the antineoplastic agent, tiazofurin (2-beta-D-ribofuranosylthiazole-4-carboxamide), has previously been shown to require intracellular anabolism of the drug to a nicotinamide adenine dinucleotide (NAD) analog (2-beta-D-ribofuranosylthiazole-4-carboxamide adenine dinucleotide or "tiazofurin adenine dinucleotide"), which then acts as a potent inhibitor of the target enzyme inosine monophosphate (IMP) dehydrogenase. Inhibition of the latter enzyme in turn brings about a profound depletion of intracellular guanosine nucleotides essential for tumor cell growth and replication. In the present study, the cytotoxicity and metabolism of tiazofurin have been examined in six human lung cancer cell lines. At the pharmacologically attainable drug concentration of 100 microM, colony survival was less than 1.5% in three cell lines ("sensitive"), while survival in the remaining three was greater than 50% ("resistant"). The metabolism of tritiated tiazofurin was examined at concentrations ranging from 0.5 to 100 microM following both brief (6 h) and protracted (14 d) exposures. The sensitive lines accumulated concentrations of tiazofurin adenine dinucleotide that were approximately 10 times those achieved by the resistant lines at both time points. We also observed tendencies for the sensitive cell lines to exhibit: (a) higher specific activities of NAD pyrophosphorylase, the enzyme required for the synthesis of tiazofurin adenine dinucleotide, (b) significantly lower levels of a phosphodiesterase which degrades the latter dinucleotide, (c) greater inhibition of the target enzyme IMP dehydrogenase, and (d) greater depressions of guanosine nucleotide pools after drug treatment. By contrast, the basal levels of IMP dehydrogenase and purine nucleotides in these six lines did not correlate in any obvious way with their responsiveness or resistance. The accumulation and monophosphorylation of parent drug were also not prognostic variables. These studies thus suggest that the extent of accumulation of tiazofurin adenine dinucleotide, as regulated by its synthetic and degradative enzyme activities, is the single most predictive determinant of the responsiveness of cultured human lung tumor cells to tiazofurin.
Abstract 5632: Mechanism of anemia response by lenalidomide in treating patients with primary myelofibrosis (PMF) and ET-MF is related to suppresion of T regulatory cells (Treg)
Authors: Muhammad I. Kafeel, Yiwu Sun, Chi Chen, Neal Hakimi, Chentyl Rathnasabapathy, Amrit Singh, Stephen Lichter, Jen Chin Wang
Journal: Cancer Research (2010)

Abstract Except allogenic bone marrow transplantation with either myeloablative or reduced intensity conditioning, there is no effective treatment for PMF. Age-related morbility and mortality factors limit this application. Anti-Jak2 treatment relieves splenomegaly but does not improve cytopenia. IMiDs on the other hand can improve anemia in up-to 20% of transfusion dependent anemic patients with PMF. In order to asses the underlying mechanism and to predict treatment responsiveness, in vitro suppression of Treg cells by lenalidomide correlated to clinical treatment response was performed. Seven patients with transfusion dependent and ESD (erythropoietin stimulating drugs) resistant PMF were studied. Mononuclear cells from blood in patients with PMF were cultured in the culture medium with FCS and Il-2 (100 IU/ml) in the presence of lenalidomide or DMSO for 6 days, the cells were then stained for Treg cells (CD4+, CD 25 +,and FoxP3+,) and analyzed by flow cytometry using Treg Detection Kit from Miltenyi Biotec Inc (Auburn, CA). Treg cells were enumerated as percentage of selected CD4 + cells. The results showed that in the 4 patients who responded to lenalidomide treatment, Treg cells were suppressed by the in vitro testing by lenalidomide, while in the three patients who were clinically refractory to lenalidomide treatment, their Treg cells were not suppressed by in vitro lenalidomide treatment. These results suggest that in transfusion dependent PMF, Treg cells may play a role in the pathogenesis of anemia and that effectiveness of lenalidomide treatment may be partly related to its suppression of Treg cells. Further studies to recruit more patients and to explore the role of Treg cells in modulating erythroipoiesis in PMF using the erythroid methylcellulose culture systems are currently in progress. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 5632.
Differential regulation of two types of intracellular calcium release channels during end-stage heart failure.
Authors: L O Go, M C Moschella, J Watras, K K Handa, B S Fyfe, A R Marks
Journal: Journal of Clinical Investigation (1995)

The molecular basis of human heart failure is unknown. Alterations in calcium homeostasis have been observed in failing human heart muscles. Intracellular calcium-release channels regulate the calcium flux required for muscle contraction. Two forms of intracellular calcium-release channels are expressed in the heart: the ryanodine receptor (RyR) and the inositol 1,4,5-trisphosphate receptor (IP3R). In the present study we showed that these two cardiac intracellular calcium release channels were regulated in opposite directions in failing human hearts. In the left ventricle, RyR mRNA levels were decreased by 31% (P < 0.025) whereas IP3R mRNA levels were increased by 123% (P < 0.005). In situ hybridization localized both RyR and IP3R mRNAs to human cardiac myocytes. The relative amounts of IP3 binding sites increased approximately 40% compared with ryanodine binding sites in the failing heart. RyR down-regulation could contribute to impaired contractility; IP3R up regulation may be a compensatory response providing an alternative pathway for mobilizing intracellular calcium release, possibly contributing to the increased diastolic tone associated with heart failure and the hypertrophic response of failing myocardium.
Effect of azelastine on sulphur dioxide induced impairment of ciliary motility in airway epithelium.
Authors: J Tamaoki, A Chiyotani, N Sakai, K Takeyama, K Konno
Journal: Thorax (1993)

OBJECTIVE--The effect of azelastine on airway mucociliary transport function was studied by measuring ciliary motility of human bronchial epithelium in vitro with a photoelectric method. METHOD--Bronchial epithelial cells were obtained by fibreoptic bronchoscopy, mounted in a Rose chamber, and perfused with Krebs-Henseleit solution. The preparations were placed on a microscope stage equipped with an illuminator, and the variations of light intensity caused by ciliary beating were detected by a photometer. RESULTS--The addition of azelastine to the perfusate increased ciliary beat frequency (CBF) in a dose dependent manner without ciliary discoordination. The mean (SE) maximal increase from the baseline value and the concentration required to produce a half maximal effect were 27.0 (4.2)% and 9.2 x 10(-6) mol/l, respectively. Exposure of the cells to the perfusate containing 3 ppm sulphur dioxide rapidly decreased CBF by 59.2 (5.0)%, and was accompanied by a reduction in intracellular cyclic AMP levels from 38.1 (4.3) to 10.1 (2.4) pmol/mg protein. This effect was prevented by pretreatment of cells with azelastine in a dose dependent manner. CONCLUSIONS--Azelastine not only stimulates ciliary motility of airway epithelium and hence mucociliary transport function, but may also protect against sulphur dioxide induced ciliary dysfunction, probably by inhibiting intracellular cyclic AMP loss.
Differential Association Between Biomarkers of Subclinical Inflammation and Painful Polyneuropathy: Results From the KORA F4 Study
Authors: Christian Herder, Brenda W.C. Bongaerts, Wolfgang Rathmann, Margit Heier, Bernd Kowall, Wolfgang Koenig, Barbara Thorand, Michael Roden, Christa Meisinger, Dan Ziegler
Journal: Diabetes Care (2014)

OBJECTIVE Inflammatory processes have been implicated in the pathogenesis of painful neuropathy in rodents, but the relationship between inflammatory biomarkers and painful distal sensorimotor polyneuropathy (DSPN) has not been assessed in population-based studies. Therefore, we investigated whether circulating levels of seven pro- and anti-inflammatory immune mediators were associated with painful DSPN in older individuals in a large population-based study. RESEARCH DESIGN AND METHODS The study population consisted of individuals with painless (n = 337) and painful DSPN (n = 54) from a source population (n = 1,047) of men and women aged 61–82 years who participated in the German KORA F4 survey (2006–2008). We measured circulating levels of seven immune mediators and assessed their associations with the presence of painful DSPN using multiple logistic regression models. RESULTS After adjustment for age and sex, we found positive associations between serum concentrations of the cytokine interleukin (IL)-6 and the soluble intercellular adhesion molecule (sICAM)-1 and painful DSPN (P = 0.004 and P = 0.005, respectively), whereas no associations were observed for C-reactive protein, IL-18, tumor necrosis factor-α, adiponectin, and IL-1 receptor antagonist (IL-1RA, P = 0.07–0.38). Associations between IL-6 and sICAM-1 and painful DSPN remained significant after additional adjustment for waist circumference, height, hypertension, cholesterol, smoking, alcohol intake, physical activity, history of myocardial infarction and/or stroke, presence of other neurological conditions, and use of nonsteroidal anti-inflammatory drugs (P = 0.005 and P = 0.016, respectively). CONCLUSIONS Painful DSPN is linked to systemic subclinical and vascular inflammation in the older population independent of anthropometric, lifestyle, and metabolic confounders.
Hydroxycarbamide-induced cutaneous ulceration with a difference
Authors: A.G. Matthews, G. Wylie
Journal: British Journal of Dermatology (2014)

Journal Article Hydroxycarbamide‐induced cutaneous ulceration with a difference Get access A.G. Matthews, A.G. Matthews Alan Lyell Centre for Dermatology Southern General Hospital 1345 Govan Road Glasgow G51 4TF U.K Search for other works by this author on: Oxford Academic Google Scholar G. Wylie G. Wylie Alan Lyell Centre for Dermatology Southern General Hospital 1345 Govan Road Glasgow G51 4TF U.K Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 171, Issue 6, 1 December 2014, Pages 1572–1574, https://doi.org/10.1111/bjd.13151 Published: 01 December 2014
Eight Hundred and Fifty-Two Operations for Stone in the Bladder
Authors: P. J. Freyer
Journal: BMJ (1894)

the form of fragments, no doubt owing to the fact that greater surface was offered to their activity.Not onily was the piper- azine solution capable of dissolvinig the uric acid conitainzd in the calculus, but it also dissolved nearly the wlhole of the otlher ingredients that were present, for out of the 50 mg.employed only 2 mg.were left undissolved.TABLB IV.-Eptriment to 8shov the Action of 1 per cent.Solution of Piperazine in Normal Urine on 50 Milliyramnies of a Cal- culue, the Composition of which had been ascertained by Ana- ly88.Temperature 390 C. Time.Piperazine.Borax.Lithium Sodiumi Potassium Citrate.Carbonate.Citrate.6 hrs.The calculusThe calculus The calculus The calculus The calculus had lost in had lost in had lost in had lost in had lost in weight weight weight weight weiglit 30 ing. 30 mg. 20 mg. 15 mg. 15mg. 12 hrs.Loss in Loss in Loss in Loss in Loss in weight weight weight weight weight 40 mg. 30mg. 20 mg. 15 mg. 25 mg. 18hrs.Loes in Loss in Loss in Loss in Loss in weight weight weight weight weight 44 mg.35 mg. 30mg. 20 mg. 28mg.24 hrs.Loss in Loss in Loss In Loss in Loss in weight weiglht weight weight weight 48mg.35mg.32mg.25mg.
Gastric-Outlet Obstruction
Authors: Luis M Franco, Natalie J Dryden
Journal: New England Journal of Medicine (2007)

A 51-year-old woman with a history of hypertension and chronic constipation presented with abdominal pain of 2 weeks' duration. The pain was continuous, worsened with eating, was associated with nausea, and radiated to her back. She reported no vomiting, fever, diarrhea, or weight loss, and her vital signs were normal. Her abdomen was distended, diffusely tender on palpation, and tympanic on percussion on the upper half and dull on the lower half. Bowel sounds were missing on the left side, and a large mass was palpated in that area. Laboratory evaluation was unremarkable. Computed tomography (CT) showed massive dilatation of . . .
Dynamics of HBV-specific CD4 and CD8 response during early phase of acute hepatitis B
Authors: G.J.M. Webster, S. Reignat, M.K. Maini, D. Brown, S.A. Whalley, G.S. Ogg, R. Williams, D. Vergani, G.M. Dusheiko, A. Bertoletti
Journal: Journal of Hepatology (2000)
A NEW CARRIER FOR SUTURE MATERIAL.
Authors: AUGUST SCHACHNER
Journal: JAMA (1901)

The ligature reel herein described was designed to replace the glass containers, which are generally considered the most aseptic arrangement at present at our disposal. This reel has all the advantages that apply to the glass arrangement and some additional ones, namely, being of metal it insures against breakage and thus is never exposed to the danger of an accident to the ligature outfit. The durability of the metal box is also greater than that of a glass one. It is true that a glass box has a slight advantage over the metal one in appearance, and for that reason the glass container may still receive the preference in hospitals. It is in portability that the metal ligature outfit comes in for its full measure of advantage over its rival, the glass outfit. When we are obliged to operate away from hospitals where we can not always judge the amount
Development and Receding of a Coronary Artery Aneurysm After Implantation of a Fully Bioresorbable Scaffold
Authors: Shimpei Nakatani, Yuki Ishibashi, Pannipa Suwannasom, Maik J. Grundeken, Evald Høj Christiansen, Yoshinobu Onuma, Patrick W. Serruys
Journal: Circulation (2015)
Fracture of an esophageal stent: a rare but significant complication
Authors: S. Chhetri, C. Selinger, S. Greer
Journal: Endoscopy (2008)

Self-expanding metal stents are commonly used to palliate malignant dysphagia. Typical complications include hemorrhage, ulceration, perforation or fistula, compression of the trachea, stent migration, and tumor ingrowth [1] [2]. We report fracture of an esophageal stent as an unusual complication.
The Benefits of Neo-Adjuvant Chemoradiotherapy for Esophageal Cancer, are They for All?
Authors: Fabio M. Gomes, Catarina Ribeiro, Ligia Costa, Sonia Oliveira, Pedro Barata, Manuel Sousa, M. Paula Custodio, Ricardo da Luz, Luisa Quaresma, Jorge Esteves, Gualdino Silva, Filomena Pina, Fernanda Cabrita, Alexandra Pupo, Mario Oliveira, Mateus Marques, Virginia Mareco, Guedes da Silva, M. Lurdes Batarda, Antonio Caldeira Fradique
Journal: Annals of Oncology (2013)
The κ Statistic
Authors: Charles C. Berry
Journal: JAMA (1992)

<h3>To the Editor.</h3> —Dr Goldman<sup>1</sup>uses the κ statistic to evaluate peer assessments of quality of care. He concluded that "physician agreement regarding quality of care is only slightly better than the level expected by chance." Of course, the real concern is not in the level of agreement per se, but in what "agreement" implies. Common sense suggests that if there is a low level of agreement, then physician judgments about quality of care are inaccurate. Goldman's conclusion is based on the κ statistic, which is an index of interrater agreement. He used a standard<sup>2</sup>that κ less than 0.40 represents "poor" agreement and a finding that few κ coefficients greater than 0.40 are reported in the literature on peer assessments. However, there are difficulties in the interpretation of κ<sup>3,4</sup>and the reported κ statistics do not support the conclusion. The difficulties in the interpretation of the
Pulmonary Acariasis in Spain
Authors: M. D. F. Taboada
Journal: BMJ (1954)

DIABETES INSIPIDUS WITH PULMONARY DISEASEMEDICBJMHNAL 437 serum cholesterol was 305 mg. per 100 ml.; serum albumin 5 g. and globulin 3.5 g. per 100 ml.; albumin/globulin ratio 1.43:1.Liver-function tests showed serum colloidal gold reaction 3+, gamma globulin (zinc sulphate) 8 units, thymnol turbidity 4 units, and thymol flocculation +.Pituitary snuff immediately controlled her polyuria and allowed her to sleep well at nights.After starting this treatment, however, she stated that her breathlessness was somewhat increased.Because of the hypochromic anaemia she was given iron, which resulted in some amelioration of the dyspnoea.A year later her condition was unaltered and a furtherx-ray film of the chest showed no substantial change.
Long-Term Pervenous Atrial Pacing
Authors: JOHN A. KASTOR, ROMAN W. DESANCTIS, ROBERT C. LEINBACH, J. WARREN HARTHORNE, IRVING N. WOLFSON
Journal: Circulation (1969)

Long-term pervenous right atrial pacing has been used in five patients with intact atrioventricular (A-V) conduction for the treatment of refractory ventricular arrhythmias in two subjects and marked sinus bradycardia in three, two of whom also had paroxysmal supraventricular arrhythmias. The pervenous method was used to avoid a thoracotomy, and atrial pacing was chosen over ventricular pacing to preserve the normal A-V contraction sequence. Reliable atrial pacing was established in four cases, but one patient required ultimate conversion to a ventricular system because of irregular atrial capture. The most constant pacing was achieved by using a curved electrode with the tip positioned in the right atrial appendage.