tbuckley/cabot-search huggingface dataset:
Randomized Phase III Trial of Amrubicin Versus Topotecan As Second-Line Treatment for Patients With Small-Cell Lung Cancer
Authors: Joachim von Pawel, Robert Jotte, David R. Spigel, Mary E.R. O'Brien, Mark A. Socinski, Jörg Mezger, Martin Steins, Léon Bosquée, Jeffrey Bubis, Kristiaan Nackaerts, José M. Trigo, Philip Clingan, Wolfgang Schütte, Paul Lorigan, Martin Reck, Manuel Domine, Frances A. Shepherd, Shaoyi Li, Markus F. Renschler
Journal: Journal of Clinical Oncology (2014)

Amrubicin, a third-generation anthracycline and potent topoisomerase II inhibitor, showed promising activity in small-cell lung cancer (SCLC) in phase II trials. This phase III trial compared the safety and efficacy of amrubicin versus topotecan as second-line treatment for SCLC.A total of 637 patients with refractory or sensitive SCLC were randomly assigned at a ratio of 2:1 to 21-day cycles of amrubicin 40 mg/m(2) intravenously (IV) on days 1 to 3 or topotecan 1.5 mg/m(2) IV on days 1 to 5. Primary end point was overall survival (OS); secondary end points included overall response rate (ORR), progression-free survival (PFS), and safety.Median OS was 7.5 months with amrubicin versus 7.8 months with topotecan (hazard ratio [HR], 0.880; P = .170); in refractory patients, median OS was 6.2 and 5.7 months, respectively (HR, 0.77; P = .047). Median PFS was 4.1 months with amrubicin and 3.5 months with topotecan (HR, 0.802; P = .018). ORR was 31.1% with amrubicin and 16.9% with topotecan (odds ratio, 2.223; P < .001). Grade ≥ 3 treatment-emergent adverse events in the amrubicin and topotecan arms were: neutropenia (41% v 54%; P = .004), thrombocytopenia (21% v 54%; P < .001), anemia (16% v 31%; P < .001), infections (16% v 10%; P = .043), febrile neutropenia (10% v 3%; P = .003), and cardiac disorders (5% v 5%; P = .759); transfusion rates were 32% and 53% (P < .001), respectively. NQO1 polymorphisms did not influence safety outcomes.Amrubicin did not improve survival when compared with topotecan in the second-line treatment of patients with SCLC. OS did not differ significantly between treatment groups, although an improvement in OS was noted in patients with refractory disease treated with amrubicin.
Comparison of Once- Versus Twice-Daily Administration of Insulin Detemir, Used With Mealtime Insulin Aspart, in Basal-Bolus Therapy for Type 1 Diabetes
Authors: Jean-Pierre Le Floch, Marc Lévy, Helen Mosnier-Pudar, Frank Nobels, Sylvie Laroche, Sophie Gonbert, Eveline Eschwege, Pierre Fontaine
Journal: Diabetes Care (2008)

The purpose of this study was to compare effects of insulin detemir once daily versus twice a day in a basal-bolus insulin regimen.In this open-label, 7-month study, 520 patients with type 1 diabetes were randomly assigned to receive detemir once daily or twice daily with mealtime insulin aspart. Insulin doses were titrated over 1 month, with patients followed up over the subsequent 3 months. Thereafter, patients were able to switch from one regimen to the other, with an additional nonrandomized 3-month follow-up, to a total of 7 months. The primary end point was A1C at 4 months, with noninferiority defined as a difference <0.4% between groups.A1C at 4 months was 8.1 +/- 0.9 versus 8.0 +/- 1.0% with once- and twice-daily detemir, respectively, with an adjusted between-group difference of 0.12% (95% CI -0.01 to 0.25%), showing noninferiority for once-daily dosing. Similar results were found in the per protocol population. Improvement in A1C was similar in both groups (-0.4 +/- 0.8 vs. -0.5 +/- 0.8%; P = 0.09, NS) but with differences in the 7-point glucose profile. Detemir doses were lower (29 +/- 18 vs. 39 +/- 20 units/day, P < 0.001), but aspart doses were higher (34 +/- 17 vs. 26 +/- 14 IU/day, P < 0.001) with once-daily detemir. At 7 months, A1C decreased slightly in patients switched from once-daily to twice-daily administration (8.2 +/- 0.8 vs. 8.0 +/- 0.8%; P = 0.34, NS) in association with increased total insulin doses (P < 0.05), but A1C increased in those switched from twice-daily to once-daily administration (7.2 +/- 0.9 vs. 7.6 +/- 0.8%, P < 0.05) in association with decreased doses (P < 0.05).Although some individuals may benefit from twice-daily dosing, the most suitable routine starting schedule for detemir in a basal-bolus regimen for type 1 diabetes is once-daily injection.
Studies on the mechanism of bacterial resistance to complement-mediated killing. II. C8 and C9 release C5b67 from the surface of salmonella minnesota S218 because the terminal complex does not insert into the bacterial outer membrane
Authors: KA Joiner, CH Hammer, EJ Brown, MM Frank
Journal: The Journal of Experimental Medicine (1982)

The mechanism for consumption of terminal complement components and release of bound components from the surface of serum-resistant salmonella minnesota S218 was studied. Consumption of C8 and C9 by S218 occurred through interaction with C5b67 on the bacterial surface because C8 and C9 were consumed when added to S218 organisms previously incubated in C8-deficient serum and washed to remove all C5b67 on the bacterial surface because C8 and C9 were consumed when added to S218 organisms previously incubated in C8- deficient serum and washed to remove al but cell bound C5b67. Rapid release of (125)I C5 and (125)I C7 from the membrane of S218 was dependent on binding of C8 because (125)I C5 and (125)I C7 deposition in C8D serum was stable and was twofold higher in C8D than in PNHA, and addition of purified C8 or C8 and C9 to S218 previously incubated in C8D serum caused rapid release of (125)I C5 and (125)I C7 from the organism. Analysis by sucrose density gradient ultracentrifugation of the fluid phase from the reaction of S218 and 10 percent PNHS revealed a peak consistent with SC5b-9, in which the C9:C7 ratio was 3.3:1, but the NaDOC extracted bound C5b-9 complex sedimented as a broad peak with C9:C7 of less than 1.2:1. Progressive elution of C5b67 and C5b-9 from S218 but not serum-sensitive S. minnesota Re595 was observed with incubation in buffers of increasing ionic strength. Greater than 90 percent of the bound counts of (125)I C5 or (125)I C9 were released from S218 by incubation in 0.1 percent trypsin, but only 57 percent of (125)I C9 were released by treatment of Re595 with trypsin. These results are consistent with the concept that C5b-9 forms on the surface of the serum-sensitive S. minnesota S218 in normal human serum, but the formed complex is released and is not bactericidal for S218 because it fails to insert into hydrophobic outer membrane domains.
Evolution of transcriptional regulatory elements within the promoter of a mammalian gene
Authors: N. Singh, K. W. Barbour, F. G. Berger
Journal: Molecular Biology and Evolution (1998)

Transcription of the murine D7Rp2e gene is highly variable among species of the genus Mus, indicating that extensive modifications in the gene's regulatory elements have occurred during evolution. Since promoter regions are well known to harbor cis-acting information that controls gene transcription, we compared the sequence and function of the D7Rp2e promoter in several Mus species, with the goal of understanding the molecular mechanisms underlying the interspecies variations in expression. Three overlapping binding sites for nuclear factors (sites A, B, and C in proximal to distal order) were identified about 300 bp upstream of the transcriptional start site. The sequences of these sites differ between the species Mus domesticus and M. pahari, which exhibit distinct D7Rp2e expression phenotypes. Site A binds a factor called RPBF-I; sites B and C bind a distinct factor that is termed RPBF-II and is likely a member of the NF-I family of transcription factors. DNase I footprinting experiments with the M. domesticus promoter show that binding of RPBF-II at site B is very strong, while binding of RPBF-I and RPBF-II at sites A and C, respectively, is weak; in contrast, with the M. pahari promoter, factor binding at sites A and C is strong, while that at site B is weak. These differences in patterns of binding-site occupancy derive from changes in the affinities of individual sites for their cognate nuclear factors. Transient transfection experiments indicate that the M. pahari binding pattern is capable of repressing transcription of a linked reporter. Such repression may contribute to the differences in D7Rp2e expression between the two species. We suggest that the species-specific footprinting patterns represent the existence of a dynamic equilibrium between two states of nuclear factor binding, the nature of which can be modified during evolution to result in new patterns of gene transcription.
Characteristics of general practitioners who frequently see drug industry representatives: national cross sectional study
Authors: C. Watkins
Journal: BMJ (2003)

<h3>ABSTRACT</h3> <h3>Background</h3> Restoration of step length symmetry is a common rehabilitation goal after stroke. Persons post-stroke often retain the capacity to walk with symmetric step lengths ("symmetric steps"); however, the resulting walking pattern remains effortful. Two key questions with direct implications for rehabilitation have emerged: 1) how do persons post-stroke generate symmetric steps, and 2) why do symmetric steps remain so effortful? <h3>Objective</h3> To understand how persons post-stroke generate symmetric steps and how the resulting gait pattern relates to the metabolic cost of transport. <h3>Methods</h3> Ten persons post-stroke walked on an instrumented treadmill under two conditions: preferred walking and symmetric stepping (using visual feedback). We recorded kinematic, kinetic, and metabolic data during both conditions. <h3>Results</h3> Persons post-stroke restored step length symmetry using energetically expensive, asymmetric patterns. Impaired paretic propulsion and abnormal vertical movement of the center of mass were evident during both preferred walking and symmetric stepping. These deficits contributed to diminished positive work performed by the paretic limb on the center of mass in both conditions. Decreased positive paretic work correlated with increased metabolic cost of transport, decreased self-selected walking speed, and increased asymmetry in limb kinematics. <h3>Conclusions</h3> It is important to consider the mechanics used to restore symmetric steps when designing interventions to improve walking after stroke. Facilitating symmetric steps via increased paretic propulsion or enabling paretic limb advancement without excessive vertical movement may enable persons post-stroke to walk with a less effortful, more symmetric gait pattern.
Percutaneous Transhepatic Biliary Drainage
Authors: Patricia K. Joseph
Journal: JAMA (1986)

Percutaneous transhepatic biliary drainage is usually used for preoperative decompression and for palliation in obstructive jaundice, but little attention has been focused on catheter complications. We retrospectively reviewed our experience with percutaneous transhepatic biliary drainage in 81 consecutive patients. There was a 10.0% failure rate and an 8.6% mortality rate. Four patients (4.9%) required emergency operations for complications and an additional ten patients (12.3%) required transfusions. The overall sepsis rate was 34.6%; prophylactic antibiotics decreased the sepsis rate. Thirty-eight patients (47.0%) required 68 manipulation procedures for catheter malfunctions. No distinguishing characteristics could be found to identify the subgroups having complications or mortalities. The efficacy of preoperative percutaneous transhepatic biliary drainage has not been proved, and the indications for palliation are not clearly defined. Further trials are needed to define the role of percutaneous transhepatic biliary drainage in patients with obstructive jaundice.
THE ACTION OF MINERAL ACID ON THE CELLULAR SUBSTANCE OF BACILLUS TYPHOSUS.
Authors: MAY WHEELER
Journal: JAMA (1904)

This research was undertaken for the purpose of ascertaining whether or not the cellular substance of the typhoid bacillus shows any tendency to uniform and definite cleavage under the influence of the mineral acids, the ultimate object being to learn something of the chemical composition and structure of the molecule making up the substance of the cell. In this paper, which must be considered only a preliminary contribution, general results only are given, with the hope of being able to go more into detail subsequently. <h3>METHODS.</h3> The material used in these studies consisted of the cellular substance of a typical typhoid bacillus, which was obtained from the mesenteric glands after death from typhoid fever, and which gave in a typical manner all the characteristic cultural manifestations of this organism. The toxieity of the living culture was tested on rabbits, guinea-pigs and white rats, and then the organism was grown
The Radionuclide Scintigraphic Appearance in a Rare Case of Epidermoid Cyst of the Testis
Authors: I GARTY, G CHAIMOVITCH, S WAJSMAN, M SUDARSKY
Journal: Clinical Nuclear Medicine (1984)

A rare case of epidermoid cyst of the testis, represented scintigraphically by an area of avascularity in the affected testicle, is described. The differential diagnosis from epididymitis and torsion of testis, and the diagnostic value fo the scintigraphic method to rule out malignant (vascular) testicular tumors, is emphasized.
Natural history of acquired immunodeficiency syndrome in hemophilic patients
Authors: Hugh C. Kim, Kenneth Nahum, Karel Raska, David J. Gocke, Martin Kosmin, George I. Karp, Parvin Saidi
Journal: American Journal of Hematology (1987)

Abstract During the 5‐year period from 1981 to 1985, we have observed 8 cases of acquired immunodeficiency syndrome (AIDS) among our 85 patients with hemophilia A. Thus, the prevalence of AIDS with hemophilia A is 9.4% in our patient population. By utilizing stored serum or plasma samples dating back to 1978, antibody against HTLV‐III was detected in all 8 cases with AIDS. Based on the time interval from the appearance of antibody to HTLV‐III to the diagnosis of AIDS in these patients, the incubation period ranged from 27 months to 60 months, with a median of 36 months. Before the diagnosis of full‐blown AIDS, all patients exhibited a variety of prodromal manifestations of non‐specific nature, including weight loss, oral candidiasis, unexplained non‐productive chronic cough, generalized lymphadenopathy, and thrombocytopenia lasting several months to several years. Serial T‐lymphocyte subset studies were available in some patients during the HTLV‐III seropositive period and showed progressive lymphopenia, depletion of T4 cells with an average absolute count of 94 ± 128 per mm 3 (mean ± 1 S. D.), and a markedly reversed T4/T8 ratio of 0.26 ± 0.19 (mean ± 1 S. D.). These findings suggest that the incubation period of AIDS is considerably long and that prospective study of serial immunologic markers and HTLV‐III markers may be warranted in hemophilic patients at risk.
Blood Pressure Profiles in Adolescents With Recently Diagnosed Type 2 Diabetes
Authors: Christine A. Brosnan, Janet C. Meininger, Paul R. Swank, Lisa R. Reyes, Patrick G. Brosnan
Journal: Diabetes Care (2002)

Type 2 diabetes in children is a recent phenomenon, and current evidence about diabetes and hypertension is based on adult studies. Adults with diabetes have changes in 24-h ambulatory blood pressure (BP) profiles, including a decrease in sleep dip (the decline in BP that normally occurs during sleep) and increased systolic blood pressure (SBP), that are associated with early cardiovascular disease (1).

This cross-sectional study compared 24-h BP and heart rate (HR) profiles of Hispanic and African-American adolescents recently diagnosed with type 2 diabetes with the profiles of two groups of 10 healthy control subjects matched for age, sex, height, and …
Validation of a Diabetic Wound Classification System: The contribution of depth, infection, and ischemia to risk of amputation
Authors: David G Armstrong, Lawrence A Lavery, Lawrence B Harkless
Journal: Diabetes Care (1998)

To validate a wound classification instrument that includes assessment of depth, infection, and ischemia based on the eventual outcome of the wound.We evaluated the medical records of 360 diabetic patients presenting for care of foot wounds at a multidisciplinary tertiary care foot clinic. As per protocol, all patients had a standardized evaluation to assess wound depth, sensory neuropathy, vascular insufficiency, and infection. Patients were assessed at 6 months after their initial evaluation to see whether an amputation had been performed.There was a significant overall trend toward increased prevalence of amputations as wounds increased in both depth (chi 2trend = 143.1, P < 0.001) and stage (chi 2trend = 91.0, P < 0.001). This was true for every subcategory as well with the exception of noninfected, nonischemic ulcers. There were no amputations performed within this stage during the follow-up period. Patients were more than 11 times more likely to receive a midfoot or higher level amputation if their wound probed to bone (18.3 vs. 2.0%, P < 0.001, chi 2 = 31.5, odds ratio (OR) = 11.1, CI = 4.0-30.3). Patients with infection and ischemia were nearly 90 times more likely to receive a midfoot or higher amputation compared with patients in less advanced wound stages (76.5 vs. 3.5%, P < 0.001, chi 2 = 133.5, OR = 89.6, CI = 25-316).Outcomes deteriorated with increasing grade and stage of wounds when measured using the University of Texas Wound Classification System.
Predictor Factors for Airway Responsiveness during Bronchial Allergen Challenge Tests: Role of Allergen-Specific IgE Levels, Cutaneous Allergen Sensitivity and Non-Specific Airway Hyperresponsiveness
Authors: C. Barnig, A. Purohit, A. Casset, C. Sohy, F. Lieutier-Colas, F. de Blay
Journal: Journal of Allergy and Clinical Immunology (2009)
Artist reignites debate over BMA sculptures
Authors: Colin Martin
Journal: BMJ (2005)

The Third Campaign: A Project by Neal White An exhibition at the Henry Moore Institute, Leeds, until 27 March www.henry-moore-fdn.co.uk Rating: ![Graphic][1]</img>![Graphic][2]</img>![Graphic][3]</img> Sculptures that caused a scandal when they were first carved for the BMA headquarters in 1908 have inspired an exhibition by contemporary artist Neal White. The sculptures, by Jacob Epstein (1880-1959), were 18 larger than life, naked figures that were commissioned to adorn the façade of the then new BMA's London headquarters on a prominent site at the corner of Agar Street and the Strand. White's exhibition is an attempt to reignite the debates that have raged over Epstein's sculptural scheme. Charles Holden (1875-1960), the architect of the Strand building, used … [1]: /embed/inline-graphic-1.gif [2]: /embed/inline-graphic-2.gif [3]: /embed/inline-graphic-3.gif
Never underestimate the force of reproduction
Authors: B. Donovan
Journal: BMJ (2000)

Papers p 486 

Whether you give weight to the philosophy of a divine human spirit or to the elegant chemistry of evolution, or to both, there is no argument about humankind's drive to reproduce. The strength of that drive manifests in many ways: physically, as the millions of spermatozoa launched with each ejaculation; behaviourally, as the early onset and frequency of sexual activity; institutionally, as the papal preclusions of contraception and abortion; and professionally, as the trivialisation of sexual medicine and fertility control. It was no accident that the first drug to be overtly rationed by the NHS was sildenafil (Viagra). Sexual function was dismissed as a “lifestyle option” rather than an issue of health and wellbeing. But, while sexual intercourse occurs less often, the proportion of humans who will have sex during their lives approaches the proportion that will breathe.1

Typically, young women who are adequately nourished are fertile. Globally, increasing numbers of young women are becoming sexually active long before they form durable partnerships.2 Access to contraception is essential but it may not …
Medical Reserves Answer Call to Service
Authors: Bridget M. Kuehn
Journal: JAMA (2012)

The ACIP also recommended expanding the use of the HPV vaccine to young males, with routine vaccination at age 11 or 12 years, catch-up vaccinations for those 13 to 21 years old, and vaccination for men between ages 22 and 26 years who are HIV positive or immunocompromised or who have sex with men. Part of the rationale for extending such vaccinations to boys was that in an environment where coverage among girls remains low—with only about one-third completing the vaccination series—also vaccinating boys becomes a more cost-effective strategy for reducing cervical cancer (MMWR Morb Mortal Wkly Rep. 2011; 60[50]:1705-1708). Additionally, the boys benefit directly from an anticipated reduction in HPV-related cancers of the anus, penis, head, and neck. The ACIP also said that it is gradually adopting a new system that will assign a grade to the evidence supporting each of the committee’s recommendations (Fryhofer SA. Ann Intern Med. 2012;156[3]:243-245). The new system will take into account such factors as the quality of the evidence, the potential benefits and risks associated with an intervention, and the values and preferences of the population being targeted for vaccination. The recommendations for HPV vaccination for males and hepatitis B vaccination for patients with diabetes were the first recommendations to be made using this approach. Schaffner said the system will be gradually phased in as older recommendations come up for renewal. “It brings the system into the 21st century,” he said.
The effectiveness of right heart catheterization in the initial care of critically ill patients. SUPPORT Investigators
Authors: A. F. Connors
Journal: JAMA (1996)

To examine the association between the use of right heart catheterization (RHC) during the first 24 hours of care in the intensive care unit (ICU) and subsequent survival, length of stay, intensity of care, and cost of care.Prospective cohort study.Five US teaching hospitals between 1989 and 1994.A total of 5735 critically ill adult patients receiving care in an ICU for 1 of 9 prespecified disease categories.Survival time, cost of care, intensity of care, and length of stay in the ICU and hospital, determined from the clinical record and from the National Death Index. A propensity score for RHC was constructed using multivariable logistic regression. Case-matching and multivariable regression modeling techniques were used to estimate the association of RHC with specific outcomes after adjusting for treatment selection using the propensity score. Sensitivity analysis was used to estimate the potential effect of an unidentified or missing covariate on the results.By case-matching analysis, patients with RHC had an increased 30-day mortality (odds ratio, 1.24; 95% confidence interval, 1.03-1.49). The mean cost (25th, 50th, 75th percentiles) per hospital stay was $49 300 ($17 000, $30 500, $56 600) with RHC and $35 700 ($11 300, $20 600, $39 200) without RHC. Mean length of stay in the ICU was 14.8 (5, 9, 17) days with RHC and 13.0 (4, 7, 14) days without RHC. These findings were all confirmed by multivariable modeling techniques. Subgroup analysis did not reveal any patient group or site for which RHC was associated with improved outcomes. Patients with higher baseline probability of surviving 2 months had the highest relative risk of death following RHC. Sensitivity analysis suggested that a missing covariate would have to increase the risk of death 6-fold and the risk of RHC 6-fold for a true beneficial effect of RHC to be misrepresented as harmful.In this observational study of critically ill patients, after adjustment for treatment selection bias, RHC was associated with increased mortality and increased utilization of resources. The cause of this apparent lack of benefit is unclear. The results of this analysis should be confirmed in other observational studies. These findings justify reconsideration of a randomized controlled trial of RHC and may guide patient selection for such a study.