tbuckley/cabot-search huggingface dataset:
Treatment of Severe Systemic Inflammatory Response Syndrome and Sepsis With a Novel Bradykinin Antagonist, Deltibant (CP-0127)&lt;subtitle&gt;Results of a Randomized, Double-blind, Placebo-Controlled Trial&lt;/subtitle&gt;
Authors: Alan M. Fein
Journal: JAMA (1997)

<h3>Objective.</h3> —To test the effect of a novel bradykinin antagonist, deltibant (CP-0127), on survival, organ dysfunction, and other outcomes in patients with the systemic inflammatory response syndrome (SIRS) and presumed sepsis. <h3>Design.</h3> —Multicenter, randomized, placebo-controlled, double-blind, parallel, dose-ranging trial. Follow-up for 28 days or until death. <h3>Setting.</h3> —A total of 47 US referral hospitals. <h3>Patients.</h3> —A total of 504 patients with SIRS and documented evidence of infection plus either hypotension or dysfunction of 2 organ systems. <h3>Interventions.</h3> —Three-day continuous intravenous infusion of either placebo or 1 of 3 doses (0.3,1.0, or 3.0 μg.kg-1.man-1) of deltibant. Concurrent therapy at the discretion of the treating physician. <h3>Main Outcome Measure.</h3> —Risk-adjusted, 28-day, log-normal intent-to-treat survival analysis. Risk adjustment was performed using a study-specific risk model derived from the APACHE III database. <h3>Results.</h3> —Deltibant had no significant effect on risk-adjusted 28-day survival. In a posthoc analysis, risk-adjusted 7-day survival showed a nonsignificant trend toward improvement (<i>P</i>=.09). The 28-day risk-adjusted survival in the prospectively defined subset of patients with gram-negative infections showed a statistically significant improvement (<i>P</i>=.005). <h3>Conclusions.</h3> —Deltibant may have some effect on survival in patients with SIRS and gram-negative sepsis; however, additional studies would be required to prove this.
Randomized Phase II Multicenter Trial of Two Schedules of Lapatinib as First- or Second-Line Monotherapy in Patients with Advanced or Metastatic Non–Small Cell Lung Cancer
Authors: Helen J. Ross, George R. Blumenschein,, Joseph Aisner, Nevena Damjanov, Afshin Dowlati, Jennifer Garst, James R. Rigas, Michael Smylie, Habib Hassani, Kimberly E. Allen, Lance Leopold, Tal Z. Zaks, Frances A. Shepherd
Journal: Clinical Cancer Research (2010)

This randomized phase II study was initially designed to test the activity of two dose schedules of lapatinib (GW572016H), an oral, reversible, dual tyrosine kinase inhibitor of epidermal growth factor receptor (EGFR) and human EGFR-2 (HER2/neu; HER2), in chemotherapy-naive patients with non-small cell lung cancer (NSCLC); it was later amended to target patients with bronchioloalveolar carcinoma or no smoking history.Patients with good performance status and recurrent or metastatic NSCLC were randomized to lapatinib (orally, 1,500 mg once daily or 500 mg twice daily) until progression or intolerance. Patients could have had a maximum of one prior systemic therapy (chemotherapy or biological therapy) for NSCLC. Safety and activity were assessed every 4 and 8 weeks, respectively. Tumors were analyzed for EGFR and HER2 mutations and/or amplifications.Of 75 patients in the nontargeted population, 1 (1.3%) had partial response and 16 (21%) had stable disease of >or=24 weeks. No complete or partial responses were observed in 56 patients in the targeted population; 14 (25%) had stable disease of >or=24 weeks. No responses were seen in three patients with EGFR mutations and five with EGFR gene amplification. No mutations in HER2 were found. One of two patients with HER2 amplification had a 51% decrease in tumor size; however, this response was unconfirmed. The most common adverse events were grade 1 or 2 diarrhea, rash, fatigue, nausea, and anorexia. Adverse events were similar across dosing regimens.Lapatinib was well tolerated, with no notable difference in toxicity between treatment groups. Lapatinib monotherapy did not induce a significant number of tumor regressions in NSCLC. Further studies may be warranted to determine whether lapatinib is active in combination with other agents in the treatment of NSCLC.
Repetitive Transcranial Magnetic Stimulation of the Right Dorsolateral Prefrontal Cortex in Posttraumatic Stress Disorder: A Double-Blind, Placebo-Controlled Study
Authors: Hagit Cohen, Zeev Kaplan, Moshe Kotler, Irena Kouperman, Regina Moisa, Nimrod Grisaru
Journal: American Journal of Psychiatry (2004)

OBJECTIVE: The efficacy of repetitive transcranial magnetic stimulation (rTMS) of the right prefrontal cortex was studied in patients with posttraumatic stress disorder (PTSD) under double-blind, placebo-controlled conditions. METHOD: Twenty-four patients with PTSD were randomly assigned to receive rTMS at low frequency (1 Hz) or high frequency (10 Hz) or sham rTMS in a double-blind design. Treatment was administered in 10 daily sessions over 2 weeks. Severity of PTSD, depression, and anxiety were blindly assessed before, during, and after completion of the treatment protocol. RESULTS: The 10 daily treatments of 10-Hz rTMS at 80% motor threshold over the right dorsolateral prefrontal cortex had therapeutic effects on PTSD patients. PTSD core symptoms (reexperiencing, avoidance) markedly improved with this treatment. Moreover, high-frequency rTMS over the right dorsolateral prefrontal cortex alleviated anxiety symptoms in PTSD patients. CONCLUSIONS: This double-blind, controlled trial suggests that in PTSD patients, 10 daily sessions of right dorsolateral prefrontal rTMS at a frequency of 10 Hz have greater therapeutic effects than slow-frequency or sham stimulation.
Early mortality in patients with community-acquired pneumonia: causes and risk factors
Authors: C. Garcia-Vidal, N. Fernández-Sabé, J. Carratalà, V. Díaz, R. Verdaguer, J. Dorca, F. Manresa, F. Gudiol
Journal: European Respiratory Journal (2008)

The first 48 h of evolution of patients with community-acquired pneumonia (CAP) are critical. The aim of the present study was to determine the frequency, causes and factors associated with early mortality in CAP. Nonimmunocompromised adults hospitalised with CAP were prospectively observed from 1995 to 2005. Early deaths, defined as death due to any cause ≤48 h after admission, were compared with all patients who survived &gt;48 h. Furthermore, early deaths were compared with late deaths (patients who died &gt;48 h) and with survivors. Of 2,457 patients, 57 (2.3%) died ≤48 h after admission. Overall mortality was 7.7%. The main causes of early mortality were respiratory failure and septic shock/multiorgan failure. Independent factors associated with early deaths were increased age, altered mental status at presentation, multilobar pneumonia, shock at admission, pneumococcal bacteraemia and discordant empiric antibiotic therapy. Currently, early mortality is relatively low and is caused by pneumonia-related factors. It occurs mainly among the elderly and in patients presenting with altered mental status, multilobar pneumonia and septic shock. Pneumococcal bacteraemia and discordant antibiotic therapy, mainly due to lack of coverage against Pseudomonas aeruginosa are also significant risk factors.
Transplantation of a Horseshoe Kidney
Authors: James A. Majeski
Journal: JAMA (1979)

HORSESHOE kidney is considered to be one of the more common congenital urological anomalies, with an incidence of 1:300 to 1:1,800.<sup>1</sup>Most individuals with a horseshoe kidney survive to old age without complications. The use of such kidneys for renal transplantation has been generally avoided because of their frequent anomalous vasculature, occasional association with other renal anomalies, and a predisposition to urine stagnation, infection, and calculus formation. We could find only one previous report of a renal transplant of a horseshoe kidney.<sup>2</sup>We report here another case of a horseshoe kidney used for renal transplantation into two recipients. <h3>Report of a Case</h3> The donor was a 21-year-old man who died following a motorcycle accident. He had no history of urinary tract disease. His BUN level was 12 mg/dL; serum creatinine level, 1.0 mg/dL; urine volume, 100 mL/hr. Urine culture had no growth, and urinalysis results were within normal
Can hepatic coma be caused by a reduction of brain noradrenaline or dopamine?
Authors: L Zieve, R L Olsen
Journal: Gut (1977)

Intraventricular infusions of octopamine which raised brain octopamine concentrations more than 20 000-fold resulted in reductions in brain noradrenaline and dopamine by as much as 90% without affecting the alertness or activity of normal rats. As this reduction of brain catecholamines is much greater than any reported in hepatic coma, we do not believe that values observed in experimental hepatic failure have aetiological significance for the encephalopathy that ensues.
296 APOPTOSIS INDUCED BY IN VIVO INTERFERON-a2B (IFN) TREATMENT IN PRENEOPLASTIC RAT LIVERS: FOXO3A AND WNT/b-CATENIN PATHWAY PARTICIPATION
Authors: J.P. Parody, M.D.L. Alvarez, M.P. Ceballos, D.E. Francés, C.E. Carnovale, M.C. Carrillo
Journal: Journal of Hepatology (2012)
Point mutations cause the somatic diversification of IgM and IgG2a antiphosphorylcholine antibodies.
Authors: N C Chien, R R Pollock, C Desaymard, M D Scharff
Journal: The Journal of Experimental Medicine (1988)

The genetic mechanism responsible for the somatic diversification of two mAbs was determined. The two PC-binding hybridomas were representative of events early and late in the immune response. The P28 cell line that produces an IgM antibody and thus represents events early in the immune response, was found to have 3 bp changes in its heavy chain variable (VH) region, with some changes in antibody affinity or specificity. The RP93 cell line that produces an IgG2a antibody and thus represents later events in the immune response, was found to have 9 bp changes in its VH region resulting in decreased affinity for PC and altered specificity. Oligonucleotides specific for linked base changes in the second hypervariable regions of both of these antibodies were used to look for previously undescribed V regions or other donor sequences that could have been responsible for these base changes. Since no donor sequences were found, we have concluded that somatic point mutation rather than gene conversion, V region replacement or the expression of an unidentified germline VH region gene is truly responsible for at least some of the somatic diversification of these antibodies.
Characterization of a Carcinogenesis Rat Model of Ovarian Preneoplasia and Neoplasia
Authors: Sherri L. Stewart, Troy D. Querec, Alexander R. Ochman, Briana N. Gruver, Rudi Bao, James S. Babb, Thang S. Wong, Theodoros Koutroukides, Aaron D. Pinnola, Andres Klein-Szanto, Thomas C. Hamilton, Christos Patriotis
Journal: Cancer Research (2004)

Abstract Animal models of ovarian cancer are crucial for understanding the pathogenesis of the disease and for testing new treatment strategies. A model of ovarian carcinogenesis in the rat was modified and improved to yield ovarian preneoplastic and neoplastic lesions that pathogenetically resemble human ovarian cancer. A significantly lower dose (2 to 5 μg per ovary) of 7,12-dimethylbenz(a)anthracene (DMBA) was applied to the one ovary to maximally preserve its structural integrity. DMBA-induced mutagenesis was additionally combined with repetitive gonadotropin hormone stimulation to induce multiple cycles of active proliferation of the ovarian surface epithelium. Animals were treated in three arms of different doses of DMBA alone or followed by hormone administration. Comparison of the DMBA-treated ovaries with the contralateral control organs revealed the presence of epithelial cell origin lesions at morphologically distinct stages of preneoplasia and neoplasia. Their histopathology and path of dissemination to other organs are very similar to human ovarian cancer. Hormone cotreatment led to an increased lesion severity, indicating that gonadotropins may promote ovarian cancer progression. Point mutations in the Tp53 and Ki-Ras genes were detected that are also characteristic of human ovarian carcinomas. Additionally, an overexpression of estrogen and progesterone receptors was observed in preneoplastic and early neoplastic lesions, suggesting a role of these receptors in ovarian cancer development. These data indicate that this DMBA animal model gives rise to ovarian lesions that closely resemble human ovarian cancer and it is adequate for additional studies on the mechanisms of the disease and its clinical management.
Role of hemolysin for the intracellular growth of Listeria monocytogenes.
Authors: D A Portnoy, P S Jacks, D J Hinrichs
Journal: The Journal of Experimental Medicine (1988)

Listeria monocytogenes insertion mutants defective in hemolysin production were generated using the conjugative transposons Tn916 and Tn1545. All of the nonhemolytic mutants (hly-) lacked a secreted 58-kD polypeptide, presumedly hemolysin, and were avirulent in a mouse model. An intracellular multiplication assay was established in monolayers of mouse bone marrow-derived macrophages, the J774 macrophage-like cell line, the CL.7 embryonic mouse fibroblast cell line, and the Henle 407 human epithelial cell line. The hly+ strain grew intracellularly in all of the tissue culture cells with a doubling time of approximately 60 min. In contrast, the hly- mutants failed to grow in the murine-derived tissue culture cells, but retained the ability to grow in the human tissue culture cells examined. Hemolytic-positive revertants were selected after passage of the hly- mutants through monolayers of J774 cells. In each case, the hemolytic revertants possessed the 58-kD polypeptide, were capable of intracellular growth in tissue culture monolayers and were virulent for mice.
Incidence of lymphoma in a large primary care derived cohort of cases of inflammatory polyarthritis
Authors: J Franklin
Journal: Annals of the Rheumatic Diseases (2005)

To determine the risk of lymphoma in a primary care derived cohort of new onset cases of inflammatory polyarthritis and assess the contribution of disease severity and standard immunosuppressive treatment.Prospective cohort study.2105 subjects with new onset inflammatory polyarthritis were recruited to the Norfolk Arthritis Register (NOAR) and followed annually for (median) 8.4 years. Occurrence of lymphoma was determined by annual morbidity review and linkage to the central hospital database serving the NOAR area. Cases of lymphoma were verified by record review. Standardised incidence ratios (SIRs) for lymphoma were calculated compared with the local, age, sex, and calendar year expected rates. Stratified analyses were undertaken for various markers of disease severity and treatment history.There were 11 cases of lymphoma during 15,548 person years of follow up, the majority of which were of large B cell type. Compared with the local population the SIR was 2.4 (95% confidence interval, 1.2 to 4.2). The risks in cases classified as rheumatoid arthritis, ever rheumatoid factor positive, or ever treated with DMARDs were all higher, the highest risk group being those treated with methotrexate: SIR = 4.9 (1.8 to 10.6).There was a doubling in risk of lymphoma in new onset cases of inflammatory polyarthritis. Patients with the most severe disease were twice as likely as other patients to develop lymphoma. These results need to be taken into account when considering reported increased risks of lymphoma compared to background population risk in users of new biological agents.
Repair versus Checkpoint Functions of BRCA1 Are Differentially Regulated by Site of Chromatin Binding
Authors: Michael Goldstein, Michael B. Kastan
Journal: Cancer Research (2015)

Abstract The product of the Brca1 tumor-suppressor gene is involved in multiple aspects of the cellular DNA damage response (DDR), including activation of cell-cycle arrests and DNA double-stranded break (DSB) repair by homologous recombination. Prior reports demonstrated that BRCA1 recruitment to areas of DNA breakage depended on RAP80 and the RNF8/RNF168 E3 ubiquitin ligases. Here, we extend these findings by showing that RAP80 is only required for the binding of BRCA1 to regions flanking the DSB, whereas BRCA1 binding directly to DNA breaks requires Nijmegen breakage syndrome 1 (NBS1). These differential recruitment mechanisms differentially affect BRCA1 functions: (i) RAP80-dependent recruitment of BRCA1 to chromatin flanking DNA breaks is required for BRCA1 phosphorylation at serine 1387 and 1423 by ATM and, consequently, for the activation of S and G2 checkpoints; and (ii) BRCA1 interaction with NBS1 upon DSB induction results in an NBS1-dependent recruitment of BRCA1 directly to the DNA break and is required for nonhomologous end-joining repair. Together, these findings illustrate that spatially distinct fractions of BRCA1 exist at the DSB site, which are recruited by different mechanisms and execute different functions in the DDR. Cancer Res; 75(13); 2699–707. ©2015 AACR.
Nationwide prevalence of sporadic and familial idiopathic pulmonary fibrosis: evidence of founder effect among multiplex families in Finland
Authors: U Hodgson
Journal: Thorax (2002)

Background: The prevalence of sporadic and familial idiopathic pulmonary fibrosis (IPF) cases in Finland was evaluated according to the revised recommendations of the American Thoracic Society. Methods: All Finnish pulmonary clinics (n=29) were included in the primary screening. Hospital data bases were used to identify patients with the diagnosis "alveolitis fibroticans idiopathica" (J84.1 in ICD-10 classification). The total number of patients with IPF was extrapolated based on the evaluation of random samples of case records in different centres. Families with more than one potentially affected member were identified from a questionnaire study and the diagnosis was verified from the medical records. Results: Using this approach, the nationwide prevalence of IPF in Finland was estimated to be 16–18/100 000. In 90% of the patients lung involvement was assessed by high resolution computed tomographic (HRCT) scanning and in 31% a surgical biopsy specimen was available, further confirming the diagnosis. Seventeen multiplex families with 2–5 affected family members were identified, giving a prevalence of 5.9/million for familial IPF in Finland. Both multiplex and sporadic families were clustered in Eastern Finland. This clustering reflects the demographic history of Finland in the 16th century and suggests that multiplex families may share a common ancestor in the last 20–25 generations. Conclusion: The familial form explained 3.3–3.7% of all Finnish cases of IPF diagnosed according to the revised international guidelines. Geographical clustering of multiplex families suggests a recent founder effect in patients with familial IPF.
ON LEAD POISONING IN CHILDHOOD
Authors: A. J. Turner
Journal: BMJ (1909)

MEDICAL JOUENAT9J.5 *vertig9 from a poisonous dose of quinine.It is, however, not necessary to give it in such large doses.'Given a grainat a time, it seems to reduce the irritation, of the vestibular nerve, probably by overcoming congestive changes.On the ground that vertigo is due to anaemia of 'the labyrinth, which, however, is probably not as a rule well founded, Lermoyez suggested; the use of 'amyl nitrite.We are all aware, of course, that in oenditions of severe anaemia vertigo is 'common, but whether this is an aural phenomenon or not, 'even 'when associated, as it often is, with tinnitus, is a doubtful point.At the same time it is quite possible that the actual cause of vertigo is not so much either con- 'gestion or anaemia as the alterations in. the pressure of 'the endolymph which may be brought about by either of -these' states.The bromides and iodides are sometimes useful, and pilocarpine, especially in patients in whom the aural condition is dependent on congenital or tertiary acquired syphilis, 'has sometimes seemed of value.Repeated lumbar puncture has been used with some, though probably -only with temporary, benefit.Patients should be advised to eschew alcohol, tea, coffee, and tobacco, to avoid as far as possible mental excitement and 'ioud noises, and to keep the bowels acting well.During a severe attack the recumbent posture should be enjoined, with ioe to the side of the head.When all other measures fail, and when life is made practically intolerable, the -advisability of destroying-the labyrinth-at any rate the 4static portion of it-should be entertained.I am referring now to cases of non-suppurative 'ear diseases.This has -been carried out in this country by Milligan,-Lake, -and Yearsley; or, as Ballance suggests may yet be possible, the vestibular nerve, as distinct from the auditory nerve, may be divided before it enters the internal auditory .meatus.
Cervical Cancer in Women With Comprehensive Health Care Access: Attributable Factors in the Screening Process
Authors: Wendy A. Leyden, M. Michele Manos, Ann M. Geiger, Sheila Weinmann, Judy Mouchawar, Kimberly Bischoff, Marianne Ulcickas Yood, Joyce Gilbert, Stephen H. Taplin
Journal: JNCI Journal of the National Cancer Institute (2005)

Invasive cervical cancer is highly preventable, yet it continues to occur, even among women who have access to cancer screening and treatment services. To reduce cervical cancer among such women, reasons for its occurrence must be better understood. We examined factors associated with the diagnosis of cervical cancer among women enrolled in health plans.We identified all cases of invasive cervical cancer (n = 833) diagnosed from January 1, 1995, through December 31, 2000, among women who were long-term members of seven prepaid comprehensive health plans and reviewed each woman's medical records for the 3 years prior to her cancer diagnosis. Women were classified into one of three categories based on Pap test histories 4-36 months before diagnosis: failure to screen with a Pap test, failure in detection by a Pap test, or failure in follow-up of an abnormal test result.The majority of cases (n = 464; 56%) were in women who had no Pap tests during the period 4-36 months prior to diagnosis. Of the remaining cases, 263 (32%) were attributed to Pap test detection failure and 106 (13%) to follow-up failure. Being older (odds ratio [OR] = 6.48, 95% confidence interval [CI] = 3.89 to 10.79) or living in an area of higher poverty (OR = 1.72, 95% CI = 1.11 to 2.67) or having a lower education level (OR= 1.52; 95% CI = 1.07 to 2.16) was associated with the likelihood of being assigned to the failure to screen category versus either of the other two categories. A total of 375 (81%) of the 464 patients who had not had Pap screening had had at least one outpatient visit 4-36 months prior to cancer diagnosis. The cancer diagnostic process was triggered by a routine screening examination in 44% of patients, whereas 53% of the patients presented with symptoms consistent with cervical cancer; the remaining 3% were identified fortuitously during the course of receiving noncervical care.To reduce the incidence of invasive cervical cancer among women with access to screening and treatment, Pap screening adherence should be increased. In addition, strategies to improve the accuracy of Pap screening could afford earlier detection of cervical cancer.