tbuckley/cabot-search huggingface dataset:
Sofosbuvir compassionate use program for patients with severe recurrent hepatitis C after liver transplantation
Authors: Xavier Forns, Michael Charlton, Jill Denning, John G. McHutchison, William T. Symonds, Diana Brainard, Theo Brandt‐Sarif, Paul Chang, Valerie Kivett, Lluís Castells, Martín Prieto, Robert J. Fontana, Thomas F. Baumert, Audrey Coilly, Maria Carlota Londoño, François Habersetzer
Journal: Hepatology (2014)

Recurrent hepatitis C virus (HCV) infection after liver transplantation (LT) is associated with accelerated progression of liver disease, frequently leading to graft loss and early death. Existing treatment options for severe recurrent HCV infection are limited by suboptimal efficacy, poor tolerability, and numerous drug interactions. We provided sofosbuvir (SOF) and ribavirin (RBV) on a compassionate‐use basis to patients with severe recurrent hepatitis C, including those with fibrosing cholestatic hepatitis (FCH) and decompensated cirrhosis who had a life expectancy of 1 year or less. All patients were to receive 24‐48 weeks of SOF plus RBV. Investigators could add pegylated interferon to the regimen at their discretion. Data from the first 104 patients who completed or prematurely discontinued treatment by January 1, 2014 are presented. Of the 104 patients analyzed, 52 had an early severe recurrence (diagnosed &lt;12 months after LT) and 52 had cirrhosis (diagnosed &gt;12 months after LT). Twelve patients who underwent retransplantation were excluded from our efficacy analysis. Of the 92 patients assessed, 54 (59%) achieved sustained virological response (SVR) at 12 weeks after the end of treatment, with a higher rate (73%; 35 of 48) in patients with early severe recurrence. Of the 103 patients assessed for clinical outcome, 59 (57%) reported clinical improvement at the last study visit, 23 (22%) were unchanged, 3 (3%) had a worsened clinical status, and 13 (13%) died. Overall, 123 serious adverse events (SAEs) occurred in 49 patients (47%). SAEs associated with hepatic decompensation were the most frequent, with 26 SAEs occurring in 19 patients (18%). Conclusion : SOF and RBV provide high rates of SVR in patients with severe recurrent HCV, including patients with early severe recurrence, FCH, and cirrhosis. (H epatology 2015;61:1485–1494)
Cross-Cultural Medicine
Authors: Jeffrey M. Borkan
Journal: JAMA (2005)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Effect of the Fv-1 Locus In Vivo: Host Range Pseudotypes of Murine Sarcoma Virus 2
Authors: James A. Otten, Fred E. Myer, Raymond W. Tennant, Arthur Brown
Journal: JNCI Journal of the National Cancer Institute (1978)

Fv-1-specific host-range pseudotypes of murine sarcoma virus (MuSV) were developed by rescue from nonproducer cells with N- or B-tropic leukemia viruses. The MuSV(B) and MuSV(N) pseudotype viruses were tested in vitro and were restricted specifically by the Fv-1 gene locus. When the pseudotype viruses were tested in vivo in mice of specific Fv-1 genotypes, tumor induction was completely restricted in nonpermissive animals, including athymic nude mice, whereas tumors grew progressively in permissive animals. All tumors regressed in adult heterozygous mice, but not in adult athymic nude mice.
Synergistic Antiproliferative Effect of Human Recombinant Interferons and Retinoic Acid in Cultured Breast Cancer Cells
Authors: C Marth, G Daxenbichler, O Dapunt
Journal: JNCI Journal of the National Cancer Institute (1986)

A combination of retinoic acid (RA) and human recombinant DNA-derived interferon-gamma (Hu-IFN-gamma) was tested with respect to the growth inhibitory action on several human mammary carcinoma cell lines (ZR-75.1, 734-B, MCF-7, and BT-20), a human lung carcinoma cell line (CCL-185), and a human laryngeal carcinoma cell line (HEP-2). The mammary carcinoma cell lines were all sensitive to Hu-IFN-gamma, and 2 of them (ZR-75.1 and 734-B) were also affected by RA. The combination of both substances led to a pronounced synergistic amplification of growth inhibition in ZR-75.1 and 734-B cells. RA also increased the antiproliferative activity of Hu-IFN-gamma in the RA-resistant BT-20 cells and to a less pronounced degree in MCF-7 cells. In contrast to these findings, no synergistic effects were observed between Hu-IFN-gamma and RA in CCL-185 and HEP-2 cells. Human recombinant DNA-derived interferon-alpha 2 amplified the action of RA only in BT-20 cells, but it did not act synergistically with RA in the other cell lines tested.
Agreement between interrupter resistance and spirometry in a large population of asthmatic children
Authors: Nicole Beydon, Bruno Mahut, Maingot Lucia, Houda Guillo, Marie-Claude La Rocca, Noria Medjahdi, Marc Koskas, Michèle Boulé, Christophe Delclaux
Journal: European Respiratory Journal (2011)

Background:  Interrupter resistance (Rint) is routinely used to assess airway patency in children, but its relationship with spirometry has never been assessed in a large population of children.   Objectives:  A retrospective study to compare baseline values and post-bronchodilator (post-BD) changes in Rint and spirometry in asthmatic children.   Methods:  Rint measures (SpiroDyn9R, Dyn9R, France) were performed before spirometry (Masterscreen, Jaeger, Germany). Statistics: correlations between baseline Rint and FEV1 or FEF2575%, and ROC study for the Rint cutoff to distinguish between children with and without reversibility in FEV1 (>12% baseline).   Results:  Data from 645 children (408 boys, median (range) age 7.9 (4.2-18.3) y) showed significant correlations between Rint and FEV1 or FEF2575% (r=0.69 and 0.71, respectively for raw data, and r=0.49 and 0.54, respectively for% of predicted; all p  Reversibility in FEV1 (270 children) was best detected by a -35% of predicted Rint decrease (AUC=0.79, 0.70 sensitivity and specificity).   Conclusion:  We found a good agreement between Rint and spirometry to assess airway caliber and study BDeffect.
National Industry's Interest in Colorectal Cancer Screening Programmes
Authors: A R Hart, T L Barone, A C B Wicks, J F Mayberry
Journal: Journal of the Royal Society of Medicine (1994)

The interest of the largest 200 British industries in developing and financing colorectal screening services for employees was determined. A standard questionnaire asked if the company would advertise screening supply names of employees to local hospitals and finance faecal occult blood testing. The reasons for rejection were noted. Eighty-six companies returned the questionnaire (43% response rate) of which 78 firms (39% of the total mailed) were prepared to advertise screening programmes at the workplace. A quarter of the companies were prepared to both advertise and release employee details. Companies willing to participate employed significantly more people (mean of 17 000 employees) than those rejecting screening (mean of 6100 employees, Mann-Whitney U test=7, P&gt;0.05). Fifty-nine industries would consider financing screening, although only five made a definite decision to do so. All companies rejecting (36/36) were concerned about releasing employee information to hospitals. If screening does reduce mortality and community programmes are developed industry could and is prepared to advertise such programmes. If a partnership between hospitals and industry is developed, concerns about employee confidentiality needs to be addressed.
Exogenous norepinephrine induces an enhanced microproteinuric response in microalbuminuric insulin-dependent diabetes mellitus.
Authors: K Hoogenberg, W J Sluiter, G Navis, T W Van Haeften, A J Smit, W D Reitsma, R P Dullaart
Journal: Journal of the American Society of Nephrology (1998)

Exogenous norepinephrine (NE) increases intraglomerular pressure in animal experiments, but it is unknown whether NE induces a microproteinuric response in humans. Moreover, it has not been studied whether possible microproteinuric and renal hemodynamic changes induced by NE are altered in insulin-dependent diabetes mellitus (IDDM) complicated by microalbuminuria. Therefore, the microproteinuric and renal hemodynamic responses to exogenous NE infusions were measured in eight matched normoalbuminuric IDDM patients (group D1), microalbuminuric IDDM patients (group D2), and control subjects (group C). As anticipated, mean arterial pressure (MAP)-NE dose-response curves were significantly shifted leftward in groups D1 and D2 compared with group C (P < 0.05), indicating a higher systemic NE responsiveness in IDDM. On separate days, NE or placebo was infused at individually determined NE threshold doses (T; delta MAP = 0 mmHg), 20% pressor doses (20% P; delta MAP = 4 mmHg), and pressor doses (P; delta MAP = 20 mmHg), with measurement of urinary albumin (UalbV), IgG excretion (UIgGV), GFR (by 125I-iothalamate), and effective renal plasma flow (by 131I-hippurate). At NE pressor dose, UalbV and UIgGV rose in all groups (P < 0.05 to 0.01), whereas urinary beta 2-microglobulin was unchanged. The increases in UalbV and UIgGV were more pronounced in the microalbuminuric group than in the other groups (P < 0.05). An NE dose-dependent fall in effective renal plasma flow and rise in filtration fraction were found in all groups (P < 0.05 to 0.001 for all), whereas GFR did not change significantly. The renal hemodynamic dose-response relationship was similar in the groups. In conclusion, exogenous NE acutely promotes glomerular protein leakage, and it is plausible that intraglomerular NE effects contribute to this phenomenon. The microproteinuric response is enhanced in microalbuminuric IDDM despite unaltered renal hemodynamic responsiveness, which may reflect a specific NE response or a general effect of vasopressor stimuli to promote glomerular protein leakage in patients with a preexistent defect in glomerular permselectivity.
Emergency Surgery: Atavistic Refuge of the General Surgeon?
Authors: B J A Lankester, D C Britton, A G Holbrook, H C Umpleby, J J T Tate, J Budd, P R Maddox, M Horrocks
Journal: Journal of the Royal Society of Medicine (2001)

A prospective audit of emergency soft-tissue surgery for an eight-week period revealed that general surgical emergency operations were more than twice as common as those undertaken in other soft-tissue specialties. The audit reveals that emergency general surgery needs an increase in resources, an increase in available staff and an increase in the role of the consultant general surgeon on call. An alternative solution would be to admit soft-tissue emergencies by specialty and develop specialist emergency services.
Psychomotor and Clinical Assessment of Flumazenil as an Antagonist of Midazolam
Authors: K M Bill, J P H Fee, R S J Clarke
Journal: Journal of the Royal Society of Medicine (1991)

The benzodiazepine antagonist flumazenil (0.01 mg/kg) has been compared with doxapram (1 mg/kg) and saline for the reversal of anaesthesia with intravenous midazolam, alfentanil, nitrous oxide in oxygen and isoflurane. The completeness of reversal was assessed by means of a four-choice reaction time test, 1 and 3 h following the antagonist. In addition, the level of sedation was graded using a five-point scale. Psychomotor testing showed that 60 min after administration of the antagonist, there were marked increases in reaction times (P &lt; 0.05) both in the control and doxapram groups, but not in those receiving flumazenil. At 180 min, however, reaction times in all groups had returned to baseline values. In contrast, there was a significant difference in the sedation scores between the saline and flumazenil groups throughout the study period (P &lt; 0.05). During the 4 h following midazolam, there was no evidence of re-sedation in any of the groups despite the relatively high midazolam dosage.
Increased Serum Concentration of Angiogenic Factors in Malignant Melanoma Patients Correlates With Tumor Progression and Survival
Authors: Selma Ugurel, Gunter Rappl, Wolfgang Tilgen, Uwe Reinhold
Journal: Journal of Clinical Oncology (2001)

To determine the predictive value of the angiogenic serum factors angiogenin, vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), and interleukin-8 (IL-8) for the prognosis of patients with malignant melanoma.Angiogenin, VEGF, bFGF, and IL-8 were measured in sera of 125 melanoma patients with different stages of disease and with or without current therapy including interferon alfa and different cytostatics in comparison with 30 healthy controls using enzyme-linked immunosorbent assay.Serum levels of angiogenin, VEGF, bFGF, and IL-8 were significantly increased in melanoma patients compared with healthy controls. Elevated serum concentrations of VEGF, bFGF, and IL-8 were associated with advanced disease stages and tumor burden. Cytostatic therapy of patients was accompanied by increased serum levels of angiogenin, bFGF, and IL-8. As shown by univariate analysis, elevated serum levels of VEGF (P = .0001 and .0036), bFGF (P < .00005 and < .00005), and IL-8 (P < .00005 and < .00005) were strongly correlated with a poor overall and progression-free survival, respectively. Multivariate analysis revealed stage of disease (P = .0238), tumor burden (P = .0347), VEGF (P = .0036), bFGF (P = .0252), and IL-8 (P = .0447) as independent predictive factors of overall survival. Tumor burden (P = .0081), VEGF (P = .0245), and IL-8 (P = .0089) were found as independent predictive factors of progression-free survival.Our data suggest that the angiogenic serum factors VEGF, bFGF, and IL-8 are useful predictive markers for overall and progression-free survival in melanoma patients.
Peak Expiratory Flow Profiles Delivered by Pump Systems
Authors: MARTIN R. MILLER, BARRIE JONES, YONG XU, OLE FIND PEDERSEN, PHILIP H. QUANJER
Journal: American Journal of Respiratory and Critical Care Medicine (2000)

Pump systems are currently used to test the performance of both spirometers and peak expiratory flow (PEF) meters, but for certain flow profiles the input signal (i.e., requested profile) and the output profile can differ. We developed a mathematical model of wave action within a pump and compared the recorded flow profiles with both the input profiles and the output predicted by the model. Three American Thoracic Society (ATS) flow profiles and four artificial flow-versus-time profiles were delivered by a pump, first to a pneumotachograph (PT) on its own, then to the PT with a 32-cm upstream extension tube (which would favor wave action), and lastly with the PT in series with and immediately downstream to a mini-Wright peak flow meter. With the PT on its own, recorded flow for the seven profiles was 2.4 ± 1.9% (mean ± SD) higher than the pump's input flow, and similarly was 2.3 ± 2.3% higher than the pump's output flow as predicted by the model. With the extension tube in place, the recorded flow was 6.6 ± 6.4% higher than the input flow (range: 0.1 to 18.4%), but was only 1.2 ± 2.5% higher than the output flow predicted by the model (range: − 0.8 to 5.2%). With the mini-Wright meter in series, the flow recorded by the PT was on average 6.1 ± 9.1% below the input flow (range: − 23.8 to 2.5%), but was only 0.6 ± 3.3% above the pump's output flow predicted by the model (range: − 5.5 to 3.9%). The mini-Wright meter's reading (corrected for its nonlinearity) was on average 1.3 ± 3.6% below the model's predicted output flow (range: − 9.0 to 1.5%). The mini-Wright meter would be deemed outside ATS limits for accuracy for three of the seven profiles when compared with the pump's input PEF, but this would be true for only one profile when compared with the pump's output PEF as predicted by the model. Our study shows that the output flow from pump systems can differ from the input waveform depending on the operating configuration. This effect can be predicted with reasonable accuracy using a model based on nonsteady flow analysis that takes account of pressure wave reflections within pump systems.
Abnormal vitamin D status negatively affects lung function and inflammation in smoking mice
Authors: Nele Heulens, Nele Cielen, Elien De Smidt, Karen Maes, Chantal Mathieu, Ghislaine Gayan-Ramirez, Wim Janssens, Hannelie Korf
Journal: European Respiratory Journal (2014)

Background : Increasing evidence suggests a role for vitamin D (vitD) in chronic obstructive pulmonary disease (COPD). Our aim was to investigate the effect of vitD status on disease progression, airway inflammation and alveolar macrophage (AM) antimicrobial function in a mouse model of smoke-induced COPD.

Methods : Mice that received a diet containing either low-, normal- or high vitD were daily exposed to cigarette smoke or ambient air. After 6 and 12 weeks of smoking, lung function and inflammatory cells in the bronchoalveolar lavage fluid were determined. The ex vivo phagocytic- and oxidative burst capacity of AM following interaction with E. coli was assessed.

Results : Mice with low- or high vitD levels showed an earlier increase in total lung capacity and compliance with smoking compared to mice with normal vitD levels. Similarly, mice with an abnormal vitD status featured an exacerbated neutrophilic inflammation after 6 and 12 weeks of smoke exposure. Smoking characteristically resulted in a significant decrease of AM phagocytic- and oxidative burst function. AM of mice with abnormal vitD levels showed a further decrease in oxidative burst capacity, but bacterial engulfment was not further affected.

Conclusion : Insufficient- or overabundant vitD levels lead to an early onset of smoke-induced emphysema, elevated neutrophilic inflammation and a more pronounced defective oxidative burst capacity of AM.

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A case of paraneoplastic pemphigus associated with triple malignancies in combination with antilaminin-332 mucous membrane pemphigoid
Authors: H. Yamada, Y. Nobeyama, K. Matsuo, T. Ishiji, T. Takeuchi, S. Fukuda, T. Hashimoto, H. Nakagawa
Journal: British Journal of Dermatology (2011)

Madam, A 68‐year‐old Japanese man presented with a 2‐month history of painful erosions on the oral mucosa and glans penis and conjunctival hyperaemia, as well as a 1‐month history of polymorphic cutaneous lesions. He was treated with systemic and topical corticosteroids for 1 month at another hospital, with no improvement. At his first visit to our hospital, he had erosive lesions on the oral mucosa, lips and glans penis (Fig. 1) and multiple vesiculobullous skin lesions with crusts surrounded by erythema scattered on the trunk and extremities. Skin biopsy from erosive lesions on the lip and lichenoid papules on the back revealed scattered necrotic keratinocytes in the epidermis, vacuolization in the basal layer, and a band‐like lymphocytic infiltration throughout the papillary dermis. Direct immunofluorescence (IF) showed linear and granular deposition of IgG on keratinocyte cell surfaces and at the dermal–epidermal junction with unclear serration pattern, while indirect IF detected antibasement membrane zone IgG antibodies at a titre of 1 : 40 at the dermal side of 1 mol L−1 Salt‐split normal human skin. The assay also detected IgG antibodies at a titre of 1 : 160 against normal human keratinocyte cell surfaces and at a titre of 1 : 160 against the cell surfaces of rat bladder epithelium, but failed to detect antibodies against normal human basement membrane zone.
Clinical experience with oral methadone administration in the treatment of pain in 196 advanced cancer patients.
Authors: F De Conno, L Groff, C Brunelli, E Zecca, V Ventafridda, C Ripamonti
Journal: Journal of Clinical Oncology (1996)

PURPOSE The aims of this study were to describe the analgesia, side effects, and dosage and the causes of suspension of treatment in a large sample of advanced cancer patients with pain after treatment with oral methadone from 7 to 90 days. PATIENTS AND METHODS In a retrospective study, data collected for 196 advanced cancer outpatients with moderate to severe pain treated at 8-hour intervals with oral methadone in solution form from February 1993 to February 1995 were analyzed at baseline (time 0) and then at 7, 15, 30, 45, 60, and 90 days. The following parameters were assessed: Karnofsky Performance Status, intensity of pain (using the Integrated Pain Score [IPS], intensity of pain, insomnia, drowsiness, confusion, dry mouth, nausea, vomiting, constipation, and dyspnea (using the Therapy Impact Questionnaire [TIQ], mean daily dose of drug administered, and reasons for withdrawal from study. The period when pain was reduced by &gt; or = 35% with respect to baseline was evaluated with the Palliation Index. The association of the degree of palliation of pain with the age of the patients, tumor site, analgesic treatment taken at baseline, and daily mean dose of methadone administered during the follow-up period was analyzed by means of the Kruskal-Wallis test. RESULTS A reduction in pain intensity with respect to baseline occurred at each analysis time, and in 55.1% of the patients the reduction during the follow-up period was &gt; or = 35% according to the Palliation Index. The mean dose of oral methadone ranged from 14 mg at day 7 to 23.65 mg at day 90. There was an overall worsening of the other symptoms, but a high percentage of the patients reported an amelioration of insomnia with respect to baseline. There was a statistically significant association (P &lt; .0001) between the Palliation Index and the analgesic therapy administered at baseline. Only 11.2% of the patients withdrew from the study due to analgesic inefficacy and 6.6% due to methadone-related side effects (10 patients with drowsiness and three with severe constipation. CONCLUSION Oral methadone administered every 8 hours was shown to be an appropriate analgesic therapy in the treatment of advanced cancer-related pain. The worsening of the other symptoms under study can be considered linked to the progression of the disease, and in fact, only a small percentage of the patients reported methadone-related side effects that warranted suspension of treatment. We consider oral methadone to be a useful analgesic therapy, and it should be considered in clinical practice for the treatment of cancer pain.