tbuckley/cabot-search huggingface dataset:
Prostate-specific antigen nadir: the optimum level after irradiation for prostate cancer.
Authors: F A Critz, A K Levinson, W H Williams, D A Holladay
Journal: Journal of Clinical Oncology (1996)

The prostate-specific antigen (PSA) nadir that reflects potential cure of prostate cancer by irradiation has not been established. This report attempts to demonstrate the PSA nadir goal for radiotherapy.From January 1984 through April 1994, 536 stage T1T2NO prostate cancer patients were treated with radioactive iodine 125 (125I) prostate implants followed by external-beam radiation. All were staged node-negative: 68% by pelvic node dissection and the remainder by computed tomographic (CT) scan. The mean pretreatment PSA level was 12.4 ng/mL (median, 8.4 ng/mL; range, 0.3 to 188 ng/mL). The median follow-up duration is 40 months (range, 12 to 138). An increasing posttreatment PSA level defined recurrence.Patients who achieved a PSA nadir < or = 0.5 ng/mL had a 95% (+/- 4%) 5-year and an 84% (+/- 12%) 10-year disease-free survival rate, compared with a 5-year disease-free survival rate of 29% (+/- 30%) for those who reached a nadir of 0.6 to 1.0 ng/mL (P = .0001). All patients with a nadir greater than 1.0 ng/mL ultimately failed. Eighty percent of all 536 patients are projected to achieve a nadir < or = 0.5 ng/mL and 90% of patients who achieve this PSA level do so within 48 months of treatment (median, 18 months). Compared with pretreatment PSA level and histologic grade, the PSA nadir is the most significant factor associated with disease-free survival.For most patients to be successfully treated for prostate cancer with radiotherapy, at least with this combination technique, the PSA nadir should become undetectable (< or = 0.5 ng/mL), similar to that after radical prostatectomy. A PSA nadir of < or = 0.5 ng/mL after radiotherapy for prostate cancer may be used as a reasonable indicator of 10-year disease-free survival.
Educational and motivational support service: a pilot study for mobile-phone-based interventions in patients with psoriasis
Authors: N. Balato, M. Megna, L. Di Costanzo, A. Balato, F. Ayala
Journal: British Journal of Dermatology (2012)

Background Psoriasis is a chronic disease which requires long‐term therapy. Therefore, adherence to therapy and patient motivation are key points in controlling the disease. Mobile‐phone‐based interventions, and in particular text messages (TM), have already been used effectively to motivate patients and improve treatment adherence in many different chronic diseases such as diabetes, cardiovascular disease and asthma. Objectives To evaluate the use of TM in improving treatment adherence and several patient outcomes such as quality of life, disease severity, patient‐perceived disease severity and the patient–physician relationship. Patients and methods Daily TM, providing reminders and educational tools, were sent for 12 weeks to a group of 20 patients with psoriasis. At the beginning and end of the study the following assessments were performed: Psoriasis Area Severity Index (PASI), Self‐Administered Psoriasis Area Severity Index (SAPASI), body surface area (BSA), Physician Global Assessment (PGA), Dermatology Life Quality Index (DLQI), evaluation of patient–physician relationship and adherence to therapy. A matched control group of 20 patients with psoriasis was used for comparison of the same outcomes. Results Both patient groups had similar scores for PASI, SAPASI, BSA, PGA and DLQI at baseline. However, after 12 weeks the intervention group reported a significantly better improvement of disease severity as well as quality of life, showing lower values of PASI, SAPASI, BSA, PGA and DLQI with respect to the control group (P <0·05). Moreover, adherence to therapy improved in a statistically significant way (P <0·001) whereas it remained stable in the control group. Similarly, TM interventions led to an optimization of patient–physician communication. Conclusions TM interventions seem to be a very promising tool for the long‐term management of patients with psoriasis, leading to an increased compliance to therapy, positive changes in self‐care behaviours and better patient–physician relationship allowing improved clinical outcomes and better control of the disease.
Inhibition of Macrophage-Mediated Tumor Cell Destruction by Oxidized Lipoproteins2
Authors: Louis B. Justement, Suman T. Patel, Howard A. I. Newman, Bruce S. Zwilling
Journal: JNCI Journal of the National Cancer Institute (1984)

Lipoproteins (LP), isolated from human sera by column chromatography and density ultracentrifugation, were tested for their ability to inhibit macrophage (Mø)-mediated tumor cell destruction. None of the LP subclasses isolated by ultracentrifugation inhibited Mø-mediated cytolysis. Chromatography on a Sephadex G-200 column, prior to or following ultracentrifugation, resulted in the isolation of very low-density lipoprotein (VLDL) and low-density lipoprotein (LDL) that prevented tumor cell destruction by Mø. High-density lipoprotein did not acquire the ability to inhibit Mø-mediated tumor cell killing under any condition. The acquisition of inhibitory activity by VLDL and LDL subclasses could be prevented by incorporation of EDTA and the bubbling of nitrogen gas into the chromatography buffer. These conditions inhibited the formation of lipid peroxides and thus prevented the formation of LP that inhibit Mø-mediated cytotoxicity. The mechanism by which oxidized LP prevents Mø from destroying tumor targets is not known. However, the mechanism does not appear to be related to a decrease in Mø viability.
Colchicine interferes with L-selectin and leukocyte function-associated antigen-1 expression on human T lymphocytes and inhibits T cell activation.
Authors: N Perico, D Ostermann, M Bontempeill, M Morigi, C S Amuchastegui, C Zoja, E Akalin, M H Sayegh, G Remuzzi
Journal: Journal of the American Society of Nephrology (1996)

Colchicine, which inhibits cell microtubule assembly by preventing polymerization of tubulin monomers, inhibits cell-mediated immune responses and promotes long-term survival of major histocompatibility complex-incompatible renal allografts in rats. Here we evaluated the effect of blocking cell microtubule assembly by colchicine on T cell and endothelial cell adhesion receptors involved in transducing signals for T cell activation. By using immunofluorescence flow cytometry analysis, evidence is presented that colchicine, in a dose-dependent fashion, downregulated L-selectin and leukocyte function-associated antigen-1, but not CD2 and CD44 on the surface of naive human peripheral blood lymphocytes. This effect was confirmed in two subsets of T lymphocytes, namely, CD45RA- and CD45RO-positive cells. However, colchicine did not influence the rapid shedding of L-selectin from T lymphocytes exposed to activating stimuli. Colchicine inhibited expression of interleukin-2 receptor on activated T lymphocytes. This effect was observed when T lymphocytes were stimulated with both anti-CD3 and anti L-selectin monoclonal antibodies. Colchicine also inhibited lymphocyte function in vitro as documented by inhibition of the human mixed lymphocyte response in a dose-dependent fashion. Moreover, colchicine downregulated surface expression of intercellular adhesion molecule-1 and E-selectin on activated human umbilical vein endothelial cells. These results indicate that blocking cell microfubule assembly inhibits surface expression of adhesion molecules on T cells and endothelial cells, and provides insights into the complex mechanisms of the action of colchicine in vivo.
Acral Lentiginous Melanoma
Authors: Mildred P Warren, Valerie M Harvey
Journal: New England Journal of Medicine (2015)

A 68-year-old man presented with a 2-year history of a nonhealing ulceration on the left heel. Physical examination revealed an ulcerated black plaque measuring 5.5 cm by 6.5 cm. An excisional biopsy showed an acral lentiginous melanoma with a Breslow depth of 2.0 mm.
Abstract 20512: Cortactin Binds to a Novel Focal Adhesion Protein, EVL, During Endothelial Cytoskeleton Rearrangement
Authors: Joseph B Mascarenhas, Mary E Brown, Ting Wang, Joe G Garcia, Dudek M Steven
Journal: Circulation (2014)

The endothelial cell (EC) cytoskeleton is a complex array of proteins intimately involved in the diverse cell shape changes critical to dynamic regulation of lung vascular barrier integrity, particularly in the phases of onset and recovery during ARDS and VILI. Cortactin is structurally designed to be a central actin filament regulatory protein with an SH3 domain that directly binds non-muscle myosin light chain kinase (nmMLCK) and other effectors, and an acidic N-terminus that directly binds to Arp2/3, the protein complex regulating actin branching. In this study, we demonstrate cortactin binding to a focal adhesion protein, EVL, an actin polymerization-enhancing effector involved in linear actin filament formation and cortactin-mediated EC cytoskeleton regulation. To confirm the binding of cortactin to other cytoskeleton effector proteins, including nmMLCK, we generated a unique GFP-tagged proline-deficient nmMLCK mutant predicted to alter cortactin SH3 binding to MLCK. EC transfected with GFP-tagged proline-deficient nmMLCK mutant construct exhibit significantly higher stress fiber density and reduced localization in the cell periphery, highlighting the regulatory influence of cortactin on nmmLCK spatial localization. Cortactin-nmMLCK interaction is increased by tyrosine phosphorylation of either nmMLCK or cortactin by c-Abl, during S1P mediated cytoskeleton rearrangement. Importantly, c-Abl-mediated nmMLCK phosphorylation reverses nmMLCK’s inhibitory effects on cortactin/Arp2/3-induced pyrene-labeled actin polymerization. Cortactin binds to EVL, at basal level, with binding promoted during cytoskeleton rearrangement stimulated by S1P. The binding with EVL is critical for the cortactin translocation and interaction with nmMLCK in lamellipodia, as the silencing of EVL by siRNA significantly attenuated these essential cellular events (lamellipodia formation, cortactin translocation to lamellipodia, and binding of cortactin with nmMLCK) during cytoskeleton rearrangement. These findings reveal novel cellular mechanisms of endothelial cytoskeleton rearrangement and barrier function in ARDS and VILI.
AMPK Activation of Muscle Autophagy Prevents Fasting-Induced Hypoglycemia and Myopathy during Aging
Authors: Adam L. Bujak, Justin D. Crane, James S. Lally, Rebecca J. Ford, Sally J. Kang, Irena A. Rebalka, Alex E. Green, Bruce E. Kemp, Thomas J. Hawke, Jonathan D. Schertzer, Gregory R. Steinberg
Journal: Cell Metabolism (2015)
Autologous bone marrow transplantation for adult poor-risk lymphoblastic lymphoma in first remission.
Authors: L F Verdonck, A W Dekker, G C de Gast, H M Lokhorst, H K Nieuwenhuis
Journal: Journal of Clinical Oncology (1992)

PURPOSE Adult patients with poor-risk lymphoblastic lymphoma (LBL) treated with intensive multiagent chemotherapy (acute lymphoblastic leukemia [ALL]-like regimens) have a poor prognosis, with a disease-free long-term survival rate of less than 20%, caused by a very high relapse rate. Thus, adult patients with poor-risk LBL are candidates for alternative intensive consolidation therapy. PATIENTS AND METHODS Nine adult patients with poor-risk LBL in first remission after treatment with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP; six patients) or ALL-like regimens (three patients), were treated with high-dose cyclophosphamide and total body irradiation (TBI) followed by nonpurged autologous bone marrow transplantation (ABMT). RESULTS Two of nine patients relapsed at 4 and 8 months, respectively, after BMT, and one patient died of acute myeloblastic leukemia (AML) 7 months after ABMT without recurrence of his lymphoma. Six patients are in unmaintained first remission with a follow-up of 12 to 113 months (median, 53 months) after transplantation. CONCLUSIONS These results suggest that intensive consolidation therapy with high-dose cyclophosphamide and TBI followed by nonpurged ABMT may improve the long-term prognosis of this disease.
Unilateral nephrectomy and cisplatin as risk factors of ifosfamide-induced nephrotoxicity: analysis of 120 patients.
Authors: R Rossi, A Gödde, A Kleinebrand, M Riepenhausen, J Boos, J Ritter, H Jürgens
Journal: Journal of Clinical Oncology (1994)

PURPOSE This study was performed to identify risk factors of ifosfamide-induced renal damage. PATIENTS AND METHODS Renal function was assessed in 120 patients at a minimum of 3 months after completion of chemotherapy including ifosfamide. The cumulative ifosfamide dose ranged from 2 to 95 g/m2 (median, 30 g/m2). Ten patients had undergone unilateral nephrectomy; combination cytostatic treatment included cisplatin in 51 and methotrexate in 57. Sixty-eight patients had received gentamicin treatment. The glomerular filtration rate was estimated using the Schwartz formula. Proximal tubular function was assessed by the percent reabsorptions of glucose and 16 amino acids, the fractional excretion of sodium, and the fractional reabsorption of phosphate. In addition, the serum bicarbonate level was measured. RESULTS Proximal tubular dysfunction--with a predominance of renal amino acid (66.3%) and phosphate loss (38.3%)--was much more frequent than both glomerular impairment and acidosis. Seven patients were identified as having renal Fanconi's syndrome, and generalized tubulopathy was noted in another 15 patients. Ifosfamide-induced nephrotoxicity was dose-dependent, with a weak linear inverse correlation between cumulative ifosfamide dose and fractional phosphate reabsorption. Unilateral nephrectomy proved to be the single most important risk factor (odds ratio for the development of renal Fanconi's syndrome, 11.4), but cisplatin also significantly enhanced ifosfamide-mediated nephrotoxicity. Methotrexate, gentamicin, and patient age at primary diagnosis had no influence on renal function. CONCLUSION Ifosfamide chemotherapy should probably be restricted in patients after unilateral nephrectomy.
Peripheral blood mononuclear cells express mutated NCCT mRNA in Gitelman's syndrome
Authors: N Abuladze, N Yanagawa, I Lee, O D Jo, D Newman, J Hwang, K Uyemura, A Pushkin, R L Modlin, I Kurtz
Journal: Journal of the American Society of Nephrology (1998)

Genetic analysis has demonstrated complete linkage between the human thiazide-sensitive sodium chloride cotransporter gene (NCCT or TSC) and Gitelman's syndrome (GS). Several genomic NCCT mutations have been reported. This study was performed to determine whether peripheral blood mononuclear cells (PBMC) express NCCT mRNA and whether defective PBMC NaCl cotransport could be demonstrated in GS. PBMC were isolated from two brothers with GS, their parents, and healthy control subjects. Northern analysis revealed that NCCT mRNA is expressed in PBMC. The sequence of full-length NCCT cDNA amplified from normal PBMC was identical to human renal NCCT cDNA. Two different mutations were detected in the patients' NCCT cDNA (compound heterozygote). In cDNA derived from the patient's maternal allele, exon 24 was deleted, resulting in a premature stop codon (after amino acid 920). cDNA derived from the patient's paternal allele had an additional 119-bp insertion between exons 3 and 4, generating a premature stop codon (after amino acid 187). The patient's genomic DNA had a previously described 5' splice site mutation in intron 24, GGT --> GTT (maternal allele), and a new 3' splice site mutation in intron 3, CAG --> CAA (paternal allele), which resulted in the activation of a nearby cryptic splice site in intron 3. The latter mutation was not present in 300 normal chromosomes. To determine the functional significance of these findings, chlorothiazide-inhibitable 22Na uptake was measured in PBMC from control subjects, the parents, and the patients with GS in the presence of bumetanide. In control PBMC, chlorothiazide inhibited 22Na uptake by approximately 9%. PBMC from the two patients with GS failed to respond to chlorothiazide. These results demonstrate that PBMC can be used for mutational analysis of NCCT mRNA in patients with GS. Furthermore, functional evidence is provided that the underlying cause of GS is defective NCCT NaCl cotransport.
Associations between obstructive sleep apnea syndrome (OSAS) and chronic airflow limitation in a general Norwegian population
Authors: Trygve Jonassen, Tomas M.L. Eagan, Sverre Lehmann
Journal: European Respiratory Journal (2012)

Background: Several studies have investigated associations between OSAS and obstructive airway disease, with inconsistent results.  Aim: To study the relationship between OSAS and pulmonary function in a general Norwegian population.  Methods: An age and sex stratified random sample of all adults aged 47-48 and 71-73 living in Bergen, Norway, were invited to a cross-sectional study. The 3506 attendants completed a questionnaire including symptoms of OSAS. Subjects were classified as having OSAS if they reported snoring, breathing cessations, and daytime sleepiness using the Karolinska Sleep Questionnaire, previously validated against polysomnography. Spirometry including bronchodilator test inhaling 400 ug Salbutamol was performed by all subjects. Logistic regression analyses, including interaction analyses between sex and pulmonary function, were used to examine associations between OSAS and pre- and postbronchodilator (postBD) FEV1, FVC and FEV1/FVC.  Results: The prevalence of OSAS was 4,8% (20/322) in subjects with chronic airflow limitation as defined by postBD FEV1/FVC 0,7 [P=0.74]. FEV1 and FVC (% of predicted) were not associated with increased risk of OSAS, after adjustment for age, sex, BMI, waist-hip ratio and smoking. Women with postBD FEV1/FVC 0.7, but this relationship was not present among men; OR 0,70 (0.31-1.58).  Conclusions: Chronic airflow limitation, assessed by post bronchodilator spirometry, was associated with OSAS among women only. There was no relationship between OSAS and FEV1 or FVC.
Cost-effectiveness of a structured treatment and teaching programme on asthma
Authors: C Trautner, B Richter, M Berger
Journal: European Respiratory Journal (1993)

The purpose of this study was to perform a cost-effectiveness analysis of the structured treatment and teaching programme for patients with asthma (ATTP) at Düsseldorf University. We investigated whether the monetary benefits outweighed the costs of the intervention. Adult patients with moderate to severe asthma participated in a 5 day in-patient programme. Follow-up was 3 yrs. The incremental costs and benefits of the intervention, compared with standard treatment, were calculated. Costs were incurred by the hospitalization and by lost productivity. Compared to the year before the programme, (average reduction) days spent in hospital (5.2 days per patient per year), days of absence from work (18.4 days per patient per year), acute severe asthma attacks (3.8 attacks per patient per year), and physician consultations (2.3 visits per patient per month), decreased in the 3 yrs after the intervention. The programme produced net benefits of DM 12,850 (in 1991 German marks) per patient within 3 yrs. Within the health care sector, the net benefits were DM 5,900. Within 3 yrs, the paying bodies saved DM 2.70, and society as a whole saved DM 5 on each DM spent for the programme. We conclude that the intervention produced net monetary benefits. This result was stable over a wide range of variation of the outcome measures. Therefore, programme deserves implementation, not only for its demonstrated medical benefits but also for its economic savings.
Global health experts warn of a “looming co-epidemic” of tuberculosis and diabetes
Authors: Sophie Cousins
Journal: BMJ (2015)

More needs to be done to tackle the growth in the number of patients who have both tuberculosis (TB) and diabetes, global health experts have said.

Over 100 delegates attending a two day summit in Bali, Indonesia, this week—organised by the International Union Against Tuberculosis and Lung Disease, the World Diabetes Foundation, and the Ministry of Health of the Government of Indonesia—signed a declaration warning that the two illnesses represented a “looming co-epidemic.”

Studies have shown that diabetes weakens the immune system, making those affected around three times more likely to …
Type II transmembrane serine protease matriptase is a mediator of pulmonary fibrosis
Authors: Olivier Bardou, Charlene Francois, Nicolas Carlier, Herve Mal, Bruno Crestani, Keren Borensztajn
Journal: European Respiratory Journal (2013)

Idiopathic pulmonary fibrosis (IPF) is a devastating lung disorder which remains refractory to therapies. Recently, type II transmembrane serine proteases have emerged as key actors in pathophysiology, by proteolysis of cell surface receptors and/or cell environment, thereby orchestrating cell crosstalks. Among them, deregulation of the matriptase contributes to various proliferative disorders. Hence, we sought to investigate the role of matriptase in pulmlonary fibrosis.  Matriptase expression and activity were analyzed in human lung material from controls and IPF patients. Human fibroblasts were stimulated with recombinant matriptase and the activation of key signaling pathways involved in IPF was analyzed. Using the murine model of bleomycin-induced pulmonary fibrosis, mice were administrated for 14 days with 0 or 0.5mg of camostat mesylate, a matriptase inhibitor, and the markers of tissue fibrosis in lung homogenate, and inflammatory cell influx in the bronchoalveolar lavage fluid (BALF) of the animals were assessed.  We show that matriptase is upregulated in the lung and BALF of IPF patients compared to controls. In fibroblasts, matriptase induced the activation of p42/44, Akt, and Smad2/3 pathways. Finally, camostat administration in bleomycin-treated mice led to a significant decrease in mortality (39.3% versus 60.4% in bleomycin-treated group). Fibronectin and collagen expression, and inflammatory cell influx, were not significantly different from saline-treated animals in the camostat group.Taken together, matriptase seems instrumental in pulmonary fibrosis, and camostat mesylat could be a promising target for thetreatment of IPF.
Assessment of exercise capacity in patients with chronic heart failure (CHF) and COPD
Authors: Carlos Andrés Quezada Loaiza, Marta Iscar Urrutia, Miguel Angel Ariza Prota, Juan Alejandro Cascón Hernandez, Herminia Buchelli, David Fole, Ramon Fernandez, Gemma Rubinos, Maria José Vazquez, Begoña Palomo, Pere Casan Clarà, Beatriz Molina, María Angeles Montoliú
Journal: European Respiratory Journal (2013)

Ergospirometry is gold standard for assessing cardiopulmonary adaptation to exercise. Exercise tolerance is prognostic factor heart failure (CHF).  OBJECTIVE: Compare exercise capacity in patients with COPD/CHF and CHF patients only.  METHODS: Prospective study 122 patients with CHF. Spirometry and Ergospirometry were performed with analysis of expired gases, up to the anaerobic threshold. Underlying heart disease, diagnosis of COPD, FVC, FEV1 and FEV1/FVC, oxygen consumption, carbon production, ventilation, and heart rate test time and met Bruce stage were assesed.  RESULTS: The mean age was 59 + 8 years. 78% male. The 27% have a diagnosis of COPD. The 29% are obese. Table I shows GOLD classification and type of heart disease.  In Table II shows VO2 ml / kg / min and the EqCO2. Bruce reached the stage for COPD / CHF: I 7% II 35% 27% III, IV 31% and for the CHF group: I 17% II 14% 34% III, IV 30% V 6%.  CONCLUSIONS:  1. Patients diagnosed with COPD and CHF have higher exercise limitation evidenced by early completion in the stress test, lower oxygen consumption and ventilatory equivalent of CO2 increased.  2. Functional assessment of patients with CHF should also include the assessment of lung function.