tbuckley/cabot-search huggingface dataset:
ABC of arterial and venous disease: Swollen lower limb---2: Lymphoedema
Authors: P. S Mortimer
Journal: BMJ (2000)

Lymph conducting pathways may become reduced in number, obliterated, obstructed, or dysfunctional (because of failure of contractility or valve incompetence). A lack of sensitive methods for investigation makes it difficult to distinguish between these mechanisms. A defect in the lymph conducting pathways leads to primary lymphoedema; in practice this means no identifiable outside cause can be found. Secondary lymphoedema is due to factors originating outside the lymphatic system.



Classification of primary lymphoedema



Congenital lymphoedema presenting at or soon after birth is rare. A family history suggests Milroy's disease. Swelling invariably affects both lower limbs, but the upper limbs and face may also swell.

Limb swelling may be the presenting and major manifestation of congenital lymphatic malformations either in a pure form—for example, diffuse lymphangioma—or in combination with a congenital vascular syndrome—for example, Klippel-Trenaunay syndrome (varicose veins, excessive long bone growth, and vascular birthmark).



Primary lymphoedema with bilateral below knee swelling due to hypoplasia of peripheral lymphatic vessels



Most forms of primary lymphoedema present after puberty with foot and ankle swelling. Women are more often affected, and the condition may be familial—for example, Meige's disease. Lymph reflux due to lymphatic vessel hypertrophy or megalymphatics is clinically distinguishable.

Lymphoedema manifesting with sudden onset of swelling of one whole leg suggests proximal obstruction. Pelvic causes of venous or lymphatic …
An Evaluation of Risk Factors for Major Adverse Cardiovascular Events During Tocilizumab Therapy
Authors: Vijay U. Rao, Andrey Pavlov, Micki Klearman, David Musselman, Jon T. Giles, Joan M. Bathon, Naveed Sattar, Janet S. Lee
Journal: Arthritis & Rheumatology (2014)

Objective To evaluate associations between lipid levels, inflammation, and rheumatoid arthritis (RA) disease activity, at baseline and during treatment, with the risk of major adverse cardiovascular events (MACE) in tocilizumab‐treated patients with RA. Methods In retrospective post hoc analyses, data were pooled for 3,986 adult patients with moderate to severe RA who received ≥1 dose of tocilizumab (4 mg/kg or 8 mg/kg) intravenously every 4 weeks in randomized controlled trials and extension studies. Cox proportional hazards modeling was used to evaluate associations between baseline characteristics and posttreatment changes in laboratory and disease characteristics (week 24) and change in disease activity and laboratory values from baseline to week 24 with the risk of future MACE during extended followup. Results We identified 50 independently adjudicated cases of MACE during 14,683 patient‐years of followup (0.34 MACE cases/100 patient‐years). At baseline, age, a history of cardiac disorders, the Disease Activity Score in 28 joints (DAS28), and the total cholesterol:high‐density lipoprotein cholesterol ratio were independently associated with MACE in multivariable models ( P &lt; 0.05 for all). During treatment, a higher DAS28 and higher swollen and tender joint counts at week 24 were associated with future MACE. In separate models, greater reductions in the DAS28 and joint counts from baseline to week 24 were inversely associated with future MACE; changes in lipid parameters were not statistically significantly associated with the risk of MACE. Conclusion In this population of patients treated with tocilizumab, an association was observed between the baseline total cholesterol:high‐density lipoprotein cholesterol ratio and an increased risk of MACE. The risk of MACE while receiving treatment, however, was associated with control of disease activity but not lipid changes. Larger studies are needed to confirm these findings.
Use of discriminant analysis to assess pulmonary functional worsening in patients with sarcoidosis by means of a panel of inflammatory markers
Authors: Gregorino Paone, Maria Rulli, Alessandro Belli, Armanda Propati, Angelo Sbrocca, Salvatore D'Antonio, Alfredo Sebastiani, Giovanni Puglisi, Giovanni Galluccio, Sandro Batzella
Journal: European Respiratory Journal (2011)

Background:  Sarcoidosis9 protean clinical course has prompted many studies to discover biomarkers which could help to trace disease progression and response to therapy.   Aims:  In our study we performed discriminant analysis, to investigate whether a panel of selected markers measured in BALF and serum from patients with sarcoidosis would help to predict pulmonary functional worsening.   Methods:  We enrolled in the study 30 consecutive individuals with sarcoidosis. At enrolment participants underwent pulmonary function tests, fiber-optic bronchoscopy and radiological evaluation. PFTs were also performed at follow-up visits during a 2 year period. Pulmonary function worsening was defined as a decline of TLC, FVC, FEV1> 15% and DLCO > 10%. BALF differential cell counts were performed in all participants and BAL and serum ECP, MPO, Tryptase, PIIIP and SIL2r concentrations were quantified by RIA and ELISA tests. Discriminant analysis was performed to optimize the accuracy of selected variables in predicting functional worsening.   Results:  Pulmonary function worsening was observed in 24% of participants. Applying discriminant analysis function a high classification rate was obtained.The following formula: CV= PMNBAL x 0.18 +ECPBAL x 1.20 -MPOBAL x 0.03 +TryptaseBAL x 1.21- PIIIPBAL x0.1 -sIL2RBAL x0.01-1.183, allowed the correct allocation of 100% of participants. The positive likelihood ratio was >20 and the negative likelihood ratio was 0.   Conclusions:  Our results show that a panel of BAL markers may be used to distinguish patients with stable disease from individuals with pulmonary function worsening and may help to decide therapeutic strategies.
Mechanical properties of ALI/ARDS lung may be heterogenous
Authors: Massimo Cressoni, Daniela Febres, Chiara Chiurazzi, Gallazzi Elisabetta, Antonella Marino, Federica Ylenia Romano, Matteo Brioni, Eleonora Carlesso, Davide Chiumello, Luciano Gattinoni
Journal: European Respiratory Journal (2011)

Introduction: ARDS is characterized by lung collapse which is partly reversible by the application of PEEP; it is common belief that recruited lung units resume normal gas/tissue ratio and mechanical properties so that optimal PEEP can be set according to EELV and compliance changes.

Methods: We retrospectively analyzed 68 ALI/ARDS patients CT scans performed at 5 and 15 cmH2O PEEP [1]. Assuming that lung expansion while increasing PEEP is homogeneous, we divided each lung along the transverse, sagittal and coronal axes in oreder to obtain 125 parallelepiped compartments with an average weight of 5 g and we estimated a surrogate compliance per gram of tissue as:

(Δ Volume of gas/Δ PEEP)/gram of tissue.

Each lung compartment was classified according to its gas/tissue ratio as shown in Table 1.

Results: In Table 1 we summarize the surrogate compliances as median [interquartile range]. As shown the median compliance of the well inflated tissue was almost double the compliance of the poorly inflated tissue while the surrogate compliance of the recruited lung units was between the surrogate compliance of well inflated and poorly inflated tissue.

View this table:

Table 1. Specific lung tissue compliances





Conclusions: As recruited regions while increasing PEEP reach a lower gas tissue ratio and a smaller compliance than well inflated tissue changes in compliance may not be used to estimate lung recruitment at bedside.

Reference: 

*   1. Gattinoni, L. et al. N Engl J Med 2006; 354:1775-1786.
Multi-Institutional Phase I/II Trial of Oral Bexarotene in Combination With Cisplatin and Vinorelbine in Previously Untreated Patients With Advanced Non–Small-Cell Lung Cancer
Authors: Fadlo R. Khuri, James R. Rigas, Robert A. Figlin, Richard J. Gralla, Dong M. Shin, Reginald Munden, Nikolaus Fox, Mi Ra Huyghe, Yin Kean, Steven D. Reich, Waun K. Hong
Journal: Journal of Clinical Oncology (2001)

PURPOSE: Bexarotene (Targretin; Ligand Pharmaceuticals, Inc, San Diego, CA) is a retinoid-X-receptor (RXR)-selective retinoid with preclinical antitumor activity in squamous cell cancers. In this phase I/II trial, we combined bexarotene with cisplatin and vinorelbine in the treatment of patients with non–small-cell lung cancer (NSCLC). PATIENTS AND METHODS: Forty-three patients who had stage IIIB NSCLC with pleural effusion or stage IV NSCLC and had received no prior therapy received bexarotene in combination with cisplatin (100 mg/m 2 ) and vinorelbine (alternating doses of 30 mg/m 2 and 15 mg/m 2 ). In the phase I portion, the daily dose of bexarotene was escalated in cohorts of three patients from 150 mg/m 2 to 600 mg/m 2 , beginning 1 week before the start of the cisplatin-vinorelbine regimen. Once the maximum-tolerated dose (MTD) of bexarotene was determined, the study entered the phase II portion. Response rate was the primary end point; median survival time and 1-year survival rate were secondary end points. RESULTS: In the phase I portion, the daily MTD of bexarotene was determined to be 400 mg/m 2 . Eight of 43 patients exhibited major responses. Seven (25%) of the 28 patients in the phase II portion responded to treatment. The median survival time in the phase II portion was 14 months; nine (32%) of the 28 patients were still alive at a minimum follow-up of 2 years. One-year and projected 3-year survival rates were 61% and 30%, respectively. The most common grade 3 and 4 adverse events were hyperlipemia, leukopenia, nausea, vomiting, pneumonia, dyspnea, anemia, and asthenia. Grade 3 and 4 laboratory abnormalities with incidences greater than 5% were decreased hemoglobin levels and WBC, absolute neutrophil, and absolute lymphocyte counts and increased prothrombin time and creatinine and amylase levels. Of the two cases of pancreatitis, one required hospitalization and both were associated with increased triglyceride levels. There was one death secondary to renal insufficiency unrelated to bexarotene treatment. CONCLUSION: In patients with advanced NSCLC, bexarotene with cisplatin and vinorelbine yielded acceptable phase II response rates (25%) and was associated with better-than-expected survival (14-month median survival time; 61% 1-year, 32% 2-year, and 30% projected 3-year survival rates). The regimen should be studied in larger clinical trials.
Survival of Adults With Systemic Sclerosis Following Lung Transplantation: A Nationwide Cohort Study
Authors: Elana J. Bernstein, Eric R. Peterson, Jessica L. Sell, Frank D'Ovidio, Selim M. Arcasoy, Joan M. Bathon, David J. Lederer
Journal: Arthritis & Rheumatology (2015)

Many transplant programs are hesitant to offer lung transplantation to patients with systemic sclerosis (SSc) due to concerns about extrapulmonary involvement that might affect survival. The aim of this study was to determine whether adults with SSc have higher 1-year mortality rates after lung transplantation compared to those with interstitial lung disease (ILD) or pulmonary arterial hypertension (PAH) not due to SSc.Using data provided by the United Network for Organ Sharing, we performed a retrospective cohort study of 229 adults with SSc, 201 with PAH, and 3,333 with ILD who underwent lung transplantation in the US between May 4, 2005 and September 14, 2012. We examined associations between diagnosis and 1-year survival after lung transplantation using stratified Cox models adjusted for recipient, donor, and procedure factors.Adults with SSc undergoing lung transplantation in the US had a multivariable-adjusted 48% relative increase in the 1-year mortality rate compared to those with non-SSc-related ILD (hazard ratio 1.48 [95% confidence interval 1.01-2.17]). However, we did not detect a difference in the risk of death at 1 year between those with SSc and those with non-SSc-related PAH (hazard ratio 0.85 [95% confidence interval 0.50-1.44]).A diagnosis of SSc may confer an increased risk of death 1 year following lung transplantation compared to a diagnosis of ILD, but this risk is similar to that of PAH, a widely accepted indication for lung transplantation. Future work should identify modifiable risk factors that can improve transplant outcomes in this population.
Effects of CPAP on albumin redox state and heart rate variability in OSA patients
Authors: Manuel Baz, Leonel Malacrida, Santamarina Gabriela, Chiappella Lilian, Lorenzo Daniel, Arcos Jose
Journal: European Respiratory Journal (2013)

We aimed to assess the redox state of plasma albumin (RedoxA) and heart rate variability (HRV) as markers of cardiovascular stress in Obstructive Sleep Apnea patients (OSA) and the effects of CPAP treatment. Methods. We studied OSA treated with CPAP for 6 months, OSA before treatment, and healthy controls. HRV was calculated from the polysomnograph (ATI Delphos©), using MATLAB© and expressed as the square root of the mean of RR2 intervals (rmssd) and very low frequency (VLF). RedoxA was measured with high pressure liquid chromatography (Hewlett Packard©) using a fluorescence detector, expressed as a percentage of total albumin and referred to as HSA-SH (albumin in reduced state), HSA-S-SR (albumin reversibly oxidated), and HSA-SO2- –SO3- (albumin irreversibly oxidated).  Results. We studied 5 healthy controls, 6 OSA nontreated patients, 6 OSA treated patients. Patients showed no differences in age, sex, comorbidities, or medication. We will express the results of controls vs untreated OSA vs CPAP treated OSA. A.RedoxA. HSA-SH: 64.9 ± 1,1 vs 46.79, vs 42,54. HSA-S-SR: 32,8 ± 0,73 vs 43,3 ± 1,63 vs 48,3 ± 5,1. HSA -SO2- –SO3-: 2,34 ± 0,7 vs 9,9 ± 2,8 vs 9,0 ± 1,9. Controls and OSA showed a significant difference. Treated vs nontreated OSA did not show statistical significance. B.HRV. Rmssd 278.3 ± 342.8 vs 42.6 ± 23.8 vs 104,7 ± 147,5 (p>0,05). VLF (%) was 37,5 ± 19.3 vs 30,8 ± 9,2 vs 48,4 ± 30,4 (p  Conclusions. OSA induces changes in albumin redox state, a fact new to our knowledge. Treatment did not improve the changes. OSA changes in HRV could be reversed by CPAP. HRV could be more sensible to detect cardiovascular stress than albumin redox state. A better study design is needed.
Relationship of Size of Blood Sample to Yield of “Positive” Patients in Studies of Circulating Tumor Cells
Authors: Joan M. Gurian, John T. West
Journal: JNCI Journal of the National Cancer Institute (1963)

Lack of comparability of studies on the prevalence of patients with circulating tumor cells, when differences in sample size and efficiency of the method employed are not considered, is pointed out. A model relating the number of repeated examinations of blood samples, the efficiency of the method, the prevalence of patients with circulating tumor cells, and the probability of detection of such patients is presented. Based on this model, a method for the estimation of both the efficiency of the technique and the prevalence of patients harboring circulating tumor cells is presented.
Initiation of dialysis.
Authors: R M Hakim, J M Lazarus
Journal: Journal of the American Society of Nephrology (1995)

The decision to initiate dialysis in a patient with progressive renal disease often depends on the physician's assessment of the patient's subjective symptoms of uremia. There is an increasing need to identify objective criteria for such a decision. Recent evidence suggests that malnutrition at the initiation of dialysis is a strong predictor of subsequent increased relative risk of death on dialysis. In this context, the role of prescribed protein restriction as well as the influence of the progression of renal disease on spontaneous dietary protein intake is examined. It is proposed that the indices of malnutrition such as progressive weight loss, serum albumin levels below 4.0 g/dL, serum transferrin levels below 200 mg/dL, and spontaneous dietary protein intake (using 24-hr urinary nitrogen measurement) below 0.8 to 0.7 g/kg per day be considered as objective criteria for the initiation of dialysis. Studies that have examined the role of "early" versus "late" dialysis have consistently shown a better outcome in the patients starting dialysis early. Other studies also suggest that early referral to nephrologists results in improved morbidity and mortality as well as hospitalization costs. An adequate vascular access, as well as social and psychological preparation of the patient, is an important early step in the process.
MYCN Expression Is Not Prognostic of Adverse Outcome in Advanced-Stage Neuroblastoma With Nonamplified MYCN
Authors: Susan L. Cohn, Wendy B. London, Donghui Huang, Howard M. Katzenstein, Helen R. Salwen, Todd Reinhart, Janice Madafiglio, Glenn M. Marshall, Murray D. Norris, Michelle Haber
Journal: Journal of Clinical Oncology (2000)

PURPOSE: The clinical significance of MYCN expression in children with neuroblastoma (NB) remains controversial. To determine the prognostic significance of MYCN expression in the absence of MYCN amplification, we analyzed MYCN mRNA and protein expression in tumors from 69 patients. PATIENTS AND METHODS: Sixty-nine NB tumor samples with nonamplified MYCN from patients with stage C or D disease were obtained from the Pediatric Oncology Group Neuroblastoma Tumor Bank. MYCN mRNA was analyzed using a real-time reverse transcriptase polymerase chain reaction assay, and MYCN protein was examined by Western blot analyses. RESULTS: The estimated 5-year event-free survival (EFS) and survival (S) rates plus SE for the cohort were 57% ± 17% and 60% ± 16%, respectively. Infants younger than 1 year had significantly higher rates of EFS and S than children ≥ 1 year of age (P = .003 and P &lt; .001, respectively); patients with stage C disease had better outcome than those with stage D NB (P &lt; .001); and patients with hyperdiploid tumors had better outcome than those with diploid NB (P &lt; .001). Surprisingly, outcome was slightly better for patients with high versus low levels of MYCN mRNA expression (4-year S, 70% ± 13% v 50% ± 16%; P = .290), and for patients with tumors that expressed MYCN protein (4-year S, 73% ± 19% v 53% ± 15%, respectively; P = .171). CONCLUSION: High levels of MYCN expression are not prognostic of adverse outcome in patients with advanced-stage NB with nonamplified MYCN. A trend associating high levels of MYCN expression with improved outcome was observed.
Quality of Life: Impact of Chronic Illness on the Partner
Authors: Jonathan Rees, Ciaran O'boyle, Ruaraidh Macdonagh
Journal: Journal of the Royal Society of Medicine (2001)

Patient quality of life is an increasingly important outcome measure in medicine and healthcare. It is now widely used in clinical trials and in patient management for assessing morbidity and the impact of treatment1. In the past, quality of life studies focused almost exclusively on changes in the quality of life of patients, but increasing attention is now being paid to the impact of chronic disease on carers. The ageing of the population and changes in medical practice resulting in shorter inpatient hospital stay and longer survival have substantially increased the burdens on carers, most of whom are partners2. In this paper, we examine research on partner quality of life and highlight some of the methodological challenges and the clinical implications. The background to this overview is collaborative research conducted in the Department of Urology in Taunton and the Department of Psychology at the Royal College of Surgeons in Ireland3,4,5,6. Further references were obtained by searching various databases (PubMed, CancerLit, PsycInfo, EMBASE and British Nursing Index) with the keywords ‘quality of life, burden, impact, partners, caregivers and carers’.
17(R)-resolvin D1 attenuates bleomycin-induced lung fibrosis in mice
Authors: Masakiyo Yatomi, Takeshi Hisada, Masaki Nishioka, Yosuke Kamide, Hiroaki Tsurumaki, Haruka Aoki, Kaori Seki, Reiko Yoshino, Akihiro Ono, Yasuhiko Koga, Kunio Dobashi, Tamotsu Ishizuka, Masatomo Mori
Journal: European Respiratory Journal (2013)

Idiopathic pulmonary fibrosis(IPF) is a destructive inflammatory disease leading to pulmonary fibrosis with limited therapeutic options. Neutrophilic inflammation plays a pivotal role in IPF. Resolvins are a family of potent lipid mediators and promote the resolution of the imflammatory response back to a non-inflamed state.17(R)-resolvin D1(17(R)-RvD1) is an aspirin-triggered epimer of resolvin D1 derived from docosahexaenoic acid and resists rapid inactivation by eicosanoid oxidoreductases. Bleomycin(BLM) is a well-established agent for inducing pulmonary inflammation and fibross. We examined anti-inflammatory and anti-fibrotic effects of 17(R)-RvD1 on lung fibrosis in BLM-treated mice.We chose continuous subctaneous administration of BLM for 1week to 8-to-10-wk-old female C57BL/6 mice. 17(R)-RvD1 was injected intraperitoneally for five days consecutively.Fourteen days after BLM treatment, 17(R)-RvD1 reduced neutophilia in bronchoaveolar fluid(BAL) and decreased gene expression of IL-1β, inflammatory cytokines,in the lung tissue compared with control mice. Twenty-eight days after BLM exposure, 17(R)-RvD1 attenuated BLM induced pulmonary fibrosis histologically and decreased hydroxyproline content. Connective tissue growth factor(CTGF) is a cysteine-rich mitogenic peptide that is implicated in various fibrotic disorders and induced in fibroblasts after activation with transforming growth factor-β (TGF-β). At 28th day, decreased gene expression of CTGF in 17(R)-RvD1-treated mice was observed. These results suggest that 17(R)-RvD1 attenuates pulmonary fibrosis through the promotion of resolution in neutrophilic inflammation.
Phase I Study in Cancer Patients of a Replication-Defective Avipox Recombinant Vaccine That Expresses Human Carcinoembryonic Antigen
Authors: John L. Marshall, Michael J. Hawkins, Kwong Y. Tsang, Ellen Richmond, James E. Pedicano, MingZhu Zhu, Jeffrey Schlom
Journal: Journal of Clinical Oncology (1999)

PURPOSE: A phase I clinical trial in patients with advanced carcinoma was conducted, using a replication-defective avipox vaccine containing the gene for the human carcinoembryonic antigen (CEA). The canarypox vector, designated ALVAC, has the ability to infect human cells but cannot replicate. PATIENTS AND METHODS: The recombinant vaccine, designated ALVAC-CEA, was administered intramuscularly three times at 28-day intervals. Each cohort of six patients received three doses of either 2.5 × 10 5 , 2.5 × 10 6 , or 2.5 × 10 7 plaque-forming units of vaccine. RESULTS: The vaccine was well tolerated at all dose levels and no significant toxicity was attributed to the treatment. No objective antitumor response was observed during the trial in patients with measurable disease. Studies were conducted to assess whether ALVAC-CEA had the ability to induce cytolytic T-lymphocyte (CTL) responses in patients with advanced cancer. Peripheral blood mononuclear cells (PBMCs) from patients with the MHC class I A2 allele were obtained before vaccine administration and 1 month after the third vaccination. Peripheral blood mononuclear cells were incubated with the CEA immunodominant CTL epitope carcinoembryonic antigen peptide-1 and interleukin 2 and quantitated using CTL precursor frequency analysis. In seven of nine patients evaluated, statistically significant increases in CTL precursors specific for CEA were observed in PBMCs after vaccination, compared with before vaccination. CONCLUSION: These studies constitute the first phase I trial of an avipox recombinant in cancer patients. The recombinant vaccine ALVAC-CEA seems to be safe and has been demonstrated to elicit CEA-specific CTL responses. These studies thus form the basis for the further clinical exploration of the ALVAC-CEA recombinant vaccine in phase I/ II studies in protocols designed to enhance the generation of human T-cell responses to CEA.