tbuckley/cabot-search huggingface dataset:
Pharmacologic rationale for regional drug delivery.
Authors: J M Collins
Journal: Journal of Clinical Oncology (1984)

Regional drug delivery is an approach designed to improve the selectivity of chemotherapy. When compared with systemic drug administration, regional delivery can potentially increase drug concentrations at tumor sites and/or lower systemic drug exposure. Pharmacokinetic analysis can evaluate or even predict the relative advantage of regional drug delivery. Based on a quantitative analysis of regional drug delivery, some drugs and sites of delivery are more favorable than others. The formulas for the therapeutic advantage of intraarterial, intrathecal, and intraperitoneal delivery have a similar structure. The ratio of total body clearance of a drug to its regional exchange rate is the principal determinant of therapeutic advantage. Thus, the most favorable circumstances for regional delivery are the use of drugs with high total body clearances and/or sites of delivery with low exchange rates. Pharmacodynamic factors must also be considered for the overall assessment of regional delivery.
Psoriasis and papillomaviruses
Authors: J.C. Sterling
Journal: British Journal of Dermatology (2011)

Funding sources None. Conflicts of interest None declared. For many years, a search for a viral trigger or cofactor for psoriasis has failed to give any clear pathogenetic lead. Among the candidates for disease‐influencing infectious agents are the cutaneous papillomaviruses, especially the betapapillomaviruses, the genotypes originally described in epidermodysplasia verruciformis. They are found commonly in the skin and skin cancers of the immunosuppressed and are not uncommon in normal individuals. With the ability to remain latent or as subclinical commensals on the skin, but with known epidermal proliferative effects, this virus group fulfils some of the possible requirements to influence development of psoriasis lesions on the skin. It is over a decade since the first report suggested a possible link between psoriasis and papillomavirus infection, when both anti‐papillomavirus antibodies and human papillomavirus (HPV) detection in patients with psoriasis were found to be higher than in normal individuals and patients with atopic dermatitis.1 de Koning et al.,2 in this issue, compare patients with psoriasis and with atopic dermatitis, using both the detection of betapapillomavirus DNA in eyebrow hair bulbs and the level of antibodies to the viral capsid coat protein, the L1 protein, in 15 β‐HPVs.
The attenuating effect of erythropoietin (EPO) on the expression of myeloperoxidase (MPO) in bleomycin-induced pulmonary fibrosis in rats
Authors: Drosos Tsavlis, Anna Tzoumaka, Georgia Kokaraki, Kokona Koliakos-Kouzi, Afroditi Papadopoulou, Dimitrios Koutsonikolas, Evangelia Spandou
Journal: European Respiratory Journal (2013)

Purpose:The enzyme MPO is well known to participate in the fibrotic pathway with inflammatory and apoptotic actions.EPO is a multiple functional cytokine with anti-inflammatory and anti-apoptotic properties.Aim of this study was to investigate the role of EPO on the expression of MPO in bleomycin (BLM)-induced pulmonary fibrosis (PF) in rats.  Methods:Fifty Wistar rats (300gr) were divided into five groups of 10 animals each: 1)control animals, 2)intratracheal (i.t) and intraperitoneal (i.p) injection of saline (0.5ml/kg), 3)BLM hydrochloride (7.5mg/kg) i.t injection, 4)BLM hydrochloride (7.5mg/kg) i.t injection followed by EPO i.p injection (2000 iu/kg), 5)saline (0.5ml/kg) i.t injection followed by EPO i.p injection (2000 iu/kg).All rats were sacrified after 14 days.The expression of MPO was immunohistochemically measured and a scale of 4 grades (A:0-25%, B:25-50%, C:50-75%, D:75-100%) was used to evaluate it.  Results:In groups 1,2 and 5 (control groups), MPO was expressed in the low grades A (80%) and B (20%).In group 3, MPO was expressed in the high grades C (20%) and D (80%).Finally, in group 4, MPO was expressed only in the low grades A (70%) and B (30%).The expression of the enzyme took place in the high grades for group 3 (BLM group) and in the lower grades for group 4 (BLM+EPO group) (p  Conclusions:Administration of EPO after the BLM i.t injection (group 4) resulted in significant lower expression of MPO in comparison with the BLM group (group 3).More studies are required to clarify the mechanisms of the protective action of EPO on PF.Maybe it is a new potential target for the therapeutic treatment of PF.
Pulmonary diffusion capacity is not associated with severity of Cheyne-Stokes respiration in heart failure patients
Authors: Olaf Oldenburg, Britta Körber, Thomas Bitter, Thomas Fischbach, Dieter Horstkotte
Journal: European Respiratory Journal (2012)

A recent study in severe heart failure (HF) patients indicates a possible pathophysiological role of an impaired pulmonary diffusion capacity and respiratory disturbance during sleep, especially the degree of Cheyne-Stokes respiration (CSR). Aim of the present study was to verify this hypothesis in a larger cohort of HF patients.  In 87 patients (83 male, age 68 ± 9 years) with polysomnography confirmed and untreated CSR due to cardiac failure (NYHA ≥ II, LV-EF ≤45%), pulmonary diffusion capacity (TLCO and KCO) were prospectively investigated using the single-breath method. Apnoea-hypopnoea-index (AHI) was 38.0 ±14/h, LV-EF 34 ± 7%, TLCO 67 ± 17% of normal and alveolar-volume corrected diffusion capacity (KCO) 85 ± 20% of normal. Correlation analysis using Spearman rank order correlation revealed no significant correlation of AHI and TLCO (r = 0.071, p = 0.516) or AHI and KCO (0.019, p = 0.863).  In our cohort of HF patients with untreated CSR no correlation of respiratory disturbance during sleep and pulmonary diffusion capacity was found. Thus, a significant role of an impaired pulmonary diffusion on CSR genesis seems to be unlikely.
Rhinovirus infection upregulates SLPI in macrophages
Authors: Rosa Sotero, Patrick Mallia, Joseph Footitt, Alexandra Nikonova, Jemima Ho, Aurica Telcian, Musa Khaitov, Rosario Maselli, Girolamo Pelaia, Sebastian Johnston
Journal: European Respiratory Journal (2011)

Background:  Antimicrobial peptides (AMPs) such as Secretory Leukoprotease Inhibitor (SLPI) and Elafin are an important component of host innate immune responses that protect against infections at mucosal surfaces. Their role in bacterial infection is well decribed but little is known regarding their role in respiratory viral infections.   Aims:  We investigated the effects of rhinovirus infection on production of SLPI and elafin by monocyte derived macrophages (MDM).   Methods:  MDM derived from healthy donors were infected with rhinovirus-16 (RV16). Cells and supernatants were harvested and SLPI and elafin mRNA and protein were measured by qPCR and ELISA respectively.   Results:  Compared to cells infected with UV-inactivated virus RV16 induced expression of SLPI mRNA (11.7-fold induction, P=0.005) and protein (53.04±9.76pg/mL vs 95.23±2.63, P=0.014) in MDM at 24 hours.  There was a trend towards upregulation of elafin at 48 hours for both mRNA (2.17-fold induction, P=0.055) and protein (13.33±13.33pg/mL vs 107.8±37.45,P=0.14) but this was not statistically significant.   Conclusions:  Rhinovirus infection of MDM upregulates production of SLPI and elafin and this is dependent on virus replication. These molecules may play an important role in the host defence response to respiratory virus infections.
Government abolishes child poverty target
Authors: Ingrid Torjesen
Journal: BMJ (2015)

The UK government has abolished its current target for assessing child poverty, a measure of material disadvantage that is based on family income, and is replacing it with a range of measures to track the life chances of disadvantaged children.

In March 1999 the then prime minister Tony Blair committed to halving child poverty by 2010 and eradicating it by 2020. Child poverty was assessed as the proportion of family households with an income below 60% of median income, which is the measure used by the European …
Abstract 5003: Association of Blood Lactate with Hypertension: The Atherosclerosis Risk in Communities Carotid MRI Study
Authors: J Hunter Young, Stephen O Crawford, Frederick L Brancati, Ron C Hoogeveen, Muhammad Amer, Christie M Ballantyne, Maria I Schmidt, Brad C Astor, Josef Coresh
Journal: Circulation (2008)

Background: The mechanism linking obesity with its downstream complications is poorly understood. Decreased aerobic capacity in obesity may play a central role in the development of hypertension. T...
Dirt-binding particles consisting of hydrogenated castor oil beads constitute a nonirritating alternative for abrasive cleaning of recalcitrant oily skin contamination in a three-step programme of occupational skin protection
Authors: V. Mahler, C. Erfurt-Berge, S. Schiemann, S. Michael, A. Egloffstein, O. Kuss
Journal: British Journal of Dermatology (2009)

In occupational fields with exposure to grease, oil, metal particles, coal, black lead or soot, cleansing formulations containing abrasive bodies (e.g. refined walnut shell, corn, wood, plastic or pumice) are used. These may constitute an irritant per se. As an alternative, hydrogenated castor oil (also known as castor wax) beads have been developed as dirt-binding particles. A polar surface contributes to their mechanical cleaning effects in removal of oily grime.Standardized examination of the in vivo effects upon the skin barrier of castor wax beads in comparison with abrasive bodies and pure detergent.Three cleansing preparations - (i) detergent, (ii) detergent containing castor wax beads, (iii) detergent containing walnut shell powder - were each repetitively applied in vivo (four times daily for 3 weeks), mimicking workplace conditions, in 30 healthy volunteers (15 with and 15 without an atopic skin diathesis) and compared vs. (iv) no treatment. The treatment effects upon the skin barrier were monitored by repeated measurements of functional parameters [transepidermal water loss (TEWL), redness] and surface topography.After a 3-week treatment, a significant global treatment effect (P < 0.0001) was found in the atopic group concerning TEWL as indicator for barrier function. A significantly higher TEWL and increasing erythema in the area treated with detergent containing walnut shell powder reflected its irritant effect compared with castor wax beads dispensed in the identical detergent. Cleaning properties of the two formulas were comparably superior to detergent alone.Castor wax beads constitute a novel nonirritating alternative for abrasive cleaning of recalcitrant oily skin contamination appropriate for individuals with an atopic skin diathesis in a three-step programme of occupational skin protection. As the skin barrier may additionally be influenced by the composition of dirt and use of skin protection and skin care measures under real workplace conditions, this component may now be used and examined further in different occupations.
Serum Amyloid A
Authors: C. Julian Rosenthal, Lee Sullivan
Journal: Journal of Clinical Investigation (1978)

In this study the presence of an amyloid A, antigenically related material was determined in four subpopulations of human leukocytes. Monocytes, granulocytes, thymus-derived lymphocytes, and bone marrow-derived and null lymphocytes were isolated from the peripheral blood of five apparently normal subjects, two patients with secondary amyloidosis, three patients with acute infections, and seven patients with metastatic cancer. Mononuclear leukocytes, isolated from the interface of a Ficoll-Hypaque gradient, were separated into monocytes, thymus-derived lymphocytes, and bone marrow-derived plus null lymphocytes by glass adherence and depletion of sheep erythrocyte rosette-forming lymphocytes. Granulocytes were isolated by sedimentation in 2% methyl cellulose from the erythrocyte-rich pellet formed at the bottom of the Ficoll-Hypaque gradient. The four isolated leukocyte subpopulations were cultured and, at varying intervals, the amyloid A content of the culture medium and of sonicated, 2 × 106 cells was determined by radioimmunoassay. Our results indicated a 2-14 times greater amount of amyloid A-related material in the sonicated granulocytes compared with the individuals' serum amyloid A levels. The mononuclear subpopulations showed a low or negligible amyloid A content. The amount of amyloid A antigenic material was further found to increase in cultured granulocytes, reaching a peak value between the 16th and 30th h of culture. The granulocytes of only two out of eight individuals tested released amyloid A antigenically related material into the culture medium. This release was found to be blocked by the presence of colchicine, vincristine, puromycin, or cycloheximide in the culture medium. In contrast, only the presence of puromycin or cycloheximide was shown to significantly inhibit the intracellular increase of amyloid A in the cultured granulocytes. Thus, it appears that among the circulating blood cells, the granulocytes produce amyloid A antigenically related material and could release it under conditions that remain to be further defined.
Topotecan for the treatment of advanced epithelial ovarian cancer: an open-label phase II study in patients treated after prior chemotherapy that contained cisplatin or carboplatin and paclitaxel.
Authors: M A Bookman, H Malmström, G Bolis, A Gordon, A Lissoni, J B Krebs, S Z Fields
Journal: Journal of Clinical Oncology (1998)

PURPOSE Topotecan, a topoisomerase I inhibitor, was evaluated in a multicenter, phase II study of women with epithelial ovarian carcinoma who relapsed after one or two prior regimens that included platinum and paclitaxel. PATIENTS AND METHODS Topotecan 1.5 mg/m2 daily was administered as a 30-minute infusion for 5 consecutive days on a 21-day cycle. Eligibility criteria included bidimensionally measurable disease, Eastern Cooperative Oncology Group performance status of 2 or less, and adequate bone marrow, liver, and renal function. Efficacy was assessed by independent radiologic review. RESULTS One hundred thirty-nine patients were treated; 81% were platinum resistant. Sixty-two patients had received one prior regimen and 77 patients had received two prior regimens. Nine patients were not assessable for response; however, all patients were included in the response analysis. The overall response rate was 13.7%; 12.4% in platinum-resistant and 19.2% in platinum-sensitive patients. Stable disease lasted at least 8 weeks in 27.3% of the patients. The median duration of response and time to progression were 18.1 and 12.1 weeks, respectively. The median survival was 47.0 weeks. Grade 4 neutropenia occurred in 82% of the patients (34% of the courses) and thrombocytopenia in 30% of the patients (9% of the courses). Infectious complications occurred in 6% of the courses. Nonhematologic toxicities were mild. There were no drug-related toxic deaths. CONCLUSION As a single agent, topotecan has modest activity in women with advanced epithelial ovarian carcinoma who have progressed or not responded after one or two prior regimens with platinum and paclitaxel. Further investigation of combination regimens is indicated in the primary therapy for ovarian cancer based on the mechanism of action and tolerability.
New WHO recommendations to improve the outcomes of preterm birth
Authors: Joshua P Vogel, Olufemi T Oladapo, Alexander Manu, A Metin Gülmezoglu, Rajiv Bahl
Journal: The Lancet Global Health (2015)

An estimated 15 million babies are born preterm annually.1 Preterm birth complications account for more than 15% of deaths in children younger than 5 years2 and survivors often have long-term consequences with respect to their health, growth, and psychosocial functioning.3,4 The most beneficial interventions available are those that improve newborn outcomes when preterm birth is inevitable (tertiary interventions) and those that focus on special care for preterm newborns. Today WHO publishes new recommendations on interventions for pregnant women in whom preterm birth is imminent (including antenatal corticosteroids, tocolytics, magnesium sulfate, antibiotics, and mode of delivery) and for care of preterm neonates (including thermal care, continuous positive airway pressure [CPAP], surfactant administration, and oxygen therapy) to improve preterm birth outcomes.
Acute fatty liver in pregnancy in the UK.
Authors: C L Ch’ng, J G C Kingham, M Morgan
Journal: Gut (2009)

We were pleased that the editors gave prominence to the article on acute fatty liver of pregnancy (AFLP) in their Digest in the July 2008 issue of Gut , but wish to point out that while Cardiff and Swansea are both cities in Wales, they are distinct. The diagnostic criteria under discussion emanate from Swansea, 40 miles to the west of the principality’s capital.

We welcome the study of AFLP in the UK by Knight et al ( Gut 2008; 57 :951–6) and congratulate the authors. We were pleased that the diagnostic criteria we proposed (Swansea criteria)1 have been independently validated. We wish to make the following comments.

Their study was entitled prospective but was in effect a recent retrospective survey and should not be used to provide an accurate assessment of incidence. Case acquisition was …
Wide geographical dissemination of the multiresistant Staphylococcus capitis NRCS-A clone in neonatal intensive-care units
Authors: M. Butin, J.-P. Rasigade, P. Martins-Simões, H. Meugnier, H. Lemriss, R.V. Goering, A. Kearns, M.A. Deighton, O. Denis, A. Ibrahimi, O. Claris, F. Vandenesch, J.-C. Picaud, F. Laurent
Journal: Clinical Microbiology and Infection (2015)
Downregulation of RARα in Mice by Antisense Transgene Leads to a Compensatory Increase in RARβ and RARγ and Development of Lymphoma
Authors: Taghi Manshouri, Yun Yang, Huai Lin, Sanford A. Stass, Armand B. Glassman, Michael J. Keating, Maher Albitar
Journal: Blood (1997)
Long-term results of a prospective randomized trial of adjuvant brachytherapy in soft tissue sarcoma.
Authors: P W Pisters, L B Harrison, D H Leung, J M Woodruff, E S Casper, M F Brennan
Journal: Journal of Clinical Oncology (1996)

PURPOSE This trial was performed to evaluate the impact of adjuvant brachytherapy on local and systemic recurrence rates in patients with soft tissue sarcoma. PATIENTS AND METHODS In a single-institution prospective randomized trial, 164 patients were randomized intraoperatively to receive either adjuvant brachytherapy (BRT) or no further therapy (no BRT) after complete resection of soft tissue sarcomas of the extremity or superficial trunk. The adjuvant radiation was administered by iridium-192 implant, which delivered 42 to 45 Gy over 4 to 6 days. The two study groups had comparable distributions of patient and tumor factors, including age, sex, tumor site, tumor size, and histologic type and grade. RESULTS With a median follow-up time of 76 months, the 5-year actuarial local control rates were 82% and 69% in the BRT and no BRT groups (P = .04), respectively. Patients with high-grade lesions had local control rates of 89% (BRT) and 66% (no BRT) (P = .0025). BRT had no impact on local control in patients with low-grade lesions (P = .49). The 5-year freedom-from-distant-recurrence rates were 83% and 76% in the BRT and no BRT groups (P = .60), respectively. Analysis by histologic grade did not demonstrate an impact of BRT on the development of distant metastasis, despite the improvement in local control noted in patients with high-grade lesions. The 5-year disease-specific survival rates for the BRT and no BRT groups were 84% and 81% (P = .65), respectively, with no impact of BRT regardless of tumor grade. CONCLUSION Adjuvant brachytherapy improves local control after complete resection of soft tissue sarcomas. This improvement in local control is limited to patients with high-grade histopathology. The reduction in local recurrence in patients with high-grade lesions is not associated with a significant reduction in distant metastasis or improvement in disease-specific survival.
Topical photodynamic therapy significantly reduces epidermal Langerhans cells during clinical treatment of basal cell carcinoma
Authors: G. Evangelou, M.D. Farrar, L. Cotterell, S. Andrew, A.D. Tosca, R.E.B. Watson, L.E. Rhodes
Journal: British Journal of Dermatology (2012)

Background Topical photodynamic therapy (PDT) is a widely applied treatment for basal cell carcinoma (BCC). PDT-induced immunosuppression leading to reduced antitumour immune responses may be a factor in treatment failure. Objectives To examine the impact of topical PDT on leucocyte trafficking following clinical treatment of BCC. Methods Superficial BCCs in eight white caucasian patients were treated with methyl aminolaevulinate (MAL)-PDT. Biopsies for immunohistochemical assessment were taken from BCCs pre-PDT, 1 h and 24 h post-PDT and from untreated healthy skin. Results Treatment of BCC with MAL-PDT produced a rapid neutrophil infiltration, commencing by 1 h and significantly increased at 24 h post-PDT (P < 0·05 compared with baseline). An associated increase in the number of blood vessels expressing E-selectin was observed at 1 h and 24 h post-PDT (both P < 0·05 compared with baseline). In contrast, the number of epidermal Langerhans cells fell sharply by 1 h post-PDT, and remained significantly reduced at 24 h post-PDT (both P < 0·05 compared with baseline). Conclusions Reduction of Langerhans cells during clinical treatment of BCC might potentially impact negatively on antitumour responses through reduced activation of tumour-specific effector cells. Investigation of modified PDT protocols with the aim to minimize immunosuppressive effects while maintaining antitumour efficacy is warranted.
Correlation of FDG-PET/CT and EBUS-TBNA for nodal staging in lung cancer
Authors: Petra Hoffknecht, Markus Enderle, Gabriela May, Heiner Schubert, Stefan Rüther, Stefan Fischer, Patrick Zardo, Nicolas J. Dickgreber
Journal: European Respiratory Journal (2013)

Positron emission tomography (PET/CT) and endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) are standard diagnostic procedures in lymph node (ln) staging in suspected malignomas.  In this retrospective single center study we aimed to investigate the efficacy of EBUS-TBNA of mediastinal and hilar ln in PET pos. and neg. cases in suspected malignomas, mainly lung cancer.  From 06/2011 to 11/2012, 86 patients underwent EBUS-TBNA. Of these, 39 patients with histologically confirmed malignoma aditionally underwent PET/CT. An average of 1,6 ln (diameter 5 to 20mm), preferably PET pos., were aspirated.  If PET/CT was pos. but TBNA neg., subsequent mediastinoscopy was recommended.  PET showed pos. mediastinal (n=24) or hilar (n=3) ln in n=27 (69%). In n=21 (78%) PET pos. ln were aspirated and cytology confirmed malignancy in n=16 (76%) (lung cancer n=13, others n=3). TBNA staged down to N0 in n=10 patients (37%). Of those n=4 were confirmed in mediastinoscopy, n=1 all PET-pos. ln had neg. cytology, n=1 thoracotomy staged up to N1 and n=4 remain unclear.  PET neg. ln were found in n=12. TBNA showed concordant N0 status in n=10 (83%), in n=2 (17%) EBUS-TBNA staged up to N2. False negative rates are 17%/5% for PET/TBNA respectively and 8% for combination of both.  However, one surgery resulted in an incidental N2 status though PET/CT and TBNA indicated N0.  Association of staging by PET and EBUS was achieved in 59%/83% for N2/N0. Overall PET/CT correctly diagnosed N status in n=26/39 (67%). EBUS in n= 33/39 (85%).  PET guided EBUS-TBNA helps to selectively aspirate lymph nodes but down staging is common in positive PET/CT ln when TBNA is performed.