tbuckley/cabot-search huggingface dataset:
Collagenase Inhibition in the Healing Colon
Authors: Howard L Young, Malcolm H Wheeler
Journal: Journal of the Royal Society of Medicine (1983)

A randomized controlled trial was performed to assess the effect of intravenous aprotinin (Trasylol) on the healing of experimental colonic anastomoses in the rabbit following a standard left colonic resection anastomosis. Assessment of tensile strength was by means of both bursting pressure and breaking strength. Those animals subjected to bursting pressure assessment received intravenous aprotinin 80 000 KIU (kallikrein inhibitory units) at the time of anaesthesia, and postoperatively 160000 KIU per day given in divided doses for three days. Control animals received saline placebo. A further group of animals received a lower loading and maintenance aprotinin dose (40 000 KIU and 60000 KIU per day respectively) with control animals receiving saline. Breaking strength was employed as the means of assessment. The mean bursting pressures were 47.7 ∓ 2.9 mmHg and 37.5 ∓ 3.4 mmHg for aprotinin and controls respectively (P≤0.05). The mean difference in collagen content of the anastomosis compared to the resected specimen was +1.25 ∓0.50 μg/mg and −1.02 ∓ 0.47 ug/mg for aprotinin and placebo groups (P ≤ 0.005). The mean breaking strength in the aprotinin group was 169.6 ∓74.5 g and 110.0 ∓65.9 g for the saline group (P≤0.02). The mean difference in collagen content of the anastomosis compared to the resected specimen was +0.95 ∓0.69 ug/mg and −1.5 ∓0.78 ug/mg for the aprotinin and saline groups respectively (P≤0.05). The significant elevation of both bursting pressure and breaking strength assessments, with a significant improvement in the collagen content of the anastomoses, may be the result of collagenase inhibition following the use of intravenous aprotinin in the experimental model.
Do phosphodiesterase 5 inhibitors improve exercise capacity in patients with COPD associated pulmonary hypertension? (3P study)
Authors: Andrew Goudie, Pippa Hopkinson, Brian Lipworth, Allan Struthers
Journal: European Respiratory Journal (2013)

Background  PH complicates COPD, negatively influencing mortality, exercise tolerance and QOL. It is unknown whether pulmonary vasodilation through PDE5-inhibition has beneficial effects in COPD associated PH.  Aims  To determine if PDE5-Is improve exercise capacity, QOL and cardiac function in COPD-PH.  Methods  A randomised, double-blind, parallel group, placebo controlled study was conducted (60 patients per arm). The active arm received 10 mg daily tadalafil for 12 weeks. Primary endpoint: 6MWD. Secondary endpoints: SGRQ, SF-36 and Minnesota questionnaires (QOL); BNP; DLCO and echo parameters. Inclusion: moderate-severe COPD and PH [RVSP >30mmHg and/or a pulmonary acceleration time (PAT)   Results (n=120)  Mean FEV1 1.06±0.41 L (41% pred.), mPAP 30±7 mmHg (PAT derived), RVSP 42±10 mmHg. At 12 weeks the mean placebo corrected Δ6MWD=0.5m. Clinically significant divergence of QOL scores favoured the active group with between group differences of -4.41 95%CI(-9.20-0.38), p=0.071 for SGRQ activity levels and 4.08 95%CI(-1.35-9.52), p=0.139 for SF-36 physical function, although not statistically significant. No significant changes were noted in BNP, DLCO, or RV function (TAPSE). A significant between group ΔPAT occurred, 9.5ms 95% CI (3.24 to 12.56), p= 0.001.  Conclusions  Tadalafil did not increase 6MWD. Clinically significant QOL score divergence of >4 points occurred in domains of activity and physical function, favouring the active group. This warrants further exploration. An expected pulmonary vasodilatory effect as determined by PAT was found in the active group without significant change in RV function.
Impairment of macrophage functions after ingestion of Plasmodium falciparum-infected erythrocytes or isolated malarial pigment.
Authors: E Schwarzer, F Turrini, D Ulliers, G Giribaldi, H Ginsburg, P Arese
Journal: The Journal of Experimental Medicine (1992)

Human monocyte-derived macrophages ingest diamide-treated red blood cells (RBC), anti-D immunoglobulin (Ig)G-opsonized RBC, or Plasmodium falciparum ring-stage parasitized RBC (RPRBC), degrade ingested hemoglobin rapidly, and can repeat the phagocytic cycle. Monocytes fed with trophozoite-parasitized RBC (TPRBC), which contain malarial pigment, or fed with isolated pigment are virtually unable to degrade the ingested material and to repeat the phagocytic cycle. Monocytes fed with pigment display a long-lasting oxidative burst that does not occur when they phagocytose diamide-treated RBC or RPRBC. The phorbol myristate acetate-elicited oxidative burst is irreversibly suppressed in monocytes fed with TPRBC or pigment, but not in monocytes fed with diamide-treated or IgG-opsonized RBC. This pattern of inhibition of phagocytosis and oxidative burst suggests that malarial pigment is responsible for the toxic effects. Pigment iron released in the monocyte phagolysosome may be the responsible element. 3% of total pigment iron is labile and easily detached under conditions simulating the internal environment of the phagolysosome, i.e., pH 5.5 and 10 microM H2O2. Iron liberated from pigment could account for the lipid peroxidation and increased production of malondialdehyde observed in monocytes fed with pigment or in RBC ghosts and liposomes incubated at pH 6.5 in presence of pigment and low amounts of H2O2. Removal of the labile iron fraction from pigment by repeated treatments with 0.1 mM H2O2 at pH 5.5 reduces pigment toxicity. It is suggested that iron released from ingested pigment is responsible for the intoxication of monocytes. In acute and chronic falciparum infections, circulating and tissue-resident phagocytes are seen filled with TPRBC and pigment particles over long periods of time. Moreover, human monocytes previously fed with TPRBC are unable to neutralize pathogenic bacteria, fungi, and tumor cells, and macrophage responses decline during the course of human and animal malaria. The present results may offer a mechanistic explanation for depression of cellular immunity in malaria.
Gemcitabine and Paclitaxel: Pharmacokinetic and Pharmacodynamic Interactions in Patients With Non–Small-Cell Lung Cancer
Authors: Judith R. Kroep, Giuseppe Giaccone, Daphne A. Voorn, Egbert F. Smit, Jos H. Beijnen, Hilde Rosing, Catharina J.A. van Moorsel, Cornelis J. van Groeningen, Pieter E. Postmus, Herbert M. Pinedo, Godefridus J. Peters
Journal: Journal of Clinical Oncology (1999)

PURPOSE: To assess possible pharmacokinetic and pharmacodynamic interactions between gemcitabine and paclitaxel in a phase I/II study in non–small-cell lung cancer (NSCLC) patients. PATIENTS AND METHODS: Eighteen patients with advanced NSCLC received the following in a 3-week schedule: gemcitabine 1,000 mg/m 2 (30 minutes, days 1 and 8) and paclitaxel 150 (n = 9) or 200 mg/m 2 (n = 9) before gemcitabine (3 hours, day 1). Plasma pharmacokinetics and pharmacodynamics in mononuclear cells were studied. RESULTS: Gemcitabine did not influence paclitaxel pharmacokinetics at 150 and 200 mg/m 2 (area under the concentration-time curve [AUC], 7.7 and 8.8 μmol/ L · h, respectively; maximum plasma concentration [C max ], 3.2 and 4.0 μmol/L, respectively), and paclitaxel did not influence that of gemcitabine (C max , 30 ± 3 μmol/L) and 2′,2′-difluorodeoxyuridine. Paclitaxel, however, dose-dependently increased the C max of gemcitabine triphosphate (dFdCTP), the active metabolite of gemcitabine, from 55 ± 10 to 106 ± 16 pmol/10 6 cells. No significant difference in the AUC of dFdCTP was observed. Moreover, the gemcitabine-paclitaxel combination significantly increased ribonucleotide levels, most pronounced for adenosine triphosphate (six- to seven-fold). Postinfusion paclitaxel AUC was related to pretreatment hepatic function (bilirubin: r = 0.79; P &lt; .001) and to the percentage decrease in platelets (r = 0.61; P = .009). The latter was also related to the duration of paclitaxel concentration above 0.1 μmol/L (r = 0.62; P = .007). Gemcitabine C max was related to the percentage decrease in platelets (r = 0.58; P = .01), pretreatment hepatic function (bilirubin: r = 0.77; P &lt; .001), and to plasma creatinine (r = 0.5; P = .03). The pharmacokinetics and pharmacodynamics were not related to response or survival. CONCLUSION: Gemcitabine and paclitaxel pharmacokinetics were related to the percentage decrease in platelets. Paclitaxel did not affect the pharmacokinetics of gemcitabine, nor did gemcitabine affect the pharmacokinetics of paclitaxel, but paclitaxel increased dFdCTP accumulation. This might enhance the antitumor activity of gemcitabine.
Chemotherapy with Cisplatin and Pemetrexed for Non-Small Cell Lung Cancer Patients: a Retrospective Single Center Study
Authors: Yoshimasa Shiraishi, Ryo Toyozawa, Eiko Inamasu, Gouji Toyokawa, Tomoyoshi Takenaka, Fumihiko Hirai, Masafumi Yamaguchi, Takashi Seto, Mitsuhiro Takenoyama, Yukito Ichinose
Journal: Annals of Oncology (2014)
Prevalence of human polyomaviruses in common and rare types of non‐Merkel cell carcinoma skin cancer
Authors: N. Scola, U. Wieland, S. Silling, P. Altmeyer, M. Stücker, A. Kreuter
Journal: British Journal of Dermatology (2012)

Little is known about the association of human polyomaviruses (HPyVs) other than Merkel cell polyomavirus (MCPyV) with nonmelanoma skin cancer.To evaluate the presence of HPyV6, HPyV7, trichodysplasia spinulosa-associated polyomavirus (TSV), also called HPyV8, and the recently discovered HPyV9 in basal cell carcinoma (BCC), actinic keratosis (AK), squamous cell carcinoma in situ (SCCis), squamous cell carcinoma (SCC), keratoacanthoma (KA), microcystic adnexal carcinoma (MAC) and atypical fibroxanthoma (AFX).Archival paraffin-embedded samples (n = 193: 41 BCC, 31 AK, 8 SCCis, 52 SCC, 42 KA, 5 MAC and 14 AFX) were analysed for the presence of the respective HPyV by polymerase chain reaction (PCR). HPyV DNA loads (HPyV DNA copies per β-globin gene copy) were determined in all HPyV-positive samples by quantitative real-time PCR. Immunohistochemical analysis of MCPyV large T-antigen (LTA) expression was performed using the monoclonal antibody CM2B4.MCPyV DNA was found in 29% of BCC, 19% of AK, 25% of SCCis, 27% of SCC, 29% of KA, 0% of MAC and 29% of AFX. MCPyV DNA loads never exceeded 0·3 MCPyV DNA copies per β-globin gene copy (median 0·004). In the immunohistochemical analysis of MCPyV LTA expression, all evaluated samples (32 MCPyV DNA-positive samples) were LTA negative. HPyV6 DNA was found in 7% of BCC, 3% of AK, 12% of SCCis, 4% of SCC, 5% of KA, and 0% of MAC and AFX. HPyV6 DNA loads never exceeded 0·7 HPyV6 DNA copies per β-globin gene copy (median 0·015). None of the 193 samples was positive for HPyV7, TSV or HPyV9 DNA.Our findings argue against a pathogenic role for MCPyV, HPyV6, HPyV7, TSV and HPyV9 in the analysed types of non-Merkel cell carcinoma skin cancer.
The effect of BODE index on quality of life and depressive symptoms in patients with COPD
Authors: Giuseppina Cuttitta, Palma Audino, Pietro Alfano, Salvatore Bucchieri, Mario Melis, Fabio Cibella, Giovanni Viegi
Journal: European Respiratory Journal (2012)

Chronic obstructive pulmonary disease (COPD) is a disorder leading to physical and mental impairment. Aim of the present study was to evaluate the effect of BODE index and its components on depressive symptoms and Quality of Life (QoL). We studied 37 consecutive COPD outpatients (26 M, aged 53-86 years). COPD diagnosis was confirmed by clinical and functional assessment. The patients were classified on the basis of GOLD and BODE stages. QoL was assessed by SF-36 questionnaire through its two components: Physical Health (PCS) and Mental Health (MCS). Depressive symptoms were assessed by the Beck Depression Inventory-II (BDI-II). 14 patients were allocated in GOLD stage I, 18 in II, and 5 in III. No patient was in GOLD stage IV. BODE index ranged 0-6. Median depression value (IQ range) was 7 (4-11). 23 subjects did not present depressive symptoms, 8 showed mild depression, and 6 moderate depression. None showed severe depression. Mean PCS and MCS were 46.4 (±10.4) and 47.5 (±9.6) respectively. PCS and MCS values lower respect to mean value of Italian general population were found in 22 and 17 subjects, respectively. A negative relationship was found between BDI-II and PCS (p=0.02). BDI-II was linearly correlated to BODE (p
Problems That Patients Feel are Appropriate to Discuss with Their GPs
Authors: S J A Spence
Journal: Journal of the Royal Society of Medicine (1992)

A descriptive study was performed to discover what problems patients felt it appropriate to discuss with their general practitioner, their use of alternative therapies, and any questions they wished their doctor had asked them in the past. Demographic data was recorded including Church attendance. Data was collected using an original questionnaire distributed to two groups of patients; 150 consecutive patients attending the surgery (surgery group) and 220 randomly selected from the adult age-sex register (home group). Chi-squared analysis was performed. A broad range of subjects appropriate to a general practice consultation was found (from influenza to spiritual problems). Prior use of homeopathy and hypnosis was widespread. Multiple attenders were more likely to be church attenders. Men in the surgery group were most likely to discuss marital, relationship and spiritual problems. Qualitative data from open questions demonstrated patients' concerns with consultation time and the exploration of feelings.
Effect of N-acetylcysteine on gas exchange after methacholine challenge and isoprenaline inhalation in the dog
Authors: O Ueno, L N Lee, P D Wagner
Journal: European Respiratory Journal (1989)

N-acetylcysteine (NAC) has antioxidant and possibly mucolytic properties. To determine whether NAC could be of benefit in acute bronchoconstriction induced by methacholine, 12 of 24 anaesthetized dogs (group 1) received NAC i.v. (loading dose 150 mg.kg-1, then 20 mg.kg-1.hr-1). The other 12 (group 2) received diluent. Nebulized methacholine (1%) was then inhaled until arterial oxygen tension (PaO2) fell to a mean of 5.5 kPa, after which isoprenaline 0.5% was inhaled in six dogs of each group to reverse bronchoconstriction. Over the next 3 h we measured total lung resistance, functional residual capacity (FRC), haemodynamic variables, and pulmonary gas exchange for respiratory and inert gases. After methacholine challenge, lung resistance increased and then fell similarly for both groups, but PaO2 was higher in the NAC group (by 0.6-1.9 kPa) throughout the observation period. The ventilation-perfusion distribution measured by inert gas elimination also showed less abnormality in the NAC treated dogs over this time. Mucus was visible during post-mortem in the large airways in about half of the dogs in both groups, with no significant differences between them. These results show that NAC produces a measurable improvement in gas exchange following methacholine challenge (both with and without subsequent isoprenaline therapy) by mechanisms that remain to be determined.
Hematopoietic Stem Cells In Friend Murine Leukemia Virus-Infected Mice Undergoing Chemotherapy: Remission and Relapse of Erythropoietin-Independent Erythropoiesis Induced by Hydroxyurea2
Authors: H. J. Seidel, Uta Opitz
Journal: JNCI Journal of the National Cancer Institute (1979)

Hydroxyurea (HU), given ip four times, each time at 500 mg/kg in 6-hour intervals, was used to treat DBA/2 mice with Friend murine leukemia virus-induced polycythemia (F-MuLV-P). In these mice a new cell type, found after virus infection, gave rise to erythropoietic colonies in vitro without addition of erythropoietin (Ep) and completely replaced Ep-dependent normal erythropoietic colonies in vitro. The colony-forming units in the spleen (CFUs), the colony-forming units in culture (CFUc), and the erythropoietic colony-forming units (CFUE) were studied. Two days after treatment, CFUs were reduced to about 20% in controls and F-MuLV-P-infected animals, and CFUc were reduced to 6-11% in controls and F-MuLV-P-infected animals. CFUE were not detectable. At day 4 after the first HU dose, when CFUs has regenerated to about normal levels, a sharp rise in Ep-dependent CFUE was seen in the marrow; this rise was not present before HU treatment. The subsequent fall at day 7 coincided with a regeneration of CFUE in the spleen, but in the spleen these CFUE were all Ep-independent. Possibly, the normal Ep-dependent CFUE during regeneration in the marrow might have derived from previously resting CFUs that were not killed by HU. The subsequent conversion to Ep independency could have been due to reinfection by F-MuLV-P persisting in the animal.
Antistatic valved holding chambers do not necessarily offer similar aerosol delivery performance
Authors: Jason Suggett, Jolyon Mitchell, Cathy Doyle, Vivian Wang, Mark Nagel
Journal: European Respiratory Journal (2013)

RATIONALE: Adoption of materials to mitigate medication losses due to electrostatic charge accumulation on VHCs has been associated with improved reliability of output. We investigated if this change has resulted in similar in vitro performance, simulating poor coordination of inhalation with inhaler actuation, for which VHCs are prescribed.

METHODS: Each VHC (n=5 devices/group) tested out-of-package. 5-actuations of fluticasone propionate (125 µg FP/actuation; Flovent®-HFA, GSK plc) was delivered at 30-s intervals to the VHC on test, sampling via a cascade impactor (CI) after 2, 5 and 10-s delay intervals, using a proprietary “delay” apparatus. FP was recovered from the CI and assayed by HPLC-spectrophotometry. Fine particle mass <4.7 µm aerodynamic diameter ( FPM<4.7µm ) provided a measure of the therapeutically beneficial medication capable of reaching the lungs.

RESULTS: Values of FPM4.7 µm (µg FP; mean ± SD) are summarized in the Table. FPM4.7 µm for the pMDI alone (no delay) was 46.2 ± 2.1 µg.

View this table:

Fine Particle Mass (µg/actuation) after Various Delay Intervals Following Inhaler Actuation





CONCLUSIONS: Although antistatic materials enable VHCs to be used without pre-washing, there are still large differences in output. Regardless of delay length, the AeroChamber Plus® VHC most closely matched the benchmark FPM4.7 µm for the pMDI without VHC.
Antibody-Induced Modulation and Shedding of Mammary Tumor Virus Antigens on the Surfaces of GR Ascites Leukemia Cells as Compared With Normal Antigens2
Authors: Jero Calafat, J. Hilgers, W. J. van Blitterswijk, M. Verbeet, Philomena C. Hageman
Journal: JNCI Journal of the National Cancer Institute (1976)

The distribution, antibody-induced redistribution, and shedding of murine mammary tumor virus (MuMTV) antigens and the surfaces of GR mouse ascites leukemia (GRSL) cells were studied by the immunoferritin technique and compared with the same activities of thy 1.2 and H-2.8 antigens. MuMTV antigens were redistributed easily and then largely shed from the cell surface; in contrast, H-2.8 antigen moved easily and probably was partially released from the plasms membrane and Thy 1.2 antigen moved slowly and was some what interiorized. The complement-dependent cytotoxicity test was used to study the possibility of antigenic modulation for these cell-surface antigens from the surface of the GRSL cells could be modulated by preincubation with anti-MuMTV serum, in contrast to H-2.8 and Thy 1.2 antigens. The results obtained with the immunoferritin technique and the cytotoxicity test correlated well and sug-ested that the shedding of MuMTV antigens from the cell surfaces may occur in vivo, providing the tumor a way to escape from the immune defense of the host. Thy 1.2 and H-2.8 antigens were present on the envolope of B and C particles, which suggested that these viruses do not select a Thy 1.2 or H-2.8-negative area of the GRSL cell surface as amaturation site.
New QOF targets focus on physical health of patients with mental health problems
Authors: Adrian O’Dowd
Journal: BMJ (2015)

GPs may be asked to adopt new quality indicators to ensure better physical health for people with mental health problems, under new proposals from the National Institute for Health and Care Excellence (NICE). On 3 August NICE published its latest set of proposals for indicators that will be the subject of imminent negotiations for the 2016-17 Quality and Outcomes Framework (QOF)—the voluntary incentive scheme that rewards general practices for implementing improvements in the quality of care.1 NICE’s proposals include new indicators alongside updates to existing indicators. New indicators have been developed to identify:
Lung function and early abnormality of glucose tolerance (GT) in cystic fibrosis (CF) patients
Authors: Alexandre Leclercq, Laurence Kessler, Vincent Rosner, Laurence Weiss, Beatrice Gauthier, Romain Kessler
Journal: European Respiratory Journal (2013)

Diabetes is a frequent complication of CF and occurs in about 50% of patients older than 30 years. Its presence is correlated with the decline of lung function. Early diagnosis is based on the oral glucose tolerance test (OGTT) which could lack sensitivity in some of these patients. Continuous glucose monitoring (CGM) could be a useful tool for evaluating early abnormalities of GT in CF patients.  In a single-center, observational, prospective, cross sectional study, we compared nutritional status, lung function and antibiotic courses of CF patients depending on the presence or absence of abnormal GT in OGTT or in CGM. Known diabetics were excluded. From June 2008 to July 2012, 68 patients were included: male 46%, mean age 25 years (12-57). 51 patients (75%) had a normal OGTT (group 1), 11 (16%) were glucose intolerant and 6 (9%) had diabetes (group 2). In group 2, FEV was lower (80,8%±23,1 Vs. 61,6%±23,1; p=0.01), FVC lower (94,5%±17,5 Vs. 77,5%±20,5; p=0.002), HbA1c higher (p=0.005), while the number of antibiotic courses was increased (0,86±1,11 Vs. 1,71±; p=0.01). Using CGM we defined 2 groups: maximum glucose   Thus, an early abnormality of GT in CF patients is associated with greater impairment of lung function. CGM seems an interesting tool to diagnose early abnormalities of glucose tolerance in CF patients.
Tumors Produced by Adenovirus 12 in &lt;italic&gt;Mastomys&lt;/italic&gt; and Mice
Authors: Alan S. Rabson, Ruth L. Kirschstein, Frances J. Paul
Journal: JNCI Journal of the National Cancer Institute (1964)

Newborn Mastomys [Rattus (Mastomys) natalensis] and newborn C3H/Bi mice were inoculated witb human adenovirus 12. Some of the animals were inoculated subcutaneously, some intracerebrally, and some by both routes. Tumors were observed in 2 of 32 Mastomys after 5 to 6 months and in 7 of 29 mice after 2½ to 6 months. Histologically, the tumors were similar to those described by Trentin and his associates and by Huebner and his associates in Syrian hamsters inoculated with adenovirus 12, and we have classified them as "undifferentiated malignant tumors." Transplantation of one of the mouse tumors was attempted, and it was serially transplantable in C3H/Bi mice. Attempts to isolate virus from the tumors were unsuccessful.