Impact of the enhanced permeability and retention (EPR) effect and cathepsins levels on the activity of polymer-drug conjugates

Polymer-drug conjugates have demonstrated clinical potential in the context of anticancer therapy. However, such promising results have, to date, failed to translate into a marketed product. Polymer-drug conjugates rely on two factors for activity: (i) the presence of a defective vasculature, for passive accumulation of this technology into the tumour tissue (enhanced permeability and retention (EPR) effect) and (ii) the presence of a specific trigger at the tumour site, for selective drug release (e.g., the enzyme cathepsin B). Here, we retrospectively analyse literature data to investigate which tumour types have proved more responsive to polymer-drug conjugates and to determine correlations between the magnitude of the EPR effect and/or expression of cathepsin B. Lung, breast and ovarian cancers showed the highest response rate (30%, 47% and 41%, respectively for cathepsin-activated conjugates and 31%, 43%, 40%, across all conjugates). An analysis of literature data on cathepsin content in various tumour types showed that these tumour types had high cathepsin content (up to 3835 ng/mg for lung cancer), although marked heterogeneity was observed across different studies. In addition, these tumour types were also reported as having a high EPR effect. Our results suggest that a pre-screening of patient population could bring a more marked clinical benefit.

Exercise Training Reduces PGE(2) Levels and Induces Recovery from Steatosis in Tumor-bearing Rats

The effects of endurance training on PGE(2) levels and upon the maximal activity of hepatic carnitine palmitoyltransferase (CPT) system were studied in rats bearing the Walker 256 carciosarcoma. Animals were randomly assigned to a sedentary control (SC), sedentary tumor-bearing (ST), exercised control (EC), and as an exercised tumor-bearing (ET) group. Trained rats ran on a treadmill (60% VO(2) max) for 60 min/day, 5 days/week, for 8 weeks. We examined the mRNA expression (RT-PCR) and maximal activity (radio-assay) of the carnitine palmitoyltransferase system enzymes (CPT I and CPT II), as well as the gene expression of fatty-acid-binding protein (L-FABP) in the liver. PGE(2) content was measured in the serum, in tumor cells, and in the liver (ELISA). CPT I and CPT II maximal activity were decreased (p < 0.01) in ST when compared with SC. In contrast, serum PGE(2) was increased (p < 0.05) in cachectic animals as compared with SC. In the liver, PGE(2) content was also increased (p < 0.05) when compared with SC. Endurance training restored maximal CPT I and CPT II activity in the tumor-bearing animals (p < 0.0001). Exercise training induced PGE(2) levels to return to control values in the liver of tumor-bearing training rats (p < 0.05) and decreased the eicosanoid content in the tumor (p < 0.01). In conclusion, endurance training was capable of reestablishing liver carnitine palmitoyltransferase (CPT) system activity associated with decreased PGE(2) levels in cachectic tumor-bearing animals, preventing steatosis.

Analysis and risk estimates to workers of Brazilian granitic industries and sandblasters exposed to respirable crystalline silica and natural radionuclides

Occupational exposure to respirable crystalline silica and to radiation emitted by natural radionuclides present both in rocks and sands was studied in the Brazilian extractive process and granite product manufacture. Respirable airborne dust samples were collected in working environments, where workers perform different tasks with distinct commercial granites types, and also in places where sandblasters work with sands from different origins. The free crystalline silica contents were determined using X-ray diffraction of the respirable particulate fraction of each sample. Dust samples from granite cutting and sandblasting ambient had the natural radionuclides concentrations measured by gamma spectrometry. Dust concentrations in the workplaces were quite variable, reaching values up to 10 times higher than the respirable particle mass threshold limit value (TLV) set by the American Conference for Governmental Industrial Hygienists of 3 mg m(-3). Also the free crystalline silica concentrations were high. reaching values up to 48 times the TLV of 0.025 mg m(-3). Additionally, our results suggest that the risk of radiation-induced cancer in the granite or marble industries is negligible. However, the combined exposure to dust, gamma radiation, and radon daughter products could result in the enhancement of lung cancer risks associated to sandblasting activities. (C) 2010 Elsevier Ltd. All rights reserved.

Occupational exposure to radon and natural gamma radiation in the La Carolina, a former gold mine in San Luis Province, Argentina

Radon and gamma radiation level measurements were carried out inside the La Carolina mine, one of the oldest gold mining camps of southern South America, which is open for touristic visits nowadays. CR-39 track-etch detectors and thermoluminescent dosimeters of natural CaF(2) and LiF TLD-100 were exposed at 14 points along the mine tunnels in order to estimate the mean (222)Rn concentration and the ambient dose equivalent during the summer season (November 2008 to February 2009). The values for the (222)Rn concentration at each monitoring site ranged from 1.8 +/- 0.1 kBq m(-3) to 6.0 +/- 0.5 kBq m(-3), with a mean value of 4.8 kBq m(-3), indicating that these measurements exceed in about three times the upper action level recommended by ICRP for workplaces. The correlations between radon and gamma radiation levels inside the mine were also investigated. Effective doses due to (222)Rn and gamma rays inside the mine were determined, resulting in negligible values to tourists. Considering the effective dose to the mine tourist guides, values exceeding 20 mSv of internal contribution to the effective doses can be reached, depending on the number of working hours inside the mine. (C) 2009 Elsevier Ltd. All rights reserved.

Objective Detection and Delineation of Oral Neoplasia Using Autofluorescence Imaging

Although the oral cavity is easily accessible to inspection, patients with oral cancer most often present at a late stage, leading to high morbidity and mortality. Autofluorescence imaging has emerged as a promising technology to aid clinicians in screening for oral neoplasia and as an aid to resection, but current approaches rely on subjective interpretation. We present a new method to objectively delineate neoplastic oral mucosa using autofluorescence imaging. Autofluorescence images were obtained from 56 patients with oral lesions and 11 normal volunteers. From these images, 276 measurements from 159 unique regions of interest (ROI) sites corresponding to normal and confirmed neoplastic areas were identified. Data from ROIs in the first 46 subjects were used to develop a simple classification algorithm based on the ratio of red-to-green fluorescence; performance of this algorithm was then validated using data from the ROIs in the last 21 subjects. This algorithm was applied to patient images to create visual disease probability maps across the field of view. Histologic sections of resected tissue were used to validate the disease probability maps. The best discrimination between neoplastic and nonneoplastic areas was obtained at 405 nm excitation; normal tissue could be discriminated from dysplasia and invasive cancer with a 95.9% sensitivity and 96.2% specificity in the training set, and with a 100% sensitivity and 91.4% specificity in the validation set. Disease probability maps qualitatively agreed with both clinical impression and histology. Autofluorescence imaging coupled with objective image analysis provided a sensitive and noninvasive tool for the detection of oral neoplasia.

Mutagenicity and DNA adduct formation of PAH, nitro-PAH, and oxy-PAH fractions of atmospheric particulate matter from Sao Paulo, Brazil

Urban particulate matter (UPM) contributes to lung cancer incidence. Here, we have studied the mutagenic activity and DNA adduct-forming ability of fractionated UPM extractable organic matter (EOM). UPM was collected with a high-volume sampler in June 2004 at two sites, one at street level adjacent to a roadway and the other inside a park within the urban area of the city of Sao Paulo, Brazil. UPM was extracted using dichloromethane, and the resulting EOM was separated by HPLC to obtain PAH, nitro-PAH, and oxy-PAH fractions which were tested for mutagenicity with the Salmonella strains TA98 and YG1041 with and without S9 metabolic activation. The PAH fraction from both sites showed negligible mutagenic activity in both strains. The highest mutagenic activity was found for the nitro-PAH fraction using YG1041 without metabolic activation; however, results were comparable for both sites. The nitro-PAH and oxy-PAH fractions were incubated with calf thymus DNA under reductive conditions appropriate for the activation of nitro aromatic compounds, then DNA adduct patterns and levels were determined with thin-layer chromatography (TLC) (32)p-postlabeling method using two enrichment procedures-nuclease PI digestion and butanol extraction. Reductively activated fractions from both sites produced diagonal radioactive zones (DRZ) of putative aromatic DNA adducts on thin layer plates with both enrichment procedures. No such DRZ were observed in control experiments using fractions from unexposed filters or from incubations without activating system. Total adduct levels produced by the nitro-PAH fractions were similar for both sites ranging from 30 to 45 adducts per 10(8) normal nucleotides. In contrast, the DNA binding of reductively activated oxy-PAH fractions was three times higher and the adduct pattern consisted of multiple discrete spots along the diagonal line on the thin layer plates. However, DNA adduct levels were not significantly different between the sampling sites. Both samples presented the same levels of mutagenic activity. The response in the Salmonella assay was typical of nitroaromatics. Although, more mutagenic activity was related to the nitro-PAH fraction in the Salmonella assay, the oxy-PAH fractions showed the highest DNA adduct levels. More studies are needed to elucidate the nature of the genotoxicants occurring in Sao Paulo atmospheric samples. (C) 2008 Elsevier B.V. All rights reserved.

Att vara anhörigvårdare till en lungcancersjuk patient

Syftet med denna systematiska litteraturstudie är att undersöka upplevelser hos anhörigvårdare till lungcancerpatienter. Artikelsökningar har skett i Cinahl och Pubmed. Tiden för anhörigvårdaren kan se olika ut, kort och intensiv eller lång och utmattande. Upplevelser så som skräck är vanligt förekommande direkt efter lungcancerdiagnosen både för patient och vårdare. Detta för att de anhöriga ställs inför ett klart hot om en kommande förlust samt skrämmande tankar kring döden. Hälsan försämras för anhörigvårdaren under vårdtiden och vissa drabbas av depression. De social relationerna försämras, vissa upphör helt då anhörigvårdaren får en känsla av att de alltid måste vara tillgängliga för den sjuke. Vårdbördan kan vara tung och emotionellt stöd kan vara nödvändigt. Trots det väljer många att inte ta emot eller söka något stöd.Inte bara hälsan förändras under sjukdomstiden utan också mycket annat, den som tidigare haft en passiv roll i hushållet kan bli tvungen att ta en mer aktiv roll i skötseln av hem och ekonomi. Trots att anhörigvårdare ofta känner sig utanför och övergivna väljer de att inte uttrycka sina känslor när de blir tillfrågade eftersom det finns en rädsla att ta fokus från patienten.

Upplevelser av lungcancervården: Patient och närståendes perspektiv : En empirisk studie med kvalitativ ansats

Syfte: Syftet var att utifrån patienters och närståendes nerskrivna berättelser ta del av deras upplevelser och erfarenheter av lungcancervården samt att utifrån dessa berättelser identifiera förbättringsidéer.Metod: Studien hade en empirisk design med kvalitativ ansats. Datainsamlingen skedde via idéböcker. Materialet analyserades genom kvalitativ innehållsanalys.Resultat: Två teman framkom i resultat. Det första temat var: Känslor av otrygghet och lidande kopplat till vården, livet och den egna sjukdomen. De tillhörande kategorierna var vårdlidande, livslidande och sjukdomslidande. Det andra temat var: Känslor av trygghet kopplat till goda mellanmänskliga relationer. Tillhörande kategori var goda mellanmänskliga relationer. Utökat psykosocialt stöd och utbildning i kommunikation till personal fanns bland de idéer för utveckling av lungcancervården som framkom.Konklusion: Denna studie visade att patienter med lungcancer kände otrygghet och lidande, till stor del orsakat av vården. Där goda möten ägde rum skapades trygghet och goda mellanmänskliga relationer. Utökat psykosocialt stöd och utbildning i kommunikation till personal fanns bland de idéer för utveckling av lungcancervården som framkom.

Sjuksköterskans främjande av livskvalitet hos lungcancerpatienter i palliativ fas : En litteraturöversikt

Bakgrund: Lungcancer är en sjukdom med dålig prognos och hög dödlighet. Många patienter behandlas därför med palliativ vård. Att ha lungcancer påverkar patientens livskvalitet, och sjuksköterskan har ett stort ansvar i att främja patientens livkvalitet. Syfte: Att beskriva vad som innefattades i begreppet livskvalitet utifrån lungcancersjuka patienter i palliativ fas, vilka faktorer som påverkade känslan av den och hur sjuksköterskan kunde främja livskvalitet utifrån sin yrkesroll. Metod: Studien genomfördes som en litteraturöversikt. Totalt användes 25 artiklar av både kvalitativ och kvantitativ ansats. Artiklar till studien söktes i databaserna CINHAL och PubMed. Resultat: Livskvalitet är ett multidimensionellt begrepp och det kan ses som någonting individuellt och unikt för varje enskild lungcancersjuk patient, och innebörden av begreppet hade olika betydelse för alla. Livskvalitet kunde påverkas utifrån både fysiska, psykiska, sociala och existentiella aspekter. Sjuksköterskan hade därför en viktig roll i att ha en helhetssyn på patienten och se denne som en enskild individ i situationen, för att livskvalitet ska kunna främjas optimalt hos patienten. Slutsats: Livskvalitet är ett oändligt begrepp, som har en unik betydelse för varje patient. Som sjuksköterska fanns inget facit på vilka åtgärder som bäst kan främja patientens livskvalitet. Dock handlar det om till stor del för sjuksköterskan att våga möta patienten i denna svåra situation och att våga lyssna på patienten.

Hälsa och livskvalitet hos personer diagnostiserade med lungcancer : En deskriptiv enkätstudie

Syfte: Syftet med studien var att undersöka skattningen av hälsa och livskvalitet utifrån kön, ålder och rökvanor hos personer med lungcancer. Vidare syftade studien till att undersöka om det fanns samband mellan specifika sjukdomssymptom och personens skattning av hälsa, livskvalitet och förekomsten av rökning eller tidigare rökning. Metod: Studien genomfördes som en deskriptiv studie. Deltagarna (n=68) var samtliga diagnostiserade med lungcancer och bosatta i Dalarna, Sverige. Resultat: Ökade besvär av vissa sjukdomssymptom, däribland svårigheter att ta en långpromenad samt trötthet, hade ett signifikant samband med en lägre skattad hälsa. Vid ökade besvär av vissa sjukdomssymptom, däribland nedstämdhet och sömnsvårigheter, sågs samband med en lägre skattning av livskvaliteten. Personer som var, eller tidigare hade varit rökare, hade i högre utsträckning besvär av vissa sjukdomssymptom som andfåddhet och svårigheter att göra ansträngande saker. Sammanfattning: Studien visade att det fanns signifikanta samband mellan vissa sjukdomssymptom och hur personen med lungcancer upplever sin hälsa och livskvalitet. Detta är viktigt att bejaka i omvårdnaden av personer som drabbats för att kunna främja hälsa och livskvalitet. Det fanns även signifikanta samband mellan vissa sjukdomssymptom och förekomsten av rökning eller tidigare rökning. Detta är en indikation på att hälso- och sjukvården bör fortsätta att arbeta tobakspreventivt för att motiverat att arbeta för att personer ska sluta röka.

Medical image classification using an efficient data mining technique

Data mining refers to extracting or "mining" knowledge from large amounts of data. It is an increasingly popular field that uses statistical, visualization, machine learning, and other data manipulation and knowledge extraction techniques aimed at gaining an insight into the relationships and patterns hidden in the data. Availability of digital data within picture archiving and communication systems raises a possibility of health care and research enhancement associated with manipulation, processing and handling of data by computers.That is the basis for computer-assisted radiology development. Further development of computer-assisted radiology is associated with the use of new intelligent capabilities such as multimedia support and data mining in order to discover the relevant knowledge for diagnosis. It is very useful if results of data mining can be communicated to humans in an understandable way. In this paper, we present our work on data mining in medical image archiving systems. We investigate the use of a very efficient data mining technique, a decision tree, in order to learn the knowledge for computer-assisted image analysis. We apply our method to the classification of x-ray images for lung cancer diagnosis. The proposed technique is based on an inductive decision tree learning algorithm that has low complexity with high transparency and accuracy. The results show that the proposed algorithm is robust, accurate, fast, and it produces a comprehensible structure, summarizing the knowledge it induces.

Families as carers-information needs in a cultural context

While the important role of family as a carer has been increasingly recognised in healthcare service provision, particularly for patients with acute or chronic illnesses, the carer’s information needs have not been well understood and adequately supported by current health information systems. In order to effectively provide continuous and home-based care for the patient, a family relative as the primary carer needs sufficient access to medical knowledge and patient’s health information. There are two challenges. First, being a family relative, the primary carer is often a non-medical practitioner. Second, in Australia, many primary carers are family relatives of patients from a non-English speaking background. They are often seen as interpreters in clinical consultation sessions. Their roles and responsibilities as an interpreter and a carer are often mixed and blurry.
Therefore, their information needs are often seen as secondary to the patient or neglected. The primary carer’s information needs are currently not yet well understood.

This paper reports finding from a case study which examines an on-line diary of a husband-carer who provided support and care for his wife, who at the time of care was a lung cancer patient. The case study examines an ongoing learning process that the husband went through, identifies information needs by the carer and cultural factors which played an important role in the husband’s interpretation of information, decision making and provision of care. The finding extends a current model of the user’s information needs in the literature and suggests implications for further research into developing health information systems to meet information needs by the family carer.

Information systems and healthcare XXVIII : the information needs of family carers in collaborative healthcare

While the important role of family carers has been increasingly recognized in healthcare service provision, particularly for patients with acute or chronic illnesses, the family carer's information needs have not been well understood or adequately supported by health information systems. In this study, we explore the information needs of a family carer by analyzing the extensive online diary of a Vietnamese family carer supporting his wife, who was a lung cancer patient. The study provides a deep understanding of the information needs of the family carer and suggests a four-stage information journey model including identification, searching, interpretation and information sharing, and collaboration. A number of themes emerge from the study including the key role of the carer, information filtering by the carer, information sharing and collaboration, and the influence of Vietnamese culture. The paper concludes with a discussion of the requirements for health information systems that meet the needs of family carers.

The decision-making journey of a family carer : information and social needs in a cultural context

While the important role of family as carer has been increasingly recognised in healthcare service provision, particularly for patients with acute or chronic illnesses, the carer's information and social needs have not been well understood and adequately supported. In order to provide continuous and home-based care for the patient, and to make informed decisions about the care, a family carer needs sufficient access to medical information in general, the patient's health information specifically, and supportive care services. Two key challenges are the carer's lack of medical knowledge and the many carers with non-English speaking and different cultural backgrounds. The informational and social needs of family carers are not yet well understood. This paper analyses the web-log of a husband-carer who provided support for his wife, who at the time of care was a lung cancer patient. It examines the decision-making journey of the carer and identifies the key issues faced in terms of informational and social practices surrounding care provision.

An epidemiological analysis of the 'autism as mercury poisoning' hypothesis

Where direct experimental research into a causal hypothesis of a disease is impossible due to ethical and practical considerations, epidemiological inference is the accepted route to establishing cause. Therefore, to examine the autism as mercury poisoning hypothesis, this paper reviews the existing scientific literature within the context of established epidemiological criteria and finds that the evidence for a causal relationship is compelling. Exposure to mercury (via vaccines and maternal dental amalgam) in utero and during infant years is confirmed; mercury poisoning is known to cause symptoms consistent with autism; animal modeling supports the link and, critically, mercury levels are higher in both the urine and blood of autistic children than in non-autistic peers. Analogous to epidemiological evidence of the smoking–lung cancer relationship, a mercury–autism relationship is confirmed. The precautionary principle demands that health professionals not take an action if there is suspicion that the action may cause severe or lifelong health effects: it does not require certainty. Therefore, given the severity, devastating lifelong impact and extremely high prevalence of autism, it would be negligent to continue to expose pregnant and nursing mothers and infant children to any amount of avoidable mercury.