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1.
BMC Palliat Care ; 20(1): 91, 2021 Jun 24.
Article in English | MEDLINE | ID: mdl-34167547

ABSTRACT

BACKGROUND: Palliative care focuses on identifying, from a holistic perspective, the needs of those experiencing problems associated with life-threatening illnesses. As older people approach the end of their lives, they can experience a complex series of problems that health-care professionals must identify and document in their patients' records. Documentation is thus important for ensuring high-quality patient care. Previous studies of documentation in older people's patient records performed in various care contexts have shown that such documentation almost exclusively concerns physical problems. This study explores, in the context of Swedish specialised palliative care, the content of documentation in older people's patient records, focusing on documented problems, wishes, aspects of wellbeing, use of assessment tools, interventions, and documentation associated with the person's death. METHODS: A retrospective review based on randomly selected records (n = 92) of older people receiving specialised palliative care, at home or in a palliative in-patient ward, who died in 2017. A review template was developed based on the literature and on a review of sampled records of patients who died the preceding year. The template was checked for inter-rater agreement and used to code all clinical notes in the patients' records. Data were processed using descriptive statistics. RESULTS: The most common clinical notes in older people's patient records concerned interventions (n = 16,031, 71%), mostly related to pharmacological interventions (n = 4318, 27%). The second most common clinical notes concerned problems (n = 2804, 12%), pain being the most frequent, followed by circulatory, nutrition, and anxiety problems. Clinical notes concerning people's wishes and wellbeing-related details were documented, but not frequently. Symptom assessment tools, except for pain assessments, were rarely used. More people who received care in palliative in-patient wards died alone than did people who received care in their own homes. CONCLUSIONS: Identifying and documenting the complexity of problems in a more structured and planned way could be a method for implementing a more holistic approach to end-of-life care. Using patient-reported outcome measures capturing more than one symptom or problem, and a systematic documentation structure would help in identifying unmet needs and developing holistic documentation of end-of-life care.


Subject(s)
Hospice Care , Terminal Care , Aged , Documentation , Humans , Palliative Care , Retrospective Studies
2.
BMC Cancer ; 19(1): 472, 2019 May 20.
Article in English | MEDLINE | ID: mdl-31109309

ABSTRACT

BACKGROUND: Breast cancer (BC) is the most common type of cancer in women worldwide. Post-treatment, patients suffer from side effects and have various rehabilitation needs, which means that individualization is fundamental for optimal rehabilitation. This systematic review (SR) of SRs aims to evaluate the current evidence on rehabilitation interventions in female patients following BC treatment. METHODS: Full-text SRs published in English from 2009 were searched in Embase, PubMed, Cinahl Complete, PsycINFO, AMED, SCOPUS, and Cochrane Library. INCLUSION CRITERIA: SRs of randomized or non-randomized controlled trials investigating the effects of rehabilitation interventions in women following BC treatment. All outcomes were considered. Methodological quality was evaluated using the AMSTAR 2 tool and interrater agreement was evaluated. Out of 1269 citations retrieved, 37 SRs were included. RESULTS: Five rehabilitation areas were identified: exercise and physical activity (PA), complementary and alternative medicine (CAM), yoga, lymphoedema treatment, and psychosocial interventions. The most solid evidence was found in exercise/PA and yoga. Exercise interventions improved outcomes such as shoulder mobility, lymphoedema, pain, fatigue and quality of life (QoL). Effects of yoga were shown on QoL, anxiety, depression, sleep disturbance, fatigue and gastrointestinal symptoms. The effect of CAM was shown on nausea, pain, fatigue, anger and anxiety but these results need to be interpreted with caution because of low methodological quality in included studies in the SRs. Among the lymphoedema treatments, positive effects were seen for resistance training on volume reduction and muscle strength and psychosocial interventions such as cognitive behavioural therapy had positive effects on QoL, anxiety, depression and mood disturbance. CONCLUSIONS: This SR of SRs show solid positive effects of exercise/PA and yoga for women following BC treatment, and provides extended knowledge of the effects of CAM, yoga, lymphoedema treatment and psychosocial interventions. It is evident that more than one intervention could have positive effects on a specific symptom and that the effects depend not only on intervention type but also on how and when the intervention is provided. The results can be used as a foundation for individualized rehabilitation and aid health care professionals in meeting patients' individual needs and preferences. TRIAL REGISTRATION: PROSPERO ( CRD42017060912 ).


Subject(s)
Breast Neoplasms/rehabilitation , Lymphedema/rehabilitation , Quality of Life/psychology , Breast Neoplasms/psychology , Exercise , Female , Humans , Lymphedema/etiology , Resistance Training , Systematic Reviews as Topic , Treatment Outcome , Yoga
3.
BMC Palliat Care ; 17(1): 20, 2018 Jan 29.
Article in English | MEDLINE | ID: mdl-29378566

ABSTRACT

BACKGROUND: A growing body of studies indicate benefits of physiotherapy for patients in palliative care, for symptom relief and wellbeing. Though physiotherapists are increasingly acknowledged as important members of palliative care teams, they are still an underutilized source and not fully recognized. The aim of this study was to explore the variety of activities described by physiotherapists in addressing the needs and problems of patients and their families in specialized palliative care settings. METHODS: Using a free-listing approach, ten physiotherapists working in eight specialized palliative care settings in Sweden described as precisely and in as much detail as possible different activities in which patients and their families were included (directly or indirectly) during 10 days. The statements were entered into NVivo and analysed using qualitative content analysis. Statements containing more than one activity were categorized per activity. RESULTS: In total, 264 statements, containing 504 varied activities, were coded into seven categories: Counteracting a declining physical function; Informing, guiding and educating; Observing, assessing and evaluating; Attending to signs and symptoms; Listening, talking with and understanding; Caring for basic needs; and Organizing, planning and coordinating. In practice, however, the activities were intrinsically interwoven. The activities showed how physiotherapists aimed, through care for the body, to address patients' physical, psychological, social and existential needs, counteracting the decline in a patient's physical function and wellbeing. The activities also revealed a great variation, in relation not only to what they did, but also to their holistic and inseparable nature with regard to why, how, when, where, with whom and for whom the activities were carried out, which points towards a well-adopted person-centred palliative care approach. CONCLUSIONS: The study provides hands-on descriptions of how person-centred palliative care is integrated in physiotherapists' everyday activities. Physiotherapists in specialized palliative care help patients and families to bridge the gap between their real and ideal everyday life with the aim to maximize security, autonomy and wellbeing. The concrete examples included can be used in understanding the contribution of physiotherapists to the palliative care team and inform future research interventions and outcomes.


Subject(s)
Palliative Care/methods , Physical Therapists/trends , Adult , Attitude of Health Personnel , Female , Humans , Male , Middle Aged , Physical Therapists/standards , Qualitative Research , Sweden , Workforce
4.
Clin Exp Allergy ; 46(10): 1355-65, 2016 10.
Article in English | MEDLINE | ID: mdl-27061126

ABSTRACT

BACKGROUND: Besides allergens, pollen release bioactive, low molecular weight compounds that modulate and stimulate allergic reactions. Clinical relevance of these substances has not been investigated to date. OBJECTIVE: To elucidate the effect of a non-allergenic, low molecular weight factors from aqueous birch pollen extracts (Bet-APE < 3 kDa) on the human allergic immune response in vivo. METHODS: Birch and grass pollen allergic individuals underwent skin prick testing with allergen alone, allergen plus Bet-APE < 3 kDa, or allergen plus pre-identified candidate substances from low molecular pollen fraction. Nasal allergen challenges were performed in non-atopic and pollen allergic individuals using a 3 day repeated threshold challenge battery. Subjects were either exposed to allergen alone or to allergen plus Bet-APE< 3 kDa. Local cytokine levels, nasal secretion weights, nasal congestion and symptom scores were determined. RESULTS: Skin prick test reactions to pollen elicited larger weals when allergens were tested together with the low molecular weight compounds from pollen. Similar results were obtained with candidate pollen-associated lipid mediators. In nasal lining fluids of allergic patients challenged with allergen plus Bet-APE < 3 kDa, IL-8 and IgE was significantly increased as compared to allergen-only challenged patients. These patients also produced increased amounts of total nasal secretion and reported more severe rhinorrhea than the allergen-only challenged group. CONCLUSIONS: Low molecular compounds from pollen enhance the allergen specific immune response in the skin and nose. They are therefore of potential clinical relevance in allergic patients.


Subject(s)
Allergens/immunology , Immunity , Immunomodulation , Plant Extracts/immunology , Pollen/immunology , Rhinitis, Allergic, Seasonal/immunology , Basophils/immunology , Basophils/metabolism , Betula/immunology , Cell Degranulation/immunology , Humans , Immunoglobulin E/blood , Immunoglobulin E/immunology , Inflammation Mediators/metabolism , Interleukin-8/metabolism , Molecular Weight , Nasal Mucosa/immunology , Nasal Mucosa/metabolism , Nasal Provocation Tests , Plant Extracts/chemistry , Pollen/chemistry , Rhinitis, Allergic, Seasonal/diagnosis , Rhinitis, Allergic, Seasonal/metabolism , Skin Tests , Symptom Assessment , Th2 Cells/immunology , Th2 Cells/metabolism
5.
Mucosal Immunol ; 9(4): 974-85, 2016 07.
Article in English | MEDLINE | ID: mdl-26555704

ABSTRACT

Matrix metalloproteinases (MMPs) are potential biomarkers for disease activity in inflammatory bowel disease (IBD). However, clinical trials targeting MMPs have not succeeded, likely due to poor understanding of the biological functions of individual MMPs. Here, we explore the role of MMP-19 in IBD pathology. Using a DSS-induced model of colitis, we show evidence for increased susceptibility of Mmp-19-deficient (Mmp-19(-/-)) mice to colitis. Absence of MMP-19 leads to significant disease progression, with reduced survival rates, severe tissue destruction, and elevated levels of pro-inflammatory modulators in the colon and plasma, and failure to resolve inflammation. There was a striking delay in neutrophil infiltration into the colon of Mmp-19(-/-) mice during the acute colitis, leading to persistent inflammation and poor recovery; this was rescued by reconstitution of irradiated Mmp-19(-/-) mice with wild-type bone marrow. Additionally, Mmp-19-deficient macrophages exhibited decreased migration in vivo and in vitro and the mucosal barrier appeared compromised. Finally, chemokine fractalkine (CX3CL1) was identified as a novel substrate of MMP-19, suggesting a link between insufficient processing of CX3CL1 and cell recruitment in the Mmp-19(-/-) mice. MMP-19 proves to be a critical factor in balanced host response to colonic pathogens, and for orchestrating appropriate innate immune response in colitis.


Subject(s)
Chemokine CX3CL1/metabolism , Colitis/immunology , Colon/immunology , Inflammatory Bowel Diseases/immunology , Intestinal Mucosa/immunology , Macrophages/immunology , Matrix Metalloproteinases, Secreted/metabolism , Animals , Cell Movement , Cells, Cultured , Colitis/chemically induced , Cytokines/metabolism , Dextran Sulfate , Disease Progression , Humans , Immunity, Innate , Inflammation Mediators/metabolism , Intestinal Mucosa/pathology , Matrix Metalloproteinases, Secreted/genetics , Mice , Mice, Inbred C57BL , Mice, Knockout , Neutrophil Infiltration/genetics
6.
J Virol Methods ; 210: 36-9, 2014 12 15.
Article in English | MEDLINE | ID: mdl-25239368

ABSTRACT

An oligonucleotide ligation assay (OLA) designed to detect Human Immunodeficiency Virus type-1 (HIV)-drug-resistance to the nevirapine (NVP) selected mutations K103N, Y181C, V106M and G190A was used to evaluate 200 archived dried blood spots (DBS) from infected infants participating in the Zimbabwean Early Infant Diagnosis (EID) Program. Consensus sequencing of specimens with indeterminate OLA results was performed to identify genetic sequence polymorphisms that appeared to compromise performance of the OLA. When consistent patterns of polymorphisms were observed the probes were redesigned, and DBS specimens with indeterminate OLA results were retested with the new Zimbabwe-specific (ZW) probes. OLA results obtained in Zimbabwe were compared to repeat testing in a US reference laboratory. 188/200 (94%) DBS yielded polymerase chain reaction (PCR) amplification of HIV pol. ZW probes reduced indeterminate OLA results from 5.2% to 2.8% of codons evaluated (p=0.02), with 98.2% concordance between results obtained in the Zimbabwean and US laboratories. Optimization of OLA probes to accommodate polymorphisms in regional HIV variants improved OLA performance, and comparison to the USA results showed successful implementation of the OLA in Zimbabwe for detection of NVP resistance mutations in DBS specimens.


Subject(s)
Anti-HIV Agents/pharmacology , Drug Resistance, Viral/genetics , HIV Infections/virology , HIV-1/genetics , Nevirapine/pharmacology , Genotype , Genotyping Techniques , HIV Infections/drug therapy , HIV-1/isolation & purification , Humans , Infant , Infant, Newborn , Oligonucleotide Probes , Point Mutation , Polymerase Chain Reaction , Sensitivity and Specificity , Zimbabwe
7.
J Appl Physiol (1985) ; 110(3): 610-8, 2011 Mar.
Article in English | MEDLINE | ID: mdl-21148341

ABSTRACT

Hyperoxia has been shown to attenuate the increase in pulmonary artery (PA) pressure associated with immersed exercise in thermoneutral water, which could serve as a possible preventive strategy for the development of immersion pulmonary edema (IPE). We tested the hypothesis that the same is true during exercise in cold water. Six healthy volunteers instrumented with arterial and PA catheters were studied during two 16-min exercise trials during prone immersion in cold water (19.9-20.9°C) in normoxia [0.21 atmospheres absolute (ATA)] and hyperoxia (1.75 ATA) at 4.7 ATA. Heart rate (HR), Fick cardiac output (CO), mean arterial pressure (MAP), pulmonary artery pressure (PAP), pulmonary artery wedge pressure (PAWP), central venous pressure (CVP), arterial and venous blood gases, and ventilatory parameters were measured both early (E, 5-6 min) and late (L, 15-16 min) in exercise. During exercise at an average oxygen consumption rate (Vo(2)) of 2.38 l/min, [corrected] CO, CVP, and pulmonary vascular resistance were not affected by inspired (Vo(2)) [corrected] or exercise duration. Minute ventilation (Ve), alveolar ventilation (Va), and ventilation frequency (f) were significantly lower in hyperoxia compared with normoxia (mean ± SD: Ve 58.8 ± 8.0 vs. 65.1 ± 9.2, P = 0.003; Va 40.2 ± 5.4 vs. 44.2 ± 9.0, P = 0.01; f 25.4 ± 5.4 vs. 27.2 ± 4.2, P = 0.04). Mixed venous pH was lower in hyperoxia compared with normoxia (7.17 ± 0.07 vs. 7.20 ± 0.07), and this result was significant early in exercise (P = 0.002). There was no difference in mean PAP (MPAP: 28.28 ± 8.1 and 29.09 ± 14.3 mmHg) or PAWP (18.0 ± 7.6 and 18.7 ± 8.7 mmHg) between normoxia and hyperoxia, respectively. PAWP decreased from early to late exercise in hyperoxia (P = 0.002). These results suggest that the increase in pulmonary vascular pressures associated with cold water immersion is not attenuated with hyperoxia.


Subject(s)
Cold Temperature/adverse effects , Exercise , Hyperoxia/complications , Hyperoxia/physiopathology , Hypertension, Pulmonary/physiopathology , Immersion/adverse effects , Pulmonary Edema/physiopathology , Adult , Female , Humans , Hypertension, Pulmonary/complications , Male , Middle Aged , Prone Position , Pulmonary Edema/complications , Young Adult
8.
J Physiol ; 586(19): 4721-33, 2008 Oct 01.
Article in English | MEDLINE | ID: mdl-18687717

ABSTRACT

The contraction of cardiomyocytes induces a systolic increase in left ventricular (LV) normal (radial, circumferential and longitudinal) and shear strains, whose functional consequences have not been evaluated, so far, in athletes. We used 2D ultrasound speckle tracking imaging (STI) to evaluate LV regional strain in high-level cyclists compared to sedentary controls. Sixteen male elite cyclists and 23 sedentary controls underwent conventional, tissue Doppler, and STI echocardiography at rest. We assessed LV long and short axis normal strains and shear strains. We evaluated circumferential-longitudinal shear strain from LV torsion, and circumferential-radial shear strain from the difference between subendocardial and subepicardial torsion. Apical radial strain (42.7 +/- 10.5% versus 52.2 +/- 14.3%, P < 0.05) and LV torsion (6.0 +/- 1.8 deg versus 9.2 +/- 3.2 deg, P < 0.01) were lower in cyclists than in controls, respectively. Rotations and torsion were higher in the subendocardial than in the subepicardial region in sedentary controls, but not in cyclists. Haemodynamic and tissue Doppler based indexes of global LV diastolic and systolic functions were not different between cyclists and controls. Athlete's heart is associated with specific LV adaptation including lower apical strain and lower myocardial shear strains, with no change in global LV diastolic and systolic function. These mechanical alterations could improve the cardiovascular adjustments to exercise by increasing the radial strain and torsional (and thus untwisting) response to exercise, a key element of diastolic filling and thus of cardiac performance in athletes.


Subject(s)
Bicycling/physiology , Heart/physiology , Stress, Mechanical , Ventricular Function, Left , Adolescent , Adult , Anthropometry , Case-Control Studies , Echocardiography, Doppler , Exercise/physiology , Humans , Image Interpretation, Computer-Assisted , Male , Rotation , Shear Strength , Torsion, Mechanical , Young Adult
9.
J Neurovirol ; 12(6): 466-71, 2006 Dec.
Article in English | MEDLINE | ID: mdl-17162662

ABSTRACT

Human T-lymphotropic virus type 1 (HTLV-1) infections are associated with varying degrees of HTLV-1 viral load and spasticity. Increased viral load is associated with higher risk of developing HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). The authors performed a cross-sectional study of 24 people with HAM/TSP in Lima, Perú, to determine if higher HTLV-1 viral load was correlated with increased muscle tone, measured with a device providing quantitative spasticity assessment (QSA). Median HTLV-1 viral load was 17.0 copies/100 peripheral blood mononuclear cells and QSA value was 39.9 Newton-meters/radian. HTLV-1 viral load was significantly correlated with QSA value (Spearman rho = .48, P = .02), suggesting viral load may play a role in expression of symptomatic neurologic disease. Longitudinal studies are needed to determine if treatments that reduce viral load will reduce muscle tone.


Subject(s)
Human T-lymphotropic virus 1/isolation & purification , Muscle Tonus/physiology , Paraparesis, Tropical Spastic/virology , Viral Load , Cross-Sectional Studies , Female , Humans , Leukocytes, Mononuclear/virology , Male , Muscle, Skeletal/physiology , Paraparesis, Tropical Spastic/physiopathology , Peru , Polymerase Chain Reaction
11.
Dtsch Tierarztl Wochenschr ; 110(10): 403-6, 2003 Oct.
Article in English | MEDLINE | ID: mdl-14650734

ABSTRACT

Subcutaneous vaccination of fancy and racing pigeons with inactivated oil-based vaccines protects against all clinical manifestations caused by the Paramyxovirus type 1. Correct application of the vaccine may occasionally result in the development of granulomas or abscess-like lesions on the site of vaccine application. Although protected against disease as proven by challenge experiments, a variable proportion of vaccinated pigeons do not react with the formation of detectable serum antibodies. The pathogenesis of granuloma and abscess-like lesion developments and the failure to form humoral antibodies are presently not understood. Questions relating to legal liability of vaccinating veterinarians are briefly discussed.


Subject(s)
Columbidae , Newcastle Disease/prevention & control , Newcastle disease virus/immunology , Vaccination/veterinary , Viral Vaccines/adverse effects , Abscess/etiology , Abscess/veterinary , Animals , Antibodies, Viral/blood , Granuloma/etiology , Granuloma/veterinary , Injections, Subcutaneous/adverse effects , Injections, Subcutaneous/veterinary , Skin/pathology , Skin Diseases/etiology , Skin Diseases/veterinary , Vaccination/adverse effects , Vaccines, Inactivated/administration & dosage , Vaccines, Inactivated/adverse effects , Viral Vaccines/administration & dosage
12.
Gen Comp Endocrinol ; 134(2): 167-74, 2003 Nov.
Article in English | MEDLINE | ID: mdl-14511987

ABSTRACT

Chicken ghrelin has recently been isolated as a hormone which stimulates growth hormone and corticosterone secretion in chicken. Ghrelin mediates these actions in mammals by binding to the growth hormone secretagogue receptor (GHS-R). In this study, we describe the partial cloning of two chicken GHS-R (cGHS-R) isoforms: cGHS-R1a and cGHS-R1c. cGHS-R1a and cGHS-R1c cDNA show, respectively, 81 and 78% homology with the corresponding parts of the human GHS-R1a cDNA. In contrast to the human GHS-R1b isoform, which is truncated after transmembrane domain 5 (TM-5), the chicken GHS-R1c isoform lacks 16 amino acids in TM-6 suggesting that this isoform is not active in ghrelin signal transduction. The cystein residues, N-linked glycosylation sites and potential phosphorylation sites, found in the human GHS-R1a, were also conserved in both chicken isoforms. RT-PCR analysis demonstrated cGHS-R1a and cGHS-R1c mRNA expression in all tissues tested, except liver and pancreas, with highest levels in the pituitary and the hypothalamus. Intermediate levels of expression were detected, in descending order, in the ovary, telencephalon, heart, adrenal gland, cerebellum, and optic lobes whereas low expression was detected in the brainstem, lung, kidney, proventriculus, duodenum, and colon. Very low expression was found in skin, stomach, and muscle. cGHS-R1c was expressed in lower amounts than cGHS-R1a in all analysed tissues. Administration of 1 microM chicken ghrelin to pituitaries in vitro resulted in a down-regulation of both cGHS-R isoforms within 15 min, whereas after 1h levels returned to control values. Growth hormone and corticosterone down-regulated cGHS-R1a and cGHS-R1c mRNA expression within 60 min of exposure, whereas growth hormone-releasing factor 1-29 (1 microM) only reduced cGHS-R1a mRNA expression after 60min. Thyrotropin-releasing hormone (1 microM) did not alter cGHS-R expression.


Subject(s)
Chickens/metabolism , Hypothalamus/metabolism , Pituitary Gland, Anterior/metabolism , Receptors, G-Protein-Coupled/genetics , Receptors, G-Protein-Coupled/metabolism , Amino Acid Sequence , Animals , Base Sequence , Chickens/genetics , Cloning, Molecular , DNA, Complementary/analysis , Gene Expression Regulation , Molecular Sequence Data , Protein Isoforms/classification , Protein Isoforms/genetics , Protein Isoforms/metabolism , RNA, Messenger/analysis , Receptors, G-Protein-Coupled/classification , Receptors, Ghrelin , Reverse Transcriptase Polymerase Chain Reaction , Sequence Alignment , Sequence Homology, Nucleic Acid , Tissue Distribution
14.
Clin Invest Med ; 24(1): 12-36, 2001 Feb.
Article in English | MEDLINE | ID: mdl-11266029

ABSTRACT

OBJECTIVES: To assess the economic impact, research output and research support of digestive diseases, and to compare them to those of other common disease entities, specifically mental, cardiovascular, respiratory, and central nervous system diseases. METHODS: Economic burden was assessed with the use of (a) published Canadian government data of direct cost from 1963 to 1993, (b) data from the Canadian Institute of Health Information and (c) recent Canadian economic studies. Research achievements were assessed on the basis of (a) research training in Canadian units, (b) individual achievements by Canadian investigators and (c) contribution to meetings and reception of awards. Research support was assessed by reviewing (a) Canadian government publications, (b) the Association of Canadian Medical Colleges, (c) the Medical Research Council (MRC) of Canada, (d) charitable organizations and (e) the Canadian Association of Gastroenterology (CAG). RESULTS: Digestive diseases are responsible for 15% of the total direct economic burden of Canadian health costs, and this figure exceeds those for mental, cardiovascular, respiratory and central nervous system diseases. Hospital discharges for digestive diseases contribute 12% of all hospitalizations and 20% of all neoplasias. Digestive diseases cause short-term loss of productivity, costing $1.14 billion/yr and exceeding the costs of mental, cardiovascular, respiratory and central nervous system diseases. Eighty-one percent of Research Fellows trained in Canadian units entered academic positions, and 63% obtained operating grants. Canadian investigators made important contributions in all areas of digestive science and received major international awards. Government support for digestive diseases was less than that for cardiovascular and neurologic research. In contrast to the highest economic burden, university staffing and residents were fewer for digestive than for mental, cardiovascular, respiratory and neurologic diseases. The number of MRC grants decreased, mainly because of organizational problems. Most charitable organizations support research specifically oriented to the disease of their interest. The CAG was the major supporter of non-specified research. CONCLUSIONS: Digestive diseases are responsible for a major economic burden. Scientists in this field have established international recognition, but research support lags behind the need to correct the economic burden and to provide future generations of scientists in the digestive sciences. There is need for government to readdress this shortcoming and to review its method of support.


Subject(s)
Health Care Costs , Research Support as Topic , Research , Canada , Digestive System , Foundations , Humans
15.
Clin Invest Med ; 24(1): 44-53, 2001 Feb.
Article in English | MEDLINE | ID: mdl-11266031

ABSTRACT

BACKGROUND: The Canadian Association of Gastroenterology (CAG) is committed to fostering the development of future Canadian investigators. Up to 1986, research fellowship support was obtained from the Medical Research Council (MRC) of Canada. Since that time, several peer-reviewed, industry-sponsored, CAG-supported research fellowships and a variety of independently funded awards have augmented this effort. In the same period, peer-reviewed operating grants (OGs) from the MRC and other agencies have been constrained. The aim of this study was to determine the success of CAG, MRC or any other Canadian research fellowships in the development of career investigators in digestive sciences and to identify factors influencing the outcomes of such training. METHODS: MRC records and the minutes of CAG annual meetings were reviewed to identify research fellowship support. Canadian program directors were requested to list research fellows affiliated with their groups between 1986 and 1997. Only fellowships providing at least 1 year of training were included. A 7-page questionnaire detailing biographic characteristics, the site and duration, and specific issues related to the quality of research training was sent to identified trainees. Significant associations between success in achieving an academic appointment or OG support and several variables of training were identified. RESULTS: Eighty-six research fellows were trained. Responses were obtained from 43 of them. The demographic characteristics of the whole group and the respondents were similar. Of the respondents, 81% of trainees obtained academic appointments. Fellowships longer than 1 year were associated with higher rates of academic posting, and MRC-funded fellows had greater success rates of academic appointments. Of eligible trainees 63% have obtained OG support. None of the other variables examined predicted success. Of the trainees responding, 85% valued the fellowship very highly. CONCLUSIONS: The establishment of the additional research fellowships has fostered the development of career investigators in digestive sciences. The high success rate of former trainees in obtaining academic appointments and OG support suggests that the fellowship programs are effective and appropriately oriented. The structure of the current programs does not require substantial revision. OG support for new investigators appears now to lag substantially.


Subject(s)
Digestive System , Fellowships and Scholarships , Research , Training Support , Canada , Career Choice , Humans , Surveys and Questionnaires , Universities
16.
J Clin Microbiol ; 39(1): 29-33, 2001 Jan.
Article in English | MEDLINE | ID: mdl-11136743

ABSTRACT

The detection of virus is used to diagnose human immunodeficiency virus type 1 (HIV-1) infection in infants due to the persistence of maternal antibodies for a year or more. An HIV-1 DNA PCR assay with simple specimen collection and processing was developed and evaluated. Whole blood was collected on filter paper that lysed cells and bound the DNA, eliminating specimen centrifugation and extraction procedures. The DNA remained bound to the filter paper during PCR amplification. Assays of copy number standards showed reproducible detection of 5 to 10 copies of HIV-1 in 5 microl of whole blood. The sensitivity of the assay did not decrease after storage of the standards on filter paper for 3 months at room temperature or after incubation at 37 or 45 degrees C for 20 h. The primers used for nested PCR of the HIV-1 pol gene amplified templates from a reference panel of multiple HIV-1 subtypes but did not amplify a subtype A or a subtype C virus from children living in Seattle. The assay had a sensitivity of 98.4% and a specificity of 98.3% for testing of 122 specimens from 35 HIV-1-infected and 16 uninfected children and 43 seronegative adults living in Washington. The assay had a sensitivity of 99% and a specificity of 100% for testing of 102 HIV-1-positive (as determined by enzyme immunoassay) Peruvian women and 6 seropositive and 34 seronegative infants. This assay, with adsorption of whole blood to filter paper and no specimen processing, provides a practical, economical, sensitive, and specific method for the diagnosis of HIV-1 subtype B infection in infants.


Subject(s)
Blood Specimen Collection/methods , DNA, Viral/blood , HIV Infections/diagnosis , HIV-1/isolation & purification , Adolescent , Adult , Child , Child, Preschool , Filtration/instrumentation , Gene Products, pol/genetics , HIV Infections/blood , HIV Infections/virology , HIV-1/classification , HIV-1/genetics , Humans , Infant , Infant, Newborn , Polymerase Chain Reaction , Sensitivity and Specificity , Viremia/virology
17.
J Hum Virol ; 4(5): 238-48, 2001.
Article in English | MEDLINE | ID: mdl-11907381

ABSTRACT

OBJECTIVES: To develop an assay for the early detection and quantification of minor human immunodeficiency virus-1 populations bearing multiple drug resistance (MDR) mutations. STUDY DESIGN/METHODS: The oligonucleotide ligation assay (OLA) is based on ligation of probe and detector oligonucleotides annealed to a polymerase chain reaction amplicon strand with detection by an enzyme immunoassay. In OLA-MDR, oligonucleotides were designed to detect MDR mutations. The method was validated with wild-type and MDR mutant clones mixed at different proportions. RESULTS: K103N mutants were detected as minor populations (5%-30%) by OLA in 6 of 18 samples from patients treated with nonnucleoside reverse transcription inhibitors and classified as wild type by sequencing. In one patient, the kinetics of the increase of MDR mutants could be followed in sequential samples, with K103N being detected earlier by OLA than by sequencing. Q151M mutants were detected as minor populations (13%-24%) by OLA but not by sequencing in 4 samples. CONCLUSIONS: Oligonucleotide ligation assay MDR exhibits higher sensitivity than sequencing for detection of minor MDR mutant populations.


Subject(s)
Drug Resistance, Multiple, Viral/genetics , HIV Infections/virology , HIV Reverse Transcriptase/genetics , HIV-1/enzymology , Mutation , HIV Infections/drug therapy , HIV-1/drug effects , HIV-1/genetics , Humans , Oligodeoxyribonucleotides , Oligonucleotide Probes , Reverse Transcriptase Inhibitors/pharmacology , Reverse Transcriptase Inhibitors/therapeutic use
18.
J Virol Methods ; 89(1-2): 39-48, 2000 Sep.
Article in English | MEDLINE | ID: mdl-10996638

ABSTRACT

Avian polyomavirus, described originally as budgerigar fledgling disease virus, has been associated with devastating contagious disease outbreaks in budgerigar aviaries. At present, this virus affects a wide range of psittacine and non-psittacine birds worldwide, and the serum neutralisation test is used for the serodiagnosis of avian polyomavirus infections. A blocking enzyme-linked immunosorbent assay was developed for the screening of large numbers of sera collected from various avian species. The assay employs a monoclonal antibody directed against the major structural protein VP1 as a blocking antibody in a sandwich blocking procedure. Either purified avian polyomavirus particles or avian polyomavirus VP1 expressed in recombinant baculovirus-infected Sf9 cells were used as antigen. The specificity of the blocking enzyme-linked immunosorbent assay was evaluated by testing sera directed against mammalian polyomaviruses. Using sera obtained from chicken infected experimentally with avian polyomavirus and a collection of psittacine field-origin sera, a good correlation was observed between the results of the blocking enzyme-linked immunosorbent assay and the serum neutralisation test. However, the blocking enzyme-linked immunosorbent assay is more rapid and more economic. Both, avian polyomavirus particles and VP1 produced by recombinant DNA technology proved to be suitable antigens.


Subject(s)
Antibodies, Monoclonal/biosynthesis , Bird Diseases/diagnosis , Capsid Proteins , Capsid/immunology , Polyomavirus Infections/veterinary , Polyomavirus/immunology , Virion/immunology , Animals , Antibodies, Monoclonal/isolation & purification , Capsid/isolation & purification , Cell Line , Chick Embryo , Chickens , Enzyme-Linked Immunosorbent Assay/methods , Insecta/cytology , Neutralization Tests/methods , Polyomavirus/isolation & purification , Polyomavirus Infections/diagnosis , Psittaciformes , Recombinant Proteins/immunology , Virion/isolation & purification
19.
20.
Mech Dev ; 67(1): 97-106, 1997 Sep.
Article in English | MEDLINE | ID: mdl-9347918

ABSTRACT

Hairless plays an important role as the major antagonist in the Notch signalling pathway in Drosophila. It appears to be a direct inhibitor of the signal transducer Su(H). Hairless encodes a pioneer protein which was dissected in a structure-function analysis; a series of deletion constructs was tested for wild type and gain of function activity in the fly as well as for Su(H) binding. Thereby, the Hairless protein was subdivided into the absolutely essential Su(H)-binding domain, similarly important N- and C-terminal domains and a central antimorphic domain. Therefore, Hairless protein might have additional functions apart from Su(H) binding and may antagonize Notch mediated cell-cell communication in a more complex way than currently anticipated.


Subject(s)
Drosophila Proteins , Drosophila/genetics , Insect Proteins/genetics , Insect Proteins/metabolism , Nuclear Proteins , Transcription Factors , Animals , Animals, Genetically Modified , Binding Sites , DNA-Binding Proteins/metabolism , Embryo, Nonmammalian/physiology , Gene Expression Regulation, Developmental , Membrane Proteins/genetics , Membrane Proteins/metabolism , Mutation , Phenotype , Receptors, Notch , Sequence Deletion , Signal Transduction , Transgenes
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