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1.
Sci Total Environ ; 878: 162939, 2023 Jun 20.
Article En | MEDLINE | ID: mdl-36934940

Pharmaceuticals are a ubiquitous group of emerging pollutants of considerable importance due to their biological potency and potential to elicit effects in wildlife and humans. Pharmaceuticals have been quantified in terrestrial, marine, fresh, and transitional waters, as well as the fauna and macro-flora that inhabit them. Pharmaceuticals can enter water ways through different human and veterinary pathways with traditional wastewater treatment, unable to completely remove pharmaceuticals, discharging often unknown quantities to aquatic ecosystems. However, there is a paucity of available information regarding the effects of pharmaceuticals on species at the base of aquatic food webs, especially on phytoplankton, with research typically focussing on fish and aquatic invertebrates. Diatoms are one of the main classes of phytoplankton and are some of the most abundant and important organisms in aquatic systems. As primary producers, diatoms generate ∼40 % of the world's oxygen and are a vital food source for primary consumers. Diatoms can also be used for bioremediation of polluted water bodies but perhaps are best known as bio-indicators for water quality studies. However, this keystone, non-target group is often ignored during ecotoxicological studies to assess the effects of pollutants of concern. Observed effects of pharmaceuticals on diatoms have the potential to be used as an indicator of pharmaceutical-induced impacts on higher trophic level organisms and wider ecosystem effects. The aim of this review is to present a synthesis of research on pharmaceutical exposure to diatoms, considering ecotoxicity, bioremediation and the role of diatoms as bio-indicators. We highlight significant omissions and knowledge gaps which need addressing to realise the potential role of diatoms in future risk assessment approaches and help evaluate the impacts of pharmaceuticals in the aquatic environment at local and global scales.


Diatoms , Environmental Pollutants , Water Pollutants, Chemical , Animals , Humans , Ecosystem , Animals, Wild , Phytoplankton , Pharmaceutical Preparations , Water Pollutants, Chemical/toxicity , Water Pollutants, Chemical/analysis , Aquatic Organisms
2.
Clin Oncol (R Coll Radiol) ; 32(2): e46-e52, 2020 02.
Article En | MEDLINE | ID: mdl-31477416

AIMS: Preoperative short-course radiotherapy (SCRT) is an important treatment option for rectal cancer. The length of time between completing SCRT and surgery may influence postoperative outcomes, but the evidence available to determine the optimal interval is limited and often conflicting. MATERIALS AND METHODS: Information was extracted from a colorectal cancer data repository (CORECT-R) on all surgically treated rectal cancer patients who received SCRT in the English National Health Service between April 2009 and December 2014. The time from radiotherapy to surgery was described across the population. Thirty-day postoperative mortality, returns to theatre, length of stay and 1-year survival were investigated in relation to the interval between radiotherapy and surgery. RESULTS: Within the cohort of 3469 patients, the time to surgery was 0-7 days for 76% of patients, 8-14 days for 19% of patients and 15-27 days for 5% of patients. There was a clear variation in relation to different patient characteristics. There was, however, no evidence of differences in postoperative outcomes in relation to interval length. CONCLUSIONS: This study suggests that the time interval between SCRT and surgery does not influence postoperative outcomes up to a year after surgery. The study provides population-level, real-world evidence to complement that from clinical trials.


Rectal Neoplasms/radiotherapy , Rectal Neoplasms/surgery , State Medicine/organization & administration , Aged , Aged, 80 and over , Cohort Studies , Female , History, 21st Century , Humans , Male , Middle Aged , Postoperative Care , Treatment Outcome , Young Adult
3.
Clin Genet ; 90(3): 258-62, 2016 09.
Article En | MEDLINE | ID: mdl-26954065

Kabuki syndrome is a heterogeneous condition characterized by distinctive facial features, intellectual disability, growth retardation, skeletal abnormalities and a range of organ malformations. Although at least two major causative genes have been identified, these do not explain all cases. Here we describe a patient with a complex Kabuki-like syndrome that included nodular heterotopia, in whom testing for several single-gene disorders had proved negative. Exome sequencing uncovered a de novo c.931_932insTT variant in HNRNPK (heterogeneous nuclear ribonucleoprotein K). Although this variant was identified in March 2012, its clinical relevance could only be confirmed following the August 2015 publication of two cases with HNRNPK mutations and an overlapping phenotype that included intellectual disability, distinctive facial dysmorphism and skeletal/connective tissue abnormalities. Whilst we had attempted (unsuccessfully) to identify additional cases through existing collaborators, the two published cases were 'matched' using GeneMatcher, a web-based tool for connecting researchers and clinicians working on identical genes. Our report therefore exemplifies the importance of such online tools in clinical genetics research and the benefits of periodically reviewing cases with variants of unproven significance. Our study also suggests that loss of function variants in HNRNPK should be considered as a molecular basis for patients with Kabuki-like syndrome.


Abnormalities, Multiple/genetics , Developmental Disabilities/genetics , Face/abnormalities , Hematologic Diseases/genetics , Intellectual Disability/genetics , Ribonucleoproteins/genetics , Vestibular Diseases/genetics , Abnormalities, Multiple/physiopathology , Base Sequence , Developmental Disabilities/physiopathology , Exome , Face/physiopathology , Female , Frameshift Mutation , Hematologic Diseases/physiopathology , Heterogeneous-Nuclear Ribonucleoprotein K , Humans , Intellectual Disability/physiopathology , Male , Nervous System Malformations/genetics , Nervous System Malformations/physiopathology , Vestibular Diseases/physiopathology
4.
Eur J Surg Oncol ; 39(4): 334-8, 2013 Apr.
Article En | MEDLINE | ID: mdl-23380200

AIM: To determine the effect of a 'no drains' policy on seroma formation and other complications in women undergoing breast cancer surgery. MATERIALS AND METHODS: Before May 2010 drains were routinely used in our unit following mastectomy ± axillary surgery and axillary lymph node dissection (ALND) ± wide local excision (WLE). Since then, a 'no drains' policy has been adopted. Data was collected prospectively between 01/12/06 and 30/11/11 to compare symptomatic seroma, wound infection, re-admission and re-operation rates in women treated with a drain and those without. RESULTS: 596 women were included in the study. 247 women underwent modified radical mastectomy (MRM) and ALND (Group 1), 184 MRM ± sentinel lymph node biopsy (SLNB)/axillary node sampling (ANS) (Group 2) and 165 ALND ± WLE (Group 3). In group 1, 149 had a drain, in group 2, 62, and in group 3, 50. Within each group, the presence or absence of a drain did not significantly affect the rate of symptomatic seroma, number of aspirations performed, wound infection rates or the incidence of complications requiring re-admission. Having a drain was associated with lower volumes of seroma aspirated. In all three groups, the presence of a drain was associated with a longer hospital stay (p < 0.001). CONCLUSION: This study suggests that MRM ± ALND/SLNB/ANS and ALND ± WLE can be performed without the use of suction drains without increasing seroma formation and other complication rates. Adopting a 'no-drains' policy may also contribute to earlier hospital discharge.


Breast Neoplasms/surgery , Mastectomy, Modified Radical/methods , Seroma/epidemiology , Suction , Case-Control Studies , Female , Humans , Incidence , Length of Stay , Mastectomy, Modified Radical/adverse effects , Middle Aged , Patient Readmission/statistics & numerical data , Prospective Studies , Reoperation/statistics & numerical data , Seroma/prevention & control , Surgical Wound Infection/epidemiology , Treatment Outcome , United Kingdom/epidemiology
5.
Phys Rev E Stat Nonlin Soft Matter Phys ; 85(1 Pt 1): 011135, 2012 Jan.
Article En | MEDLINE | ID: mdl-22400540

From microscopic models, a Langevin equation can, in general, be derived only as an approximation. Two possible conditions to validate this approximation are studied. One is, for a linear Langevin equation, that the frequency of the Fourier transform should be close to the natural frequency of the system. The other is by the assumption of "slow" variables. We test this method by comparison with an exactly soluble model and point out its limitations. We base our discussion on two approaches. The first is a direct, elementary treatment of Senitzky. The second is via a generalized Langevin equation as an intermediate step.


Algorithms , Models, Chemical , Models, Molecular , Quantum Theory , Computer Simulation
6.
Genes Immun ; 13(2): 120-8, 2012 Feb.
Article En | MEDLINE | ID: mdl-21881596

Previously-proposed rheumatoid arthritis (RA) HLA-DRB1 susceptibility and protective models were compared, based on amino acids at positions 67-74 and autoantibody combinations. 3 657 RA patients and 1 357 controls were studied using logistic regression, with secondary stratification by anti-citrullinated peptide antibodies(ACPA) and rheumatoid factor(RF). Susceptibility models were based on previously defined HLA-DRB1 shared epitope(SE) subgroups. (70)DERAA(74), D(70) and I(67) protective models were compared, adjusting for HLA-DRB1 SE. A hierarchy of risk was observed within the HLA-DRB1 SE, particularly for ACPA-positive and RF-positive RA: HLA-DRB1(*)0401∼(*)0404>(*)0101∼(*)1001 ((*)0404>(*)0101: P=0.0003). HLA-DRB1(*)0401/(*)0404 compound heterozygosity conferred a risk similar to (*)0401 homozygosity (P=0.70). Protective effects of D(70) and I(67) were similar. Predictions of the D(70) model fitted the data better than those of the I(67) model. The protective effect of D(70) showed a gene-dose effect (OR 0.82, 95% CI 0.73-0.92, P=5.8 × 10(-4)), but was only seen in RA patients positive for RF or ACPA. HLA-DRB1 SE alleles were also associated with ACPA-negative, RF-positive RA (OR 1.42 (1.15-1.76), P=0.0012). In conclusion, HLA-DRB1 SE alleles show heterogeneity in RA susceptibility; their major effect appears to be mediated by ACPA positivity, but a significant association of HLA-DRB1 SE with RF-positive, ACPA-negative RA was also observed. D(70) specifically protected against antibody-positive RA.


Arthritis, Rheumatoid/genetics , Arthritis, Rheumatoid/immunology , Autoantibodies/immunology , Genetic Predisposition to Disease , HLA-DRB1 Chains/genetics , HLA-DRB1 Chains/immunology , Alleles , England , Female , Genetics, Population , Genotype , Humans , Male
7.
Seizure ; 18(3): 180-3, 2009 Apr.
Article En | MEDLINE | ID: mdl-18835729

INTRODUCTION: There is little published data on the duration of depressed consciousness following epileptic seizures. A prolonged recovery time may be a symptom of underlying brain pathology. This prospective paediatric cohort study investigates whether recovery is prolonged following symptomatic seizures. METHODS: Children aged 1-16 years, who had a witnessed seizure in which consciousness was impaired, were recruited. One hundred and twenty eight children (158 seizures) were studied. Seizure aetiology was classified as febrile, idiopathic, remote symptomatic, acute symptomatic and acute on remote symptomatic. At least hourly Paediatric Coma Scale recordings were used to assess recovery time. RESULTS: Recovery time was longest for children with acute on remote symptomatic seizures (4.0 h, range 0.89-10.5), followed by those with acute symptomatic seizures (1.94 h, range 0-35.27), remote symptomatic seizures (1.5h, range 0.07-85.5) and idiopathic seizures (0.83 h, range 0.07-13.13). Children with febrile seizures recovered the quickest (0.3h, range 0.05-9). Recovery time was significantly longer (p<0.001, CI 1.96-5.38) following seizures for which rescue antiepileptic drugs were administered compared to those for which it was not. Age, sex, type and duration of seizure did not independently affect recovery time. DISCUSSION: Symptomatic seizures take longer to recover than seizures of other aetiologies. It is recommended that a febrile child who presents with a seizure, who has not fully recovered within 30 min, should be investigated for an acute symptomatic aetiology. A high index of suspicion is also needed if children with apparent idiopathic seizures have not fully recovered within 1.5h.


Consciousness Disorders/etiology , Epilepsy/complications , Adolescent , Child , Child, Preschool , Cohort Studies , Epilepsy/classification , Epilepsy/etiology , Female , Humans , Infant , Male , Severity of Illness Index , Time Factors
8.
Endothelium ; 15(1): 17-31, 2008.
Article En | MEDLINE | ID: mdl-18568942

The purpose of this investigation was to test the hypothesis that chronic N(G)-nitro-l-arginine methyl ester (l-NAME) treatment produces differential effects on conduit artery and resistance arteriole relaxation responses to endothelium-dependent and -independent vasodilators in arteries that perfuse skeletal muscle of swine. To test this hypothesis, conduit skeletal muscle arteries and second-order skeletal muscle (2A) arterioles were harvested from 14 Yucatan swine that were chronically administered l-NAME and from 16 controls. In vitro assessments of vasorelaxation to increasing doses of acetylcholine (ACH), bradykinin (BK), and sodium nitroprusside (SNP) were performed in both conduit and 2A arterioles. l-NAME treatment produced a significant reduction in both BK and ACH relaxation responses in the conduit arteries. In contrast, the relaxation response and/or sensitivity to SNP were significantly greater in the intact, but not denuded, conduit arterial rings from chronically l-NAME-treated swine. There were no significant effects of chronic l-NAME treatment on vasodilation of skeletal muscle arterioles. These findings suggest (1) that unlike arterioles, skeletal muscle conduit arteries do not functionally compensate for a lack of NO through the upregulation of alternative vasodilator pathways; (2) that the greater relaxation response in conduit arteries of chronically l-NAME-treated swine to SNP can be explained by alterations to the endothelium.


Arteries/drug effects , Arterioles/drug effects , Endothelium, Vascular/physiology , Muscle, Skeletal/blood supply , Nitric Oxide Synthase Type III/antagonists & inhibitors , Vasodilation/drug effects , Acetylcholine/pharmacology , Animals , Arteries/enzymology , Arterioles/enzymology , Blood Pressure/drug effects , Brachial Artery/drug effects , Brachial Artery/enzymology , Bradykinin/pharmacology , Dose-Response Relationship, Drug , Endothelium, Vascular/drug effects , Endothelium, Vascular/enzymology , Enzyme Inhibitors/pharmacology , Female , Femoral Artery/drug effects , Femoral Artery/enzymology , Forelimb/blood supply , Gene Expression Regulation, Enzymologic , Hindlimb/blood supply , Inhibitory Concentration 50 , NG-Nitroarginine Methyl Ester/pharmacology , Nitric Oxide Synthase Type III/genetics , Nitric Oxide Synthase Type III/metabolism , Nitroprusside/pharmacology , Regional Blood Flow , Swine , Swine, Miniature , Time Factors , Vasodilator Agents/pharmacology
9.
J Physiol Pharmacol ; 59 Suppl 7: 57-70, 2008 Dec.
Article En | MEDLINE | ID: mdl-19258657

Peripheral arterial insufficiency is a progressive degenerative disease associated with an increased morbidity and mortality. It decreases exercise tolerance and often presents with symptoms of intermittent claudication. Enhanced physical activity is one of the most effective means of improving the life of affected patients. While this occurs for a variety of reasons, vascular remodeling can be an important means for improved oxygen exchange and blood flow delivery. Relevant exercise-induced signals stimulate angiogenesis, within the active muscle (e.g. hypoxia), and arteriogenesis (enlargement of pre-existing vessels via increased shear stress) to increase oxygen exchange and blood flow capacity, respectively. Evidence from pre-clinical studies shows that the increase in collateral blood flow observed with exercise progresses over time of training, is accompanied by significant enlargement of isolated collateral vessels, and enhances the responses observed with angiogenic growth factors (e.g. VEGF, FGF-2). Thus, enhanced physical activity can be an effective means of enlarging the structure and function of the collateral circuit. Interestingly, disrupting normal NO production (via L-NAME) eliminates this increase in collateral blood flow induced by training, but does not disturb the increase in muscle capillarity within the active muscle. Similarly, inhibiting VEGF receptor kinase activity eliminates the increase in collateral-dependent blood flow, and lessens, but does not eliminate, angiogenesis within the calf muscle. These findings illustrate distinctions between the processes influencing angiogenesis and arteriogenesis. Further, sympathetic modulation of the collateral circuit does not eliminate the increase in collateral circuit conductance induced by exercise training. These findings indicate that structural enlargement of the collateral vessels is essential to realize the increase in collateral-dependent blood flow capacity caused by exercise training. This raises the potential that meaningful vascular remodeling can occur in patients with intermittent claudication who actively participate in exercise training.


Exercise Therapy , Intermittent Claudication/therapy , Peripheral Vascular Diseases/therapy , Animals , Exercise Tolerance , Humans , Intercellular Signaling Peptides and Proteins/metabolism , Intermittent Claudication/physiopathology , NG-Nitroarginine Methyl Ester/metabolism , Neovascularization, Physiologic , Nitric Oxide/metabolism , Peripheral Vascular Diseases/physiopathology
10.
Water Sci Technol ; 55(3): 151-60, 2007.
Article En | MEDLINE | ID: mdl-17410851

Three data sources (physico-chemistry, bio-monitoring and eco-toxicology) are currently used in South Africa to establish environmental water quality conditions. Environmental water quality in turn is key information required for the "ecological reserve determination" of river reaches. Bio-monitoring in South Africa has been limited in recent times mostly to the use of the SASS procedure which relies on invertebrates only. This paper describes the re-introduction of a diatom-based water quality assessment as an added-value bio-monitoring tool. A specific example is discussed citing the response of diatom assemblages to diffuse pollution from acid mine drainage and how effective diatoms are as indicators of ecological integrity and river recovery measured downstream of the area of impact. The advantages of applying this bio-monitoring technique over other biological measures are presented in the context of technological advances in rapid image processing, species identification and software applications of diatom-based water quality indices. The valuable records of the diatom assemblages of the past, held in the South African Diatom Collection at the CSIR (KwaZulu-Natal), can now be accessed and interpreted as historical environmental water quality reference points for several rivers in South Africa.


Acids/chemistry , Diatoms/drug effects , Mining , Water Pollutants, Chemical/toxicity , Water Pollution/analysis , Diatoms/classification , Diatoms/growth & development , Environmental Monitoring/methods , Rivers , South Africa , Water Pollutants, Chemical/analysis
11.
Br J Surg ; 94(1): 6-16, 2007 Jan.
Article En | MEDLINE | ID: mdl-17205497

BACKGROUND: Optical techniques using previously unexploited properties of light interaction with tissue may be valuable in the detection, diagnosis and staging of colorectal neoplasia. METHODS: A Medline search (1990 to present) was conducted on optical diagnostics in the detection of colorectal neoplasia. The reference list of each identified article was reviewed for further relevant papers. RESULTS AND CONCLUSION: Chromoendoscopy is the only optical adjunct to colonoscopy that has been tested in large randomized clinical trials. It improves the detection of small and flat colorectal adenomas, and of neoplasia in chronic ulcerative colitis and hereditary non-polyposis colorectal cancer. All other techniques are the subject of ongoing research and the practicality of population screening with any of the methods has yet to be established. Optical techniques may, however, permit immediate clinical diagnosis, removing the need for histological analysis. They may also improve the diagnosis of early colonic neoplasia.


Colonoscopy/methods , Colorectal Neoplasms/diagnosis , Female , Fluoroscopy/methods , Humans , Male , Sensitivity and Specificity , Tomography, Optical Coherence/methods
12.
J Clin Endocrinol Metab ; 91(2): 646-53, 2006 Feb.
Article En | MEDLINE | ID: mdl-16278270

CONTEXT: Autoimmune thyroid diseases (AITD), comprising Graves' disease and autoimmune hypothyroidism, are characterized by loss of immunological self-tolerance to thyroid antigens. These are complex diseases arising from a combination of genetic and environmental factors. An understanding of the genetic susceptibility factors for AITD could help to target treatments more effectively and identify people at risk for these conditions. OBJECTIVE: The objective of this study was to identify regions of genetic linkage to AITD that could potentially harbor genetic susceptibility factors for these conditions. DESIGN: The study design was a genome-wide screen performed on affected relative pairs with AITD. SETTING: Patients were recruited through hospital endocrinology clinics. PARTICIPANTS: Some 1119 Caucasian relative pairs affected with AITD (Graves' disease or autoimmune hypothyroidism) were recruited into the study. INTERVENTION: Blood samples were obtained from each participant for DNA analysis, and clinical questionnaires were completed. MAIN OUTCOME MEASURE: The study aimed to identify regions of genetic linkage to AITD. RESULTS: Three regions of suggestive linkage were obtained on chromosomes 18p11 (maximum LOD score, 2.5), 2q36 (maximum LOD score, 2.2), and 11p15 (maximum LOD score, 2.0). No linkage to human leukocyte antigen was found. CONCLUSIONS: The absence of significant evidence of linkage at any one locus in such a large dataset argues that genetic susceptibility to AITD reflects a number of loci, each with a modest effect. Linkage analysis may be limited in defining such loci, and large-scale association studies may prove to be more useful in identifying genetic susceptibility factors for AITD.


Graves Disease/genetics , Hypothyroidism/genetics , Chromosome Mapping , Chromosomes, Human/genetics , Cohort Studies , Family , Genetic Linkage/genetics , Genetic Predisposition to Disease , Genome, Human , Humans , Lod Score , Statistics, Nonparametric
13.
Eur J Vasc Endovasc Surg ; 28(3): 270-3, 2004 Sep.
Article En | MEDLINE | ID: mdl-15288630

BACKGROUND: The aim of this study was to examine whether there was any survival advantage in men following elective repair of an abdominal aortic aneurysm (AAA) detected by ultrasound screening compared to those with an AAA detected incidentally. METHODS: A total of 424 men underwent elective AAA repair between 1990 and 1998; 181 were detected in an aneurysm screening programme and 243 were diagnosed incidentally. Follow-up survival data were collected until 2003 (minimum 5 years) and survival curves were compared using regression analysis. RESULTS: The postoperative 30-day mortality rate was significantly lower in men whose aneurysms were detected by screening (4.4%), compared with those detected incidentally (9.0%). Similarly, 5-year survival (78% vs. 65%) and 10-year survival rates (63% vs. 40%) were better after repair of a screen-detected AAA (p<0.0003 at all time intervals, by log rank testing). Multivariate analysis showed that this was largely due to the older age of men who had repair of an incidental AAA (71.2 vs. 67.1 years). CONCLUSION: Men who had elective repair of an AAA detected by screening had a better late survival rate than men whose aneurysm was discovered incidentally because they were younger at the time of surgery.


Aortic Aneurysm/mortality , Aortic Aneurysm/surgery , Aged , Elective Surgical Procedures , Humans , Incidental Findings , Male , Survival Rate , Time Factors
14.
Food Addit Contam ; 21(6): 572-7, 2004 Jun.
Article En | MEDLINE | ID: mdl-15204535

A simple, sensitive and reliable liquid chromatography-mass spectrometry method with direct injection of diluted samples is reported for the determination of propamocarb residues in wine. Red and white wines were diluted 40- and 20-fold, respectively, using water. Liquid chromatography was performed with a mobile-phase gradient and detection was by electrospray mass spectrometry in a positive ionization mode. Propamocarb was detected as the protonated molecular species at m/z 189. Using matrix-matched calibrant solutions, a calibrated range equivalent to 0.05-2.0 mg kg(-1) in red and white wines and limits of detection of 0.025 mg kg(-1) for white wine and of 0.05 mg kg(-1) for red wine (0.00125 microg ml(-1) of sample solution injected) were readily achievable. Recovery of propamocarb hydrochloride from wine spiked before dilution was in the range 91-115%. The chromatograms were free of isobaric interferences. In a small wine survey (72 samples), no residues of propamocarb were detected above 0.1 mg kg(-1).


Carbamates/analysis , Food Contamination/analysis , Fungicides, Industrial/analysis , Pesticide Residues/analysis , Wine/analysis , Chromatography, Liquid/methods , Food Analysis/methods , Humans , Spectrometry, Mass, Electrospray Ionization/methods
16.
Thorax ; 57(12): 1034-9, 2002 Dec.
Article En | MEDLINE | ID: mdl-12454297

BACKGROUND: Uncontrolled studies suggest that psychosocial factors and health behaviour may be important in asthma death. METHODS: A community based case-control study of 533 cases, comprising 78% of all asthma deaths under age 65 years and 533 hospital controls individually matched for age, district and asthma admission date corresponding to date of death was undertaken in seven regions of Britain (1994-98). Data were extracted blind from anonymised copies of primary care records for the previous 5 years and non-blind for the earlier period. RESULTS: 60% of cases and 63% of controls were female. The median age in both groups was 53. Cases had an earlier age of asthma onset, more chronic obstructive lung disease, and were more obese. 48% of cases and 42% of controls had a health behaviour problem; repeated non-attendance/poor inhaler technique was related to increased risk of death. Overall, 85% and 86%, respectively, had a psychosocial problem. Four psychosocial factors were associated with increased risk of death (psychosis, alcohol/drug abuse, financial/employment problems, learning difficulties) and two with reduced risk (anxiety/prescription of antidepressant drugs and sexual problems). While alcohol/drug abuse lost significance after adjustment for psychosis, other associations appeared independent of each other and of indicators of severity and co-morbidity. None of the remaining 13 factors including family problems, domestic abuse, bereavement, and social isolation were significantly related to risk of asthma death. CONCLUSION: There was an apparently high burden of psychosocial problems in both cases and controls. The associations between health behaviour, psychosocial factors, and asthma death are varied and complex with a limited number of factors showing positive relationships.


Asthma/mortality , Adolescent , Adult , Age of Onset , Asthma/psychology , Asthma/therapy , Case-Control Studies , Child , Child, Preschool , Female , Health Behavior , Humans , Infant , Infant, Newborn , Male , Middle Aged , Patient Compliance , Psychology, Social , Risk Factors , United Kingdom/epidemiology
17.
Osteoporos Int ; 12(10): 844-8, 2001.
Article En | MEDLINE | ID: mdl-11716187

We determined to survey the general practice population regarding their attitudes to and knowledge of osteoporosis as a baseline prior to publication of national guidelines for the management of osteoporosis. All 2515 general practitioners registered in the 10 Health Authorities of the North Thames region, London, UK were surveyed by a postal questionnaire. Responses relating to epidemiology, public health and education on osteoporosis were analyzed. The overall response was 1153 (46%). General practitioners who responded were younger, predominantly female and in group practice. There is considerable awareness of the importance of preventing osteoporosis. General practitioners are active in identifying groups at risk, particularly those who are aged 40 years and older. A prevention strategy for osteoporosis is viewed as effective. However, two thirds of general practitioners remain unconvinced about the efficacy of drug therapy. Education on osteoporosis is considered inadequate. General practitioners would welcome further information on management issues and access to osteoporosis services. In conclusion, educational initiatives will be important both at undergraduate and postgraduate levels to increase awareness and knowledge of osteoporosis. General practitioners are aware of the public health impact of this condition and express a preference for educational material of direct relevance to the care of their patients. Therefore better cooperation between primary and secondary care should lead to ways of breaking down barriers to change in clinical practice and promoting fully integrated care of patients with osteoporosis.


Osteoporosis , Attitude of Health Personnel , Clinical Competence , Family Practice , Female , Humans , Male , Needs Assessment , Osteoporosis/diagnosis , Osteoporosis/prevention & control , Osteoporosis/therapy , Physicians, Family/psychology
18.
J Biol Chem ; 276(39): 36075-8, 2001 Sep 28.
Article En | MEDLINE | ID: mdl-11495894

The human multidrug resistance P-glycoprotein (P-gp), a member of the ATP-binding cassette (ABC) superfamily of transporters, is frequently responsible for the failure of chemotherapy by virtue of its ability to export hydrophobic cytotoxic drugs from cells. Elucidating the inter- and intramolecular interactions of this protein is critical to understanding its cellular function and mechanism of action. Toward this end, we have used both biochemical and genetic techniques to probe potential oligomerization interactions of P-gp. Differentially epitope-tagged P-gp molecules did not co-immunoprecipitate when co-expressed in HEK293 cells or when co-translated in vitro, demonstrating that P-gp is monomeric in both the presence and absence of detergents. The two cytoplasmic domains of P-gp did not interact with each other in vivo when co-expressed as gene fusions in yeast. In contrast, the homologous domains of the transporter associated with antigen processing (TAP), which reside on separate polypeptides and must form a heterodimeric transporter (TAP1/TAP2), did interact in this system, suggesting a role for these domains in TAP dimerization. Implications for understanding the subunit organization of ABC transporters are discussed.


ATP Binding Cassette Transporter, Subfamily B, Member 1/chemistry , ATP Binding Cassette Transporter, Subfamily B, Member 1/metabolism , Cell Line , DNA/metabolism , Detergents/pharmacology , Dose-Response Relationship, Drug , Electrophoresis, Polyacrylamide Gel , Epitopes/chemistry , Humans , Octoxynol/pharmacology , Precipitin Tests , Protein Binding , Protein Biosynthesis , Protein Structure, Tertiary , Two-Hybrid System Techniques
19.
J Exp Mar Biol Ecol ; 258(2): 195-214, 2001 Apr 15.
Article En | MEDLINE | ID: mdl-11278010

Dissolved oxygen (DO) is proving to be one of the most important abiotic factors determining growth and survival of juvenile estuarine fish. In shallow, throughout estuarine systems, low DO can occur in two broad categories: a diel oscillating pattern resulting in repeated nocturnal hypoxia due to the photosynthesis-respiration cycle of algal populations, or as prolonged bottom water hypoxia or anoxia caused by stratification. A series of laboratory experiments was conducted to characterize the physiological performance of juvenile southern flounder, Paralichthys lethostigma, (55-65 mm TL) exposed to four treatments of DO: (1) constant normoxia (6.50+/-0.50 mg O(2) l(-1)), (2) constant hypoxia (2.79+/-0.19 mg O(2) l(-1)), (3) constant intermediate hypoxia (4.74+/-0.18 mg O(2) l(-1)), and (4) an oscillating oxygen environment cycling dielly between the normoxic and hypoxic levels (2.8-6.2 mg O(2) l(-1), daily mean=4.40 mg O(2) l(-1)). Routine respiration was positively correlated with DO level and increased significantly during the day in the oscillating treatment in response to increasing DO. Ventilation rates were negatively correlated with the DO level in the constant treatments and increased significantly at night in the oscillating treatment in response to nocturnal hypoxia. Similarly, hematocrit levels were negatively related to DO levels in the constant treatments after 5 and 26 days of exposure to the treatments. Hematocrit levels also increased significantly the oscillating treatment, apparently in response to the episodic nocturnal hypoxia. Growth was significantly reduced in the 2.8 mg O(2) l(-1) treatment and the oscillating treatment but not in the 4.7 mg O(2) l(-1) treatment. Acclimation was evident by an increase in growth rates from week 2 to week 3 and a decrease in hematocrit levels between 5 and 26 days of exposure in the 2.7 and 4.5 mg O(2) l(-1) treatments but was not evident in the normoxic or oscillating treatments. These results suggest that a juvenile fish must remain in even moderately low DO in order for acclimation to occur. The research presented demonstrates that correctly assessing habitat quality in terms of DO requires knowledge of a fish's physiological and environmental history.

20.
Eur Psychiatry ; 16(1): 49-56, 2001 Feb.
Article En | MEDLINE | ID: mdl-11246292

The aim was to investigate associations of a history of features of DSM-III-R conduct disorder (CD) with features of DSM-III-R personality disorders (PDs) and psychopathy, in inpatient psychiatric practice. Fifty-six psychiatric inpatients, without a history of specified 'psychoses', were assessed by the SCID structured interview for DSM-III-R PDs and the 'Psychopathy Checklist Revised' (PCL-R). In a sample in which 59% had borderline PD, significant associations between a history of CD criteria and the adult features of antisocial PD (APD) were relatively specific compared with other PDs, but were weaker in women. However, significant correlations between the number of positive CD criteria and PCL-R scores were similar in both genders. The relatively specific associations between CD and adult features of APD are likely to be relevant to psychiatric patients who show various presentations of PD, if these include some adult features of APD. The findings inform the understanding of the development and classification of PDs.


Conduct Disorder/etiology , Personality Disorders/psychology , Adolescent , Adult , Aged , Antisocial Personality Disorder/diagnosis , Antisocial Personality Disorder/epidemiology , Conduct Disorder/diagnosis , Conduct Disorder/epidemiology , Female , Humans , Male , Middle Aged , Personality Disorders/diagnosis , Personality Disorders/epidemiology , Prevalence , Psychiatric Status Rating Scales , Severity of Illness Index , Sex Distribution
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