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1.
Rev Sci Tech ; 38(1): 251-260, 2019 05.
Article in English | MEDLINE | ID: mdl-31564726

ABSTRACT

One Health Surveillance (OHS) implements the One Health approach to improving health by collecting data and producing information to support integrated action across the animal health, human health and environment sectors. The purpose of this study was to survey the biosurveillance community to assess its OHS practices and capabilities, its attitudes towards OHS (perceived value), and the factors that motivate its members to implement OHS practices. The authors used a convenience sample of 185 professionals from multiple domains and 44 nations. They examined the extent to which these professionals implemented OHS, gathered their opinions on the value of OHS, assessed their perceptions of the capacity to perform specific OHS tasks and identified their priorities for change. Over 85% of all respondents said that they considered OHS to be beneficial, with no significant differences between work domains or country income groups; over 50% indicated that they already applied OHS. Obtaining access to data collected by other domains was both the most frequent challenge and the most difficult to improve. The highest priority for improvement was having the ability to send and receive electronic data. Respondents from low-income or middle-income countries were more motivated to make improvements than stakeholders from high-income countries. These findings provide a snapshot of current opinions and practices and, together with suggestions for improvements from professionals in the field, can help to target priority needs for OHS information, training and resources.


La surveillance Une seule santé opérationnalise la méthode Une seule santé pour une meilleure santé à travers la collecte de données et la production d'informations visant à soutenir la mobilisation transversale des secteurs de la santé animale, de la santé publique et de la santé environnementale en vue d'une action intégrée. Les auteurs présentent les résultats d'une enquête menée auprès des professionnels en charge de la biosurveillance afin d'évaluer leurs pratiques et capacités en matière de surveillance Une seule santé, leurs attitudes à l'égard de cette surveillance (c'est-à-dire leur perception de l'intérêt de la démarche) et les facteurs susceptibles de les motiver à la mettre en oeuvre. Les auteurs ont procédé à un échantillonnage de commodité de 185 intervenants issus de plusieurs secteurs dans 44 pays. Ils ont ensuite analysé le niveau de mise en oeuvre de la surveillance Une seule santé chez ces intervenants, recueilli leurs opinions concernant l'intérêt de la démarche, évalué la perception qu'ils avaient de leur capacité à mener à bien certaine tâches spécifiques dans ce domaine et identifié leurs priorités en vue du changement. Plus de 85 % des répondants ont déclaré considérer la surveillance Une seule santé comme étant bénéfique, résultat ne présentant pas de corrélation significative avec le secteur professionnel des personnes interrogées ni avec le niveau de revenu de leur pays ; plus de 50 % des répondants ont par ailleurs indiqué qu'ils appliquaient déjà les principes d'une surveillance Une seule santé. La difficulté la plus fréquente et qui paraissait la plus difficile à résoudre était celle de pouvoir accéder aux données enregistrées par d'autres secteurs. La première des priorités identifiées en vue d'une amélioration concernait la capacité d'envoyer et de recevoir des données électroniques. La motivation à introduire des améliorations était plus forte chez les répondants des pays à revenu faible ou intermédiaire que chez les parties prenantes des pays à revenus élevés. Ces résultats, qui offrent un instantané des opinions et des pratiques actuelles assorti de propositions concrètes d'amélioration formulées par les professionnels de terrain devraient pouvoir contribuer à cibler les besoins prioritaires en matière d'information, de formation et de ressources dédiées à la surveillance Une seule santé.


Practicar la vigilancia en clave de Una sola salud significa traducir esta idea en la práctica con el fin de mejorar la salud reuniendo datos y generando información a partir de la cual actuar de forma integrada en los sectores de la sanidad animal, la salud humana y el medio ambiente. Los autores describen un estudio de los círculos dedicados a la vigilancia biológica que tenía por objetivo evaluar sus procedimientos y capacidades de vigilancia en clave de Una sola salud, sus actitudes al respecto (valor atribuido) y los factores que los motivan a instaurar procedimientos concebidos desde la lógica de Una sola salud. Para ello los autores utilizaron una muestra de conveniencia de 185 profesionales de múltiples disciplinas y 44 países. Tras determinar en qué medida esos profesionales practicaban la vigilancia en clave de Una sola salud, les pidieron su opinión sobre la utilidad de este tipo de vigilancia, evaluaron la capacidad que subjetivamente se atribuían de efectuar labores específicas de vigilancia en clave de Una sola salud y determinaron aquellos cambios que esas personas juzgaban prioritarios. Más de un 85% de los encuestados dijo considerar beneficiosa la vigilancia en clave de Una sola salud, sin que se observaran diferencias significativas por ámbito de trabajo o por países según el grupo de ingresos. Más de un 50% afirmó que ya aplicaba este tipo de vigilancia. El problema señalado con más frecuencia y juzgado a la vez más difícil de resolver era el del acceso a datos obtenidos desde otros ámbitos de trabajo. El aspecto que más urgía mejorar era el de la capacidad de enviar y recibir datos electrónicos. Los encuestados de países de nivel bajo o medio de ingresos mostraban mayor motivación a la hora de introducir mejoras que sus homólogos de países de ingresos altos. Estas conclusiones, que ofrecen una «instantánea¼ de las opiniones y prácticas imperantes, pueden ayudar, junto con las propuestas de mejora procedentes de esos profesionales que trabajan sobre el terreno, a seleccionar las necesidades prioritarias de información, formación y recursos para la práctica de la vigilancia en clave de Una sola salud.


Subject(s)
Motivation , One Health , Workforce , Animals , Humans , Surveys and Questionnaires , Workforce/standards , Workforce/trends
2.
Transbound Emerg Dis ; 64(3): 899-905, 2017 Jun.
Article in English | MEDLINE | ID: mdl-26681114

ABSTRACT

Larvae (maggots) of Cochliomyia hominivorax, the New World Screwworm fly, are voracious consumers of living flesh that have a negative economic impact by decreasing productivity, predisposing to other pathogens, and, in severe cases, causing death of domestic livestock. Screwworm caused extensive financial losses to the livestock industry in North America prior to its eradication. Sterile insect technique (SIT) was used to eradicate screwworm throughout North and Central America and continues to be the main tool to control it in eastern Panama. The goal of this study was to evaluate the temporal and spatial trends of screwworm myiasis cases reported in the Province of Darien and Comarca Embera (border with Colombia), Panama, from 2001 to 2011. We hypothesized that screwworm cases would vary seasonally and be spatially clustered near Colombia as a result of effective eradication strategies in Panama and the presence of an autochthonous population of flies in western Colombia. Temporal and spatial data were retrieved from COPEG-USDA records (Panama) and analysed by anova, Ripley's K function, discrete Poisson spatial statistic scan and Getis-Ord Gi*. No significant temporal trend was found, but cases were spatially distributed in four clusters. One cluster of cases occurred from 2001 to 2003 and was considered a focal temporal and spatial cluster. One cluster occurred in 2001 and 2007 indicating more rare outbreaks in an area with fewer cattle. The two remaining clusters contained cases from 2004 to 2011 and 2001 to 2011 suggesting regular breaks in the control barrier due to occasional failures of the SIT programme, difficulties implementing border quarantine strategies, livestock smuggling or the movement of infested wildlife.


Subject(s)
Diptera/classification , Disease Outbreaks/veterinary , Livestock/parasitology , Screw Worm Infection/veterinary , Animals , Larva , Panama/epidemiology , Retrospective Studies , Screw Worm Infection/epidemiology , Seasons , Spatial Analysis , Time Factors
3.
Genes Immun ; 15(4): 233-40, 2014 Apr.
Article in English | MEDLINE | ID: mdl-24598798

ABSTRACT

SHIP-1 has an important role in controlling immune cell function through its ability to downmodulate PI3K signaling pathways that regulate cell survival and responses to stimulation. Mice deficient in SHIP-1 display several chronic inflammatory phenotypes including antibody-mediated autoimmune disease, Crohn's disease-like ileitis and a lung disease reminiscent of chronic obstructive pulmonary disease. The ileum and lungs of SHIP-1-deficient mice are infiltrated at an early age with abundant myeloid cells and the mice have a limited lifespan primarily thought to be due to the consolidation of lungs with spontaneously activated macrophages. To determine whether the myeloid compartment is the key initiator of inflammatory disease in SHIP-1-deficient mice, we examined two independent strains of mice harboring myeloid-restricted deletion of SHIP-1. Contrary to expectations, conditional deletion of SHIP-1 in myeloid cells did not result in consolidating pneumonia or segmental ileitis typical of germline SHIP-1 deficiency. In addition, other myeloid cell abnormalities characteristic of germline loss of SHIP-1, including flagrant splenomegaly and enhanced myelopoiesis, were absent in mice lacking SHIP-1 in myeloid cells. This study indicates that the spontaneous inflammatory disease characteristic of germline SHIP-1 deficiency is not initiated solely by LysM-positive myeloid cells but requires the simultaneous loss of SHIP-1 in other hematolymphoid lineages.


Subject(s)
Lung/immunology , Macrophage Activation , Macrophages/immunology , Myelopoiesis/immunology , Phosphoric Monoester Hydrolases/immunology , Pneumonia/immunology , Animals , Chronic Disease , Ileum/enzymology , Ileum/immunology , Inflammation/enzymology , Inflammation/immunology , Inflammation/pathology , Inositol Polyphosphate 5-Phosphatases , Lung/enzymology , Lung/pathology , Macrophages/enzymology , Macrophages/pathology , Mice , Mice, Knockout , Myelopoiesis/genetics , Phosphatidylinositol 3-Kinases/genetics , Phosphatidylinositol 3-Kinases/immunology , Phosphatidylinositol 3-Kinases/metabolism , Phosphatidylinositol-3,4,5-Trisphosphate 5-Phosphatases , Phosphoric Monoester Hydrolases/genetics , Phosphoric Monoester Hydrolases/metabolism , Pneumonia/enzymology , Pneumonia/genetics
4.
Qual Saf Health Care ; 17(6): 409-15, 2008 Dec.
Article in English | MEDLINE | ID: mdl-19064655

ABSTRACT

BACKGROUND: In 2005, guidance on how to prevent wrong site surgery in the form of a national safety alert was issued to all NHS hospital trusts in England and Wales by the National Patient Safety Agency. OBJECTIVE: To investigate the response to the alert among clinicians in England and Wales 12-15 months after it had been issued. METHODS: A before-after study, using telephone/face-to-face interviews with consultant surgeons and senior nurses in ophthalmology, orthopaedics and urology in 11 NHS hospitals in England & Wales in the year prior to the alert and 12-15 months after. The interviews were coded and analysed thematically. RESULTS: The study revealed marked heterogeneity in organisational processes in response to a national alert. There was a significant change in surgeons' self-reported practice, with only 48% of surgeons routinely marking patients prior to the alert and 85% after (p<0.001). However, inter-specialty differences remained and change in practice was not always matched by change in attitude. Compliance with the detailed recommendations about how marking should be carried out was inconsistent. There were unintended consequences in terms of greater bureaucracy and concerns about diffusion of responsibility and hastily performed marking to enable release of patients from wards. CONCLUSION: The alert was effective in promoting presurgical marking and encouraging awareness of safety issues in relation to correct site surgery. However, care should be taken to monitor unintended consequences and whether change is sustained. Greater flexibility for local adaptation coupled with better design and early testing of safety alerts prior to national dissemination may facilitate more sustainable changes in practice.


Subject(s)
Diffusion of Innovation , Medical Errors/prevention & control , Safety Management/methods , Attitude of Health Personnel , England , Humans , Interviews as Topic , Nursing Staff, Hospital , Physicians , State Medicine , Surveys and Questionnaires , Wales
5.
Br J Anaesth ; 101(4): 511-7, 2008 Oct.
Article in English | MEDLINE | ID: mdl-18723517

ABSTRACT

BACKGROUND: Hip fractures are common in the elderly and have a high 30 day postoperative mortality. The ability to recognize patients at high risk of poor outcomes before operation would be an important clinical advance. This study has determined key prognostic factors predicting 30 day mortality in a hip fracture population, and incorporated them into a scoring system to be used on admission. METHODS: A cohort study was conducted at the Queen's Medical Centre, Nottingham, over a period of 7 yr. Complete data were collected from 4967 patients and analysed. Forward univariate logistic regression was used to select the independent predictor variables of 30 day mortality, and then multivariate logistic regression was applied to the data to construct and validate the scoring system. RESULTS: The variables found to be independent predictors of mortality at 30 days were: age (66-85 yr, > or =86 yr), sex (male), number of co-morbidities (> or =2), mini-mental test score (< or =6 out of 10), admission haemoglobin concentration (< or =10 g dl(-1)), living in an institution, and presence of malignant disease. These variables were subsequently incorporated into a risk score, the Nottingham Hip Fracture Score. The number of deaths observed at 30 days, and the number of deaths predicted by the scoring system, indicated good concordance (chi(2) test, P=0.79). The area (SE) under the receiver operating characteristic curve was 0.719 (0.018), which demonstrated a reasonable predictive value for the score. CONCLUSIONS: We have developed and validated a scoring system that reliably predicts the probability of mortality at 30 days for patients after hip fracture.


Subject(s)
Femoral Neck Fractures/surgery , Trauma Severity Indices , Age Factors , Aged , Aged, 80 and over , England/epidemiology , Epidemiologic Methods , Female , Femoral Neck Fractures/mortality , Humans , Male , Postoperative Complications/mortality , Prognosis , Psychiatric Status Rating Scales , Residence Characteristics , Sex Factors
7.
J Clin Microbiol ; 41(3): 1087-90, 2003 Mar.
Article in English | MEDLINE | ID: mdl-12624034

ABSTRACT

The performance of Etest in fluconazole and voriconazole testing of 279 isolates of uncommon Candida spp. was assessed in comparison with the National Committee for Clinical Laboratory Standards (NCCLS)-approved standard broth microdilution (BMD) method. The NCCLS method employed RPMI 1640 broth medium, and MICs were read after incubation for 48 h at 35 degrees C. Etest MICs were determined with RPMI agar containing 2% glucose and were read after incubation for 48 h at 35 degrees C. The isolates include Candida krusei, C. lusitaniae, C. guilliermondii, C. kefyr, C. rugosa, C. lipolytica, C. pelliculosa, C. dubliniensis, C. famata, C. zeylanoides, C. inconspicua, and C. norvegensis. Overall agreement between Etest and BMD MICs was 96% for fluconazole and 95% for voriconazole. Where a discrepancy was observed between Etest and the reference method, the Etest tended to give lower values with both fluconazole and voriconazole. The Etest method using RPMI agar appears to be a useful method for determining fluconazole and voriconazole susceptibilities of uncommon species of Candida.


Subject(s)
Antifungal Agents/pharmacology , Candida/drug effects , Fluconazole/pharmacology , Microbial Sensitivity Tests/methods , Pyrimidines/pharmacology , Triazoles/pharmacology , Blood/microbiology , Humans , Voriconazole
8.
J Clin Microbiol ; 41(1): 97-9, 2003 Jan.
Article in English | MEDLINE | ID: mdl-12517832

ABSTRACT

The performance of the Etest for voriconazole and amphotericin B susceptibility testing of 162 isolates of Cryptococcus neoformans was assessed against the National Committee for Clinical Laboratory Standards (NCCLS) broth microdilution method. The NCCLS method employed RPMI 1640 broth medium, and MICs were read after incubation for 72 h at 35 degrees C. MICs were determined by Etest for all 162 isolates with RPMI 1640 agar containing 2% glucose (RPG agar) and were read after incubation for 72 h at 35 degrees C. The Etest results for both voriconazole and amphotericin B correlated well with reference MICs. Agreement was 94% for voriconazole and 99% for amphotericin B. When discrepancy was noted between the results obtained by Etest and broth microdilution for voriconazole, the Etest generally provided a higher MIC. The Etest method using RPG agar appears to be a useful method for determining the susceptibility of C. neoformans to voriconazole and amphotericin B.


Subject(s)
Amphotericin B/pharmacology , Antifungal Agents/pharmacology , Cryptococcus neoformans/drug effects , Microbiological Techniques/methods , Pyrimidines/pharmacology , Triazoles/pharmacology , Humans , Microbial Sensitivity Tests/methods , Voriconazole
9.
Arch Dis Child ; 87(6): 489-92, 2002 Dec.
Article in English | MEDLINE | ID: mdl-12456545

ABSTRACT

AIMS: To compare the privately borne and NHS costs of hospital at home (HAH) and conventional inpatient care for children with selected acute conditions. METHODS: Prospective economic evaluation using cost minimisation analysis within a randomised controlled trial, in paediatric wards of a district general hospital, and private homes in the local catchment area in Wirral, Merseyside. Subjects were children who fulfilled the criteria for admission to HAH, suffering from breathing difficulties (n = 202), diarrhoea and vomiting (n = 125), or fever (n = 72). RESULTS: Direct costs borne by families are reduced by 41% for HAH patients ( pound 23.31 v pound 13.76, p = 0.001). There is no evidence that HAH transfers the burden of care to parents, and there is no difference in absence rates from paid employment. Patients and their careers expressed a strong preference for HAH. Comparison of NHS costs is equivocal, depending on how HAH is implemented alongside the conventional hospital service. CONCLUSION: Paediatric HAH schemes are unlikely to reduce NHS costs and do not increase privately borne costs. They will, however, significantly increase patient and career satisfaction with care provision for sick children with appropriate conditions.


Subject(s)
Home Care Services, Hospital-Based/economics , Hospitals, Pediatric/economics , Caregivers/economics , Child , Cost Savings/economics , Costs and Cost Analysis/economics , Databases, Factual , Employment/economics , England , Financing, Personal/economics , Health Care Costs/trends , Humans , Patient Satisfaction/economics , Prospective Studies , State Medicine/economics , Travel/economics
10.
Arch Dis Child ; 87(5): 371-5, 2002 Nov.
Article in English | MEDLINE | ID: mdl-12390903

ABSTRACT

AIMS: To assess the clinical effectiveness of a paediatric hospital at home service compared to conventional hospital care. METHODS: A total of 399 children suffering from breathing difficulty (n = 202), diarrhoea and vomiting (n = 125), or fever (n = 72) were randomised to Hospital at Home or in-patient paediatric care. Main outcome measures were: comparative clinical effectiveness as measured by readmission rate within three months (used as a proxy for parental coping with illness); and length of stay/care and comparative satisfaction of both patients and carers. RESULTS: Clinical effectiveness of both services was not significantly different. Length of care was one day longer in the Hospital at Home group; however, most parents and children preferred home care. CONCLUSIONS: Hospital at Home is a clinically acceptable form of care for these groups of acute paediatric illness. Readmission rates within three months failed to show any advantage in terms of parental coping. Parents and patients expressed a strong preference for hospital at home.


Subject(s)
Diarrhea/therapy , Home Care Services, Hospital-Based/statistics & numerical data , Hospitals, Pediatric/statistics & numerical data , Outcome Assessment, Health Care , Respiration Disorders/therapy , Vomiting/therapy , Acute Disease , Adolescent , Child , Child, Preschool , Female , Health Services Research , Home Care Services, Hospital-Based/standards , Hospitals, Pediatric/standards , Humans , Infant , Length of Stay/statistics & numerical data , Male , Patient Readmission/statistics & numerical data , Treatment Outcome
11.
Emerg Med J ; 19(3): 265-7, 2002 May.
Article in English | MEDLINE | ID: mdl-11971849

ABSTRACT

Colchicine overdose is uncommon but potentially life threatening. It is a safe drug when used according to established therapeutic guidelines but causes serious systemic effects if ingested in doses that exceed the recommendations. Overdose must therefore be recognised early and treated appropriately to optimise the outcome. A fatal case of colchicine overdose caused by inappropriate self medication is reported and to the best of the authors' knowledge, there has been no report of fatal accidental overdose in the United Kingdom. The pharmacology of colchicine, the clinical features associated with overdose, and the options for treatment are discussed.


Subject(s)
Colchicine/poisoning , Gout Suppressants/poisoning , Adult , Colchicine/therapeutic use , Drug Overdose , Fatal Outcome , Gout/drug therapy , Gout Suppressants/therapeutic use , Heart Arrest/chemically induced , Humans , Male , Multiple Organ Failure/chemically induced
12.
Health Soc Care Community ; 9(2): 108-17, 2001 Mar.
Article in English | MEDLINE | ID: mdl-11560727

ABSTRACT

This mainly qualitative study compared 40 families' experience of hospital and home care. This is one aspect of a randomised, controlled trial, which aimed to evaluate the clinical and cost effectiveness of a paediatric hospital at home service (HAH) for acute illness in children. This paper builds upon previous work that has aimed to examine parents' and children's views as service users. Forty families from a larger sample population took part in structured interviews. Eleven children aged 5 to 12 years took part in semistructured interviews. A drawing technique was the chosen method of augmentation in the children's interviews. Research findings showed that HAH is an acceptable alternative to hospital care where there are essentially nursing needs. Thirty-six (90%) parents and seven children stated a clear preference for HAH. The parents' preference was based on a perception that their child's illness wasn't serious or life threatening and therefore could be managed at home with appropriate support from health professionals. The social and financial costs of hospital care compared with HAH were the other main drivers, rather than a comparison of the quality of nursing care of their child.


Subject(s)
Home Care Services/standards , Hospitals, Pediatric/standards , Patient Satisfaction/statistics & numerical data , Quality of Health Care/statistics & numerical data , Acute Disease , Adult , Chi-Square Distribution , Child , Child, Hospitalized , Child, Preschool , Continuity of Patient Care , Female , Home Care Services/organization & administration , Hospitals, Pediatric/organization & administration , Humans , Interviews as Topic , Male , Parents , Randomized Controlled Trials as Topic , United Kingdom
13.
Am J Physiol ; 274(6): L951-7, 1998 06.
Article in English | MEDLINE | ID: mdl-9609734

ABSTRACT

The possibility that significant changes in endothelin (ET)A- and ETB-receptor density and function occur in airway smooth muscle cells (ASMCs) during cell growth and extended cell culture was investigated in sheep tracheal ASMCs. As in intact tracheal smooth muscle tissue from this species, early-passage sheep ASMCs contained a homogeneous population of ETA receptors. However, growth of ASMCs from seeding to postconfluence and repeated passage of ASMCs (6th to 14th passages) was associated with a substantial increase in ETB-receptor density, with no change in ETA-receptor density. ET-1-induced stimulation of ETB receptors increased the intracellular Ca2+ concentration in single ASMCs. Interestingly, a 2-day period of serum deprivation completely eliminated the increase in ETB-receptor density and the ETB receptor-mediated change in intracellular Ca2+ concentration. In summary, growth and repeated passage of sheep ASMCs were associated with a profound and selective increase in the density and function of the ETB receptor, a receptor subtype not present in early-passage ASMCs and not detected in intact sheep tracheal airway smooth muscle.


Subject(s)
Muscle, Smooth, Vascular/chemistry , Receptors, Endothelin/analysis , Receptors, Endothelin/physiology , Trachea/chemistry , Animals , Calcium/metabolism , Cell Division , Cells, Cultured , Culture Media, Serum-Free , Endothelin-1/metabolism , Endothelin-1/pharmacology , Kinetics , Muscle, Smooth, Vascular/physiology , Receptor, Endothelin A , Receptor, Endothelin B , Sheep , Trachea/physiology
14.
Br J Pharmacol ; 125(8): 1768-78, 1998 Dec.
Article in English | MEDLINE | ID: mdl-9886769

ABSTRACT

1. The aim of the current study was to characterize the ET receptor subtypes in cultured airway smooth muscle cells derived from rat trachea and human bronchus using radioligand binding techniques and to investigate the coupling of ET receptors to intracellular calcium signalling mechanisms using endothelin receptor-selective agonists (sarafotoxin S6c) and antagonists (BQ-123, BQ-788) and digital image fluorescence microscopy. 2. Confluent rat airway smooth muscle cells in culture possessed a mixed ET receptor population (30% ETA : 70% ETB), with a density of approximately 3400+/-280 ETA and 8000+/-610 ETB receptors/cell (n = 3 experiments). The density of ETB, but not ETA receptors increased substantially in serum-containing medium. However, a 2-day period of serum deprivation, which inhibited cellular growth, substantially reduced ETB receptor density such that the ET receptor subtype proportions were approximately equal (55% ETA; 45% ETB) and similar to those previously observed in intact rat tracheal smooth muscle. 3. Challenge of rat airway smooth muscle cells in culture with endothelin- 1 elicited a concentration-dependent biphasic increase in [Ca2+]i (EC50: 16 nM), that comprised an initial transient peak [Ca2+]i increase (typically 350 nM) followed by a modest sustained component. The endothelin-1-induced biphasic [Ca2+]i increase was primarily due to ETA receptor activation, although a modest and inconsistent ETB response was observed. The ETA-mediated [Ca2+]i increase was due primarily to the mobilization of IP3-sensitive and to a lesser extent ryanodine-sensitive intracellular calcium stores. In contrast, ETB receptor activation was exclusively coupled to extracellular calcium influx. 4. Somewhat surprisingly, human airway smooth muscle cells in culture contained a homogeneous population of ETA receptors at a density of 6100+/-800 receptors cell(-1) (n = 3 experiments). Serum deprivation was without effect on either ET receptor subtype proportion or ETA receptor density. Challenge of human airway smooth muscle cells with endothelin-1 provoked a concentration-dependent increase in [Ca2+]i (EC50: 15 nM), with a peak [Ca2+]i increase to greater than 700 nM. Furthermore, the ETA-mediated calcium response in these human airway smooth muscle cells in culture was entirely dependent upon the mobilization of calcium from intracellular stores. 5. In summary, rat cultured tracheal airway smooth muscle cells contained both ETA and ETB receptors. ETA receptors, the numbers of which remained constant during cell growth, were linked to the release of Ca2+ from intracellular stores and a strong rise in [Ca2+]i in the majority of airway smooth muscle cells. In stark contrast, the numbers of ETB receptors increased significantly during cell growth, an effect that was diminished substantially by incubation in serum-free medium. Moreover, despite the greater number of ETB receptors, their activation in a small number of airway smooth muscle cells produced only a weak rise in [Ca2+]i, which appeared to be attributable to the influx of extracellular Ca2+. In contrast, the populations of ET receptors and their linkage to [Ca2+]i were markedly different in the human cultured airway smooth muscle cells used in the current study compared to that previously observed in intact human isolated bronchial smooth muscle.


Subject(s)
Calcium/physiology , Muscle, Smooth/metabolism , Receptors, Endothelin/metabolism , Adolescent , Animals , Binding, Competitive/drug effects , Bronchi/cytology , Bronchi/drug effects , Bronchi/physiology , Caffeine/pharmacology , Calcium/metabolism , Cell Division/drug effects , Cell Division/physiology , Cells, Cultured , Culture Media, Serum-Free/pharmacology , Dose-Response Relationship, Drug , Endothelin Receptor Antagonists , Endothelin-1/drug effects , Endothelin-1/metabolism , Endothelin-1/pharmacology , Enzyme Inhibitors/pharmacology , Humans , Iodine Radioisotopes , Male , Muscle, Smooth/cytology , Muscle, Smooth/drug effects , Oligopeptides , Peptides, Cyclic/pharmacology , Piperidines , Radioligand Assay , Rats , Rats, Wistar , Receptor, Endothelin A , Receptor, Endothelin B , Receptors, Endothelin/drug effects , Ryanodine/pharmacology , Signal Transduction , Thapsigargin/pharmacology , Viper Venoms/pharmacology
15.
Annu Rev Pharmacol Toxicol ; 35: 129-44, 1995.
Article in English | MEDLINE | ID: mdl-7598489

ABSTRACT

It has been proposed that a number of chemical-induced cell injuries result from disruption of the ability of the cell to control calcium. Many of the techniques used to develop this theory have relied on indirect measurements of intracellular calcium. The advent of digital imaging fluorescence microscopy has allowed a more direct examination of the relationship between calcium and cell damage. Results indicate that cytosolic calcium does not play a central role in the initiation of oxidative injury in a number of cell types. Changes in calcium homeostasis occur well after the appearance of other indications of cell injury. However, recent studies indicate that a mitochondrial lesion occurs relatively early in the time course of oxidative cell injury. Calcium may play a role in the development of this lesion.


Subject(s)
Calcium/physiology , Cell Physiological Phenomena , Adenosine Triphosphate/metabolism , Cell Death , Mitochondria/physiology , Oxidative Stress
16.
Hosp Community Psychiatry ; 36(2): 150-3, 1985 Feb.
Article in English | MEDLINE | ID: mdl-3882541

ABSTRACT

Posttraumatic stress disorder is now well known to occur among Vietnam combat veterans. The interest in this diagnosis may have caused an unintentional neglect of veterans with problems that do not meet the strict criteria of DSM-III for this disorder. The authors studied 300 Vietnam veterans admitted to a general hospital to determine their level of symptomatology and to gather data on this previously unstudied group. More than 75 percent of the sample were medical-surgical patients; about 50 percent had high levels of depression and symptoms of posttraumatic stress disorder, or both. Combat veterans were considerably more symptomatic; more than 50 percent of the patients with the highest levels of combat activity were on nonpsychiatric wards. The authors suggest the need to identify Vietnam veterans on medical and surgical wards. Reluctance to talk about war experiences makes Vietnam veterans a group likely to be overlooked.


Subject(s)
Hospitals, General/statistics & numerical data , Veterans/psychology , Adult , Humans , Mental Disorders/psychology , Stress Disorders, Post-Traumatic/psychology , United States , United States Department of Veterans Affairs , Vietnam
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