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1.
BMC Health Serv Res ; 18(1): 536, 2018 07 11.
Artigo em Inglês | MEDLINE | ID: mdl-29996820

RESUMO

BACKGROUND: Research on team effectiveness in healthcare has focussed on whether effective teams yield positive outcomes for patients and on the effectiveness of team interventions to improve performance. Limited understanding exists of what works for whom within an effective team, or how and why the context in which the team operates enables team members both as individuals and as a collective to enact behaviours that promote positive outcomes. METHODS: This realist synthesis of the literature explores the relationship between team interventions, underlying teamwork mechanisms generated by those interventions, and the resultant impact on patient outcomes in an acute hospital context. A systematic search of five healthcare and healthcare management academic databases: PubMed, PsychINFO, CINAHL, ABInform, Emerald Management and three grey literature databases: ERIC, OpenDOAR and Open Grey was undertaken. Five experts in the field were also contacted to source relevant literature. Using PRISMA guidelines, relevant studies published between January 2006 and January 2017 were systematically searched by a team of three people. Drawing on realist methodology, data were synthesised using context, mechanism and outcome configurations as the unit of analysis to identify enablers and barriers to effective team interventions. RESULTS: Out of 3347 papers retrieved, 18 were included in the final synthesis. From these, five contextual enablers were identified: an inter-disciplinary focus and flattened hierarchy; effective communication; leadership support and alignment of team goals with organisational goals; credibility of intervention; and appropriate team composition with physician involvement. Ten recurring mechanisms were identified, the most frequently occurring of which was shared responsibility. CONCLUSIONS: The advantage of using realist synthesis to extrapolate data from the literature is that it considers the context and mechanisms that will impact effectiveness of healthcare team interventions. This methodological approach provides a different perspective to other types of syntheses and offers insight as to why certain contextual elements may yield more success than others. Findings therefore tend to have more practical implications. Specificity of detail in terms of how external drivers impact on healthcare team interventions was limited in the articles extracted for analysis. This broader perspective is therefore an important consideration for future research.


Assuntos
Equipe de Assistência ao Paciente/organização & administração , Desenvolvimento de Pessoal/organização & administração , Prática Clínica Baseada em Evidências , Pesquisa sobre Serviços de Saúde , Humanos , Liderança , Cultura Organizacional , Equipe de Assistência ao Paciente/normas
2.
Chem Commun (Camb) ; 54(32): 3959-3962, 2018 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-29561051

RESUMO

We report solid-state Nuclear Magnetic Resonance (ssNMR) studies on amyloid-like protein complexes formed by DIX domains that mediate key protein interactions in the Wnt signalling pathway. Our results provide insight into the 3D fold of the self-associated Axin-DIX domain and identify a potential lipid cofactor.


Assuntos
Amiloide/química , Proteína Axina/química , Fragmentos de Peptídeos/química , Via de Sinalização Wnt , Proteína Axina/metabolismo , Sítios de Ligação , Humanos , Espectroscopia de Ressonância Magnética , Fragmentos de Peptídeos/metabolismo , Fosfatidiletanolaminas/química , Fosfatidiletanolaminas/metabolismo , Ligação Proteica , Domínios Proteicos
3.
Anaesthesia ; 65(4): 396-408, 2010 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-20402876

RESUMO

While some speculation surrounds annual private practice incomes of anaesthetists, little is known of the hours of work needed to generate any presumed income (the hourly rate). The benefit maxima of five private medical insurers are published in fee schedules and data on the duration of common operations are now also known. In this study we combined these to generate estimates for hourly rates of reimbursement across 78 common operations in eight surgical subspecialties, for anaesthetists and surgeons. We expected to find significant differences between insurers as a result of market competition, and we expected differences between anaesthetists and surgeons. The median (IQR [range]) rate of reimbursement for anaesthetists was pound167 (132-211 [68-570]).h(-1) with significant variation across subspecialties (p < 0.001); for example, cardiac surgery was best reimbursed at pound283 (257-308 [229-398]).h(-1) and orthopaedics the least at pound146 (133-159 [81-246]).h(-1). Contrary to expectations, the rates of payment to anaesthetists by insurers were similar (p > 0.17). Patterns of reimbursement for surgeons were similar to those for anaesthetists, except that surgeons were reimbursed at about twice the rate. We conclude there is a confluence of insurer reimbursement levels and we discuss potential implications of this finding. Our results also have implications for how incentives between the NHS and private practice, or within a private practice group, might be optimally managed.


Assuntos
Anestesiologia/economia , Renda/estatística & dados numéricos , Reembolso de Seguro de Saúde/economia , Especialidades Cirúrgicas/economia , Algoritmos , Custos e Análise de Custo/estatística & dados numéricos , Humanos , Setor Privado/economia , Medicina Estatal/economia , Reino Unido
4.
J Antimicrob Chemother ; 56(6): 1042-6, 2005 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-16286361

RESUMO

BACKGROUND: Tigecycline is a minocycline derivative, belonging to a chemical class prone to oxidation and to medium-related effects on susceptibility. We therefore studied the effect of medium type and age on the tigecycline MICs found in broth and on agar by the Clinical Laboratory Standards Institute and British Society for Applied Chemotherapy methods. METHODS: MICs of tigecycline, minocycline and tetracycline were determined for 96 non-fastidious bacteria and 20 streptococci using Mueller-Hinton broth (MHB), Mueller-Hinton agar (MHA), Iso-Sensitest broth (ISB) and Iso-Sensitest agar (ISA) as: (i) freshly-prepared media; (ii) fresh media but with the antibiotic added 1 day before inoculation and (iii) media stored for 7 days before antibiotic addition and use. RESULTS: MICs of tigecycline in fresh MHB were up to two doubling dilutions higher than on or in MHA, ISA or ISB. Media with tigecycline or classical tetracyclines added a day before use gave raised MICs, though rarely by more than one dilution. MICs of tigecycline (less so classical tetracyclines) were increased in 7-day-old MHB or ISB, even though the antibiotic was freshly added. This latter effect was greatest for the most susceptible strains and was absent or much reduced for organisms with MICs > or = 8 mg/L; it did not occur in the corresponding agar dilution tests. Addition of blood to MHB largely abrogated the effect, as did steaming the broth before adding the antibiotic. CONCLUSIONS: The raised MICs of tigecycline in aged broth probably reflect inactivation by dissolved oxygen. This accords with the lack of any MIC increase in newly-steamed (i.e. degassed) MHB or on aged agar (which is melted at 100 degrees C before use). Blood, which also abrogated the effect, may increase reducing capacity, protecting the tigecycline. At a practical level, broth MIC determinations for tigecycline should always employ fresh media.


Assuntos
Antibacterianos/farmacologia , Bactérias/efeitos dos fármacos , Meios de Cultura/química , Testes de Sensibilidade Microbiana , Minociclina/análogos & derivados , Tetraciclinas/farmacologia , Minociclina/farmacologia , Oxirredução , Tigeciclina , Fatores de Tempo
5.
J Antimicrob Chemother ; 54(4): 735-43, 2004 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-15347638

RESUMO

OBJECTIVES: During 2003, the Health Protection Agency's Antibiotic Resistance Monitoring and Reference Laboratory began to receive isolates of Escherichia coli for confirmation of extended-spectrum beta-lactamase production with a phenotype implying a CTX-M-type beta-lactamase, i.e. MICs of cefotaxime > or = 8-fold higher than MICs of ceftazidime. Many were referred as being from community patients. We examined 291 CTX-M-producing isolates from the UK and investigated the genetic basis of their phenotype. METHODS: PCR was used to detect alleles encoding CTX-M enzymes and to assign these to their blaCTX-M phylogenetic groups. Selected alleles were sequenced. Producers were compared by analysis of banding patterns generated by pulsed-field gel electrophoresis of XbaI-digested genomic DNA. MICs were determined by an agar dilution method or by Etest. RESULTS: Of 291 CTX-M-producing E. coli isolates studied from 42 UK centres, 70 (24%) were reportedly from community patients, many of whom had only limited recent hospital contact. Community isolates were referred by 12 centres. Two hundred and seventy-nine (95.9%) producers contained genes encoding group 1 CTX-M enzymes and 12 contained blaCTX-M-9-like alleles. An epidemic CTX-M-15-producing strain was identified, with 110 community and inpatient isolates referred from six centres. Representatives of four other major strains also produced CTX-M-15, as did several sporadic isolates examined. Most producers were multi-resistant to fluoroquinolones, trimethoprim, tetracycline and aminoglycosides as well as to non-carbapenem beta-lactams. CONCLUSIONS: CTX-M-producing E. coli are a rapidly developing problem in the UK, with CTX-M-15 particularly common. The diversity of producers and geographical scatter of referring laboratories indicates wide dissemination of blaCTX-M genes. Because of the public health implications, including for the treatment of community-acquired urinary tract infections, the spread of these strains--and CTX-M-15 beta-lactamase in particular--merits close monitoring.


Assuntos
Farmacorresistência Bacteriana/genética , Infecções por Escherichia coli/epidemiologia , Escherichia coli/genética , beta-Lactamases/biossíntese , Alelos , Antibacterianos/farmacologia , Infecções Comunitárias Adquiridas/epidemiologia , Infecções Comunitárias Adquiridas/microbiologia , Conjugação Genética , Infecção Hospitalar/epidemiologia , Infecção Hospitalar/microbiologia , Eletroforese em Gel de Campo Pulsado , Escherichia coli/efeitos dos fármacos , Escherichia coli/enzimologia , Escherichia coli/isolamento & purificação , Infecções por Escherichia coli/microbiologia , Genes Bacterianos/genética , Humanos , Testes de Sensibilidade Microbiana , Fenótipo , Reino Unido/epidemiologia , beta-Lactamases/genética
6.
Emerg Med J ; 21(3): 355-61, 2004 May.
Artigo em Inglês | MEDLINE | ID: mdl-15107383

RESUMO

A simple algorithm has been produced to assist front line ground ambulance personnel, air ambulance crews, and immediate care doctors attending trauma patients in selecting the most appropriate mode of transport from the incident scene to hospital.


Assuntos
Resgate Aéreo , Algoritmos , Ferimentos e Lesões/terapia , Tomada de Decisões , Meio Ambiente , Humanos , Fatores de Risco , Fatores de Tempo , Triagem/métodos , Reino Unido
7.
Clin Exp Immunol ; 132(3): 436-42, 2003 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-12780690

RESUMO

The circulating and cervical B cell responses to Chlamydia trachomatis plasmid protein pgp3 were characterized in children and adults with ocular or genital chlamydial infection using the enzyme-linked immunospot assay (ELISPOT) and ELISA. No pgp3-specific ASCs were detected in healthy controls, but predominantly IgA ASCs were detected in UK adults with uncomplicated cervicitis or urethritis (P = 0.03, 0.019). In patients with extragenital complications or pelvic inflammatory disease a mixed response with more IgG and IgM ASCs was evident, suggesting a breach of mucosal immune compartmentalization with more extensive infection. In women with chlamydial cervicitis, ASCs secreting predominantly IgA, but also IgG, to pgp3 were present in cervix at presentation, with a frequency 30-50 times higher than blood. Cervical ASC numbers, especially IgG, fell markedly six weeks after antibiotic treatment. We detected principally IgA pgp3-specific antibody secreting cells (ASCs) in children resident in a Gambian endemic area, with a trend towards suppression of IgA responses during intense trachomatous inflammation (P = 0.06), as previously reported for other chlamydial antigens, and in keeping with the findings in genital disease. These data provide a rationale for further studies of immune responses to pgp3 in humans and animal models of chlamydia-induced disease, and its potential use in diagnostic assays and protective immunization strategies.


Assuntos
Antígenos de Bactérias/imunologia , Proteínas de Bactérias/imunologia , Infecções por Chlamydia/imunologia , Chlamydia trachomatis/imunologia , Tracoma/imunologia , Cervicite Uterina/imunologia , Adulto , Antibacterianos/uso terapêutico , Anticorpos Antibacterianos/biossíntese , Especificidade de Anticorpos , Células Produtoras de Anticorpos/imunologia , Criança , Infecções por Chlamydia/tratamento farmacológico , Ensaio de Imunoadsorção Enzimática/métodos , Feminino , Humanos , Imunidade nas Mucosas , Imunoglobulina A/biossíntese , Imunoglobulina G/biossíntese , Imunoglobulina M/biossíntese , Masculino , Tracoma/microbiologia , Uretrite/imunologia , Uretrite/microbiologia , Cervicite Uterina/tratamento farmacológico , Cervicite Uterina/microbiologia
8.
J Chromatogr B Biomed Sci Appl ; 762(2): 147-54, 2001 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-11678374

RESUMO

We developed a simple capillary electrophoresis (CE) method to measure nitrite and nitrate concentrations in submicroliter samples of rat airway surface liquid (ASL), a thin (10-30 microm) layer of liquid covering the epithelial cells lining the airways of the lung. The composition of ASL has been poorly defined, in large part because of the small sample volume (approximately 1-3 microl per cm2 of epithelium) and difficulty of harvesting ASL. We have used capillary tubes for ASL sample collection, with microanalysis by CE using a 50 mM phosphate buffer (pH 3), with 0.5 mM spermine as a dynamic flow modifier, and direct UV detection at 214 nm. The limit of detections (LODs), under conditions used, for ASL analysis were 10 microM for nitrate and 30 microM for nitrite (SIN= 3). Nitrate and nitrite were also measured in rat plasma. The concentration of nitrate was 102+/-12 microM in rat ASL and 70+/-1.0 microM in rat plasma, whereas nitrite was 83+/-28 microM in rat ASL and below the LOD in rat plasma. After instilling lipopolysaccharide intratracheally to induce increased NO production, the nitrate concentration in ASL increased to 387+/-16 microM, and to 377+/-88 microM in plasma. The concentration of nitrite increased to 103+/-7.0 microM for ASL and 138+/-17 microM for plasma.


Assuntos
Eletroforese Capilar/métodos , Nitratos/sangue , Nitritos/sangue , Animais , Ratos , Reprodutibilidade dos Testes , Sensibilidade e Especificidade
9.
Eur J Pharmacol ; 423(1): 57-61, 2001 Jun 29.
Artigo em Inglês | MEDLINE | ID: mdl-11438307

RESUMO

The role of the thromboxane A(2)/prostaglandin H(2) receptor in endothelin-1 contraction was investigated in aortic rings from rats exposed to normoxia (21% O(2)) or hypoxia (10% O(2)) for 12 h. Indomethacin (10 microM) and SQ 29,548 (0.1 microM, thromboxane A(2)/prostaglandin H(2) receptor antagonist) reduced maximum tension and increased EC(50) in endothelium-intact and -denuded rings from normoxic animals. Neither inhibitor had any effect on rings from hypoxic rats. Thromboxane A(2) and/or prostaglandin H(2) contribute to the response to endothelin-1 in aortas from normoxic rats but not from rats exposed to hypoxia. Loss of prostanoid-enhancement of endothelin-1 contraction contributes to impair vascular reactivity after hypoxia.


Assuntos
Aorta Torácica/efeitos dos fármacos , Endotelina-1/farmacologia , Hipóxia/fisiopatologia , Receptores de Prostaglandina/fisiologia , Vasoconstrição/efeitos dos fármacos , Acetilcolina/farmacologia , Animais , Aorta Torácica/fisiologia , Compostos Bicíclicos Heterocíclicos com Pontes , Relação Dose-Resposta a Droga , Endotélio Vascular/fisiologia , Ácidos Graxos Insaturados , Hidrazinas/farmacologia , Técnicas In Vitro , Masculino , Fenilefrina/farmacologia , Ratos , Ratos Sprague-Dawley , Receptores de Prostaglandina/antagonistas & inibidores , Receptores de Tromboxano A2 e Prostaglandina H2 , Vasoconstritores/farmacologia , Vasodilatadores/farmacologia
10.
J Cardiovasc Risk ; 8(3): 159-63, 2001 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-11455848

RESUMO

BACKGROUND: Chronic infection with organisms such as Chlamydia pneumoniae is thought to cause coronary heart disease. We investigated whether myocardial infarction deaths are associated with large household size and overcrowding, as these are factors that may facilitate the transmission of infection. DESIGN: Ecological study of England and Wales. METHODS: Population data were obtained from the 1991 National Census and mortality data were obtained from the Office of National Statistics. For various categories of household size and overcrowding, we calculated mortality rates standardized for age, sex and deprivation. RESULTS: Standardized mortality rates for acute respiratory infections were associated with household size and overcrowding, while rates for myocardial infarction and gastric carcinoma, both putatively associated with chronic infection, were associated with household size. For combined deaths from causes other than myocardial infarction, there were small associations with household size and overcrowding. In the case of myocardial infarction, the association was generally strongest in the age group 45-54.9 years. For this age group, the standardized mortality rate ratio for the category of largest size household was 2.7 in the year 1991. CONCLUSIONS: There is an association between household size and mortality from myocardial infarction. Chronic infection is a possible cause.


Assuntos
Morte , Características da Família , Infarto do Miocárdio/mortalidade , Infarto do Miocárdio/psicologia , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Inglaterra/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fatores Sexuais , País de Gales/epidemiologia
11.
Am J Forensic Med Pathol ; 21(3): 220-4, 2000 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-10990280

RESUMO

Typical and atypical exit wounds are well described in the forensic literature. Included in the descriptions of atypical exit wounds are perforating, "shored" exit wounds, in which the perforation of the skin is associated with an abrasion, whether or not the bullet fully exits the body. The authors describe an atypical, incomplete, shored exit wound in which the skin was abraded by supporting material at the site the bullet was recovered, but there was no associated perforation of the skin. Recognition of this injury pattern can be important in reconstruction of the crime scene in relation to the victim at the time of the shooting.


Assuntos
Pele/lesões , Pele/patologia , Ferimentos por Arma de Fogo/patologia , Adulto , Idoso , Autopsia , Dorso , Feminino , Humanos , Masculino , Postura , Tórax
12.
BMJ ; 321(7255): 204-7, 2000 Jul 22.
Artigo em Inglês | MEDLINE | ID: mdl-10903649

RESUMO

OBJECTIVE: To determine whether there is an independent association between infection with Chlamydia pneumoniae and ischaemic heart disease. DESIGN: Prospective study using a nested case-control design. SETTING: Medical centre in London run by BUPA, a private medical organisation. PARTICIPANTS: 21 520 professional men aged 35-64 who attended for a medical examination in London between 1975 and 1982. MAIN OUTCOME MEASURE: Death from ischaemic heart disease. RESULTS: The distributions of concentrations of IgG and IgA antibodies to C pneumoniae were similar in the 647 men who subsequently died of ischaemic heart disease and in 1294 age matched controls who did not. There was no material association with heart disease irrespective of the cut-off point chosen to define seropositivity. At a cut-off point that defines 15% of controls as positive, for example, the odds ratios were 1.26 (95% confidence interval 0.95 to 1.68) for IgG and 1.09 (0.82 to 1.43) for IgA. CONCLUSIONS: No material association was found between infection with C pneumoniae and ischaemic heart disease. The size and prospective design of the study and the socioeconomic homogeneity of the cohort minimise both random and systematic error.


Assuntos
Infecções por Chlamydia/complicações , Chlamydophila pneumoniae , Infarto do Miocárdio/mortalidade , Adulto , Anticorpos Antibacterianos/sangue , Estudos de Casos e Controles , Chlamydophila pneumoniae/imunologia , Humanos , Imunoglobulina A/sangue , Imunoglobulina G/sangue , Londres/epidemiologia , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/microbiologia , Estudos Prospectivos , Fatores de Risco
13.
Circ Res ; 86(6): 671-5, 2000 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-10747003

RESUMO

The goal of this study was to determine whether hypoxia alters expression of endothelial nitric oxide synthase (eNOS) in the systemic circulation. Rats breathed either air or 10% oxygen for 12 hours, 48 hours, or 7 days. Thoracic aortas were excised and either mounted in organ bath myographs or frozen in liquid nitrogen for later extraction of protein and RNA. eNOS protein (Western blotting) was decreased (20% of normoxic control) after 12 hours, 48 hours, and 7 days of hypoxia. eNOS mRNA (ribonuclease protection assay) was similarly reduced. Acetylcholine (10(-4) mol/L) reversed phenylephrine (10(-5) mol/L) preconstriction by 53.3+/-5.6% in aortic rings from normoxic rats and 26.1+/-4.8% in rings from rats exposed to hypoxia for 48 hours (P<0.05), with comparable impairment of relaxation by the calcium ionophore A23187 (10(-5) mol/L). Responses to diethylamine nitric oxide and 8-bromo-cGMP were unaffected. Aortic cGMP levels after incubation with acetylcholine (10(-6) mol/L) averaged 14.0+/-1.8 fmol/mg in rings from normoxic rats compared with 8.7+/-1.0 fmol/mg in rings from hypoxic rats (P<0. 05). Similarly, nitrate concentration (by capillary electrophoresis) in the media in which the rings were incubated was reduced in the hypoxic group (5.6+/-0.23 micromol/L for hypoxic rats and 7.8+/-0.7 micromol/L for normoxic rats). Impaired endothelial NO release may handicap the vascular responses that defend vital organ function during hypoxia.


Assuntos
Aorta/enzimologia , Hipóxia/enzimologia , Óxido Nítrico Sintase/metabolismo , Animais , Aorta/metabolismo , GMP Cíclico/biossíntese , Regulação para Baixo , Endotélio Vascular/fisiologia , Masculino , Dados de Sequência Molecular , Nitratos/sangue , Nitratos/metabolismo , Óxido Nítrico Sintase/genética , Óxido Nítrico Sintase Tipo III , RNA Mensageiro/metabolismo , Ratos , Ratos Sprague-Dawley , Fatores de Tempo , Vasodilatação/fisiologia
14.
J Forensic Sci ; 45(6): 1259-66, 2000 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-11110179

RESUMO

We evaluated the impact and penetration characteristics of the Remington Copper Solid sabot shotgun slug with standardized ballistic tests and used this information to predict tissue wounding patterns. This unique ammunition, first distributed in 1993, is composed of a solid copper, hollow-point slug with longitudinal slots cut into the nose. The slug is fitted into a hard plastic sabot with 8 finger-like projections and loaded into a shotgun shell with two plastic wads separating it from the underlying gunpowder charge. The ammunition was fired through a 12-gage shotgun using a rifled barrel, a smooth-bore barrel with rifled choke, and a smooth-bore barrel with a smooth modified choke into targets consisting of poster board and 10% ballistic gelatin at a variety of distances. The copper slug and plastic sabot created single 8-fingered asterisk-shaped defects in the poster board when fired at distances of less than 7 to 9 ft (approximately 2 to 3 m). All three barrel types performed similarly. At greater distances, the sabot impacted the targets separately from the slugs and created variably shaped defects that reflected base-first, nose-first, and side-first impacts. Increasing muzzle-to-target distances generally increased the impact distances between the slug and sabot. There was no predictable relationship between the sabot and slug impact points for any of the three barrel types. With each barrel tested, the wads created separate defects from the slug at distances greater than 5 ft (1.5 m). The distances between the slug and the wad impact points increased with increasing muzzle-to-target distances up to 40 ft (12 m), after which the wads generally no longer struck the targets. The slug created atypical defects at distances between 7 and 150 ft (approximately 2 to 45 m), probably due to yawing or tumbling. When the slug impacted the gelatin block in a nose-first orientation, the slotted nose portion tended to fragment and radially deposit pieces in the gelatin that were visible on radiographs. When the slug struck the gelatin target in a side-first orientation, it passed through the gelatin intact. The slug, sabot, and wads of this unique projectile separate and create independent impact points in a stereotypical manner independent of barrel type. This pattern of separation allows estimates to be made of ranges of fire. Wounds created in human tissues by this ammunition would likely have similar asterisk-shaped configurations, and nose fragments may be deposited in tissues and seen radiographically. Rectangular wounds created by the tumbling or yawing slug might be mistaken for intermediate target wounds.

15.
Anesthesiology ; 93(6): 1456-64, 2000 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-11149441

RESUMO

BACKGROUND: Cerebral arteriolar tone is modulated in response to changes in transmural pressure and luminal flow. The effect of flow on the relation between pressure and diameter has not been fully evaluated in these vessels. This study was conducted to investigate this interaction and to determine the role of the endothelium in mediating it. METHODS: Rat pial arterioles from the territory of the posterior cerebral artery were mounted in a perfusion myograph. In some arterioles, the endothelium was removed by air perfusion. Diameters were recorded at pressures from 20 to 200 mmHg in the presence and absence of flow (10 microl/min). The response to flow (0-30 microl/min) was recorded at 60 and 120 mmHg. RESULTS: In the absence of flow, endothelium-intact arterioles demonstrated tone at distending pressures between 40 and 140 mmHg. In the presence of flow, tone did not develop until pressure exceeded 100 mmHg, and the vessels remained active at pressures up to 200 mmHg. Endothelium-denuded arterioles developed tone at the same pressure when perfused as when unperfused, but perfused vessels were able to maintain active tone at higher pressures. At 60 mmHg, flow caused dilation if the endothelium was intact and constriction if it had been removed. At 120 mmHg, flow caused constriction. Endothelium-dependent flow-relaxation was inhibited by N(G)-nitro-L-arginine methyl ester (10(-5) M) and abolished by indomethacin (10(-5) M). CONCLUSION: Flow inhibits the development of pial arteriolar tone at low intraluminal pressures through endothelium-dependent mechanisms. Conversely, perfusion extends the upper limit of the myogenically regulated pressure range through endothelium-independent activation of arteriolar smooth muscle contraction.


Assuntos
Endotélio Vascular/fisiologia , Tono Muscular/fisiologia , Músculo Liso Vascular/fisiologia , Pia-Máter/irrigação sanguínea , Animais , Arteríolas/efeitos dos fármacos , Arteríolas/fisiologia , Pressão Sanguínea/fisiologia , Fármacos Cardiovasculares/farmacologia , Endotélio Vascular/efeitos dos fármacos , Inibidores Enzimáticos/farmacologia , Indometacina/farmacologia , Masculino , Tono Muscular/efeitos dos fármacos , Músculo Liso Vascular/efeitos dos fármacos , NG-Nitroarginina Metil Éster/farmacologia , Artéria Cerebral Posterior , Ratos , Ratos Sprague-Dawley , Vasoconstrição/efeitos dos fármacos , Vasoconstrição/fisiologia , Vasodilatação/efeitos dos fármacos , Vasodilatação/fisiologia
16.
Diabetes Technol Ther ; 2(2): 185-97, 2000.
Artigo em Inglês | MEDLINE | ID: mdl-11469258

RESUMO

BACKGROUND: Orally inhaled insulin may provide a convenient and effective therapy for prandial glucose control in patients with diabetes. This study evaluated the influence of formulation pH and concentration and different respiratory maneuvers on pharmacokinetic and pharmacodynamic properties of inhaled insulin. METHODS: Three, open-label crossover studies in a total of 23 healthy subjects were conducted in which the safety, pharmacokinetics, and pharmacodynamics of insulin inhalation were compared to subcutaneous (SC) injection into the abdomen of commercially available regular insulin. A novel, aerosol generating system (AERx Diabetes Management System, Aradigm Corporation, Hayward, CA) was used to deliver aqueous insulin bolus aerosols to the lower respiratory tract from formulations at pH 3.5 or 7.4 and concentrations of U250 (250 U/mL) or U500 (500 U/mL). RESULTS: Time to maximum insulin concentration in serum (Tmax) after SC dosing occurred approximately 50-60 minutes with the time to minimum plasma glucose concentration (i.e., maximum hypoglycemic effect), (TGmin), occurring later, at around 100-120 minutes. In contrast, pulmonary delivery led to a significantly earlier Tmax (7-20 minutes) and TGmin (60-70 minutes), parameters that were shown to be largely unaffected by changing the pH or concentration of the insulin. However, investigation of changes in inhaled volume (achieved by different programming of the AERx system) for administration of the same sized aerosol bolus revealed significant effects. Significantly slower absorption and time to peak hypoglycemic activity occurred when aerosol delivery of insulin occurred during a shallow (approximately 40% vital capacity) as opposed to a deep (approximately 80% vital capacity) inspiration. In addition, it was shown that serum concentration of insulin increased immediately after a series of forced expiraratory maneuvers 30 minutes after inhaled delivery. CONCLUSIONS: Pulmonary delivery of aqueous bolus aerosols of insulin in healthy subjects resulted in rapid absorption with an associated hypoglycemic effect quicker than is achieved after subcutaneous dosing of regular insulin. Inhaled insulin pharmacokinetics and pharmacodynamics were independent of formulation variables (pH, concentration) but affected by certain respiratory maneuvers.


Assuntos
Glicemia/metabolismo , Insulina/administração & dosagem , Insulina/farmacologia , Administração por Inalação , Adulto , Aerossóis , Glicemia/efeitos dos fármacos , Estudos Cross-Over , Jejum , Humanos , Injeções Subcutâneas , Insulina/sangue , Masculino , Valores de Referência , Segurança , Fatores de Tempo
17.
Anaesthesia ; 54(12): 1201-3, 1999 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-10594419

RESUMO

An intriguing case of transient language disturbance following anaesthesia is described which may throw some light on the way languages are stored in the brain. A review of the existing literature and its relevance to this unique case is discussed.


Assuntos
Anestesia Geral/efeitos adversos , Hipoglicemia/complicações , Transtornos da Linguagem/etiologia , Multilinguismo , Glicemia/análise , Humanos , Transtornos da Linguagem/sangue , Masculino , Pessoa de Meia-Idade
18.
J Am Coll Cardiol ; 34(5): 1435-9, 1999 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-10551689

RESUMO

OBJECTIVE: To determine whether current vascular Chlamydia pneumoniae (CPn) infection as diagnosed by circulating CPn DNA is more common in subjects with coronary artery disease (CAD). BACKGROUND: Serological, pathological and animal studies have associated CPn with CAD and preliminary trials suggest antibiotics may prevent adverse coronary events. C. pneumoniae is thought to disseminate systemically within macrophages. We therefore detected CPn DNA in blood to determine whether its presence was a predictor of CAD. METHODS: One thousand, two hundred and five subjects attending for diagnostic and interventional coronary arteriography were recruited. The mononuclear cell layer and platelets were separated from collected blood and the polymerase chain reaction (PCR) was used to detect CPn DNA. RESULTS: Circulating CPn DNA was found in 8.8% of 669 men with CAD compared with 2.9% of 135 men with normal coronary arteries (odds ratio [OR] 3.2, 95% confidence interval [CI] 1.1-8.9). In men with CAD, those with CPn DNA had higher mean platelet counts than those without CPn DNA. Monocyte counts and indirect fibrinogen levels were also raised but not significantly so. By contrast, no association of circulating CPn DNA and CAD was seen in women. CONCLUSIONS: Circulating CPn DNA is a predictor of CAD in men. Unlike serology, it is a specific indicator of current infection and is a means of identifying subjects who may potentially benefit from antichlamydial therapy.


Assuntos
Infecções por Chlamydia/complicações , Chlamydophila pneumoniae/isolamento & purificação , Doença das Coronárias/microbiologia , DNA Bacteriano/sangue , Monócitos/microbiologia , Idoso , Chlamydophila pneumoniae/genética , Doença Crônica , Angiografia Coronária , Doença das Coronárias/sangue , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase , Fatores de Risco , Fatores Sexuais
20.
J Med Assoc Thai ; 82(6): 581-6, 1999 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-10443080

RESUMO

Adolescent males are considered to be an important genital chlamydial reservoir. However, there has been little information on urethral chlamydial infection in Thai adolescent males. About one fourth of males who are genital chlamydial reservoirs are asymptomatic. An appropriate means of defining the extent of chlamydial infection in adolescent males would be a non-invasive screening survey, instead of the conventional method of a deep swab cell culture, which is painful. The objectives of this study were to estimate the prevalence and to determine what factors should indicate the use of a screening test for urethral chlamydial infection in adolescent males residing in Chiang Mai. Chlamydial urethritis was detected by examining urine deposits for chlamydial antigen by enzyme immunoassay (EIA).


Assuntos
Infecções por Chlamydia/diagnóstico , Chlamydia/isolamento & purificação , Programas de Rastreamento/métodos , Uretrite/microbiologia , Adolescente , Adulto , Distribuição de Qui-Quadrado , Infecções por Chlamydia/epidemiologia , Infecções por Chlamydia/urina , Estudos Transversais , Humanos , Masculino , Prevalência , Tailândia/epidemiologia
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