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This study examines the association between the ASA physical status classification score at hip fracture surgery and severe postoperative complications in patients aged 60 and older. Among both men and women, ASA scores consistently predict a wide range of complications including infections, cardiovascular complications, hospital readmissions, and death. INTRODUCTION: Hip fractures are common in aging populations and associated with poor prognosis. This study examines how the American Society of Anaesthesiologists (ASA) physical status classification is related to severe complications among hip fracture patients including infections, cardiovascular diseases, hospital readmissions, and death. METHODS: Based on a linkage of the Swedish National Inpatient Register with the Swedish National Registry for Hip Fractures (RIKSHÖFT), this study includes patients aged 60+ with first hip fracture between 1998 and 2017. We estimated associations between ASA score and complications during the hospital stay and during 1 year after hip fracture using multivariable-adjusted logistic regression and Cox proportional hazard regression. RESULTS: The study population included 170,193 hip fracture patients of which 24% died and 39% were readmitted to hospital within 1 year. The most common complications were urinary tract infections, pneumonia, second hip fractures, and heart failure. Among both men and women, higher ASA scores were consistently associated with higher risks for all complications included in this study. The strongest associations were observed for heart failure, myocardial infarction, pneumonia, and death. CONCLUSION: ASA scores are routinely assessed in clinical practice and predict a wide range of postoperative complications among hip fracture patients. Since many complications may be preventable through adequate drug treatment, rehabilitation, and risk awareness, future studies should examine the mechanisms linking ASA scores to complication risk in order to improve preventive strategies. Particularly, the high risk of cardiovascular complications among patients with high ASA scores deserves clinical and scientific attention.
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Infecções Cardiovasculares , Fraturas do Quadril , Idoso , Estudos de Coortes , Feminino , Fraturas do Quadril/epidemiologia , Fraturas do Quadril/cirurgia , Humanos , Masculino , Pessoa de Meia-Idade , Readmissão do Paciente , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Estudos Retrospectivos , Fatores de RiscoRESUMO
OBJECTIVES: Few studies have assessed cognitive impairment among healthy people living with HIV (PLWH) who are stable on antiretroviral treatment (ART) in sub-Saharan Africa. METHODS: We conducted a cross-sectional study among a random sample of stable adult PLWH from rural Tanzania on ART for more than 1 year and without immunological failure or pre-existing neurological disease. We evaluated the prevalence and risk factors for neurocognitive impairment (NCI), assessed through neuropsychological tests, functional and depression questionnaires and defined as a mean Z-score ≤ -1 in two or more cognitive domains. RESULTS: Among 243 participants [median age = 44.3 years (interquartile range: 36-52] and 71% female] we found a rate of NCI of 19.3% (95% confidence interval: 14.8-24.8%). Memory and psychomotor domains demonstrated the highest impairment. Independent predictors of NCI were age and self-reported alcohol use. Other classical risk factors were not associated with HIV-associated NCI. CONCLUSION: Despite effective ART roll-out, NCI remained a prevalent condition in this healthy rural Tanzanian population of PLWH on ART. Age and alcohol use were key risk factors.
Assuntos
Infecções por HIV , Adulto , Antirretrovirais/uso terapêutico , Estudos Transversais , Feminino , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , Infecções por HIV/epidemiologia , Humanos , Masculino , Inquéritos e Questionários , Tanzânia/epidemiologiaRESUMO
This report presents a case of endotracheal metastasis in which elective veno-venous extracorporeal membrane oxygenation (VV ECMO) was used to undergo tracheal laser-surgery prior to establishment of a definitive airway. Specifically, we describe the respiratory and airway management in an adult patient from the preclinical phase throughout elective preoperative ECMO implantation to postoperative ECMO weaning and decannulation in the Intensive Care Unit. This case report lends further supports to the idea that the extracorporeal membrane oxygenation could be electively used to provide safe environment for surgery in situations where the standard maneuvers of sustaining adequate gas exchange are anticipated to fail.
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OBJECTIVES: To test the hypothesis that a screening and treatment intervention for early cryptococcal infection would improve survival among HIV-infected individuals with low CD4 cell counts. METHODS: Newly enrolled patients at Family AIDS Care and Education Services (FACES) in Kenya with CD4 ≤ 100 cells/µl were tested for serum cryptococcal antigen (sCrAg). Individuals with sCrAg titre ≥ 1:2 were treated with high-dose fluconazole. Cox proportional hazard models of Kaplan-Meier curves were used to compare survival among individuals with CD4 ≤ 100 cells/µl in the intervention and historical control groups. RESULTS: The median age was 34 years [IQR: 29,41], 54% were female, and median CD4 was 43 cells/µl [IQR: 18,71]. Follow-up time was 1224 person-years. In the intervention group, 66% (514/782) were tested for sCrAg; of whom, 11% (59/514) were sCrAg positive. Mortality was 25% (196/782) in the intervention group and 25% (191/771) in the control group. There was no significant difference between the intervention and control group in overall survival [hazard ratio (HR): 1.1 (95%CI:0.9,1.3)] or three-month survival [HR: 1.0 (95%CI:0.8,1.3)]. Within the intervention group, sCrAg-positive individuals had significantly lower survival rates than sCrAg-negative individuals [HR:1.8 (95%CI: 1.0, 3.0)]. CONCLUSIONS: A screening and treatment intervention to identify sCrAg-positive individuals and treat them with high-dose fluconazole did not significantly improve overall survival among HIV-infected individuals with CD4 counts ≤ 100 cells/µl compared to a historical control, perhaps due to intervention uptake rates or poor efficacy of high-dose oral fluconazole.
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Infecções Oportunistas Relacionadas com a AIDS/mortalidade , Antígenos de Fungos/sangue , Cryptococcus neoformans/imunologia , Meningite Criptocócica/mortalidade , Infecções Oportunistas Relacionadas com a AIDS/tratamento farmacológico , Infecções Oportunistas Relacionadas com a AIDS/imunologia , Adulto , Antirretrovirais/uso terapêutico , Antifúngicos/uso terapêutico , Contagem de Linfócito CD4 , Estudos de Casos e Controles , Feminino , Fluconazol/uso terapêutico , Humanos , Estimativa de Kaplan-Meier , Quênia , Masculino , Meningite Criptocócica/tratamento farmacológico , Meningite Criptocócica/imunologia , Taxa de Sobrevida , Resultado do TratamentoRESUMO
BACKGROUND: Inner hair cells encode sound into action potentials in the auditory nerve. Spiral ganglion neurons form the afferent innervation of inner hair cells via the hair cell synapse. The structure and function of this ribbon-type synapse is considered to have a major impact on the sound encoding process itself. In this study we have used conventional confocal microscopy as well as super-resolution techniques to investigate the synaptic organization in the inner hair cells of mice. MATERIAL AND METHODS: Functionally relevant proteins of the afferent inner hair cell synapse were selectively marked using immunohistochemical methods and investigated with conventional confocal and super-resolution 4Pi- and stimulated emission depletion (STED) techniques. RESULTS: Synapse and innervation density was mapped over the entire tonotopic axis. We found inner hair cells in the region of best hearing to have about twice the number of afferent fibres compared to the apex or base of the cochlea. For the first time 4Pi and STED microscopic techniques were employed to resolve the fine structure of these synapses beyond the resolution of conventional light microscopy. With 4Pi a resolution of approximately 100 nm in the z-axis direction is feasible. In practice STED delivers an effective resolution between 150 and 30 nm, depending on the power of the lasers employed. Synapses at different tonotopic positions of the cochlea exhibit no relevant structural differences at this level of resolution. The 4Pi and STED microscopic techniques are capable of showing the structure of afferent synapses in the organ of Corti with unsurpassed resolution. These images contribute to our understanding of sound-encoding mechanisms in the inner ear.
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Vias Aferentes/ultraestrutura , Células Ciliadas Auditivas Internas/ultraestrutura , Aumento da Imagem/métodos , Microscopia Confocal/métodos , Imagem Óptica/métodos , Sinapses/ultraestrutura , Animais , Camundongos , Camundongos Endogâmicos C57BL , Reprodutibilidade dos Testes , Sensibilidade e EspecificidadeRESUMO
Tetrabenazine (TBZ), a benzoquinolizine derivative, binds with high affinity to the vesicular monoamine transporter-2 (VMAT2), inhibiting uptake of cytosolic monoamines. The current study aimed to provide preclinical evidence supporting the potential use of TBZ as a treatment for methamphetamine abuse. Effects of TBZ on function of the dopamine transporter (DAT) and serotonin transporter (SERT) in striatal and hippocampal synaptosomes, respectively, and on VMAT2 function in isolated striatal synaptic vesicles were determined. Effect of TBZ (acute, 0.1-3.0 mg/kg, s.c.; repeated, 1.0 mg/kg for 7 days) on locomotor activity in methamphetamine-sensitized rats was assessed. Ability of TBZ (0.1-3.0 mg/kg; s.c.) or vehicle to decrease the discriminative effect of methamphetamine also was determined. Ability of TBZ (acute, 0.1-1.0 mg/kg, s.c.; repeated, 0.1 or 1.0 mg/kg for 7 days) to specifically decrease methamphetamine self-administration was determined; for comparison, a separate group of rats was assessed for effects of TBZ on food-maintained responding. Results show that TBZ was 11-fold more potent inhibiting DAT than SERT, and 2.5-fold more potent inhibiting VMAT2 than DAT. Results from behavioral studies showed that the lowest dose of TBZ transiently increased methamphetamine self-administration, whereas higher TBZ doses decreased methamphetamine self-administration. Also, TBZ at high doses decreased methamphetamine locomotor sensitization and discriminative stimulus effects, as well as food-maintained responding. Thus, despite acting as a potent VMAT2 inhibitor, these preclinical results indicate that TBZ lacks behavioral specificity as an inhibitor of methamphetamine-induced reinforcement, diminishing its viability as a suitable treatment for methamphetamine abuse.
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Inibidores da Captação Adrenérgica/farmacologia , Aprendizagem por Discriminação/efeitos dos fármacos , Metanfetamina/administração & dosagem , Atividade Motora/efeitos dos fármacos , Tetrabenazina/farmacologia , Proteínas Vesiculares de Transporte de Monoamina/antagonistas & inibidores , Animais , Aprendizagem por Discriminação/fisiologia , Masculino , Metanfetamina/antagonistas & inibidores , Atividade Motora/fisiologia , Ratos , Ratos Sprague-Dawley , Autoadministração , Proteínas Vesiculares de Transporte de Monoamina/metabolismoRESUMO
Previous research using outbred rats indicates that individual differences in activity in a novel environment predict sensitivity to the reinforcing effect of psychostimulant drugs. The current study examined if the link between responses related to novelty and amphetamine self-administration is heritable. Twelve inbred rat strains were assessed for locomotor activity in a novel environment, preference for a novel environment, and intravenous amphetamine self-administration (acquisition, extinction and amphetamine-induced reinstatement). Strain differences were observed in activity in a novel environment, novelty preference and amphetamine self-administration, indicating a genetic influence for each of these behaviors. While there was no relation between activity in an inescapable novel environment and amphetamine self-administration, strain-dependent differences in novelty preference were positively correlated with the amount of amphetamine self-administered. There was also a positive correlation between the dose-dependent rate of amphetamine self-administration and magnitude of reinstatement. These results show that the activity in an inescapable novel environment and the preference for a novel environment are different genetically, and thus likely to reflect different behavioral constructs. Moreover, these results implicate a genetic influence on the relation between novelty seeking and stimulant self-administration, as well as on the relation between stimulant reward and reinstatement.
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Transtornos Relacionados ao Uso de Anfetaminas/genética , Transtornos Relacionados ao Uso de Anfetaminas/psicologia , Comportamento Exploratório/fisiologia , Animais , Estimulantes do Sistema Nervoso Central/farmacologia , Condicionamento Operante/fisiologia , Dextroanfetamina/farmacologia , Relação Dose-Resposta a Droga , Extinção Psicológica , Masculino , Ratos , Ratos Endogâmicos BN , Ratos Endogâmicos BUF , Ratos Endogâmicos Dahl , Ratos Endogâmicos Lew , Ratos Endogâmicos SHR , Ratos Endogâmicos , Ratos Endogâmicos WKY , Recidiva , Esquema de Reforço , Autoadministração , Especificidade da EspécieRESUMO
At the large excitatory calyx of Held synapse, the quantal size during an evoked EPSC and the number of active zones contributing to transmission are not known. We developed a nonstationary variant of EPSC fluctuation analysis to determine these quantal parameters. AMPA receptor-mediated EPSCs were recorded in slices of young (postnatal 8-10 d) rats after afferent fiber stimulation, delivered in trains to induce synaptic depression. The means and the variances of EPSC amplitudes were calculated across trains for each stimulus number. During 10 Hz trains at 2 mm Ca(2+) concentration ([Ca(2+)]), we found linear EPSC variance-mean relationships, with a slope that was in good agreement with the quantal size obtained from amplitude distributions of spontaneous miniature EPSCs. At high release probability with 10 or 15 mm [Ca(2+)], competitive antagonists were used to partially block EPSCs. Under these conditions, the EPSC variance-mean plots could be fitted with parabolas, giving estimates of quantal size and of the binomial parameter N. With the rapidly dissociating antagonist kynurenic acid, quantal sizes were larger than with a slowly dissociating antagonist, suggesting that the effective glutamate concentration was increased at high release probability. Considering the possibility of multivesicular release and moderate saturation of postsynaptic AMPA receptors, we conclude that the binomial parameter N (637 +/- 117; mean +/- SEM) represents an upper limit estimate of the number of functional active zones. We estimate that during normal synaptic transmission, the probability of vesicle fusion at single active zones is in the range of 0.25-0.4.
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Tronco Encefálico/fisiologia , Potenciais Pós-Sinápticos Excitadores/fisiologia , Sinapses/metabolismo , Transmissão Sináptica/fisiologia , Animais , Tronco Encefálico/citologia , Estimulação Elétrica , Antagonistas de Aminoácidos Excitatórios/farmacologia , Potenciais Pós-Sinápticos Excitadores/efeitos dos fármacos , Técnicas In Vitro , Fusão de Membrana/fisiologia , Tamanho da Partícula , Ratos , Ratos Wistar , Receptores de AMPA/antagonistas & inibidores , Receptores de AMPA/metabolismo , Processamento de Sinais Assistido por Computador , Vesículas Sinápticas/metabolismoRESUMO
OBJECTIVE: To report a case of secondary amenorrhea and infertility caused by an inhibin-B-producing ovarian fibrothecoma. DESIGN: Case report. SETTING: Academic medical center. PATIENT: A 37-year-old woman with a 2-year history of secondary amenorrhea and infertility. INTERVENTION(S): Operative removal of a 5-cm ovarian fibrothecoma. MAIN OUTCOME MEASURE(S): Luteinizing hormone, FSH, E2, inhibin-B, TSH, and prolactin measured preoperatively and postoperatively. Immunostaining of tumor cells for inhibin and LH. RESULT(S): Preoperative hormone levels were as follows: FSH, 1.7 mIU/mL; LH, 23.4 mIU/mL; E2, 31 pg/mL; and inhibin B, 1,154 pg/mL. Three weeks postoperatively, the FSH was 1.5 mIU/mL, LH decreased to 7.1 mIU/mL, E2 increased to 276 pg/mL, and inhibin-B decreased to 17 pg/mL. The fibrothecoma did not stain for LH but was strongly positive for inhibin. Regular menstrual cycles resumed 28 days postoperatively. CONCLUSION(S): Inhibin-B produced by an ovarian tumor profoundly suppressed FSH levels and resulted in secondary amenorrhea and infertility. Use of sensitive and specific immunoassays for inhibin-A and -B may aid in the differential diagnosis of hormonally active ovarian tumors.
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Amenorreia/etiologia , Infertilidade Feminina/etiologia , Inibinas/metabolismo , Neoplasias Ovarianas/complicações , Neoplasias Ovarianas/metabolismo , Tumor da Célula Tecal/complicações , Tumor da Célula Tecal/metabolismo , Adulto , Feminino , Humanos , Técnicas Imunoenzimáticas , Microscopia Eletrônica , Neoplasias Ovarianas/patologia , Neoplasias Ovarianas/terapia , Tumor da Célula Tecal/patologia , Tumor da Célula Tecal/terapiaRESUMO
The size of a pool of readily releasable vesicles at a giant brainstem synapse, the calyx of Held, was probed with three independent approaches. Using simultaneous pre- and postsynaptic whole-cell recordings, two forms of presynaptic Ca2+ stimuli were applied in rapid succession: uncaging of Ca2+ by flash photolysis and the opening of voltage-gated Ca2+ channels. The ensuing transmitter release showed a nearly complete cross-inhibition between the two stimuli, indicating the depletion of a limited pool of about 700 transmitter quanta. The pool size was confirmed in experiments using enhanced extracellular Ca2+ concentrations, as well as short, high-frequency stimulus trains. The results reveal a surprisingly large pool of functionally available vesicles, of which a fraction of about 0.2 is released by a single presynaptic action potential under physiological conditions.
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Tronco Encefálico/fisiologia , Neurotransmissores/fisiologia , Sinapses/fisiologia , Potenciais de Ação , Algoritmos , Animais , Cálcio/metabolismo , Canais de Cálcio/metabolismo , Canais de Cálcio/fisiologia , Estimulação Elétrica , Potenciais Pós-Sinápticos Excitadores/fisiologia , Técnicas In Vitro , Ativação do Canal Iônico , Técnicas de Patch-Clamp , Fotólise , RatosRESUMO
In the course of studying the circulating TCR repertoire in humans, we noted several individuals with an increase in the percentage of CD8+ T cells expressing a particular V region. In some cases, these CD8 expansions were dramatic, occupying over 40% of the total CD8 repertoire. Using a panel of mAbs to different TCR V regions, we found that over 30% of healthy adults (> 35 years of age) harbor an expansion that alters the peripheral blood CD8 TCR repertoire. A wide range of V regions were expressed by these expansions. Considering that the mAbs used cover only a portion of the V beta repertoire, the data suggest that over 70% of adults are likely to harbor such expansions. Junctional region sequencing showed that the CD8 subset expansions were clonal, and serial studies as long as 4 years showed that they persisted indefinitely. Expansions were not identified in the CD4 population. Discordant expression of one large V beta 6.7+ clone was found in one identical twin set, suggesting the possibility that an environmental exposure is involved in their generation and/or expansion. In one large family, we found five family members with a large CD8 subset expansion. Remarkably similar usage of J beta regions was noted, and two individuals demonstrated V beta 3-expressing clones with homologous CDR3 regions, differing by only one major substitution. The repertoire data from this family suggest that the T cell clones have arisen in response to a common Ag. Studies of patients with rheumatoid arthritis found a significantly increased frequency of circulating CD8 subset expansions that expressed a different V region repertoire compared with the healthy individuals studied. Overall, our results emphasize a frequent alteration in the human CD8 TCR repertoire, most likely related to an environmental exposure, in both healthy individuals and patients with rheumatoid arthritis. The presence of these expansions will be important to consider in any study of human TCR repertoire, and their implication for health and disease will be important to understand.
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Artrite Reumatoide/imunologia , Linfócitos T CD8-Positivos/imunologia , Ativação Linfocitária/imunologia , Receptores de Antígenos de Linfócitos T alfa-beta/imunologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Sequência de Aminoácidos , Sequência de Bases , Linfócitos T CD4-Positivos/imunologia , Divisão Celular/imunologia , Criança , Células Clonais , Humanos , Pessoa de Meia-Idade , Dados de Sequência Molecular , Receptores de Antígenos de Linfócitos T alfa-beta/genéticaRESUMO
An investigation into the effects of verapamil and some dihydropyridine derivatives on plasma melatonin levels was undertaken in baboons. In a number of separate experiments, groups of young male chacma baboons (mean body weight 13 kg) received intraperitoneal injections of the drugs, under ketamine anaesthesia, roughly 30 minutes prior to the following time points: 1200, 1800, 0000, 0200, 0600 and 1200 h. Lights went off at 1800 h and came on at 0600 h. The drugs used, and their respective dosages (expressed per kg body mass), were verapamil up to 4 mg/kg, nifedipine at 0.2 mg/kg, nitrendipine at 0.5 mg/kg and nisoldipine at 0.1 mg/kg. Blood samples, taken at the said time points, were assayed for melatonin. The nighttime peak of the plasma melatonin cycle was significantly depressed by all three dihydropyridine calcium antagonists (up to 40%), while verapamil, even at the relatively high total dose of 24 mg/kg per day, had no significant effect on the circulating plasma melatonin levels.
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Bloqueadores dos Canais de Cálcio/farmacologia , Melatonina/sangue , Animais , Masculino , Nifedipino/análogos & derivados , Nifedipino/farmacologia , Nisoldipino , Nitrendipino/farmacologia , Papio , Verapamil/farmacologiaAssuntos
Albinismo/metabolismo , Melatonina/metabolismo , Adulto , População Negra , Ritmo Circadiano , Humanos , África do SulRESUMO
In baboons kept under controlled lighting conditions, microtubules (MT) are readily seen in the perikaryal cytoplasm and in the perivascular processes of pinealocytes. A significant increase in the number of MT, single synaptic ribbons (SR) and the formation of synaptic ribbon fields (RF, i.e. organelles which consist of multiple dense rodlets or plates, and vesicles), occur during the dark phase of a circadian light-dark cycle. MT may act as "tracks" for the oriented flow of vesicles derived from the smooth endoplasmic reticulum, to cytoplasmic sites where RF are being formed. The origin of the dense rodlets of RF remains unknown. Structural differences between SR and RF indicate that the latter organelles are not directly involved in impulse propagation between adjacent baboon pinealocytes. RF may function as storage organelles for some of the pineal secretory products which are formed in large amounts during the dark phase.
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Ritmo Circadiano , Microtúbulos/ultraestrutura , Glândula Pineal/ultraestrutura , Sinapses/ultraestrutura , Animais , Escuridão , Retículo Endoplasmático/ultraestrutura , Luz , Masculino , Microscopia Eletrônica , PapioRESUMO
Microfilaments (MF, 5-8 nm in diameter) are a prominent feature of the pinealocyte cytoplasm of baboons (Papio ursinus) kept under controlled lighting conditions. MF occurred as a filamentous network in these cells during the light phase of the diurnal light-dark cycle, while a close structural association was noted between MF and the membranes of the smooth endoplasmic reticulum (SER). This association was especially evident during the dark period. Increased numbers of single synaptic ribbons (SR, vesicle-crowned rodlets), together with large aggregations of SR, i.e., ribbon fields (RF), were seen in the pinealocyte cytoplasm of baboons killed during the dark phase. It is suggested that the vesicles of RF may arise from those of the SER and that MF may play a role in the movement of SER-vesicles to those areas of the cytoplasm where new RF are being formed.
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Citoplasma/ultraestrutura , Citoesqueleto/ultraestrutura , Retículo Endoplasmático/ultraestrutura , Papio/anatomia & histologia , Glândula Pineal/ultraestrutura , Animais , Haplorrinos , Masculino , Microtúbulos/ultraestruturaAssuntos
Grânulos Citoplasmáticos/efeitos dos fármacos , Miocárdio/ultraestrutura , Antagonistas da Serotonina/farmacologia , Serotonina/metabolismo , Animais , Química Encefálica/efeitos dos fármacos , Depressão Química , Fenclonina/farmacologia , Fluorometria , Masculino , Miocárdio/metabolismo , RatosAssuntos
Renda , Humanos , Prática Institucional/economia , Prática Privada/economia , África do SulAssuntos
Dispositivos Intrauterinos , Gravidez Tubária , Adulto , Feminino , Humanos , Gravidez , Gravidez Tubária/diagnósticoRESUMO
An analysis of 1,686 surgically treated carcinomas of the breast in one community showed no statistically significant differences in five- and ten-year survival for simple, modified radical, or radical mastectomy. Further confirmation was obtained by computation of relative survival which in addition showed that older women more nearly approach normal life expectancy than younger ones. Bilaterality was found to be a decreasing function of age. Patients with medial and lateral tumors did not have significantly different rates of survival or sites of distant metastases.