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1.
Brain Behav Immun ; 110: 125-139, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-36863493

RESUMO

Neuroimmune pathways regulate brain function to influence complex behavior and play a role in several neuropsychiatric diseases, including alcohol use disorder (AUD). In particular, the interleukin-1 (IL-1) system has emerged as a key regulator of the brain's response to ethanol (alcohol). Here we investigated the mechanisms underlying ethanol-induced neuroadaptation of IL-1ß signaling at GABAergic synapses in the prelimbic region of the medial prefrontal cortex (mPFC), an area responsible for integrating contextual information to mediate conflicting motivational drives. We exposed C57BL/6J male mice to the chronic intermittent ethanol vapor-2 bottle choice paradigm (CIE-2BC) to induce ethanol dependence, and conducted ex vivo electrophysiology and molecular analyses. We found that the IL-1 system regulates basal mPFC function through its actions at inhibitory synapses on prelimbic layer 2/3 pyramidal neurons. IL-1ß can selectively recruit either neuroprotective (PI3K/Akt) or pro-inflammatory (MyD88/p38 MAPK) mechanisms to produce opposing synaptic effects. In ethanol naïve conditions, there was a strong PI3K/Akt bias leading to a disinhibition of pyramidal neurons. Ethanol dependence produced opposite IL-1 effects - enhanced local inhibition via a switch in IL-1ß signaling to the canonical pro-inflammatory MyD88 pathway. Ethanol dependence also increased cellular IL-1ß in the mPFC, while decreasing expression of downstream effectors (Akt, p38 MAPK). Thus, IL-1ß may represent a key neural substrate in ethanol-induced cortical dysfunction. As the IL-1 receptor antagonist (kineret) is already FDA-approved for other diseases, this work underscores the high therapeutic potential of IL-1 signaling/neuroimmune-based treatments for AUD.


Assuntos
Alcoolismo , Etanol , Camundongos , Masculino , Animais , Etanol/farmacologia , Interleucina-1beta/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Fator 88 de Diferenciação Mieloide/metabolismo , Camundongos Endogâmicos C57BL , Córtex Pré-Frontal/metabolismo , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo
2.
Neuropharmacology ; 168: 107752, 2020 05 15.
Artigo em Inglês | MEDLINE | ID: mdl-31476352

RESUMO

The pituitary adenylate cyclase-activating polypeptide (PACAP) system plays a central role in the brain's emotional response to psychological stress by activating cellular processes and circuits associated with threat exposure. The neuropeptide PACAP and its main receptor PAC1 are expressed in the rodent central amygdala (CeA), a brain region critical in negative emotional processing, and CeA PACAPergic signaling drives anxiogenic and stress coping behaviors. Despite this behavioral evidence, PACAP's effects on neuronal activity within the medial subdivision of the CeA (CeM, the major output nucleus for the entire amygdala complex) during basal conditions and after psychological stress remain unknown. Therefore, in the present study, male Wistar rats were subjected to either restraint stress or control conditions, and PACAPergic regulation of CeM cellular function was assessed using immunohistochemistry and whole-cell patch-clamp electrophysiology. Our results demonstrate that PACAP-38 potentiates GABA release in the CeM of naïve rats, via its actions at presynaptic PAC1. Basal PAC1 activity also enhances GABA release in an action potential-dependent manner. Notably, PACAP-38's facilitation of CeM GABA release was attenuated after a single restraint stress session, but after repeated sessions returned to the level observed in naïve animals. A single restraint session also significantly decreased PAC1 levels in the CeM, with repeated restraint sessions producing a slight recovery. Collectively our data reveal that PACAP/PAC1 signaling enhances inhibitory control of the CeM and that psychological stress can modulate this influence to potentially disinhibit downstream effector regions that mediate anxiety and stress-related behaviors. This article is part of the special issue on 'Neuropeptides'.


Assuntos
Núcleo Central da Amígdala/metabolismo , Neurônios GABAérgicos/metabolismo , Polipeptídeo Hipofisário Ativador de Adenilato Ciclase/farmacologia , Estresse Psicológico/metabolismo , Sinapses/metabolismo , Ácido gama-Aminobutírico/metabolismo , Animais , Núcleo Central da Amígdala/efeitos dos fármacos , Neurônios GABAérgicos/efeitos dos fármacos , Potenciais Pós-Sinápticos Inibidores/efeitos dos fármacos , Potenciais Pós-Sinápticos Inibidores/fisiologia , Masculino , Ratos , Ratos Wistar , Receptores de Polipeptídeo Hipofisário Ativador de Adenilato Ciclase/metabolismo , Restrição Física/efeitos adversos , Restrição Física/psicologia , Estresse Psicológico/psicologia , Sinapses/efeitos dos fármacos
3.
Alcohol Alcohol ; 53(6): 642-649, 2018 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-29309503

RESUMO

AIMS: Stress induces neuroimmune responses via Toll-like receptor 4 (TLR4) activation. Here, we investigated the role of TLR4 in the effects of the stress peptide corticotropin-releasing factor (CRF) on GABAergic transmission in the central nucleus of the amygdala (CeA) following restraint stress. METHODS: Tlr4 knock out (KO) and wild-type rats were exposed to no stress (naïve), a single restraint stress (1 h) or repeated restraint stress (1 h per day for 3 consecutive days). After 1 h recovery from the final stress session, whole-cell patch-clamp electrophysiology was used to investigate the effects of CRF (200 nM) on CeA GABAA-mediated spontaneous inhibitory postsynaptic currents (sIPSCs). RESULTS: TLR4 does not regulate baseline GABAergic transmission in the CeA of naive and stress-treated animals. However, CRF significantly increased the mean sIPSC frequencies (indicating enhanced GABA release) across all genotypes and stress treatments, except for the Tlr4 KO rats that experienced repeated restraint stress. CONCLUSIONS: Overall, our results suggest a limited role for TLR4 in CRF's modulation of CeA GABAergic synapses in naïve and single stress rats, though TLR4-deficient rats that experienced repeated psychological stress exhibit a blunted CRF cellular response. SHORT SUMMARY: TLR4 has a limited role in CRF's activation of the CeA under basal conditions, but interacts with the CRF system to regulate GABAergic synapse function in animals that experience repeated psychological stress.


Assuntos
Núcleo Central da Amígdala/metabolismo , Hormônio Liberador da Corticotropina/farmacologia , Estresse Psicológico/metabolismo , Transmissão Sináptica/fisiologia , Receptor 4 Toll-Like/fisiologia , Ácido gama-Aminobutírico/metabolismo , Animais , Núcleo Central da Amígdala/efeitos dos fármacos , Hormônio Liberador da Corticotropina/metabolismo , Potenciais Pós-Sinápticos Inibidores/efeitos dos fármacos , Potenciais Pós-Sinápticos Inibidores/fisiologia , Masculino , Ratos , Ratos Transgênicos , Ratos Wistar , Restrição Física , Estresse Psicológico/psicologia , Transmissão Sináptica/efeitos dos fármacos , Receptor 4 Toll-Like/deficiência
4.
Equine Vet J ; 48(6): 704-709, 2016 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-26671764

RESUMO

REASONS FOR PERFORMING STUDY: Foals of mares infected with Leptospira interrogans serovar Pomona type kennewicki (Lk) may be aborted/stillborn or delivered as healthy foals. Is fetal survival explained in part by the immune response of the fetus to Leptospira antigens? OBJECTIVES: To describe an outbreak of Leptospira abortion in which infected mares delivered dead/sick or normal foals and determine specificities of antibody in a collection of 54 fetuses from similar outbreaks. STUDY DESIGN: Outbreak investigation in combination with a case-control study of a larger set of samples from aborted fetuses. METHODS: Serology and polymerase chain reaction (PCR) on urine and amniotic fluids were used to diagnose infection during an outbreak of Leptospira abortion. Specificities of immunoglobulin (Ig)M, IgGa and IgGb for recombinant proteins of Lk in archived fluids of fetuses from similar outbreaks were compared by ELISA with those of fluids of fetuses not infected with Leptospira spp. RESULTS: Five fetuses of 11 infected mares in an outbreak survived in utero in the presence of persistent placental infection and were healthy at foaling. Fetuses of 6 mares in the outbreak were aborted or died soon after birth. Significantly greater (P<0.05) IgM reactivity with all recombinant proteins and with Lk sonicate was observed in 54 archived fluids from Leptospira infected fetuses than in fluids of 30 of non-Leptospira infected fetuses. Low levels of IgGa and IgGb specific for LipL32 and Lk sonicate and traces of LigA and Hsp15 specific IgGa were detected in a minority of archived fluids from Leptospira infected fetuses. CONCLUSION: Although mainly mediated by IgM, a high level of immune competence in aborted fetuses was evidenced by the multiplicity of Leptospira proteins targeted. This is likely to contribute to survival of foals in mares with evidence of placental infection at foaling as detailed in a typical outbreak.


Assuntos
Doenças dos Cavalos/microbiologia , Imunoglobulina M/isolamento & purificação , Leptospira interrogans/isolamento & purificação , Leptospirose/veterinária , Complicações Infecciosas na Gravidez/veterinária , Feto Abortado/imunologia , Feto Abortado/microbiologia , Aborto Animal/epidemiologia , Aborto Animal/imunologia , Aborto Animal/microbiologia , Animais , Especificidade de Anticorpos , Surtos de Doenças/veterinária , Feminino , Doenças dos Cavalos/epidemiologia , Cavalos , Kentucky/epidemiologia , Leptospirose/epidemiologia , Leptospirose/imunologia , Gravidez , Complicações Infecciosas na Gravidez/epidemiologia , Complicações Infecciosas na Gravidez/microbiologia
5.
Psychoneuroendocrinology ; 51: 122-34, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-25306217

RESUMO

Vasopressin signaling has important effects on the regulation of social behaviors and stress responses, and is considered a promising pathway to target for new therapeutics of stress-induced psychiatric disorders. Although there is evidence for sex differences in the behavioral effects of arginine vasopressin (AVP), few data have directly compared the effects of stress on endogenous AVP signaling in males and females. We used California mice (Peromyscus californicus) to study the short and long term effects of social defeat stress on AVP immunoreactive cells in the paraventricular nucleus (PVN) and the posteromedial bed nucleus of the stria terminalis (BNSTmp). Acute exposure to defeat increased AVP/c-fos cells in the PVN and SON of both males and females. In contrast, there were sex differences in the long term effects of defeat. Males but not females exposed to defeat had less avp mRNA in the PVN, and in two experiments defeat reduced the number of AVP positive cells in the caudal PVN of males but not females. Interestingly, during relatively benign social encounters with a target mouse, there was a rapid decrease in AVP percent staining (including cell bodies and fibers) in the PVN of males but not females. Defeat reduced AVP percent staining in males, but did not block the socially induced decrease in percent staining. When mice were tested in resident-intruder tests, males exposed to defeat were no less aggressive than control males whereas aggression was abolished in females. However, bouts of aggression were positively correlated with the number of AVP neurons in the BNSTmp of control males but not stressed males, suggesting that different mechanisms mediate aggression in control and stressed males. These data show that while acute AVP responses to defeat are similar in males and females, the long term effects of defeat on AVP are stronger in males.


Assuntos
Arginina Vasopressina/metabolismo , Núcleo Hipotalâmico Paraventricular/metabolismo , Caracteres Sexuais , Comportamento Social , Estresse Psicológico/metabolismo , Animais , Feminino , Masculino , Peromyscus , Núcleos Septais/metabolismo , Predomínio Social , Núcleo Supraóptico/metabolismo
6.
Equine Vet J ; 47(2): 171-4, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-24750279

RESUMO

REASONS FOR PERFORMING STUDY: A comprehensive evaluation of the real-time PCR assay for leptospirosis in comparison with other diagnostic assays on a large-scale basis is fundamental in validating the assay and determining the causes of equine abortions. OBJECTIVES: To compare and evaluate the diagnostic value of real-time PCR assay for leptospirosis with traditional methods in equine leptospiral abortions. STUDY DESIGN: Cross-sectional observational study. METHODS: A Leptospira spp. fluorescent antibody test (FAT), microscopic agglutination test (MAT) and real-time PCR (targeting the LipL32 gene) were compared and evaluated in equine fetal necropsy specimens (placenta, kidney, liver and heart blood) and maternal serum (when available) in 339 equine fetuses. RESULTS: From a total of 339 equine fetuses necropsied, 21 cases (6.19%) were diagnosed as leptospiral abortion. The majority of leptospiral abortions occurred in January (8 cases) and February (5 cases). Real-time PCR detected 21 of 21 cases, whereas MAT and FAT detected 19 and 18 (including 2 suspicious cases) cases, respectively. Comparing tissues, placenta yielded somewhat similar cycle of threshold values by real-time PCR compared with kidney, whereas kidney was the best specimen for the diagnosis of leptospirosis by the FAT test. In all MAT positive cases, the predominant titre in fetal heart blood was to serovar Pomona (ranging 1:100 to 1:204,800) with little or no cross-reaction to serovar Grippotyphosa. CONCLUSIONS: The results indicate that real-time PCR is an effective method for the diagnosis of leptospiral abortion in horses. However, MAT should continue to be used in clinical cases for serovar determination.


Assuntos
Aborto Animal/diagnóstico , Testes de Aglutinação/veterinária , Imunofluorescência , Doenças dos Cavalos/diagnóstico , Leptospirose/veterinária , Reação em Cadeia da Polimerase em Tempo Real/veterinária , Aborto Animal/microbiologia , Testes de Aglutinação/métodos , Animais , Estudos Transversais , Feminino , Doenças dos Cavalos/microbiologia , Doenças dos Cavalos/patologia , Cavalos , Leptospira/isolamento & purificação , Leptospirose/complicações , Gravidez , Complicações Infecciosas na Gravidez/veterinária
7.
J Nutr Health Aging ; 18(4): 429-36, 2014 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-24676326

RESUMO

OBJECTIVE: There are limited data on combinations of co-morbid conditions to guide efforts to improve therapeutic strategies in patients with multiple co-morbid conditions. To some extent, this may be due to limited data on combinations of co-morbid conditions in patient groups. Our goal was to determine the most common co-morbid medical conditions in older residents of U.S. nursing homes and identify sex differences in prevalences and changes across the agespan of nursing residents. DESIGN: Cross sectional analysis of National Nursing Home Survey (NNHS)--a nationally representative sample with comprehensive medical data on nursing home residents. SETTING: 1174 Nursing homes. PARTICIPANTS: Long term stay residents of U.S. Nursing Homes aged 65 years and older (11,734 :8745 women, 2989 men). MEASUREMENTS: Determination of the prevalences of the most frequent two and three disease combinations identified using Clinical Classifications Software (CCS) for ICD-9-CM and a composite vascular disease diagnosis (atherosclerosis and/or coronary artery disease, and/or peripheral arterial disease, and/or cerebrovascular disease or stroke) from the most recent and only NNHS survey with comprehensive medical diagnosis information. RESULTS: Frequent 2-disease combinations were: hypertension (HTN) + dementia (DEM) in 27%, HTN + any Vascular (Vasc) disease (26%), HTN + depression(DEP) 21%, HTN + arthritis(ARTH) 20%, DEM + Vasc (21%), DEM+Depression 19%, Arthritis + DEM 17%, DEP + Vasc (16%), ARTH + Vasc (15%), followed by HTN + GERD (14%) and ARTH + DEP (14%). Frequent 3-disease combinations: HTN +VASC+ DEP in 13%, HTN +DEM +DEP (11%), and HTN+Arthritis+DEM (10%). HTN was in 80% of the top 3-disease combinations, Vasc in 50%, HTN+VASC in 35%, DEM or DEP in 40%, ARTH in 25% and GERD in 20%. Combinations with anemia, arthritis, dementia, heart failure, osteroporosis, thyroid disease were higher in women, COPD combinations higher in men. As age increased, dementia, depression, arthritis, and anemia with hypertension were common co-morbid combinations, diabetes and heart failure were not. CONCLUSIONS: Hypertension, vascular disease, dementia, arthritis, depression, and gastro-esophageal reflux disease were part of the most prevalent co-morbid conditions. Multimorbidity patterns can be identified in nursing home residents and vary with age and by sex.


Assuntos
Doença Crônica/epidemiologia , Comorbidade , Inquéritos Epidemiológicos , Casas de Saúde , Distribuição por Idade , Idoso , Idoso de 80 Anos ou mais , Artrite/epidemiologia , Estudos Transversais , Demência/epidemiologia , Depressão/epidemiologia , Feminino , Refluxo Gastroesofágico/epidemiologia , Avaliação Geriátrica , Humanos , Hipertensão/epidemiologia , Masculino , Prevalência , Distribuição por Sexo , Estados Unidos/epidemiologia , Doenças Vasculares/epidemiologia
8.
Ann Oncol ; 24 Suppl 7: vii36-40, 2013 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-24001761

RESUMO

Aging is associated with polymorbidity and polypharmacy. In the absence of a consensual definition, polypharmacy has been defined according to the number of drugs that an individual takes or to the presence of the risk of at least one severe drug interaction. In older cancer patients, polypharmacy is at least as common as it is in individuals of the same age without cancer. The management of cancer itself may result in the addition of more medications to counteract the adverse effects of antineoplastic treatment. Polypharmacy may be necessary to control the multiple health conditions of the older person, but it may represent a risk factor for more complications from antineoplastic therapy, and it may affect the outcome of cancer treatment. Polypharmacy is also associated with increased cost. The criteria proposed for the management of polypharmacy include the assessment that all medical conditions are properly treated, the avoidance of drug interactions, and of drugs that may compromise the outcome of antineoplastic treatment and the choice of drugs with the lowest risk of complications in older individuals.


Assuntos
Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/prevenção & controle , Neoplasias/tratamento farmacológico , Polimedicação , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Envelhecimento , Antineoplásicos/efeitos adversos , Antineoplásicos/uso terapêutico , Interações Medicamentosas , Humanos , Neoplasias/mortalidade , Resultado do Tratamento
9.
Poult Sci ; 89(10): 2265-72, 2010 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-20852118

RESUMO

The role of thyroid hormones in the expression of photosensitivity-photorefractoriness in female turkeys was investigated through the use of an antithyroidal agent, 6-n-propyl-2-thiouracil (PTU). In experiment 1, females held continuously from hatch on long day lengths (16L:8D; LD) and fed 0.1% PTU from 0 to 16 wk, began laying eggs at 26 wk of age, peaking at 75% hen-day egg production by 29 wk, whereas controls initiated lay 3 wk earlier but only achieved less than 50% hen-day egg production. In experiment 2, PTU treatment from 10 to 18 wk severely suppressed plasma triiodothyronine and thyroxine, as confirmed by RIA. Egg production of PTU and control hens held on LD from hatch began by 23 wk, with PTU hens reaching a substantially greater rate of lay than controls. Eggs were smaller initially in both treatments but exceeded 75 g by 28 wk. In experiment 3, recycled hens on short day lengths (8L:16D) received PTU for 2 wk before LD and 12 wk thereafter; a subset of these hens was killed after 48 h of LD for immunohistochemical analysis of fos-related antigen (FRA) expression in the tuberal hypothalamus as a marker of photoinduced neuronal activity. The PTU treatment completely forestalled egg production until its withdrawal; egg production then rose sharply to control levels before resuming, along with controls, a typical seasonal decline. The PTU treatment did not impair photoinduced FRA expression. Together, these results demonstrate the following: 1) that a period of pharmacological suppression of triiodothyronine and thyroxine can substitute for short day exposure in conferring photosensitivity on juvenile-aged turkeys (and is actually superior to short day exposure), 2) that reproductive development does not limit egg production of turkey hens photostimulated as young as approximately 20 wk of age, and 3) that effects of thyroid suppression on photostimulation lie downstream of photoinduced FRA expression. Taken together, these results suggest that there is ample physiological potential to substantially advance the age of photoinduced egg production in commercial flocks.


Assuntos
Oviposição/fisiologia , Maturidade Sexual/fisiologia , Hormônios Tireóideos/metabolismo , Perus/fisiologia , Envelhecimento , Animais , Antitireóideos/farmacologia , Feminino , Oviposição/efeitos dos fármacos , Propiltiouracila/farmacologia
10.
J Neuroendocrinol ; 20(11): 1260-9, 2008 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-18752654

RESUMO

For many temperate-zone avian species, termination of breeding occurs when individuals no longer respond to previously stimulatory day lengths, a condition called photorefractoriness. Long day lengths induce significantly greater expression of c-fos and fos-related antigens (FRAs) in the tuberal hypothalamus of the photosensitive hen than that of the photorefractory hen. The tuber is also a site of photoinducible glial expression of type 2 iodothyronine deiodinase (Dio2), which converts thyroxine into its active form, triiodothyronine (T3). T3 induces withdrawal of glial processes from gonadotrophin-releasing hormone (GnRH) I nerve terminals, which is believed to permit the efficient release of GnRH I into the associated portal vasculature. Using a riboprobe, we tested whether long days induce Dio2 mRNA expression in the turkey tuber and, if so, whether this expression is reduced in photorefractory hens. Long days significantly induced rostral and caudal tuberal hypothalamic Dio2 expression in photosensitive hens. Photorefractory hens had reduced expression of Dio2 with most subjects expressing no detectable mRNA in the rostral tuber and variably attenuated amounts throughout the medial and caudal tuber. We also performed double-label immunohistochemistry to identify co-localisation between FRAs and glial fibrillary acidic protein, a glial marker. FRAs were present in the nuclei of a few astrocytes in the median eminence and infundibular nucleus of the tuber. The temporal and spatial coincidence between FRA and Dio2 expression, their mutual association with glia, and the attenuation of their response during photorefractoriness suggests that the two events are linked and that photorefractoriness involves a reduced capacity for photo-inducible gene expression within glia of the tuberal hypothalamus.


Assuntos
Hipotálamo , Iodeto Peroxidase , Fotoperíodo , RNA Mensageiro/metabolismo , Perus , Animais , Ritmo Circadiano/fisiologia , Feminino , Proteína Glial Fibrilar Ácida/genética , Proteína Glial Fibrilar Ácida/metabolismo , Hipotálamo/citologia , Hipotálamo/enzimologia , Hibridização In Situ , Iodeto Peroxidase/genética , Iodeto Peroxidase/metabolismo , Luz , Proteínas Proto-Oncogênicas c-fos/genética , Proteínas Proto-Oncogênicas c-fos/metabolismo , Perus/anatomia & histologia , Perus/metabolismo , Iodotironina Desiodinase Tipo II
11.
Harefuah ; 143(2): 116-20, 166, 2004 Feb.
Artigo em Hebraico | MEDLINE | ID: mdl-15143701

RESUMO

During the last two years, 11 homeless-disabled people were treated at our rehabilitation ward. All of the patients were Jewish, six were new immigrants from Russia, their age ranged between 34 to 60 years, most of these patients had completed at least high school education, and all had managed to have a "normal" social-working life until the crisis which led them to the street. Six became alcoholics and one was a narcotic-drug user. None of these patients suffered from malnutrition or mental disorder, and after the rehabilitation process was over, they became independent, performing the activities of daily living. Most of them decided to return to their previous street--living place, despite their disabilities. This new combination of relatively young disabled-homeless people at our rehabilitation facility demands novel and different rehabilitation approaches.


Assuntos
Atenção à Saúde , Pessoas Mal Alojadas/estatística & dados numéricos , Reabilitação/métodos , Adulto , Emigração e Imigração , Humanos , Israel/epidemiologia , Pessoa de Meia-Idade , Pobreza , Desemprego
12.
Am J Med ; 110(7): 551-7, 2001 May.
Artigo em Inglês | MEDLINE | ID: mdl-11347622

RESUMO

PURPOSE: Little is known about the factors that influence housestaff attitudes toward pharmaceutical industry promotions or, how such attitudes correlate with physician behaviors. We studied these attitudes and practices among internal medicine housestaff. SUBJECTS AND METHODS: Confidential surveys about attitudes and behaviors toward industry gifts were distributed to 1st- and 2nd-year residents at a university-based internal medicine residency program. RESULTS: Ninety percent of the residents (105 of 117) completed the survey. A majority of respondents considered seven of nine types of promotions appropriate. Residents judged the appropriateness of promotions on the basis of their cost (median percentage of items considered appropriate 100% for inexpensive items vs. 60% for expensive ones) more than on the basis of their educational value (80% for educational items vs.75% for noneducational ones; P < .001 for comparison of appropriateness based on cost vs. educational value). Behaviors were often inconsistent with attitudes; every resident who considered conference lunches (n = 13) and pens (n = 18) inappropriate had accepted these gifts. Most respondents (61%)stated that industry promotions and contacts did not influence their own prescribing, but only 16% believed other physicians were similarly unaffected (P< .0001). Nonetheless, more than two thirds of residents agreed that it is appropriate for a medical institution to have rules on industry interactions with residents and faculty. CONCLUSIONS: Residents hold generally positive attitudes toward gifts from industry, believe they are not influenced by them, and report behaviors that are often inconsistent with their attitudes. Thoughtful education and policy programs may help residents learn to critically appraise these gifts.


Assuntos
Publicidade/métodos , Atitude do Pessoal de Saúde , Indústria Farmacêutica , Internato e Residência , Adulto , Feminino , Humanos , Masculino , Inquéritos e Questionários
13.
J Clin Microbiol ; 39(3): 1042-7, 2001 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-11230425

RESUMO

Little is known about patterns of tuberculosis (TB) transmission among populations in developing countries with high rates of TB and human immunodeficiency virus (HIV) infection. To examine patterns of TB transmission in such a setting, we performed a population-based DNA fingerprinting study among TB patients in Botswana. Between January 1997 and July 1998, TB patients from four communities in Botswana were interviewed and offered HIV testing. Their Mycobacterium tuberculosis isolates underwent DNA fingerprinting using IS6110 restriction fragment length polymorphism, and those with matching fingerprints were reinterviewed. DNA fingerprints with >5 bands were considered clustered if they were either identical or differed by at most one band, while DNA fingerprints with < or =5 bands were considered clustered only if they were identical. TB isolates of 125 (42%) of the 301 patients with completed interviews and DNA fingerprints fell into 20 different clusters of 2 to 16 patients. HIV status was not associated with clustering. Prior imprisonment was the only statistically significant risk factor for clustering (risk ratio, 1.5; 95% confidence interval, 1.1 to 2.0). In three communities where the majority of eligible patients were enrolled, 26 (11%) of 243 patients overall and 26 (25%) of 104 clustered patients shared both a DNA fingerprint and strong antecedent epidemiologic link. Most of the increasing TB burden in Botswana may be attributable to reactivation of latent infection, but steps should be taken to control ongoing transmission in congregate settings. DNA fingerprinting helps determine loci of TB transmission in the community.


Assuntos
Epidemiologia Molecular , Mycobacterium tuberculosis/genética , Vigilância da População , Tuberculose Pulmonar/epidemiologia , Infecções Oportunistas Relacionadas com a AIDS/epidemiologia , Infecções Oportunistas Relacionadas com a AIDS/microbiologia , Adulto , Botsuana/epidemiologia , Impressões Digitais de DNA/métodos , Elementos de DNA Transponíveis , Feminino , Humanos , Masculino , Mycobacterium tuberculosis/isolamento & purificação , Estudos Prospectivos , Tuberculose Pulmonar/microbiologia
14.
J Gen Intern Med ; 16(12): 793-9, 2001 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-11903757

RESUMO

OBJECTIVE: Little is known about patients who skip doses or otherwise avoid using their medications because of cost. We sought to identify which elderly patients are at highest risk of restricting their medications because of cost, and how prescription coverage modifies this risk. DESIGN AND PARTICIPANTS: Cross-sectional study from the 1995-1996 wave of the Survey of Asset and Health Dynamics Among the Oldest Old, a population-based survey of Americans age 70 years and older. MEASUREMENTS: Subjects were asked the extent of their prescription coverage, and whether they had taken less medicine than prescribed for them because of cost over the prior 2 years. We used bivariate and multivariate analyses to identify risk factors for medication restriction in subjects who lacked prescription coverage. Among these high-risk groups, we then examined the effect of prescription coverage on rates of medication restriction. MAIN RESULTS: Of 4,896 seniors who regularly used prescription medications, medication restriction because of cost was reported by 8% of subjects with no prescription coverage, 3% with partial coverage, and 2% with full coverage (P <.01 for trend). Among subjects with no prescription coverage, the strongest independent predictors of medication restriction were minority ethnicity (odds ratio [OR], 2.9 compared with white ethnicity; 95% confidence interval [95% CI], 2.0 to 4.2), annual income <$10,000 (OR, 3.8 compared with income > or =$20,000; 95% CI, 2.4 to 6.1), and out-of-pocket prescription drug costs >$100 per month (OR, 3.3 compared to costs < or =$20; 95% CI, 1.5 to 7.2). The prevalence of medication restriction in members of these 3 risk groups was 21%, 16%, and 13%, respectively. Almost half (43%) of subjects with all 3 risk factors and no prescription coverage reported restricting their use of medications. After multivariable adjustment, high-risk subjects with no coverage had 3 to 15 times higher odds of medication restriction than subjects with partial or full coverage (P <.01). CONCLUSIONS: Medication restriction is common in seniors who lack prescription coverage, particularly among certain vulnerable groups. Seniors in these high-risk groups who have prescription coverage are much less likely to restrict their use of medications.


Assuntos
Seguro de Serviços Farmacêuticos/economia , Seguro de Serviços Farmacêuticos/estatística & dados numéricos , Honorários por Prescrição de Medicamentos/estatística & dados numéricos , Recusa do Paciente ao Tratamento/estatística & dados numéricos , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Estudos Transversais , Feminino , Humanos , Masculino , Fatores de Risco , Fatores Socioeconômicos , Estados Unidos
16.
Surg Endosc ; 12(5): 416-20, 1998 May.
Artigo em Inglês | MEDLINE | ID: mdl-9569361

RESUMO

BACKGROUND: Diagnostic laparoscopy has been used in abdominal trauma patients, although its role is not well defined. The safety of laparoscopic evaluation in trauma patients with severe intraabdominal hemorrhage has not yet been analyzed. The purpose of this study is to evaluate the hemodynamic and metabolic effects of CO2 pneumoperitoneum (COI) in hemorrhaged animals through a retroperitoneal hematoma (RH). METHODS: Twenty-two 15-20-kg mongrel dogs were monitored for systemic and pulmonary hemodynamics, inferior vena cava pressure, and arterial blood gases. After 1 h of baseline, all animals were submitted to a RH. After 45 min the dogs were randomized into two groups. Control (CTR): dogs were submitted only to a RH; pneumoperitoneum (PN): dogs were submitted to a RH and 45 min later they were insufflated to an intraabdominal pressure of 10 mmHg with medical-grade CO2 gas for 30 min. Echocardiography was performed, only in PN animals, at baseline, 45 and 60 min after RH. RESULTS: RH induced a shock condition with low, sustained levels of arterial pressure, cardiac index, left ventricular stroke index, base excess, and oxygen delivery which were further depressed following COI. Three deaths occurred in the PN group, all of them toward the end of COI. During COI, hypercapnia was observed in one animal. COI did not impair systolic function or ejection fraction. CONCLUSIONS: COI with an IAP of 10 mmHg may be deleterious in animals with hemorrhagic shock due to an intraabdominal lesion. These findings could be clinically significant in abdominal trauma patients.


Assuntos
Dióxido de Carbono , Hematoma/complicações , Hemodinâmica , Pneumoperitônio Artificial , Espaço Retroperitoneal , Choque Hemorrágico/fisiopatologia , Animais , Volume Sanguíneo , Dióxido de Carbono/sangue , Cães , Concentração de Íons de Hidrogênio , Laparoscopia , Oxigênio/sangue , Choque Hemorrágico/sangue , Choque Hemorrágico/etiologia
17.
Rev. Assoc. Med. Bras. (1992) ; 42(1): 19-24, jan.-mar. 1996. tab
Artigo em Português | LILACS | ID: lil-172028

RESUMO

Os pacientes com síndrome da imunodefiência adquirida (SIDA) podem apresentar quadro de abdome agudo com manifestaçoes clínicas muito variadas, levando a erros e retardos no diagnóstico pré-operatório e retardos freqüentes na açao cirúrgica. Objetivo. Estudar os dados clínicos, critérios diagnósticos, etiologia, conduta cirúrgica e morbimortalidade dos pacientes com SIDA submetidos à laparotomia exploradora. Métodos. Foram estudados, retrospectivamente, os dados de 31 pacientes com SIDA atendidos no Serviço de Cirurgia de Emergência do Hospital das Clínicas da Faculdade de Medicina da Universidade de Sao Paulo, no período de 1986 a 1993, com diagnóstico clínico de abdome agudo e submetidos à laparotomia exploradora. Resultados. A principal manifestaçao clínica foi a dor abdominal, e o diagnóstico de abdome agudo foi a baseado em exame físico, exames laboratoriais e métodos de imagem. A causa mais freqüente de abdome agudo foi a perfuraçao do trato gastrointestinal, sendo a infecçao por citomegalovírus a etiologia mais freqüente da perfuraçao. Todos os doentes apresentaram algum tipo de complicaçao pós-operatória, prevalecendo a infecçao da ferida cirúrgica. A mortalidade foi de 42 por cento, em decorrência de sepse e falência de múltiplos órgaos e sistemas. Conclusoes. Basedos nestes dados, concluímos que os sinais clínicos de abdome agudo nos doentes com SIDA sao menos evidentes; as estomias devem ser a conduta de eleiçao. A morbimortalidade é extremamente elevada devido ao estado imuno-comprometido, ao retardo diagnóstico e a laparotomias nao terapêuticas.


Assuntos
Humanos , Masculino , Feminino , Adolescente , Adulto , Pessoa de Meia-Idade , Abdome Agudo/cirurgia , Síndrome da Imunodeficiência Adquirida/complicações , Abdome Agudo/diagnóstico , Abdome Agudo/etiologia , Abdome Agudo/mortalidade , Infecções Oportunistas Relacionadas com a AIDS , Emergências , Laparotomia/efeitos adversos , Laparotomia/mortalidade , Complicações Pós-Operatórias , Estudos Retrospectivos
18.
Am J Kidney Dis ; 27(1): 143-6, 1996 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-8546130

RESUMO

Visual hallucinations are a rare event in chronic renal failure and not related to uremia per se. Unreported in the literature is visual hallucinations occurring in association with the new macrolide antibiotic, clarithromycin. We describe such a case in a patient with end-stage renal disease (ESRD) maintained on continuous ambulatory peritoneal dialysis (CAPD). The combination of a relatively high dose of clarithromycin in face of chronic renal failure in a functionally anephric patient, with underlying aluminum intoxication, may have facilitated the appearance of this neurotoxic side effect. It is important to understand the pharmacokinetics of medications in face of chronic renal failure, the possibility of drug interactions, and how these factors should help guide medication therapy in the ESRD patient.


Assuntos
Antibacterianos/efeitos adversos , Claritromicina/efeitos adversos , Alucinações/induzido quimicamente , Falência Renal Crônica/terapia , Diálise Peritoneal Ambulatorial Contínua , Humanos , Masculino , Pessoa de Meia-Idade
19.
Rev Assoc Med Bras (1992) ; 42(1): 19-24, 1996.
Artigo em Português | MEDLINE | ID: mdl-8935671

RESUMO

UNLABELLED: Patients with Acquired Immunodeficiency Syndrome (AIDS) may present acute abdomen with modified clinical manifestations which may lead to errors and delays in preoperative diagnosis, with frequent delays in treatment. PURPOSE: To study clinical signs, diagnostic criteria, etiology, surgical management and mortality in patients with AIDS submitted to exploratory laparotomy. METHODS: We reviewed the records of thirty-one AIDS patients admitted in the period 1986-1993 at the Emergency Surgical Service--Hospital das Clínicas, University of São Paulo submitted to exploratory celiotomy due to acute abdome. RESULTS: Abdominal pain was the most frequent symptom and the diagnosis of acute abdome was made based upon physical examination, laboratory tests and imaging techniques. Gastrointestinal tract perforation was the most frequent cause of acute abdome, mainly due to Cytomegalovírus infection. All patients presented postoperative complication, specially wound infection. Mortality rate was 42% due to sepsis and multiple organ failure. CONCLUSION: Based upon these data we conclude that: AIDS patients usually present masked clinical signs of acute abdomen; stomas should be formally indicated. Mortality is extremely high due to immunocompromised state, delayed diagnosis and treatment and non therapeutic celiotomies.


Assuntos
Abdome Agudo/cirurgia , Síndrome da Imunodeficiência Adquirida/complicações , Infecções Oportunistas Relacionadas com a AIDS , Abdome Agudo/diagnóstico , Abdome Agudo/etiologia , Abdome Agudo/mortalidade , Adolescente , Adulto , Emergências , Feminino , Humanos , Laparotomia/efeitos adversos , Laparotomia/mortalidade , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias , Estudos Retrospectivos
20.
J Trauma ; 36(3): 442-3, 1994 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-8145339

RESUMO

Multiple injuries of iliac veins are uncommon and frequently fatal. An unusual case in which there were injuries of the four iliac veins by gunshot is described. Prompt control of hemorrhage is required. Because our patient was in unstable condition, ligation of the four iliac veins was performed and the abdomen was packed. After a complicated course, the patient was discharged after 40 days in good condition. Although venous repair is often recommended, ligation in extensive injuries may be necessary, and is usually well tolerated in young, previously healthy individuals like our patient.


Assuntos
Traumatismos Abdominais/complicações , Veia Ilíaca/lesões , Ferimentos por Arma de Fogo/complicações , Adolescente , Hematoma/etiologia , Humanos , Veia Ilíaca/cirurgia , Masculino
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