RESUMO
OBJECTIVE: This is the second of 3 planned articles reporting on a prospective, multicenter, randomized controlled trial assessing the efficacy of fish skin graft in the management of diabetic foot ulcers in comparison with the standard of care (collagen alginate dressing). MATERIALS AND METHODS: The primary end point of this prospective randomized trial is the number of closed wounds at 12 weeks. RESULTS: As of the time of this writing, 94 patients had completed the protocol. At 12-week follow-up, healing was achieved in 63.0% of index ulcers (29 of 46 patients) in the acellular fish skin graft group compared with 31.3% in the control group (15 of 48 patients) (P =.0036). In both groups, the mean time to healing was 7 weeks. The median number of applications of the fish skin graft to achieve healing was 6. CONCLUSION: A clinically and statistically significant difference in healing was observed between patients treated with acellular fish skin graft and those treated with a collagen alginate dressing. The data support the completion of this prospective randomized trial.
Assuntos
Diabetes Mellitus , Pé Diabético , Ácidos Graxos Ômega-3 , Alginatos , Animais , Bandagens , Colágeno/uso terapêutico , Pé Diabético/terapia , Estudos Prospectivos , Resultado do TratamentoRESUMO
A 21-y-old man who presented with polyuria and polydipsia was discovered to have diabetes insipidus due to eosinophilic granuloma of the hypothalamus. 18F-FDG PET/CT, which was performed as a metastatic work-up, revealed an intensely 18F-FDG-avid hypothalamic mass and no other sites of disease.
Assuntos
Granuloma Eosinófilo/diagnóstico por imagem , Fluordesoxiglucose F18 , Hipotálamo/diagnóstico por imagem , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Humanos , Masculino , Adulto JovemRESUMO
BACKGROUND: Oral pharmacological treatment for overactive bladder (OAB) consists of antimuscarinics and the beta-3 adrenergic agonist mirabegron. Antimuscarinic adverse events (AEs) such as dry mouth, constipation, and blurry vision can result in frequent treatment discontinuation rates, leaving part of the OAB population untreated. Antimuscarinics also contribute to a patient's anticholinergic cognitive burden (ACB), so the Beers Criteria recommends cautious use of antimuscarinics in elderly patients who take multiple anticholinergic medications or have cognitive impairment. Since mirabegron does not affect the cholinergic pathways, it is unlikely to contribute to a patient's ACB. OBJECTIVE: To estimate the health care costs associated with the pharmacological treatment of OAB with mirabegron and antimuscarinics from U.S. commercial payer and Medicare Advantage perspectives, using a budget impact model. METHODS: For this budget impact model, 2 analyses were performed. The primary analysis estimated the budgetary impact of increasing the use of mirabegron in a closed patient cohort treated with oral pharmacological treatments. The secondary analysis modeled the economic impact in an open cohort by allowing untreated patients to begin treatment with mirabegron after potential contraindication, intolerance, or lack of effectiveness of antimuscarinics. The analyses were performed over a 3-year time horizon. The economic impact of increased mirabegron use was quantified using direct medical costs, including prescription costs and health resource utilization (HRU) costs. Costs of comorbidities included pharmacy and medical costs of treating OAB-related urinary tract infections (UTI), skin rashes, and depression. An analysis of a large single-site integrated health network database was commissioned to quantify ACB-related HRU in terms of the increases in yearly outpatient and emergency department visits. Based on this analysis, the model associated each unit increase in ACB score with increased HRU and probability of mild cognitive impairment. Clinical outcomes of increased use of mirabegron were presented as the number of AEs and comorbidity episodes that could be avoided. One-way sensitivity analyses were performed to quantify the expected budget impact over the range of uncertainty for the key input variables. RESULTS: Primary analysis calculated the impact of increasing the use of mirabegron from 4.5% to 5.3%, 7.1%, and 9.4% in years 1, 2, and 3, respectively, among oral pharmacological OAB treatments that included generic and branded antimuscarinics: oxybutynin, tolterodine, trospium, darifenacin, fesoterodine, and solifenacin. For a 1 million-member U.S. commercial payer plan, the total prescription costs increased, and the total medical costs decreased during the 3-year time horizon, yielding increases of $0.005, $0.016, and $0.031 from current per member per month (PMPM) costs and $0.90, $2.92, and $5.53 from current per treated member per month (PTMPM) costs, an average of less than 2% of current OAB treatment costs. For the Medicare Advantage plan, the resulting incremental PMPM costs were $0.010, $0.034, and $0.065, and the incremental PTMPM costs were $0.93, $3.04, and $5.76; all were less than 4% of the current cost. The secondary analysis estimated the budgetary effects of reducing the untreated population by 1% annually by initiating treatment with mirabegron. For a commercial payer, this resulted in PMPM cost increases of $0.156, $0.311, and $0.467 from the current value, while the incremental PTMPM cost increased by $6.17, $11.67, and $16.61. For the Medicare Advantage plan, the incremental increases in PMPM costs were $0.277, $0.553, and $0.830, and in PTMPM costs were $6.42, $12.15, and $17.29. Clinically, treating more OAB patients resulted in fewer OAB-related comorbidities from both health plan perspectives, since most events associated with nontreatment could be avoided. In the Medicare Advantage population of the secondary analysis, the total numbers of avoided events were predicted as 452 UTIs, 2,598 depression diagnoses, and 3,020 skin rashes during the time horizon of the model. CONCLUSIONS: Mirabegron addresses an unmet need for therapy for certain OAB patients, for whom antimuscarinics are not recommended because of a risk of cognitive impairment and who are intolerant to the anticholinergic AEs. Using mirabegron involves moderate additional economic cost to a commercial or Medicare Advantage health plan for which medical cost savings can offset a substantial part of increased pharmacy costs. DISCLOSURES: Funding for this study was provided by Astellas. Perk, Wielage, T. Klein, and R. Klein are employed by Medical Decision Modeling, a contract research company that was paid to perform the described outcomes research and build the model contained in this study. Campbell and Perkins are employed by the Regenstrief Institute, which conducted a database analysis for this research. Campbell reports consultancy fees from Astellas, as well as pending grants from Merck, Sharpe, and Dohme Corp. Posta, Yuran, and Ng are employed by Astellas Pharma Global Development, the developer of mirabegron. Study concept and design were contributed by Perk, Wielage, R. Klein, and Ng. Campbell, T. Klein, and Perkins took the lead in data collection, assisted by Perk, Wielage, and Ng. Data interpretation was performed by Posta and Yuran, along with Perk, Wielage, R. Klein, Ng, Campbell, and Perkins. The manuscript was written by Perk and R. Klein, along with Wielage, T. Klein, Posta, Yuran, and Ng, and revised by all the authors.
Assuntos
Acetanilidas/economia , Orçamentos , Custos de Cuidados de Saúde , Tiazóis/economia , Bexiga Urinária Hiperativa/economia , Agentes Urológicos/economia , Acetanilidas/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Orçamentos/tendências , Custos de Cuidados de Saúde/tendências , Humanos , Seguro Saúde/economia , Seguro Saúde/tendências , Medicare Part C/economia , Medicare Part C/tendências , Pessoa de Meia-Idade , Antagonistas Muscarínicos/economia , Antagonistas Muscarínicos/uso terapêutico , Tiazóis/uso terapêutico , Resultado do Tratamento , Estados Unidos/epidemiologia , Bexiga Urinária Hiperativa/tratamento farmacológico , Bexiga Urinária Hiperativa/epidemiologia , Agentes Urológicos/uso terapêuticoRESUMO
OBJECTIVE: To analyze patients with kidney cancer referred for evaluation at a high-volume genetics service at a comprehensive cancer center and identify factors associated with positive tests for hereditary cancer syndromes. METHODS: A retrospective review of patients referred to the Clinical Genetics Service at Memorial Sloan-Kettering Cancer Center was performed, and patients with a personal history of kidney cancer were identified. Patient and disease characteristics were reviewed. In all, 4 variables including age at diagnosis of kidney tumor, presence of syndromic manifestations, family history of kidney cancer, and number of primary malignancies were evaluated for association with positive test results in 2 groups: patients tested for renal cell carcinoma syndromes and Lynch syndrome. Guidance for genetic testing strategy in patients with kidney cancer is provided. RESULTS: Between 1999 and 2012, 120 patients with a history of kidney cancer were evaluated by the Clinical Genetics Service. The mean age at kidney cancer diagnosis was 52 years (interquartile range: 42-63), with 57% being women. A family history of kidney cancer was reported by 39 patients (33%). Time between diagnosis of first cancer and genetic consultation was <1 year in 54%, 2 to 5 years in 23%, and>5 years in the remaining 23%. Overall, 95 patients were tested for genetic abnormalities with 27 (28%) testing positive. Testing for renal cell carcinoma (RCC)-related syndromes was performed on 43 patients, with 13 testing positive (30%). Lynch syndrome testing was positive in 9 patients (32%) after 28 were tested. In RCC-associated syndromes, young age of diagnosis was associated with positive test results. Conversely, syndromic manifestations and increasing number of primary malignancies were associated with positive Lynch testing. CONCLUSIONS: The discovery of inherited kidney cancer syndromes has provided a unique opportunity to identify patients at increased risk for cancer. Factors associated with positive genetic testing are unique to different syndromes. These data suggest that in kidney cancer patients evaluated for hereditary cancer syndromes, young age is associated with diagnosis of RCC syndromes, whereas syndromic manifestations and multiple primaries are found in Lynch syndrome. These results, along with clinical awareness, may be useful for practicing urologists to select patients with kidney cancer to refer for genetic counseling.
Assuntos
Carcinoma de Células Renais/genética , Neoplasias Colorretais Hereditárias sem Polipose/genética , Neoplasias Renais/genética , Síndromes Neoplásicas Hereditárias/genética , Adolescente , Adulto , Idoso , Carcinoma de Células Renais/diagnóstico , Criança , Pré-Escolar , Neoplasias Colorretais Hereditárias sem Polipose/diagnóstico , Feminino , Aconselhamento Genético , Predisposição Genética para Doença/genética , Testes Genéticos , Humanos , Lactente , Neoplasias Renais/diagnóstico , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Mutação , Síndromes Neoplásicas Hereditárias/diagnóstico , Encaminhamento e Consulta , Estudos Retrospectivos , Adulto JovemRESUMO
A sunken soft-spot or fontanel is a sign for dehydration in infants. Around the world, folk illnesses, such as caída de la mollera in some Latin American cultures, often incorporate this sign as a hallmark of illness, but may or may not incorporate re-hydration therapies in treatment strategies. This report describes a study of lay descriptions of causes, symptoms, and treatments for caída de la mollera in three diverse Latin American populations. A mixed-methods approach was used. Representative community-based samples were interviewed in rural Guatemala, Guadalajara, Mexico, and Edinburgh, Texas, with a 132 item questionnaire on the causes, susceptibility, symptoms, and therapies for caída de la mollera. Cultural consensus analysis was used to estimate community beliefs about caída. Interviews conducted in rural Guatemala (n = 60), urban Mexico (n = 62), and rural Texas on the Mexican border (n = 61) indicated consistency in thematic elements within and among these three diverse communities. The high degree of consistency in the illness explanatory models indicated shared beliefs about caída de la mollera in each of the communities and a core model shared across communities. However, an important aspect of the community beliefs was that rehydration therapies were not widely endorsed. The consistency in explanatory models in such diverse communities, as well as the high degree of recognition and experience with this illness, may facilitate communication between community members, and health care providers/public health intervention planners to increase use of rehydration therapies for caída de la mollera. Recommendations for culturally informed and respectful approaches to clinical communication are provided.
Assuntos
Desidratação/etnologia , Desidratação/terapia , Hidratação/métodos , Conhecimentos, Atitudes e Prática em Saúde/etnologia , Hispânico ou Latino/psicologia , Adulto , Desidratação/fisiopatologia , Feminino , Guatemala/epidemiologia , Humanos , Lactente , Masculino , Medicina Tradicional , México/epidemiologia , População Rural , Texas/epidemiologia , População UrbanaRESUMO
Onchocerciasis (river blindness), which is close to being eliminated from Guatemala through semiannual administration of ivermectin, is still transmitted in one area of the country that coincidentally receives an annual influx of migrant workers to harvest coffee. Migrant workers generally are not included in semiannual ivermectin treatments, but if infected could serve as a reservoir. We report on two studies undertaken to measure the exposure to onchocerciasis (presence of IgG4 antibodies to a recombinant Onchocerca volvulus antigen, OV-16) among migrant workers. During two coffee harvest seasons, 170 migrant workers with a history of working in the disease-endemic area were tested and 1 (0.6%, 95% confidence interval = 0-3.2%) was seropositive. This low rate of exposure in migrant workers indicates that they are unlikely to play a significant role in transmission of onchocerciasis and may indicate that transmission in the last remaining disease-endemic area of Guatemala is decreasing significantly.
Assuntos
Onchocerca volvulus , Oncocercose/epidemiologia , Migrantes , Adolescente , Adulto , Agricultura , Animais , Anti-Helmínticos/administração & dosagem , Anti-Helmínticos/uso terapêutico , Café , Feminino , Guatemala/epidemiologia , Humanos , Ivermectina/administração & dosagem , Ivermectina/uso terapêutico , Masculino , Exposição Ocupacional , Projetos Piloto , Vigilância da População , Estações do Ano , Adulto JovemRESUMO
Previous studies have shown that use of complementary and alternative medicine (CAM) is prevalent among HIV-infected persons, but have focused primarily on men who have sex with men. To determine factors associated with CAM use in an inner city population, individuals (n = 93) recruited from two established cohort studies were interviewed between October and November 2004. The interview assessed the use of dietary supplements and other CAM therapies, reasons for CAM use, and use of prescription medications. Study participants were 52% male and 47% HIV infected. Median age was 50 years, and 60% reported illicit drug use ever. CAM use during the prior 6 months was reported by 94%, with 48% reporting daily use of a dietary supplement. Vitamin C, vitamin E, and soy were used more often by HIV-infected than uninfected persons (p < 0.05). Prevention of illness was the most common reason for dietary supplement use (27%). HIV-infected persons were more likely than uninfected persons (95% versus 67%) to report use of both dietary supplements and prescription medications within the past 6 months (p < 0.001). In multivariate analysis, HIV infection (odds ratio [OR] 3.1, CI 1.3, 7.7) was the only factor associated with daily dietary supplement use whereas gender, race/ethnicity, working in the last year, homelessness, and financial comfort were not associated. CAM use among persons with or at risk for HIV infection due to drug use or high-risk heterosexual behaviors is common, and is used almost exclusively as an adjunct and not an alternative to conventional health care.
Assuntos
Terapias Complementares , Infecções por HIV/prevenção & controle , Adulto , Coleta de Dados , Suplementos Nutricionais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Razão de Chances , Risco , Inquéritos e Questionários , População UrbanaRESUMO
We developed a new empirical scoring function, HYDE, for the evaluation of protein-ligand complexes. HYDE estimates binding free energy based on two terms for dehydration and hydrogen bonding only. The essential feature of this scoring function is the integrated use of log P-derived atomic increments for the prediction of free dehydration energy and hydrogen bonding energy. Taking the dehydration of atoms within the interface into account shows that some atoms contribute favorably to the overall score, while others contribute unfavorably. For instance, hydrogen bond functions are penalized if they are dehydrated unless they can overcompensate this loss by forming a hydrogen bond with excellent geometry. The main stabilizing contribution represents the removal of apolar groups from the water: the hydrophobic effect. Initial studies using the DUD dataset show that with HYDE, there is a significant decrease in false positives, a reasonable categorization of compounds as either non-binders, weak, medium or strong binders, and in particular, there is a generally applicable and thermodynamically sensible cutoff score below which there is a high likelihood that the compound is indeed a binder.
Assuntos
Simulação por Computador , Avaliação Pré-Clínica de Medicamentos , Compostos Orgânicos/química , Proteínas/química , Sítios de Ligação , Bases de Dados Factuais , Dessecação , Avaliação Pré-Clínica de Medicamentos/métodos , Ligação de Hidrogênio , Interações Hidrofóbicas e Hidrofílicas , Ligantes , Modelos Moleculares , Estrutura Molecular , Compostos Orgânicos/farmacologia , Proteínas/efeitos dos fármacos , Reprodutibilidade dos Testes , Relação Estrutura-Atividade , Termodinâmica , Água/químicaRESUMO
BACKGROUND: The molecular mechanisms responsible for the survival and preservation of function for adult parasympathetic ganglion neurons following injury remain incompletely understood. However, advances in the neurobiology of growth factors, neural development, and prevention of cell death have led to a surge of clinical interest for protective and regenerative neuromodulatory strategies, as surgical therapies for prostate, bladder, and colorectal cancers often result in neuronal axotomy and debilitating loss of sexual function or continence. In vitro studies have identified neurturin, a glial cell line-derived neurotrophic factor, as a neuromodulator for pelvic cholinergic neurons. We present the first in vivo report of the effects of neurturin upon the recovery of erectile function following bilateral cavernous nerve crush injury in the rat. METHODS: In these experiments, groups (n = 8 each) consisted of uninjured controls and animals treated with injection of albumin (blinded crush control group), extended release neurotrophin-4 or neurturin to the site of cavernous nerve crush injury (100 mug per animal). After 5 weeks, recovery of erectile function (treatment effect) was assessed by cavernous nerve electrostimulation and peak aortic pressures were measured. Investigators were unblinded to specific treatments after statistical analyses were completed. RESULTS: Erectile dysfunction was not observed in the sham group (mean maximal intracavernous pressure [ICP] increase of 117.5 +/- 7.3 cmH2O), whereas nerve injury and albumin treatment (control) produced a significant reduction in ICP elevation of 40.0 +/- 6.3 cmH2O. Neurturin facilitated the preservation of erectile function, with an ICP increase of 55% at 62.0 +/- 9.2 cmH2O (p < 0.05 vs control). Extended release neurotrophin-4 did not significantly enhance recovery of erectile function with an ICP change of 46.9 +/- 9.6. Peak aortic blood pressures did not differ between groups. No significant pre- and post-treatment weight differences were observed between control, neurotrophin-4 and neurturin cohorts. All animals tolerated the five-week treatment course. CONCLUSION: Treatment with neurturin at the site of cavernous nerve crush injury facilitates recovery of erectile function. Results support further investigation of neurturin as a neuroprotective and/or neuroregenerative agent facilitating functional recovery after cavernous or other pelvic autonomic nerve injuries.
RESUMO
Adverse effects of age on the outcome of brain injury are well documented, but the mechanism is not well understood. Enhanced expression of proinflammatory cytokines and chemokines has long been linked to neuronal and glial responses to brain injury. In the present study, we used retrograde degeneration of thalamus as a model for secondary neuron death after cortical injury. We investigated the inflammatory component of glial responses to injury by determining mRNA expression of cytokines (TNF-alpha, IL-6, IL-1beta and IFN-gamma), chemokines (MCP-1 and RANTES) and iNOS in thalamus at day 0, 1, 3 and 7 after visual cortex ablation in mice aged 24 (old) and 4 months (young). Old mice demonstrated higher basal expression of TNF-alpha, IL-6, IL-1beta, MCP-1, RANTES and iNOS than young mice, while basal IFN-gamma expression was lower in the brains of older mice. Following injury, thalami of old mice demonstrated higher gene expression of TNF-alpha, IL-1beta, MCP-1, RANTES, and iNOS than young mice. Maximal expression of these five genes was observed 1 day following injury. IL-6 showed maximal gene expression 3 days after injury. By contrast, the increases in IFN-gamma expression after injury were smaller in old than in young mice. Our data demonstrate that both the baseline levels and the responses to injury of specific inflammatory molecules increase during aging. The increased expression of these critical molecules in inflammatory cascades may be responsible for increased secondary neuron death after injury in aging brain, suggesting that strategies to reduce these age-specific differences may help in the development of specific targets for pharmacologic intervention for the aging population.
Assuntos
Lesões Encefálicas/metabolismo , Quimiocinas/metabolismo , Citocinas/metabolismo , Expressão Gênica/fisiologia , Neurônios/metabolismo , Fatores Etários , Animais , Lesões Encefálicas/complicações , Lesões Encefálicas/genética , Morte Celular/fisiologia , Quimiocinas/genética , Citocinas/genética , Masculino , Camundongos , Camundongos Endogâmicos C57BL , RNA Mensageiro/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa/métodos , Tálamo/citologia , Tálamo/metabolismo , Fatores de TempoRESUMO
OBJECTIVE: To evaluate the cost-effectiveness of tamsulosin, doxazosin, or terazosin as initial treatments for moderate benign prostatic hyperplasia (BPH) over a 3-year time horizon from a health-system-payer perspective. METHODS: A decision-analytic model is used to project the course of treatment at 6-month intervals over 3 years following initiation of therapy with tamsulosin, doxazosin, or terazosin. Treatment failure is defined as failure to attain and maintain a 25% improvement in the American Urological Association (AUA) symptom score from baseline. In the model, finasteride is added for patients who fail on their initial therapy and, in the event of finasteride treatment failure, patients progress to transurethral resection of the prostate (TURP) and, if needed, a second TURP. The ranges of values for treatment failure rates and clinical event cost parameters used in the decision model are derived from the literature. Only direct medical costs related to BPH and its treatment are included. Since 2 comparators are available generically (doxazosin and terazosin) drug acquisition costs are defined by the list prices at Drugstore.com. All costs are discounted by 3% per year. Effectiveness is measured as successful medical treatment without surgery over 3 years. RESULTS: For base-case model parameters, discounted BPH-related total direct medical costs over 3 years are 4084 dollars, 4323 dollars, and 4695 dollars for generic terazosin, generic doxazosin, and tamsulosin, respectively. The model estimates a medical treatment success rate (no TURP) at 3 years of 72.3% for tamsulosin, compared with 68.2% for both terazosin and doxazosin. The incremental cost for tamsulosin versus terazosin is 610 dollars over 3 years, which yields an incremental cost-effectiveness ratio of 14,609 dollars per success. Generic doxazosin is dominated (higher cost but equal effectiveness compared with terazosin). Higher rates of twice-daily (or 2 units per day) dosing are associated with higher incremental cost-effectiveness ratios. The decision-model results also are sensitive to the estimated costs of TURP and hypotensive adverse events. CONCLUSION: As an initial medical therapy for moderate BPH, tamsulosin is more effective than generic terazosin or doxazosin, with an incremental cost of about 203 dollars per year (or about 17 dollars per month) over 3 years.
Assuntos
Antagonistas Adrenérgicos alfa/uso terapêutico , Análise Custo-Benefício , Doxazossina/uso terapêutico , Farmacoeconomia , Finasterida/uso terapêutico , Prazosina/análogos & derivados , Prazosina/uso terapêutico , Hiperplasia Prostática/tratamento farmacológico , Sulfonamidas/uso terapêutico , Antagonistas Adrenérgicos alfa/economia , Técnicas de Apoio para a Decisão , Doxazossina/economia , Inibidores Enzimáticos/uso terapêutico , Custos de Cuidados de Saúde , Humanos , Masculino , Prazosina/economia , Hiperplasia Prostática/economia , Hiperplasia Prostática/cirurgia , Sulfonamidas/economia , Tansulosina , Ressecção Transuretral da Próstata , Resultado do TratamentoRESUMO
To systematically study and document regional variations in descriptions of nervios, we undertook a multisite comparative study of the illness among Puerto Ricans, Mexicans, Mexican Americans, and Guatemalans. We also conducted a parallel study on susto (Weller et al. 2002, Culture, Medicine and Psychiatry 26(4): 449-472), which allows for a systematic comparison of these illnesses across sites. The focus of this paper is inter- and intracultural variations in descriptions in four Latino populations of the causes, symptoms, and treatments of nervios, as well as similarities and differences between nervios and susto in these same communities. We found agreement among all four samples on a core description of nervios, as well as some overlap in aspects of nervios and susto. However, nervios is a much broader illness, related more to continual stresses. In contrast, susto seems to be related to a single stressful event.
Assuntos
Transtornos de Ansiedade/etnologia , Diversidade Cultural , Hispânico ou Latino/psicologia , Medicina Tradicional , Estresse Psicológico/etnologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Transtornos de Ansiedade/diagnóstico , Transtornos de Ansiedade/terapia , Atitude Frente a Saúde/etnologia , Connecticut , Comparação Transcultural , Feminino , Guatemala/etnologia , Humanos , Entrevistas como Assunto , Masculino , México/etnologia , Pessoa de Meia-Idade , Porto Rico/etnologia , Reprodutibilidade dos Testes , Fatores Sexuais , Estresse Psicológico/diagnóstico , Estresse Psicológico/terapia , TexasRESUMO
The mechanisms regulating retrograde neuronal degeneration and subsequent death of thalamic neurons following cortical injury are not well understood. However, the delay in the onset of retrograde cell death and observed morphological changes are consistent with apoptosis. Our previous studies demonstrated that monocyte chemoattractant protein-1 (MCP-1), a beta-chemokine that attracts cells of monocytic origin to sites of injury, is rapidly and specifically expressed in the lateral geniculate nucleus following visual cortical lesions. To determine the potential role of MCP-1 in retrograde degeneration, the present study examined the effect of genetic deletion of MCP-1 (MCP-1 KO or -/-) or its high affinity receptor CCR2 (CCR2 KO or -/-) on thalamic microglial activation and neuronal cell death following aspiration lesions of the visual cortex in adult mice. Deletion of the MCP-1 gene delayed microglial activation and transiently improved the survival of thalamic neurons. Deletion of the CCR2 receptor resulted in a significant increase in apoptosis as measured by nucleosomal fragmentation after injury compared to wild-type mice, but did not alter neuron survival, suggesting that glial apoptosis is increased in the receptor knockout mice. Investigation of Bcl-2, Bax, Fas, Fas ligand (FasL) and activated caspase-3, key regulators of apoptosis that can be modulated by cytokines, revealed complex alterations of mRNA and protein levels in MCP-1(-/-) and CCR2(-/-) mice. As examples, Bcl-2 protein was detected in wild-type, but not in MCP-1(-/-) mice. Caspase-3 activity was higher in MCP-1(-/-) mice compared to wild-type and CCR2(-/-) mice at 5 days after injury. High levels of activated caspase-3 correlate with the beginning of a period of delayed, but rapid cell death in the thalami of MCP-1(-/-) mice. In summary, our data strongly suggest that MCP-1 is involved in early microglial response to axotomy and that modulation of this chemokine could provide a novel strategy for improved neuronal survival following injury to the central nervous system.
Assuntos
Quimiocina CCL2/genética , Microglia/patologia , Degeneração Neural/fisiopatologia , Tálamo/patologia , Animais , Apoptose/genética , Apoptose/fisiologia , Caspase 3 , Caspases/metabolismo , Sobrevivência Celular/genética , Sobrevivência Celular/fisiologia , Feminino , Expressão Gênica/genética , Expressão Gênica/fisiologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Microglia/fisiologia , Microssomos/fisiologia , Degeneração Neural/patologia , Proteínas Proto-Oncogênicas/genética , Proteínas Proto-Oncogênicas c-bcl-2/genética , Receptores CCR2 , Receptores de Quimiocinas/genética , Regulação para Cima/genética , Regulação para Cima/fisiologia , Proteína X Associada a bcl-2 , Receptor fas/genéticaRESUMO
Persons with lactose intolerance are unable to digest significant amounts of lactose because of a genetically inadequate amount of the enzyme lactase. Common symptoms include abdominal pain and bloating, excessive flatus, and watery stool following the ingestion of foods containing lactose. Lactase deficiency is present in up to 15 percent of persons of northern European descent, up to 80 percent of blacks and Latinos, and up to 100 percent of American Indians and Asians. A sizable number of adults believe they are lactose intolerant but do not actually have impaired lactose digestion, and some persons with lactase deficiency can tolerate moderate amounts of ingested lactose. A diagnosis of lactose intolerance can usually be made with a careful history supported by dietary manipulation. If necessary, diagnosis can be confirmed by using a breath hydrogen or lactose tolerance test. Treatment consists primarily of avoiding lactose-containing foods. Lactase enzyme supplements may be helpful. The degree of lactose malabsorption varies greatly among patients with lactose intolerance, but most of them can ingest up to 12 oz of milk daily without symptoms. Lactose-intolerant patients must ensure adequate calcium intake.
Assuntos
Intolerância à Lactose/diagnóstico , Intolerância à Lactose/terapia , Cálcio da Dieta/administração & dosagem , Medicina de Família e Comunidade , Humanos , Lactase , Intolerância à Lactose/dietoterapia , beta-Galactosidase/uso terapêuticoRESUMO
Susto, a folk illness not recognized by biomedical practitioners as a disease, is now formally part of the diagnostic classification system in psychiatry as a "culture-bound syndrome." Susto has been reported among diverse groups of Latin Americans, but most of those reports are several decades old and many were conducted in Indian communities. This study focuses on contemporary descriptions of susto and uses a cross-cultural, comparative design to describe susto in three diverse Latino populations. Mestizo/ladino populations were interviewed in Guatemala, Mexico, and south Texas. An initial set of open-ended interviews was conducted with a sample of "key" informants at each site to obtain descriptive information about susto. A structured interview protocol was developed for use at all three sites, incorporating information from those initial interviews. A second set of structured interviews was then conducted with a representative sample at each site. Results indicate a good deal of consistency in reports of what susto is: what causes it, its symptoms, and how to treat it. There appear to be, however, some notable regional variations in treatments and a difference between past descriptions and contemporary reports of etiology.