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1.
bioRxiv ; 2024 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-38562792

RESUMO

Zoonotic pathogens pose a significant risk to human health, with spillover into human populations contributing to chronic disease, sporadic epidemics, and occasional pandemics. Despite the widely recognized burden of zoonotic spillover, our ability to identify which animal populations serve as primary reservoirs for these pathogens remains incomplete. This challenge is compounded when prevalence reaches detectable levels only at specific times of year. In these cases, statistical models designed to predict the timing of peak prevalence could guide field sampling for active infections. Here we develop a general model that leverages routinely collected serosurveillance data to optimize sampling for elusive pathogens. Using simulated data sets we show that our methodology reliably identifies times when pathogen prevalence is expected to peak. We then apply our method to two putative Ebolavirus reservoirs, straw-colored fruit bats (Eidolon helvum) and hammer-headed bats (Hypsignathus monstrosus) to predict when these species should be sampled to maximize the probability of detecting active infections. In addition to guiding future sampling of these species, our method yields predictions for the times of year that are most likely to produce future spillover events. The generality and simplicity of our methodology make it broadly applicable to a wide range of putative reservoir species where seasonal patterns of birth lead to predictable, but potentially short-lived, pulses of pathogen prevalence.

2.
Pathol Res Pract ; 250: 154788, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37729782

RESUMO

BRAF mutant metastatic melanoma was regularly treated in the past with a BRAF inhibitor (BRAFi) alone or in combination with inhibitors of the mitogen-activated protein kinase kinase (MEKi), which is still a common treatment. This combination therapy strongly reduced the occurrence of keratoacanthomas and squamous cell carcinoma, which was frequently seen when BRAFi was used as monotherapy. Here we addressed the question whether MEK inhibition counteracts squamous cell carcinoma development in part by promoting keratinocyte differentiation. Exposure of human immortalized keratinocytes to different concentrations of MEKi revealed a significant increase in the expression of differentiation-associated keratins K10 and K1 as determined by qRT-PCR and immunofluorescence staining. Taken together, the present study suggests that in a combined treatment of melanoma with BRAFi/MEKi, MEKi reduces the incidence of squamous cell carcinomas by promoting keratinocyte differentiation under combined BRAFi/MEKi treatment in melanoma. This might open further treatment perspectives for skin cancer treatment.

3.
Toxicon ; 219: 106928, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36210603

RESUMO

BACKGROUND: Vinegaroons (Mastigoproctus giganteus), also known as whip scorpions, are arachnids commonly found in the southwestern United States, parts of Mexico, and southern Florida. They do not bite, but have special teeth on the inside of the trochanters of the front appendages, used to crush prey. They are best known for having pygidial gland secretions containing 83% acetic acid, which are sprayed upon potential predators. There are no published descriptions of injury to human related to vinegaroon exposures. Our primary aim was to characterize types of exposures and clinical effects reported to a poison center that serves an area indigenous to this animal. METHODS: The database from a regional poison center was searched for all cases from 1998 to 2022 regarding human exposures to the vinegaroon. Data captured included age, sex, exposure route, type and duration of symptoms, and part of the body affected. RESULTS: There were 50 exposures reported, with age range from 5 months to 54 years. Females represented 32 cases, males 17, and one unknown. Bites were more commonly described (36 cases), with 13 cases reported skin exposure to secretions, 3 ocular exposures, and 2 ingestions. Location of injury was upper extremities in 16 cases, lower in 11 cases, and torso in 3 cases. Symptoms were present in 88% and included pain, skin erythema, numbness or tingling, itching, and swelling. Ocular exposure were associated with pain in all 3 cases, with blurred vision in one case; effects lasted 1 h, 17 h, and more than 5 days. Four non-ocular exposures were followed to outcome, with duration of effects ranging from less than 1 h to more than 2 days. DISCUSSION/CONCLUSION: In a large series of vinegaroon exposures, females predominated, with most exposures occurring from skin contact with secretions. The most common symptoms were pain, erythema, numbness, itching, and swelling, which resolved in less than two days. Ocular exposures were associated with more symptoms and longer duration of effects.


Assuntos
Mordeduras e Picadas , Venenos , Masculino , Animais , Feminino , Humanos , Lactente , Centros de Controle de Intoxicações , Hipestesia , Escorpiões , Dor , Prurido , Estudos Retrospectivos
4.
Toxicon ; 186: 78-82, 2020 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-32771392

RESUMO

Envenomations during pregnancy have consequences affecting both maternal and fetal outcomes. U.S. poison center data on envenomations offers a comparative view of envenomations in pregnant and non-pregnant women. The National Poison Data System of the American Association of Poison Control Centers was searched for cases of envenomation during pregnancy between January 1, 2009 and December 31, 2018 and compared with exposures to non-pregnant females of childbearing age. Odds ratios and descriptive statistics were used where appropriate. There were a total of 3,555 venomous animal exposures in pregnant women during this 10-year period, most commonly with scorpion stings. These were compared with 87,553 envenomations in non-pregnant women of childbearing age during that time period. Overall, drug treatment was administered in 350 (9.9%) cases of envenomation in pregnant women compared with 21,381 (24.4%) of non-pregnant patients. Antihistamines were less likely to be used in pregnant patients with scorpion (1.8% v. 9.2%), hymenoptera (bee, wasp, or hornet) (12.4% v. 37.1%), black widow spider (2.8% v. 8.1%), and caterpillar (10.4% v. 37.7%) exposures. There was an increased likelihood of antivenom use during pregnancy with rattlesnake envenomations (85.0% v. 58.9%) and black widow spider bites (4.8% v. 2.2%). There were no maternal deaths, and most maternal outcomes were coded as having no (1.0%) or minor (87.6%) effects. Three fetal deaths occurred, all following snakebites and all before 20 weeks gestation. Two were attributed as related, and one as of uncertain relationship to the exposure, by the managing poison centers. Most envenomations caused no or minor effects to pregnant women.


Assuntos
Picadas de Escorpião/epidemiologia , Mordeduras de Serpentes/epidemiologia , Picada de Aranha/epidemiologia , Adulto , Animais , Feminino , Humanos , Centros de Controle de Intoxicações , Gravidez , Estados Unidos/epidemiologia
5.
Toxicon ; 186: 42-45, 2020 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-32763251

RESUMO

Two antivenoms are available for rattlesnake envenomations in the U.S., Fab (CroFab®, BTG, UK), and F(ab')2 (Anavip®, Bioclon, Mexico) antivenom (AV) with F(ab')2AV released in October 2018. The F(ab')2AV Phase 3 comparative clinical trial demonstrated similar efficacy in treating venom-caused hematologic toxicity, similar rates of Types I and III hypersensitivity reactions, and a lower rate of recurrent hematological effects than FabAV. We hypothesized that a post-marketing, comparative study of effectiveness and rates of hypersensitivity reactions in treating rattlesnake envenomations in New Mexico would demonstrate similar outcomes. Patients eligible for the study presented to a New Mexico healthcare facility between May and October 2019 and were known/suspected to have a rattlesnake bite. Exclusion criteria for antivenom comparison were those with a dry bite, lost to follow-up, or late presentation. All cases were included for patient/bite demographics, initial local control, hematological control, number of maintenance/control doses, development of persistent, recurrent or late-, new-onset hematologic effects, and hypersensitivity reactions. We used Fisher's exact tests for analysis and 0.05 cutoff to determine significance. There were 54 rattlesnake-bitten patients in New Mexico with 17 excluded for comparison of antivenom because of dry bites, loss to follow-up, and one case of late presentation. Thirty-seven patients remained for comparative analysis between F(ab')2AV (n = 11) and FabAV (n = 26). There were no significant demographic differences between F(ab')2 and Fab-treated patients. No patient had a Type I hypersensitivity reaction. No rescue doses were given. The rate of recurrent, persistent or late-, new-onset of hematologic effects was 0% with F(ab')2AV and 29% with FabAV. No patient was readmitted. No patient had bleeding complications. Type III hypersensitivity reactions were similar between F(ab')2AV (36%) and FabAV (25%). The results of our study are consistent with the Phase 3 clinical comparative trial and indicate no significant differences in safety or effectiveness between FabAV and F(ab')2AV. F(ab')2AV offers the advantages of not requiring maintenance doses and may have a lower rate of late hematologic effects in treating rattlesnake envenomations.


Assuntos
Antivenenos , Fragmentos Fab das Imunoglobulinas , Mordeduras de Serpentes , Adolescente , Animais , Venenos de Crotalídeos , Crotalus , Feminino , Humanos , Masculino , Marketing , México , Pessoa de Meia-Idade , New Mexico
6.
Toxicon ; 184: 55-56, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32505639

RESUMO

The use of Fab antivenom (Crotalidae Polyvalent Immune Fab (Ovine) (CroFab); Boston Scientific) against North American Crotalidae envenomation is associated with the development of late- (≥4 days post-envenomation), new-onset of hematological abnormalities. Although attempts have been made to identify predictive indicators during the acute phase of an envenomation, of patients who are not at-risk of late-, new-onset of hematological abnormalities, there has been at least one prior report of a patient who developed thrombocytopenia that was unpredicted by current indicators. We add three cases of unpredicted, late-, new-onset of hematological abnormalities in patients with Fab-treated rattlesnake bite.


Assuntos
Antivenenos/uso terapêutico , Mordeduras de Serpentes/tratamento farmacológico , Trombocitopenia/induzido quimicamente , Afibrinogenemia/induzido quimicamente , Animais , Venenos de Crotalídeos , Crotalus , Humanos , Fragmentos Fab das Imunoglobulinas , Ovinos , Mordeduras de Serpentes/complicações
7.
Respir Med Case Rep ; 30: 101082, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32461882

RESUMO

Mucormycosis is a life-threatening infection caused by fungi in the Mucorales species. It most often affects immunocompromised hosts, including diabetics patients. It can affect a variety of organ systems with pulmonary manifestations being the second most common. In severe cases, significant bronchial necrosis and angioinvasion can be seen. Due to its rarity, such extensive cases are not often reported in literature. We present a case of a 32-year-old man who presented with severe bronchial necrosis, including bronchomediastinal fistula, due to Rhizopus. Despite prompt treatment, he developed massive hemoptysis from invasion of the pulmonary vasculature and died. We also provide a brief review of mucormycosis.

8.
Eur J Nutr ; 58(6): 2207-2217, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-29974226

RESUMO

PURPOSE: Differences in resting energy expenditure (REE) between men and women mainly result from sex-related differences in lean body mass (LBM). So far, a little is known about whether REE and LBM are reflected by a distinct human metabolite profile. Therefore, we aimed to identify plasma and urine metabolite patterns that are associated with REE and LBM of healthy subjects. METHODS: We investigated 301 healthy male and female subjects (18-80 years) under standardized conditions in the cross-sectional KarMeN (Karlsruhe Metabolomics and Nutrition) study. REE was determined by indirect calorimetry and LBM by dual X-ray absorptiometry. Fasting blood and 24 h urine samples were analyzed by targeted and non-targeted metabolomics methods using GC × GC-MS, GC-MS, LC-MS, and NMR. Data were evaluated by predictive modeling of combined data using different machine learning algorithms, namely SVM, glmnet, and PLS. RESULTS: When evaluating data of men and women combined, we were able to predict REE and LBM with high accuracy (> 90%). This, however, was a clear effect of sex, which is supported by the high degree of overlap in identified important metabolites for LBM, REE, and sex, respectively. The applied machine learning algorithms did not reveal a metabolite pattern predictive of REE or LBM, when analyzing data for men and women, separately. CONCLUSIONS: We could not identify a sex independent predictive metabolite pattern for REE or LBM. REE and LBM have no impact on plasma and urine metabolite profiles in the KarMeN Study participants. Studies applying metabolomics in healthy humans need to consider sex specific data evaluation.


Assuntos
Metabolismo Basal/fisiologia , Composição Corporal/fisiologia , Metaboloma/fisiologia , Absorciometria de Fóton , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos Transversais , Feminino , Voluntários Saudáveis , Humanos , Masculino , Pessoa de Meia-Idade , Valores de Referência , Fatores Sexuais , Adulto Jovem
9.
Radiat Prot Dosimetry ; 183(4): 404-416, 2019 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-30272224

RESUMO

Environmental radiation monitoring networks have been established in Europe and world-wide for the purpose of protecting population and environment against ionizing radiation. Some of these networks had been established during the cold war period and were improved after the Chernobyl accident in 1986. Today, the German Federal Office for Radiation Protection (BfS) operates an early warning network with roughly 1800 ambient dose equivalent rate (ADER) stations equally distributed over the German territory. The hardware and software of all network components are developed in-house allowing the continuous optimization of all relevant components. A probe characterization and quality assurance and control program are in place. Operational and technical aspects of the network and data harmonization techniques are described. The latter allows for calculating of the terrestrial and net ADER combined with uncertainties mainly from site specific effects. Harmonized data are finally used as input to the German emergency management system and the European radiological data exchange platform.


Assuntos
Monitoramento de Radiação/métodos , Monitoramento de Radiação/normas , Proteção Radiológica/normas , Poluentes Radioativos/análise , Europa (Continente) , Humanos , Doses de Radiação , Monitoramento de Radiação/instrumentação , Software
10.
Nanoscale ; 7(26): 11328-33, 2015 Jul 14.
Artigo em Inglês | MEDLINE | ID: mdl-26067094

RESUMO

We report on a combined ultra-fast in situ SAXS and WAXS study along a free-jet providing insight into the evolution of the morphology and crystalline structure of CdS quantum dots in the very early stage of nucleation between 100 µs and 2.5 ms with a time resolution down to 10 µs. Accessing this yet unexplored time regime provides direct evidence of a two-step mechanism via formation of prenucleation clusters followed by nanoparticle nucleation from coalescing precursors. Using ab initio calculations, the latter species is identified as Cd13S4(SH)18 clusters, the stability of which results from a compact surface and inner structure.

11.
Rev Sci Instrum ; 84(2): 025111, 2013 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-23464255

RESUMO

In the growing field of in operando and in situ X-ray experiments, there exists a large disparity in the types of environments and equipment to control them. This situation makes it challenging to conduct multiple experiments with a single mechanical interface to the diffractometer. Here, we describe the design and implementation of a modular instrument mounting system that can be installed on a standard six-circle diffractometer (e.g., 5021 Huber GmbH). This new system allows for the rapid changeover of different chambers and sample heaters and permits accurate sample positioning (x, y, z, and azimuthal rotation) without rigid coupling to the chamber body. Isolation of the sample motion from the chamber enclosure is accomplished through a combination of custom rotary seals and bellows. Control of the pressure and temperature has been demonstrated in the ranges of 10(-6)-10(3) Torr and 25°C-900°C, respectively. We have utilized the system with several different modular instruments. As an example, we provide in situ sputtering results, where the growth dynamics of epitaxial LaGaO3 thin films on (001) SrTiO3 substrates were investigated.

12.
Clin Toxicol (Phila) ; 51(1): 3-15, 2013 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-23298218

RESUMO

CONTEXT: Envenomations during pregnancy pose all the problems of envenomation in the nonpregnant state with additional complexity related to maternal physiologic changes, medication use during pregnancy, and the well-being of the fetus. OBJECTIVE: We review the obstetric literature and management options available to prevent maternal morbidity and mortality while limiting adverse obstetric outcomes after envenomation in pregnancy. METHODS: In January 2012, we searched the U.S. National Library of Medicine Medline/PubMed, Toxline, Reprotox, Google Scholar and Micromedex databases, core surgery and internal medicine textbooks, and references of retrieved articles for the years 1966 through 2011. Search terms included "envenomation in pregnancy," "stings in pregnancy," "antivenom use in pregnancy," "anaphylaxis in pregnancy," and variants of these with known venomous animals. Reference lists generated further case reports and articles. We included English language articles and abstracts. Levels of Evidence (LOE) for the reports cited and Grades of Recommendations (GOR) based on LOE for our recommendations use the National Guidelines Clearinghouse metric of the US DHHS. RESULTS: Recommendations for the management of envenomation in pregnancy are guided primarily by studies on nonpregnant persons and case reports of pregnancy. Clinically significant envenomations in pregnancy are reported for snakes, spiders, scorpions, jellyfish, and hymenoptera (bees, wasps, hornets, and ants). Adverse obstetric outcomes including miscarriage, preterm birth, placental abruption, and stillbirth are associated with envenomation in pregnancy. The limited available literature suggests that adverse outcomes are primarily related to venom effects on the mother. Optimization of maternal health such as management of anaphylaxis and antivenom administration is likely the best approach to improve fetal outcomes despite potential risks to the fetus of medication administration during pregnancy. Obstetric evaluation and fetal monitoring are imperative in cases of severe envenomation. CONCLUSION: The medical literature regarding envenomation in pregnancy includes primarily retrospective reviews and case series. The limited available evidence suggests that optimal management includes a venom-specific approach, including supportive care, antivenom administration in appropriate cases, treatment of anaphylaxis if present, and fetal assessment. The current available evidence suggests that antivenom use is safe in pregnancy and that what is good for the mother is good for the fetus. Further research is needed to clarify the optimal management schema for envenomation in pregnancy.


Assuntos
Antivenenos/uso terapêutico , Mordeduras e Picadas/terapia , Complicações na Gravidez/terapia , Anafilaxia/tratamento farmacológico , Anafilaxia/etiologia , Anafilaxia/prevenção & controle , Animais , Antivenenos/efeitos adversos , Mordeduras e Picadas/tratamento farmacológico , Mordeduras e Picadas/fisiopatologia , Árvores de Decisões , Feminino , Monitorização Fetal , Humanos , Gravidez , Complicações na Gravidez/tratamento farmacológico , Complicações na Gravidez/fisiopatologia
13.
Clin Toxicol (Phila) ; 51(2): 96-105, 2013 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-23331216

RESUMO

CONTEXT: Over two million poisoning exposures are reported to U.S. poison control centers annually. A broad population-based survey of toxic exposures and the correlated patterns of reported kidney injury (acute or chronic) have not been systematically characterized. OBJECTIVE: Our objective was to study the demographic and exposure patterns associated with indicators for serious kidney complications (ISKC), as defined by the variables in the NPDS. MATERIALS AND METHODS: This was a retrospective, case-control study using the data elements available in the NPDS. We assessed data related to patient characteristics, substance exposure, and management. Cases and controls were derived from adult and pediatric exposures documented in NPDS (2001-2007) as having "renal effects." For substance-specific analyses, cases were restricted to those involving single substances or single entity pharmaceutical preparations. ISKC cases presented with one or more of the following NPDS codes: increased creatinine, and/or oliguria/anuria, and/or renal failure. Controls were subjects with "renal effects" but did not have increased creatinine, nor anuria/oliguria, nor renal failure. Univariate and multivariate logistic regression analyses identified factors associated with ISKC and determined the relationship between these factors. RESULTS: From the approximate 16.8 million exposures reported to the NPDS within the study timeframe, there were 16,444 single substance exposures with renal effects of which 9,074 cases experienced ISKC (55.2%) compared to 7,370 controls without ISKC. Cases with ISKC tended to be males, adults, and reported to involve intentional exposures. Cases with ISKC had higher rates of reported hemodialysis/hemofiltration (27.7%; N = 2,517) and death (10.9%; N = 990) compared to controls, respectively, (2.1%; N = 155) and (0.8%; N = 60), p < 0.001. Substances considered a priori to be nephrotoxic were associated with a higher risk of ISKC. DISCUSSION AND CONCLUSION: The NPDS provided insight into the subjects and types of exposures that associate with ISKC. Subjects with ISKC experienced higher rates of morbidity and mortality compared to subjects without ISKC. We identified subject characteristics and classes of compounds associated with ISKC. We hope that the hypotheses generated from this study of the NPDS will raise awareness of the possible risk factors and complications associated with ISKC.


Assuntos
Nefropatias/induzido quimicamente , Nefropatias/epidemiologia , Intoxicação/complicações , Intoxicação/epidemiologia , Injúria Renal Aguda/induzido quimicamente , Adolescente , Adulto , Fatores Etários , Idoso , Anuria/etiologia , Estudos de Casos e Controles , Criança , Pré-Escolar , Cuidados Críticos , Bases de Dados Factuais , Feminino , Produtos Domésticos/intoxicação , Humanos , Lactente , Nefropatias/mortalidade , Testes de Função Renal , Masculino , Pessoa de Meia-Idade , Análise Multivariada , New Mexico/epidemiologia , Razão de Chances , Intoxicação/mortalidade , Estudos Retrospectivos , Fatores Sexuais , Tentativa de Suicídio , Estados Unidos/epidemiologia , Adulto Jovem
14.
Clin Toxicol (Phila) ; 51(1): 50-3, 2013 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-23194005

RESUMO

BACKGROUND: There are few reports of acetaminophen overdose in hypothermic patients and even fewer reports describing profound hypothermia. The kinetics, risk of hepatotoxicity, and the possible dose adjustments to N-acetylcysteine (NAC) therapy are not known in this setting. CASE REPORT: A 37-year-old female was found unconscious outside in December and was brought by ambulance to a tertiary care Emergency Department (ED) following a presumed overdose of acetaminophen and diphenhydramine. She later confirmed the ingestion and reported the ingestion had occurred approximately 18 hours prior to being found. On arrival, she was profoundly hypothermic, with a core rectal temperature of 17°C. Her initial serum acetaminophen concentration was 232 mcg/mL 19 hours post ingestion of a reported dose of approximately 50 grams of acetaminophen and 2.5 grams of diphenhydramine. Active rewarming was started immediately and IV NAC was initiated using the standard treatment protocol. The patient did not develop serious signs of hepatic injury or NAC toxicity. The patient's AST and ALT peaked 12 hours after admission at 84 IU/L (ref 10-37 U/L) and 104 IU/L (ref 12-78 U/L), respectively. Her INR peaked 2 hours after admission at 1.46 (ref < 1.2). DISCUSSION: Despite the significant ingestion of acetaminophen, delayed presentation, prolonged period of decreased responsiveness, and profound hypothermia, the patient did not develop any signs/symptoms of liver injury. NAC was administered in a standard dose during her rewarming period without apparent toxicity. The patient's absorption and/or metabolism of acetaminophen were likely slowed by her hypothermia and possibly by the anticholinergic coingestant. Initiation of IV NAC at a standard dose was apparently safe and effective in preventing hepatotoxicity as the patient was rewarmed. CONCLUSIONS: Profound hypothermia may be protective of hepatic injury in acetaminophen overdose. Delayed absorption from the coingestant, diphenhydramine, may also have played a role. IV NAC was given in a standard dose without apparent toxicity in the setting of profound hypothermia. Lastly, IV NAC, in standard dosing, appeared to be effective in preventing hepatotoxicity during rewarming in a patient with a potentially hepatotoxic concentration of acetaminophen with a coingestion of the anticholinergic agent, diphenhydramine.


Assuntos
Acetaminofen/intoxicação , Analgésicos não Narcóticos/intoxicação , Antagonistas Colinérgicos/intoxicação , Difenidramina/intoxicação , Overdose de Drogas/tratamento farmacológico , Hipotermia/terapia , Medicamentos sem Prescrição/intoxicação , Acetaminofen/sangue , Acetaminofen/farmacocinética , Acetilcisteína/administração & dosagem , Acetilcisteína/uso terapêutico , Adulto , Analgésicos não Narcóticos/sangue , Analgésicos não Narcóticos/farmacocinética , Doença Hepática Induzida por Substâncias e Drogas/prevenção & controle , Antagonistas Colinérgicos/sangue , Antagonistas Colinérgicos/farmacocinética , Difenidramina/sangue , Difenidramina/farmacocinética , Combinação de Medicamentos , Overdose de Drogas/metabolismo , Overdose de Drogas/fisiopatologia , Overdose de Drogas/terapia , Feminino , Humanos , Hipotermia/etiologia , Infusões Intravenosas , Medicamentos sem Prescrição/análise , Medicamentos sem Prescrição/farmacocinética , Reaquecimento , Resultado do Tratamento
15.
Phys Med Biol ; 57(22): 7709-24, 2012 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-23123792

RESUMO

High spatial resolution γ-imaging can be achieved with scintillator readout by low-noise, fast, electron-multiplying charge-coupled devices (EMCCDs). Previously we have shown that false-positive events due to EMCCD noise can be rejected by using the sum signal from silicon photomultipliers (SiPMs) mounted on the sides of the scintillator. Here we launch a next generation hybrid CCD-SiPM camera that utilizes the individual SiPM signals and maximum likelihood estimation (MLE) pre-localization of events to discriminate between true and false events in CCD frames. In addition, SiPM signals are utilized for improved energy discrimination. The performance of this hybrid detector was tested for a continuous CsI:Tl crystal at 140 keV. With a pre-localization accuracy of 1.06 mm (full-width-at-half-maximum) attained with MLE the signal-to-background ratio (SBR) was improved by a factor of 5.9, 4.0 or 2.2 compared to the EMCCD-only readout, at the cost of rejecting, respectively, 47%, 9% or 4% of the events. Combining the pre-localization and SiPM energy estimation improved the energy resolution from 50% to (19 ± 3)% while maintaining the spatial resolution at 180 µm.


Assuntos
Equipamentos e Provisões Elétricas , Câmaras gama , Cintilografia/instrumentação , Silício
16.
Rofo ; 184(8): 734-9, 2012 Aug.
Artigo em Alemão | MEDLINE | ID: mdl-22618479

RESUMO

PURPOSE: To introduce automated detection and volumetric segmentation of the spleen in spiral CT scans with the THESEUS-MEDICO software. The consistency between automated volumetry (aV), estimated volume determination (eV) and manual volume segmentation (mV) was evaluated. MATERIALS AND METHODS: Retrospective evaluation of the CAD system based on methods like "marginal space learning" and "boosting algorithms". 3 consecutive spiral CT scans (thoraco-abdominal; portal-venous contrast agent phase; 1 or 5 mm slice thickness) of 15 consecutive lymphoma patients were included. The eV: 30 cm³ + 0.58 (width × length × thickness of the spleen) and the mV as the reference standard were determined by an experienced radiologist. RESULTS: The aV could be performed in all CT scans within 15.2 (± 2.4) seconds. The average splenic volume measured by aV was 268.21 ± 114.67 cm³ compared to 281.58 ± 130.21 cm³ in mV and 268.93 ± 104.60 cm³ in eV. The correlation coefficient was 0.99 (coefficient of determination (R²) = 0.98) for aV and mV, 0.91 (R² = 0.83) for mV and eV and 0.91 (R² = 0.82) for aV and eV. There was an almost perfect correlation of the changes in splenic volume measured with the new aV and mV (0.92; R² = 0.84), mV and eV (0.95; R² = 0.91) and aV and eV (0.83; R² = 0.69) between two time points. CONCLUSION: The automated detection and volumetric segmentation software rapidly provides an accurate measurement of the splenic volume in CT scans. Knowledge about splenic volume and its change between two examinations provides valuable clinical information without effort for the radiologist.


Assuntos
Diagnóstico por Computador/métodos , Imageamento Tridimensional/métodos , Linfoma/diagnóstico por imagem , Software , Tomografia Computadorizada de Feixe Cônico Espiral/métodos , Baço/diagnóstico por imagem , Adulto , Idoso , Meios de Contraste , Feminino , Humanos , Linfoma/patologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Tamanho do Órgão , Reconhecimento Automatizado de Padrão , Estudos Retrospectivos
17.
Eur J Pharm Biopharm ; 80(3): 615-20, 2012 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-22285524

RESUMO

Bacteria and fungi are located in the stratum corneum and the hair follicles. Therefore, the development and assessment of efficient drugs requires standard in vivo investigation methods permitting a differentiation between intercellular and follicular penetration and storage of topically applied anti-microbial substances. In the present study, the penetration and storage of Isoconazole nitrate in the stratum corneum and hair follicles was investigated by differential stripping after a 14-day topical application period and during a follow-up period of a further 21 days. One week after the application had terminated, Isoconazole nitrate could still be detected in concentrations above the minimal inhibition concentration in the stratum corneum and the hair follicles. In some subjects, Isoconazole nitrate could even be detected 14 days after the last application. No relevant changes in TEWL values were measured, indicating that the investigated compound did not induce an impairment of the barrier function. The study showed that differential stripping is suited to investigate the penetration and storage of topically applied substances into the stratum corneum and the hair follicles. Also, the hair follicles are a long-term reservoir for topically applied substances. This is of clinical importance, where a long-lasting therapeutic effect beyond the application time is required.


Assuntos
Anti-Infecciosos Locais/administração & dosagem , Anti-Infecciosos Locais/farmacocinética , Folículo Piloso/metabolismo , Miconazol/análogos & derivados , Pele/metabolismo , Administração Tópica , Adulto , Feminino , Seguimentos , Humanos , Masculino , Miconazol/administração & dosagem , Miconazol/farmacocinética , Testes de Sensibilidade Microbiana/métodos , Absorção Cutânea , Adulto Jovem
18.
Clin Pharmacol Ther ; 90(5): 662-5, 2011 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-21975349

RESUMO

The link between cyclobenzaprine (Flexeril) administration and serotonin syndrome (SS) is subject to debate. Establishing such a connection is difficult because of the limited number of case reports available and the almost complete ignorance of its preclinical pharmacology. In this context, evidence is provided here that cyclobenzaprine blocks the serotonin and norepinephrine transporters and binds to another set of five serotonin receptors. SS should be considered when indicative signs occur in the context of cyclobenzaprine use.


Assuntos
Amitriptilina/análogos & derivados , Antidepressivos Tricíclicos/efeitos adversos , Síndrome da Serotonina/induzido quimicamente , Amitriptilina/efeitos adversos , Amitriptilina/metabolismo , Amitriptilina/farmacologia , Antidepressivos Tricíclicos/metabolismo , Antidepressivos Tricíclicos/farmacologia , Humanos , Proteínas da Membrana Plasmática de Transporte de Norepinefrina/antagonistas & inibidores , Ligação Proteica , Receptores de Serotonina/metabolismo , Proteínas da Membrana Plasmática de Transporte de Serotonina/efeitos dos fármacos , Proteínas da Membrana Plasmática de Transporte de Serotonina/metabolismo
19.
Poult Sci ; 90(10): 2275-80, 2011 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-21934010

RESUMO

The use of protective, probiotic cultures in poultry farming may serve as a useful strategy to improve food product safety from the beginning of the food chain and thus to protect consumer health. The objective of this study was to investigate the effect of the probiotic strain Bifidobacterium longum PCB133 on innate and adaptive immune responses in turkeys beginning at 2 wk of age, under farming conditions. The vaccination efficiency against Newcastle disease virus served as the primary endpoint. At 2 wk of age, male turkeys (British United Turkey Big 6 strain) were randomly assigned to the control (n = 25) or probiotic group (n = 25). Turkeys in the probiotic group received the probiotic B. longum PCB133 (at least 3 × 10(7) cfu/d) incorporated into the daily feed ration for 5 wk, until slaughter at 7 wk of age. At the beginning of the probiotic intervention, birds in both groups were vaccinated against Newcastle disease. Birds were weighed weekly throughout the intervention period, and finally blood sera and heparinized blood were collected for immune function tests (lymphocyte proliferation, phagocytosis, respiratory burst), and for the determination of Newcastle disease virus antibody titers. No effects on BW gain and on the proliferation of blood lymphocytes were elicited by the 5-wk intervention with the probiotic. Concerning the primary endpoint of the study (i.e., specific antibody production as a response to vaccination against Newcastle disease), no adjuvant effect of the probiotic could be determined. In addition, innate immune functions tested were not significantly affected. In conclusion, first scientific evidence on the application of the probiotic strain B. longum PCB133 in turkeys beginning at 2 wk of age does not support an improvement in live performance, humoral immunity, or innate immunity.


Assuntos
Imunidade Adaptativa , Bifidobacterium , Imunidade Inata , Probióticos/administração & dosagem , Perus/imunologia , Animais , Dieta , Ativação Linfocitária/imunologia , Masculino , Doença de Newcastle/imunologia , Doença de Newcastle/prevenção & controle , Vírus da Doença de Newcastle/imunologia , Vacinação/veterinária
20.
Radiologe ; 51(7): 602-9, 2011 Jul.
Artigo em Alemão | MEDLINE | ID: mdl-21698344

RESUMO

Malignant tumors of the female pelvis account for 12-13% of newly diagnosed solid neoplasms among women in the USA and Germany. German guidelines advocate diagnostic imaging for local recurrence and metastasis while there are no recommendations for primary tumors. As excretory urography has been replaced by the excretory phase of computed tomography urography (CTU) in many institutions, two independent observers retrospectively evaluated CTUs of primary or recurrent female pelvic tumors to rule out associations between CTU findings and subsequent urologic measures. Among 31 CTUs of 27 women (age 29-84 years, mean 57 years) with 15 primary and 13 recurrent tumors, 83-100% of unremarkable proximal, middle and distal ureter segments were completely delineated in the excretory phase (delay 6-29 min, mean 16 min). The most common pathological findings included distal ureter obstruction (n=19, 61%), bladder compression (n=13, 42%) and bladder invasion (n=8, 26%). Out of 20 pathologically altered urinary tracts 8 were subsequently subjected to urologic measures (2-tailed Fisher exact test, p=0.0215) but none of the 10 unremarkable urinary tracts were treated. It appears that CTU is a sensible pre-therapeutic test for the urinary tract for primary and recurrent female pelvic tumors.


Assuntos
Recidiva Local de Neoplasia/diagnóstico por imagem , Neoplasias Pélvicas/diagnóstico , Intensificação de Imagem Radiográfica/métodos , Tomografia Computadorizada por Raios X/métodos , Urografia/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Pessoa de Meia-Idade , Adulto Jovem
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