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1.
Front Pediatr ; 8: 588, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33072664

RESUMO

The neonatal intensive care unit (NICU) is a very noisy place as compared to the intrauterine environment. To protect the neonate's health, international guidelines suggest avoiding noise levels above 45 dB in NICUs, but this recommendation is not normally met. The incubator acoustic isolation and the acoustic features of the NICU play important roles in determining the noise measured inside the incubator. In this study, the influence of two types of rooms, one with sound-absorbent covering and the other with reverberant surfaces, on the acoustic isolation of a neonatal incubator was evaluated using three acoustic isolation indexes: the level difference, the apparent sound reduction index, and the standardized level difference. Results show that the acoustic isolation of the incubator is very poor, with a level difference below 11 dBA at all frequencies. At 62.5 Hz, the level difference measured in both rooms exhibits a negative value, indicating that the incubator amplifies the noise coming from the NICU. Isolation of the incubator is poor, and the reverberation time (RT) of the containing room influences RT of the incubator, which is consequently higher when the containing room is reverberant; for example, the incubator RT in the reverberant NICU is 0.72 s higher at 500 Hz than that in a room with sound-absorbent covering.

3.
Rev Invest Clin ; 72(5)2020 05 07.
Artigo em Inglês | MEDLINE | ID: mdl-33057321

RESUMO

BACKGROUND: The incidence of renal cell carcinoma (RCC) is increasing globally due to an aging population and widespread use of imaging studies. OBJECTIVE: The aim of this study was to describe the characteristics and perioperative outcomes of RCC surgery in very elderly patients (VEP), ≥ 75 years of age. METHODS: This is a retrospective comparative study of 3656 patients who underwent the treatment for RCC from 1990 to 2015 in 28 centers from eight Latin American countries. We compared baseline characteristics as well as clinical and perioperative outcomes according to age groups (less than 75 vs. ≥75 years). Surgical complications were classified with the Clavien-Dindo score. We performed logistic regression analysis to identify factors associated with perioperative complications. RESULTS: There were 410 VEP patients (11.2%). On bivariate analysis, VEP had a lower body mass index (p less than 0.01) and higher ASA score (ASA > 2 in 26.3% vs. 12.4%, p < 0.01). There was no difference in performance status and clinical stage between the study groups. There were no differences in surgical margins, estimated blood loss (EBL), complication, and mortality rates (1.3% vs. 0.4%, p = 0.17). On multivariate regression analysis, age ≥75 years (odds ratio [OR] 2.33, p less than 0.01), EBL ≥ 500 cc (OR 3.34, p less than 0.01), and > pT2 stage (OR 1.63, p = 0.04) were independently associated with perioperative complications. CONCLUSIONS: Surgical resection of RCC was safe and successful in VEP. Age ≥75 years was independently associated with 30-day perioperative complications. However, the vast majority were low-grade complications. Age alone should not guide decision-making in these patients, and treatment must be tailored according to performance status and severity of comorbidities.

4.
Oncology (Williston Park) ; 34(10): 421-426, 2020 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-33058108

RESUMO

A woman, aged 44 years, presented at the general oncology outpatient clinic with bloating, abdominal pain, and significant unintended weight loss. Her past medical history included a bilateral inguinal hernia surgical repair at age 6, and primary amenorrhea since age 15. The patient never underwent additional studies to identify the cause of the primary amenorrhea.

5.
BMC Urol ; 20(1): 85, 2020 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-32615971

RESUMO

BACKGROUND: To evaluate demographic, clinical and pathological characteristics of small renal masses (SRM) (≤ 4 cm) in a Latin-American population provided by LARCG (Latin-American Renal Cancer Group) and analyze predictors of survival, recurrence and metastasis. METHODS: A multi-institutional retrospective cohort study of 1523 patients submitted to surgical treatment for non-metastatic SRM from 1979 to 2016. Comparisons between radical (RN) or partial nephrectomy (PN) and young or elderly patients were performed. Kaplan-Meier curves and log-rank tests estimated 10-year overall survival. Predictors of local recurrence or metastasis were analyzed by a multivariable logistic regression model. RESULTS: PN and RN were performed in 897 (66%) and 461 (34%) patients. A proportional increase of PN cases from 48.5% (1979-2009) to 75% (after 2009) was evidenced. Stratifying by age, elderly patients (≥ 65 years) had better 10-year OS rates when submitted to PN (83.5%), than RN (54.5%), p = 0.044. This disparity was not evidenced in younger patients. On multivariable model, bilaterality, extracapsular extension and ASA (American Society of Anesthesiologists) classification ≥3 were predictors of local recurrence. We did not identify significant predictors for distant metastasis in our series. CONCLUSIONS: PN is performed in Latin-America in a similar proportion to developed areas and it has been increasing in the last years. Even in elderly individuals, if good functional status, sufficiently fit to surgery, and favorable tumor characteristics, they should be encouraged to perform PN. Intending to an earlier diagnosis of recurrence or distant metastasis, SRM cases with unfavorable characteristics should have a more rigorous follow-up routine.

6.
Int Braz J Urol ; 46(suppl.1): 156-164, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32618462

RESUMO

PURPOSE: To explore the current situation faced by Latin American urology departments during the COVID-19 Outbreak in terms of knowledge, actions, prioritization of urology practices, and implementation of internal clinical management protocols for inpatients and outpatients. MATERIAL AND METHODS: A non-validated, structured, self-administered, electronic survey with 35 closed multiple choice questions was conducted in Spanish, Portuguese, Italian, and English and Deutsch versions from April 1st to April 30th, 2020. The survey was distributed through social networks and the official American Confederation of Urology (CAU) website. It was anonymous, mainly addressed to Latin American urologists and urology residents. It included 35 questions exploring different aspects: 1) Personal Protective Equipment (PPE) and internal management protocols for healthcare providers; 2) Priority surgeries and urological urgencies and 3) Inpatient and outpatient care. RESULTS: Of 864 surveys received, 846 had at least 70% valid responses and were included in the statistical analyses. Surveys corresponded to South America in 62% of the cases, Central America and North America in 29.7%. 12.7% were residents. Regarding to PPE and internal management protocols, 88% confirmed the implementation of specific protocols and 45.4% have not received training to perform a safe clinical practice; only 2.3% reported being infected with COVID-19. 60.9% attended urgent surgeries. The following major uro-oncologic surgeries were reported as high priority: Radical Nephrectomy (RN) 58.4%, and Radical Cystectomy (RC) 57.3%. When we associate the capacity of hospitalization (urologic beds available) and percentage of high-priority surgery performed, we observed that centers with fewer urological beds (10-20) compared to centers with more urological beds (31-40) performed more frequently major urologic cancer surgeries: RN 54.5% vs 60.8% (p=0.0003), RC 53.1% vs 64.9% (p=0.005) respectively. CONCLUSIONS: At the time of writing (May 13th 2020) our data represents a snapshot of COVID-19 outbreak in Latin American urological practices. Our findings have practical implications and should be contextualized considering many factors related to patients and urological care: The variability of health care scenarios, institutional capacity, heterogeneity and burden of urologic disease, impact of surgical indications and decision making when prioritizing and scheduling surgeries in times of COVID-19 pandemic.


Assuntos
Infecções por Coronavirus/epidemiologia , Pneumonia Viral/epidemiologia , Urologia/tendências , Betacoronavirus , Hospitais/estatística & dados numéricos , Humanos , América Latina , Pandemias , Inquéritos e Questionários , Procedimentos Cirúrgicos Urológicos/estatística & dados numéricos
7.
Transbound Emerg Dis ; 2020 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-32668083

RESUMO

Recent anthropic activity related to the construction of the Bosquesur Green Park in a large urban setting in Madrid (Spain) has resulted in the largest reported community outbreak of human leishmaniosis in Europe. Previous phylogenetic and molecular-typing studies of parasite isolates have implicated the Leishmania infantum ITS-Lombardi genotype in this outbreak. In an unusual scenario, visceral leishmaniosis (VL) is affecting a significant number of individuals, suggesting that an increase in parasite virulence has occurred. In this work, using an in vivo BALB/c model of VL, we aimed to investigate the properties of emergent virulence of the L. infantum POL2FL7 and BOS1FL1 isolates obtained from Phlebotomus perniciosus collected in the outbreak area and compare them with those of the well-characterized strain BCN150 MON-1 isolated from a dog. The P. perniciosus specimens were collected during an entomological survey conducted in the transmission season of 2012. We observed a range of virulence phenotypes from moderately to highly aggressive after 5 weeks of infection. IV challenge of mice with outbreak isolates from sand flies induced higher splenic and liver parasite burdens, higher serological titres of specific anti-Leishmania antibodies and impaired capacities to control infection, as revealed by the arginine metabolism and low ratios of Th1/Th2 cytokine profiles analysed, compared with the corresponding measures evaluated in mice infected with the BCN150 strain. The BOS1FL1 isolate showed the highest degree of virulence among the isolates, superior to that of POL2FL7, as evidenced by the analysed biomarkers and the histopathological severity of liver lesions. These results provide insight into how L. infantum isolates from sand flies collected in the outbreak area have been able to affect not only immunosuppressed patients but also middle-aged people with normal immunocompetence in the largest human VL outbreak in Europe.

8.
Int. braz. j. urol ; 46(supl.1): 156-164, July 2020. tab
Artigo em Inglês | LILACS-Express | LILACS | ID: biblio-1134280

RESUMO

ABSTRACT Purpose: To explore the current situation faced by Latin American urology departments during the COVID-19 Outbreak in terms of knowledge, actions, prioritization of urology practices, and implementation of internal clinical management protocols for inpatients and outpatients. Material and Methods: A non-validated, structured, self-administered, electronic survey with 35 closed multiple choice questions was conducted in Spanish, Portuguese, Italian, and English and Deutsch versions from April 1st to April 30th, 2020. The survey was distributed through social networks and the official American Confederation of Urology (CAU) website. It was anonymous, mainly addressed to Latin American urologists and urology residents. It included 35 questions exploring different aspects: 1) Personal Protective Equipment (PPE) and internal management protocols for healthcare providers; 2) Priority surgeries and urological urgencies and 3) Inpatient and outpatient care. Results: Of 864 surveys received, 846 had at least 70% valid responses and were included in the statistical analyses. Surveys corresponded to South America in 62% of the cases, Central America and North America in 29.7%. 12.7% were residents. Regarding to PPE and internal management protocols, 88% confirmed the implementation of specific protocols and 45.4% have not received training to perform a safe clinical practice; only 2.3% reported being infected with COVID-19. 60.9% attended urgent surgeries. The following major uro-oncologic surgeries were reported as high priority: Radical Nephrectomy (RN) 58.4%, and Radical Cystectomy (RC) 57.3%. When we associate the capacity of hospitalization (urologic beds available) and percentage of high-priority surgery performed, we observed that centers with fewer urological beds (10-20) compared to centers with more urological beds (31-40) performed more frequently major urologic cancer surgeries: RN 54.5% vs 60.8% (p=0.0003), RC 53.1% vs 64.9% (p=0.005) respectively. Conclusions: At the time of writing (May 13th 2020) our data represents a snapshot of COVID-19 outbreak in Latin American urological practices. Our findings have practical implications and should be contextualized considering many factors related to patients and urological care: The variability of health care scenarios, institutional capacity, heterogeneity and burden of urologic disease, impact of surgical indications and decision making when prioritizing and scheduling surgeries in times of COVID-19 pandemic.

9.
Int. braz. j. urol ; 46(supl.1): 98-103, July 2020.
Artigo em Inglês | LILACS-Express | LILACS | ID: biblio-1134284

RESUMO

ABSTRACT Purpose: To provide a summary and recommendations for the set-up of strategies for cancer patients care in genitourinary oncology clinics during the pandemic and in the recovery period. Material and Methods: A non-systematic review of available literature on the management of urological malignancies during the COVID-19 pandemic was performed to summarize recommendations to improve the diagnosis and treatment of urological cancers during and after the contingence, including clinical and research aspects. Results: Urological cancer diagnosis and management should be tailored according to the severity of the COVID-19 crisis in each region and the aggressiveness of each tumor. Clinicians should adhere to strict protocols in order to prioritize the attention of patients with high-risk malignancies while optimizing resources to avoid the saturation of critical care services. Conclusions: During the COVID-19 pandemic urological cancer care has been severely impaired. For proper patient management, multidisciplinary approach is encouraged tailoring therapy according to COVID-19 regional behavior and local institutional resources. Patients with high-risk malignancies should be prioritized.

10.
Int Braz J Urol ; 46(suppl.1): 98-103, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32549077

RESUMO

PURPOSE: To provide a summary and recommendations for the set-up of strategies for cancer patients care in genitourinary oncology clinics during the pandemic and in the recovery period. MATERIAL AND METHODS: A non-systematic review of available literature on the management of urological malignancies during the COVID-19 pandemic was performed to summarize recommendations to improve the diagnosis and treatment of urological cancers during and after the contingence, including clinical and research aspects. RESULTS: Urological cancer diagnosis and management should be tailored according to the severity of the COVID-19 crisis in each region and the aggressiveness of each tumor. Clinicians should adhere to strict protocols in order to prioritize the attention of patients with high-risk malignancies while optimizing resources to avoid the saturation of critical care services. CONCLUSIONS: During the COVID-19 pandemic urological cancer care has been severely impaired. For proper patient management, multidisciplinary approach is encouraged tailoring therapy according to COVID-19 regional behavior and local institutional resources. Patients with high-risk malignancies should be prioritized.


Assuntos
Infecções por Coronavirus/epidemiologia , Pneumonia Viral/epidemiologia , Neoplasias Urogenitais/terapia , Betacoronavirus , Humanos , Oncologia/métodos , Pandemias , Assistência ao Paciente
11.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-32345490

RESUMO

The genera Phlebovirus transmitted by Diptera belonging to the Psychodidae family are a cause of self-limited febrile syndrome in the Mediterranean basin in summer and autumn. Toscana virus can also cause meningitis and meningoencephalitis. In Spain, Toscana, Granada, Naples, Sicily, Arbia and Arrabida-like viruses have been detected. The almost widespread distribution of Phlebotomus genus vectors, and especially Phlebotomus perniciosus, in which several of these viruses have been detected, makes it very likely that there will be regular human infections in our country, with this risk considered moderate for Toscana virus and low for the other ones, in areas with the highest vector activity. Most of the infections would be undiagnosed, while only Toscana virus would have a greater impact due to the potential severity of the illness.

12.
PLoS Negl Trop Dis ; 14(4): e0008253, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32324738

RESUMO

BACKGROUND: In the Mediterranean basin, Leishmania infantum is the causative agent of visceral leishmaniasis (VL), a zoonosis in which the dog is the primary domestic reservoir, although wildlife may have a leading role in the sylvatic cycle of the disease in some areas. Infections without disease are very frequent. There is limited information regarding the role that VL patients and asymptomatic infected individuals could be playing in the transmission of L. infantum. Xenodiagnosis of leishmaniasis has been used in this descriptive study to explore the role of symptomatic and asymptomatic infected individuals as reservoirs in a recent focus of leishmaniasis in southwestern Madrid, Spain. METHODOLOGY AND MAIN FINDINGS: Asymptomatic blood donors (n = 24), immunocompetent patients who were untreated (n = 12) or treated (n = 11) for visceral leishmaniasis (VL), and immunocompromised patients with VL (n = 3) were enrolled in the study. Their infectivity to Phlebotomus perniciosus was studied by indirect xenodiagnosis on peripheral blood samples. Quantitative polymerase chain reaction of blood samples from immunocompetent patients untreated for VL and immunocompromised untreated, treated and under secondary prophylaxis for VL was performed. Antibodies against Leishmania were studied by indirect fluorescent antibody and rK39-immunochromatographic tests. A lymphoproliferative assay with a soluble Leishmania antigen was used to screen for leishmaniasis infection in the healthy population. Sixty-two xenodiagnostic tests were carried out and 5,080 sand flies were dissected. Positive xenodiagnosis was recorded in four patients, with different sand fly infection rates: 1 immunosuppressed HIV / L. infantum coinfected asymptomatic patient, 1 immunosuppressed patient with multiple myeloma and symptomatic active VL, and 2 immunocompetent patients with untreated active VL. All blood donors were negative for both xenodiagnosis and conventional PCR. CONCLUSIONS / SIGNIFICANCE: There is no consensus amongst authors on the definition of an 'asymptomatic case' nor on the tools for screening; we, therefore, have adopted one for the sake of clarity. Immunocompetent subjects, both infected asymptomatics and those treated for VL, are limited in number and appear to have no epidemiological relevance. The impact is limited for immunocompetent patients with untreated active VL, whilst immunosuppressed individuals undergoing immunosuppressive therapy and immunosuppressed individuals HIV / L. infantum coinfected were the most infectious towards sand flies. It is noteworthy that the HIV / L. infantum coinfected patient with asymptomatic leishmaniasis was easily infectious to sand flies for a long time, despite being under continuous prophylaxis for leishmaniasis. Accordingly, screening for latent Leishmania infection in HIV-infected patients is recommended in scenarios where transmission occurs. In addition, screening for VL in HIV-infected patients who have spent time in VL-endemic areas should also be implemented in non-endemic areas. More research is needed to better understand if some asymptomatic coinfected individuals contribute to transmission as 'super-spreaders'.


Assuntos
Reservatórios de Doenças , Transmissão de Doença Infecciosa , Leishmania infantum/isolamento & purificação , Leishmaniose Visceral/epidemiologia , Leishmaniose Visceral/transmissão , Adulto , Animais , Anticorpos Antiprotozoários/sangue , Doenças Assintomáticas/epidemiologia , DNA de Protozoário/sangue , Feminino , Humanos , Leucócitos Mononucleares/imunologia , Masculino , Pessoa de Meia-Idade , Psychodidae/parasitologia , Espanha/epidemiologia
13.
PLoS Negl Trop Dis ; 14(3): e0008077, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-32214313

RESUMO

BACKGROUND: Phlebotomus (Larroussius) perniciosus and Canis familiaris are respectively the only confirmed vector and reservoir for the transmission of Leishmania (L.) infantum MON-1 in Tunisia. However, the vector and reservoir hosts of the two other zymodemes, MON-24 and MON-80, are still unknown. The aim of this study was to analyze the L. infantum life cycle in a Tunisian leishmaniasis focus. For this purpose, we have focused on: i) the detection, quantification and identification of Leishmania among this sand fly population, and ii) the analysis of the blood meal preferences of Larroussius (Lar.) subgenus sand flies to identify the potential reservoirs. METHODOLOGY AND FINDINGS: A total of 3,831 sand flies were collected in seven locations from the center of Tunisia affected by human visceral leishmaniasis. The collected sand flies belonged to two genus Phlebotomus (Ph.) (five species) and Sergentomyia (four species). From the collected 1,029 Lar. subgenus female sand flies, 8.26% was positive to Leishmania by ITS1 nested PCR. Three Leishmania spp. were identified: L. infantum 28% (24/85), L. killicki 13% (11/85), and L. major 22% (19/85). To identify the blood meal sources in Ph. Lar. subgenus sand flies, engorged females were analyzed by PCR-sequencing targeting the vertebrate cytochrome b gene. Among the 177 analyzed blood-fed females, 169 samples were positive. Sequencing results showed seven blood sources: cattle, human, sheep, chicken, goat, donkey, and turkey. In addition, mixed blood meals were detected in twelve cases. Leishmania DNA was found in 21 engorged females, with a wide range of blood meal sources: cattle, chicken, goat, chicken/cattle, chicken/sheep, chicken/turkey and human/cattle. The parasite load was quantified in fed and unfed infected sand flies using a real time PCR targeting kinetoplast DNA. The average parasite load was 1,174 parasites/reaction and 90 parasites/reaction in unfed and fed flies, respectively. CONCLUSION: Our results support the role of Ph. longicuspis, Ph. perfiliewi, and Ph. perniciosus in L. infantum transmission. Furthermore, these species could be involved in L. major and L. killicki life cycles. The combination of the parasite detection and the blood meal analysis in this study highlights the incrimination of the identified vertebrate in Leishmania transmission. In addition, we quantify for the first time the parasite load in naturally infected sand flies caught in Tunisia. These findings are relevant for a better understanding of L. infantum transmission cycle in the country. Further investigations and control measures are needed to manage L. infantum transmission and its spreading.


Assuntos
DNA/análise , Comportamento Alimentar , Conteúdo Gastrointestinal/química , Conteúdo Gastrointestinal/parasitologia , Especificidade de Hospedeiro , Leishmania infantum/isolamento & purificação , Phlebotomus/fisiologia , Animais , DNA/genética , Impressões Digitais de DNA , DNA Espaçador Ribossômico/genética , Transmissão de Doença Infecciosa , Feminino , Humanos , Leishmania infantum/genética , Masculino , Phlebotomus/parasitologia , Reação em Cadeia da Polimerase , Análise de Sequência de DNA , Tunísia
14.
Transbound Emerg Dis ; 67(3): 1393-1400, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-31885197

RESUMO

Phlebotomine sand flies are the only known vectors of Leishmania spp. protozoan which causes leishmaniasis in 98 countries. In Spain, 11 sand fly species are described, but only Phlebotomus perniciosus and Phlebotomus ariasi are proven vectors of the disease. On the other hand, Sergentomyia minuta is one of the most abundant and ubiquitous sand flies in this territory, although scarce information is available about this species. Sand flies from this genus are known for their preference to feed on cold-blooded animals and are traditionally involved in the transmission of reptile Leishmania. However, studies have suggested that Sergentomyia spp. could be implicated in the transmission of human pathogenic Leishmania. This study analyses blood meal preferences and Leishmania sp. infection of S. minuta sand flies from the largest human leishmaniasis outbreak in Europe. Sand flies were collected during entomological surveillance carries out from 2012 to 2017 in the active season of these dipterans, from May to October. Molecular detection of Leishmania spp. showed 68 positive specimens of S. minuta out of 377 (18%). The analysis of blood meal preferences by amplification of 359 bp fragment of cytochrome b gene revealed that blood preference of S. minuta is not only limited to reptiles, but they also feed on mammals, including humans. Results suggest the presence of a Leishmania sp., related to Leishmania tarentolae, cycle in S. minuta from the studied area. Although there is no evidence about its incrimination in the L. infantum transmission more investigation is needed to elucidate the intravectorial cycle of Leishmania spp. in S. minuta sand flies, their feeding behaviour and their potential contribution in Leishmania spp. epidemiology in the country.


Assuntos
Comportamento Alimentar , Leishmania infantum , Leishmaniose Visceral/epidemiologia , Leishmaniose Visceral/parasitologia , Psychodidae/parasitologia , Animais , Surtos de Doenças , Feminino , Humanos , Reação em Cadeia da Polimerase , Estações do Ano , Espanha/epidemiologia
15.
Nefrología (Madrid) ; 39(5): 506-512, sept.-oct. 2019. tab, graf
Artigo em Espanhol | IBECS | ID: ibc-189866

RESUMO

El objetivo del presente estudio fue evaluar las concentraciones valle (Cpvalle) y la pauta posológica de tacrolimus tras la conversión de Prograf o Advagraf a Envarsus (nueva forma farmacéutica con tecnología Meltdose que mejora la absorción de fármacos liposolubles) en pacientes con trasplante renal estable, y su función renal. Se seleccionaron los pacientes trasplantados renales estables que fueron convertidos a Envarsus. Se definieron dos periodos: basal y conversión (Envarsus), y se estratificaron en función de la forma farmacéutica utilizada en el periodo basal. Se incluyeron 61 pacientes (24 con Advagraf y 37 con Prograf), con una edad media de 52 años. El tiempo medio postrasplante en el momento de la conversión a Envarsus fue de 76,3 meses y el seguimiento medio en el periodo basal y conversión fue de 10,1 y 11,6 meses, respectivamente. En el grupo Prograf y Envarsus las medianas Cpvalle fueron 6,6 vs 6,4 ng/ml (p = 0,636), con una dosis diaria media que disminuyó significativamente de 3 a 2 mg (p < 0,001), respectivamente, manteniendo el filtrado renal. Las medianas Cpvalle en los grupos Advagraf y Envarsus fueron 5,7 y 6,3 ng/ml (p = 0,07), con una mediana de dosis diaria de 7 y 4 mg (p < 0,001), respectivamente, e igual función renal. En pacientes trasplantados renales estables la conversión de Advagraf a Envarsus ha permitido reducir la dosis de tacrolimus un 42,9% y la de Prograf un 33,3% para mantener unas Cpvalle similares, sin que se altere la función renal


The aim of this study was to evaluate the trough concentrations (Cptrough) and the tacrolimus dosage regimen after the conversion of Prograf or Advagraf to Envarsus (new pharmaceutical form with MeltDose technology that improves the absorption of fat-soluble drugs) in patients with stable renal transplantation, and their renal function. We selected stable renal transplant patients who were converted to Envarsus. Two periods were defined: Baseline and Conversion (Envarsus) and they were stratified according to the pharmaceutical form used in the Baseline period. Sixty-one patients were included (24 with Advagraf and 37 with Prograf), with an average age of 52 years. The mean post-transplant time at the time of conversion to Envarsus was 76.3 months and the mean follow-up in the Baseline and Conversion period was 10.1 months and 11.6 months, respectively. In the Prograf and Envarsus group, the Cptrough medians were 6.6 vs 6.4 ng/mL (P = .636), with a mean daily dose that decreased significantly from 3 mg to 2 mg (P < .001), respectively, maintaining the filtration rate. The median Cptrough values in the Advagraf and Envarsus groups were 5.7 ng/mL and 6.3 ng/mL (P=.07), with a median daily dose of 7 mg and 4 mg (P<.001), respectively, and the same renal function. In stable renal transplant patients, the conversion from Advagraf to Envarsus has allowed the dose of tacrolimus to be reduced by 42.9% and, in the case of Prograf, by 33.3%, maintaining similar Cptrough values, without renal function being altered


Assuntos
Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Tacrolimo/uso terapêutico , Transplante de Rim , Tacrolimo/farmacocinética , Estudos Retrospectivos , Disponibilidade Biológica
16.
FASEB J ; 33(12): 13367-13385, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31553893

RESUMO

Heme is an essential molecule synthetized through a broadly conserved 8-step route that has been lost in trypanosomatid parasites. Interestingly, Leishmania reacquired by horizontal gene transfer from γ-proteobacteria the genes coding for the last 3 enzymes of the pathway. Here we show that intracellular amastigotes of Leishmania major can scavenge heme precursors from the host cell to fulfill their heme requirements, demonstrating the functionality of this partial pathway. To dissect its role throughout the L. major life cycle, the significance of L. major ferrochelatase (LmFeCH), the terminal enzyme of the route, was evaluated. LmFeCH expression in a heterologous system demonstrated its activity. Knockout promastigotes lacking lmfech were not able to use the ferrochelatase substrate protoporphyrin IX as a source of heme. In vivo infection of Phlebotomus perniciosus with knockout promastigotes shows that LmFeCH is not required for their development in the sandfly. In contrast, the replication of intracellular amastigotes was hampered in vitro by the deletion of lmfech. However, LmFeCH-/- parasites produced disease in a cutaneous leishmaniasis murine model in a similar way as control parasites. Therefore, although L. major can synthesize de novo heme from macrophage precursors, this activity is dispensable being an unsuited target for leishmaniasis treatment.-Orrego, L. M., Cabello-Donayre, M., Vargas, P., Martínez-García, M., Sánchez, C., Pineda-Molina, E., Jiménez, M., Molina, R., Pérez-Victoria, J. M. Heme synthesis through the life cycle of the heme auxotrophic parasite Leishmania major.


Assuntos
Ferroquelatase/metabolismo , Heme/biossíntese , Leishmania major/crescimento & desenvolvimento , Leishmaniose Cutânea/metabolismo , Proteínas de Protozoários/metabolismo , Psychodidae/metabolismo , Virulência , Sequência de Aminoácidos , Animais , Coproporfirinogênio Oxidase/metabolismo , Feminino , Ferroquelatase/química , Ferroquelatase/genética , Leishmaniose Cutânea/parasitologia , Macrófagos/metabolismo , Macrófagos/parasitologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Conformação Proteica , Protoporfirinogênio Oxidase/metabolismo , Proteínas de Protozoários/química , Proteínas de Protozoários/genética , Psychodidae/parasitologia , Homologia de Sequência
17.
Eur J Pharm Sci ; 138: 105016, 2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31356869

RESUMO

We aim to optimize the paediatric dosing regimen of isoniazid, rifampicin and pyrazinamide for the first-line treatment of tuberculosis, based on a fixed dose combination (FDC) mini-tablet using simulations. An optimization problem was set up to determine the 3 strengths of the drugs of the mini-tablet and 4 cutoff points that define the weight bands of a dosing chart, simultaneously. Using Monte Carlo simulations, first, exposure targets were determined for the 3 drugs, from published population pharmacokinetic models for adults, assuming that the approved doses for adults are de facto efficacious. Then optimal strengths and cutoff points were determined by matching children exposures generated from population pharmacokinetic models to the adults targets. The optimal dosing strengths of the FDC tablet were found to be 95 mg of rifampicin, 200 mg of pyrazinamide and 75 mg of isoniazid, and the 4 body weight bands for 1 to 4 mini-tablets, respectively were: 4 to 8 kg, 8 to 12 kg, 12 to 18 kg and 18 to 28 kg. Children with body weight ≥ 28 kg will be treated with adult dosages. The higher doses proposed were evaluated to be much closer to the adult targets compared to the existing recommended by WHO paediatric doses.


Assuntos
Antituberculosos/administração & dosagem , Comprimidos/administração & dosagem , Tuberculose/tratamento farmacológico , Adulto , Criança , Humanos , Isoniazida/administração & dosagem , Pirazinamida/administração & dosagem , Rifampina/administração & dosagem
18.
PLoS Negl Trop Dis ; 13(5): e0007288, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-31071080

RESUMO

BACKGROUND: Leishmania development in the sand fly gut leads to highly infective forms called metacyclic promastigotes. This process can be routinely mimicked in culture. Gene expression-profiling studies by transcriptome analysis have been performed with the aim of studying promastigote forms in the sand fly gut, as well as differences between sand fly-and culture-derived promastigotes. FINDINGS: Transcriptome analysis has revealed the crucial role of the microenvironment in parasite development within the sand fly gut because substantial differences and moderate correlation between the transcriptomes of cultured and sand fly-derived promastigotes have been found. Sand fly-derived metacyclics are more infective than metacyclics in culture. Therefore, some caution should be exercised when using cultured promastigotes, depending on the experimental design. The most remarkable examples are the hydrophilic acidic surface protein/small endoplasmic reticulum protein (HASP/SHERP) cluster, the glycoprotein 63 (gp63), and autophagy genes, which are up-regulated in sand fly-derived promastigotes compared with cultured promastigotes. Because HASP/SHERP genes are up-regulated in nectomonad and metacyclic promastigotes in the sand fly, the encoded proteins are not metacyclic specific. Metacyclic promastigotes are distinguished by morphology and high infectivity. Isolating them from the sand fly gut is not exempt from technical difficulty, because other promastigote forms remain in the gut even 15 days after infection. Leishmania major procyclic promastigotes within the sand fly gut up-regulate genes involved in cell cycle regulation and glucose catabolism, whereas metacyclics increase transcript levels of fatty acid biosynthesis and ATP-coupled proton transport genes. Most parasite's signal transduction pathways remain uncharacterized. Future elucidation may improve understanding of parasite development, particularly signaling molecule-encoding genes in sand fly versus culture and between promastigote forms in the sand fly gut. CONCLUSIONS: Transcriptome analysis has been demonstrated to be technically efficacious to study differential gene expression in sand fly gut promastigote forms. Transcript and protein levels are not well correlated in these organisms (approximately 25% quantitative coincidences), especially under stress situations and at differentiation processes. However, transcript and protein levels behave similarly in approximately 60% of cases from a qualitative point of view (increase, decrease, or no variation). Changes in translational efficiency observed in other trypanosomatids strongly suggest that the differences are due to translational regulation and regulation of the steady-state protein levels. The lack of low-input sample strategies does not allow translatome and proteome analysis of sand fly-derived promastigotes so far.


Assuntos
Leishmania/crescimento & desenvolvimento , Leishmania/genética , Proteínas de Protozoários/genética , Psychodidae/parasitologia , Animais , Trato Gastrointestinal/parasitologia , Genômica , Leishmania/classificação , Leishmania/isolamento & purificação , Proteínas de Protozoários/metabolismo , Transcriptoma
19.
Nefrologia ; 39(5): 506-512, 2019.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-30850218

RESUMO

The aim of this study was to evaluate the trough concentrations (Cptrough) and the tacrolimus dosage regimen after the conversion of Prograf or Advagraf to Envarsus (new pharmaceutical form with MeltDose technology that improves the absorption of fat-soluble drugs) in patients with stable renal transplantation, and their renal function. We selected stable renal transplant patients who were converted to Envarsus. Two periods were defined: Baseline and Conversion (Envarsus) and they were stratified according to the pharmaceutical form used in the Baseline period. Sixty-one patients were included (24 with Advagraf and 37 with Prograf), with an average age of 52years. The mean post-transplant time at the time of conversion to Envarsus was 76.3months and the mean follow-up in the Baseline and Conversion period was 10.1months and 11.6months, respectively. In the Prograf and Envarsus group, the Cptrough medians were 6.6 vs 6.4 ng/mL (P=.636), with a mean daily dose that decreased significantly from 3mg to 2mg (P<.001), respectively, maintaining the filtration rate. The median Cptrough values in the Advagraf and Envarsus groups were 5.7ng/mL and 6.3ng/mL (P=.07), with a median daily dose of 7mg and 4mg (P<.001), respectively, and the same renal function. In stable renal transplant patients, the conversion from Advagraf to Envarsus has allowed the dose of tacrolimus to be reduced by 42.9% and, in the case of Prograf, by 33.3%, maintaining similar Cptrough values, without renal function being altered.


Assuntos
Imunossupressores/administração & dosagem , Imunossupressores/sangue , Rim/fisiologia , Tacrolimo/administração & dosagem , Tacrolimo/sangue , Transplantados , Disponibilidade Biológica , Preparações de Ação Retardada , Esquema de Medicação , Feminino , Seguimentos , Humanos , Imunossupressores/farmacocinética , Transplante de Rim , Masculino , Pessoa de Meia-Idade , Nefrologistas , Estudos Retrospectivos , Tacrolimo/farmacocinética , Fatores de Tempo
20.
Clin Infect Dis ; 69(2): 251-258, 2019 07 02.
Artigo em Inglês | MEDLINE | ID: mdl-30357373

RESUMO

BACKGROUND: On the Indian subcontinent, visceral leishmaniasis (VL) incidence is on track to reach elimination goals by 2020 in nearly all endemic districts. Although not included in official targets, previous data suggest post-kala-azar dermal leishmaniasis (PKDL) patients can act as an infection reservoir. METHODS: We conducted xenodiagnosis on 47 PKDL patients and 15 VL patients using laboratory-reared Phlebotomus argentipes. In direct xenodiagnosis, flies were allowed to feed on the patient's skin for 15 minutes. For indirect xenodiagnosis, flies were fed through a membrane on the patient's blood. Five days later, blood-fed flies were dissected and examined by microscopy and/or polymerase chain reaction (PCR). A 3-mm skin snip biopsy (PKDL) or venous blood (VL) was processed by quantitative PCR. RESULTS: Twenty-seven PKDL patients (57.4%) had positive results by direct and/or indirect xenodiagnosis. Direct was significantly more sensitive than indirect xenodiagnosis (55.3% vs 6.4%, P < .0001). Those with positive xenodiagnosis had median skin parasite loads >1 log10 unit higher than those with negative results (2.88 vs 1.66, P < .0001). In a multivariable model, parasite load, nodular lesions, and positive skin microscopy were significantly associated with positive xenodiagnosis. Blood parasite load was the strongest predictor for VL. Compared to VL, nodular PKDL was more likely and macular PKDL less likely to result in positive xenodiagnosis, but neither difference reached statistical significance. CONCLUSIONS: Nodular and macular PKDL, and VL, can be infectious to sand flies. Active PKDL case detection and prompt treatment should be instituted and maintained as an integral part of VL control and elimination programs.


Assuntos
Reservatórios de Doenças , Transmissão de Doença Infecciosa , Insetos Vetores/parasitologia , Leishmania donovani/isolamento & purificação , Leishmaniose Cutânea/transmissão , Leishmaniose Visceral/transmissão , Psychodidae/parasitologia , Adulto , Animais , Feminino , Humanos , Insetos Vetores/fisiologia , Leishmaniose Cutânea/parasitologia , Leishmaniose Visceral/parasitologia , Masculino , Pessoa de Meia-Idade , Psychodidae/fisiologia
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