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1.
Rev Med Chil ; 151(2): 185-196, 2023 Feb.
Artigo em Espanhol | MEDLINE | ID: mdl-38293854

RESUMO

BACKGROUND: Severity assessment in adult patients with community-acquired pneumonia (CAP) allows to guide the site of care (ambulatory or hospitalization), diagnostic workup and treatment. AIM: To examine the performance of twelve severity predictive indexes (CRB65, CURB65, PSI, SCAP, SMART-COP, REA-ICU, ATS minor criteria, qSOFA, CALL, COVID GRAM, 4C, STSS) in adult patients hospitalized for CAP associated with SARS-CoV-2. MATERIAL AND METHODS: Prospective clinical study conducted between April 1 and September 30, 2020 in adult patients hospitalized for CAP associated with COVID-19 in a clinical hospital. The recorded adverse events were admission to the critical care unit, use of mechanical ventilation (MV), prolonged length of stay, and hospital mortality. The predictive rules were compared based on their sensitivity, specificity, predictive values, and area under the receiver operator characteristic (ROC) curve. RESULTS: Adverse events were more common and hospital stay longer in the high-risk categories of the different prognostic indices. CURB-65, PSI, SCAP, COVID GRAM, 4 C and STSS predicted the risk of death accurately. PSI, SCAP, ATS minor criteria, CALL and 4 C criteria were sensitive in predicting the risk of hospital mortality with high negative predictive value. The performance of different prognostic indices decreased significantly for the prediction of ICU admission, use of mechanical ventilation, and prolonged hospital length of stay. CONCLUSIONS: The performance of the prognostic indices differs significantly for the prediction of adverse events in immunocompetent adult patients hospitalized for community-acquired pneumonia associated with COVID-19.


Assuntos
COVID-19 , Infecções Comunitárias Adquiridas , Pneumonia , Adulto , Humanos , SARS-CoV-2 , Estudos Prospectivos , Prognóstico , Infecções Comunitárias Adquiridas/diagnóstico , Índice de Gravidade de Doença , Estudos Retrospectivos
2.
Rev Med Chil ; 149(8): 1107-1118, 2021 Aug.
Artigo em Espanhol | MEDLINE | ID: mdl-35319696

RESUMO

BACKGROUND: COVID-19 is a serious public health problem worldwide. AIM: To describe the clinical features of COVID-19 infection in adult patients consulting at an Emergency Service. MATERIAL AND METHODS: Descriptive prospective study of adult patients with suspected COVID-19 consulting between April 1 and July 31, 2020, at the Emergency Service of a clinical hospital. Clinical features, chronic comorbidities and demographic data were recorded. RESULTS: We assessed 2,958 adult patients aged 42 ± 15 years (46% males). In 54% of them, COVID-19 infection was confirmed, 40% had preexisting diseases, especially hypertension (15%), hypothyroidism (6%), diabetes (6%), asthma (5%) and obesity (6%). The main clinical manifestations associated with COVID-19 were general malaise (79%), anorexia (38%), myalgia (64%), fever (52%), headache (70%), anosmia/dysgeusia (60%), cough (56%), dyspnea (54%) and diarrhea (36%). In the multivariate analysis, the main clinical predictors of COVID-19 infection were malaise, anorexia, fever, myalgia, headache, nasal congestion, cough, expectoration, anosmia/dysgeusia, and history of close contact with a SARS-CoV-2 patient. Odynophagia and chest discomfort were negative predictors of the disease. The history of fever associated with anorexia, cough, and dyspnea or anosmia/dysgeusia and close contact with a SARS-CoV-2 patient had high specificity and positive predictive value for COVID-19 infection. CONCLUSIONS: Clinical features of COVID-19 infection were highly unspecific in these patients. Clinical diagnostic prediction models could be useful to support healthcare decision making at primary care setting.


Assuntos
COVID-19 , Serviços Médicos de Emergência , Adulto , COVID-19/complicações , COVID-19/diagnóstico , COVID-19/epidemiologia , Tosse/etiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , SARS-CoV-2
3.
Rev Med Chil ; 148(10): 1387-1397, 2020 Oct.
Artigo em Espanhol | MEDLINE | ID: mdl-33844708

RESUMO

BACKGROUND: In December 2019, coronavirus disease 2019 (COVID-19) emerged in Wuhan city and spread rapidly throughout China and the world. AIM: To describe the clinical features, risk factors, and predictors of hospitalization in adult patients treated for acute respiratory infections associated with coronavirus SARS-CoV-2. MATERIAL AND METHODS: Descriptive prospective study of ambulatory and hospitalized adult patients with confirmed COVID-19 attended between April 1 and May 31, 2020. Clinical features, chronic comorbidities and demographic data were recorded, and patients were followed for two months as outpatients. RESULTS: We assessed 1,022 adults aged 41 ± 14 years (50% men) with laboratory-confirmed COVID-19. One-third had comorbidities, specially hypertension (12.5%), hypothyroidism (6.6%), asthma (5.4%) and diabetes (4.5%). Hospital admission was required in 11%, 5.2% were admitted to critical care unit and 0.9% were connected to mechanical ventilation. Common symptoms included fatigue (55.4%), fever (52.5%), headache (68.6%), anosmia/dysgeusia (53.2%), dry cough (53.4%), dyspnea (27.4%) and diarrhea (35.5%). One third of patients reported persistence of symptoms at one-month follow-up, specially fatigue, cough and dyspnea. In the multivariate analysis, age, fever, cough, dyspnea and immunosuppression were associated with hospitalization and ICU admission. Age, male sex and moderate-severe dyspnea were associated with requirement of mechanical ventilation. The main predictors of prolonged clinical course were female sex, presence of comorbidities, history of dyspnea, cough, myalgia and abdominal pain. CONCLUSIONS: Clinical features of COVID-19 were highly unspecific. Prediction models for severity, will help medical decision making at the primary care setting.


Assuntos
COVID-19 , Infecções por Coronavirus , Adulto , Comorbidade , Infecções por Coronavirus/epidemiologia , Feminino , Hospitalização , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Estudos Retrospectivos , SARS-CoV-2
4.
Rev Med Chil ; 147(8): 983-992, 2019 Aug.
Artigo em Espanhol | MEDLINE | ID: mdl-31859962

RESUMO

BACKGROUND: C-reactive protein (CRP) is used to monitor patients' response during treatment of infectious diseases. Morbidity and mortality associated with community-acquired pneumonia (CAP) is high, particularly in hospitalized patients. Better risk prediction during hospitalization could improve management and ultimately reduce mortality rates. AIM: To evaluate CRP measured at admission and the third day of hospitalization as a predictor for adverse events in CAP. MATERIAL AND METHODS: A prospective cohort study of adult patients hospitalized with CAP at an academic hospital. Major adverse outcomes were admission to ICU, mechanical ventilation, prolonged hospital length of stay, hospital complications and 30-day mortality. Predictive associations between CRP (as absolute levels and relative decline at third day) and adverse events were analyzed. RESULTS: Eight hundred and twenty-three patients were assessed, 19% were admitted to ICU and 10.6% required mechanical ventilation. The average hospital stay was 8.8 ± 8.2 days, 42% had nosocomial complications and 8.1% died within 30 days. Ninety eight percent of patients had elevated serum CRP on admission to the hospital (18.1 ± 14.1 mg/dL). C-reactive protein measured at admission was associated with the risk of bacterial pneumonia, bacteremic pneumonia, septic shock and use of mechanical ventilation. Lack of CRP decline within three days of hospitalization was associated with high risk of complications, septic shock, mechanical ventilation and prolonged hospital stay. CONCLUSIONS: CRP responses at third day of hospital admission was a valuable predictor of adverse events in hospitalized CAP adult patients.


Assuntos
Proteína C-Reativa/análise , Infecções Comunitárias Adquiridas/sangue , Imunocompetência , Pneumonia/sangue , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Área Sob a Curva , Biomarcadores/sangue , Infecções Comunitárias Adquiridas/imunologia , Infecções Comunitárias Adquiridas/mortalidade , Feminino , Humanos , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Pneumonia/imunologia , Pneumonia/mortalidade , Valor Preditivo dos Testes , Prognóstico , Estudos Prospectivos , Fatores de Risco , Choque Séptico/sangue , Choque Séptico/mortalidade , Fatores de Tempo , Adulto Jovem
5.
Diagnostics (Basel) ; 14(9)2024 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-38732308

RESUMO

Standard troponin has long been pivotal in diagnosing coronary syndrome, especially Non-ST-Segment Elevation Myocardial Infarction (NSTEMI). The recent introduction of high-sensitivity troponin (hs-cTnI) has elevated it to the gold standard. Yet, its nuanced role in predicting angiographic lesions and clinical outcomes, notably in specific populations like obesity, remains underexplored. Aim: To evaluate the association between hs-cTnI magnitude in NSTEMI patients and angiographic findings, progression to acute heart failure, and its performance in obesity. Methods: Retrospective study of 208 NSTEMI patients at a large university center (2020-2023). Hs-cTnI values were assessed for angiographic severity, acute heart failure, and characteristics in the obese population. Data collected and diagnostic performance were evaluated using manufacturer-specified cutoffs. Results: 97.12% of patients had a single culprit vessel. Hs-cTnI elevation correlated with angiographic stenosis severity. Performance for detecting severe coronary disease was low, with no improvement using a higher cutoff. No association was found between hs-cTnI and the culprit vessel location. Hs-cTnI did not predict acute heart failure progression. In the obese population, hs-cTnI levels were higher, but acute heart failure occurred less frequently than in non-obese counterparts. Conclusions: In NSTEMI, hs-cTnI elevation is associated with significant stenosis, but not with location or acute heart failure. Obesity correlates with higher hs-cTnI levels but a reduced risk of acute heart failure during NSTEMI.

6.
Microbiol Spectr ; 11(2): e0258522, 2023 04 13.
Artigo em Inglês | MEDLINE | ID: mdl-36722967

RESUMO

Since the discovery of blaNDM-1, NDM ß-lactamases have become one of the most widespread carbapenemases worldwide. To date, 43 different NDM variants have been reported but some, such as blaNDM-23, have not been characterized in detail yet. Here, we describe the emergence of a novel blaNDM-23 allele from a blaNDM-1 ancestor and the multidrug resistance plasmid that has disseminated it through a Klebsiella pneumoniae ST437 clone in several Spanish hospitals. Between 2016 and 2019, 1,972 isolates were collected in an epidemiological survey for extended-spectrum-ß-lactamase (ESBL)-producing Klebsiella pneumoniae in the Comunitat Valenciana (Spain). Three carbapenem-resistant strains failed to be detected by carbapenemase-producing Enterobacteriaceae (CPE) screening tests. These isolates carried a blaNDM-23 gene. To characterize this gene, its emergence, and its dissemination, we performed antimicrobial susceptibility tests, hybrid sequencing with Illumina and Nanopore technologies, and phylogenetic analyses. The MICs of the blaNDM-23 allele were identical to those of the blaNDM-1 allele. The blaNDM-23 allele was found in 14 isolates on a 97-kb nonmobilizable, multidrug-resistant plasmid carrying 19 resistance genes for 9 different antimicrobial families. In this plasmid, the blaNDM-23 gene is in the variable region of a complex class 1 integron with a singular genetic environment. The small genetic distance between blaNDM-23-producing isolates reflects a 5-year-long clonal dispersion involving several hospitals and interregional spread. We have characterized the genomic and epidemiological contexts in the emergence and community spread of a new blaNDM-23 allele in a multidrug resistance (MDR) plasmid of Klebsiella pneumoniae. IMPORTANCE At a time when antimicrobial resistance has become one of the biggest concerns worldwide, the emergence of novel alleles and extremely drug-resistant plasmids is a threat to public health worldwide, especially when they produce carbapenem resistance in one of the most problematic pathogens, such as Klebsiella pneumoniae. We used genomic epidemiology to describe the emergence of a novel NDM-23 allele and identify it in a MDR plasmid that has disseminated through a K. pneumoniae ST437 clone in several hospitals in Spain. Using bioinformatic and phylogenetic analyses, we have traced the evolutionary and epidemiological route of the new allele, the hosting plasmid, and the strain that carried both of them from Pakistan to Spain. A better understanding of the NDM-producing K. pneumoniae populations and plasmids has made evident the spread of this clone through the region, enhancing the importance of genomic surveillance in the control of antimicrobial resistance.


Assuntos
Infecções por Klebsiella , Klebsiella pneumoniae , Humanos , Antibacterianos/farmacologia , Filogenia , Plasmídeos/genética , beta-Lactamases/genética , Carbapenêmicos , Farmacorresistência Bacteriana Múltipla/genética , Testes de Sensibilidade Microbiana , Infecções por Klebsiella/epidemiologia
7.
Cancers (Basel) ; 15(24)2023 Dec 18.
Artigo em Inglês | MEDLINE | ID: mdl-38136432

RESUMO

BACKGROUND: Central nervous system (CNS) neoplasms are highly frequent solid tumours in children and adolescents. While some studies have shown a rise in their incidence in Europe, others have not. Survival remains limited. We addressed two questions about these tumours in Spain: (1) Is incidence increasing? and (2) Has survival improved? METHODS: This population-based study included 1635 children and 328 adolescents from 11 population-based cancer registries with International Classification of Childhood Cancer Group III tumours, incident in 1983-2007. Age-specific and age-standardised (world population) incidence rates (ASRws) were calculated. Incidence time trends were characterised using annual percent change (APC) obtained with Joinpoint. Cases from 1991 to 2005 (1171) were included in Kaplan-Meier survival analyses, and the results were evaluated with log-rank and log-rank for trend tests. Children's survival was age-standardised using: (1) the age distribution of cases and the corresponding trends assessed with Joinpoint; and (2) European weights for comparison with Europe. RESULTS: ASRw 1983-2007: children: 32.7 cases/106; adolescents: 23.5 cases/106. The overall incidence of all tumours increased across 1983-2007 in children and adolescents. Considering change points, the APCs were: (1) children: 1983-1993, 4.3%^ (1.1; 7.7); 1993-2007, -0.2% (-1.9; 1.6); (2) adolescents: 1983-2004: 2.9%^ (0.9; 4.9); 2004-2007: -7.7% (-40; 41.9). For malignant tumours, the trends were not significant. 5-year survival was 65% (1991-2005), with no significant trends (except for non-malignant tumours). CONCLUSIONS: CNS tumour incidence in Spain was found to be similar to that in Europe. Rises in incidence may be mostly attributable to changes in the registration of non-malignant tumours. The overall malignant CNS tumour trend was compatible with reports for Southern Europe. Survival was lower than in Europe, without improvement over time. We provide a baseline for assessing current paediatric oncology achievements and incidence in respect of childhood and adolescent CNS tumours.

8.
Nutrients ; 14(12)2022 Jun 16.
Artigo em Inglês | MEDLINE | ID: mdl-35745229

RESUMO

INTRODUCTION: Obesity and overweight affect more than one-third of the world's population and pose a major public health problem. OBJECTIVE: To evaluate the impact of an educational intervention on dietary habits and physical exercise in patients with overweight admitted to departments of internal medicine, comprising a pre-discharge educational session with follow-up and reinforcement by telephone at 3, 6, and, 12 months post-discharge. Outcome variables were weight, systolic (SBP) and diastolic (DBP) blood pressures, health-related quality of life (HRQOL), hospital readmissions, emergency department visits, and death. METHOD: A randomized experimental study with a control group was performed in hospitalized non-diabetic adults aged ≥18 years with body mass index (BMI) ≥25 Kg/m2. RESULTS AND CONCLUSIONS: The final sample included 273 patients. At three months post-discharge, the intervention group had lower SBP and DPB and improved dietary habits (assessed using the Pardo Questionnaire) and VAS-assessed HRQOL in comparison to the control group but a worse EQ-5Q-5L-assessed HRQOL. There were no between-group differences in hospital readmissions, emergency department visits, or mortality at any time point. Both groups evidenced a progressive improvement over the three follow-up periods in weight, SBP, and dietary habits but a worsening of EQ-5D-5L-value-assessed HRQOL. DISCUSSION: The intervention group showed greater improvements over the short term, but between-group differences disappeared at 6 and 12 months. Weight loss and improvements in key outcomes were observed in both groups over the follow-up period. Further research is warranted to determine whether a minimum intervention with an educational leaflet, follow-up phone calls, and questionnaires on overweight-related healthy habits, as in the present control group, may be an equally effective strategy without specific individual educational input.


Assuntos
Sobrepeso , Qualidade de Vida , Adolescente , Adulto , Assistência ao Convalescente , Hospitais , Humanos , Sobrepeso/terapia , Alta do Paciente
9.
Artigo em Inglês | MEDLINE | ID: mdl-34769772

RESUMO

Overweight can be an additional problem in patients admitted to hospital. OBJECTIVE: To analyze gender differences in pre-admission dietary habits and physical exercise and in HRQoL at hospital discharge among hospitalized adults with overweight. METHODS: Cross-sectional study in non-diabetic patients enrolled in a clinical trial with body mass index (BMI) ≥ 25 Kg/m2 at admission. Bivariate analyses used Pearson's chi-square test and Fisher's exact test for qualitative variables and the Mann-Whitney test for numerical variables. RESULTS: The study included 148 males and 127 females. At admission, women had higher BMI (p = 0.016) than men and a larger percentage consumed drugs for depression (p = 0.030) and anxiety (p = 0.049), and followed a religion-based diet (p = 0.022). Pre-admission, women had healthier habits related to dietary caloric intake (p = 0.009) and greater adherence to recommendations for a healthy diet (p = 0.001). At discharge, women described worse self-perceived health (p = 0.044) and greater pain/discomfort (p = 0.004) in comparison to men. CONCLUSIONS: Pre-admission, women had better habits related to a healthy diet and did not differ from men in habits related to physical exercise but had a higher BMI. At discharge, women reported worse self-perceived health and greater pain/discomfort. These differences should be considered for the adequate clinical management of patients with overweight.


Assuntos
Obesidade , Qualidade de Vida , Adulto , Índice de Massa Corporal , Estudos Transversais , Dieta , Exercício Físico , Comportamento Alimentar , Feminino , Humanos , Masculino , Sobrepeso/epidemiologia
10.
Rev. méd. Chile ; 151(2): 185-196, feb. 2023. ilus, tab
Artigo em Espanhol | LILACS | ID: biblio-1522082

RESUMO

BACKGROUND: Severity assessment in adult patients with community-acquired pneumonia (CAP) allows to guide the site of care (ambulatory or hospitalization), diagnostic workup and treatment. AIM: To examine the performance of twelve severity predictive indexes (CRB65, CURB65, PSI, SCAP, SMART-COP, REA-ICU, ATS minor criteria, qSOFA, CALL, COVID GRAM, 4C, STSS) in adult patients hospitalized for CAP associated with SARS-CoV-2. MATERIAL AND METHODS: Prospective clinical study conducted between April 1 and September 30, 2020 in adult patients hospitalized for CAP associated with COVID-19 in a clinical hospital. The recorded adverse events were admission to the critical care unit, use of mechanical ventilation (MV), prolonged length of stay, and hospital mortality. The predictive rules were compared based on their sensitivity, specificity, predictive values, and area under the receiver operator characteristic (ROC) curve. RESULTS: Adverse events were more common and hospital stay longer in the high-risk categories of the different prognostic indices. CURB-65, PSI, SCAP, COVID GRAM, 4 C and STSS predicted the risk of death accurately. PSI, SCAP, ATS minor criteria, CALL and 4 C criteria were sensitive in predicting the risk of hospital mortality with high negative predictive value. The performance of different prognostic indices decreased significantly for the prediction of ICU admission, use of mechanical ventilation, and prolonged hospital length of stay. CONCLUSIONS: The performance of the prognostic indices differs significantly for the prediction of adverse events in immunocompetent adult patients hospitalized for community-acquired pneumonia associated with COVID-19.


Assuntos
Humanos , Adulto , Pneumonia , Infecções Comunitárias Adquiridas/diagnóstico , COVID-19 , Prognóstico , Índice de Gravidade de Doença , Estudos Prospectivos , Estudos Retrospectivos , SARS-CoV-2
11.
Int J Surg ; 51: 164-169, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29409791

RESUMO

OBJECTIVES: To assess the minimally invasive surgery into the step-up approach procedures as a standard treatment for severe acute pancreatitis and comparing its results with those obtained by classical management. METHODS: Retrospective cohort study comparative with two groups treated over two consecutive, equal periods of time were defined: group A, classic management with open necrosectomy from January 2006 to June 2010; and group B, management with the step-up approach with minimally invasive surgery from July 2010 to December 2014. RESULTS: In group A, 83 patients with severe acute pancreatitis were treated, of whom 19 underwent at least one laparotomy, and in 5 any minimally invasive surgery. In group B, 81 patients were treated: minimally invasive surgery was necessary in 17 cases and laparotomy in 3. Among operated patients, the time from admission to first interventional procedures was significantly longer in group B (9 days vs. 18.5 days; p = 0.042). There were no significant differences in Intensive Care Unit stay or overall stay: 9.5 and 27 days (group A) vs. 8.5 and 21 days (group B). Mortality in operated patients and mortality overall were 50% and 18.1% in group A vs 0% and 6.2% in group B (p < 0.001 and p = 0.030). CONCLUSIONS: The combination of the step-up approach and minimally invasive surgery algorithm is feasible and could be considered as the standard of treatment for severe acute pancreatitis. The mortality rate deliberately descends when it is used.


Assuntos
Procedimentos Cirúrgicos Minimamente Invasivos/métodos , Pancreatite/cirurgia , Doença Aguda , Humanos , Laparotomia/métodos , Tempo de Internação , Pancreatite/mortalidade , Estudos Retrospectivos
12.
Surgery ; 141(2): 173-8, 2007 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-17263972

RESUMO

BACKGROUND: Acute pancreatitis is one of the main causes of intra-abdominal hypertension, which may lead to multiple physiologic alterations. The aim of this study was to determine the relationship between acute pancreatitis and intra-abdominal hypertension, and to evaluate the utility of intra-abdominal pressure (IAP) as a marker of severity in acute pancreatitis. METHODS: From July 2002 to July 2004, 45 patients admitted for acute pancreatitis were included in this prospective, observational study. The diagnostic criteria for acute pancreatitis were compatible clinical manifestations and a 3-fold increase in serum amylase levels. Severe pancreatitis was defined as Apache II score >or=8. IAP was determined every 12 hours, and the maximum and the mean values were used for analysis and correlated with prognostic factors of acute pancreatitis. RESULTS: A statistical relationship was observed between maximum IAP and the typical prognostic factors of acute pancreatitis. Maximum IAP had a significant relationship with the computed tomography severity index and the number of complementary tests required. The maximum IAP was significantly greater in patients who died and in patients requiring vasoactive drugs, total parenteral nutrition, or operative treatment related to complications. The maximum IAP was also greater in patients who developed systemic inflammatory response syndrome, multiorgan failure, increase in number and/or volume of intra-abdominal collections, those who required aspiration of the necrosis for suspected infection, those who demonstrated the presence of microorganisms, and those with positive blood cultures. CONCLUSION: The maximum IAP is a useful, inexpensive, and easy method to measure prognostic marker of the evolution and complications of acute pancreatitis.


Assuntos
Cavidade Abdominal/fisiopatologia , Hipertensão/fisiopatologia , Pancreatite/fisiopatologia , Doença Aguda , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pressão , Índice de Gravidade de Doença
13.
J Photochem Photobiol B ; 85(1): 56-64, 2006 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-16765603

RESUMO

Photodynamic therapy (PDT) involves a non invasive treatment of small and superficial cancers using a photosensitive drug and light to kill tumoral cells. 5,10,15-meso-tri-(meta-O-beta-D-glucosyloxyphenyl)-20-phenylporphyrin [m-TPP(glu)3] is a new photosensitizer (PS) with more enhanced photocytotoxicity relative to 5,10,15,20-meso-tetra-(meta-hydroxyphenyl) chlorin [m-THPC] (Foscan). It was injected intravenously once to healthy rats at three different doses (0.25, 0.5 and 1 mg kg(-1)) and compared to m-THPC (0.3 mg kg(-1)). Pharmacokinetic parameters for both photosensitizers were derived from plasma concentration-time data using a non-compartmental analysis and a two-compartment pharmacokinetic model. m-TPP(glu)3 is more rapidly eliminated throughout the organism than m-THPC. Its mean plasma clearance is 19 mL h(-1) kg(-1) (6 mL h(-1) kg(-1) for m-THPC), and its mean residence time is 5h (20 h for m-THPC). The area under curve (AUC) and initial mean serum concentration (C0) were found to be proportional to the dose. As for Foscan, no metabolite of m-TPP(glu)3 was detected in plasma. The biodistribution study demonstrates that the most significant amount of m-TPP(glu)3 was concentrated in organs such as lung, liver and spleen which are rich in reticulo-endothelial cells. Maximum concentrations were reached in organs 14 h after IV administration. At 48 h, the photosensitizer was essentially eliminated from all organs. Because of its shorter elimination time, m-TPP(glu)3 is more attractive than m-THPC as a PDT agent since secondary side effects of shorter duration could be expected.


Assuntos
Glucosídeos/farmacocinética , Fotoquimioterapia , Fármacos Fotossensibilizantes/farmacocinética , Porfirinas/farmacocinética , Animais , Relação Dose-Resposta a Droga , Glucosídeos/administração & dosagem , Glucosídeos/sangue , Injeções Intravenosas , Masculino , Mesoporfirinas/administração & dosagem , Mesoporfirinas/farmacocinética , Mesoporfirinas/uso terapêutico , Fármacos Fotossensibilizantes/administração & dosagem , Fármacos Fotossensibilizantes/sangue , Porfirinas/administração & dosagem , Porfirinas/sangue , Ratos , Ratos Sprague-Dawley , Distribuição Tecidual
14.
Curr Drug Targets ; 17(14): 1626-1648, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26844561

RESUMO

The protein-folding problem has been extensively studied during the last fifty years. The understanding of the dynamics of global shape of a protein and the influence on its biological function can help us to discover new and more effective drugs to deal with diseases of pharmacological relevance. Different computational approaches have been developed by different researchers in order to foresee the threedimensional arrangement of atoms of proteins from their sequences. However, the computational complexity of this problem makes mandatory the search for new models, novel algorithmic strategies and hardware platforms that provide solutions in a reasonable time frame. We present in this revision work the past and last tendencies regarding protein folding simulations from both perspectives; hardware and software. Of particular interest to us are both the use of inexact solutions to this computationally hard problem as well as which hardware platforms have been used for running this kind of Soft Computing techniques.


Assuntos
Biologia Computacional/instrumentação , Proteínas/química , Algoritmos , Biologia Computacional/métodos , Humanos , Modelos Moleculares , Conformação Proteica , Dobramento de Proteína , Software
15.
Rev. méd. Chile ; 149(8): 1107-1118, ago. 2021. tab
Artigo em Espanhol | LILACS | ID: biblio-1389568

RESUMO

Background: COVID-19 is a serious public health problem worldwide. Aim: To describe the clinical features of COVID-19 infection in adult patients consulting at an Emergency Service. Material and Methods: Descriptive prospective study of adult patients with suspected COVID-19 consulting between April 1 and July 31, 2020, at the Emergency Service of a clinical hospital. Clinical features, chronic comorbidities and demographic data were recorded. Results: We assessed 2,958 adult patients aged 42 ± 15 years (46% males). In 54% of them, COVID-19 infection was confirmed, 40% had preexisting diseases, especially hypertension (15%), hypothyroidism (6%), diabetes (6%), asthma (5%) and obesity (6%). The main clinical manifestations associated with COVID-19 were general malaise (79%), anorexia (38%), myalgia (64%), fever (52%), headache (70%), anosmia/dysgeusia (60%), cough (56%), dyspnea (54%) and diarrhea (36%). In the multivariate analysis, the main clinical predictors of COVID-19 infection were malaise, anorexia, fever, myalgia, headache, nasal congestion, cough, expectoration, anosmia/dysgeusia, and history of close contact with a SARS-CoV-2 patient. Odynophagia and chest discomfort were negative predictors of the disease. The history of fever associated with anorexia, cough, and dyspnea or anosmia/dysgeusia and close contact with a SARS-CoV-2 patient had high specificity and positive predictive value for COVID-19 infection. Conclusions: Clinical features of COVID-19 infection were highly unspecific in these patients. Clinical diagnostic prediction models could be useful to support healthcare decision making at primary care setting.


Assuntos
Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Serviços Médicos de Emergência , COVID-19/complicações , COVID-19/diagnóstico , COVID-19/epidemiologia , Estudos Prospectivos , Tosse/etiologia , SARS-CoV-2
16.
Artigo em Inglês | MEDLINE | ID: mdl-15939678

RESUMO

This paper reports, for the first time, a reversed-phase high performance liquid chromatographic method for the simultaneous determination of seven glucoconjugated and non-glucoconjugated porphyrins and chlorins, using near infra-red fluorescence detection. Chromatographic separation was performed on nucleosil-CN analytical column using an isocratic acetonitrile-0.1% (w/v) TFA at pH 1.8 (55:45, v/v) as mobile phase. Wavelength gradient was employed for sensitive detection, porphyrins derivates were monitored at lambda(exc) = 440 nm and lambda(emi) = 680 nm; and chlorins derivates at lambda(exc) = 420 nm, lambda(emi) = 650 nm. The method was validated and applied to monitor the biodegradation of a tri glucoconjugated chlorin derivative, TPC(glu)3, in spiked samples of human serum.


Assuntos
Cromatografia Líquida de Alta Pressão/métodos , Glucosídeos/análise , Glucosídeos/isolamento & purificação , Porfirinas/análise , Porfirinas/isolamento & purificação , Humanos , Raios Infravermelhos , Porfirinas/sangue , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Espectrometria de Fluorescência/métodos
17.
J Photochem Photobiol B ; 81(3): 154-62, 2005 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-16169241

RESUMO

Glucoconjugated analogues of the meta-hydroxyphenyl porphyrin (m-THPP) and meta-hydroxyphenyl chlorin (m-THPC) has been recently synthesized. The characteristics of their triplet states have been determined with regard to their involvement in the photodynamic (PDT) efficiency. In the case of porphyrin derivatives, triplet quantum yields (Phi(T)) were ranging from 0.42 to 0.55 and triplet life times (tau(T)) from 1 to 5 micros. High reaction rate constants (k(q)) with molecular oxygen (k(q): 1.2-1.6 x 10(9)s(-1)) have been found. The triplet lifetimes of chlorin derivatives were about four times higher than those of porphyrins whereas the Phi(T) and k(q) values remained quite similar. Singlet oxygen yields of glucosylated and non-glucosylated porphyrins and chlorins were not significantly different within experimental errors (Phi(Delta)((1)O(2)): 0.41-0.58). Furthermore, it has been shown that glucoconjugated photosensitizers could undergo associations with the methyl-beta-cyclodextrin (Me-beta-CD) which exhibit high triplet lifetimes and singlet oxygen yields ranging from 0.27 to 0.48.


Assuntos
Ciclodextrinas/química , Glicoconjugados/química , Porfirinas/química , Dicroísmo Circular , Fármacos Fotossensibilizantes/química , Oxigênio Singlete/química , Espectrometria de Fluorescência , beta-Ciclodextrinas/química
18.
Rev. méd. Chile ; 148(10): 1387-1397, oct. 2020. tab
Artigo em Espanhol | LILACS | ID: biblio-1389230

RESUMO

BACKGROUND: In December 2019, coronavirus disease 2019 (COVID-19) emerged in Wuhan city and spread rapidly throughout China and the world. AIM: To describe the clinical features, risk factors, and predictors of hospitalization in adult patients treated for acute respiratory infections associated with coronavirus SARS-CoV-2. MATERIAL AND METHODS: Descriptive prospective study of ambulatory and hospitalized adult patients with confirmed COVID-19 attended between April 1 and May 31, 2020. Clinical features, chronic comorbidities and demographic data were recorded, and patients were followed for two months as outpatients. RESULTS: We assessed 1,022 adults aged 41 ± 14 years (50% men) with laboratory-confirmed COVID-19. One-third had comorbidities, specially hypertension (12.5%), hypothyroidism (6.6%), asthma (5.4%) and diabetes (4.5%). Hospital admission was required in 11%, 5.2% were admitted to critical care unit and 0.9% were connected to mechanical ventilation. Common symptoms included fatigue (55.4%), fever (52.5%), headache (68.6%), anosmia/dysgeusia (53.2%), dry cough (53.4%), dyspnea (27.4%) and diarrhea (35.5%). One third of patients reported persistence of symptoms at one-month follow-up, specially fatigue, cough and dyspnea. In the multivariate analysis, age, fever, cough, dyspnea and immunosuppression were associated with hospitalization and ICU admission. Age, male sex and moderate-severe dyspnea were associated with requirement of mechanical ventilation. The main predictors of prolonged clinical course were female sex, presence of comorbidities, history of dyspnea, cough, myalgia and abdominal pain. CONCLUSIONS: Clinical features of COVID-19 were highly unspecific. Prediction models for severity, will help medical decision making at the primary care setting.


Assuntos
Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Infecções por Coronavirus/epidemiologia , COVID-19 , Comorbidade , Estudos Prospectivos , Estudos Retrospectivos , SARS-CoV-2 , Hospitalização
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