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BACKGROUND: To report the risk of exudation recurrence and long-term outcomes in patients with choroidal neovascularization secondary to angioid streaks, according to its morphology and characteristics by optical coherence tomography angiography. METHODS: Retrospective analysis of electronic medical records from three hospitals. We enrolled patients with a clinical diagnosis of angioid streaks choroidal neovascularization that had a minimum follow-up of 12 months. From each record, we extracted general demographic data, best corrected visual acuity (baseline, before and after each disease recurrence and last on file), type of treatment, time between last intravitreal injection and disease recurrence, and classification of the neovascular lesion morphology by optical coherence tomography, and optical coherence tomography angiography. Patients with myopic choroidal neovascularization were used as controls. Interobserver agreement was assessed with a Cohen-Kappa test. The Odds ratio was calculated with a chi2 test for significance. Visual acuity change through time was evaluated with an ANOVA for repeated measurements with an alpha value of 0.05 for statistical significance. RESULTS: We enrolled 30 patients in the study group and 14 in the control group. In the study group, the baseline and final BCVA were 0.861 ± 0.59 and 1.095 ± 0.61 logMAR (p = 0.1) respectively. CONTROL GROUP: 1.045 ± 0.57 and 0.617 ± 0.53 logMAR (p < 0.05). In the study group, the predominant CNV type by OCTA was mixed (37%), and interlacing (57%) in the control group. Mixed and cog-wheel patterns at baseline had increased Odds for recurrence in the study group (p = 0.09). Patients in the study group required more intravitreal injections on each recurrence episode to achieve disease control (3.5 ± 1.5 vs.1.4 ± 0.2, p < 0.01). CONCLUSIONS: The benefits of anti-VEGF treatment are lost over time in patients with angioid streaks and CNV. Lesion characteristics by optical coherence tomography angiography could help physicians predict the risk of recurrence. TRIAL REGISTRATION: Retrospective registered, and IRB approved.
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The PumAB type-II toxin-antitoxin (TA) system is encoded by pumAB genes that are organized into an operon. This system is encoded by the pUM505 plasmid, isolated from a Pseudomonas aeruginosa clinical strain. The pumA gene encodes a putative RelE toxin protein (toxic component), whereas the pumB gene encodes a putative HTH antitoxin protein. The expression of the PumAB system in Escherichia coli confers plasmid stability. In addition, PumA toxin overexpression in P. aeruginosa possesses the capability to increase bacterial virulence, an effect that is neutralized by the PumB antitoxin. The aim of this study was to establish the mechanism of regulation of the PumAB toxin-antitoxin system from pUM505. By an in silico analysis of the putative regulatory elements, we identified two putative internal promoters, PpumB and PpumB-AlgU (in addition to the already reported PpumAB), located upstream of pumB. By RT-qPCR assays, we determined that the pumAB genes are transcribed differentially, in that the mRNA of pumB is more abundant than the pumA transcript. We also observed that pumB could be expressed individually and that its mRNA levels decreased under oxidative stress, during individual expression as well as co-expression of pumAB. However, under stressful conditions, the pumA mRNA levels were not affected. This suggests the negative regulation of pumB by stressful conditions. The PumB purified protein was found to bind to a DNA region located between the PpumAB and the pumA coding region, and PumA participates in PumB binding, suggesting that a PumA-PumB complex co-regulates the transcription of the pumAB operon. Interestingly, the pumA mRNA levels decreased after incubation in vitro with PumB protein. This effect was repressed by ribonuclease inhibitors, suggesting that PumB could function as an RNAse toward the mRNA of the toxin. Taken together, we conclude that the PumAB TA system possesses multiple mechanisms to regulate its expression, as well as that the PumB antitoxin generates a decrease in the mRNA toxin levels, suggesting an RNase function. Our analysis provides new insights into the understanding of the control of TA systems from mobile plasmid-encoded genes from a human pathogen.
Assuntos
Antitoxinas , Toxinas Bacterianas , Sistemas Toxina-Antitoxina , Humanos , Antitoxinas/genética , Antitoxinas/metabolismo , Toxinas Bacterianas/genética , Sistemas Toxina-Antitoxina/genética , Proteínas Reguladoras de Apoptose/metabolismo , Escherichia coli/genética , Escherichia coli/metabolismo , Endorribonucleases/genética , Endorribonucleases/metabolismo , RNA Mensageiro , Ribonucleases/genética , Ribonucleases/metabolismo , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Regulação Bacteriana da Expressão GênicaRESUMO
INTRODUCTION: Epileptic seizures can be associated with peri-ictal heart rhythm disorders and even sudden death (SUDEP). Few paediatric studies have been conducted on the subject. AIM: To determine heart rhythm disorders in paediatric patients with epilepsy who were studied with video-electroencephalogram (video-EEG). METHODS: Prospective, observational study in patients under 18 years of age admitted for video-EEG at the Hospital Clinico Red de Salud UC-Christus, Santiago, Chile. A neurological and cardiological evaluation and electrocardiogram (ECG) were performed, in addition to a Holter ECG simultaneously with the video-EEG. RESULTS: Twenty-five patients were studied, 12 with refractory epilepsies, 23/25 focal and 20 on polytherapy. Altogether 768 hours of video-EEG were recorded, including 281 seizures in 15 patients: 157 clinical and 103 generalised. There were no serious arrhythmias, only non-specific or probably benign disorders, mainly incomplete right bundle branch block in 11 patients, which were more frequent in refractory epilepsies (p<0.036). Heart rate variation occurred mainly in seizures >30 seconds. No patient presented SUDEP. CONCLUSIONS: This is the first prospective study, with a new technique, using video-EEG and Holter ECG simultaneously in paediatrics. Despite the high number of seizures and refractory patients, we found no serious heart rhythm disorders, consistent with the clinical evaluation. Right bundle branch block is considered a non-pathological cardiological finding, but was highly prevalent in our sample compared to the normal population, especially in refractory epilepsy. Given that this is a serious event in epilepsy, it is important to further investigate such studies to assess preventive measures.
TITLE: Alteraciones electrocardiográficas periictales en pacientes pediátricos con epilepsia. Un estudio prospectivo.Introducción. Las crisis epilépticas pueden asociarse a alteraciones del ritmo cardíaco periictales e incluso a muerte súbita (SUDEP). Existen escasos estudios pediátricos al respecto. Objetivo. Determinar las alteraciones del ritmo cardíaco en pacientes pediátricos con epilepsia estudiados con videoelectroencefalograma (video-EEG). Métodos. Estudio prospectivo, observacional, en pacientes menores de 18 años ingresados para video-EEG en el Hospital Clínico Red de Salud UC-Christus, Santiago, Chile. Se realizó una evaluación neurológica y cardiológica, electrocardiograma (ECG) y Holter ECG simultáneo al video-EEG. Resultados. Se estudió a 25 pacientes, 12 con epilepsias refractarias, 23/25 focales y 20 en tratamiento con politerapia. Se registraron 768 horas de video-EEG, incluyendo 281 crisis epilépticas en 15 pacientes: 157 clínicas y 103 generalizadas. No hubo arritmias graves; sólo alteraciones inespecíficas o probablemente benignas, principalmente bloqueo incompleto de la rama derecha en 11 pacientes, más frecuente en las epilepsias refractarias (p menor de 0,036). La variación de la frecuencia cardíaca ocurrió principalmente en crisis > 30 segundos. Ningún paciente ha presentado SUDEP. Conclusiones. Éste es el primer estudio prospectivo, con una nueva técnica, usando simultáneamente video-EEG y Holter ECG en pediatría. Pese al alto número de crisis y pacientes refractarios, no encontramos alteraciones graves del ritmo cardíaco, en concordancia con la evaluación clínica. El bloqueo de la rama derecha se considera un hallazgo cardiológico no patológico, pero tuvo una alta prevalencia en nuestra muestra, comparada con la población normal, especialmente en la epilepsia refractaria. Dado que la SUDEP es un evento grave en la epilepsia, es importante ahondar más en este tipo de estudios para evaluar medidas preventivas.
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Arritmias Cardíacas/fisiopatologia , Eletroencefalografia , Epilepsia/fisiopatologia , Arritmias Cardíacas/complicações , Criança , Pré-Escolar , Eletroencefalografia/métodos , Epilepsia/complicações , Feminino , Humanos , Masculino , Estudos Prospectivos , Gravação em VídeoRESUMO
Pseudomonas aeruginosa plasmid pUM505 possesses a pathogenicity island that contains the pumAB genes that encode products with sequence similarity to Toxin-Antitoxin (TA) modules. RT-PCR assays on the overlapping regions of the pumAB genes generated a bicistronic messenger RNA, suggesting that they form an operon. When the pumAB genes were cloned into the pJET vector, recombinant plasmid pJET-pumAB was maintained under nonselective conditions in Escherichia coli cells after six daily subcultures, whereas pJET without pumAB genes was lost. These data indicate that pumAB genes confer post-segregational plasmid stability. In addition, overexpression of the PumA protein in the E. coli BL21 strain resulted in a significant growth inhibition, while BL21 co-expressing the PumA and PumB proteins did not show growth inhibition. These results indicate that pumAB genes encode a TA system where the PumB protein counters the toxic effects of the PumA toxin. Furthermore, P. aeruginosa PAO1 transformants with the pumA gene increased Caenorhabditis elegans and mouse mortality rate and improved mouse organ invasion, effects neutralized by the PumB protein. Moreover, purified recombinant His-PumA protein decreased the viability of C. elegans, indicating that the PumA protein could acts as a toxin. These results indicate that PumA has the potential to promoter the PAO1 virulence against C. elegans and mice when is expressed in absence of PumB. This is the first description, to our knowledge, of a plasmid-encoded TA system that confers plasmid stability and encoded a toxin with the possible ability to increase the P. aeruginosa virulence.
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Toxinas Bacterianas/genética , Toxinas Bacterianas/toxicidade , Genes Bacterianos/genética , Plasmídeos/genética , Pseudomonas aeruginosa/genética , Sistemas Toxina-Antitoxina/genética , Fatores de Virulência/genética , Animais , Antitoxinas/genética , Proteínas de Bactérias/genética , Sequência de Bases , Caenorhabditis elegans/efeitos dos fármacos , Modelos Animais de Doenças , Escherichia coli/efeitos dos fármacos , Escherichia coli/genética , Escherichia coli/crescimento & desenvolvimento , Regulação Bacteriana da Expressão Gênica , Vetores Genéticos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Óperon/genética , Infecções por Pseudomonas/microbiologia , Infecções por Pseudomonas/mortalidade , Pseudomonas aeruginosa/patogenicidade , RNA Bacteriano/análise , Proteínas Recombinantes/genética , Análise de Sequência , Virulência/genéticaRESUMO
Los quistes foliculares pigmentados son quistes epiteliales muy infrecuentes. Se describen como lesiones papulares pigmentadas, de carácter benigno, que generalmente se ubican en la cabeza o cuello. Surgen de manera única, siendo la variante múltiple aún menos frecuente. A continuación, se presenta el caso de un hombre joven, con antecedentes de VIH en terapia antiretroviral, quien consultó por la presencia de múltiples lesiones perianales, asintomáticas, de larga data, cuyo resultado histológico resultó compatible con: quistes pigmentados foliculares múltiples.
Pigmented follicular cysts are a very rare epithelial cysts. They are described as a benign papular lesion, that is usually located in the head or neck. They arise as unique, being the multiple variant even less frequent. We present the case of a young man with a history of HIV in antiretroviral therapy, who consulted for the presence of multiple, long-term asymptomatic perianal lesions whose histological result was: compatible with multiple follicular pigmented cysts.
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The most commonly used drugs against pain act by inhibiting the cyclooxygenases (COXs). Metamizol (dipyrone) inhibits the COXs and is widely used in Europe and Latin America as a non-opioid analgesic. One target of metamizol and other non-opioid analgesics is the periaqueductal grey matter (PAG), where they trigger descending inhibition of spinal nociceptive transmission. Also, cannabinoids exert an analgesic action at several structures in the peripheral and central nervous system, including the PAG. The present study investigates whether the antinociceptive action of metamizol in the lateral-ventrolateral (LVL) PAG during inflammation is related to endocannabinoids. In anaesthetized rats, unitary action potentials were recorded from spinal nociceptive neurons with receptive fields in the ipsilateral hind paw. Inflammation of the paw induced neuronal hyperexcitability, which was attenuated by intra-LVL-PAG microinjection of metamizol either at the beginning of inflammation or when hyperexcitability was fully established. In both cases, the antinociceptive effect of metamizol was reduced by a microinjection of AM251, an antagonist at the CB1 cannabinoid receptor, either into the LVL-PAG or into the rostral ventromedial medulla (RVM). The RVM is a downstream structure that funnels PAG-derived descending inhibition into the spinal cord. These results show that endocannabinoids and their CB1 receptor (1) contribute at the LVL-PAG to the antinociceptive effects of metamizol, and possibly other non-opioid analgesics; and (2) participate in the PAG-derived activation of RVM descending antinociceptive influences.
Assuntos
Anti-Inflamatórios não Esteroides/uso terapêutico , Moduladores de Receptores de Canabinoides/metabolismo , Dipirona/uso terapêutico , Endocanabinoides , Hiperalgesia/tratamento farmacológico , Inflamação/tratamento farmacológico , Bulbo/efeitos dos fármacos , Substância Cinzenta Periaquedutal/efeitos dos fármacos , Potenciais de Ação/efeitos dos fármacos , Animais , Anti-Inflamatórios não Esteroides/farmacologia , Dipirona/farmacologia , Hiperalgesia/metabolismo , Inflamação/metabolismo , Masculino , Bulbo/metabolismo , Microinjeções , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Nociceptores/efeitos dos fármacos , Medição da Dor/efeitos dos fármacos , Substância Cinzenta Periaquedutal/metabolismo , Piperidinas/farmacologia , Pirazóis/farmacologia , Ratos , Ratos Sprague-Dawley , Receptor CB1 de Canabinoide/antagonistas & inibidoresRESUMO
Between 1989 and 2002, 178 renal transplants were performed in 168 pediatric patients in Chile. The mean age was 10.9 +/- 3.7 years (range 1 to 17.9). End-state renal disease etiologies were: congenital renal hypoplasia/dysplasia, chronic glomerulonephritis, and reflux nephropathy. Seventy received a graft from a living donor (LD), and 108 from a cadaveric donor (CD). Only 9% received antibody induction. Acute rejection episodes were reported in 76 patients: 38% in LD recipients and 48% in CD recipients (P = NS). One-, 3-, and 5-year graft survivals were 88%, 84%, and 76%, respectively, for LD and 86%, 79%, and 68% for CD recipients. Actuarial graft survival was significantly better among those patients with serum creatinine < 1 mg/dL at 1 year posttransplant compared with those with creatinine > 1 mg/dL (P < .05). The graft survival rate has improved from the first period (1989 to 1996) to the second period (1997 to 2002); (P = .05). Patient survival rates at 1, 3, and 5 years were 98%, 98%, and 98%, respectively, for LD, and 95%, 94%, and 94% for CD. Global height/age Z-score decreased from -0.7 at birth to -1.5 when dialysis started, and to -2.4 at the time of transplantation. The Z-score height/age at 1, 3, and 5 years posttransplantation was -2.25, -2.24, and -2.5. No significant differences were observed in transplant outcomes comparing patients younger than 7 years with those older ones. In conclusion, pediatric renal transplant has been performed in Chile with acceptable morbidity. The patient and graft survivals are similar to the reported international experience. In the last period there was a significant improvement in graft survival.
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Transplante de Fígado/fisiologia , Adolescente , Cadáver , Criança , Pré-Escolar , Feminino , Seguimentos , Sobrevivência de Enxerto , Humanos , Lactente , Nefropatias/cirurgia , Transplante de Fígado/mortalidade , Doadores Vivos , Masculino , Reoperação , Estudos Retrospectivos , Análise de Sobrevida , Fatores de Tempo , Doadores de TecidosRESUMO
UNLABELLED: An open, single arm, prospective clinical trial to assess the efficacy and safety of basiliximab (Simulect) combined with cyclosporine microemulsion (Neoral), steroids, and azathioprine was performed in four centers in Chile, two adult and two pediatric. The 23 patients who were enrolled were followed for 12 months. There were four acute rejection episodes (three adults and one child) and three graft losses (two adults and one child) during the study. Renal function in both adult and pediatric patients at 6 and 12 months was good. Basiliximab was well tolerated. The incidence of infections was low, with only one CMV infection. There were no deaths. CONCLUSIONS: The incidence of acute rejection episodes among renal allograft recipients treated with basiliximab is low, showing that the drug is well tolerated. In particular the number of CMV infections is extremely low.
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Anticorpos Monoclonais/uso terapêutico , Imunossupressores/uso terapêutico , Transplante de Rim/imunologia , Proteínas Recombinantes de Fusão , Adulto , Fatores Etários , Anticorpos Monoclonais/efeitos adversos , Azatioprina/uso terapêutico , Basiliximab , Criança , Ciclosporina/uso terapêutico , Quimioterapia Combinada , Emulsões , Rejeição de Enxerto/epidemiologia , Humanos , Imunossupressores/efeitos adversos , Transplante HomólogoRESUMO
Entamoeba histolytica causes amebic colitis and liver abscess in developing countries such as Mexico and India. Entamoeba dispar is morphologically identical but is not associated with disease. Here we determined the ploidy of E. histolytica and developed PCR-based methods for distinguishing field isolates of E. histolytica or E. dispar. Fluorescence in situ hybridization showed that E. histolytica trophozoites are diploid for five "single-copy" probes tested. Intergenic sequences between superoxide dismutase and actin 3 genes of clinical isolates of E. histolytica from the New and Old Worlds were identical, as were those of E. dispar. These results suggest a bottleneck or demographic sweep in entamoebae which infect humans. In contrast, E. histolytica and E. dispar genes encoding repeat antigens on the surface of trophozoites (Ser-rich protein) or encysting parasites (chitinase) were highly polymorphic. chitinase alleles suggested that the early axenized strains of E. histolytica, HM-1 from Mexico City, Mexico, and NIH-200 from Calcutta, India, are still present and that similar E. dispar parasites can be identified in both the New and Old Worlds. Ser-rich protein alleles, which suggested the presence of the HM-1 strain in Mexico City, included some E. histolytica genes that predicted Ser-rich proteins with very few repeats. These results, which suggest diversifying selection at chitinase and Ser-rich protein loci, demonstrate the usefulness of these alleles for distinguishing clinical isolates of E. histolytica and E. dispar.
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Entamoeba/genética , Entamebíase/epidemiologia , Actinas/genética , Sequência de Aminoácidos , Animais , Proteínas de Bactérias/genética , Sequência de Bases , Quitinases/genética , Demografia , Diploide , Entamoeba/citologia , Entamoeba histolytica/citologia , Entamoeba histolytica/genética , Humanos , Hibridização in Situ Fluorescente , Índia/epidemiologia , Íntrons , México/epidemiologia , Epidemiologia Molecular , Dados de Sequência Molecular , Reação em Cadeia da Polimerase/métodos , Alinhamento de Sequência , Homologia de Sequência de Aminoácidos , SerinaRESUMO
PURPOSE: Ureter is one of the best tissues for bladder augmentation. The amount of ureteral segment available is extremely variable among patients. We compared results in patients who underwent ureterocystoplasty with 2 ureters, 1 complete ureter or a distal segment only after transureteroureterostomy. MATERIALS AND METHODS: During a 6-year period we performed 32 ureterocystoplasties at 2 pediatric centers in Argentina (16) and Chile (16). Median patient age at surgery was 9 years (range 4 months to 20 years). Clinical presentation included urinary infection, hydronephrosis, incontinence and undiversion. The diagnosis was neurogenic bladder in 20 cases, infravesical obstruction in 7, massive reflux in 3 and ureterocele in 2. All patients had poor bladder compliance and vesicoureteral reflux. We used different options to augment the bladder, including 2 ureters in 5 patients, bilateral nephrectomy in 3, a complete duplex system in 1 and a bilateral partial ureter in 1 (group 1); a complete ureter in 14 (group 2), and a distal segment of ureter with transureteroureterostomy in 13 (group 3). When transureteroureterostomy was performed, a suprapubic tube remained indwelling for 2 weeks and a Double-J stent was placed for 1 month. Median followup was 16 months (range 4 months to 6 years). Clinical and radiological evaluations, including ultrasound, cystography, urodynamics, renal scan and renal function measurement, were done 4 months postoperatively and twice yearly thereafter as needed. RESULTS: We noted no significant difference in bladder capacity when 1 or 2 ureters were used. Median increase in bladder capacity in groups 1 and 2 was 375% (range 80 to 800). All patients who received a complete segment of ureter had clinical improvement, decreased hydronephrosis and resolution of reflux with improved bladder compliance. When a partial segment of ureter was used median capacity increased 230% (range 40 to 400) with clinical improvement in 12 patients (92.3%). Compliance improved, which led to longer intervals between clean intermittent catheterizations. No patient has needed repeat augmentation to date. CONCLUSIONS: There is a difference in median increased bladder capacity when a segment of distal ureter is used to augment the bladder versus 1 or 2 whole ureters. However, the use of distal ureter still represents a safe alternative for augmenting the bladder and simultaneously resolving massive reflux. Ureterocystoplasty is an excellent choice for increasing bladder capacity and improving bladder compliance despite the different amounts of tissue available.
Assuntos
Ureter/transplante , Bexiga Urinária/cirurgia , Derivação Urinária/métodos , Urodinâmica , Adolescente , Adulto , Criança , Pré-Escolar , Seguimentos , Humanos , Lactente , Complicações Pós-Operatórias/epidemiologia , Estudos RetrospectivosAssuntos
Disenteria Amebiana/parasitologia , Entamoeba histolytica/isolamento & purificação , Entamoeba/isolamento & purificação , Fezes/parasitologia , Animais , Sequência de Bases , Criança , Disenteria Amebiana/epidemiologia , Humanos , México/epidemiologia , Dados de Sequência Molecular , Homologia de Sequência do Ácido NucleicoRESUMO
Epidermal growth factor concentrations and amounts per ejaculate were determined in 162 infertile men and in a control group of 50 pregnancy-proven fertile men. No differences were found between those groups. The group of infertile patients was divided into sub-groups according to their sperm density. EGF values in those sub-groups were not significantly different. There was no correlation between EGF concentrations and the variables of the sperm analysis that were measured. All these data suggest that EGF is not an index of gonadal function. This may be due to the fact that probably most EGF in seminal plasma is of prostatic origin.
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Fator de Crescimento Epidérmico/metabolismo , Sêmen/metabolismo , Túbulos Seminíferos/fisiologia , Humanos , Infertilidade Masculina/metabolismo , Masculino , Radioimunoensaio , Túbulos Seminíferos/metabolismoAssuntos
Hematúria/diagnóstico , Criança , Eritrócitos/química , Feminino , Glomerulonefrite/complicações , Hematúria/etiologia , Humanos , MasculinoRESUMO
Along one year, cardiorespiratory resuscitation was done to 71 patients, aged 3 days to 10 years (median 3.5 month), in a pediatric intensive care unit. Although 39 patients (55%) recovered through first-stage treatment, in 17 the arrest was recurrent and they died in the following 24 hours. Only 12 (16.9%) children definitely survived. No patients requiring reanimation for more than 10 min, survived. Asystole was the most frequent arrhythmia (92%). There were only 4 cases of ventricular fibrillation, all occurred in patients with congenital heart disease, and no one recovered. Survivors have not evidence of neurological deficiencies, and only one died along one year follow up, because of congenital heart disease.
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Parada Cardíaca/mortalidade , Ressuscitação , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Recém-Nascido , Unidades de Terapia Intensiva Pediátrica , Masculino , Prognóstico , Estudos ProspectivosRESUMO
Se presentan 17 casos de fracturas de Le Fort correspondientes al 3.18% de las 533 fracturas maxilo-faciales observadas en el Instituto Traumatológico y Clínica de las Condes en los 6 años comprendidos entre 1980 y 1986. La casuística se clasifica de acuerdo a edad, sexo, etiología, tiempo de evolución, tipo de fractura según la tipificación clásica de Le Fort, presentación clínica, lesiones asociadas, mortalidad y tratamiento. Se discuten las alternativas terapéuticas, las que varían ampliamente e incluyen medidas generales como reposo y analgésicos y maniobras quirúrgicas de reducción, inmovilización y reconstrucción primaria. Se concluye que el óptimo manejo de éstos pacientes se basa sobre un diagnóstico correcto, un tratamiento quirúrgico oportuno y la adecuada atención de las complicaciones debidas al trauma