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BACKGROUND: Toxoplasma gondii is traditionally known as a parasite of felids, with possible infection in intermediate hosts such as dogs and humans, and thus a disease of public health significance. Published data on the prevalence of toxoplasmosis in dogs and cats in Singapore is scanty, and this paper documents a suspect clinical case of toxoplasmosis in a free-roaming puppy trapped from an offshore island of Singapore. CASE PRESENTATION: A 12-week-old puppy presented with hindlimb weakness and sarcopenia, with rapidly progressing ascending paralysis and respiratory distress, one week after trapping. Toxoplasmosis was suspected after indirect fluorescence antibody testing (IFAT) revealed anti-T. gondii antibodies. The puppy responded quickly to clindamycin treatment and was discharged from hospital after 10 days. CONCLUSION: While rare and undocumented, veterinary clinicians in Singapore are advised to also include toxoplasmosis infection as a differential diagnosis in dogs presenting with similar clinical signs. This is especially so for dogs which have access to the outdoors.
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Enfermedades de los Gatos , Enfermedades de los Perros , Toxoplasma , Toxoplasmosis Animal , Humanos , Perros , Animales , Gatos , Toxoplasmosis Animal/diagnóstico , Toxoplasmosis Animal/tratamiento farmacológico , Toxoplasmosis Animal/epidemiología , Enfermedades de los Gatos/diagnóstico , Enfermedades de los Gatos/tratamiento farmacológico , Enfermedades de los Gatos/epidemiología , Singapur , Enfermedades de los Perros/diagnóstico , Enfermedades de los Perros/tratamiento farmacológico , Enfermedades de los Perros/epidemiología , Anticuerpos Antiprotozoarios , Estudios SeroepidemiológicosRESUMEN
BACKGROUND: Bacillus Calmette-Guerin (BCG) is a live attenuated strain of Mycobacterium bovis that has been used as immunotherapy against several malignancies. In particular, intravesical instillation of BCG has become a well-accepted adjuvant treatment for bladder cancer. BCG vascular infections are a rare complication of BCG therapy. Many aspects of these infections, including the presentations, risk factors, and treatment strategies, are poorly understood. Through a systematic review of the existing literature, we aimed to identify potential associations between this condition and patient characteristics, presentations, its treatments, and outcomes. METHODS: We searched the PubMed, MEDLINE, and Embase databases for cases of BCG vascular infections from inception to June 2021. English-language reports of BCG vascular infections were included. RESULTS: A total of 74 cases of BCG vascular infections were included. Seventy-three (99%) cases were male patients, all of whom were exposed to BCG through bladder instillation. Fifty (68%) cases were diagnosed more than 12 months after exposure to BCG. Twenty-six (35%) cases presented with arterial rupture at the time of diagnosis. Concurrent BCG infections in nonvascular locations were present in 37 (50%) cases. The most common locations of BCG vascular infection were the abdominal aorta (57%), prosthetic grafts (15%), and thoracic aorta (12%). The most common treatment for BCG infection was open repair with synthetic graft in situ replacement for the abdominal aorta and endovascular repair for the thoracic aorta. The 30-day mortality, among the 59 cases where these data were reported, was 10%. CONCLUSIONS: We observed that many aspects of BCG vascular infections are similar to other forms of vascular infections. The high incidence of rupture or fistulation and the propensity toward abdominal aortic involvement and its prognosis are similar to those described in other vascular infections. However, our study also highlights 2 idiosyncratic features of BCG vascular infections: association with male sex and concurrent musculoskeletal infections.
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Mycobacterium bovis , Neoplasias de la Vejiga Urinaria , Administración Intravesical , Vacuna BCG/efectos adversos , Femenino , Humanos , Masculino , Resultado del Tratamiento , Neoplasias de la Vejiga Urinaria/tratamiento farmacológicoRESUMEN
Cardiac myxomas are the most common benign cardiac tumors in adults that can present with peripheral embolization. Complete detachments of myxomas are rare and tend to cause aortoiliac embolism. We report a case of a middle-aged woman with bilateral popliteal artery and segmental renal artery embolisms secondary to a completely detached cardiac myxoma. This case highlights cardiac myxomas as an important cause of acute limb ischemia and that it is not excluded by a normal echocardiogram result.
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Embolia/etiología , Neoplasias Cardíacas/complicaciones , Isquemia/etiología , Mixoma/complicaciones , Anticoagulantes/uso terapéutico , Angiografía por Tomografía Computarizada , Diagnóstico Diferencial , Ecocardiografía , Embolia/diagnóstico por imagen , Embolia/terapia , Embolización Terapéutica , Femenino , Neoplasias Cardíacas/diagnóstico por imagen , Neoplasias Cardíacas/terapia , Humanos , Isquemia/diagnóstico por imagen , Isquemia/terapia , Extremidad Inferior/diagnóstico por imagen , Imagen por Resonancia Magnética , Persona de Mediana Edad , Mixoma/diagnóstico por imagen , Mixoma/terapia , Arteria Poplítea , Arteria RenalRESUMEN
BACKGROUND: Median arcuate ligament syndrome (MALS) is a condition characterized by chronic abdominal symptoms associated with median arcuate ligament compression of the celiac artery. The selection of patients is difficult in the management of MALS. This study aimed to identify factors that predict outcomes of surgical and nonoperative treatment in these patients. METHODS: Patients referred with a possible diagnosis of MALS between 1998 and 2013 were identified retrospectively. Only patients with chronic symptoms and radiologically confirmed celiac artery compression were included. The clinical features, investigations, and management were documented. Outcome was assessed using the Visick score, Gastrointestinal Symptom Rating Scale, and 12-Item Short Form Health Survey by telephone interview and review of medical records. RESULTS: There were 67 patients, 43 (64%) treated surgically and 24 (36%) managed without surgery, with a median follow-up of 25 months and 24 months, respectively. After surgical treatment, 16 (37%) were asymptomatic, 24 (56%) were partially improved, 3 (7%) had no changes in symptoms, and none had worsening of symptoms. Postexertional pain predicted improvement after surgery (P = .022). Vomiting (P = .046) and unprovoked pain (P = .006) were predictors of poor surgical outcome. After nonoperative management, 1 (4%) was asymptomatic, 7 (29%) were partially improved, 12 (50%) had no changes in symptoms, and 4 (17%) had worsening of symptoms. No outcome predictors of nonoperative treatment were identified. CONCLUSIONS: MALS was more likely to respond to decompression if patients had postexertional pain. Patients who presented with vomiting and unprovoked pain were unlikely to respond to surgery. In contrast with previous studies, postprandial pain was not found to be predictive of outcome.
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Arteria Celíaca/anomalías , Arteria Celíaca/cirugía , Constricción Patológica/terapia , Descompresión Quirúrgica/métodos , Laparoscopía , Procedimientos Quirúrgicos Vasculares , Dolor Abdominal/etiología , Adulto , Anciano , Arteria Celíaca/diagnóstico por imagen , Arteria Celíaca/fisiopatología , Constricción Patológica/complicaciones , Constricción Patológica/diagnóstico por imagen , Constricción Patológica/cirugía , Descompresión Quirúrgica/efectos adversos , Femenino , Humanos , Laparoscopía/efectos adversos , Masculino , Síndrome del Ligamento Arcuato Medio , Persona de Mediana Edad , Selección de Paciente , Queensland , Estudios Retrospectivos , Factores de Riesgo , Encuestas y Cuestionarios , Factores de Tiempo , Resultado del Tratamiento , Grado de Desobstrucción Vascular , Procedimientos Quirúrgicos Vasculares/efectos adversos , Vómitos/etiología , Adulto JovenRESUMEN
The use of α,ω-dienes as functionalization reagents for olefinic carbon-hydrogen bonds has been rarely studied. Reported herein is the rhodium(I)-catalyzed rearrangement of prochiral 1,6-heptadienes into [2,2,1]-cycloheptane derivatives with concomitant creation of at least three stereogenic centers and complete diastereocontrol. Deuterium-labeling studies and the isolation of a key intermediate are consistent with a group-directed C-H bond activation, followed by two consecutive migratory insertions, with only the latter step being diastereoselective.
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Alcadienos/química , Rodio/química , Catálisis , Ciclización , EstereoisomerismoRESUMEN
Spontaneous isolated mesenteric arterial dissection (SIMAD) is an uncommon subset of non-traumatic dissection of the mesenteric arteries without concurrent aortic dissection. Due to the widespread use of computer tomography angiography, SIMAD cases have been increasingly reported in the past 20 years. Common risk factors associated with SIMAD include male gender, age 50-60 years, hypertension and smoking. This review summarises the diagnostic pathway and management of SIMAD based on contemporary literature and proposes a treatment algorithm for SIMAD. The presentation of SIMAD can be divided into symptomatic and asymptomatic cases. Symptomatic patients should be carefully assessed to detect the development of complications, particularly bowel ischemia or vessel rupture. Although these complications are rare, they necessitate urgent surgical management. The vast majority of symptomatic SIMAD cases are uncomplicated and can be managed safely with conservative treatment that includes antihypertensive therapy, bowel rest, with or without antithrombotic therapy. For asymptomatic SIMAD cases, expectant management with outpatient surveillance imaging appears to be a safe strategy.
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Disección Aórtica , Isquemia Mesentérica , Humanos , Masculino , Persona de Mediana Edad , Arteria Mesentérica Superior/cirugía , Arterias Mesentéricas/diagnóstico por imagen , Isquemia Mesentérica/diagnóstico por imagen , Isquemia Mesentérica/terapia , Isquemia Mesentérica/etiología , Angiografía por Tomografía Computarizada , Disección Aórtica/diagnóstico por imagen , Disección Aórtica/terapia , Resultado del Tratamiento , Estudios RetrospectivosRESUMEN
BACKGROUND: Thoracic outlet syndrome (TOS) refers to a group of compressive disorders that occur in the thoracic outlet and can affect the brachial plexus, subclavian artery and vein. Neurogenic TOS (nTOS) is the most common form of TOS, accounting for approximately 97% of cases. nTOS and its resulting compressive brachial plexopathy can lead to potentially disabling symptoms and reduced quality of life. OBJECTIVE: This article reviews the current literature on nTOS and summarises the pathophysiology, diagnostic pathways and the management options for nTOS. DISCUSSION: nTOS is an uncommon but disabling disorder with no single 'rule-in' test, often resulting in diagnostic delays and late referral. Initial management is non-operative with targeted physiotherapy. If this is unsuccessful, symptoms can be relieved with scalene botulinum toxin injections and surgical intervention.
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Medicina , Síndrome del Desfiladero Torácico , Humanos , Calidad de Vida , Síndrome del Desfiladero Torácico/diagnóstico , Síndrome del Desfiladero Torácico/terapia , Ceguera , Derivación y ConsultaRESUMEN
Hypertension and type 2 diabetes mellitus (T2DM) are important, intertwined public health issues. People with both conditions face significantly elevated risks of cardiovascular (CV) and renal complications. To optimize patient care, a multidisciplinary expert panel met to review recent evidence on optimal blood pressure (BP) targets, implications of albuminuria, and treatment regimens for hypertensive patients with T2DM, with the aim of providing recommendations for physicians in Hong Kong. The panel reviewed the relevant literature, obtained by searching PubMed for the publication period from January 2015 to June 2021, to address five discussion areas: (i) BP targets based on CV/renal benefits; (ii) management of isolated systolic or diastolic hypertension; (iii) roles of angiotensin II receptor blockers; (iv) implications of albuminuria for CV/renal events and treatment choices; and (v) roles and tools of screening for microalbuminuria. The panel held three virtual meetings using a modified Delphi method to address the discussion areas. After each meeting, consensus statements were derived and anonymously voted on by every panelist. A total of 17 consensus statements were formulated based on recent evidence and expert insights regarding cardioprotection and renoprotection for hypertensive patients with T2DM.
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Rabbit haemorrhagic disease (RHD) is a significant and debilitating viral disease affecting lagomorphs. In September 2020, Singapore reported its first cases of RHD virus (RHDV) infection in domesticated rabbits. The initial findings reported that the outbreak strain belonged to genotype GI.2 (RHDV2/RHDVb), and epidemiological investigations could not identify the definitive source of the virus origin. Further recombination detection and phylogenetic analyses of the Singapore outbreak strain revealed that the RHDV was a GI.2 structural (S)/GI.4 non-structural (NS) recombinant variant. Sequence analyses on the National Centre for Biotechnology Information (NCBI) database showed high homology to recently emerged Australian variants, which were prevalent in local Australian lagomorph populations since 2017. Time-structured and phylogeographic analyses for the S and NS genes revealed a close genetic relationship between the Singapore RHDV strain and the Australian RHDV variants. More thorough epidemiological inquiries are necessary to ascertain how an Australian RHDV was introduced into the Singapore rabbit population, and opportune development of RHDV diagnostics and vaccines will be important to safeguard lagomorphs from future RHDV infection and disease management.
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Objectives: To evaluate the association of illicit drug use with bone mineral density (BMD) and hip geometric parameters at the narrow neck. Methods: This is a cross-sectional matched cohort study conducted in the Hong Kong Chinese population. Associations with illicit drug use were estimated using linear regression for BMD (lumbar spine and femoral neck) and hip geometrical parameters (cross-sectional area [CSA], cross-sectional moment of inertia [CSMI], section modulus [SM], average cortical thickness [ACT] and BMD at the narrow neck) after adjusting for age, body mass index (BMI), smoking status, drinking status, physical activity, and history of antipsychotic and antidepressant use. Mean difference and 95% confidence intervals (95% CI) were calculated between 108 illicit drug users and 108 controls using an adjusted linear model and cluster-robust standard errors after matching by age and sex. The false discovery rate was used to correct for multiple testing. Results: Illicit drug users had a significantly lower BMD (g/cm2) at the lumbar spine (mean difference: -0.062; 95% CI: -0.108 to -0.015), and femoral neck (mean difference: -0.058; 95% CI: -0.106 to -0.010) in the fully adjusted model. Illicit drug users also had a significantly lower CSA (mean difference: -0.238 cm2; 95% CI: -0.462 to -0.013), ACT (mean difference: -0.018 cm; 95% CI: -0.030 to -0.006) and BMD (mean difference: -0.070 g/cm2; 95% CI: -0.128 to -0.012) at the narrow neck. Conclusions: Illicit drug use is associated with lower BMD and bone strength. Future studies evaluating the risk of illicit drug use with fragility fracture are warranted.
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Get in the ring! The first examples of transition-metal-catalysed C-C bond activation of 3-azetidinones and 3-oxetanones are reported. In the presence of a nickel catalyst and alkynes, a regioselective and high-yielding [4+2] cycloaddition occurs, leading to the formation of pyridinones, pyranones and eventually 4,5-disubstituted 3-hydroxypyridines (see scheme).
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Alquinos/química , Azetidinas/química , Níquel/química , Éteres Fenílicos/química , Elementos de Transición/química , Catálisis , Ciclización , Estructura Molecular , EstereoisomerismoRESUMEN
Background: Fibromuscular dysplasia is a non-inflammatory, non-atherosclerotic vascular disease that commonly affects renal and carotid arteries but involvement of virtually any vascular territory has been observed.Research Design/ Study sample: This is a case report of a ruptured left gastric artery aneurysm as the first presentation of fibromuscular dysplasia.Data collection: After written consent from the patient, relevant clinical notes and imaging were retrospectively reviewed and critically analysed.Purpose: This case reiterates the importance of considering fibromuscular dysplasia as an uncommon cause of visceral artery aneurysms. In addition, this case shows that the impact of visceral artery vasospasm on endovascular access should not be underestimated and subsequent attempts can be successful after a period of resuscitation.Results: After initial difficulty in endovascular treatment due to visceral vasospasm, the case was successfully managed with with staged open ligation and endovascular embolization after a period of resuscitation.Conclusions: FMD is an important differential diagnosis to consider in cases of visceral aneurysms.
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Aneurisma Roto , Aneurisma , Displasia Fibromuscular , Aneurisma/diagnóstico por imagen , Aneurisma/etiología , Aneurisma/cirugía , Aneurisma Roto/diagnóstico por imagen , Aneurisma Roto/etiología , Aneurisma Roto/cirugía , Displasia Fibromuscular/complicaciones , Displasia Fibromuscular/diagnóstico por imagen , Displasia Fibromuscular/terapia , Artería Gástrica , Humanos , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
Rabbit haemorrhagic disease (RHD) is a highly contagious viral disease affecting lagomorphs. The first documented cases of RHD in Singapore occurred in adult pet European rabbits in September 2020. Singapore subsequently declared the outbreak resolved in December 2020. Epidemiological investigations ruled out introductions via importation of infected rabbits and contaminated feed. The source could not be definitively determined. However, the findings suggested that the incident involved both inter- and intra-household transmission and veterinary clinic-household transmission. This incident demonstrated the importance of sustained application of biosecurity measures, epidemiological investigations including active case finding, control measures such as expedient vaccine dissemination and risk communications. It showed that even without a wild lagomorph population, an urbanized city-state like Singapore could still encounter emerging diseases such as RHD. Given its social impact on rabbit owners, the National Parks Board, Singapore and private veterinarians worked together to communicate with rabbit owners in order to urge them to adopt biosecurity measures and to address their concerns.
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Infecciones por Caliciviridae , Virus de la Enfermedad Hemorrágica del Conejo , Lagovirus , Animales , Infecciones por Caliciviridae/epidemiología , Infecciones por Caliciviridae/prevención & control , Infecciones por Caliciviridae/veterinaria , Brotes de Enfermedades/prevención & control , Brotes de Enfermedades/veterinaria , Virus de la Enfermedad Hemorrágica del Conejo/genética , Filogenia , Conejos , Singapur/epidemiologíaRESUMEN
STUDY DESIGN: Clinical audit via retrospective review of a database. PURPOSE: To report an early experience using ultrasound-guided lumbar spinal injection for axial and radicular pain in an Asian multiethnic cohort. OVERVIEW OF LITERATURE: Ultrasound-guided spine injection therapy is a comparatively new technique in the management of axial and radicular pain from degenerative lumbar spinal conditions, which may be a reasonable alternative to conventional fluoroscopic or computed tomography-guided injection. METHODS: A retrospective review was conducted, involving all patients who underwent ultrasound-guided lumbar spine injection therapy at a single institution over 1 year. Patients were evaluated by two interventionists, who then performed standardized ultrasound-guided lumbar facet joint and pararadicular spinal injections. RESULTS: There were 42 patients treated at our Sports Medicine Centre; with 27 patients (64.3%) receiving facet joint injections and 18 patients (42.9%) receiving nerve root injections. The majority (90.5%) of patients experienced an improvement of >30% in pain intensity at 3 months post-injection, using the Numerical Rating Scale pain score (p<0.001); with 40 patients (95.2%) reporting a reduction in Oswestry Disability Index score (p<0.001). No complications were reported. CONCLUSIONS: Our initial experience confirms the safety, feasibility, and effectiveness of ultrasound-guided lumbar spinal injection for the treatment of axial and radicular pain in an Asian multiethnic cohort.
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Eccrine spiradenoma is a benign adnexal tumor of the sweat gland. Giant vascular eccrine spiradenoma is a rare variant of eccrine spiradenoma, characterized by its large size and florid vascularity. Its rarity and clinical appearance give rise to typical misdiagnosis as angiomatous lesions. We present a case of a giant vascular eccrine spiradenoma that was initially diagnosed as a thrombosed varix on the basis of clinical presentation and ultrasound features. This case reintroduces this rare condition and also highlights the differential diagnoses of lower limb skin nodules that may masquerade as a thrombosed varix.
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True aneurysms of the internal thoracic artery (ITA) are rare and are associated with vasculitides, connective tissue diseases, and infections. We report a case of a 3-cm immunoglobulin G4-positive ITA aneurysm that was excised by a hybrid approach involving open ligation of the ITA origin and video-assisted thoracoscopic aneurysmectomy. This novel technique was able to acquire tissue for histopathologic diagnosis through a minimally invasive means.
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OBJECTIVE: Frailty has been associated with worse outcomes in older trauma patients. Specifically, the utility of lean cross-sectional psoas muscle area (LPA) was examined as a potentially simple objective measure of frailty. METHODS: Five hundred and fifty-four patients over the age of 65 were admitted with trauma between 2011 and 2014. Two hundred and twenty-five of these had adequate computed tomography imaging available for analysis. Cross-sectional area of the psoas muscle at the inferior endplate of L4 was quantified. RESULTS: Multivariate regression analysis showed no significant correlation between LPA and outcomes of mortality (P = 0.82) or inpatient complications (P = 0.22). Injury Severity Score (ISS) had a strong association with both mortality (odds ratio (OR) 9.5; 95% confidence interval (CI) 2.9-30.9) and inpatient complications (OR 9.9; 95% CI 3.5-27.7). Age also had an association with mortality (OR 1.09; 95% CI 1.03-1.16) and inpatient complications (OR 1.06; 95% CI 1.01-1.12). CONCLUSION: Lean psoas area was not an independent predictor of mortality or complications in a cohort of injured older patients.
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Fragilidad/diagnóstico por imagen , Músculos Psoas/diagnóstico por imagen , Tomografía Computarizada por Rayos X , Heridas y Lesiones/diagnóstico por imagen , Anciano , Envejecimiento , Composición Corporal , Distribución de Chi-Cuadrado , Estudios Transversales , Femenino , Anciano Frágil , Fragilidad/mortalidad , Fragilidad/fisiopatología , Evaluación Geriátrica , Humanos , Puntaje de Gravedad del Traumatismo , Modelos Logísticos , Masculino , Análisis Multivariante , Oportunidad Relativa , Valor Predictivo de las Pruebas , Músculos Psoas/fisiopatología , Estudios Retrospectivos , Factores de Riesgo , Heridas y Lesiones/mortalidad , Heridas y Lesiones/fisiopatologíaRESUMEN
The poor regioselectivity of the [4 + 2] cycloaddition of 3-azetidinones with internal alkynes bearing two alkyl substituents via nickel-catalyzed carbon-carbon activation is addressed using 1,3-enynes as substrates. The judicious choice of substitution on the enyne enables complementary access to each regioisomer of 3-hydroxy-4,5-alkyl-substituted pyridines, which are important building blocks in medicinal chemistry endeavors.
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Histologic low-grade chronic renal lesions in 144 adults with primary immunoglobulin A (IgA) nephropathy were correlated with clinical parameters of disease progression over a median follow-up of 93 months. Using chronicity-based histologic grading, 50, 59, and 35 patients were glomerular grade (GG) 1a, GG1b, and GG2; 83 and 61 patients were tubulointerstitial grade (TIG) 1 and TIG2; and 25 patients had hyaline arteriolosclerosis. On follow-up, GG and TIG were predictive of disease progression by impairment of renal function, development of hypertension, and significant proteinuria (>1 g/d). Hyaline arteriolosclerosis correlated only with the development of hypertension. Histologic lesions GG1a or TIG1 predicted a significant low risk for disease progression compared with other renal lesions, regardless of the renal manifestation at the time of biopsy. Combined GG1a, TIG1, and isolated hematuria at the time of biopsy enhanced the sensitivity to determine early IgA nephropathy and to define a nonearly cohort with a higher risk of disease progression appropriate for recruitment into clinical therapeutic trials within realistic time frames. The significant risk of progression in other low-grade lesions, such as GG1b or TIG2, suggests that the point of no return in IgA nephropathy may occur much earlier than perceived and that delayed biopsy in these patients no longer may be justified.
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Glomerulonefritis por IGA/patología , Adolescente , Adulto , Distribución por Edad , Biopsia , Comorbilidad , Progresión de la Enfermedad , Supervivencia sin Enfermedad , Femenino , Estudios de Seguimiento , Glomerulonefritis por IGA/epidemiología , Humanos , Hipertensión/epidemiología , Incidencia , Glomérulos Renales/patología , Túbulos Renales/patología , Masculino , Persona de Mediana Edad , Proteinuria/epidemiología , Distribución por SexoRESUMEN
Analytical methods were developed for a directed enzyme evolution research programme, which pursued high performance enzymes to produce high quality L-ribose using large scale biocatalytic reaction. A high throughput HPLC method with evaporative light-scattering detection was developed to test ribose and ribitol in the enzymatic reaction, a ß-cyclobond 2000 analytical column separated ribose and ribitol in 2.3 min, a C(18) guard column was used as an on-line filter to clean up the enzyme sample matrix and a short gradient was applied to wash the column, the enzymatic reaction solution can be directly injected after quenching. Total run time of each sample was approx. 4 min which provided capability of screening 4×96-well plates/day/instrument. Meanwhile, a capillary electrophoresis method was developed for the separation of ribose enantiomers, while 7-aminonaphthalene-1,3-disulfonic acid was used as derivatisation reagent and 25 mM tetraborate with 5 mM ß-cyclodextrin was used as electrolyte. 0.35%of D-ribose in L-ribose can be detected which can be translated into 99.3% ee of L-ribose. Derivatisation reagent and sample matrix did not interfere with the measurement.