Comparative proteomic analysis of lung tissue from guinea pigs with leptospiral pulmonary haemorrhage syndrome (LPHS) reveals a decrease in abundance of host proteins involved in cytoskeletal and cellular organization

Leptospiral pulmonary haemorrhage syndrome (LPHS) is a particularly severe form of leptospirosis. LPHS is increasingly recognized in both humans and animals and is characterized by rapidly progressive intra-alveolar haemorrhage leading to high mortality. The pathogenic mechanisms of LPHS are poorly understood which hampers the application of effective treatment regimes. In this study a 2-D guinea pig proteome lung map was created and used to investigate the pathogenic mechanisms of LPHS. Comparison of lung proteomes from infected and non-infected guinea pigs via differential in-gel electrophoresis revealed highly significant differences in abundance of proteins contained in 130 spots. Acute phase proteins were the largest functional group amongst proteins with increased abundance in LPHS lung tissue, and likely reflect a local and/or systemic host response to infection. The observed decrease in abundance of proteins involved in cytoskeletal and cellular organization in LPHS lung tissue further suggests that infection with pathogenic Leptospira induces changes in the abundance of host proteins involved in cellular architecture and adhesion contributing to the dramatically increased alveolar septal wall permeability seen in LPHS. BIOLOGICAL SIGNIFICANCE The recent completion of the complete genome sequence of the guinea pig (Cavia porcellus) provides innovative opportunities to apply proteomic technologies to an important animal model of disease. In this study, the comparative proteomic analysis of lung tissue from experimentally infected guinea pigs with leptospiral pulmonary haemorrhage syndrome (LPHS) revealed a decrease in abundance of proteins involved in cellular architecture and adhesion, suggesting that loss or down-regulation of cytoskeletal and adhesion molecules plays an important role in the pathogenesis of LPHS. A publically available guinea pig lung proteome map was constructed to facilitate future pulmonary proteomics in this species.

An unusual stroke-like clinical presentation of Creutzfeldt-Jakob disease: acute vestibular syndrome

INTRODUCTION Vertigo and dizziness are common neurological symptoms in general practice. Most patients have benign peripheral vestibular disorders, but some have dangerous central causes. Recent research has shown that bedside oculomotor examinations accurately discriminate central from peripheral lesions in those with new, acute, continuous vertigo/dizziness with nausea/vomiting, gait unsteadiness, and nystagmus, known as the acute vestibular syndrome. CASE REPORT A 56-year-old man presented to the emergency department with acute vestibular syndrome for 1 week. The patient had no focal neurological symptoms or signs. The presence of direction-fixed, horizontal nystagmus suppressed by visual fixation without vertical ocular misalignment (skew deviation) was consistent with an acute peripheral vestibulopathy, but bilaterally normal vestibuloocular reflexes, confirmed by quantitative horizontal head impulse testing, strongly indicated a central localization. Because of a long delay in care, the patient left the emergency department without treatment. He returned 1 week later with progressive gait disturbance, limb ataxia, myoclonus, and new cognitive deficits. His subsequent course included a rapid neurological decline culminating in home hospice placement and death within 1 month. Magnetic resonance imaging revealed restricted diffusion involving the basal ganglia and cerebral cortex. Spinal fluid 14-3-3 protein was elevated. The rapidly progressive clinical course with dementia, ataxia, and myoclonus plus corroborative neuroimaging and spinal fluid findings confirmed a clinicoradiographic diagnosis of Creutzfeldt-Jacob disease. CONCLUSIONS To our knowledge, this is the first report of an initial presentation of Creutzfeldt-Jacob disease closely mimicking vestibular neuritis, expanding the known clinical spectrum of prion disease presentations. Despite the initial absence of neurological signs, the central lesion location was differentiated from a benign peripheral vestibulopathy at the first visit using simple bedside vestibular tests. Familiarity with these tests could help providers prevent initial misdiagnosis of important central disorders in patients presenting vertigo or dizziness.

Cetoacidosis inducida por corticoides y gatifloxacina en una mujer joven no diabética

Objetivo: Comunicar un caso de cetoacidosis inducida por corticoides y gatifloxacina y discutir los mecanismos de esta inusual y seria complicación. Caso clínico: Mujer de 32 años, ingresa por neumonía adquirida en la comunidad de 5 días de evolución. Antecedentes: AR probable diagnosticada 4 meses antes tratada con metotrexate y corticoides intermitente. Examen físico: regular estado general, IMC 21, Tº 38ºC, FR 32/min, derrame pleural derecho, FC 96/min, PA 110/70, artralgias sin artritis. Exámenes complementarios: Hto 23%, GB 16300/mm3, VSG 96mm/1ºh, glucemia 0.90mg/dl, función hepática y amilasa normales, uremia 1.19g/l, creatinina 19mg/l. Hemocultivos (2) y esputo positivos para Neumococo penicilina-sensible. La neumonía responde a gatifloxacina. Deteriora la función renal hasta la anuria con acidosis metabólica. Se interpreta como glomerulonefritis lúpica rápidamente progresiva por proteinuria de 2g/24hs, FR (+) 1/1280, FAN (+) 1/320 homogéneo, Anti ADN (+) , complemento bajo: C3 29.4mg/dl y C4 10mg/dl, Ac anti Ro, La, Scl70, RNP y anticardiolipinas positivos. Se indica metilprednisolona EV (3 bolos 1g), complicándose con hiperglucemias de >6 g/l y cetoacidosis con cetonuria (+); Ac anti ICA y antiGAD negativos con HbA1C 5.2%. Es tratada en UTI (insulina y hemodiálisis). La paciente mejora, se desciende la dosis de corticoides, con normalización de la glucemia sin tratamiento hipoglucemiante. Comentarios 1) La presencia de HbA1C nomal, Ac anti ICA y GAD negativos permite descartar con razonable grado de certeza una diabetes tipo1 asociada al lupus. 2) El desarrollo de la cetoacidosis durante el tratamiento con corticoides y gatifloxacina y su resolución posterior avalan el rol etiológico de los mismos. 3) La cetoacidosis puede explicarse por estimulación de la gluconeogénesis y la insulinoresistencia a nivel de receptor y post-receptor generada por los fármacos potenciado por el estado inflamatorio relacionado con el lupus y la sepsis.

Enfermedad de Creutzfeld Jakob, desafío diagnóstico : reporte de dos casos en la ciudad de Mendoza

La enfermedad de Creutzfeldt-Jakob (ECJ) es una afección neurodege-nerativa rápidamente progresiva y mortal producida por priones. Es la más común de las encefalopatías espongiformes. La hipótesis prevalente sugiere que se inicia y propaga por conversión de una proteína priónica normal (PrP) en una isoforma conformacional anormal (PrPreS), que se acumula en el cerebro causando destrucción neuronal. Se reporta el caso de dos pacientes asistido en el Servicio de Neurología del Hospital Lagomaggiore de la ciudad de Mendoza en el período de 2 años: mujer de 49 años con cuadro de deterioro cognitivo rápidamente progresivo asociado a trastorno de la marcha y ataxia de 2 meses de evolución; y varón de 54 años con conductas inapropiadas y desorientación temporo-espacial de 20 días de evolución. Ambos con EEG compatible y proteína 14.3.3 positiva, falleciendo semanas después del diagnóstico. Se discute ambos casos, los cuales representaron un desafío diagnóstico dada la baja frecuencia y escaso reconocimiento de esta entidad en nuestro medio, debiendo debe ser considerado en pacientes que evolucionan a una demencia rápidamente progresiva.

Síndrome demencial reversível : caso clínico

Trabalho Final do Curso de Mestrado Integrado em Medicina, Faculdade de Medicina, Universidade de Lisboa, 2014

Alterações metabólicas e risco cardiovascular em crianças infectadas verticalmente pelo VIH-1 na era do tratamento anti-retroviral combinado : um caso clínico

Trabalho Final do Curso de Mestrado Integrado em Medicina, Faculdade de Medicina, Universidade de Lisboa, 2014

A Rare Complication of Tracheal Intubation: Tongue Perforation

Aim. To describe the subsequent treatment of airway trauma sustained during laryngoscopy and endotracheal intubation. Methods. A rare injury occurring during laryngoscopy and endotracheal intubation that resulted in perforation of the tongue by an endotracheal tube and the subsequent management of this unusual complication are discussed. A 65-year-old female with intraparenchymal brain hemorrhage with rapidly progressive neurologic deterioration had the airway secured prior to arrival at the referral institution. The endotracheal tube (ETT) was noted to have pierced through the base of the tongue and entered the trachea, and the patient underwent operative laryngoscopy to inspect the injury and the ETT was replaced by tracheostomy. Results. Laryngoscopy demonstrated the ETT to perforate the base of the tongue. The airway was secured with tracheostomy and the ETT was removed. Conclusions. A wide variety of complications resulting from direct and video-assisted laryngoscopy and tracheal intubation have been reported. Direct perforation of the tongue with an ETT and ability to ventilate and oxygenate subsequently is a rare injury.

Beyond maternal death: improving the quality of maternal care through national studies of ‘near-miss’ maternal morbidity

Knight M, Acosta C, Brocklehurst P, Cheshire A, Fitzpatrick K, Hinton L, Jokinen M, Kemp B, Kurinczuk JJ, Lewis G, Lindquist A, Locock L, Nair M, Patel N, Quigley M, Ridge D, Rivero-Arias O, Sellers S, Shah A on behalf of the UKNeS coapplicant group. Background Studies of maternal mortality have been shown to result in important improvements to women’s health. It is now recognised that in countries such as the UK, where maternal deaths are rare, the study of near-miss severe maternal morbidity provides additional information to aid disease prevention, treatment and service provision. Objectives To (1) estimate the incidence of specific near-miss morbidities; (2) assess the contribution of existing risk factors to incidence; (3) describe different interventions and their impact on outcomes and costs; (4) identify any groups in which outcomes differ; (5) investigate factors associated with maternal death; (6) compare an external confidential enquiry or a local review approach for investigating quality of care for affected women; and (7) assess the longer-term impacts. Methods Mixed quantitative and qualitative methods including primary national observational studies, database analyses, surveys and case studies overseen by a user advisory group. Setting Maternity units in all four countries of the UK. Participants Women with near-miss maternal morbidities, their partners and comparison women without severe morbidity. Main outcome measures The incidence, risk factors, management and outcomes of uterine rupture, placenta accreta, haemolysis, elevated liver enzymes and low platelets (HELLP) syndrome, severe sepsis, amniotic fluid embolism and pregnancy at advanced maternal age (≥ 48 years at completion of pregnancy); factors associated with progression from severe morbidity to death; associations between severe maternal morbidity and ethnicity and socioeconomic status; lessons for care identified by local and external review; economic evaluation of interventions for management of postpartum haemorrhage (PPH); women’s experiences of near-miss maternal morbidity; long-term outcomes; and models of maternity care commissioned through experience-led and standard approaches. Results Women and their partners reported long-term impacts of near-miss maternal morbidities on their physical and mental health. Older maternal age and caesarean delivery are associated with severe maternal morbidity in both current and future pregnancies. Antibiotic prescription for pregnant or postpartum women with suspected infection does not necessarily prevent progression to severe sepsis, which may be rapidly progressive. Delay in delivery, of up to 48 hours, may be safely undertaken in women with HELLP syndrome in whom there is no fetal compromise. Uterine compression sutures are a cost-effective second-line therapy for PPH. Medical comorbidities are associated with a fivefold increase in the odds of maternal death from direct pregnancy complications. External reviews identified more specific clinical messages for care than local reviews. Experience-led commissioning may be used as a way to commission maternity services. Limitations This programme used observational studies, some with limited sample size, and the possibility of uncontrolled confounding cannot be excluded. Conclusions Implementation of the findings of this research could prevent both future severe pregnancy complications as well as improving the outcome of pregnancy for women. One of the clearest findings relates to the population of women with other medical and mental health problems in pregnancy and their risk of severe morbidity. Further research into models of pre-pregnancy, pregnancy and postnatal care is clearly needed.

A Rare Cause of Myoclonus: A Cupric Conundrum

A woman aged 22 years presented with a 3-year history of jerks when brushing her teeth and a tremor when carrying drinks. Examination revealed a bilateral jerky tremor, stimulus-sensitive myoclonus, and difficulty with tandem gait. Thyroid and liver function test results were normal, but she had rapidly progressive renal failure. Serum copper, ceruloplasmin, and manganese levels were normal, but her urinary copper level was elevated on 2 occasions. Pathological findings on organ biopsy prompted genetic testing to confirm the diagnosis. The differential diagnosis, tissue biopsy findings, and final genetic diagnosis are discussed.

A Case of Infectious Purpura Fulminans: An Unusual Organism and Method of Diagnosis

Infectious purpura fulminans is a rapidly progressive skin necrosis that carries a mortality rate of 30%. Here, we described a case of infectious purpura fulminans caused by Capnocytophaga diagnosed by a blood film.

Guillain-Barré Syndrome with Absent Brainstem Reflexes: a Case Report

A 41-year-old man was admitted to an intensive care unit following respiratory arrest. One day prior to admission, he had complaints of nausea and pain involving lower limbs. On the night of admission he developed diplopia, dysphagia, and rapidly progressive quadriparesis. He developed respiratory failure requiring mechanical lung ventilation 24 hours later. On the fifth day of hospital stay the patient became comatose with absent brainstem reflexes and appeared to be brain dead. The cerebrospinal fluid showed albuminocytological dissociation. The electroencephalogram revealed an alpha rhythmical activity. The electrophysiological evaluation revealed an inexcitability of all nerves. Guillain-Barré syndrome was suspected. With supportive treatment the patient had a remarkable recovery and now is able to independently conduct his daily activities.

Anti-Signal Recognition Particle Myopathy in a Geriatric Patient

Anti-signal recognition particle (SRP) myopathy is a rare idiopathic inflammatory myositis that usually affects middle-age women, and is characterized by rapidly progressive proximal and symmetrical muscle weakness, elevated creatine kinase levels, severe necrotizing immune-mediated myopathy, presence of anti-SRP autoantibodies and poor response to steroid therapy. We report a geriatric case of a previously independent patient, presenting with slow onset of proximal paraparesis, myalgia and severe gait impairment. The patient was treated with steroid and azathioprine, with laboratory and pain response but modest muscle strength improvement. The clinical presentation of this unusual patient was atypical, which hampered the correct diagnosis.

Pseudoangiomatous Stromal Hyperplasia in Pediatric Age: A Case Report and Review of Literature

Pseudoangiomatous stromal hyperplasia (PASH) is a rare benign disease, characterized by abnormal proliferation of fibroglandular stroma. It was first described in 1986. The authors present a case of a twelve year-old girl with a history of kidney transplantation due to nephrotic syndrome with rapidly progressive and painful breast asymmetry with approximately six months duration. No lymphadenopathy or other signs or symptoms were associated. Ultrasound didn’t reveal specific findings. Breast magnetic resonance (MR) showed a massive heterogeneous nodular mass with regular contours and contrast enhancement. Given the degree of breast asymmetry as well as the patient’s symptoms, surgical excision of the tumor was preferred over core biopsy. Histopathological and immunohistochemical examination showed pseudoangiomatous stromal hyperplasia. The authors describe the clinical presentation, imaging and histological features as well as therapeutic approach in these patients

Evaluación del desempeño de pruebas diagnósticas de tuberculosis en pacientes VIH positivo en dos hospitales públicos de Bogotá

La tuberculosis TB es una de las principales causas de muerte en el mundo en individuos con infección por VIH. En Colombia esta coinfección soporta una carga importante en la población general convirtiéndose en un problema de salud pública. En estos pacientes las pruebas diagnósticas tienen sensibilidad inferior y la enfermedad evoluciona con mayor frecuencia hacia formas diseminadas y rápidamente progresivas y su diagnóstico oportuno representa un reto en Salud. El objetivo de este proyecto es evaluar el desempeño de las pruebas diagnósticas convencionales y moleculares, para la detección de TB latente y activa pacientes con VIH, en dos hospitales públicos de Bogotá. Para TB latente se evaluó la concordancia entre las pruebas QuantiFERON-TB (QTF) y Tuberculina (PPD), sugiriendo superioridad del QTF sobre la PPD. Se evaluaron tres pruebas diagnósticas por su sensibilidad y especificidad, baciloscopia (BK), GenoType®MTBDR plus (Genotype) y PCR IS6110 teniendo como estándar de oro el cultivo. Los resultados de sensibilidad (S) y especificidad (E) de cada prueba con una prevalencia del 19,4 % de TB pulmonar y extrapulmonar en los pacientes que participaron del estudio fue: BK S: 64% E: 99,1%; Genotype S: 77,8% E: 94,5%; PCRIS6110 S: 73% E: 95,5%, de la misma forma se determinaron los valores predictivos positivos y negativos (VPP y VPN) BK: 88,9% y 94,8%, Genotype S: 77,8% E: 94,5%; PCRIS6110 S: 90% y 95,7%. Se concluyó bajo análisis de curva ROC que las pruebas muestran un rendimiento diagnóstico similar por separado en el diagnóstico de TB en pacientes con VIH, aumentando su rendimiento diagnostico cuando se combinan