A rare case of skin metastasis from a chordoma.

Chordoma is an uncommon, indolent malignant tumor arising from notochordal remnants. The incidence of distant metastasis varies between 30 and 40% in different series. Even though local involvement of the skin by direct invasion of chordoma is common, distant skin metastasis are rare, with less than 30 cases reported in the literature. The present clinical case illustrates the slow-growing natural history of a sacral chordoma, which evolved with lung metastasis, followed three years later by skin metastasis, thus giving us the opportunity to review the diagnostic approach, as well as the clinical and histopathological characteristics of this rare tumor.

Founder effect of Fabry disease due to p.F113L mutation: Clinical profile of a late-onset phenotype.

BACKGROUND: Knowledge on clinical profiles of late-onset phenotypes of Fabry disease (FD) is essential to better define their natural history. Our study aims to demonstrate a founder effect of FD due to the GLA gene mutation c.337T>C (p.F113L) in the Portuguese region of Guimarães; and to characterize the clinical profile of this late-onset phenotype in a large cohort of genetically related adult patients, living in the same region. METHODS AND RESULTS: FD screening was performed in 150 adult patients with hypertrophic cardiomyopathy (HCM) and found 25 Fabry patients (16.6%). The p.F113L mutation was found in 21 of them, leading to a genealogy study and haplotype analysis of the p.F113L patients. Genealogy research revealed a 12-generation family tree with a common ancestor to p.F113L patients, suggesting a founder effect that was supported by haplotype findings. Pedigree analysis was performed and 120 consecutive p.F113L patients underwent a predefined diagnostic evaluation of FD multiorgan involvement. This late-onset phenotype was characterized by common and/or potentially severe cardiac manifestations (left ventricular hypertrophy 40.8%, atrial fibrillation 5%, non-sustained ventricular tachycardia 12.5%, atrioventricular block 18.3%, bifascicular block 13.4%). Extracardiac manifestations included albuminuria>30 mg/24 h 36.1%, chronic kidney disease≥G3 7.6%, brain white matter lesions 54.4%, stroke 3.3%, sensorineural deafness 44.5%, cornea verticillata 13.9%. Plasma lyso-GB3 was undetectable in females, regardless of clinical manifestations. CONCLUSION: A founder effect of FD due to p.F113L mutation was documented by genealogy and genetics in a Portuguese region. In this late-onset phenotype, although cardiac manifestations carry the highest prognostic impact, extracardiac involvement is common.

Signalling mechanisms that regulate metabolic profile and autophagy of acute myeloid leukaemia cells.

Acute myeloid leukaemia (AML) comprises a heterogeneous group of hematologic neoplasms characterized by diverse combinations of genetic, phenotypic and clinical features representing a major challenge for the development of targeted therapies. Metabolic reprogramming, mainly driven by deregulation of the nutrient-sensing pathways as AMPK, mTOR and PI3K/AKT, has been associated with cancer cells, including AML cells, survival and proliferation. Nevertheless, the role of these metabolic adaptations on the AML pathogenesis is still controversial. In this work, the metabolic status and the respective metabolic networks operating in different AML cells (NB-4, HL-60 and KG-1) and their impact on autophagy and survival was characterized. Data show that whereas KG-1 cells exhibited preferential mitochondrial oxidative phosphorylation metabolism with constitutive co-activation of AMPK and mTORC1 associated with increased autophagy, NB-4 and HL-60 cells displayed a dependent glycolytic profile mainly associated with AKT/mTORC1 activation and low autophagy flux. Inhibition of AKT is disclosed as a promising therapeutical target in some scenarios while inhibition of AMPK and mTORC1 has no major impact on KG-1 cells' survival. The results highlight an exclusive metabolic profile for each tested AML cells and its impact on determination of the anti-leukaemia efficacy and on personalized combinatory therapy with conventional and targeted agents.

Hydroxymethylbilane synthase gene mutations and polymorphisms in Brazilian families with acute intermittent porphyria.

Acute intermittent porphyria (AIP), an autosomal dominant disorder, is caused by a deficiency of hydroxymethylbilane synthase (HMBS). In the present study, we sought to establish a correlation between HMBS activity with the presence of mutations and polymorphisms. Enzyme activity was measured in red blood cells of four Brazilian unrelated AIP families (n = 124) and in blood donors (n = 80). The HMBS mutations in AIP family members were studied by PCR-SSCP followed by direct sequencing. Six intragenic SNPs (1345 G>A, 1500 T>C, 2377 C>A, 2478 A>G, 3581 A>G, and 7064 C>A) were determined by PCR-RFLP. Abnormal SSCP patterns in exons 7, 9, 12, and 15 were observed. DNA sequencing analysis revealed one nonsense mutation, R149X, two missense mutations, G111R and L338P, and one deletion, CT 730-731. All mutation carriers had lower enzyme activity. All polymorphisms, except 2377 C>A and 7064 C>A, showed no significant differences compared with previous reports. Mutation screening allowed the detection of the missense mutation, L338P, and the 730_731delCT deletion, two as yet unreported mutations in Brazilian AIP patients. Our findings also showed a high frequency of 2478 A>G and 3581 A>G polymorphism combinations suggesting that these polymorphisms contributed to enzymatic activity reduction in our study population.

Pregnancy and neonatal outcomes of women receiving compounded 17-alpha hydroxyprogesterone at San Juan City hospital.

OBJECTIVE: To describe the pregnancy and neonatal outcomes of women receiving 17alpha-hydroxyprogesterone to prevent subsequent preterm birth in our institution. METHODS: Forty-two patient received treatment by VITA healthcare and their charts were reviewed for results and outcomes. RESULTS: An increase in average gestational age at the time of delivery was noticed as well as an increase in weeks gained compared to previous preterm birth. DISCUSSION: More than 75% of the patients prolonged their pregnancy with the use of 17alpha-hydroxyprogesterone. Continuation of the study and stratifying patients will help in identifying other risk factors and establishing criteria for improved prevention of preterm birth and prognosis.

Symmetrical Drug-related Intertriginous and Flexural Exanthema (Baboon Syndrome).

Baboon syndrome, also called symmetrical drug-related intertriginous and flexural exanthema (SDRIFE), is an erythematous maculopapular rash that presents in skin folds in a symmetrical pattern. This condition may develop after the patient starts a particular agent. Treatment consists of stopping the associated trigger and medicating with topical or systemic corticosteroids. A 30-year-old man with odynophagia, otalgia and fever was prescribed amoxicillin. He developed erythematous and pruriginous lesions in the cubital fossa and inguinal regions. He attended the emergency department (ED) where he was prescribed penicillin. Lesions continued to progressively worsen with a bilateral symmetrical pattern in the axillary region and later in the nape folds, popliteal regions, and on the perineum and buttocks. The patient presented to the ED for a second time, where he was diagnosed with baboon syndrome and prescribed topical steroids with clear improvement. LEARNING POINTS: It is important to identify adverse drug effects.Baboon syndrome is rare and secondary to the use of particular drugs.The diagnosis is based mainly on the patient's clinical presentation.

Nicolau syndrome due to a traumatic finger injury with a needle : a case report with an exclusive photographic documentation.

INTRODUCTION: Nicolau syndrome, also known as livedo-like dermatitis or embolia cutis medicamentosa, is a rare complication usually after intra-muscular or intra-articular injection of various drugs. It is difficult to find photographic documentation of this syndrome from the initial stages due to its rarity and unpredictable evolution. CASE PRESENTATION: We report the case of a 54-year-old Portuguese woman who developed Nicolau Syndrome after a traumatic finger injury with a sewing needle. She developed an ulcer and cutaneous necrosis. She was treated with surgical debridement, antibiotic, analgesics and sterile dressings. The ulcer healed completely within 18 weeks with scarring. CONCLUSIONS: Although Nicolau syndrome develops very rarely, it is an important cause for morbidity. It is an iatrogenic condition. The Nicolau Syndrome following a traumatic injury with a needle without drugs, as far as we know, has never been reported in the published literature especially with photographic records from the beginning of the process.

Natural history of the late-onset phenotype of Fabry disease due to the p.F113L mutation.

BACKGROUND: The common GLA gene mutation p.F113L causes late-onset phenotype of Fabry disease (FD) with predominant cardiac manifestations. A founder effect of FD due to this mutation was found in the Portuguese region of Guimarães. Our study aims to deepen the knowledge on the natural history of this late-onset variant. METHODS: 203 consecutive adult Fabry patients with p.F113L mutation (79 males; mean age 46 ± 18 years), from this region, were submitted at baseline to a predefined diagnostic protocol. The occurrence of FD manifestations was analyzed in each decade of age in both genders. RESULTS: In males, left ventricular hypertrophy (40.2%) and late gadolinium enhancement (21.4%) arose over 30 years; heart failure (HF) (21.9%), ventricular tachycardia (8.9%) and conduction disorders over 40 years; and bifascicular (13.1%) and complete atrioventricular blocks (5.9%) beyond 50 years of age. Cardiac manifestations occurred more commonly and 1-2 decades earlier in males; their frequency increased with age. Septum and posterior wall thickness, LV mass, QRS interval duration and pro-BNP levels increased with age in both genders. Mean survival free from HF (64 ± 1 vs. 76 ± 2 years) and pacemaker (71 ± 2 vs. 86 ± 1 years) was higher in females (p < .001). Albuminuria A2/A3 (33.7%), brain white matter lesions (50.3%) and sensorineural deafness (44.7%) arose before 30 years of age in both genders, increasing with age. Renal failure and stroke were rare. Lysosomal inclusions were demonstrated in podocytes of patients with proteinuria. CONCLUSION: This study improves the knowledge on natural history of late-onset variants of FD, carrying major impact on clinical decisions and guidelines.

Proteolytic systems and AMP-activated protein kinase are critical targets of acute myeloid leukemia therapeutic approaches.

The therapeutic strategies against acute myeloid leukemia (AML) have hardly been modified over four decades. Although resulting in a favorable outcome in young patients, older individuals, the most affected population, do not respond adequately to therapy. Intriguingly, the mechanisms responsible for AML cells chemoresistance/susceptibility are still elusive. Mounting evidence has shed light on the relevance of proteolytic systems (autophagy and ubiquitin-proteasome system, UPS), as well as the AMPK pathway, in AML biology and treatment, but their exact role is still controversial. Herein, two AML cell lines (HL-60 and KG-1) were exposed to conventional chemotherapeutic agents (cytarabine and/or doxorubicin) to assess the relevance of autophagy and UPS on AML cells' response to antileukemia drugs. Our results clearly showed that the antileukemia agents target both proteolytic systems and the AMPK pathway. Doxorubicin enhanced UPS activity while drugs' combination blocked autophagy specifically on HL-60 cells. In contrast, KG-1 cells responded in a more subtle manner to the drugs tested consistent with the higher UPS activity of these cells. In addition, the data demonstrates that autophagy may play a protective role depending on AML subtype. Specific modulators of autophagy and UPS are, therefore, promising targets for combining with standard therapeutic interventions in some AML subtypes.

Black oesophagus.

Acute oesophageal necrosis, also known as 'Black Oesophagus', is a rare endoscopic finding since its first description by Goldenberg in 1990. In endoscopic studies, the frequency ranged from 0.01% to 0.2%. The aetiology is undefined and is probably multifactorial. A 62-year-old woman, with chronic alcoholism, was admitted to the internal medicine department for dehydration and marked malnutrition problems. Melaena was detected, and oesophagogastroduodenoscopy showed black mucosa of the lower two-thirds of the oesophagus and candidiasis. The patient gradually recovered after conservative treatments (intravenous proton pump inhibitor and total parental nutrition) and fluconazole. Oesophagus stricture was developed after 1 month, and balloon dilatation was performed successfully.

Fat necrosis of the newborn--report on two cases.

Subcutaneous fat necrosis of the newborn is an uncommon disorder occurring during the prenatal stage. Generally occurring in full-term neonates or during the first four weeks after a traumatic delivery, the disorder is characterized by the appearance of hard subcutaneous nodules or plaques on the trunk, buttocks or thighs. It is normally a benign and transient condition, although it may be complicated by hypocalcemia, which requires close monitoring until skin lesions are cured. The authors describe two cases of subcutaneous fat necrosis of the newborn, one occurring in a full-term neonate and the other in a premature newborn, both related to traumatic delivery and fetal distress.

Acute hepatitis associated with the use of levofloxacin.

BACKGROUND: Levofloxacin is a fluoroquinolone used globally to treat respiratory, skin, and genitourinary tract infections. It is generally well tolerated and there is a very low risk for liver injury in patients taking this antibiotic. OBJECTIVE: We report an acute case of hepatitis following treatment with levofloxacin for pneumonia. CASE SUMMARY: A 77-year-old white male (height, 162 cm; weight, 58 kg) with chronic bronchitis presented to the emergency department of the Hospital Curry Cabral, Lisbon, Portugal, with respiratory difficulty and productive cough. The patient had a history of chronic bronchitis, arterial hypertension, hypercholesterolemia, and benign prostatic hyperplasia, and was being treated with salmeterol 50 µg plus fluticasone 250 µg BID, and amlodipine 5 mg, simvastatin 20 mg, alfuzosin 10 mg, and finasteride 5 mg once daily. Initially, the patient refused admission and was sent home, medicated with levofloxacin 500 mg once daily (single dose) for pneumonia and acetaminophen 1 g (as needed, maximum TID) if axillary temperature exceeded 38.0°C (100.4°F). Three days later, the patient returned for a follow-up visit, and despite clinical and radiologic improvement, blood tests revealed a slight aggravation of anemia. On the seventh day of treatment with levofloxacin, the patient showed an elevation of transaminases. The temporal relation between the use of levofloxacin and the liver injury, the exclusion of other causes of hepatitis, and a compatible liver biopsy (conducted 14 days after identification of hepatitis) was consistent with the diagnosis of levofloxacin-associated hepatotoxicity. Levofloxacin treatment was stopped and the patient made a full recovery. The Naranjo Adverse Drug Reaction Probability Scale score for this association was "probable" (score 7) and the Roussel Uclaf Causality Assessment Method Scale score was "highly probable" (score 9). Unlike the 5 reported cases in the literature, this is the only case in which both a liver biopsy was performed in the course of the disease and the patient survived. CONCLUSION: The acute hepatitis observed in this elderly patient was probably associated with the administration of levofloxacin.

Acne e cefaleias - uma relação que não deve ser esquecida / Acne and headache - a relationship that should not be forgotten

OBJETIVO: As cefaleias podem traduzir patologia grave, e a presença de sinais e sintomas de hipertensão intracraniana (HIC) alerta para a necessidade de investigação etiológica. Descreve-se o caso de uma adolescente com cefaleias e medicada com minociclina, fármaco amplamente utilizado em dermatologia. DESCRIÇÃO DE CASO: Adolescente de 12 anos com cefaleias, náuseas e vómitos, de agravamento progressivo, associados à diplopia horizontal intermitente e zumbido pulsátil. Medicada nas 6 semanas prévias com minociclina oral e adapaleno tópico por acne. Ao exame objetivo constatada limitação na abdução do olho direito e edema bilateral da papila, simétrico, não inflamatório. O estudo imagiológico excluiu massas intracranianas e foi realizada punção lombar com medição da pressão intracraniana (PIC) que se revelou superior a 50 cm de água. O vírus Epstein-Barr foi o único achado positivo no despiste infeccioso do líquido cefalorraquidiano. Iniciou acetazolamida e suspendeu a minociclina, com melhora dos sintomas. COMENTÁRIO: Dada a prevalência de acne nos adolescentes e a prescrição de tetraciclinas no seu tratamento, é essencial estar alerta para os sinais de HIC, de modo a instituir um tratamento atempado que previna a perda visual permanente(AU)

OBJECTIVE: Headaches can reflect serious pathologies, and the signs and symptoms of intracranial hypertension (ICH) indicate the need for etiological investigation. This case study describes an adolescent girl with headaches taking minocycline, a drug widely used in dermatology. CASE DESCRIPTION: A twelve-year-old female with progressively more severe headaches, nausea and vomiting, with horizontal diplopia and intermittent pulsatile tinnitus, medicated with oral minocycline and topical adapalene for acne over the previous six weeks. An objective examination revealed abduction limitation of the right eye and symmetrical non-inflammatory bilateral papilledema. The imaging study excluded intracranial mass and intracranial pressure at the lumbar puncture, higher than 50 cm of water. The Epstein-Barr virus was the only positive finding in the infectious examination of the cerebrospinal fluid. After switching to acetazolamide and taking her off minocycline, the symptoms improved. REMARK: Due to the prevalence of acne among adolescents and the prescription of tetracyclines for its treatment, it is vital to be alert for signs of ICH, with rapid treatment preventing permanent loss of sight(AU)

Necrose adiposa do recém-nascido: a propósito de dois casos clínicos / Fat necrosis of the newborn: report on two cases

A necrose adiposa subcutânea do recém-nascido é uma paniculite rara do período neonatal. Surge, geralmente, em recém-nascidos de termo ou pós-termo, nas primeiras 4 semanas de vida, e em associação com trauma obstétrico. Caracteriza-se pelo aparecimento de placas ou nódulos subcutâneos duros, localizados ao tronco, nádegas ou coxas. O seu curso é, geralmente, benigno e autolimitado, embora possa acompanhar-se de hipercalcemia, o que obriga a uma vigilância periódica até à resolução das lesões cutâneas. Os autores descrevem 2 casos de necrose adiposa subcutânea do recém-nascido, um num recémnascido de termo, outro num prematuro, ambos associados a partos traumáticos e a sofrimento fetal.

Subcutaneous fat necrosis of the newborn is an uncommon disorder occurring during the prenatal stage. Generally occurring in full-term neonates or during the first four weeks after a traumatic delivery, the disorder is characterized by the appearance of hard subcutaneous nodules or plaques on the trunk, buttocks or thighs. It is normally a benign and transient condition, although it may be complicated by hypocalcemia, which requires close monitoring until skin lesions are cured. The authors describe two cases of subcutaneous fat necrosis of the newborn, one occurring in a full-term neonate and the other in a premature newborn, both related to traumatic delivery and fetal distress.

Actitud ante la muerte en los Médicos de Familia / Attitude to death in family physicians

Se realizó un estudio descriptivo para caracterizar las actitudes ante la muerte en una muestra de 50 Médicos de Familia del Policlínico ôPlazaö. Se utilizó una versión cubana de un instrumento diseñado anteriormente para estudiar las actitudes ante la muerte. Se intentaba a su vez, establecer los primeros indicadores de validez y confiabilidad de esta versión denominada convencionalmente: cuestionario de actitudes ante la muerte (CAM), que incluía 33 reactivos, agrupados para su interpretación en 6 subescalas: evitación, aceptación, temor, pasaje, salida y perspectiva profesional. El procesamiento de las respuestas incluyó estadísticas descriptivas y pruebas de decisión con ayuda del sistema SSPS-PC+. Las actitudes prevalentes en los médicos eran de evitación y temor, en un contexto ambivalente dado por las actitudes positivas de aceptación de la muerte como un hecho natural, que se traduce en afrontamiento profesional no consecuente. En general, se encuentran actitudes que revelan la insuficiente preparación de los Médicos de Familia investigados para la aproximación realista a la muerte

Actitud ante la muerte en los Médicos de Familia / Attitude to death in family physicians

Se realizó un estudio descriptivo para caracterizar las actitudes ante la muerte en una muestra de 50 Médicos de Familia del Policlínico ôPlazaö. Se utilizó una versión cubana de un instrumento diseñado anteriormente para estudiar las actitudes ante la muerte. Se intentaba a su vez, establecer los primeros indicadores de validez y confiabilidad de esta versión denominada convencionalmente: cuestionario de actitudes ante la muerte (CAM), que incluía 33 reactivos, agrupados para su interpretación en 6 subescalas: evitación, aceptación, temor, pasaje, salida y perspectiva profesional. El procesamiento de las respuestas incluyó estadísticas descriptivas y pruebas de decisión con ayuda del sistema SSPS-PC+. Las actitudes prevalentes en los médicos eran de evitación y temor, en un contexto ambivalente dado por las actitudes positivas de aceptación de la muerte como un hecho natural, que se traduce en afrontamiento profesional no consecuente. En general, se encuentran actitudes que revelan la insuficiente preparación de los Médicos de Familia investigados para la aproximación realista a la muerte(AU)