RESUMO
Chronic rhinitis is a troublesome condition for sufferers. It is tempting to label all patients with chronic nasal symptoms as having allergic rhinitis (AR), but many such patients have other causes of chronic rhinitis that need a specific diagnosis and management strategy. Even when the patient fully fits the definition of AR, their condition will be best served by combining medication with ongoing patient education.
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Doença Crônica , Rinite/diagnóstico , Doença Crônica/terapia , Transtornos da Motilidade Ciliar/diagnóstico , Fibrose Cística/diagnóstico , Diagnóstico Diferencial , Humanos , Educação de Pacientes como Assunto , Doenças da Imunodeficiência Primária/diagnóstico , Rinite/etiologia , Rinite/terapia , África do SulAssuntos
Infecções por Coronavirus , Pandemias , Pneumonia Viral , Monofosfato de Adenosina/análogos & derivados , África , Alanina/análogos & derivados , Betacoronavirus , COVID-19 , Infecções por Coronavirus/tratamento farmacológico , Método Duplo-Cego , Humanos , SARS-CoV-2 , Tratamento Farmacológico da COVID-19RESUMO
BACKGROUND: Efforts have been made worldwide to improve awareness and treatment of primary immunodeficiency (PID). This has also gained momentum on the African continent albeit at a slower pace. Objective. This review reports on the current status of PID on the African continent regarding its prevalence, distribution, genetic mutations and challenges in diagnosis and treatment of affected patients. Method. We evaluated all studies published from the African continent in the field of PID dealing with prevalence, epidemiology, case reports and genetic findings. Results. The prevalence of PID on the African continent has been estimated to be as high as 902 631 individuals. PID still is mostly underdiagnosed in Africa and although progress has been made in parts of the continent many challenges still remain regarding awareness, diagnosis, registration and care of these patients. Conclusion. Given the unique genetic mutations reported in PID patients on the African continent and the feasibility of hematopoietic stem cell transplantation and gene therapy, increased awareness should be encouraged and new therapeutic options considered.
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Mutação , Doenças da Imunodeficiência Primária/epidemiologia , África/epidemiologia , Terapia Genética/métodos , Transplante de Células-Tronco Hematopoéticas/métodos , Humanos , Prevalência , Doenças da Imunodeficiência Primária/diagnóstico , Doenças da Imunodeficiência Primária/genéticaRESUMO
Although the neonatal mortality rate in South Africa (SA) has remained stagnant at 12 deaths per 1 000 live births, the infant and under-5 mortality rates have significantly declined since peaking in 2003. Policy changes that have influenced this decline include policies to prevent vertical HIV transmission, earlier treatment of children living with HIV, expanded immunisation policies, strengthening breastfeeding practices, and health policies to contain tobacco and sugar use. The Sustainable Development Goals (2016 - 2030) have shifted the focus from keeping children alive, as expressed in the Millennium Development Goals (1990 - 2015), to achieving optimal health through the 'Survive, thrive and transform' global agenda. This paper focuses on important remaining causes of childhood mortality and morbidity in SA, specifically respiratory illness, environmental pollution, tuberculosis, malnutrition and vaccine-preventable conditions. The monitoring of maternal and child health (MCH) outcomes is crucial, and has improved in SA through both the District Health Information and Civil Registration and Vital Statistics systems, although gaps remain. Intermittent surveys and research augment the routinely collected data. However, availability and use of local data to inform quality and effectiveness of care is critical, and this requires ownership at the collection point to facilitate local redress. Potential game changers to improve MCH outcomes include mobile health and community-based interventions. In SA, improved MCH remains a crucial factor for human capital development. There is a pressing need to focus beyond childhood mortality and to ensure that each child thrives.
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Saúde da Criança , Política de Saúde , Saúde do Lactente , Fármacos Anti-HIV/uso terapêutico , Aleitamento Materno , Mortalidade da Criança , Transtornos da Nutrição Infantil/epidemiologia , Transtornos da Nutrição Infantil/mortalidade , Transtornos da Nutrição Infantil/prevenção & controle , Pré-Escolar , Poluição Ambiental/prevenção & controle , Poluição Ambiental/estatística & dados numéricos , Feminino , Infecções por HIV/prevenção & controle , Infecções por HIV/transmissão , Humanos , Lactente , Fórmulas Infantis , Mortalidade Infantil , Transtornos da Nutrição do Lactente/epidemiologia , Transtornos da Nutrição do Lactente/mortalidade , Transtornos da Nutrição do Lactente/prevenção & controle , Recém-Nascido , Transmissão Vertical de Doenças Infecciosas/prevenção & controle , Saúde Materna , Morbidade , Gravidez , Doenças Respiratórias/epidemiologia , Doenças Respiratórias/mortalidade , África do Sul/epidemiologia , Desenvolvimento Sustentável , Tuberculose/epidemiologia , Tuberculose/mortalidade , Doenças Preveníveis por Vacina/epidemiologia , Doenças Preveníveis por Vacina/mortalidade , Vacinas/uso terapêuticoRESUMO
The fields of cell and gene therapy are moving rapidly towards providing innovative cures for incurable diseases. A current and highly topical example is immunotherapies involving T-cells that express chimeric antigen receptors (CAR T-cells), which have shown promise in the treatment of leukaemia and lymphoma. These new medicines are indicative of the changes we can anticipate in the practice of medicine in the near future. Despite their promise, they pose challenges for introduction into the healthcare sector in South Africa (SA), including: (i) that they are technologically demanding and their manufacture is resource intensive; (ii) that the regulatory system is underdeveloped and likely to be challenged by ethical, legal and social requirements that accompany these new therapies; and (iii) that costs are likely to be prohibitive, at least initially, and before economies of scale take effect. Investment should be made into finding novel and innovative ways to introduce these therapies into SA sooner rather than later to ensure that SA patients are not excluded from these exciting new opportunities.
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Terapia Baseada em Transplante de Células e Tecidos/economia , Difusão de Inovações , Terapia Genética/economia , Custos de Cuidados de Saúde , Acessibilidade aos Serviços de Saúde , Leucemia/terapia , Linfoma/terapia , Classe Social , Antígenos CD19/economia , Antígenos CD19/uso terapêutico , Produtos Biológicos , Terapia Baseada em Transplante de Células e Tecidos/ética , Terapia Genética/ética , Terapia Genética/legislação & jurisprudência , Humanos , Imunoterapia Adotiva/economia , Imunoterapia Adotiva/ética , Imunoterapia Adotiva/legislação & jurisprudência , Receptores de Antígenos de Linfócitos T/uso terapêutico , África do SulRESUMO
BACKGROUND: Soluble triggering receptor expressed on myeloid cells-1 (sTREM-1) is demonstrating promise as an inflammatory biomarker of acute infection in various pulmonary conditions; including community acquired pneumonia, ventilator associated pneumonia and non-tuberculous mycobacterial infection. INTRODUCTION: The expression of sTREM-1 has been poorly studied in all forms of bronchiectasis, both in the context of cystic fibrosis (CF) and non-cystic fibrosis bronchiectasis. METHOD: Induced sputum samples were collected for sTREM-1 determination in children with HIV-associated bronchiectasis and CF-bronchiectasis. The presence or absence of an exacerbation was noted at study entry. Lung function parameters (FEV1, FVC, FEV1 /FVC, FEF(25-75)) were measured using the Viasys SpiroPro Jaeger Spirometer (Hoechberg, Germany). RESULT: A total of twenty-six children with HIV-associated bronchiectasis and seventeen with CF were included. With respect to sTREM-1, the levels were readily detected in both groups, but were significantly higher in children with HIV-associated bronchiectasis (1244.0 pg/ml (iqr 194.5; 3755.3 pg/ml) and 204.9 pg/ml (iqr 66.9; 653.6 pg/ml) P = 0.003. There was a positive correlation between sTREM-1 and IL-8 as well as sputum neutrophil elastase in the HIV-bronchiectasis group (r = 0.715 and r = 0.630), respectively both P < 0.005. sTREM-1 was not further increased in subjects presenting with an acute pulmonary exacerbation in the HIV-associated bronchiectasis and in CF participants (P = 0.971 and P = 0.481), respectively. In the CF group sTREM-1 strongly correlated with FVC% predicted and FEV1 % predicted (r = 0.950 and r = 0.954), both P < 0.005. CONCLUSION: The pulmonary innate immune functions are over-active in HIV-associated bronchiectasis, with readily detected sTREM-1 values, which were higher than those in CF. sTREM-1 does not correlate with markers of HIV-disease activity but does correlate with markers of neutrophilic inflammation. In CF sTREM-1 has a negative correlation with pulmonary function parameters.
Assuntos
Bronquiectasia/metabolismo , Fibrose Cística/metabolismo , Glicoproteínas de Membrana/metabolismo , Receptores Imunológicos/metabolismo , Adolescente , Biomarcadores/metabolismo , Criança , Feminino , Infecções por HIV/metabolismo , Humanos , Interleucina-8/metabolismo , Elastase de Leucócito/metabolismo , Escarro/metabolismo , Receptor Gatilho 1 Expresso em Células MieloidesRESUMO
BACKGROUND: Colonisation of the airway by Pseudomonas spp. in cystic fibrosis has been reported to be an important determinant of decline in pulmonary function. OBJECTIVE: To assess pulmonary function decline and the presence of bacterial colonisation in patients with cystic fibrosis (CF) attending a CF clinic in a developing country. METHODS: A retrospective audit of patients attending the CF clinic at Steve Biko Academic Hospital, Pretoria, South Africa, was performed. The data included spirometric indices and organisms routinely cultured from airway secretions (Pseudomonas aeruginosa (PA) and Staphylococcus aureus (SA)). RESULTS: There were 29 study subjects. Analysis of variance for ranks (after determining that baseline pulmonary function, age, gender and period of follow-up were not contributing to pulmonary function decline) revealed a median decline in forced expiratory volume in 1 second, forced vital capacity and forced expiratory flow over 25 - 75% expiration of 12%, 6% and 3%, respectively, for individuals colonised by PA. There was no pulmonary function decline in individuals not colonised by PA, or in individuals colonised by SA. CONCLUSION: Pulmonary function decline in this South African centre is significantly influenced by chronic pseudomonal infection. Other influences on this phenomenon should be explored.
Assuntos
Fibrose Cística/fisiopatologia , Pulmão/fisiopatologia , Infecções por Pseudomonas/fisiopatologia , Pseudomonas aeruginosa , Criança , Doença Crônica , Fibrose Cística/complicações , Feminino , Humanos , Masculino , Infecções por Pseudomonas/complicações , Estudos Retrospectivos , África do Sul , Espirometria , Infecções Estafilocócicas/fisiopatologiaRESUMO
INTRODUCTION: Cystic fibrosis (CF) is the most common genetic disorder in Caucasians. Presentation of CF in non-Caucasians is less well studied. OBJECTIVE: This audit was undertaken to determine the phenotypic expression of the 3120+1G>A mutation in black and mixed race children in South Africa. METHODS: A multi-centre retrospective chart review of clinical, laboratory and spirometry data of non-Caucasian CF patients in four CF centres in South Africa was collected. Data was collected at diagnosis and after a five-year follow-up period. Ethical approval was granted for the study. RESULTS: A total of 30 participants were enrolled of whom 14 (47%) were homozygous and 16 (53%) heterozygous for the 3120+1G>A mutation. The mean age of diagnosis was 13 months. Twenty-four (80%) patients had malnutrition (mean weight z-score -3.6) or failure to thrive (77%) at presentation. Twenty (67%) presented with non-specific abdominal symptoms, whilst fifteen (50%) had recurrent respiratory tract infections. Pseudomonas aeruginosa was detected at a mean age of 21 months. The mean FEV1 was 73% predicted (95% CI 54.0-91.1) at study entry and 68% predicted (95% CI 49.74-87.06) at follow-up. CONCLUSION: Failure to thrive and a diagnosis of protein energy malnutrition (kwashiorkor) are the common presenting features of CF in children with the 3120+1G>A mutation. Meconium ileus is a rare presenting feature of CF in black and mixed race children with this deletion in South Africa.
Assuntos
População Negra/genética , Regulador de Condutância Transmembrana em Fibrose Cística/genética , Fibrose Cística/genética , Mutação , Feminino , Humanos , Lactente , Masculino , Fenótipo , Estudos Retrospectivos , África do SulRESUMO
Non-cystic fibrosis-related bronchiectasis is a chronic inflammatory lung disease, which is regarded as an "orphan" lung disease, with little research devoted to the study of this condition. Bronchiectasis results in impaired quality of life and mortality if left untreated. The tools available in the armamentarium for the management of bronchiectasis entail antibiotic therapy traditionally used to treat exacerbations, stratagems to improve mucociliary clearance, and avoidance of toxins. Macrolides have been known for the last two decades to have not only anti-bacterial effects but immunomodulatory properties as well. In cystic fibrosis, the use of macrolides is well documented in subjects colonized with Pseudomonas aeruginosa, to improve quality of life and lung function. There is currently emerging evidence to suggest the benefit of macrolides in subjects not colonized with Pseudomonas aeruginosa. This beneficial effect has been less explored in the context of bronchiectasis from other causes. The purpose of this paper is to review the current literature on the use of macrolides in non-cystic fibrosis related bronchiectasis in paediatrics.
Assuntos
Bronquiectasia/tratamento farmacológico , Macrolídeos/uso terapêutico , Administração por Inalação , Criança , Citocinas/metabolismo , Farmacorresistência Bacteriana , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Humanos , Imunidade Inata , Inflamação , Macrolídeos/administração & dosagem , Modelos Biológicos , Pseudomonas aeruginosa/metabolismo , Qualidade de Vida , Fatores de RiscoRESUMO
BACKGROUND: Human immunodeficiency virus (HIV) infected children have an eleven-fold risk of acute lower respiratory tract infection. This places HIV-infected children at risk of airway destruction and bronchiectasis. OBJECTIVE: To study predisposing factors for the development of bronchiectasis in a developing world setting. METHODS: Children with HIV-related bronchiectasis aged 6-14 years were enrolled. Data were collected on demographics, induced sputum for tuberculosis, respiratory viruses (respiratory syncytial virus), influenza A and B, parainfluenza 1-3, adenovirus and cytomegalovirus), bacteriology and cytokines. Spirometry was performed. Blood samples were obtained for HIV staging, immunoglobulins, immunoCAP®-specific immunoglobulin E (IgE) for common foods and aeroallergens and cytokines. RESULTS: In all, 35 patients were enrolled in the study. Of 161 sputum samples, the predominant organisms cultured were Haemophilus influenzae and parainfluenzae (49%). The median forced expiratory volume in 1 second of all patients was 53%. Interleukin-8 was the predominant cytokine in sputum and serum. The median IgE level was 770 kU/l; however, this did not seem to be related to atopy; 36% were exposed to environmental tobacco smoke, with no correlation between exposure and CD4 count. CONCLUSION: Children with HIV-related bronchiectasis are diagnosed after the age of 6 years and suffer significant morbidity. Immune stimulation mechanisms in these children are intact despite the level of immunosuppression.
Assuntos
Infecções Oportunistas Relacionadas com a AIDS/epidemiologia , Bronquiectasia/epidemiologia , Coinfecção/epidemiologia , Infecções por HIV/epidemiologia , Tuberculose Pulmonar/epidemiologia , Infecções Oportunistas Relacionadas com a AIDS/diagnóstico , Infecções Oportunistas Relacionadas com a AIDS/imunologia , Adolescente , Terapia Antirretroviral de Alta Atividade , Técnicas Bacteriológicas , Bronquiectasia/diagnóstico , Bronquiectasia/imunologia , Criança , Coinfecção/diagnóstico , Coinfecção/imunologia , Citocinas/isolamento & purificação , Países em Desenvolvimento , Infecções por HIV/diagnóstico , Infecções por HIV/tratamento farmacológico , Infecções por HIV/imunologia , Humanos , Testes Imunológicos , Mediadores da Inflamação/isolamento & purificação , Mycobacterium tuberculosis/isolamento & purificação , Medição de Risco , Fatores de Risco , África do Sul/epidemiologia , Espirometria , Escarro/imunologia , Escarro/microbiologia , Escarro/virologia , Tuberculose Pulmonar/diagnóstico , Tuberculose Pulmonar/imunologiaRESUMO
We report a patient with myelodysplasia and bone marrow fibrosis. We managed him with regular blood transfusion for a period of 16 months. A modest dose of calcitriol (1,25-dihydroxycholecalciferol) 0.75 microg daily for 12 weeks resulted in a gradual but complete response in his haemoglobin level. There were significant bone marrow changes in that the fibrosis has completely disappeared although the marrow cytology remained dysplastic. The normal haemoglobin level persists despite an intensive venesection programme aimed at reducing iron overload. We conclude that calcitriol should be given for at least 12 weeks in patients with myelodysplasia especially if there is a fibrotic element in the bone marrow. The role of venesection in maintaining remission is a speculative.
Assuntos
Calcitriol/administração & dosagem , Síndromes Mielodisplásicas/terapia , Flebotomia , Mielofibrose Primária/terapia , Idoso , Antineoplásicos/administração & dosagem , Contagem de Células Sanguíneas , Terapia Combinada , Hemoglobinas/análise , Humanos , Masculino , Síndromes Mielodisplásicas/complicações , Mielofibrose Primária/complicações , Indução de Remissão/métodos , Resultado do TratamentoRESUMO
A 39-yr-old man with stage IV Hodgkin's disease (HD) involving bone marrow was being evaluated for autologous bone marrow transplantation when he developed diplopia, prompting a lumbar puncture tap for cerebral spinal fluid (CSF) examination. Cytologic examination of the CSF revealed numerous Reed-Sternberg (RS) cells in a polymorphous inflammatory background of small lymphocytes, monocytes, rare plasma cells, and eosinophils. However, magnetic resonance imaging (MRI) studies of the brain and spinal cord failed to reveal evidence of leptomeningeal disease or intracranial masses. Repeat CSF examination again demonstrated cytologic evidence of HD. Immunocytochemical stains established that the RS cells and mononuclear Hodgkin's cells were positive for CD30 and CD20 but negative for CD15; this phenotype was identical to that of RS cells in the initial diagnostic bone marrow biopsy, confirming CSF involvement by HD. The patient was treated with intrathecal methotrexate, 15 mg, 6 days after his bone marrow transplant. After treatment, all subsequent CSF cytology specimens were negative for tumor. In this case of disseminated HD, cytologic examination allowed for early detection of CNS involvement by lymphoma prior to development of radiographically detectable lesions.
Assuntos
Líquido Cefalorraquidiano/citologia , Doença de Hodgkin/diagnóstico , Imuno-Histoquímica , Adulto , Biópsia , Células da Medula Óssea/patologia , Líquido Cefalorraquidiano/química , Humanos , Masculino , Reação em Cadeia da PolimeraseRESUMO
This article reviews the use of systemic chemotherapy for the treatment of metastatic melanoma, including single-agent chemotherapy, combination chemotherapy with and without tamoxifen, and biochemotherapy.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Melanoma/tratamento farmacológico , Melanoma/patologia , Neoplasias Cutâneas/tratamento farmacológico , Neoplasias Cutâneas/patologia , Adulto , Feminino , Humanos , Masculino , Melanoma/fisiopatologia , Metástase Neoplásica , Neoplasias Cutâneas/fisiopatologia , Tamoxifeno/uso terapêuticoRESUMO
Platelet-derived growth factor (PDGF) is a polypeptide growth factor which has been implicated as a major mitogen involved in wound healing. The PDGF appears to promote periodontal regeneration; however, its distribution in gingival tissues is not known and how it participates in gingival wound healing is unclear. Using highly specific antibodies we have studied the distribution of PDGF A and B chains and alpha- and beta-PDGF receptors in healing human gingival wounds. Wounds were created by making a 0.75 mm deep incision in the papilla and healthy gingiva and biopsies were obtained from the same site after 8 h and 1, 3, 7, 14 and 21 d. Frozen sections were immunostained with affinity purified antibodies. The results showed that both epithelium and fibrin clot manifested positive immunostaining for anti-PDGF-A and B-chain antibodies. Staining was present in unwounded and wounded epithelia, and in the fibrin clot it appeared to be more intense for the PDGF-A chain. Blood vessels in connective tissue were also positive while other areas were largely negative. No significant staining was detectable in healthy tissues for anti-PDGF-alpha or -beta receptor antibodies. However, the wound site began to manifest positive immunostaining fro anti-beta-receptor antibody after 3 d of healing, became maximal at 7 d, and then decreased. Our data indicate, but do not prove, that gingival epithelium may be a source of PDGF A and B chains and that the A chain may have a more prominent role to play during early stages of healing. Expression of PDGF beta-receptor appears later at the wound site, indicating that the PDGF B isomer may regulate later wound healing events.
Assuntos
Gengiva/lesões , Fator de Crescimento Derivado de Plaquetas/análise , Receptores do Fator de Crescimento Derivado de Plaquetas/análise , Adulto , Anticorpos , Becaplermina , Biópsia , Coagulação Sanguínea , Vasos Sanguíneos/patologia , Corantes , Tecido Conjuntivo/patologia , Epitélio/lesões , Epitélio/patologia , Fibrina , Seguimentos , Expressão Gênica , Gengiva/patologia , Humanos , Imuno-Histoquímica , Mitógenos/análise , Periodonto/fisiologia , Fator de Crescimento Derivado de Plaquetas/genética , Proteínas Proto-Oncogênicas c-sis , Receptores do Fator de Crescimento Derivado de Plaquetas/genética , Regeneração , Fatores de Tempo , CicatrizaçãoRESUMO
Pulmonary vascular inflammatory disorders may involve all components of the pulmonary vasculature, including capillaries. The principal histopathologic features of pulmonary capillaritis include capillary wall necrosis with infiltration by neutrophils, interstitial erythrocytes, and/or hemosiderin, and interalveolar septal capillary occlusion by fibrin thrombi. Immune complex deposition is variably present. Patients often present clinically with diffuse alveolar hemorrhage, which is characterized by dyspnea and hemoptysis; diffuse, bilateral, alveolar infiltrates on chest radiograph; and anemia. Pulmonary capillaritis has been reported with variable frequency and severity as a manifestation of Wegener's granulomatosis, microscopic polyarteritis, systemic lupus erythematosus, Goodpasture's syndrome, idiopathic pulmonary renal syndrome, Behçet's syndrome, Henoch-Schönlein purpura, IgA nephropathy, antiphospholipid syndrome, progressive systemic sclerosis, and diphenylhydantoin use. In addition to history, physical examination, and routine laboratory studies, certain ancillary laboratory tests, such as antineutrophil cytoplasmic antibodies, antinuclear antibodies, and antiglomerular basement membrane antibodies, may help diagnose an underlying disease. Diagnosis of pulmonary capillaritis can be made by fiberoptic bronchoscopy with transbronchial biopsy, but thoracoscopic biopsy is often employed. Since many disorders can result in pulmonary capillaritis with diffuse alveolar hemorrhage, it is crucial for clinicians and pathologists to work together when attempting to identify an underlying disease. Therapy depends on the disorder that gave rise to the pulmonary capillaritis and usually includes corticosteroids and cyclophosphamide or azathioprine. Since most diseases that result in pulmonary capillaritis are treated with immunosuppression, infection must be excluded aggressively.
Assuntos
Hemorragia/diagnóstico , Pulmão/irrigação sanguínea , Alvéolos Pulmonares/patologia , Vasculite/diagnóstico , Anemia/diagnóstico , Broncoscopia , Capilares/patologia , Diagnóstico Diferencial , Dispneia/diagnóstico , Eritrócitos/patologia , Fibrina , Hemoptise/diagnóstico , Hemorragia/tratamento farmacológico , Hemorragia/etiologia , Hemorragia/patologia , Hemossiderina , Humanos , Imunossupressores/uso terapêutico , Pneumopatias/diagnóstico , Pneumopatias/tratamento farmacológico , Pneumopatias/etiologia , Pneumopatias/patologia , Necrose , Neutrófilos/patologia , Embolia Pulmonar/patologia , Toracoscopia , Vasculite/tratamento farmacológico , Vasculite/etiologia , Vasculite/patologiaRESUMO
Necrotizing fasciitis is an uncommon soft-tissue infection, usually caused by toxin-producing, virulent bacteria, which is characterized by widespread fascial necrosis with relative sparing of skin and underlying muscle. It is accompanied by local pain, fever, and systemic toxicity and is often fatal unless promptly recognized and aggressively treated. The disease occurs more frequently in diabetics, alcoholics, immunosuppressed patients, i.v. drug users, and patients with peripheral vascular disease, although it also occurs in young, previously healthy individuals. Although it can occur in any region of the body, the abdominal wall, perineum, and extremities are the most common sites of infection. Introduction of the pathogen into the subcutaneous space occurs via disruption of the overlying skin or by hematogenous spread from a distant site of infection. Polymicrobial necrotizing fasciitis is usually caused by enteric pathogens, whereas monomicrobial necrotizing fasciitis is usually due to skin flora. Tissue damage and systemic toxicity are believed to result from the release of endogenous cytokines and bacterial toxins. Due to the paucity of skin findings early in the disease, diagnosis is often extremely difficult and relies on a high index of suspicion. Definitive diagnosis is made at surgery by demonstration of a lack of resistance of normally adherent fascia to blunt dissection. Treatment modalities include surgery, antibiotics, supportive care, and hyperbaric oxygen. Early and adequate surgical debridement and fasciotomy have been associated with improved survival. Initial antibiotic therapy should include broad aerobic and anaerobic coverage. If available, hyperbaric oxygen therapy should be considered, although to our knowledge, there are no prospective, randomized clinical trials to support this. Mortality rates are as high as 76%. Delays in diagnosis and/or treatment correlate with poor outcome, with the cause of death being overwhelming sepsis syndrome and/or multiple organ system failure.
Assuntos
Fasciite Necrosante , Fasciite Necrosante/diagnóstico , Fasciite Necrosante/etiologia , Fasciite Necrosante/terapia , HumanosAssuntos
Adenocarcinoma Papilar/diagnóstico , Obstrução das Vias Respiratórias/diagnóstico , Fluxo Expiratório Forçado/fisiologia , Neoplasias da Traqueia/diagnóstico , Adenocarcinoma Papilar/fisiopatologia , Adenocarcinoma Papilar/cirurgia , Obstrução das Vias Respiratórias/fisiopatologia , Obstrução das Vias Respiratórias/cirurgia , Asma/fisiopatologia , Broncoscopia , Diagnóstico Diferencial , Feminino , Humanos , Terapia a Laser , Pessoa de Meia-Idade , Traqueia/fisiopatologia , Traqueia/cirurgia , Neoplasias da Traqueia/fisiopatologia , Neoplasias da Traqueia/cirurgiaRESUMO
The expression of common fragile sites at 69 bands was evaluated in 20 normal children and in 15 children with newly diagnosed acute leukemia using medium with folate (FA+) and without folate (FA-). As expected, the FA- medium significantly increased expression of aberrations in all study groups but the differences were larger for normal children than leukemic children. The major effect of the FA- medium was a generalized increase in aberration frequency over all sites rather than site-specific increases. A tendency toward clumping of aberrations within cells was exhibited in both media. Aberrations were seen at 81% (FA+) and 83% (FA-) of the 69 bands, with 4 sites - 3p14, 6p21, 9q13, and 17q23 - recorded in most of the study individuals. In addition, 12 sites not previously recorded as common or rare sites had significant levels of expression in at least one study group.
Assuntos
Fragilidade Cromossômica , Ácido Fólico/farmacologia , Leucemia/genética , Linfócitos/ultraestrutura , Doença Aguda , Adolescente , Células Cultivadas , Criança , Pré-Escolar , Sítios Frágeis do Cromossomo , Meios de Cultura , Feminino , Humanos , Lactente , MasculinoRESUMO
Using isolated healthy human leucocytes and erythrocytes as model cells, we investigated the inhibitory effect of ethanol, its metabolites and of other toxic alcohols on the active fluxes of rubidium (Rb: equivalent to K) and sodium (Na), and on Na,K-ATPase activity. Ethanol (80 mmol X l-1) inhibited total and ouabain-sensitive 86Rb influx and 22Na efflux in leucocytes, this being dose-related for total, ouabain-sensitive and ouabain-insensitive fluxes at higher concentrations. In erythrocytes inhibition occurred at 20 mmol X l-1 for 86Rb influx, dose-related at higher concentrations as for leucocytes. 22Na efflux was inhibited at 80 mmol X l-1 and above. Acetaldehyde (0.1 and 0.2 mmol X l-1), 1,2-propanediol (0.8 mmol X l-1) and 2,3-butanediol (0.4 mmol X l-1) inhibited all fractions of 86Rb influx in erythrocytes, but not in leucocytes. Methanol, 2-propanol and 1,2-ethanediol (16 and 32 mmol X l-1) inhibited 86Rb influx in erythrocytes, but not in leucocytes. The order of potency was 2-propanol greater than 1,2-ethanediol greater than methanol. Na,K-ATPase activity was inhibited in lysed leucocyte and erythrocyte preparations only at very high concentrations of the alcohols--suggesting that inhibition is due to an alteration in membrane structure and not to a direct effect on the enzyme.