RESUMO
BACKGROUND: In obesity, metabolic stress and inflammation in injured tissues could favour enhanced shedding of procoagulant microparticles (MPs). At sites of endothelium injury, the swift recruitment of procoagulant leukocyte-derived MPs enables the initiation of blood coagulation and thrombus growth. OBJECTIVES: In obese females, we sought to evaluate the impact of a very low-calorie diet (VLCD) on procoagulant MP levels, fibrinolytic status, inflammation and endothelium damage. METHODS: Circulating biomarkers of vascular damage, fibrinolytic status, platelet activation and inflammation were measured before, 30 and 90 days after starting a short-term VLCD. MPs were measured by flow cytometry and capture assays. Their procoagulant potential was quantified using functional prothrombinase assays and their cellular origin were determined using flow cytometry (endothelium, platelet, leukocyte, lymphocyte and erythrocyte-derived MP) or capture assays. RESULTS: A total of 24 obese females (39 ± 10 years) with a mean body mass index of 35 ± 4 kg m(-2) were prospectively enroled. Procoagulant leukocyte-derived MPs were associated with the waist circumference at baseline (r=0.534; P=0.010) and at 90 days follow-up (r=0.487; P=0.021). At 90 days, weight reduction (-9.8%) was associated with a lowering of blood pressure, improvement of metabolic parameters and a significant reduction of plasminogen activator inhibitor-1 (PAI-1) (-38%), procoagulant platelet-derived MPs (-43%), leukocyte-derived MPs (-28%) and leptin (-32%) levels. CONCLUSION: In obese females, a short-term VLCD results in an overall improvement of the haemostatic balance characterized by the reduction of PAI-levels, diminished release of platelet and leukocyte-derived MPs and a reduction in leptin levels, an adipocyte-derived cytokine.
Assuntos
Fatores de Coagulação Sanguínea/metabolismo , Plaquetas/metabolismo , Restrição Calórica , Leptina/sangue , Leptina/metabolismo , Leucócitos/metabolismo , Obesidade/sangue , Inibidor 1 de Ativador de Plasminogênio/metabolismo , Adolescente , Adulto , Idoso , Biomarcadores/sangue , Endotélio Vascular/metabolismo , Eritrócitos/metabolismo , Feminino , Hemostasia , Humanos , Pessoa de Meia-Idade , Obesidade/dietoterapia , Obesidade/metabolismo , Estudos Prospectivos , Tromboplastina/metabolismo , Trombose/metabolismo , Redução de Peso , Adulto JovemAssuntos
Inibidores dos Fatores de Coagulação Sanguínea/sangue , Fator VIII/antagonistas & inibidores , Fator VIII/imunologia , Hemofilia A/imunologia , Hemofilia A/terapia , Terapia de Imunossupressão/métodos , Adulto , Anticorpos Monoclonais Murinos/administração & dosagem , Inibidores dos Fatores de Coagulação Sanguínea/imunologia , Fator VIII/administração & dosagem , Humanos , Tolerância Imunológica , Masculino , Rituximab , Fatores de TempoRESUMO
UNLABELLED: Although antiplatelet therapy with ASA-clopidogrel reduces the risk of cardiovascular episodes after PCI, a substantial number of events occur during follow-up. Sustained platelet reactivity under dual antiplatelet therapy was recently associated with increased risk of recurrent atherothrombotic events after PCI. Whereas it appears significant to determine clopidogrel responsiveness, the accurate platelet function assay is still under investigation. OBJECTIVES: (i) to determine the proportion of "low-responders" or "resistants" patients during coronary syndrome (ii) to identify determinants of interindividual variability response to clopidogrel (iii) to compare aggregometry and VASP phosphorylation measured by flow cytometry. Patients were treated by clopidogrel (300 mg loading dose and 75 mg maintenance dose) and ASA (160 mg) (N=27). Additional treatment by GPIIbIIIa antagonists was given to high-risk patients (N=9). Platelet function was monitored by ADP aggregometry (5, 10, 20 microM) and VASP phosphorylation before any treatment by clopidogrel (d0) and at least five days after (d5). The platelet reactivity index (PRI), expressed as percentage, is the difference in VASP fluorescence intensity between resting (+ PGE1) and activated (ADP) platelets. At d5, low responsiveness to clopidogrel was defined by either (i) a PRI > 67.3% corresponding to the mean value -2SD measured in untreated patients (dO) (ii) or an absolute change (delta d0-d5) in aggregation (ADP 10 microM) < to 30%. RESULTS: PRI, platelet aggregometry to ADP was significantly reduced following clopidogrel treatment (P < 0.01). A wide inter-individual variability to clopidogrel was observed at d5 (PRI from 11 to 83%). Whatever the platelet function used, a large proportion of patients were detected as "low-responders" (37% by VASP, 44% by ADP aggregometry). Absolute change in ADP aggregation was correlated to the variation of PRI (R = 0.559; P = 0.02). Contrary to ADP aggregometry, PRI was not influenced by GPIIbIIIa antagonists or prior administration of ASA. However, the conformity of the two methods to evaluate clopidogrel responsiveness was only 66%. No differences in platelet aggregometry could be observed at d5 between "low" and "good-responders" defined by VASP analysis. At d5, a higher PRI value could be detected in male and patients with history of dyslipemia. CONCLUSION: During coronary syndrome, impaired platelet responsiveness to clopidogrel was observed in a large proportion of patients whatever the platelet function assay used. VASP analysis was found insensitive to GPIIbIIIa or aspirin administration. Possible mechanisms linking clopidogrel "resistance" measured by VASP assay and enhanced thrombogenicity remain to be characterized. Indeed, clopidogrel "resistance" defined by VASP analysis was not associated with higher platelet aggregation.
Assuntos
Difosfato de Adenosina/farmacologia , Plaquetas/efeitos dos fármacos , Proteínas Sanguíneas/metabolismo , Moléculas de Adesão Celular/metabolismo , Proteínas dos Microfilamentos/metabolismo , Infarto do Miocárdio/terapia , Fosfoproteínas/metabolismo , Inibidores da Agregação Plaquetária/uso terapêutico , Agregação Plaquetária/efeitos dos fármacos , Ticlopidina/análogos & derivados , Idoso , Aspirina/uso terapêutico , Clopidogrel , Resistência a Medicamentos , Feminino , Citometria de Fluxo , Fluoresceína-5-Isotiocianato , Corantes Fluorescentes , Seguimentos , Humanos , Masculino , Infarto do Miocárdio/sangue , Fosforilação/efeitos dos fármacos , Complexo Glicoproteico GPIIb-IIIa de Plaquetas/antagonistas & inibidores , Síndrome , Ticlopidina/uso terapêuticoRESUMO
INTRODUCTION: Hemophilic arthropathy is painful and disabling. We report a retrospective study of ankle fusion with intra- and peri-operative clotting factor perfusion. The objective was to assess the efficacy of maintaining perioperative clotting factor rates close to 100%, and report long-term results. The study hypothesis was that results would be good, without early hemorrhagic complications. MATERIAL AND METHOD: Between 2000 and 2013, 12 ankle fusions were performed in 9 patients, with a mean age of 39years (range, 19-58years). Anti-hemophilic factor perfusion was controlled by the reference physician of the Regional Hemophilia Treatment Center. Clinical AOFAS and Olerud scores and the Pettersson radiologic score were used for assessment. Mean preoperative AOFAS score was 22 (range, 2-55) and mean Olerud score 7 (range, 5-12). Mean preoperative factor VIII concentration was <1% (range, <1-3%). RESULTS: Mean follow-up was 8years (range, 2-16years). Mean AOFAS score at follow-up was 69 (range, 35-92) and mean Olerud score 70 (range, 30-100). Improvement mainly concerned the Pain dimension. Statistical analysis found a significant difference between pre- and post-operative clinical scores (AOFAS, P=0.004; Olerud, P=0.004). Mean factor VIII concentration at surgery was 90% (range, 24-117%), and 109% (range, 75-152%) the day following surgery. There were no cases of hematoma or surgical site infection. Radiologic fusion was systematic at a mean 3.5 months (range, 3-4months). CONCLUSION: The study hypothesis was confirmed. Ankle fusion in advanced hemophilic arthropathy improved function and quality of life. Perioperative clotting factor perfusion contributed to these good results, providing supplementary prevention of hemorrhagic risk. LEVEL OF EVIDENCE: IV, retrospective study.
Assuntos
Articulação do Tornozelo/fisiopatologia , Articulação do Tornozelo/cirurgia , Artrodese , Hemofilia A/fisiopatologia , Adulto , Artralgia/fisiopatologia , Artralgia/cirurgia , Parafusos Ósseos , Coagulantes/administração & dosagem , Fator VIII/administração & dosagem , Fator VIII/análise , Feminino , Seguimentos , Humanos , Infusões Intravenosas , Masculino , Pessoa de Meia-Idade , Osseointegração , Assistência Perioperatória , Qualidade de Vida , Estudos Retrospectivos , Adulto JovemRESUMO
AIM: Obesity is a risk factor for cardiovascular diseases and venous thromboembolism. Circulating procoagulant microparticles (MP) have been described in various clinical situations associated with thrombosis and in diabetic patients. The aim of this preliminary study was to evaluate the presence of MP in obese patients without any other vascular risk factor in particular diabetes. METHODS: Fifty-eight obese women <50 year-old without other cardiovascular risk factors were recruited from a single out-patient nutrition clinic. They were compared to 45 age-matched healthy normal weight controls. Main outcome was MP levels in patients and controls. Relationships between MP concentrations and parameters reflecting insulin resistance in patients were also studied. RESULTS: Obese patients were 33.3 +/- 1.2 years old and had a mean BMI of 42.4 +/- 0.9 kg/m2. There vas a greater proportion of smokers in the obese group (34.5 vs 15.6%). Mean MP levels were markedly higher in obese patients compared to controls (10.6 +/- 0.5 vs 3.2 +/- 0.3 nMPSeq, P < 0.001). There was no difference in MP concentrations between smokers and non smokers. In the obese group, there was a negative correlation between MP and BMI (r = -0.265, P < 0.05) but no relationship could be established between MP concentrations and markers of insulin resistance. CONCLUSION: This increase in circulating MP levels reflects cell activation and could account for the increased risk of thrombotic complications in obesity. Further studies are ongoing to explore the relationships between MP levels and coagulation markers and to assess the effect of weight reduction.
Assuntos
Fatores de Coagulação Sanguínea/análise , Obesidade Mórbida/sangue , Obesidade/sangue , Fragmentos de Peptídeos/sangue , Adulto , Idoso , Doenças Cardiovasculares/epidemiologia , Feminino , França/epidemiologia , Humanos , Pessoa de Meia-Idade , Fatores de Risco , Fumar/epidemiologia , Tromboembolia/epidemiologiaRESUMO
Proximal spinal muscular atrophy (SMA) is an autosomal recessive disease characterized by degeneration of alpha-motor neurons and muscular atrophy. The causal survival motor neuron (SMN) gene maps to a complex region of chromosome 5q13 harbouring an inverted duplication. Thus, there are two SMN genes, SMN1 and SMN2, but SMN1-deficiency alone causes SMA. In this study we demonstrate, for the first time, down-regulation of SMN promoter activity during cellular differentiation. Specifically, the minimal SMN promoter is four times more active in undifferentiated embryonal carcinoma P19 cells compared to cells treated with retinoic acid (RA) to initiate neuronal differentiation. This effect is mediated by sequences contained within the minimal core promoter that we have confined to the 257 nucleotides upstream of exon 1. We have identified seven regions that are highly conserved between the mouse and human SMN core promoters and this region contains the consensus sequence for a number of transcription factors. Most notably, AhR, HNF-3 and N-Oct3 have already been shown to respond to RA treatment of EC cells, while E47, HNF-3, MAZ, N-Oct3 and Pit-1a have been implicated in embryonic, muscle or neural development. In addition, we have mapped two strong transcription initiation sites upstream of SMN exon 1. The novel -79 site identified in this study is preferentially utilized during human foetal development. Furthermore, analysis of RNA from SMA patients with deletions of the entire SMN1 gene or chimpanzees that lack SMN2 suggests that the level of transcription initiation at these sites may be different for the SMN1 and SMN2 genes. Taken together, this work provides the first demonstration of transcriptional regulation of these genes during cellular differentiation and development. Deciphering the underlying mechanisms responsible for regulating SMN transcription may provide important clues towards enhancing SMN2 gene expression, one target for the treatment of SMA.
Assuntos
Diferenciação Celular/genética , Proteínas do Tecido Nervoso/genética , Animais , Sequência de Bases , Sítios de Ligação/genética , Cloranfenicol O-Acetiltransferase/genética , Cloranfenicol O-Acetiltransferase/metabolismo , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico , DNA/genética , Feminino , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Camundongos , Dados de Sequência Molecular , Atrofia Muscular Espinal/genética , Regiões Promotoras Genéticas/genética , Proteínas de Ligação a RNA , Proteínas Recombinantes de Fusão/efeitos dos fármacos , Proteínas Recombinantes de Fusão/genética , Proteínas Recombinantes de Fusão/metabolismo , Proteínas do Complexo SMN , Homologia de Sequência do Ácido Nucleico , Proteína 1 de Sobrevivência do Neurônio Motor , Proteína 2 de Sobrevivência do Neurônio Motor , Fatores de Transcrição/metabolismo , Sítio de Iniciação de Transcrição , Transcrição Gênica , Tretinoína/farmacologia , Células Tumorais CultivadasRESUMO
Gastroesophageal variceal bleeding due to portal hypertension should be treated by endoscopic sclerotherapy. This procedure, however, has some limitations. It has been established that vasoactive drugs are effective for controlling active variceal bleeding. We report the results of a randomized controlled trial comparing terlipressin to hemostatic tube (Linton-Michel tube) for the treatment of bleeding gastroesophageal varices in cirrhotic patients. Thirty-seven cirrhotic patients with a total of 40 episodes of gastroesophageal variceal bleeding were included in this trial. Patients were randomly assigned to intravenous terlipressin or Linton-Michel tube (LM tube), for 24 h. During this period, hemostasis was defined as obtaining of hemodynamic and hematocrit stabilization and/or absence of hematemesis or melena. Bleeding recurrence was assessed during a 1-month period after treatment. Twenty bleeding episodes were treated with terlipressin (Group I) and 20 with LM tube (Group II). Both groups of patients were similar in age, sex distribution, etiology of cirrhosis and degree of hepatic insufficiency. Bleeding was controlled in 70% of patients from Group I and in 95% from Group II (p < 0.05) during treatment. Bleeding recurred in 14% of patients in Group I vs. 36% in Group II 1 week following the treatment (p > 0.05) and in 16.6% in Group I vs. 83.3% in Group II 1 month after treatment (p < 0.05). Complications were more frequent in Group II than in Group I (65 vs. 15%, p < 0.05). Mortality rate was similar in both groups 1 month after treatment. In conclusion, hemostatic tubes were superior to terlipressin for the control of active gastroesophageal variceal bleeding within the first 24 h. Complications and bleeding recurrence were more frequent in patients treated by hemostatic tube within a period of 1 month after treatment. Mortality rate was similar in both groups of patients.
Assuntos
Anti-Hipertensivos/uso terapêutico , Cateterismo , Varizes Esofágicas e Gástricas/terapia , Hemorragia Gastrointestinal/terapia , Técnicas Hemostáticas , Cirrose Hepática/complicações , Lipressina/análogos & derivados , Adulto , Idoso , Anti-Hipertensivos/efeitos adversos , Cateterismo/efeitos adversos , Varizes Esofágicas e Gástricas/tratamento farmacológico , Varizes Esofágicas e Gástricas/etiologia , Feminino , Hemorragia Gastrointestinal/tratamento farmacológico , Hemorragia Gastrointestinal/mortalidade , Hemodinâmica/efeitos dos fármacos , Técnicas Hemostáticas/efeitos adversos , Humanos , Hipertensão Portal/tratamento farmacológico , Hipertensão Portal/etiologia , Lipressina/efeitos adversos , Lipressina/uso terapêutico , Masculino , Pessoa de Meia-Idade , Recidiva , Taxa de Sobrevida , Terlipressina , Resultado do TratamentoRESUMO
A case of pulmonary endocarditis caused by Streptococcus D bovis in a female patient with colorectal adenocarcinoma is reported. The M-mode and two-dimensional echocardiographic and pulsed doppler ultrasound findings are described. A review of the literature shows that Streptococcus D bovis pulmonary endocarditis is rare. Any septicaemia or endocarditis caused by this organism calls for invasive exploration of the digestive tract, and especially the colon.
Assuntos
Adenocarcinoma/complicações , Neoplasias do Colo/complicações , Endocardite Bacteriana/etiologia , Insuficiência da Valva Pulmonar/etiologia , Infecções Estreptocócicas , Idoso , Ecocardiografia , Feminino , Humanos , Insuficiência da Valva Pulmonar/cirurgia , UltrassonografiaRESUMO
We report the case of a 40 year-old woman, pregnant for 4 months, with acute hepatitis revealed by jaundice, fever and high serum aminotransferase levels. Infection by Listeria monocytogenes was demonstrated by blood cultures. The course of the disease was characterized by abortion and complete recovery of hepatitis within 4 weeks after antibiotic administration. This report shows that listeriosis can cause acute severe hepatitis.
Assuntos
Hepatite/microbiologia , Listeria monocytogenes/isolamento & purificação , Listeriose/microbiologia , Aborto Espontâneo , Doença Aguda , Adulto , Amoxicilina/administração & dosagem , Amoxicilina/uso terapêutico , Feminino , Hepatite/tratamento farmacológico , Hepatite/patologia , Humanos , Listeriose/tratamento farmacológico , Listeriose/patologia , Gravidez , Complicações Infecciosas na Gravidez , Segundo Trimestre da GravidezRESUMO
OBJECTIVES: The effectiveness of the association of lactulose with neomycin in the treatment of acute hepatic encephalopathy has never been assessed. The aim of this study was to compare the effects of lactulose-neomycin combination versus placebo in acute hepatic encephalopathy. METHODS: Eighty patients with cirrhosis were randomly treated for 5 days with placebo (n = 40) or with lactulose-neomycin (n = 40). Both groups were similar for all variables. RESULTS: The course of encephalopathy was similar in both groups. In the lactulose-neomycin group: 26 PATIENTS recovered, 3 remained unchanged, 3 worsened, 6 died, 2 were lost to follow-up. In the placebo group: 28 recovered, 2 remained unchanged, 2 worsened, 6 died, one was lost the follow-up, one dropped out of the study. Lactulose-neomycin treatment was not well tolerated in a significant number of patients. CONCLUSION: Lactulose-neomycin combination should not be used in the treatment of acute hepatic encephalopathy.
Assuntos
Encefalopatia Hepática/tratamento farmacológico , Lactulose/uso terapêutico , Cirrose Hepática/complicações , Neomicina/uso terapêutico , Doença Aguda , Idoso , Quimioterapia Combinada , Feminino , Encefalopatia Hepática/etiologia , Humanos , Masculino , Pessoa de Meia-Idade , PlacebosRESUMO
OBJECTIVES: The intrafamilial transmission of hepatitis C virus infection was assessed in the family members of patients with chronic hepatitis C. METHODS: The presence of serum anti-hepatitis C virus (HCV) antibodies and epidemiological features were studied in 193 relatives (104 heterosexual partners, 89 children) of 113 patients with chronic hepatitis C. The presence of serum anti-HCV antibodies was detected by an ELISA 2 test and confirmed by a RIBA 2 test. In all patients, liver injury was ascertained by biopsy (31 cirrhosis, 82 chronic active hepatitis). RESULTS: Eleven of 104 (10.6%) regular heterosexual partners were positive for anti-HCV antibodies. In 8 of these, risk factors were detected (drug addiction: n = 6, blood transfusion: n = 1, occupational exposure: n = 1). Only 3 of 96 (3.2%) regular heterosexual partners without percutaneous risk factors were positive for HCV. Among couples with heterosexual partners negative for anti-HCV antibodies, the mean duration of the sexual relationship was 12 years. Serum anti-HCV antibodies were present in 1 of 89 (1.1%) children without history of blood transfusion or drug addiction. None of the 35 children born after supposed maternal contamination were positive for serum anti-HCV antibodies. CONCLUSIONS: We conclude that the prevalence of serum anti-HCV antibodies, assessed with second generation tests, in sexual partners of patients with chronic hepatitis C, is lower than previously reported with first generation anti-HCV tests but higher than in the general population (3.2% vs approximately equal to 1%). Serum anti-HCV antibodies were very rarely detected in children from patients with chronic hepatitis C.
Assuntos
Hepatite C/transmissão , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Hepatite C/epidemiologia , Hepatite C/genética , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Fatores de Risco , Parceiros SexuaisRESUMO
INTRODUCTION: In order to meet the evolution of pneumococcus resistance to beta-lactam antibiotics, a new formulation of amoxicillin (AMX) and clavulanic acid (CA), with twice as much AMX (1 g/125 mg vs. 500 mg/125 mg) was developed for the treatment of acute pneumonia in patients at risk. This formulation can also be used in the treatment of acute maxillary sinusitis using a 1 g/125 mg regimen twice-daily. OBJECTIVES: Compare the sinusal penetration of AMX and CA (1 g/125 mg twice-daily vs. 500 mg/125 mg three times a day) when administered at both regimens to demonstrate equivalent pharmacokinetic and pharmacodynamic behaviour of the former when compared to the latter. METHODS: Concentrations of AMX and CA were measured in the anterior ethmoid, maxillary, posterior ethmoid sinus and in the middle nasa concha in 62 patients undergoing surgery for nasosinusal polyps. Patients randomised in two groups corresponding to 2 oral regimens, received either 1 g/125 mg twice a day or 500 mg/125 mg three times a day for 4 days. The last dose in both groups was administered 1 h 30, 3, 5 or 8 hrs prior to surgery. Serum samples were taken simultaneously to tissue samples. AMX and CA were measured by high performance liquid chromatography. Exogenous and above all endogenous blood contamination were taken into account with the hematocrit as well as blood and tissue haemoglobin concentrations. Comparisons of tissue concentrations were made for each sampling time, according to values obtained for a specific tissue with both doses on one hand, and on the other to values obtained with a specific dose in different tissues. The calculated pharmacodynamic parameters, which are considered to be predictive for bacteriological and clinical efficacy, result directly from tissue concentrations of AMX. tissue inhibitory quotients (IQtissue = Tissue concentration/MIC). time above MICs for serum and tissue concentrations (T > MIC). RESULTS: As regards AMX, whatever the dose, at 1 h 30 and at 3 hrs, tissue concentrations did not differ significantly whatever the tissue studied (from 1.1 to 2.5 micrograms/g). Conversely, at 5 and 8 hrs, they were greater than after the 1 g/125 mg regimen given twice-daily (0.06-0.7 vs. 0.7-1.8 micrograms/g). If we consider a given dose, the comparison between the various tissues showed identical concentrations in the four tissues studied at each sampling time, except in two cases with the dose of 500 mg/125 mg 3 times a day. T > MIC for serum and tissue showed higher values than those required for AMX/pneumococcus association (40-50%) with, nevertheless, greater tissue values for the 1 g/125 mg dose given twice-daily when MIC was of 1 microgram/ml (40-52% vs. 50-66%). The maximum tissue inhibitory quotients were also greater with the twice-daily 1 g/125 mg dose, when calculated with MIC 50 or 90 of S. Pneumoniae, H. influenzae, M. catarrhalis or S. pyogenes. As for CA, concentrations were equivalent for both doses at each sampling time and greater than those required in vitro during respectively 4 and 5 hours for beta-lactamases H. influenzae and M. catarrhalis. DISCUSSION-CONCLUSION: A least an equivalence between both dose regimens was observed, with occasionally a superiority of the twice-daily 1 g/125 mg dose, in terms of pharmacokinetics, tissue penetration and pharmacodynamics for both AMX and CA. This new regimen therefore appears more appropriate for the treatment of acute maxillary sinusitis in adults.
Assuntos
Combinação Amoxicilina e Clavulanato de Potássio/administração & dosagem , Combinação Amoxicilina e Clavulanato de Potássio/farmacocinética , Antibacterianos/administração & dosagem , Antibacterianos/farmacocinética , Quimioterapia Combinada/administração & dosagem , Quimioterapia Combinada/farmacocinética , Sinusite Maxilar/tratamento farmacológico , Seios Paranasais/metabolismo , Doença Aguda , Combinação Amoxicilina e Clavulanato de Potássio/farmacologia , Antibacterianos/farmacologia , Química Farmacêutica , Quimioterapia Combinada/farmacologia , Seio Etmoidal/metabolismo , Feminino , Humanos , Masculino , Seio Maxilar/metabolismo , Pessoa de Meia-Idade , Fatores de Tempo , Conchas Nasais/metabolismoAssuntos
Acenocumarol/efeitos adversos , Transtornos da Coagulação Sanguínea/induzido quimicamente , Hemorragia Gastrointestinal/etiologia , Hérnia Hiatal/complicações , Piroxicam/efeitos adversos , Transtornos da Coagulação Sanguínea/complicações , Interações Medicamentosas , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
Elective orthopaedic surgery is regularly withheld from patients with haemophilia and high inhibitor titre despite the presence of severe arthropathy and urgent medical need. A knee joint arthroplasty was performed in a patient with severe haemophilia A and a high inhibitor titre using recombinant factor VIIa (rFVIIa) as the sole coagulation factor. There was no abnormal bleeding during surgery although an increased blood loss through surgical drains did occur during the first 6 h postoperatively. Rehabilitation was started on day 1 and continued for 3 months. Walking commenced on day 4. After 1 year of follow-up, the clinical outcome of surgery was considered excellent with no pain, knee mobility at 0-5-90 degrees, and an International Knee Society score of 95/100. No rFVIIa-associated side-effects or thrombotic complications were reported. In conclusion, knee joint arthroplasty is now an option for haemophilia patients with a high inhibitor titre. An international review of all available data on elective orthopaedic surgery in inhibitor patients is required so that the optimal treatment regime can be defined and the short- and long-term risk-benefit ratio of surgery compared to that of noninhibitor patients.
Assuntos
Artroplastia do Joelho/reabilitação , Fator VIIa/administração & dosagem , Hemofilia A/cirurgia , Adulto , Perda Sanguínea Cirúrgica/prevenção & controle , Hemofilia A/tratamento farmacológico , Hemofilia A/imunologia , Humanos , Isoanticorpos/sangue , Masculino , Proteínas Recombinantes/administração & dosagemRESUMO
The Yucatan micropig has been used to develop an experimental model of chronic bacteremia. This animal exhibits clinical and biological characteristics that are close to those in humans, and the pharmacokinetic behaviours of many classes of drugs in this model are similar to those in man. Six adult female were intravenously inoculated with a mean Escherichia coli inoculum of 5.1 x 10(9) bacteria. During five days of spontaneous evolution, the medical follow-up includes biological, clinical and bacteriological parameters. A systemic inflammatory syndrome, a sepsis, an organ insufficiency and positive blood cultures mimic the human disease. In all animals there is an adynamia, a lack of motor coordination, an anorexia, a tachypnea, a fever, a leuconeutropenia followed by an hyperleucocytosis, an anemia, a thrombopenia, an acute tubulonephritis and an elevated sedimentation rate. In some cases, there is an increase of the C reactive protein, in others, an increase of IL-6 and IL-8. At day five, all animals are alive, and five micropigs have positive blood cultures. This chronic, reproducible model is thus suitable for further antibacterial treatments evaluations.
Assuntos
Bacteriemia , Modelos Animais , Porco Miniatura , Injúria Renal Aguda/etiologia , Reação de Fase Aguda , Animais , Anorexia/etiologia , Ataxia/etiologia , Bacteriemia/sangue , Bacteriemia/complicações , Bacteriemia/microbiologia , Bacteriemia/patologia , Doença Crônica , Progressão da Doença , Infecções por Escherichia coli/sangue , Infecções por Escherichia coli/complicações , Infecções por Escherichia coli/patologia , Febre/etiologia , Doenças Hematológicas/etiologia , Interleucina-6/sangue , Interleucina-8/sangue , Insuficiência de Múltiplos Órgãos/etiologia , Nefrite Intersticial/etiologia , Reprodutibilidade dos Testes , Porco Miniatura/microbiologia , Síndrome de Resposta Inflamatória Sistêmica/etiologiaRESUMO
BACKGROUND/AIMS: The mechanisms of hepatocarcinogenesis are still poorly understood. The development of hepatocellular carcinoma has recently been shown to be associated with increased DNA synthesis in cirrhosis. The aim of this work was to determine whether the high rate of hepatocyte regeneration observed in cirrhotic liver with hepatocellular carcinoma is associated with the presence of a growth factor that could be detectable in the serum. METHODS: Adult human hepatocytes in primary culture, allowing the evaluation of the release of circulating hepatotrophic factors, were used. These cultures were treated for 48 h with serum from patients with cirrhosis with and without hepatocellular carcinoma, from patients with liver metastasis, and from healthy subjects. The rate of DNA synthesis in these cultures was assessed by measuring the amount of [3H]-thymidine incorporation into genomic DNA. RESULTS: On average, the synthesis of DNA was increased 2.5-, 2.2-, 2.1-, and 2.3-fold, respectively, in response to serum from patients with cirrhosis with hepatocellular carcinoma, from patients with cirrhosis without hepatocellular carcinoma, from patients with liver metastasis, and from healthy subjects. CONCLUSIONS: We conclude that the hepatotrophic activity of the serum is not significantly different in patients with cirrhosis with or without hepatocellular carcinoma. These results suggest that the increased DNA synthesis in hepatocytes of cirrhotic liver with hepatocellular carcinoma might be due to proliferative factor(s) acting by paracrine or autocrine pathways.
Assuntos
Carcinoma Hepatocelular/fisiopatologia , DNA/biossíntese , Cirrose Hepática/fisiopatologia , Neoplasias Hepáticas/fisiopatologia , Regeneração Hepática/fisiologia , Adulto , Idoso , Carcinoma Hepatocelular/complicações , Carcinoma Hepatocelular/metabolismo , Estudos de Casos e Controles , Divisão Celular/fisiologia , Células Cultivadas , Fator de Crescimento Epidérmico/uso terapêutico , Feminino , Humanos , Fígado/citologia , Fígado/efeitos dos fármacos , Cirrose Hepática/complicações , Cirrose Hepática/metabolismo , Neoplasias Hepáticas/complicações , Neoplasias Hepáticas/secundário , Masculino , Pessoa de Meia-Idade , Proteínas Recombinantes/uso terapêutico , Valores de ReferênciaRESUMO
In this paper we have described the case of a 7-yr-old Moroccan osteopetrotic boy, who had received a bone marrow transplant (BMT). He was transplanted from his older brother and, despite immunosuppressive therapy, developed chronic graft-versus-host disease and was placed on corticotherapy. Seven months after the bone marrow transplant, graft versus host disease (GVHD) was stabilized, but corticotherapy had inhibited growth. There was evidence of normalizing bone, his hearing was better but he had not recovered vision. Dental findings before the bone marrow transplant revealed some missing teeth, failure of teeth to erupt and decayed teeth but no enamel hypoplasia. The patient had developed one carious lesion on one unerupted tooth: bacteria seem to have found a way through the gubernaculum dentale. The scanning electronmicrographs showed decayed tooth and tissues fitted into each other. Since the bone marrow transplant, no tooth has erupted. We think that, in this case, failure of tooth eruption would be the sign of osteopetrosis.