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1.
Ethique Sante ; 19(4): 210-216, 2022 Dec.
Artigo em Francês | MEDLINE | ID: mdl-36065408

RESUMO

This article is a focus on the organizational measures, decision-making and ethical questions during the different COVID-10 waves in specialized rehabilition center for persons with severe handicap and disability. The a posteriori analysis leads to a reflection on the responsability, decision-making and ethical questions.

2.
World J Urol ; 33(8): 1205-11, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-25373933

RESUMO

OBJECTIVE: To assess preoperative renal tumor biopsy (RTB) accuracy. MATERIALS AND METHODS: As part of the prospective NEPHRON study, data from 1,237 renal tumors were collected, including the use and results of RTB and final histology following nephrectomy. During the 6 months period of inclusion, 130 preoperative biopsies were performed. We used the kappa coefficient of the McNemar test to determine the concordance between the biopsy and the nephrectomy specimen (NS) regarding four parameters: malignant/benign status, histological subtype, Fuhrman grade and microscopic necrosis. RESULTS: Preoperative biopsies were performed in 9.7 and 11.4 % of the 667 radical and 570 partial nephrectomies, respectively. Tumor biopsy was inconclusive in 7.7 % of the cases. In 117 cases, a comparison between RTB and NS was available. Benign tumors accounted for three (2.6 %) and five (4.3 %) of the RTB and NS, respectively (κ = 0.769, good). With seven (6 %) discordant results in terms of histological subtype characterization between RTB and final pathology, RTB accuracy was considered excellent (κ = 0.882). In 33 cases (31.7 %), Fuhrman grade was underestimated at biopsy resulting in an intermediate concordance level (κ = 0.498). Tumor microscopic necrosis was identified in 12 RTB (10.4 %) versus 33 NS (28.4 %) (κ = 0.357, poor). CONCLUSIONS: RTB provides good to excellent diagnostic performance for discriminating malignancy and tumor histological subtype. However, its performance is intermediate or even poor when considering prognostic criteria like Fuhrman grade or microscopic necrosis. Thus, this possible inaccuracy should be taken into consideration when using RTB for accurate guidance of treatment strategy.


Assuntos
Adenoma Oxífilo/patologia , Carcinoma Papilar/patologia , Carcinoma de Células Renais/patologia , Neoplasias Renais/patologia , Adenoma Oxífilo/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Biópsia com Agulha de Grande Calibre , Carcinoma Papilar/cirurgia , Carcinoma de Células Renais/cirurgia , Feminino , França , Humanos , Neoplasias Renais/cirurgia , Masculino , Pessoa de Meia-Idade , Nefrectomia , Néfrons , Tratamentos com Preservação do Órgão , Estudos Prospectivos , Adulto Jovem
3.
Knee Surg Sports Traumatol Arthrosc ; 23(9): 2494-501, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-24748271

RESUMO

PURPOSE: Calcaneus insertional tendinopathy in runners is common and involves important therapeutic controversies. The object of this study was to determine the delay and level of return to sport after insertional surgery in runners, with and without tendon damage. METHODS: Eighteen runners underwent surgery for insertional calcaneus tendinopathy. Nine required an exostosectomy/bursectomy, and nine others required a tendon reinsertion/autograft. All patients were clinically assessed pre- and post-operatively with AOFAS scores and post-operatively with ATRS. This series included analysis of "pure conflicts" and "severe insertional lesion" scores. If the insertional tendon was free or the lesion was smaller than 50 %, the group was classified as "pure conflict/minor tendon damage". In the situation in which a loss of tendon occurred or the tendon lesion was greater than 50 %, the group was classified as "major tendon damage". Pre-operatively, the AOFAS "overall", "pure conflicts/minor tendon damage" and "major tendon damage" groups' scores were 58.5 ± 15, 68.2 ± 8.8 and 48.9 ± 13.9/100, respectively. RESULTS: Post-operatively, the AOFAS "overall", "pure conflicts/minor tendon" and "major tendon damage" groups' scores were 93.7 ± 8.2, 93.2 ± 10.2 and 95.2 ± 5.7/100, respectively. The AOFAS score gain for each group was, respectively, 35.2 ± 19, 24 ± 17 and 46.3 ± 14.1. The ATRS "overall", "pure conflicts/minor tendon damage" and "major tendon damage" groups' scores were 81.5 ± 14.9, 78.3 ± 20.1 and 84.7 ± 6.7/100, respectively. The global sport recovery delay was 9.3 ± 4.1 months; it was 6 ± 3.3 months for the pure conflict/minor tendon damage subgroup and 10 ± 4.6 months for the severe tendon damages subgroup. CONCLUSION: Achilles insertional tendinopathy surgery on this population results in few complications with good functional results if the surgical technique is adapted to the type of tendon injury. The clinical relevance of this study is that it highlights the various forms of calcaneus insertional tendinopathy and various treatment options. The authors show that in the case of major tendon damage, time to return to sport is longer.


Assuntos
Tendão do Calcâneo/lesões , Corrida/lesões , Tendinopatia/cirurgia , Tendão do Calcâneo/cirurgia , Adulto , Calcâneo , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Recuperação de Função Fisiológica , Resultado do Tratamento
4.
Ann Oncol ; 23(3): 618-624, 2012 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-21642515

RESUMO

BACKGROUND: Circulating tumor cells (CTCs) are a prognostic marker in metastatic breast cancer, but comparisons with serum tumor markers (CA 15-3, carcinoembryonic antigen and lactate dehydrogenase) variations are needed. PATIENTS AND METHODS: CTCs were counted with CellSearch® at baseline, before cycle 2 (C2) and cycle 3 or 4 (C3/4) in 267 metastatic breast cancer patients on first-line chemotherapy with/without targeted therapy. RESULTS: Baseline CTC detection rate was 65% with ≥1 CTC/7.5 ml threshold and 44% with ≥5 CTC/7.5 ml and was independent of subtypes (luminal, triple negative, human epithelial growth factor receptor 2 (HER2)+). CTCs were associated with tumor markers, bone/liver involvement, tumor burden and performance status. CTC detection ≥1 CTC/7.5 ml was a strong prognostic factor for progression-free survival (PFS), P < 0.0001. Threshold of CTC ≥5 was statistically significant for PFS and overall survival (OS), P = 0.03 on multivariate analysis. Among patients with ≥5 CTC/7.5 ml at baseline, 50% had <5 CTC/7.5 ml at C2. Changes were correlated with both PFS and OS (P < 0.0001). All patients receiving anti-HER2 therapy had <5 CTC/7.5 ml after three cycles of treatment. CONCLUSION: This is the largest prospective series validating the prognostic value of CTC independently from serum tumor marker. Elevated CTCs before C2 are an early predictive marker of poor PFS and OS, which could be used to monitor treatment benefit. CTC decrease under treatment seems stronger with targeted therapy.


Assuntos
Antineoplásicos/uso terapêutico , Biomarcadores Tumorais/sangue , Neoplasias da Mama/sangue , Neoplasias da Mama/tratamento farmacológico , Células Neoplásicas Circulantes/efeitos dos fármacos , Adulto , Neoplasias da Mama/mortalidade , Intervalo Livre de Doença , Humanos , Imuno-Histoquímica , Estimativa de Kaplan-Meier , Pessoa de Meia-Idade , Metástase Neoplásica , Estadiamento de Neoplasias , Valor Preditivo dos Testes , Prognóstico , Modelos de Riscos Proporcionais
5.
Prog Urol ; 20(6): 430-4, 2010 Jun.
Artigo em Francês | MEDLINE | ID: mdl-20538207

RESUMO

GOAL: It is generally considered that kidney grafts should be preserved at 4 degrees C during cold storage. However, actual temperature conditions are not known. We decided to study the temperature levels during preservation with the Biotainer storage can and Vitalpack transport pack. MATERIAL: Temperature was monitored using the Thermobouton probe during preservation of pig kidneys, in the same conditions used with human grafts. The probe recorded the temperature level every 10 minutes during four days. We compared the results found with the new storage can with results obtained in the same conditions with the storage can formerly used by our team. We also studied the best position of the probe for temperature monitoring and the influence of the amount of ice within the transport pack on the temperature level. We then monitored the temperature during the conservation of actual human kidney grafts harvested at our institution from August 2007 to May 2008. RESULTS: The temperature levels were the same regardless of the position of the probe within the transport pack. The lowest temperature was maintained during 15 hours, and the temperature level stayed below 5 degrees C for 57 hours with the new storage can. The former storage can maintained the lowest temperature level for 80 minutes, and temperature reached 5 degrees C after 10 hours 40 minutes. Temperature levels were similar when 2 or 4 kg of crushed ice were used. We observed similar results when monitoring the conservation of human grafts. CONCLUSION: The new storage can affords more stable temperature levels when compared to the formerly used can. Since temperature is stable during conservation, continuous monitoring in everyday practice does not seem warranted.


Assuntos
Temperatura Corporal , Transplante de Rim , Preservação de Órgãos/métodos , Animais , Temperatura Baixa , Humanos , Suínos
6.
Ann Readapt Med Phys ; 51(1): 16-23, 2008 Jan.
Artigo em Francês | MEDLINE | ID: mdl-17765999

RESUMO

AIM: The aim of this study was to determine the mechanisms involved in muscle weakness in elderly patients with unilateral knee osteoarthritis. SUBJECTS: We investigated 7 patients with unilateral knee osteoarthritis. METHOD: We measured knee position sense and isometric maximal voluntary contraction (MVC) of the knee extensors. Electromyographic (EMG) measurement of biceps femoris (BF), rectus femoris (RF), vastus lateralis (VL) and vastus medialis (VM) involved different levels of contraction (25, 50, 75 and 100% MVC). Neuromuscular efficiency of quadriceps was also calculated (MVC/EMG). Ultrasonography was used to investigate the VL architectural parameters at the median part of the VL for different levels of contraction (25, 50, and 75% MVC). All tests were performed on the osteoarthritic and healthy knees. RESULTS: The quadriceps MVC of the affected knee was reduced by 30%. The VL thickness of the affected knee was 10% smaller than that of the unaffected knee. VL activity seen on EMG did not differ between knees, but RF, VM and BF activity was greater in the unaffected than affected knee. Neuromuscular efficiency was higher (26%) in the unaffected knee. Knee position sense was reduced by 33% in the affected knee. CONCLUSION: Quadriceps weakness associated with knee osteoarthritis seems to be related to changes in muscle rather than pennation angle and changes in fascicule length.


Assuntos
Músculo Esquelético/fisiopatologia , Osteoartrite do Joelho/fisiopatologia , Idoso , Eletromiografia , Feminino , Humanos , Contração Isométrica/fisiologia , Masculino , Debilidade Muscular/fisiopatologia , Músculo Esquelético/diagnóstico por imagem , Ultrassonografia
7.
Rev Chir Orthop Reparatrice Appar Mot ; 94(4): 407-12, 2008 Jun.
Artigo em Francês | MEDLINE | ID: mdl-18555869

RESUMO

We report the case of a 47-year-old female patient who developed predominantly anterior multidirectional glenohumeral instability. After rehabilitation, this patient was treated surgically with an anterior coracoid bone block using the Latarjet technique. The second postoperative day, the control scan revealed posterior glenohumeral dislocation. The patient underwent a second operation for a posterior iliac block. At last clinical follow-up (six years), the patient had normal shoulder motion; shoulder function was considered excellent using the clinical scores. We recall the pathogenic hypotheses explaining multidirectional shoulder instability and discuss the proposed treatments. This case illustrates the difficult diagnosis and therapeutic management of multidirectional instability. Under general anesthesia, examination showed that posterior laxity predominated while paradoxically, the patient presented predominantly anteromedial dislocations. This case is also exceptional by the development of posterior dislocation, an unusual postoperative complication after an anterior bone block; we describe the therapeutic options. In the event of multidirectional instability with bone injuries, we recommend a block in the direction of the instability. Preoperative examination under general anesthesia can be helpful in understanding the mechanism of residual postoperative instability, which would require complementary surgical stabilization.


Assuntos
Instabilidade Articular/cirurgia , Articulação do Ombro/cirurgia , Feminino , Humanos , Pessoa de Meia-Idade , Procedimentos Ortopédicos/métodos , Falha de Tratamento
8.
Arch Pediatr ; 25(1): 42-44, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-29248324

RESUMO

Progressive cerebellar ataxias are well-known hereditary neurological disorders. Among them, spinocerebellar ataxia type 7 (SCA7) is inherited as an autosomal dominant trait and is ascribed to the expansion of a CAG trinucleotide repeat within the ATXN7 gene. An anticipation phenomenon can occur during paternal transmission and sometimes is responsible for a severe infantile form. The specificity of SCA7 is the retinal involvement with retinitis pigmentosa and cone rod dystrophy. We describe a familial form with two siblings who died of a severe infantile form. Diagnosis was made in their father, who had a recent history of macular atrophy and presented with gait disturbance thereafter. Retrospectively, substantial triplet repeat expansion was confirmed in the two affected infants. These infantile forms are rare and difficult to diagnose in the absence of suggestive family symptoms.


Assuntos
Ataxias Espinocerebelares/diagnóstico , Ataxias Espinocerebelares/genética , Ataxina-7/genética , Encéfalo/diagnóstico por imagem , Evolução Fatal , Humanos , Lactente , Imageamento por Ressonância Magnética , Masculino , Linhagem , Expansão das Repetições de Trinucleotídeos
9.
Respir Med Case Rep ; 23: 173-175, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29719811

RESUMO

Homozygous or compound heterozygous for frameshift or nonsense mutations in the ATP-binding cassette transporter A3 (ABCA3) is associated with neonatal respiratory failure and death within the first year of life without lung transplantation. We report the case of a newborn baby girl who developed severe respiratory distress soon after birth. She was diagnosed with compound heterozygous frameshift mutation of the ABCA3 gene. Despite extensive treatment (intravenous corticosteroids pulse therapy, oral corticosteroids, azithromycin, and hydroxychloroquine), she developed chronic respiratory failure. As the parents refused cardio-pulmonary transplantation and couldn't resolve to an accompaniment of end of life, a tracheostomy was performed resulting in continuous mechanical ventilation. A neurodevelopmental delay and an overall muscular dystrophy were noted. At the age of 5 years, after 2 episodes of pneumothorax, the patient died from severe respiratory failure. To our knowledge, this was the first case of a child with compound heterozygous frameshift mutation who posed such an ethical dilemma with a patient surviving till the age of five years.

10.
Ann Urol (Paris) ; 41(5): 254-9, 2007 Oct.
Artigo em Francês | MEDLINE | ID: mdl-18265751

RESUMO

Ureteral stenosis is the most frequent complication after kidney transplantation. The diagnosis is based on an elevated creatinine level and a dilatation of the urinary cavity. The first step of the management is a urinary diversion with endo-ureteral prosthesis or a nephrostomy placement. The surgical gold standard is the pyelo-ureterostomy. This is a safe and efficient technique in the treatment of this complication. We describe the different surgical alternatives and the endo-urologic management of the stenosis.


Assuntos
Transplante de Rim/efeitos adversos , Obstrução Ureteral/etiologia , Obstrução Ureteral/cirurgia , Constrição Patológica , Humanos , Procedimentos Cirúrgicos Urológicos/métodos
11.
Arch Pediatr ; 24(7): 640-646, 2017 Jul.
Artigo em Francês | MEDLINE | ID: mdl-28583781

RESUMO

Macrophage activation syndrome (MAS) is a rarely reported complication of Kawasaki disease (KD). It must be sought during KD with unusual clinical signs, such as enlargement of the liver or spleen, cytopenia (including thrombocytopenia), and elevated serum triglycerides. Here, we report four cases from a single center. The first is the description of a case of KD occurring in an 11-month-old child 15 days after the occurrence of infectious spondylitis. For the second, acute myocarditis heralded KD in a 5-year-old child. A 15-year-old boy had multiorgan failure with shock. The last case describes an infant with atypical KD. All had hepatosplenomegaly, thrombocytopenia, and increased serum ferritin. For all of them, hemophagocytosis was present on the bone marrow smears. The condition rapidly evolved favorably with intravenous immunoglobulins or steroids. The extensive microbiological work-up was unrevealing. None had any coronary sequelae after the episode. KD should be added to the list of inflammatory conditions that may be complicated by MAS that modifies the presentation mimicking toxic shock or infection-associated activation syndrome and makes the diagnosis difficult. This association does not appear to have a prognostic impact on the course of the disease in the literature, confirmed by the analysis of this small series.


Assuntos
Síndrome de Ativação Macrofágica/etiologia , Síndrome de Linfonodos Mucocutâneos/complicações , Adolescente , Pré-Escolar , Feminino , Ferritinas/sangue , Hepatomegalia/etiologia , Humanos , Lactente , Síndrome de Ativação Macrofágica/diagnóstico , Masculino , Esplenomegalia/etiologia , Trombocitopenia/etiologia
12.
Transplant Proc ; 38(7): 2281-2, 2006 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-16980064

RESUMO

SUBJECT: This article reports preliminary findings relating to the use of a new preservation solution, the Solution de Conservation des Organes et des Tissus (SCOT), in renal transplantation. This fourth-generation solution combines an extracellular-like composition with 20 kDa polyethylene-glycol, known for its cell-protection capacity and immunocamouflage properties. METHODS: We have reported preliminary data obtained in 29 transplantations (25 cadaveric donors and 4 living related donors) between December 2004 and November 2005. The SCOT solution was used for both in situ flush and static preservation. We compared primary organ nonfunction and delayed graft function rates as well as blood creatinine levels in recipients of grafts processed with SCOT solution, versus University of Wisconsin solution (paired for age with the previous group) and with EuroCollins solution (historic data). RESULTS: We observed delayed graft-function in 10% of the SCOT-processed group, 14% in the University of Wisconsin solution group, and 23% of the EuroCollins group. No case of primary organ nonfunction was reported. Creatinine levels in both SCOT and University of Wisconsin solution groups were similar. We did not observe any humoral or cellular graft rejection in the first 3 months after transplantation. In light of these preliminary results, the use of SCOT is safe for kidney preservation in the human setting. Further experience is warranted to assess the clinical consequences of its immunocamouflage properties as described in animal models.


Assuntos
Rim , Soluções para Preservação de Órgãos , Adenosina , Alopurinol , Creatinina/sangue , França , Glutationa , Humanos , Insulina , Transplante de Rim , Polietilenoglicóis , Rafinose
13.
Arch Pediatr ; 23(1): 56-60, 2016 Jan.
Artigo em Francês | MEDLINE | ID: mdl-26563723

RESUMO

Infantile pyknocytosis is a neonatal hemolytic disorder which causes anemia and icterus and is characterized by the presence of an increased number of distorted red blood cells called pyknocytes. Resolution spontaneously occurs in the first semester of life. It has been generally described as a rare entity, with an occasional family history. We report seven cases of infantile pyknocytosis observed in our hospital in 3 years. Most of the infants presented with hemolytic icterus and profound anemia that was reaching its peak by the 3rd week of life. Three neonates received one to three red blood cell transfusions, according to former recommendations. However, the following four received a treatment with recombinant erythropoietin administered subcutaneously. Only one of these four cases required a transfusion. All of them were free of hematological disease 2-3 months after completion of treatment. Infantile pyknocytosis is a recognized cause of neonatal hemolytic anemia, which requires careful examination of red cell morphology on a peripheral blood smear. The cause of this transient disorder remains unknown. Our observations show that recombinant erythropoietin therapy is effective in treating infantile pyknocytosis and increases the reticulocyte response, thus improving the hemoglobin level.


Assuntos
Anemia Hemolítica/terapia , Anemia Neonatal/terapia , Eritrócitos Anormais/patologia , Eritropoetina/uso terapêutico , Transfusão de Eritrócitos , Feminino , Humanos , Lactente , Recém-Nascido , Masculino
14.
Rev Chir Orthop Reparatrice Appar Mot ; 91(3): 248-56, 2005 May.
Artigo em Francês | MEDLINE | ID: mdl-15976669

RESUMO

PURPOSE OF THE STUDY: We reviewed retrospectively 24 feet with sequelae of transtalar process fractures of the calcaneum in order to identify the lesion pattern and determine optimal management options, both for acute and sequelar lesions. MATERIAL AND METHODS: There were fourteen men and nine women, mean age 42 years (19-73). Twenty-three had subtalar osteoarthritis, eight had calcaneocuboid osteoarthritis, and fifteen had lateral submalleolar conflicts. There were twelve fibular tendon dislocations or fissurations, three tarsal tunnel syndromes, and two plantar splinters. Prior to treatment, all patients complained of pain. Preoperatively, walking distance was less than 500 m for thirteen patients, 2000-3000 m for four, and greater than 3000 m for five. Mean subtalar joint motion was 30% (0-100%) compared with the healthy side and mean frontal misalignment of the rear foot was 6 degrees valgus. Physical examination, podoscopy and x-rays were obtained in all patients. The Kitaoka score was noted. RESULT: Mean follow-up was 36 months (24-72). Sequelae were treated with a single procedure or with combinations: subtalar arthrodesis (n = 23) including one in association with calcaneocuboid arthrodesis, tension on fibular tendons (n = 7), neurolysis of the posterior tibial nerve (n = 3), resection of plantar splinters (n = 2), resection of the lateral shell (n = 14), and osteotomy (n = 2) to lower the greater tubercle of the calcaneum because of pain when wearing shoes. The mean Kitaoka function score was 31.7/100 (14-79) preoperatively. After treatment, the mean score was 81.7/100 (31-94), giving a 73.2% gain. The outcome was considered good in sixteen feet, fair in six, and poor in two. Mean walking distance was greater than 3000 m for 18 patients. Mean frontal misalignment of the rear foot under loading was 4.5 degrees valgus and the podoscopy demonstrated flat foot in thirteen patients. Three subtalar arthrodesis required revision for nonhealing. DISCUSSION: Initial treatment of a fracture, particularly an articular fracture, of the calcaneum must avoid disabling postoperative pain and shoe wearing problems. These sequelae basically concern: subtalar and calcaneocuboid arthritis, lateral submalleolar conflict, fibular tendon injury, plantar splinters, tarsal tunnel syndrome, loss of height, and misalignment of the rear foot. At the sequelar stage, the physical examination is primordial to confirm the lesion and search for any complication which could develop later postoperatively when walking distance becomes longer. For nine patients with residual pain, four resulted from lesions which were missed at the preoperative physical examination. Arthrodesis of the subtalar joint should be preferred over realignment of the rear foot and can be associated with the treatment of conflicts. This management scheme allows treating during a single operative time all sequelae, thus limiting recovery time. A scan of the ankle and foot with or without opacification of the fibular tendons is needed to confirm the physical examination which, for us, remains the key to successful surgery.


Assuntos
Traumatismos do Tornozelo/cirurgia , Artrodese , Fraturas Fechadas/cirurgia , Adulto , Idoso , Traumatismos do Tornozelo/patologia , Feminino , Fraturas Fechadas/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Osteoartrite/complicações , Dor/etiologia , Amplitude de Movimento Articular , Recidiva , Reoperação , Estudos Retrospectivos , Resultado do Tratamento , Caminhada , Suporte de Carga
15.
Artigo em Inglês | MEDLINE | ID: mdl-28596863

RESUMO

BACKGROUND: The objective of this study was to evaluate the impact of a brief parenting intervention, 'Parents Make the Difference'(PMD), on parenting behaviors, quality of parent-child interactions, children's cognitive, emotional, and behavioral wellbeing, and malaria prevention behaviors in rural, post-conflict Liberia. METHODS: A sample of 270 caregivers of children ages 3-7 were randomized into an immediate treatment group that received a 10-session parent training intervention or a wait-list control condition (1:1 allocation). Interviewers administered baseline and 1-month post-intervention surveys and conducted child-caregiver observations. Intent-to-treat estimates of the average treatment effects were calculated using ordinary least squares regression. This study was pre-registered at ClinicalTrials.gov (NCT01829815). RESULTS: The program led to a 55.5% reduction in caregiver-reported use of harsh punishment practices (p < 0.001). The program also increased the use of positive behavior management strategies and improved caregiver-child interactions. The average caregiver in the treatment group reported a 4.4% increase in positive interactions (p < 0.05), while the average child of a caregiver assigned to the treatment group reported a 17.5% increase (p < 0.01). The program did not have a measurable impact on child wellbeing, cognitive skills, or household adoption of malaria prevention behaviors. CONCLUSIONS: PMD is a promising approach for preventing child abuse and promoting positive parent-child relationships in low-resource settings.

16.
Hum Gene Ther ; 10(3): 375-83, 1999 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-10048390

RESUMO

Cell encapsulation offers a safe and manufacturable method for the systemic delivery of therapeutic proteins from genetically engineered cells. However, control of dose delivery remains a major issue with regard to clinical application. We generated populations of immortalized murine NIH 3T3 fibroblasts that secrete mouse erythropoietin (Epo) in response to stimulation by doxycycline or mifepristone. Engineered cells were introduced into AN69 hollow fibers, which were implanted in the peritoneal cavity or recipient mice. Animals receiving doxycycline or mifepristone showed stable polyhemia and increased serum Epo concentrations over a 6-month observation period, whereas animals not receiving the inducer drug had normal hematocrits. Epo secretion could be switched on and off, depending on the presence of doxycycline in the drinking water. In contrast, polyhemia was hardly reversible after subcutaneous injections of mifepristone. These data show that a permanent and regulated systemic delivery of a therapeutic protein can be obtained by the in vivo implantation of engineered allogeneic cells immunoprotected in membrane polymers.


Assuntos
Doxiciclina/farmacologia , Eritropoetina/metabolismo , Mifepristona/farmacologia , Células 3T3 , Animais , Southern Blotting , Cápsulas , Relação Dose-Resposta a Droga , Doxiciclina/administração & dosagem , Eritropoetina/sangue , Regulação da Expressão Gênica , Técnicas de Transferência de Genes , Terapia Genética/métodos , Hematócrito , Camundongos , Mifepristona/administração & dosagem , Retroviridae , Fatores de Tempo
17.
Transplantation ; 70(1): 78-85, 2000 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-10919579

RESUMO

BACKGROUND: Encapsulating cells prevents the immune destruction of allogeneic cells in the subcutaneous site as well as allogeneic and xenogeneic cells in the central nervous system. However, when encapsulated xenogeneic cells are implanted s.c., they may be subject to rejection by the host. METHODS: Murine C2C12 myoblasts engineered to secrete mouse erythropoietin (mEpo) were used to evaluate the response of control versus FK506-treated xenogeneic recipients (Fischer rats) to encapsulated myoblasts implanted in the s.c. site. RESULTS: Encapsulated C2C12 mEpo cells were rapidly eliminated in immunocompetent Fischer rats. Devices transplanted into nude rats induced a sustained increase in the hematocrit, associated with an extended viability of the encapsulated cells. Short-term immunosuppression with FK506, for periods lasting either 1, 2, or 4 weeks after implantation, permitted the long-term survival of encapsulated C2C12 mEpo cells in Fischer rats. Animals increased their hematocrits to more than 70% and maintained these levels for 13 weeks, independent of the duration of FK506 treatment. Unencapsulated C2C12 mEpo cells injected i.m. in immunosuppressed animals were rejected over this same period. CONCLUSIONS: Encapsulation alone cannot protect xenogeneic myoblasts from immune destruction in the s.c. site. These results highlight the importance of combining the technique of cell encapsulation with transient immunosuppression to achieve long-term survival of xenografted myoblasts in a peripheral immunoreactive site.


Assuntos
Transplante de Células , Imunossupressores/uso terapêutico , Fibras Musculares Esqueléticas/citologia , Tacrolimo/uso terapêutico , Transplante Heterólogo/imunologia , Animais , Sobrevivência Celular , Células Cultivadas , Eritropoetina/fisiologia , Camundongos , Camundongos Endogâmicos C3H , Camundongos Endogâmicos DBA , Ratos , Ratos Endogâmicos F344 , Ratos Nus
18.
Transplantation ; 63(12): 1798-803, 1997 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-9210507

RESUMO

BACKGROUND: New strategies to improve the outcome of encapsulated porcine islet transplantation may involve the transfer of gene sequences affecting islet viability. While adenoviral vectors appear as the most efficient gene transfer system so far established for islets, non-viral-based vectors are most likely to fulfill microbiological safety criteria and be retained in the clinical setting. Our aim was to standardize the procedures of gene transfer into adult porcine islets using cationic liposome DOTAP. METHODS: Porcine islets obtained by collagenase digestion and density gradient purification were lipofected with plasmids coding for luciferase or beta-galactosidase under the control of simian virus 40 or cytomegalovirus promoter. The following parameters were explored: exposure time to vector (1-48 hr), DNA amount (1-15 microg/500 islets), and DOTAP to DNA ratio (2-16). Reporter gene expression was determined 48-72 hr after lipofection. RESULTS: Efficiency and reproducibility of transfection were maximal with the following procedure: 3-hr exposure time followed by islet washing, 12 microg of DNA per 500 islets (150 microm equivalent), and DOTAP to DNA ratio of 12 microl/microg. Freshly isolated islets in large aliquots (n=4000 in 50-ml tubes) were efficiently transduced with this procedure, and distribution of gene expression was homogenous when islets were subsequently plated in 500-islet aliquots. Luciferase gene expression was detected for a minimum of 7 days after lipofection. Gene expression was also evident up to 4 weeks after islet transplantation beneath the kidney capsule of athymic mice. Transfection of islets using the beta-galactosidase vector yielded 25% positive islets. Islet viability was not adversely affected. CONCLUSIONS: This islet lipofection procedure may help achieve the local release of a bioactive peptide in the graft environment and have therapeutic applications in islet transplantation.


Assuntos
Técnicas de Transferência de Genes , Ilhotas Pancreáticas , Lipossomos , Animais , Cátions , Sobrevivência Celular , DNA/análise , Ácidos Graxos Monoinsaturados/metabolismo , Corantes Fluorescentes/metabolismo , Regulação da Expressão Gênica , Ilhotas Pancreáticas/citologia , Luciferases/genética , Luciferases/metabolismo , Camundongos , Camundongos Nus , Fosfatidiletanolaminas , Compostos de Amônio Quaternário/metabolismo , Espermina/análogos & derivados , Suínos , Transfecção/métodos , beta-Galactosidase/genética , beta-Galactosidase/metabolismo
19.
J Thorac Cardiovasc Surg ; 104(2): 385-90, 1992 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-1495300

RESUMO

Regional ischemia may induce cervical anastomosis leakage or stenosis or graft necrosis after esophageal reconstruction by retrosternal interposition of an ileocolic graft. These complications may be related to systemic or local hemodynamic alterations. This study was designed to evaluate the relationship between immediate postoperative arterial blood supply to the graft, arterial patency monitored by angiography, and clinical outcome. Eight patients (mean age 30 +/- 4 years; standard deviation) were studied. Miniaturized Doppler implantable microprobes were sutured to the single artery supplying the graft and connected to an 8 MHz pulsed Doppler flowmeter. Systemic hemodynamic parameters and mesenteric hemodynamic data were collected 3 hours after the end of the surgical procedure. These data were compared with the angiogram of the right superior colic artery supplying the graft, systematically performed on the fifteenth postoperative day, and with the clinical course of follow-up for 3 months. Five patients (group 1) had excellent clinical and angiographic results. Mean mesenteric blood flow in these patients was 51 +/- 49 ml.min-1 (+/- standard deviation, ranging from 9 to 122). Three patients (group 2) had a poor clinical outcome. One had early complete graft necrosis and the two others had leakage of the cervical anastomosis with poor distal arterial vascularization of the graft on the angiogram. Mean mesenteric blood flow was nul in the first patient and, respectively, 24 and 28 ml.min-1 in the two others. Cardiac output and mean arterial pressure were in the same range for all patients. Phasic velocity shape analysis revealed that the three group 2 patients had an end-systolic or end-diastolic reverse flow pattern that was not observed in the five group 1 patients, which suggested a submaximal increase in downstream vascular resistance. This reverse flow pattern seems to be a good predictor of ischemia-related complications. We conclude that perioperative pulsed Doppler blood flow monitoring in an ileocolic graft may be useful for the diagnosis and prevention of ischemic complications.


Assuntos
Esofagoplastia/métodos , Isquemia/diagnóstico por imagem , Complicações Pós-Operatórias/diagnóstico por imagem , Adulto , Velocidade do Fluxo Sanguíneo/fisiologia , Queimaduras Químicas/cirurgia , Cáusticos/efeitos adversos , Colo/cirurgia , Estenose Esofágica/induzido quimicamente , Estenose Esofágica/cirurgia , Humanos , Íleo/cirurgia , Isquemia/epidemiologia , Complicações Pós-Operatórias/epidemiologia , Valor Preditivo dos Testes , Próteses e Implantes , Circulação Esplâncnica/fisiologia , Ultrassonografia
20.
J Thorac Cardiovasc Surg ; 107(1): 68-73, 1994 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-8283921

RESUMO

Esophageal replacement after esophagogastric injury caused by ingestion of lye may require the interposition of a retrosternal ileocolic graft. In this new anatomic situation, the mesenteric circulation supplying the graft is subjected to the intrathoracic pressure surrounding the graft. Thus, mesenteric blood flow supplying the graft may be impaired when intrathoracic pressure is increased during mechanical ventilation. This study was designed to evaluate the effect of increasing intrathoracic pressure by application of a positive end-expiratory pressure on mesenteric blood flow supplying esophageal ileocolic grafts. Eight cases were studied in the immediate postoperative period. Miniaturized implantable Doppler microprobes were sutured to the single artery supplying the graft and connected to an 8 MHz pulsed Doppler flowmeter. Two sets of measurements were successively performed with zero end-expiratory pressure ventilation and after application of a 15 cm water positive end-expiratory pressure. Positive end-expiratory pressure induces mean arterial pressure (-12%); p < 0.05) and cardiac output (-17%; p < 0.05) decrease. Mesenteric blood flow also decreases (-38%; p < 0.05) as did the mesenteric blood flow/cardiac output ratio, suggesting a potential mesenteric vasoconstriction assessed by mesenteric vascular resistance increase and mesenteric diastolic blood flow velocity decrease. These results suggest that, in the particular anatomic situation of the graft, increased intrathoracic pressure induces mesenteric blood flow decrease in relation to systemic hemodynamic alterations associated with perivisceral pressure increase. This change may be deleterious to graft perfusion.


Assuntos
Esofagoplastia , Mesentério/irrigação sanguínea , Respiração com Pressão Positiva , Adulto , Velocidade do Fluxo Sanguíneo , Pressão Sanguínea , Queimaduras Químicas/cirurgia , Débito Cardíaco , Colo/transplante , Esôfago/lesões , Humanos , Íleo/transplante , Resistência Vascular
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