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1.
Mol Ther ; 25(3): 816-825, 2017 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-28143739

RESUMEN

Critical limb ischemia (CLI) is the most severe presentation of peripheral arterial disease. We developed cell-based therapy entailing intra-arterial injection of autologous venous endothelial cells (ECs) modified to express angiopoietin 1, combined with autologous venous smooth muscle cells (SMCs) modified to express vascular endothelial growth factor. This combination promoted arteriogenesis in animal models and was safe in patients with limiting claudication. In an open-label, phase Ib study, we assessed the safety and efficacy of this therapy in CLI patients who failed or were unsuitable for surgery or intravascular intervention. Of 23 patients enrolled, 18 with rest pain or non-healing ulcers (Rutherford categories 4 and 5) were treated according to protocol, and 5 with significant tissue loss (Rutherford 6) were treated under compassionate treatment. Patients were assigned randomly to receive 1 × 107 or 5 × 107 (EC-to-SMC ratio, 1:1) of the cell combination. One-year amputation-free survival rate was 72% (13/18) for Rutherford 4 and 5 patients; all 5 patients with Rutherford 6 underwent amputation. Of the 12 with unhealing ulcers at dosing, 6 had complete healing and 2 others had >66% reduction in ulcer size. Outcomes did not differ between the dose groups. No severe adverse events were observed related to the therapy.


Asunto(s)
Proteínas Angiogénicas/genética , Terapia Genética , Isquemia/genética , Isquemia/terapia , Extremidad Inferior/irrigación sanguínea , Anciano , Anciano de 80 o más Años , Terapia Combinada , Células Endoteliales/metabolismo , Femenino , Expresión Génica , Técnicas de Transferencia de Gen , Terapia Genética/efectos adversos , Terapia Genética/métodos , Vectores Genéticos/administración & dosificación , Vectores Genéticos/genética , Humanos , Isquemia/diagnóstico , Isquemia/etiología , Masculino , Persona de Mediana Edad , Miocitos del Músculo Liso/metabolismo , Calidad de Vida , Retroviridae/genética , Transducción Genética , Transgenes , Resultado del Tratamiento
2.
Br J Haematol ; 139(2): 310-1, 2007 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-17897308

RESUMEN

The prothrombin time/International Normalized Ratio is an accurate parameter for following most warfarin-treated patients. However, it reflects mostly factor VII levels, and significant disproportionate alterations in other vitamin K-dependent factors may not be reflected properly. We report a rare case of a woman who developed arterial thrombosis whilst receiving therapeutic doses of warfarin, and was found to have a significant and unbalanced protein S deficiency. Discontinuation of warfarin resulted in complete normalization of coagulation factors, and no further thrombotic events under treatment with enoxaparin, with a follow-up of 2.5 years.


Asunto(s)
Anticoagulantes/efectos adversos , Deficiencia de Proteína S/sangre , Trombosis/etiología , Warfarina/efectos adversos , Anticoagulantes/uso terapéutico , Enoxaparina/uso terapéutico , Femenino , Estudios de Seguimiento , Humanos , Relación Normalizada Internacional , Persona de Mediana Edad , Trombosis/sangre , Trombosis/prevención & control , Warfarina/uso terapéutico
3.
Isr Med Assoc J ; 8(10): 672-4, 2006 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-17125110

RESUMEN

BACKGROUND: Post-transfusion purpura is a rare syndrome characterized by severe thrombocytopenia and bleeding caused by alloimunization to human platelet specific antigens following a blood component transfusion. The suggested incidence is 1:50,000-100,000 transfusions, most often occurring in multiparous women. The diagnosis is not easy because these patients, who are often critically ill or post-surgery, have alternative explanations for thrombocytopenia such as infection, drugs, etc. OBJECTIVES: To describe patients with initially misdiagnosed PTP and to emphasize the diagnostic pitfalls of this disorder. PATIENTS AND RESULTS: During a period of 11 years we diagnosed six patients with PTP, four women and two men. The incidence of PTP was approximately 1:24,000 blood components transfused. We present the detailed clinical course of three of the six patients in whom the diagnosis was particularly challenging. The patients were initially misdiagnosed as having heparin-induced thrombocytopenia, systemic lupus erythematosus complicated by autoimmune thrombocytopenia, and disseminated intravascular coagulation. A history of recent blood transfusion raised the suspicion of PTP and the diagnosis was confirmed by appropriate laboratory workup. CONCLUSIONS: PTP seems to be more frequent than previously described. The diagnosis should be considered in the evaluation of life-threatening thrombocytopenia in both men and women with a recent history of blood transfusion.


Asunto(s)
Púrpura/diagnóstico , Reacción a la Transfusión , Anciano , Formación de Anticuerpos , Antígenos de Plaqueta Humana/inmunología , Diagnóstico Diferencial , Ensayo de Inmunoadsorción Enzimática/métodos , Femenino , Hemorragia/etiología , Humanos , Masculino , Errores Médicos/prevención & control , Persona de Mediana Edad , Púrpura/complicaciones , Púrpura/etiología , Enfermedades Raras , Trombocitopenia/etiología
5.
Isr Med Assoc J ; 5(5): 322-5, 2003 May.
Artículo en Inglés | MEDLINE | ID: mdl-12811946

RESUMEN

BACKGROUND: The chronic progressive course of peripheral arterial occlusive disease with its limb-threatening and life-threatening potential is associated with physical, psychological and social distress for elderly patients and their families. OBJECTIVE: To evaluate the influence of infra-inguinal bypass surgery for limb salvage, and social support, on quality of life in elderly patients (over 60 years old). METHODS: Sixty patients aged 60 years and above diagnosed with limb-threatening ischemia were evaluated using the SF-36 generic questionnaire for quality of life, and the MOS-SS questionnaire for social support. Thirty patients (group I) were evaluated in the hospital prior to reconstructive surgery and 30 postoperative patients (group II) were evaluated at home at least 6 months after infra-inguinal bypass operations. Both groups were comparable in terms of age, gender, prevalence of ischemic heart disease, diabetes, and other athero-sclerosis risk factors. RESULTS: All quality of life parameters were higher among patients who underwent limb salvage surgery (group II) as compared to preoperative patients (group I), yet the obtained values were lower than those in the general population. Patients in the surgical intervention group had higher levels of function, lower pain levels, and higher emotional and social well-being and, in addition, were spared limb amputation. The findings also indicate that the social support dimensions (emotional support, receipt of information, affection and positive social interaction), as measured in terms of perceived availability, do not operate as one entity. Different types of social support were more beneficial along different stages of the disease. CONCLUSION: Peripheral arterial occlusive disease causes severe impairment of the quality of life in elderly patients. Arterial reconstructive surgery improves the quality of life though it still remains low compared to the general population. Social support is beneficial in the treatment of these patients, and the social worker in the vascular surgery department has a key role in identifying the various needs of the patients along the path of their chronic illness.


Asunto(s)
Arteriopatías Oclusivas/cirugía , Conducto Inguinal/irrigación sanguínea , Conducto Inguinal/cirugía , Recuperación del Miembro , Enfermedades Vasculares Periféricas/cirugía , Arteria Poplítea/cirugía , Calidad de Vida , Apoyo Social , Arterias Tibiales/cirugía , Factores de Edad , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Periodo Posoperatorio
6.
Vasc Endovascular Surg ; 37(2): 111-5, 2003.
Artículo en Inglés | MEDLINE | ID: mdl-12669142

RESUMEN

Chronic venous insufficiency, which traditionally has been attributed to failure of the deep venous system, may result from reflux in the superficial venous system. Chronic venous insufficiency is common in elderly patients, but surgical treatment is seldom offered to this patient population. We evaluated the results of superficial venous surgery for the treatment of severe chronic venous insufficiency in a cohort of elderly patients. The authors assessed patients aged 70 years or more with chronic venous insufficiency that had failed conventional conservative treatment. The superficial and deep venous systems were thoroughly investigated by duplex ultrasonography. Associated medical conditions were reevaluated and their treatment optimized. Twenty-eight patients (11 men, 17 women), aged between 70 and 89 years (mean 79), underwent superficial venous surgery. Open ulcers, active dermatitis and recurrent erysipelas were evident in 12, 9 and 7 patients, respectively. Limb swelling and severe pain were present in 25 (89%). The operations were performed under general or regional anesthesia with overnight hospitalization. Surgical treatment consisted of ligation of the points of reflux at the junctions of the superficial and deep systems, as defined by the duplex examination (21 saphenofemoral junctions, 5 saphenopopliteal junctions, 10 perforator veins), and stripping of the long saphenous vein to knee level (15 patients). Postoperative ambulatory treatment was continued until the wounds were completely closed. All ulcers healed completely within 8 weeks. No cardiac, respiratory, or renal complications were encountered. Wound infection at the groin occurred in 1 patient. Cellulitis of the calf area developed in 4 patients. Two ulcers recurred during follow-up of 1 to 5 years (mean 2.5). Surgery of the superficial venous system for treatment of severe chronic venous insufficiency is effective and can be achieved with minimal morbidity in selected elderly patients. The risk/benefit ratio for this procedure has been reduced sufficiently to ensure a major improvement in the quality of life of such patients.


Asunto(s)
Várices/etiología , Várices/cirugía , Insuficiencia Venosa/complicaciones , Insuficiencia Venosa/cirugía , Factores de Edad , Anciano , Anciano de 80 o más Años , Enfermedad Crónica , Estudios de Cohortes , Femenino , Estudios de Seguimiento , Humanos , Masculino , Evaluación de Resultado en la Atención de Salud , Calidad de Vida , Índice de Severidad de la Enfermedad , Ultrasonografía , Várices/diagnóstico por imagen , Insuficiencia Venosa/diagnóstico por imagen
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