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1.
Osteoporos Int ; 33(11): 2259-2274, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-35748896

RESUMO

Patients with CKD have a 4-fivefold higher rate of fractures. The incidence of fractures increases with deterioration of kidney function. The process of skeletal changes in CKD patients is characterized by compromised bone strength because of deterioration of bone quantity and/or quality. The fractures lead to a deleterious effect on the quality of life and higher mortality in patients with CKD. The pathogenesis of bone loss and fracture is complex and multi-factorial. Renal osteodystrophy, uremic milieu, drugs, and systemic diseases that lead to renal failure all contribute to bone damage in CKD patients. There is no consensus on the optimal diagnostic method of compromised bone assessment in patients with CKD. Bone quantity and mass can be assessed by dual-energy x-ray absorptiometry (DXA) or quantitative computed tomography (QCT). Bone quality on the other side can be assessed by non-invasive methods such as trabecular bone score (TBS), high-resolution bone imaging methods, and invasive bone biopsy. Bone turnover markers can reflect bone remodeling, but some of them are retained by kidneys. Understanding the mechanism of bone loss is pivotal in preventing fracture in patients with CKD. Several non-pharmacological and therapeutic interventions have been reported to improve bone health. Controlling laboratory abnormalities of CKD-MBD is crucial. Anti-resorptive therapies are effective in improving BMD and reducing fracture risk, but there are uncertainties about safety and efficacy especially in advanced CKD patients. Accepting the prevalent of low bone turnover in patients with advanced CKD, the osteo-anabolics are possibly promising. Parathyroidectomy should be considered a last resort for intractable cases of renal hyperparathyroidism. There is a wide unacceptable gap in osteoporosis management in patients with CKD. This article is focusing on the updated management of CKD-MBD and osteoporosis in CKD patients. Chronic kidney disease deteriorates bone quality and quantity. The mechanism of bone loss mainly determines pharmacological treatment. DXA and QCT provide information about bone quantity, but assessing bone quality, by TBS, high-resolution bone imaging, invasive bone biopsy, and bone turnover markers, can guide us about the mechanism of bone loss.


Assuntos
Distúrbio Mineral e Ósseo na Doença Renal Crônica , Fraturas Ósseas , Osteoporose , Insuficiência Renal Crônica , Absorciometria de Fóton/métodos , Densidade Óssea , Distúrbio Mineral e Ósseo na Doença Renal Crônica/complicações , Distúrbio Mineral e Ósseo na Doença Renal Crônica/terapia , Fraturas Ósseas/etiologia , Humanos , Osteoporose/diagnóstico , Osteoporose/etiologia , Osteoporose/terapia , Qualidade de Vida , Insuficiência Renal Crônica/complicações , Insuficiência Renal Crônica/terapia
2.
Leukemia ; 32(2): 376-382, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-28663581

RESUMO

Novel anti-myeloma agents have improved patient response rates, which are historically based on reductions of the M-protein. These methods can be inaccurate for quantifying M-proteins at low concentrations. We compared the consistency and clinical impact of response assignment by electrophoretic and heavy+light chain (HLC) immunoassays post-consolidation in 463 newly diagnosed patients. The two methods gave similar assignments in patients with partial (PR; 79% agreement) or complete response (⩾CR; 92%). However, in patients achieving very good PR (VGPR) there was poor concordance between methods (45%). Median progression-free survival (PFS) for standard VGPR patients was 34.5 months; HLC responses stratified these patients further into PR, VGPR and ⩾CR, with median PFS of 21.3, 28.9 months and not reached, respectively; P<0.001. At this time, abnormal HLC ratios had better concordance with multiparametric flow cytometry (sensitivity 10-4) (37 and 34% positive, respectively), compared to immunofixation (62% positive). In addition, HLC-pair suppression was identified in 38% of patients and associated with shorter PFS (30.6 months vs not reached; P<0.001). We conclude that HLC monitoring could augment electrophoretic assessments in patients achieving VGPR. The prognostic significance of HLC responses might partly depend on the patients' ability to recover their immune system, as determined by normalisation of HLC measurements.


Assuntos
Cadeias Pesadas de Imunoglobulinas/imunologia , Cadeias Leves de Imunoglobulina/imunologia , Mieloma Múltiplo/imunologia , Adulto , Idoso , Feminino , Humanos , Imunoeletroforese/métodos , Masculino , Pessoa de Meia-Idade , Proteínas do Mieloma/imunologia , Prognóstico , Intervalo Livre de Progressão
4.
Leukemia ; 30(10): 2047-2054, 2016 10.
Artigo em Inglês | MEDLINE | ID: mdl-27118410

RESUMO

We describe the use and outcomes of allogeneic hematopoietic stem cell transplantation (allo-HSCT) for multiple myeloma (MM) in Europe between January 1990 and December 2012. We identified 7333 patients, median age at allo-HSCT was 51 years (range: 18-78), of whom 4539 (62%) were males. We distinguished three groups: (1) allo-HSCT upfront (n=1924), (2) tandem auto-allo-HSCT (n=2004) and (3) allo-HSCT as a second line treatment and beyond (n=3405). Overall, there is a steady increase in numbers of allo-HSCT over the years. Upfront allo-HSCT use increased up to year 2000, followed by a decrease thereafter and represented 12% of allo-HSCTs performed in 2012. Tandem auto-allo-HSCT peaked around year 2004 and contributed to 19% of allo-HSCTs in 2012. Allo-HSCT as salvage after one or two or three autografts was steadily increasing over the last years and represented 69% of allo-HSCTs in 2012. Remarkable heterogeneity in using allo-HSCT was observed among the different European countries. The 5-year survival probabilities from time of allo-HSCT for the three groups after year 2004 were 42%, 54% and 32%, respectively. These results show that the use of allo-HSCT is increasing in Europe, especially as second line treatment and beyond. There is an unmet need for well-designed prospective studies investigating allo-HSCT as salvage therapy for MM.


Assuntos
Transplante de Células-Tronco Hematopoéticas/métodos , Mieloma Múltiplo/terapia , Adolescente , Adulto , Idoso , Europa (Continente) , Feminino , Transplante de Células-Tronco Hematopoéticas/tendências , Humanos , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/mortalidade , Taxa de Sobrevida , Transplante Homólogo , Resultado do Tratamento , Adulto Jovem
5.
Transplant Proc ; 46(10): 3620-8, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25498100

RESUMO

BACKGROUND: Mycophenolate mofetil (MMF) is an effective immunosuppressive agent that has been frequently used in laboratory animals including swine; however, the pharmacokinetic properties of MMF in swine have not been studied. This short-term study was designed to evaluate the feasibility and the pharmacokinetic profiles of MMF therapy in neonatal swine. MATERIALS AND METHODS: Twelve neonatal pigs were randomized into four groups including one control and three treated groups with oral MMF administered at 0.5, 1, and 2 g/m(2)/d for 4 days, divided by 2 half-doses at 9:00 and 17:00 (except day 4 during which MMF was not administered at 17:00). Blood samples were collected at 9:00 on days 0, 2, 3 and 4 for complete blood count and hepatic/renal function examination; the trough concentration of plasma mycophenolic acid (MPA) was also determined. On days 2 and 4, blood was collected to determine the area under the curve (AUC) of plasma MPA concentration. Animal body-weight growth and manifestations of MMF side-effects such as anorexia, vomiting, and diarrhea were also observed. RESULTS: MMF has no acute hepatic/renal toxicity in newborn pigs; however, less body-weight growth was observed in treated groups. In the control group, a spontaneous increase of lymphocyte count was observed; in contrast, MMF therapy with doses of 1 and 2 g/m(2)/d reduced both lymphocyte and monocyte counts of piglets. Oral MMF had high bioavailability in neonatal swine. MPA-AUC0-12h of doses 0.5, 1, and 2 g/m(2)/d was 22.00 ± 3.32, 57.57 ± 34.30, and 140.00 ± 19.70 µg × h/mL, respectively. Neither MPA trough concentration (MPA-C0), nor MPA maximum concentration (MPA-Cmax) or MPA-AUC0-6h had high correlation with MMF-dose. For surveillance of MPA exposure, MPA-C0 had significant correlation with MPA-AUC0-12h (Spearman's ρ = 0.933, AUC0-12h = 17.882 × C0 + 14.479, r(2) = 0.966). CONCLUSION: To reach adequate drug exposure and to reduce dose-dependent side effects, an MMF dose of 1 g/m(2)/d is recommended to be used as an initial dose for immunosuppressive therapy in piglets, and MPA-C0 monitoring is the most practical strategy for experimental transplantation study.


Assuntos
Rejeição de Enxerto/tratamento farmacológico , Ácido Micofenólico/análogos & derivados , Transplante de Órgãos , Animais , Animais Recém-Nascidos , Modelos Animais de Doenças , Seguimentos , Rejeição de Enxerto/sangue , Imunossupressores/farmacocinética , Ácido Micofenólico/farmacocinética , Suínos
6.
Leuk Res ; 38(10): 1145-53, 2014 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-24906663

RESUMO

The treatment of chronic myelogenous leukemia (CML) has been revolutionized by the introduction of tyrosine kinase inhibitors (TKI), however, with the exception of ponatinib, none of the existing licensed agents seem to eradicate the reservoir of Philadelphia positive stem cells, thus sustaining the disease over time, and retaining activity in cells and patients harboring an ABL T315I mutation. Omacetaxine mepesuccinate (OMA), formerly known as homoharringtonine, is a cephalotaxus alkaloid derivative and an inhibitor of protein synthesis without tyrosine kinase activity developed 35 years ago by Chinese investigators in the treatment of leukemia. This compound demonstrates specific activity in CML and has been recently commercialized in the U.S. for the treatment of patients in chronic or accelerated phase CML with resistance and/or intolerance to two or more tyrosine kinase inhibitors or harboring a T315I ABL mutation. CML patients with a T315I mutation experienced poor overall survival rates in the pre-ponatinib era (median for CP CML 24 months). Recent studies demonstrate the activity of OMA even in such a poor prognosis population. We hereby detail the development of OMA as an effective agent in CML in these patients.


Assuntos
Antineoplásicos Fitogênicos/administração & dosagem , Harringtoninas/administração & dosagem , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Animais , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Mepesuccinato de Omacetaxina , Humanos , Infusões Subcutâneas
7.
Bone Marrow Transplant ; 49(5): 664-70, 2014 May.
Artigo em Inglês | MEDLINE | ID: mdl-24488049

RESUMO

BK virus (BKV) reactivation has been increasingly associated with the occurrence of late-onset hemorrhagic cystitis (HC) after allogeneic hematopoietic SCT (allo-HSCT) resulting in morbidity and sometimes mortality. We investigated the incidence, risk factors and outcome of BKV-HC in 323 consecutive adult patients undergoing allo-HSCT over a 5-year period. BK viremia values for HC staging were evaluated, as well as the medico-economic impact of the complication. Forty-three patients developed BKV-HC. In univariate analysis, young age (P=0.028), unrelated donor (P=0.0178), stem cell source (P=0.0001), HLA mismatching (P=0.0022) and BU in conditioning regimen (P=0.01) were associated with a higher risk of developing BKV-HC. In multivariate analysis, patients receiving cord blood units (CBUs) (P=0.0005) and peripheral blood stem cells (P=0.011) represented high-risk subgroups for developing BKV-HC. BK viremia was directly correlated to HC severity (P=0.011) with a 3 to 6-log peak being likely associated with grades 3 or 4 HC. No correlation was found between BKV-HC and acute graft versus host disease or mortality rate. Patients with BKV-HC required a significantly longer duration of hospitalization (P<0.0001), more RBC (P=0.0003) and platelet transfusions (P<0.0001). Over the 5-year study period, the financial cost of the complication was evaluated at \[euro]2 376 076 ($3 088 899). Strategies to prevent the occurrence of late-onset BKV-HC after allo-HSCT are urgently needed, especially in CBU and peripheral blood stem cell recipients. BK viremia correlates with the severity of the disease. Prospective studies are required to test prophylactic approaches.


Assuntos
Vírus BK , Cistite/virologia , Neoplasias Hematológicas/terapia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Infecções por Polyomavirus/epidemiologia , Infecções Tumorais por Vírus/epidemiologia , Adolescente , Adulto , Idoso , Antivirais/uso terapêutico , Cidofovir , Cistite/economia , Cistite/epidemiologia , Citosina/análogos & derivados , Citosina/uso terapêutico , Feminino , Doença Enxerto-Hospedeiro/economia , Doença Enxerto-Hospedeiro/epidemiologia , Custos de Cuidados de Saúde , Neoplasias Hematológicas/economia , Neoplasias Hematológicas/epidemiologia , Transplante de Células-Tronco Hematopoéticas/economia , Custos Hospitalares , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Organofosfonatos/uso terapêutico , Infecções por Polyomavirus/tratamento farmacológico , Infecções por Polyomavirus/economia , Fatores de Risco , Transplante Homólogo , Infecções Tumorais por Vírus/tratamento farmacológico , Infecções Tumorais por Vírus/economia , Viremia/complicações , Viremia/tratamento farmacológico , Viremia/imunologia , Adulto Jovem
8.
Physiol Res ; 63(1): 47-55, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24182334

RESUMO

Recent studies demonstrated remote effects of renal ischemia/reperfusion (I/R) injury on some organs such as brain, liver, and lungs. We investigated the effects of renal I-R injury on function, histology and oxidative stress state of pancreas. Twenty-four male adult Sprague-Dawley rats were divided equally into 2 groups; sham group: rats underwent midline laparotomy and dissection of renal pedicles without renal ischemia, and ischemic group: rats underwent bilateral renal ischemia for 45 min. Renal functions (serum creatinine and BUN), pancreatic functions (serum amylase, lipase and insulin) and fasting blood glucose were measured at 2 h, 1 day, 3 days and 7 days after ischemia. Also, pancreatic histology and malondialdehyde (MDA), catalase and reduced glutathione (GSH) were examined at 2 h and 7 days after ischemia. The ischemic rats showed significant increase in serum creatinine and BUN with significant increase in serum amylase and lipase at 2 h, 1 day and 3 days after ischemia. Blood glucose and fasting insulin showed no significant change apart from significant increase in insulin in sham group at 1 day after ischemia. Pancreas isolated from ischemic rats showed significant increase in histopathological damage score and significant increase in MDA and catalase enzyme with decrease in GSH. In conclusion, bilateral renal ischemia for 45 min caused significant impairment of pancreatic functions and histology. This might be due to deficiency of antioxidant and increased lipid peroxidations in pancreatic tissues.


Assuntos
Injúria Renal Aguda/metabolismo , Estresse Oxidativo/fisiologia , Pâncreas/lesões , Pâncreas/metabolismo , Traumatismo por Reperfusão/metabolismo , Injúria Renal Aguda/complicações , Injúria Renal Aguda/patologia , Animais , Masculino , Pâncreas/patologia , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley , Traumatismo por Reperfusão/complicações , Traumatismo por Reperfusão/patologia
9.
Eur J Clin Microbiol Infect Dis ; 31(6): 991-7, 2012 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-21909650

RESUMO

Invasive aspergillosis (IA) during induction chemotherapy of acute myeloid leukemia (AML) could worsen the prognosis. Our objective was to study how the development of IA during AML interferes with the therapeutic strategy and to evaluate its impact on the short- and long-term survival. Newly diagnosed AML patients between the years 2004 and 2007 were retrospectively analyzed. The outcome was death of the patient. A Cox proportional hazards model with the diagnosis of IA and post-induction response evaluation as the main exposure was fitted. Overall, 262 patients were analyzed and 58 IA were observed. The 2-year survival of patients having had remission of AML was 54% and, for patients with failure of chemotherapy, it was 5% (p < 0.001). The 2-year survival of patients having had IA was 14%, and without IA, it was 32% (p = 0.01). Multivariate analysis showed that IA was associated with a higher risk of death in case of remission compared to no IA (hazard ratio [HR] = 1.66 [1.05-2.65], p = 0.031) and also in case of failure (HR = 6.43, p < 0.001). IA was associated with an increased risk of death for patients if they were either in remission or in failure after induction chemotherapy.


Assuntos
Aspergilose/epidemiologia , Aspergilose/mortalidade , Fungemia/epidemiologia , Fungemia/mortalidade , Leucemia Mieloide Aguda/complicações , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/administração & dosagem , Feminino , Humanos , Hospedeiro Imunocomprometido , Leucemia Mieloide Aguda/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Análise de Sobrevida
10.
Int J Biol Sci ; 7(6): 715-28, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-21697998

RESUMO

Phytotherapy is frequently considered to be less toxic and free from side effects than synthetic drugs. Hence, the present study was designed to investigate the protective use of crude water extract of Morus alba leaves on ocular functions including cataractogenesis, biochemical diabetic and hypercholesterolemic markers, retinal neurotransmitters and retinopathy of rat pups maternally subjected to either diabetes and/or hypercholesterolemia. Application of crude water extract of Morus alba resulted in amelioration of the alterations of maternal serum glucose, LDL, HDL, total cholesterol and creatine phosphokinase activity as well as retinal neurotransmitters including acetylcholine (ACE), adrenaline (AD), nor-adrenaline (NAD), serotonin (5-HT), histamine (HS), dopamine (DA) and gamma amino butyric acid (GABA). The retina of pups of either diabetic and/or hypercholesterolemia mothers exhibited massive alterations of retinal neurotransmitters. The alterations of retinal neurotransmitters were correlated with the observed pathological alterations of retinal pigmented epithelium, photoreceptor inner segment and ganglion cells and increased incidence of DNA fragmentation and apoptosis cell death. However, protection with Morus alba extract led to amelioration of the pathological alterations of retinal neurons and estimated neurotransmitters. Furthermore, a striking incidence of cataract was detected in pups of either diabetic and/or hypercholesterolemic mothers. Highest cataractogenesis was observed in pups of combined -treated groups. Our data indicate that experimental maternal diabetes alone or in combination with hypercholesterolemia led to alteration in the ocular structures of their pups, with an increasing incidence of cataract and retinopathy, and the effects of the extract might be attributed to the hypoglycaemic, antihypercholesterolemic and anti-oxidative potential of flavonoids, the major components of the plant extract.


Assuntos
Retinopatia Diabética/prevenção & controle , Morus/química , Fitoterapia , Extratos Vegetais/uso terapêutico , Retina/efeitos dos fármacos , Animais , Apoptose/efeitos dos fármacos , Catarata/etiologia , Catarata/patologia , Ensaio Cometa , Dano ao DNA/efeitos dos fármacos , Diabetes Gestacional/sangue , Diabetes Gestacional/induzido quimicamente , Diabetes Gestacional/tratamento farmacológico , Retinopatia Diabética/complicações , Retinopatia Diabética/congênito , Retinopatia Diabética/patologia , Feminino , Hipercolesterolemia/sangue , Hipercolesterolemia/tratamento farmacológico , Masculino , Neurotransmissores/metabolismo , Extratos Vegetais/farmacologia , Gravidez , Efeitos Tardios da Exposição Pré-Natal/prevenção & controle , Ratos , Retina/metabolismo , Retina/ultraestrutura , Estreptozocina
12.
Leukemia ; 24(10): 1725-31, 2010 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-20703257

RESUMO

We analyzed 368 chronic lymphocytic leukemia patients who underwent allogeneic hematopoietic stem cell transplantation reported to the EBMT registry between 1995 and 2007. There were 198 human leukocyte antigen (HLA)-identical siblings; among unrelated transplants, 31 were well matched in high resolution ('well matched' unrelated donor, WMUD), and 139 were mismatched (MM), including 30 matched in low resolution; 266 patients (72%) received reduced-intensity conditioning and 102 (28%) received standard. According to the EBMT risk score, 11% were in scores 1-3, 23% in score 4, 40% in score 5, 22% in score 6 and 4% in score 7. There was no difference in overall survival (OS) at 5 years between HLA-identical siblings (55% (48-64)) and WMUD (59% (41-84)), P=0.82. In contrast, OS was significantly worse for MM (37% (29-48) P=0.005) due to a significant excess of transplant-related mortality. Also OS worsened significantly when EBMT risk score increased. HLA matching had no significant impact on relapse (siblings: 24% (21-27); WMUD: 35% (26-44), P=0.11 and MM: 21% (18-24), P=0.81); alemtuzumab T-cell depletion and stem cell source (peripheral blood) were associated with an increased risk. Our findings support the use of WMUD as equivalent alternative to HLA-matched sibling donors for allogeneic HSCT in CLL, and justify the application of EBMT risk score in this disease.


Assuntos
Doença Enxerto-Hospedeiro/prevenção & controle , Antígenos HLA/metabolismo , Transplante de Células-Tronco Hematopoéticas , Leucemia Mielogênica Crônica BCR-ABL Positiva/metabolismo , Leucemia Mielogênica Crônica BCR-ABL Positiva/terapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Seguimentos , Doença Enxerto-Hospedeiro/etiologia , Teste de Histocompatibilidade , Humanos , Leucemia Mielogênica Crônica BCR-ABL Positiva/imunologia , Masculino , Pessoa de Meia-Idade , Sistema de Registros , Estudos Retrospectivos , Irmãos , Taxa de Sobrevida , Transplante Homólogo , Resultado do Tratamento
13.
Indian J Nephrol ; 18(2): 58-63, 2008 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-20142904

RESUMO

BACKGROUND: Nephrotic dyslipidemia is a risk factor for the development of systemic atherosclerosis; and may aggravate glomerulosclerosis and enhance progression of glomerular disease. We aimed to assess the efficacy and safety of Monascus purpureus Went rice vs. fluvastatin therapy in the management of nephrotic dyslipidemia. MATERIALS AND METHODS: Seventy-two patients with persistent idiopathic nephrotic syndrome (NS) with secondary dyslipidemia were included. They were randomly allocated into three age and sex-matched groups. The first group comprised 20 cases and were given M. purpureus Went rice in a dose of 600 mg twice/day for 1 month then once daily, the second group comprised 30 cases were given fluvastatin in a daily dose of 20 mg. The remaining 22 received no antidyslipidemic therapy and constituted a control group. All of these patients were subjected to thorough laboratory investigations including renal function tests and lipogram. Moreover, the neuromuscular status was evaluated with electromyography and nerve conduction velocity. RESULTS: Our results showed that both fluvstatin and M. purpureus Went rice were well tolerated with no evidence of significant side effects including neuromuscular functions. Both of them significantly reduced cholesterol after 6 months and 1 year. CONCLUSION: Monascus purpureus Went rice is safe, effective, and economic treatment strategy for nephrotic dyslipidemia.

14.
Neth Heart J ; 15(2): 61-6, 2007.
Artigo em Inglês | MEDLINE | ID: mdl-17612662

RESUMO

BACKGROUND: In practice the benefit of cardiovascular medicines is less consistent than it is in clinical trials. This is due to multiple uncontrolled factors that co-determine the efficacy of the new treatment. In statistical terms, they interact with the new treatment. Interaction effects are rarely assessed in cardiovascular trials. OBJECTIVE: To review (1) important factors that may interact with the treatment efficacy, (2) how to examine such factors, and (3) why so. RESULTS: Important factors include (a) possible risk factors such as specific patient characteristics, and concomitant medications, and (b) study-specific aspects such as heterogeneities of investigators, health centres, and individual patients including patient compliance. Such factors can be assessed by comparing subgroups. A common but incorrect approach is the comparison of the significances of difference between treatment modalities in either subgroup. Instead, a direct comparison of effect sizes relative to the standard errors is adequate. As an alternative, regression modelling is adequate and convenient. Results of interaction assessments are post-hoc and, therefore, of an exploratory and unconfirmed nature. So, why should they be performed? In cardiovascular research the effects of patient characteristics and drug-drug interactions on drug efficacies are numerous. It is valuable to account at least post-hoc for such mechanisms. Second, current cardiovascular trials involve heterogeneous health centres, investigators, and patient groups. Accounting for these heterogeneities can be helpful to better predict individual responses in future patients. CONCLUSION: Cardiovascular trials enrolling patient groups at risk for heterogeneity should include at least a post-hoc assessment for interaction. Correct and incorrect methods for that purpose are described. Interaction assessments are helpful to better predict the efficacy/safety of new cardiovascular medicines in the future treatment of subgroups of patients. (Neth Heart J 2007;15:61-6.).

16.
Int Urol Nephrol ; 39(2): 609-18, 2007.
Artigo em Inglês | MEDLINE | ID: mdl-17279435

RESUMO

INTRODUCTION: Haemodialysis (HD) patients appear to have particular susceptibility for cardiovascular (CV) diseases with lipid abnormalities among its significant contributors. However, there is controversy concerning the combined effect on lipid constituents during HD of the three commonly used variables; the type of heparin, dialysis membrane and the constituent of dialysate buffer bases. Consequently, this controlled prospective study was thought of. PATIENTS: Randomly 63 patients were assigned from Urology and Nephrology haemodialysis (HD) unit, Mansoura, Egypt for the planned study. Their mean age was 45.79 +/- 13.11 years. Fourteen patients with end-stage renal disease (ESRD) served as control group for the remaining 49 HD patients. They were subdivided according to the HD duration (< and > 1 year), anticoagulant used (unfractionated [UFH] and low-molecular weight heparin [LMWH, Enoxaparin), membrane type (Hemophane [HP] and polysulfone [PS] membrane) and dialysate buffer bases (bicarbonate versus acetate based). METHODS: Determining the fasting lipid value of total cholesterol (TC) and triglycerides (TG) as well as lipoproteins including low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C) and lipoprotein (a) [Lp (a)] was completed. RESULTS: Bicarbonate dialysate was associated with significantly lower TG (134.7 +/- 11 mg/dl vs. 153 +/- 14 mg/dl, p = 0.004), higher HDL-C (33.1 +/- 3 vs. 28.3 +/- 2, p = 0.0002) and subsequently better atherosclerosis risk ratio [TC/HDL-C (ARR)] (6.02 +/- 0.09 vs. 5.3 +/- 0.9, p = 0.001) despite its insignificant effect on TC and LDL-C. However, logarithm (log) Lp (a) level was significantly higher (1.92 +/- 0.05 vs. 1.82 +/- 0.04 p = 0.001) in comparison with acetate dialysate. Membrane type was not influential in those dialyzed for < 1 year before intervention while after a year of HD, PS (n = 11) compared to HP filters (n = 11) significantly lowered TC (151.7 +/- 16 vs. 172.6 +/- 12, p = 0.003), TG (127.8 +/- 15 vs. 155.7 +/- 15, p = 0.004), LDL-C (122.1 +/- 5 vs. 130.6 +/- 7, p = 0.006) levels as well as ARR (5.9 +/- 0.5 vs. 5.4 +/- 0.3, p = 0.02). Likewise was the reduction in log Lp (a) (1.9 +/- 0.03 vs. 1.8 +/- 0.04, p = 0.002) with insignificant effect on HDL-C. After 6 months, Enoxaparin caused significant improvement of TC (0.0004), TG (p = 0.018), LDL-C (p = 0.006), HDL-C (0.041) and Lp (a) (0.047) compared to UFH. Patients who continued on Enoxaparin for 3 more months displayed an even better attenuation in most of lipid parameters whilst continuation of UFH was insignificant. Switching few patients (n = 4) from UFH to LMWH for 3 months resulted in significant lowering of TC (153 +/- 7 vs. 177.7 +/- 3, p = 0.01), TG (127.5 +/- 5 vs. 137.3 +/- 4, p = 0.03) and LDL-C (124.7 +/- 5 vs. 127.5 +/- 5, p = 0.005). However, switching equal number of patients from LMWH to UFH caused no significant change. CONCLUSION: Dyslipidaemia in Egyptian haemodialysis patients was improved when bicarbonate-based haemodialysis, the use of polysulfone membrane, and more so when the low-molecular weight heparin Enoxaparin were used.


Assuntos
Colesterol/sangue , Heparina/uso terapêutico , Falência Renal Crônica/sangue , Falência Renal Crônica/terapia , Diálise Renal , Triglicerídeos/sangue , Egito , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
17.
Transplant Proc ; 36(6): 1850-2, 2004.
Artigo em Inglês | MEDLINE | ID: mdl-15350496

RESUMO

Sensitization can present a virtually insurmountable barrier to kidney transplantation. Ten to twenty percent of patients on waiting lists for renal transplantation have developed broadly reactive cytotoxic antibodies against HLA antigens caused by pregnancy, blood transfusion, or a prior failed allograft. These sensitized end-stage renal disease patients often wait more than 5 years for a kidney to be offered. Potent immunosuppressives, plasma exchange and/or immunoadsorption have been used but the risk of infection limited their use. Some reports, have demonstrated in small numbers of patients the use of Intravenous Immunoglobulin (IVIG) as potential modality for the treatment of these sensitized patients. The goal of this study was to investigate the extent of the efficacy and to assess the utility of this modality of treatment on a relatively larger number of patients. The study included 11 patients with end stage renal disease who were waiting for living related renal allotransplantation. All patients had persistently positive crossmatches with their living related donors and PRA titer >/=20%. They received IVIG for a period of two weeks and a total of 6 doses. None of these patients, however, attained significant suppression of anti-HLA antibodies titer or a negative crossmatch reaction. We found that IVIG alone couldn't effectively inhibit preformed anti-HLA antibodies to allow successful renal transplantation.


Assuntos
Imunoglobulinas Intravenosas/uso terapêutico , Imunossupressores/uso terapêutico , Transplante de Rim/imunologia , Adulto , Transfusão de Sangue , Feminino , Antígenos HLA/imunologia , Teste de Histocompatibilidade , Humanos , Falência Renal Crônica/cirurgia , Doadores Vivos , Masculino , Seleção de Pacientes , Diálise Renal
18.
Trans R Soc Trop Med Hyg ; 98(6): 331-6, 2004 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-15099987

RESUMO

In Egypt, the etiology of chronic renal failure (CRF) is not well defined. A hospital-based case-control study was initiated in February 1998, to determine whether hantavirus infection is involved in chronic renal disease (CRD) in Egypt. The study enrolled 350 study patients with a history of CRF and 695 matched controls with CRD due to renal calculus or renal cancer, but with normal renal functions. Sera from cases and controls were tested for anti-hantavirus IgG using ELISA with a cell-lysate antigen from Hantaan virus prototype strain 76-118. A demographic questionnaire was completed for each study participant. Five of the 350 cases (1.4%), and seven of the 695 controls (1.0%) were antibody-positive to hantavirus, with a titer > or =1:400. The difference in antibody prevalence between the study cases and the control cases was not statistically significant (P = 0.48). All antibody-positive study cases and controls had been exposed to rodents. Data indicated that in Egypt, hantavirus seroprevalence in CRD patients is low, and hantavirus infections do not appear to be a significant cause of CRF.


Assuntos
Anticorpos Antivirais/sangue , Infecções por Hantavirus/complicações , Falência Renal Crônica/virologia , Orthohantavírus/imunologia , Adulto , Estudos de Casos e Controles , Egito/epidemiologia , Feminino , Infecções por Hantavirus/epidemiologia , Humanos , Imunoglobulina G/sangue , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Estudos Soroepidemiológicos
19.
Nefrologia ; 23 Suppl 2: 131-4, 2003.
Artigo em Inglês | MEDLINE | ID: mdl-12778870

RESUMO

The factors that affect bone mineral density (BMD) and the long term progress of BMD after transplantation in children is still unknown. Therefore we performed a cross-sectional study to determine BMD in 83 recipients who received living renal allotransplants in Mansoura Urology & Nephrology Center between 1981 and 2001 (mean age at transplantation 13.2 +/- 3.1 years) by dual energy x-ray absorptiometry at various time intervals up to 16 years after transplantation (mean duration after transplantation was 48 +/- 34 months, range 6-192 months). The Z-score for lumbar spine was -2.28 +/- 2.06 and -1.44 +/- 1.44 for the total body. Osteopenia/osteoporosis were present in about two thirds of our kidney transplant recipients. The significant predictors for osteopenia/osteoporosis by univariate analysis were cyclosporine based immunosuppression, the cumulative steroid dose/m2 surface area, graft dysfunction and the urinary deoxypyridinoline. Using logistic regression analysis the cumulative steroid dose/m2 surface area and the urinary deoxypyridinoline were the major significant predictors for bone loss.


Assuntos
Doenças Ósseas Metabólicas/epidemiologia , Transplante de Rim , Osteoporose/epidemiologia , Complicações Pós-Operatórias/epidemiologia , Adolescente , Corticosteroides/efeitos adversos , Densidade Óssea , Doenças Ósseas Metabólicas/etiologia , Criança , Pré-Escolar , Creatinina/sangue , Egito/epidemiologia , Feminino , Rejeição de Enxerto , Humanos , Imunossupressores/efeitos adversos , Falência Renal Crônica/complicações , Falência Renal Crônica/cirurgia , Falência Renal Crônica/terapia , Modelos Lineares , Masculino , Osteoporose/etiologia , Complicações Pós-Operatórias/etiologia , Diálise Renal/efeitos adversos , Fatores de Risco
20.
Int Urol Nephrol ; 35(4): 543-51, 2003.
Artigo em Inglês | MEDLINE | ID: mdl-15198164

RESUMO

This study included 128 patients with crescentic glomerulonephritis (CGN) having sufficient clinical and histopathological data and were followed up in our institute for a mean period of 34 +/- 28 months. There were 49 males and 79 females with mean age 22.7 +/- 14 years. We studied the effect of clinical, laboratory and histopathological parameters on kidney function and patient survival at the end point of the study. The multivariate analysis revealed that serum creatinine at presentation, nephrotic range proteinuria during the follow up period, percentage of glomeruli affected by crescents, percentage of fibrous crescents and absence of cellular infiltration were significant risk factors affecting the kidney function at termination of the study. The only risk factor which correlated significantly with the patient mortality was the serum creatinine at last follows up.


Assuntos
Glomerulonefrite/patologia , Adolescente , Adulto , Criança , Egito , Feminino , Glomerulonefrite/fisiopatologia , Humanos , Masculino , Estudos Retrospectivos , Análise de Sobrevida , Resultado do Tratamento
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