Assuntos
Anti-Infecciosos Urinários/uso terapêutico , Nitroquinolinas/uso terapêutico , Infecções Urinárias/tratamento farmacológico , Infecções Urinárias/microbiologia , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Anti-Infecciosos Urinários/administração & dosagem , Anti-Infecciosos Urinários/efeitos adversos , Feminino , Humanos , Masculino , Nitroquinolinas/administração & dosagem , Nitroquinolinas/efeitos adversos , Estudos Prospectivos , Resultado do TratamentoRESUMO
BACKGROUND: Update of the 2010 published evidence-based S3 guideline on epidemiology, diagnostics, therapy and management of uncomplicated, bacterial, outpatient-acquired urinary tract infections in adult patients. The guideline contains current evidence for the rational use of antimicrobial substances, avoidance of inappropriate use of certain antibiotic classes and development of resistance. METHODOLOGY: The update was created under the leadership of the German Association of Urology (DGU). A systematic literature search was conducted for the period 01 January 2008 to 31 December 2015. International guidelines have also been taken into account. Evidence level and risk of bias were used for quality review. RESULTS: Updated information on bacterial susceptibility, success, collateral damage and safety of first- and second-line antibiotics was given. For the treatment of uncomplicated cystitis the first line antibiotics are fosfomycin trometamol, nitrofurantoin, nitroxoline, pivmecillinam, trimethoprim (with consideration of the local resistance rates). Fluoroquinolones and cephalosporins should not be used as first choice antibiotics. In the case of uncomplicated pyelonephritis of mild to moderate forms, preferably cefpodoxime, ceftibuten, ciprofloxacin or levofloxacin should be used as oral antibiotics. CONCLUSION: The updated German S3 guideline provides comprehensive evidence- and consensus-based recommendations on epidemiology, diagnostics, therapy, prevention and management of uncomplicated bacterial outpatient acquired urinary tract infections in adult patients. Antibiotic stewardship aspects have significantly influenced the therapeutic recommendations. A broad implementation in all clinical practice settings is necessary to ensure a foresighted antibiotic policy and thus t improve clinical care.
Assuntos
Antibacterianos/administração & dosagem , Infecções Bacterianas/epidemiologia , Infecções Bacterianas/prevenção & controle , Bacteriúria/epidemiologia , Bacteriúria/prevenção & controle , Guias de Prática Clínica como Assunto , Prevenção Secundária/normas , Alergia e Imunologia/normas , Infecções Bacterianas/diagnóstico , Bacteriúria/diagnóstico , Relação Dose-Resposta a Droga , Esquema de Medicação , Medicina Baseada em Evidências , Alemanha , Humanos , Prevalência , Fatores de Risco , Terapêutica , Urologia/normasAssuntos
Anti-Infecciosos Urinários/uso terapêutico , Infecções Urinárias/tratamento farmacológico , Anti-Infecciosos Urinários/efeitos adversos , Bacteriúria/diagnóstico , Bacteriúria/tratamento farmacológico , Bacteriúria/etiologia , Cefalosporinas/efeitos adversos , Cefalosporinas/uso terapêutico , Doença Crônica , Cistite/diagnóstico , Cistite/tratamento farmacológico , Cistite/etiologia , Farmacorresistência Bacteriana , Fluoroquinolonas/efeitos adversos , Fluoroquinolonas/uso terapêutico , Fosfomicina/efeitos adversos , Fosfomicina/uso terapêutico , Humanos , Testes de Sensibilidade Microbiana , Nitrofurantoína/efeitos adversos , Nitrofurantoína/uso terapêutico , Pielonefrite/diagnóstico , Pielonefrite/tratamento farmacológico , Pielonefrite/etiologia , Recidiva , Fatores de Risco , Sepse/diagnóstico , Sepse/tratamento farmacológico , Sepse/etiologia , Trometamina/efeitos adversos , Trometamina/uso terapêutico , Infecções Urinárias/diagnóstico , Infecções Urinárias/etiologiaRESUMO
BACKGROUND: Urinary tract infections (UTI) belong to the most frequent bacterial infections in outpatients. Increasing antibiotic resistance rates and a new appreciation of the epidemiological side effects of antibiotics ("collateral damage") have warranted an update of the guidelines on uncomplicated UTI as an S3 clinical guideline. METHODS: The guideline was developed by the Deutsche Gesellschaft für Urologie (DGU) in collaboration with the Deutsche Gesellschaft für Allgemein- und Familienmedizin (DEGAM), Deutsche Gesellschaft für Gynäkologie und Geburtshilfe (DGGG), Deutsche Gesellschaft für Hygiene und Mikrobiologie (DGHM), Deutsche Gesellschaft für Infektiologie (DGI), Deutsche Gesellschaft für Nephrologie (DGfN), Paul-Ehrlich-Gesellschaft für Chemotherapie (PEG) and a patient representative. The systematic review of the literature on the topics of the guideline was performed for the time period of 1 January 1998 to 30 April 2008 in the databases of the Cochrane Library and MEDLINE. International guidelines of the years 1999-2007 were included. RESULTS: Uncomplicated UTI comprise uncomplicated cystitis and uncomplicated pyelonephritis. The leading uropathogen is Escherichia coli. The choice of the antibiotic substance follows the five primary aspects: (1) individual patient risk and antibiotic pretreatment; (2) bacterial spectrum and antibiotic susceptibility; (3) effectivity of the antimicrobial substance demonstrated in clinical studies; (4) epidemiological effects ("collateral damage"); and (5) adverse effects. If antibiotics such as trimethoprim/sulfamethoxazole or fluoroquinolones have previously been given, the risk for pathogens to become resistant against these substances is increased. Because of increasing resistance rates of E. coli against trimethoprim/sulfamethoxazole also in uncomplicated UTI, trimethoprim alone or in combination with sulfamethoxazole is no longer regarded as the first-line agent in the empiric treatment of uncomplicated cystitis, unless the regional resistance rate is below 20%. The antibiotic resistance rates of fluoroquinolones in uncomplicated UTI are still below 10% in Germany, but there is a significant emergence of resistance compared to earlier years. Moreover, fluoroquinolones and group 3 cephalosporins exhibit negative epidemiological effects resulting in selection of multi-resistant pathogens. Because these antibiotic classes are needed in therapy of life-threatening infections, such effects should be taken seriously. For substances like fosfomycin, nitrofurantoin or mecillinam"collateral damage" has not been documented or only to a lesser degree. Therefore, for empiric therapy of frequent uncomplicated cystitis fosfomycin-trometamol, nitrofurantoin or pivmecillinam (not listed in Germany) are recommended as first-line antibiotics. For oral first-line treatment of uncomplicated pyelonephritis, fluoroquinolones are still recommended in sufficiently high dosage due to the resistance rates of E. coli still being below 10% and the superior effectivity compared to other antibiotics. Asymptomatic bacteriuria (ASB) should only be treated in exceptional cases such as pregnant women or prior to expected mucocutaneous traumatising interventions of the urinary tract. CONCLUSION: The S3 guideline on uncomplicated urinary tract infections is a comprehensive set of evidence- and consensus-based recommendations dealing with epidemiology, diagnosis, therapy and management of uncomplicated bacterial UTI of adult outpatients. A broad implementation in all disciplines taking care of patients with UTI is necessary in order to ensure a prudent antibiotic policy in these frequent infections and thus improve patient care.
Assuntos
Infecções Bacterianas/terapia , Infecções Comunitárias Adquiridas/terapia , Guias de Prática Clínica como Assunto , Infecções Urinárias/terapia , Urologia/normas , Adulto , Infecções Bacterianas/diagnóstico , Infecções Comunitárias Adquiridas/diagnóstico , Resistência Microbiana a Medicamentos , Feminino , Alemanha , Humanos , Masculino , Gravidez , Complicações Infecciosas na Gravidez/diagnóstico , Complicações Infecciosas na Gravidez/tratamento farmacológico , Infecções Urinárias/diagnósticoRESUMO
Urinary tract infections (UTI) are the most common bacterial infectious diseases seen in the community, in most cases caused by E. coli. The treatment strategy differs depending on localization (lower vs. upper UT), acute uncomplicated vs. complicated infection, as well as for chronic disease and asymptomatic bacteriuria, the known or susceptible causative uropathogen with the (local) resistance pattern and the morbidity of the patient. There is a considerable worrying increase in the resistance rate of E. coli to TMP/SMX, quinolones and others. Most patients with uncomplicated, in the community acquired UTI are treated safely and effectively as out-patients. The available data support a short-course therapy with 3 days as the current standard therapy for lower UTI, but with a 7-14 days treatment for upper and complicated UTI. Recurrent UTI is best managed by low-dose antimicrobial prophylaxis for 3-6 (12 ore more) months. Besides that, new approaches to preventive strategies must prove their value in specific patient groups.
Assuntos
Antibacterianos/uso terapêutico , Infecções Urinárias/tratamento farmacológico , Adulto , Fatores Etários , Idoso , Bacteriúria/tratamento farmacológico , Bacteriúria/etiologia , Terapia Combinada , Infecção Hospitalar/tratamento farmacológico , Infecção Hospitalar/etiologia , Infecções por Escherichia coli/tratamento farmacológico , Infecções por Escherichia coli/etiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Gravidez , Fatores de Risco , Prevenção Secundária , Fatores Sexuais , Infecções Urinárias/etiologiaRESUMO
Acute and chronic rejections are important denominators for the long-term function of renal grafts. One important indicator of cell damage is enzymatic DNA fragmentation. To investigate possible mechanisms, the rate of DNA fragmentation (TUNEL staining), the expression of tissue transglutaminase II (a marker of advanced DNA damage), and 8-hydroxy-2'-deoxyguanosine (8-OhdG), an indicator of oxidative injury of nucleic acids, were studied by immunohistochemistry. Semithin sections of renal biopsies revealed 23 patients to show acute interstitial rejections (Banff 97 IA, IB); eight patients, acute vascular rejection (Banff 97 IIA, IIB); and 20 patients, chronic allograft nephropathy (Banff 97 I to III). Correlations were calculated between apoptotic cells and serum creatinine at the time of biopsy and after 6 months. In acute rejection, the proximal tubular cells were apoptotic, particularly in regions with mononuclear infiltrates. In consecutive sections, these apoptotic tubular cells also showed damage by reactive oxygen species (positive 8-OhdG staining). Patients with acute interstitial rejection revealed the highest number of tubular DNA fragmentation (14.9 +/- 10.3) versus chronic allograft nephropathy (9.2 +/- 5.6) as TUNEL-positive cells per 80,000 micro m(2) (P < .05). Patients with acute vascular rejection showed a low degree of tubular apoptosis (6.8 +/- 5.1). There was no significant difference in glomerular DNA fragmentation between acute interstitial and chronic rejections: acute interstitial rejection = 7.1 +/- 5.9 versus chronic allograft nephropathy=6.1 +/- 3.9 TUNEL-positive cells per 80,000 micro m(2). There was a significant negative correlation between the degree of tubular (P < .01) and glomerular (P < .05) apoptosis and the serum creatinine at the time of biopsy as well as after 6 months in all patients irrespective of the Banff class. However, there was heterogeneity in the correlation between renal function and the degree of apoptosis in the glomerular and tubular compartments in the various Banff classes. A positive correlation (P < .01) was observed between the degree of tubular apoptosis and serum creatinine at 6 months after biopsy among patients with acute vascular rejection (Banff 97 IIA, IIB). The present data revealed a high degree of tubular DNA fragmentation associated with oxidative stress in acute interstitial rejection. Nevertheless, apoptosis did not generally negatively influence future renal function and may be important to clear proliferating cells. Apoptosis may also play a different pathophysiological role depending on the type of rejection.
Assuntos
Fragmentação do DNA , Rejeição de Enxerto/genética , Transplante de Rim/fisiologia , Doença Aguda , Biópsia , Doença Crônica , Creatinina/sangue , Humanos , Transplante de Rim/patologia , Estudos RetrospectivosRESUMO
BACKGROUND: Experimental data suggest that apoptosis plays an important pathophysiological role in glomerulonephritis by restoring tissue structure after proliferation of intrinsic renal cells and infiltration of leukocytes. Relatively little is known of apoptosis in human glomerulonephritis, particularly in predicting renal function during follow-up. METHODS: In order to colocalize different markers for cell damage in renal tissue from patients with different forms of glomerulonephritis (GN), a series of semithin sections from 34 kidney biopsies were studied retrospectively. Normal kidney from a nephrectomy specimen with a small renal adenocarcinoma served as a control. DNA fragmentation, expression of tissue transglutaminase II, BAX and BCL-2 were visualized immunohistochemically. In some renal biopsies, immunohistochemical staining for activated caspase 3 was performed. Proinflammatory markers (C-reactive protein, leukocytes), serum creatinine, creatinine clearance, total proteinuria, albuminuria, alpha(1)-microglobulin and IgG excretion were determined at the time of biopsy. Serum creatinine and total proteinuria were assessed 6 and 12 months after renal biopsy. RESULTS: Nuclei with different degrees of DNA fragmentation were mainly found in epithelial cells of tubules, but also in glomerular cells, regardless of the form of GN studied. Transglutaminase II expression was found only in cells with a strong staining for DNA fragmentation. DNA fragmentation localized to glomerular cells was more pronounced in proliferative than in non-proliferative forms of GN, being most abundant in patients with rapid progressive GN. Staining for activated caspase 3 in selected biopsies confirmed the presence of apoptosis. BAX and BCL-2 staining was detected within the same cells, but exhibited a different intracellular distribution. In proliferative GN, the extent of DNA damage in tubular epithelial cells significantly corresponds with the concentration of serum creatinine (p < 0.04) and with urinary excretion of alpha(1)-microglobulin (p < 0.01) at the time of biopsy. A significant correlation (p < 0.01) was seen between glomerular DNA fragmentation and follow-up total proteinuria 12 months after biopsy for proliferative forms of GN. The damaged glomerular area (e.g. mesangial sclerosis) significantly correlated with DNA fragmentation in proliferative, but not in nonproliferative GN at the time of biopsy. Furthermore, glomerular damaged showed a significant correlation with tubular DNA damage in proliferative GN. CONCLUSION: In glomerular cells, apoptosis may be important for the clearance of proliferating cells whereas in tubules, cell damage showed dependence on the degree of tubular injury mediated by inflammation and/or proteinuria. Although the degree of apoptosis in tubular cells correlates with serum creatinine in proliferative GN at the time of biopsy, it is of limited use to predict future renal function.
Assuntos
Fragmentação do DNA , Glomerulonefrite/genética , Glomerulonefrite/patologia , Adulto , Apoptose , Biomarcadores/metabolismo , Biópsia , Doença Crônica , Progressão da Doença , Feminino , Seguimentos , Glomerulonefrite/complicações , Glomerulonefrite/metabolismo , Glomerulonefrite por IGA/etiologia , Humanos , Imuno-Histoquímica , Glomérulos Renais/patologia , Túbulos Renais/metabolismo , Masculino , Pessoa de Meia-Idade , Proteinúria/etiologia , Estudos Retrospectivos , Transglutaminases/metabolismoRESUMO
The interactions of host-specific and microbial factors are responsible for recurrent urinary tract infections (rUTI). The anatomical properties of the female urogenital tract favor colonization by uropathogens. Local factors such as glucose concentration of the urine, stability of the lactobacilli population, the influence of estrogens, the activity of Tamm-Horsfall protein or of defensins, and disturbance of the systemic defense mechanisms dictate the course of an infection. The most prominent uropathogen is E. coli. It expresses various virulence factors including adhesions, toxins, iron uptake systems, and a capsule. It is still unclear if there are virulence factors characteristic for E. coli strains causing rUTI. The formation of intracellular reservoirs by invasion of uroepithelial cells by E. coli could be another, as yet little noticed cause for rUTI. Therefore, in cases of rUTI the application of intracellularly active antibiotics should be considered.
Assuntos
Infecções por Escherichia coli/microbiologia , Infecções Urinárias/microbiologia , Animais , Anti-Infecciosos Urinários/uso terapêutico , Anticorpos Antibacterianos/urina , Aderência Bacteriana/fisiologia , Creatinina/urina , Epitélio/imunologia , Epitélio/microbiologia , Escherichia coli/efeitos dos fármacos , Escherichia coli/imunologia , Escherichia coli/patogenicidade , Infecções por Escherichia coli/etiologia , Infecções por Escherichia coli/imunologia , Feminino , Humanos , Tolerância Imunológica/imunologia , Camundongos , Recidiva , Fatores de Risco , Ureia/urina , Infecções Urinárias/etiologia , Infecções Urinárias/imunologia , VirulênciaRESUMO
OBJECTIVE: The essential amino acid L-methionine is a potential compound in the prophylaxis of recurrent or relapsing urinary tract infection due to acidification of urine. As an intermediate of L-methionine metabolism, homocysteine is formed. The objective was to study the metabolism of L-methionine and homocysteine, and to assess whether there are differences between patients with chronic urinary tract infection and healthy control subjects. DESIGN: A randomized placebo-controlled double-blind intervention study with cross-over design. SETTING: Department of Nutritional Physiology, Institute of Nutrition in cooperation with the Department of Internal Medicine III, Friedrich Schiller University of Jena, Germany. SUBJECTS: Eight female patients with chronic urinary tract infection and 12 healthy women (controls). INTERVENTIONS: After a methionine-loading test, the volunteers received 500 mg L-methionine or a placebo three times daily for 4 weeks. MAIN OUTCOME MEASURES: Serum and urinary concentrations of methionine, homocysteine, cystathionine, cystine, serine, glycine and serum concentrations of vitamin B12, B6 and the state of folate. RESULTS: Homocysteine plasma concentrations increased from 9.4+/-2.7 micromol/l (patients) and 8.9+/-1.8 micromol/l (controls) in the placebo period to 11.2+/-4.1 micromol/l (P=0.031) and 11.0+/-2.3 micromol/l (P=0.000), respectively, during L-methionine supplementation. There were significant increases in serum methionine (53.6+/-22.0 micromol/l; P=0.003; n=20) and cystathionine (0.62+/-0.30 micromol/l; P=0.000; n=20) concentrations compared with the placebo period (33.0+/-12.0 and 0.30+/-0.10 micromol/l; n=20). Simultaneously, renal excretion of methionine and homocysteine was significantly higher during L-methionine intake. CONCLUSIONS: Despite an adequate vitamin status, the supplementation of 1500 mg of L-methionine daily significantly increases homocysteine plasma concentrations by an average of 2.0 micromol/l in patients and in control subjects. An optimal vitamin supplementation, especially with folate, might prevent such an increase.
Assuntos
Aminoácidos/sangue , Homocisteína/sangue , Metionina/farmacologia , Infecções Urinárias/prevenção & controle , Adulto , Idoso , Aminoácidos/urina , Estudos Cross-Over , Suplementos Nutricionais , Método Duplo-Cego , Feminino , Ácido Fólico/sangue , Homocisteína/metabolismo , Homocisteína/urina , Humanos , Metionina/sangue , Metionina/urina , Pessoa de Meia-Idade , Infecções Urinárias/sangue , Infecções Urinárias/urina , Vitamina B 12/sangue , Vitamina B 6/sangueRESUMO
Diabetes mellitus is increasing, and in some countries is the single most important cause, for end-stage renal disease. In general, primarily elderly patients on renal replacement therapy, are not only affected by diabetes-related long-term complications, but also frequently with a wide range of co-morbidities. Apart from cardiac complications, the patients are subject to a wide range of vascular (i.e. peripheral vascular disease, stroke) and infectious complications. In the past this has been reflected by a relatively poor survival rate on dialysis, and minimized chances to obtain renal transplantation. Today, several renal replacement strategies are available, including the main 3: hemodialysis, peritoneal dialysis or kidney transplantation. For patients with diabetes mellitus, hemodialysis is the most commonly used therapy. Each dialysis unit should achieve an optimal dialysis adequacy represented by a single pool Kt/V of at least 1.2. The most important independent predictor of patient survival with hemodialysis treatment is age. Other factors related to complications are left ventricular hypertrophy, arterial hypertension, hypervolaemia and chronic anemia. Moreover, medial arterial calcification, malnutrition, gastrointestinal disorders and dialysis against low potassium dialysate are related to increased morbidity and mortality as well. An integral part of treatment is the availability of good vascular access. The survival rates of fistulas show a nearly twofold higher rate of failure for synthetic grafts compared with arteriovenous fistulas. The role of peritoneal dialysis in renal replacement therapy in patients with diabetic nephropathy is well established and used world-wide. Most patients with residual renal function start with continuous ambulatory peritoneal dialysis (CAPD), but automated peritoneal dialysis can also be used. An unresolved problem associated with CAPD is the glucose absorption and caloric intake. The optimum adjustment of blood glucose values is made more difficult. Death rates of diabetic patients on peritoneal dialysis remain higher than in non-diabetics. The changes in peritoneal membrane thickness and vascular alterations in relationship to the duration of dialysis are caused mainly by glucose and glucose degradation products, such as advanced glycation endproduct (AGEs). Therefore, new peritoneal dialysis solutions are needed to reduce the complications and to delay a long-time function of the peritoneal membrane. Peritonitis remains still the major cause of discontinuation of dialysis but there is no increased risk in diabetic patients. Nevertheless, an integrative care of end-stage renal disease patients with diabetic nephropathy should be offered to the patient, starting on peritoneal dialysis and switch to hemodialysis if problems arise. During the whole time patients should be kept on the renal transplantation waiting list.
Assuntos
Nefropatias Diabéticas/complicações , Falência Renal Crônica/etiologia , Falência Renal Crônica/terapia , Diálise Peritoneal , Diálise Renal , Nefropatias Diabéticas/mortalidade , Humanos , Falência Renal Crônica/mortalidade , Diálise Peritoneal/métodos , Prognóstico , Diálise Renal/métodos , Taxa de Sobrevida , Fatores de TempoRESUMO
A predisposition to urinary tract infection (UTI) is associated with the expression of P1 as well as the presence of ABO blood group antigen on the boundary layer and with the secretor state. Infectious microorganisms interfere with specific molecules on epithelial cells, these are antigens of the P and ABO blood group system. The blood group phenotype was examined in 53 women (age 42 +/- 12 years) with chronic non-obstructive UTI. The diagnosis was established on the basis of clinical history as well as clinical laboratory and radiological findings. The ABO phenotype and the P1 antigen were analysed by anti-A and anti-B as well as anti-P1 serum. The Lewis phenotyping was performed by incubating erythrocytes with anti-Le(a) and anti-Le(b) serum. In all patients, the blood group status were investigated. The proportion of persons with B-phenotype was 23% (the incidence of this feature in the German population is 14.5%). P1 antigen was found in 76% patients. In comparison with P1 antigen-negative individuals, P1 antigen-positive persons have a longer disease history and suffer more frequently from symptomatic events as well as destructive renal changes. The Le (a)-antigen was detected in 82% and the Le (b)-phenotype was observed in 18% of patients. The blood group phenotypes (ABO, Lewis and P1 antigens) represent an interesting natural aspect of local defence system against the invasive efforts of uropathogens. Antigen structures on uroepithelial cells for example, the glycolipids of the P antigen, serve as receptors for adhesion of microorganisms.
Assuntos
Sistema ABO de Grupos Sanguíneos/classificação , Sistema ABO de Grupos Sanguíneos/imunologia , Infecções por Escherichia coli/imunologia , Escherichia coli/patogenicidade , Infecções Urinárias/imunologia , Adulto , Doença Crônica , Infecções por Escherichia coli/microbiologia , Feminino , Globosídeos/classificação , Globosídeos/imunologia , Proteínas Hemolisinas/metabolismo , Humanos , Pessoa de Meia-Idade , Fenótipo , Infecções Urinárias/microbiologia , VirulênciaRESUMO
BACKGROUND: The determination of D-dimer concentration is an essential part in the diagnostic procedure of thromboembolic diseases, e.g. deep vein thrombosis, pulmonary embolism. D-dimers are the products of fibrin hydrolysis with elevated levels in fibrinolytic processes. QUESTION: In the clinical practice problems exist in the interpretation of increased D-dimer concentrations, especially without thromboembolic disease. Before starting further expensive imaging diagnostics other reasons (i.e. pregnancy, neoplasma, systemic inflammatory disease, advanced arteriosclerosis) should be considered in differential diagnosis. CONCLUSION: The determination of the concentration of D-dimers is involved in the diagnostic strategy in thromboembolic diseases. However, this parameter is not suited for routine screening. Its high predictive-negative value is proved for the exclusion of thrombosis or pulmonary embolism in case of negative test result. Since a range of diseases and physiological conditions lead to increased D-dimer values, a positive D-dimer result does not verify the diagnosis of thromboembolism.
Assuntos
Antifibrinolíticos/análise , Produtos de Degradação da Fibrina e do Fibrinogênio/análise , Tromboembolia/diagnóstico , Doenças Cardiovasculares/sangue , Fibrinólise , Humanos , Neoplasias/sangue , Tromboembolia/sangue , Tromboembolia/etiologia , Tromboembolia/fisiopatologiaRESUMO
BACKGROUND: The beta-chemokines MCP-1 (CCL2) and RANTES (CCL5) have been shown to play important roles in acute renal transplant rejection (AR) and chronic allograft nephropathy (CAN). The potential relationship of expression of these chemokines, their chemokine receptors CCR1, CCR2, CCR5, and the cell populations of inflammatory infiltrate, histological and clinical diagnoses were investigated in biopsies at the time of AR and compared with biopsies of CAN. METHODS: In 24 renal transplant biopsies with AR (n = 15) and CAN (n = 9), the expression of MCP-1 and RANTES, their receptors CCR1, CCR2, and CCR5 and the infiltration with monocytes/macrophages and T cells were studied. RESULTS: As previously described, chemokine and chemokine receptor expression was found mainly in mononuclear cells infiltrating the interstitium and glomeruli. In the tubulointerstitial area and glomeruli the expression of MCP-1, RANTES, and their receptors correlated with an infiltration by monocytes/macrophages. Biopsies with CAN revealed a lower expression of MCP-1, RANTES, CCR1, CCR2 and CCR5 in tubulointerstitial cells, and a significantly lower infiltration with MRP14-positive monocytes/macrophages than biopsies with AR. In AR, MCP-1 and CCR1 showed a lower expression compared to RANTES, CCR2, and CCR5. CONCLUSIONS: The positive correlation between chemokines and chemokine receptors and infiltrating leukocytes during acute rejection, the lower but detectable expression of MCP-1, RANTES, CCR1, CCR2 and CCR5 in CAN, and the differences in the quantity of expression between the different chemokines and chemokine receptors point to a complex regulation of chemokine expression in renal allografts. Since chemokines are not only involved in inflammation but also in tissue regeneration, this could have impact on the development of CAN.
Assuntos
Quimiocina CCL2 , Quimiocina CCL5/biossíntese , Citocinas/biossíntese , Rejeição de Enxerto/metabolismo , Nefropatias/metabolismo , Transplante de Rim , Biossíntese de Proteínas , Receptores CCR5/biossíntese , Receptores de Quimiocinas/biossíntese , Adulto , Biópsia , Quimiocina CCL5/análise , Doença Crônica , Citocinas/análise , Feminino , Humanos , Imuno-Histoquímica , Nefropatias/etiologia , Glomérulos Renais/química , Transplante de Rim/efeitos adversos , Transplante de Rim/patologia , Túbulos Renais/química , Masculino , Pessoa de Meia-Idade , Proteínas/análise , Receptores CCR1 , Receptores CCR2 , Receptores CCR5/análise , Receptores de Quimiocinas/análiseRESUMO
The aim of this study was to investigate the relationship between the presence and titre of antibodies against C1q (anti-C1q Ab) and disease activity and renal involvement in patients with systemic lupus erythematosus (SLE). Anti-C1q Ab were measured in 79 patients with SLE (70 women and 9 men; mean age 41.7 years; mean disease duration 8.4 years): 19 patients had active disease with lupus nephritis, 8 active disease without nephritis, 26 inactive disease with nephritis and 26 inactive disease without nephritis. Anti-dsDNA antibodies (EIA and immunofluorescence), antiendothelial cell antibodies (AECA) and complement levels (C3, C4, total haemolytic complement activity) were determined in parallel. Anti-C1q Ab were positive in 49%, anti-dsDNA Ab in 61% and AECA in 19% of the patients, respectively. Significantly higher titres of anti-C1q Ab were found in patients with active disease compared with those with inactive SLE ( P < 0.01). Serum levels of anti-C1q Ab showed a positive correlation with anti-dsDNA Ab and SLEDAI score ( P < 0.01) and a negative correlation with C3 ( P < 0.05), C4 ( P < 0.01) and CH50U ( P < 0.01). The presence of anti-C1q Ab was not different between patients with or without nephritis. In patients with ( P < 0.05) and without nephritis ( P < 0.01) the frequency of anti-C1q Ab was significantly higher in active patients compared with inactive patients. Both anti-C1q and anti-ds-DNA Ab were detectable in 74% of patients with active nephritis but only in 30% of all other patients ( P=0.001). None of the patients with active nephritis was negative for anti-C1q and anti-dsDNA Ab, whereas 37% of the patients without active nephritis were negative for both antibodies ( P < 0.01). Sensitivity, specificity, positive and negative predictive values for active lupus nephritis among SLE patients were 100%, 50%, 51.9% and 100% for anti-dsDNA Ab (EIA) and 74%, 70%, 57% and 89.4% for positive findings of both anti-dsDNA and anti-C1q Ab. The presence and titre of anti-C1q-Ab in SLE are related to disease activity. Absence of anti-dsDNA Ab excludes active nephritis; positive findings of both anti-dsDNA Ab and anti-C1q Ab are of relatively high specificity for active nephritis.
Assuntos
Anticorpos Anti-Idiotípicos/imunologia , Autoanticorpos/imunologia , Complemento C1q/imunologia , Lúpus Eritematoso Sistêmico/imunologia , Nefrite Lúpica/imunologia , Adolescente , Adulto , Idoso , Anticorpos Anti-Idiotípicos/análise , Autoanticorpos/análise , Biomarcadores/sangue , Estudos de Coortes , Complemento C1q/análise , Complemento C3/análise , Complemento C3/imunologia , Complemento C4/análise , Complemento C4/imunologia , Feminino , Humanos , Lúpus Eritematoso Sistêmico/diagnóstico , Nefrite Lúpica/diagnóstico , Masculino , Pessoa de Meia-Idade , Probabilidade , Prognóstico , Medição de Risco , Sensibilidade e Especificidade , Índice de Gravidade de Doença , Estatísticas não ParamétricasRESUMO
BACKGROUND AND OBJECTIVE: The most common method used for testing dynamic renal function is creatinine clearance, but it has some limitations, e. g. variable muscle mass and tubular secretion of creatinine. The use of radionuclides as an exact method is limited in terms of availability, cost and time needed for examination. We compared the plasma clearance of iohexol with the established (99m)Tc-diethylenetriaminepentaacetate acid (DTPA) clearance. The aim of the present study was to validate iohexol clearance as a simple and suitable method for measuring to determine GFR with a comparable sensitivity to radioisotopic methods. METHODS: 120 patients (49 females, 71 males), mean age of 56 (range 20 to 84) years with normal renal function and different stages of renal failure, mean creatinine clearance of 61.6 +/- 44,9 (range 1.8 - 181.1) ml/min/1.73 m2 received a bolus injection of 10 ml iohexol, a non-ionic low osmolar x-ray contrast medium. Using the one-compartment model, plasma samples were taken after 150, 240 and 480 minutes. The total plasma disappearance of iohexol was measured by x-ray fluorescence analysis and the clearance was calculated. The (99m)Tc-DTPA clearance was determined in accordance with a standard protocol. RESULTS: A high correlation was found between the clearance of iohexol and (99m)Tc-DTPA (r = 0.95). The average deviation between Iohexol and (99m)Tc-DTPA clearance was 7.4 ml/min/1.73 m2. Allergic and nephrotoxic side effects were not observed. CONCLUSION: Iohexol clearance is a valid method for measuring GFR in patients at any stages of renal failure. It is easy to perform and inexpensive.
Assuntos
Meios de Contraste/farmacocinética , Taxa de Filtração Glomerular , Iohexol/farmacocinética , Insuficiência Renal/diagnóstico , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Taxa de Depuração Metabólica , Pessoa de Meia-Idade , Compostos Radiofarmacêuticos/farmacocinética , Valores de Referência , Insuficiência Renal/metabolismo , Espectrometria por Raios X/métodos , Pentetato de Tecnécio Tc 99m/farmacocinéticaRESUMO
BACKGROUND: Postexercise proteinuria, hematuria and changes in serum electrolyte balance as well as increased levels of plasma indicators for muscle leakage are believed to be transient and of benign character. METHODS: A group of 51 healthy athletes took part in a 100 km race over 14.25 hours. All of them had to reach the finish together. Urine and blood samples were collected before (a) and immediately after running (b) as well as 6 hours after the race (c). RESULTS: The serum concentrations of potassium (4.8 +/- 0.5 (a) vs. 4.0 +/- 0.3 (c) mmol/l), protein (73.1 +/- 5.2 (a) vs. 71.1 +/- 3.9 (c) g/l) and albumin (44.0 +/- 2.85 (a) vs. 42.9 +/- 2.8 (c) g/l) decreased significantly (p < 0.0001, p < 0.05, p < 0.05, respectively) but remained within physiological ranges. The serum sodium concentration decreased immediately after the race (136.9 +/- 4.5 (a) vs. 131.1 +/- 2.4 (b) micromol/l, p < 0.0001). The fractional sodium excretion decreased 6 hours, but not immediately after the race (0.78 +/- 0.59 (a) vs. 0.48 +/- 0.82 (c), p < 0.05). Myoglobin (31.8 +/- 6.9 (a), 291.5 +/- 197.2 (b) and 182.2 +/- 135.3 (c) microg/l, p < 0.0001) and creatine kinase (1.13 +/- 0.45 (a), 10.76 +/- 6.9 (b) and 9.46 +/- 15.5 (c) pmol/l, p < 0.0001) increased dramatically. Troponin I was also significantly increased at finish (0.0186 +/- 0.0121 (a) vs. 0.0213 +/- 0.0165 (b) ng/ml, p < 0.05) and positively correlated with myoglobin and creatine kinase, but remained far below the pathologic range. Serum creatinine and urea remained almost unchanged. Glucosuria and hematuria occurred 6 hours after the run in 9.1% and 6.8%, respectively. The erythrocytes examined by phase-contrast microscopy were not damaged in terms of dysmorphic cells. Glomerular-type proteinuria was found in 11.4% of the participants 6 hours after the race. CONCLUSIONS: We conclude that long lasting, mild exertion is harmless for renal function, electrolyte balance and skeletal muscle as well as myocardial metabolism in healthy persons.
Assuntos
Exercício Físico/fisiologia , Nefropatias/fisiopatologia , Rim/fisiopatologia , Células Musculares/fisiologia , Equilíbrio Hidroeletrolítico/fisiologia , Adulto , Feminino , Hemodinâmica/fisiologia , Humanos , Nefropatias/sangue , Nefropatias/urina , Masculino , Pessoa de Meia-Idade , Músculo Esquelético/fisiopatologia , Valores de Referência , Corrida/fisiologia , Fatores de TempoRESUMO
BACKGROUND: The increased oxidative stress of uraemia is caused both by an increased generation of oxygen-free radicals and a decrease of antioxidative forces. There are, however, conflicting data concerning disturbances of the radical-scavenging power of red blood cells (RBCs) in uraemic patients. METHODS: The antioxidant capacities of the RBCs of 10 haemodialysis (HD) patients and 10 controls were examined after treatment with 0.324 mM tert-butylhydroperoxide (t-BOOH) in phosphate-buffered saline at 37 degrees C using electron paramagnetic resonance (EPR) with 5,5-dimethylpyrroline-N-oxide (DMPO) as a spin trap and glutathione (GSH) regeneration as an indicator of hexose monophosphate shunt (HMPS) activity. EPR investigations were also done after pre-incubation with N-ethylmaleimide (NEM) to inhibit the GSH system. Furthermore, we determined the RBC redox state in 15 HD patients and 15 controls. RESULTS: There was no difference between HD patients and controls in the elimination of t-BOOH-generated free radicals in the RBCs. A more than 20-fold increase in radical concentration was observed after GSH trapping with NEM. In this case, we found a delayed decrease of the relative radical concentration in HD patients compared with controls with a significant difference after 7 min (2.2+/-0.26 vs 1.60+/-0.21; P=0.005) and after 10 min (1.82+/-0.41 vs 0.83+/-0.44; P=0.001). GSH regeneration via HMPS did not differ between the RBCs of HD patients (99.5+/-13.5 nmol/min x ml RBC) and those of the controls (94.2+/-16.9 nmol/min x ml RBC). There were no differences in the RBC concentrations of GSH, GSSG, NADP, NADPH, and in the GSH/GSSG and NADP/NADPH ratios between HD patients and controls. CONCLUSIONS: These data suggest a strong antioxidant potential in the GSH system of erythrocytes without any evidence of a disturbance in HD patients. The HMPS pathway also appears not to be impaired in the RBCs of HD patients. However, the slower radical elimination in the RBCs of HD patients after inhibition of GSH-depending radical scavengers as compared with controls indicates a defect in the antioxidant forces outside the GSH system, and could be one reason for the reduced lifespan of RBCs in HD patients.
Assuntos
Antioxidantes/metabolismo , Espectroscopia de Ressonância de Spin Eletrônica , Eritrócitos/metabolismo , Diálise Renal , Adulto , Idoso , Estudos de Viabilidade , Feminino , Sequestradores de Radicais Livres/antagonistas & inibidores , Glutationa/fisiologia , Humanos , Masculino , Pessoa de Meia-Idade , Via de Pentose Fosfato/fisiologia , Espécies Reativas de Oxigênio/sangue , Valores de Referência , terc-Butil Hidroperóxido/farmacologiaRESUMO
The purpose of this review is to give an introduction in the class of fluoroquinolones, which has become a large class of substances, and to discuss the use, role, and place of these drugs in the treatment of urinary tract infections. The classification of the fluoroquinolones contains four groups. Antibacterial spectrum, pharmacokinetics, and indications are the main criteria. The various fluoroquinolones differ in their antibacterial spectrum, the antibacterial activity, and pharmacokinetic properties. Therefore selection, use, and dosage regime of the substances should be carried out under respective clinical requirements and medical points of view. The physician has to consider the specific indications for each substance in each individual case. Fluoroquinolones are suitable antibacterial agents for various urinary tract infections and are a valuable and useful addition to the antimicrobial treatment.