Psychonephrology: psychological aspects in autosomal dominant polycystic kidney disease.

The biological, physical and psychological burden of a chronic disease has an impact on the quality of life of people who suffer from it. The perception of quality of life is affected by psychological disorders such as anxiety and depression that have a high prevalence in people with chronic kidney disease (CKD). These factors are also linked to lower life expectancy. It is therefore surprising that the psychological aspects of people with autosomal dominant polycystic kidney disease (ADPKD) have received so little attention in the medical literature, despite their importance for the overall health of these patients. The relatively new discipline called psychonephrology provides a broader view of the impact that these aspects have on individuals with chronic kidney disease, with a consequent practical application. In this article, we examine the consequences and prevalence of psychological problems that can be related to CKD and ADPKD. Firstly, we will focus on the field of CKD and ADPKD within the scope of psychonephrology. Secondly, the article introduces the concept of quality of life as a basic pillar of health that is affected when a person is diagnosed with CKD. Thirdly, we will present a summary of the main research related to anxiety and depression disorders in CKD and ADPKD. The article will conclude by synthesising findings from the different lines of research undertaken.

Aspectos vasculares y metabólicos de manidipino / Vascular and metabolic properties of manidipine

En el tratamiento de la hipertensión y la diabetes, la combinación de bloqueantes del sistema renina-angiotensina y de los canales de calcio se presenta como una de las opciones más eficaces. Sin embargo, no todos los bloqueantes de calcio se comportan del mismo modo. Manidipino, a diferencia de otros derivados dihidropiridínicos de tercera generación, bloquea los canales de calcio T presentes en las arteriolas glomerulares eferentes, disminuyendo la presión intraglomerular y la microalbuminuria. Además, los canales T están relacionados con proliferación, inflamación, fibrosis, vasoconstricción y activación del sistema renina-angiotensina. La inhibición de estos factores podría explicar la acción no hemodinámica del manidipino frente a otros bloqueantes (AU)

The combination of renin-angiotensin system blockers with calcium channel blockers appears to be one of the most effective options for treating hypertension and diabetes. Nevertheless, not all calcium blockers behave in the same manner. Manidipine, unlike other third-generation dihydropyridine derived drugs, blocks T-type calcium channels present in the efferent glomerular arterioles, reducing intraglomerular pressure and microalbuminuria. In addition, T-type channels are related to proliferation, inflammation, fibrosis, vasoconstriction and activation of the renin-angiotensin system. The inhibition of these factors could explain the non-haemodynamic effects of manidipine as compared to other blockers (AU)

Vascular and metabolic properties of manidipine.

The combination of renin-angiotensin system blockers with calcium channel blockers appears to be one of the most effective options for treating hypertension and diabetes.Nevertheless, not all calcium blockers behave in the same manner. Manidipine, unlike other third-generation dihydropyridine derived drugs, blocks T-type calcium channels present in the efferent glomerular arterioles, reducing intraglomerular pressure and microalbuminuria. In addition,T-type channels are related to proliferation, inflammation,fibrosis, vasoconstriction and activation of the renin-angiotensin system. The inhibition of these factors could explain the non-haemodynamic effects of manidipine as compared to other blockers.

Guía práctica a los estudios de asociación genética. Consideraciones sobre su utilidad clínica / No disponible

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[Cardio-metabolic properties of manidipine: beyond lowering arterial pressure?]. / Propiedades cardiometabólicas del manidipino: ¿más allá de la reducción de la presión arterial?

From its introduction in the decade of the 70's the evolution of the calcium channel blockers has allowed to resolve the uncertainty initially generated by those first generation drugs. These, are characterized by a smaller oral availability, a fast vasodilator action and a short duration of action. Manidipine arises as a dihydropyridine calcium antagonist of third generation with real additional advantages regarding to previous generations. They show high lipophilia, a more prolonged action and as well as a prolonged average life at the level of his receptor and, in addition, some theoretical advantages among others calcium antagonists, improvements on the renal function by reducing the intraglomerular pressure and microalbuminuria. Nevertheless, the clinical evaluation of these last properties still depends on the results derived from clinical trials. Besides to go deep in its role in their antihypertensive effect, we presented a brief review on new cardiometabolic aspects of these dihydropyridines calcium antagonists focusing in manidipine.

Propiedades cardiometabólicas del manidipino: ¿más allá de la reducción de la presión arterial? / No disponible

Desde su introducción en la década de los 70, la evolución de los calcioantagonistas ha permitido solventar la incertidumbre inicialmente generada por aquellos fármacos deprimera generación. Éstos se caracterizan por una menor disponibilidad oral, una acción vasodilatadora rápida y corta acción. El manidipino surge como un derivado dihidropiridínico de tercera generación con ventajas adicionales reales frente a las generaciones anteriores, como son su alta lipofilicidad, su acción más prolongada y una vida media prolongada a nivel del receptor y, además, algunas ventajas teóricas entre otras, mejoras sobre la función renal reduciendo la presión intraglomerular y la microalbuminuria. Sin embargo, la evaluación clínica de estas últimas propiedades depende aún de los resultados que se deriven de la experiencia clínica. Además de ahondar ensu papel en la reducción de la presión arterial, presentamos una breve revisión sobre nuevos aspectos cardiometabólicos de los calcioantagonistas dihidropiridínicos, centrándonos en el manidipino (AU)

From its introduction in the decade of the 70’s the evolution of the calcium channel blockers has allowed to resolve the uncertainty initially generated by those first-generation drugs. These, are characterized by a smaller oral availability, a fast vasodilator action and a short duration of action. Manidipine arises as a dihydropyridinecalcium antagonist of third generation with real additional advantages regarding to previous generations. They show high lipophilia, a more prolonged action and as well as a prolonged average life at the level of his receptor and, in addition, some theoretical advantages among others calcium antagonists, improvements on the renal function by reducing the intraglomerular pressure and microalbuminuria. Nevertheless, the clinical evaluation of these last properties still depends on the results derived from clinical trials. Besides to go deep in its role in their antihypertensive effect, we presented a brief review on new cardiometabolic aspects of these dihydropyridines calcium antagonists focusing in manidipine (AU)

Insight into the role of CYBA A640G and C242T gene variants and coronary heart disease risk. A case-control study.

The CYBA gene variants have been inconsistently associated with coronary heart disease (CHD) risk. A case-control study was conducted genotyping 619 subjects to explore the contribution of C242T and A640G to CHD risk in the population. A significant risk was found associated with GG homozygosity (odds ratio (OR) 2.132, 95% confidence interval, 1.113-4.085). The C242T variant was associated with CHD risk in women. Bias due to population stratification was analysed. Phenotype changes linked to these polymorphisms were evaluated. Superoxide measurements revealed higher production as indicated by the presence of the G and T alleles. Differences in mRNA concentration in heterozygous A640G samples were analysed. Higher levels of G allele mRNA compared with A allele mRNA were found. NAD(P)H oxidase p22phox sub-unit expression was evaluated with Western blot. Experiments revealed a gradual relationship in p22phox protein expression according to genotypes of the analysed variants. Those GG TT double homozygous showed increased p22phox protein expressions regarding AA CC double homozygous. This study has demonstrated increased expression and activity of the NAD(P)H system components during atherogenesis and the results could help explain the relevance of the A640G variant as a CHD marker.

Rosiglitazone but not losartan prevents Nrf-2 dependent CD36 gene expression up-regulation in an in vivo atherosclerosis model.

BACKGROUND: Thiazolidinediones exert anti-inflammatory and anti-oxidative roles and attenuate atherosclerosis by mechanisms partially independent of their metabolizing actions. High doses of angiotensin type 1 receptor (AT1R) blocker losartan (LST) seem to promote fat cell formation by preserving PPARgamma activity. METHODS: C57BL/6J diet-induced atherosclerotic susceptible mice randomly received a normal or a high-fat high-cholesterol (HFHC) diet and were treated with rosiglitazone (RG), LST or a vehicle for 12 weeks. RESULTS: HFHC was associated with increased PPARgamma gene expression without an over regulation of PPARgamma responsive genes, whereas RG and LST treatments were found to maintain PPARgamma activity without resulting in increased PPARgamma gene expression. A better anti-inflammatory and antioxidant profile in mice treated with RG regarding LST was observed in spite of a similar PPARgamma preserved activity. Chromatin immunoprecipitation (ChIP) assays revealed that animals under HFHC diet treated with RG showed a significant nuclear factor erythroid 2-like 2 (Nrf2)-dependent down-regulation of the expression of the CD36 gene. CONCLUSION: The PPARgamma agonist RG exerts antioxidant properties that significantly reduced Nrf-2-dependent CD-36 up-regulation in mice under HFHC diet. Because LST treatment was also associated with a preserved PPARgamma activity, our data suggests that these RG antioxidant effects are partially independent of its PPARgamma metabolizing properties.

PPAR-gamma, hipertensión arterial y riñón / PPAR-Gamma, arterial hypertesnion and the kidney

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[Arterial blood pressure variations: homocysteine and nitric oxide synthase gene polymorphisms (NOS3)]. / Presión arterial, homocisteína y variantes polimórficas del gen de la óxido nítrico sintasa (NOS3).

BACKGROUND: The nitric oxide synthase (NOS3) G894T gene polymorphism seems as a genetic determinant of total homocysteine (tHcy) concentrations through an effect on folate catabolism. We tested for a significant contribution to blood pressure values for the NOS3 G894T and 4a/b gene polymorphisms and whether those changes could explain the modulating effect on tHcy concentrations. PATIENTS AND METHODS: We analyzed 158 healthy men. The NOS3 gene polymorphisms were determined by polymerase chain reaction (PCR) and restriction fragment analysis (G894T) and by PCR (4a/b). Total homocysteine concentrations were evaluated by the fluorescence polarization immunoassay method. RESULTS: In our population we did not obtain a significant contribution of the G894T to blood pressure variations. However, tHcy mean concentration values differed according G894T genotypes (P = 0.01). Interestingly, we did not obtain a significant modulating effect on tHcy concentrations according to 4a/b genotypes although the 4a/b genotype distribution was statistically associated with blood pressure variations. CONCLUSION: Our results showed a modulating effect of the NOS3 4a/b gene variant on tHcy concentrations that is at least partially provoked by discrete blood pressure increments. Nevertheless, our multivariate analysis did not show a statistical significant role for the NOS3 G894T gene polymorphism on tHcy concentrations.

Efecto del Valsartán sobre la presión arterial y función renal en pacientes con hipertensión arterial y diabetes mellitus tipo 2. Estudio Lapaval / Valsartan in patients with arterial hypertension and type 2 diabetes mellitus. The lapaval study

La hipertensión arterial junto a la diabetes mellitus son importantes determinantesde la aparición y evolución de la nefropatía diabética, y a la vez situación de elevadoriesgo cardiovascular. La renoprotección mediante el bloqueo del sistema reninaangiotensinaes una alternativa válida para este tipo de pacientes. Objetivo: Evaluar el efecto de valsartán, un antagonista específico de los receptorestipo 1 de la angiotensina II sobre la presión arterial y función renal en pacientesdiabéticos tipo 2 con albuminuria e hipertensión arterial.Pacientes y método: Se trata de un estudio prospectivo observacional, llevado acabo en dos hospitales con pacientes procedentes de las diferentes unidades deAtención Primaria. Se analizaron 74 pacientes diabéticos tipo 2 con cifras de presiónarterial de 140/90 mm Hg, con presencia de micro o macroalbuminuria y a) cifras decreatinina en sangre inferiores a 1,5 mg/dl (grupo 1) o b) cifras de creatinina en sangreentre 1,5 y 2 mg/dl (grupo 2), seguidos durante 12 semanas. El tratamiento seinició con valsartán 80 mg/día, incrementando a 160 mg/día y añadiendo posteriormentetorasemida a dosis de 5 mg/día si no se lograban alcanzar las cifras diana depresión arterial. El grado de reducción de la presión arterial fue analizado comparativamentecon un esfigmomanómetro de mercurio y un monitor semiautomáticoOmron HEM 705 CP.Resultados: En todos los pacientes objeto de estudio la presión arterial sistólica(PAS) y diastólica (PAD), pero no la presión de pulso, disminuyeron significativamente(p < 0,001) a lo largo del periodo analizado, pasando de 150,7 ± 12,8 a130,8 ± 9,6 y de 94,7 ± 7,7 a 76,8 ± 6,3 mm Hg respectivamente. En el grupo 2 sólose halló una reducción significativa de la presión arterial diastólica (101,4 ± 8,8 a79,4 ± 5,6; p < 0,001). Los valores más bajos de presión arterial se obtuvieron siemprecon el monitor semiautomático. Al final del estudio, el 9,5% de los pacientes semantenía con valsartán 80 mg/día, al 48,6% de los pacientes se le dobló la dosis yel 36,5% de los pacientes necesitó la adición de un segundo o tercer fármaco al valsartán160 mg/día para alcanzar la diana terapéutica de presión arterial. Hubo unareducción significativa de la microalbuminuria (75,5 ± 9,5 a 54,7 ± 7,3 µg/min; p < 0,001) y macroalbuminuria (n = 20; 0,93 ± 0,4 a 0,68 ± 0,4 g/d; p < 0,001) entodos los pacientes analizados respecto a sus valores basales.Conclusión: El valsartán disminuye significativamente las cifras de PAS y PAD, alcanzándoseen todos los casos el objetivo establecido, precisándo para ello los tresregímenes terapéuticos. El valsartán a dosis de 160 mg/día alcanzó un significativo ymayor efecto en la reducción de la micro y macroalbuminuria. No se encontraronmodificaciones en las cifras de creatinina en sangre, aclaramiento de creatinina,HbA1c y potasio sérico. Los valores de HDL-colesterol aumentaron significativamente.La tasa de acontecimientos adversos fue mínima

Arterial hypertension and diabetes mellitus give rise to a situation of high cardiovascularrisk. The potential renoprotection from inhibition of the renin-angiotensinsystem is a valid option in this type of patient.Objective: Evaluate the effect of valsartan on blood pressure (BP) and renal functionin albuminuric patients with type 2 diabetes and arterial hypertension.Patients and methods: This was a prospective, observational study. Seventy-fourdiabetic patients with a blood pressure of 140/90 mmHg, with micro or macroalbuminuriaand a) blood creatinine levels lower 1.5 mg/dl (group 1) or b) blood creatininelevels between 1.5 and 2 mg/dl (group 2), were studied and followed up fora 12-week period. Treatment was started with valsartan 80 mg/d, increasing to 160mg/d, adding torasemide at a dose of 5 mg/d if the target blood pressure of 130/85mmHg has not been achieved. The degree of BP reduction was analyzed comparativelyusing a mercury sphygmomanometer and a semi-automatic monitor, the OmronHEM 705 CP.Results: All patients showed a significant reduction of the systolic (SBP) anddiastolic (DBP) blood pressures (p< 0.001) over the study period, decreasingfrom 150.7 ± 12.8 to 130.8 ± 9.6 and from 94.7 ± 7.7 to 76.8 ± 6.3 mmHg, respectively.A significant reduction was observed only for diastolic blood pressure(101.4 ± 8.8 to 79.4 ± 5.6; p < 0.001) in the group 2 of patients. Lowest BP valueswere always obtained with the semiautomatic device. At the end of the study,9.5% maintained valsartan 80 mg/d and 36.5% required the addition of a secondor third drug to valsartan 160 mg in order to achieve the therapeutic target BP. Asignificant reduction was observed in the microalbuminuria (75.5 ± 9.5 to 54.7 ±7.3 µg/min; p < 0.001) and macroalbuminuria (n = 20; 0.93 ± 0.4 to 0.68 ± 0.4g/day; p < 0.001).Conclusion: Valsartan significantly reduced SBP and DBP. Valsartan at 160 mg/dhad a significantly greater effect in reducing micro and macroalbuminuria. No changeswere observed in renal function, HbA1c or serum potassium. The rate of adverseevents was very low

[Valsartan in patients with arterial hypertension and type 2 diabetes mellitus. The lapaval study]. / Efecto del valsartin sobre la presión arterial y función renal en pacientes con hipertensión arterial y diabetes mellitus tipo 2. Estudio Lapaval.

UNLABELLED: Arterial hypertension and diabetes mellitus give rise to a situation of high cardiovascular risk. The potential renoprotection from inhibition of the renin-angiotensin system is a valid option in this type of patient. OBJECTIVE: Evaluate the effect of valsartan on blood pressure (BP) and renal function in albuminuric patients with type 2 diabetes and arterial hypertension. PATIENTS AND METHODS: This was a prospective, observational study. Seventy-four diabetic patients with a blood pressure of > or = 140/90 mmHg, with micro or macroalbuminuria and a) blood creatinine levels lower 1.5 mg/dl (group 1) or b) blood creatinine levels between 1.5 and 2 mg/dl (group 2), were studied and followed up for a 12-week period. Treatment was started with valsartan 80 mg/d, increasing to 160 mg/d, adding torasemide at a dose of 5 mg/d if the target blood pressure of 130/85 mmHg has not been achieved. The degree of BP reduction was analyzed comparatively using a mercury sphygmomanometer and a semi-automatic monitor, the Omron HEM 705 CP. RESULTS: All patients showed a significant reduction of the systolic (SBP) and diastolic (DBP) blood pressures (p< 0.001) over the study period, decreasing from 150.7 +/- 12.8 to 130.8 +/- 9.6 and from 94.7 +/- 7.7 to 76.8 +/- 6.3 mmHg, respectively. A significant reduction was observed only for diastolic blood pressure (101.4 +/- 8.8 to 79.4 +/- 5.6; p < 0.001) in the group 2 of patients. Lowest BP values were always obtained with the semiautomatic device. At the end of the study, 9.5% maintained valsartan 80 mg/d and 36.5% reqcuired the addition of a second or third drug to valsartan 160 mg in order to achieve the therapeutic target BP A significant reduction was observed in the microalbuminuria (75.5 +/- 9.5 to 54.7 +/- 7.3 microg/min; p < 0.001) and macroalbuminuria (n = 20; 0.93 +/- 0.4 to 0.68 +/- 0.4 g/day; p < 0.001). CONCLUSION: Valsartan significantly reduced SBP and DBP Valsartan at 160 mg/d had a significantly greater effect in reducing micro and macroalbuminuria. No changes were observed in renal function, HbA1c or serum potassium. The rate of adverse events was very low.

[Genes and kidney disease. Candidate genes]. / Genes y enfermedad renal. Generalidades. Genes candidatos.

Molecular biology techniques have provided important advances in the search for causal relationships in complex diseases supporting traditional epidemiologic studies. Genetic epidemiology allows us to detect genetic variants that could be related to the onset and progression of different diseases. In cardiovascular and renal diseases, this approach linking traditional risk factors to new described ones and those allelic variants, which contribute to the development of these manifestations permits a better understanding of individual disease susceptibility. This is usually afforded through case-control studies evaluating allelic variants of candidate genes previously associated with the disease. Even in this candidate gene search, association-based methods are more powerful than linkage studies in complex traits if we assume that some of the typed polymorphisms are causative although with subtle phenotypic effects. Some brief examples may illustrate the progress in the understanding of renal and cardiovascular diseases.

Genes y enfermedad renal. Generalidades. Genes candidatos / Genes and kidney disease. Candidate genes

La biología molecular ha aportado importantes avances en el conocimiento del origen de enfermedades complejas, deducidas de lo aportado por los estudios epidemiológicos. La epidemiología genética nos permite detectar variantes genéticas relacionadas con la progresión de las enfermedades. En las enfermedades cardiovasculares y renales ésta relación de los factores de riesgo clásicos con los nuevos y las variantes alélicas de aquellos genes candidatos nos va a permitir igualmente identificar la susceptibilidad de cada individuo a una determinada enfermedad. Esto normalmente se realiza a través de estudios casos-controles. Damos más valor a los estudios de asociación que a los estudios de desequilibrio de ligamiento. Se presenta en este trabajo las técnicas más básicas de biología molecular y ejemplos de enfermedades renales monogénicas (AU)

Molecular biology techniques have provided important advances in the search for causal relationships in complex diseases supporting traditional epidemiologic studies. Genetic epidemiology allows us to detect genetic variants that could be related to the onset and progression of different diseases. In cardiovascular and renal diseases, this approach linking traditional risk factors to new described ones and those allelic variants, which contribute to the development of these manifestations permits a better understanding of individual disease suceptibility. This is usually afforded through case-control studies evaluating allelic variants of candidate genes previously associated with the disease. Even in this candidate gene search, association-based methods are more powerful than linkage studies in complex traits if we assume that some of the typed polymorphisms are causative although with subtle phenotypic effects. Some brief examples may illustrate the progress in the understanding of renal and cardiovascular diseases (AU)

Association of angiotensinogen M235T and A(-6)G gene polymorphisms with coronary heart disease with independence of essential hypertension: the PROCAGENE study. Prospective Cardiac Gene.

OBJECTIVES: We examined the relationship between the angiotensinogen (AGT) gene M235T polymorphism, the variant promoter of the AGT gene A(-6)G and the angiotensin-converting enzyme (ACE) gene insertion/deletion (I/D) polymorphism and coronary heart disease (CHD) in native Gran Canaria Island habitants, who have the highest rates of CHD in Spain. BACKGROUND: Some studies subject that the ACE (I/D) polymorphism could be associated with CHD, while AGT (M235T) has been related to essential hypertension. METHODS: We studied 304 subjects with angiographic evidence of coronary artery disease and a clinical diagnosis of myocardial infarction or unstable angina and 315 age- and gender-matched controls. Blood was drawn and DNA extracted. Angiotensin-converting enzyme (I/D) gene polymorphism was analyzed by polymerase chain reaction (PCR) and AGT gene polymorphisms by restriction fragment length polymorphism-PCR and mutagenically-separated PCR. RESULTS: The ACE (I/D) polymorphism showed no association with CHD, whereas the frequency distribution of AGT (M235T) genotypes among patients and controls (235T: 29.1% and 19.0%; M235T: 48.5% and 50.2%; M235: 22.4% and 30.8%, respectively) was statistically different (p = 0.005) and not related to the presence of essential hypertension. Similar results were observed with the AGT A(-6)G polymorphism. In multiple logistic regression analysis, CHD odds ratio associated with 235T and M235 homozygotes were 1.7 (1.1 to 2.6) and 0.54 (0.36 to 0.82), respectively. CONCLUSIONS: This study shows that genetic variation of the AGT (M235T), but not the ACE (I/D), genotypes contributes to the presence of CHD independently of blood pressure profile in a subset of the Spanish population with a high prevalence of cardiovascular disease.

Effects of the angiotensinogen gene M235T and A(-6)G variants on blood pressure and other vascular risk factors in a Spanish population.

Angiotensinogen (AGT) gene polymorphism has shown significant differences in the allelic frequencies between hypertensive and normotensive subjects. This allele frequency varies among ethnic groups. There are still some controversies related to the 235T-variant as a marker for essential hypertension. As part of an extensive case-control study carried out in a Spanish population, we selected the 237 subjects with a diagnosis of essential hypertension according to the established criteria. A group of 242 normotensives matched for age and gender was used as control. Smoking habits, a previous diabetes and hypertension medical history, body mass index (BMI) and blood pressure (BP) values were recorded. Glucose, plasma creatinine, lipid profile with Lp(a), homocysteine and microalbuminuria were measured. Angiotensinogen M235T-gene polymorphism was determined by polymerase chain reaction (PCR) from genomic DNA. A(-6)G polymorphism was determined by mutagenically separated PCR (MS-PCR). BP values, BMI and microalbuminuria were significantly higher in hypertensive subjects; 31.6% of hypertensives and 40.1% normotensives were active smokers. M235T-genotype frequencies were not different in the hypertensive and normotensive population. Similarly, homocigotic AA predominate in the hypertensives but without statistical significance. The association of 235T-genotype or the changes in the promoter activity due to A(-6) substitution with essential hypertension was not confirmed in the multivariate regression analyses. Only a previous family history of hypertension and BMI were significantly associated with hypertension. Journal of Human Hypertension (2000) 14, 789-793

Aminoglycoside resistance mechanisms in clinical isolates of Pseudomonas aeruginosa from the Canary Islands.

Strains of Pseudomonas aeruginosa resistant to aminoglycoside antibiotics were selected from 152 clinical isolates. We identified two patterns of resistance correlating with the resistance mechanism characterized by changes in permeability, enzymatic modification due to the acetylating enzyme, AAC(6')-II, or a combination of both. We detected enzymatic activity of the phosphorylase enzyme, APH(3'), in all the isolates. We compared the mechanisms of resistance detected by three methods i.e., radioenzymatic assay, phenotype of resistance and DNA probes. The phenotype of resistance was tested using a kit developed by Schering-Plough Corp. Hybridization was made with 18 DNA probes for the most frequent genes encoding for aminoglycoside-modifying enzymes. All isolates with AAC(6') activity hybridized with the aac(6')-Ib probes and to a minor degree, with the aac(6')-IIb probe. None of the isolates showed hybridization with aph(3')-I, aph(3')-II, or aph(3')-III DNA probes. Serotyping of the strains showed that the O:11 serotype was the most frequent one in strains whose resistance was due to the AAC(6') enzyme. The O:6 serotype was associated with changes in permeability. Encoding of the resistance mechanism seemed to be chromosomal in all the strains.