[Effect of antihypertensive combinations on arterial pressure, albuminuria, and glycemic control in patients with type II diabetic nephropathy: a randomized study]. / Efecto de dos combinaciones antihipertensivas sobre la presión arterial, albuminuria y control glucémico en pacientes con nefropatía diabética tipo 2: un estudio aleatorizado.

Type II diabetic patients with albuminuria are at high risk for cardiovascular complications; the intense antihypertensive treatment required often involves using drug combinations. The aim of the present study was to compare the effect of two different, renin-angiotensin blocking combinations, on blood pressure (BP), albuminuria and glycemic control. Its design was prospective, randomised, controlled, of parallel branches, and performed in one Endocrinology Department, in Spain. 77 type-II diabetic patients, with stable albuminuria (30-1,000 mg/day) were included. After a pre-inclusion time of 2 weeks, patients were randomised to verapamil SR/trandolapril 180/2 (VT) or losartan/hydrochlorothiazide (LH) 20/12.5 mg/day. Duration of treatment was 1 year. The evaluated parameters were changes in blood pressure, urinary albumin excretion for 24 hours, glycated hemoglobin and plasmatic urea. Overall BP significantly decreased from 161.6 +/- 18.7/83.6 +/- 10.2 mmHg to 137.2 +/- 15.7/70.9 +/- 8.3 mmHg (p < 0.0005). Values, by treatment, were: For VT, 164.3 +/- 18.5/87.2 +/- 10.7 mmHg at baseline and 135.0 +/- 15.1/71.3 +/- 8.4 mmHg at conclusion. For LH, 158.8 +/- 17.4/80.1 +/- 8.4 mmHg at baseline and 139.3 +/- 16.1/70.5 +/- 8.2 mmHg at conclusion. Albuminuria significantly decreased from 308.2 +/- 544.7 mg/day to 198.0 +/- 285.3 mg/day. Both parameters showed no significant difference between treatments. Glycated hemoglobin decreased from 7.59 +/- 1.3% to 7.14 +/- 1.2% in the VT group, and from 7.96 +/- 1.29% to 7.84 +/- 1.62% in the LH group (ANOVA, p = 0.022). Changes adjusted from baseline values showed a trend to the difference between both treatments (p = 0.092). Plasmatic urea increased from 39.8 +/- 12.7 to 40.5 +/- 11.1 mg/dL in the TV group and from 43.4 +/- 12.0 mg/dL to 52.4 +/- 19.4 mg/dL in the LH group (ANOVA, p = 0.028). In conclusion, both treatments reduce blood pressure and albuminuria in a similar way in type II diabetic patients. The verapamil/trandolapril combination contributes to a better carbohydrate metabolism than losartan/hydroclorothiazide.

Role of sibutramine in the treatment of obese Type 2 diabetic patients receiving sulphonylurea therapy.

AIMS: To investigate whether the satiety-inducing agent sibutramine affected body weight and associated anthropometry in overweight and obese (body mass index (BMI) > 27) Type 2 diabetic patients on sulphonylurea therapy. METHODS: A randomized, placebo-controlled trial was undertaken in 134 patients with stable metabolic control on chronic sulphonylurea therapy. Patients were placed on moderate caloric restriction and received treatment with either sibutramine (15 mg/day) or placebo for 6 months. RESULTS: Fifty-three of 69 sibutramine-treated and 57/65 placebo-treated patients completed the study. Both groups showed progressive weight loss. At the end of the trial weight loss was two times greater in the sibutramine group (mean +/- SEM; -4.5 +/- 0.5 kg) than placebo (-1.7 plus minus 0.5 kg, P < 0.001 vs. sibutramine). There was a trend for more patients to lose > 5% of initial body weight in the sibutramine group than placebo. BMI (P < 0.001) and waist circumference (P < 0.001) were also decreased to a greater extent by sibutramine. Mean reductions in HbA(1c) were commensurate with weight loss in both the sibutramine and placebo (- 0.78 +/- 0.17% and -0.73 +/- 0.23%; P = 0.84). Sibutramine was well tolerated with only two patients withdrawn due to potentially drug-related serious adverse events (palpitations). CONCLUSIONS: Sibutramine, in conjunction with moderate caloric restriction, enhances weight loss and reduces waist circumference in overweight and obese Type 2 diabetic patients receiving sulphonylurea therapy. This is associated with additional improvements in glycaemic control in a limited number of patients losing > or = 10% of their baseline body weight.

Efecto de dos combinaciones antihipertensivas sobre la presión arterial, albuminuria y control glucémico en pacientes con nefropatía diabética tipo 2: un estudio aleatorizado / Effect of two different antihypertensive drug combinations over blodd pressure, albuminuria and glycemic control in patients with diabetic nephropathy type II

Los pacientes diabéticos tipo 2 con albuminuria presentan un elevado riesgo de complicaciones cardiovasculares; el intenso tratamiento antihipertensivo que precisan implica con frecuencia el uso de combinaciones. El objetivo del presente estudio fue comparar el efecto de dos diferentes combinaciones, basadas en el bloqueo del sistema renina-angiotensina, sobre la PA, albuminuria y control glucémico. El diseño fue prospectivo, aleatorizado, de ramas paralelas, controlado y llevado a cabo en un único Servicio de Endocrinología, en España. Se incluyeron 77 diabéticos tipo 2 con albuminuria estable entre 30 y 1.000 mg/día. Tras un período de pre-inclusión de dos semanas, las pacientes fueron aleatorizados a verapamil SR/trandolapril 180/2 (VT) o losartan/hidroclorotiazida (LH) 20/12,5 mg/día. La duración del tratamiento fue un año. Los parámetros evaluados fueron los cambios en la presión arterial, excreción urinaria de albúmina (24 horas), hemoglobina glicosilada y urea plasmática. La PA global descendió significativamente de 161,6 ñ 18,7 / 83,6 ñ 10,2 mmHg a 137,2 ñ 15,7 / 70,9 ñ 8,3 mmHg (p < 0,0005). Por tratamientos, los valores fueron: Para VT, 164,3 ñ 18,5 / 87,2 ñ 10,7 mmHg inicial y 135,0 ñ 15,1 / 71,3 ñ 8,4 mmHg final. Para LH, 158,8 ñ 17,4 / 80,1ñ 8,4 mmHg inicial y 139,3 ñ 16,1 / 70,5 ñ 8,2 mm Hg final. La albuminuria se redujo significativamente de 308,2 ñ 544,7 mg/día a 198,0 ñ 285,3 mg/día; en ambos parámetros sin diferencias significativas entre tratamientos. La hemoglobina glicosilada descendió de 7,59 ñ 1,30 por ciento a 7,14 ñ 1,20 por ciento en el grupo VT y de 7,96 ñ 1,29 por ciento a 7,84 ñ 1,62 por ciento en el grupo LH (ANOVA, p = 0,022).Los cambios ajustados por los valores basales alcanzaron diferencias casi significativas entre tratamientos (p = 0,092). La urea plasmática pasó de 39,8 ñ 12,7 mg/dL a 40,5 ñ 11,1 mg/dL en el grupo TV y de 43,4 ñ 12,0 mg/dL a 52,4 ñ 19,4 mg/dL en el grupo LH (ANOVA, p = 0,028). En conclusión, en NEFROLOGÍA. Vol. XXII. Número 2. 2002 pacientes diabéticos tipo 2 con albuminuria estable, ambos tratamientos reducen la presión arterial y la albuminuria de forma similar. La combinación verapamil/trandolapril contribuye mejor al control metabólico hidrocarbonado que losartan/hidroclorotiazida (AU)

[Use of alternating antipyretics in the treatment of fever in Spain]. / Utilización de la alternancia de antipiréticos en el tratamiento de la fiebre en España.

OBJECTIVE: To assess the frequency of the use of alternating antipyretics among Spanish pediatricians and to analyze the factors that determine this practice. METHODS: An anonymous survey of practicing pediatricians was conducted. Data on the use of antipyretics were collected. Factors related to alternating antipyretics were assessed by using multivariate correlation analyses. RESULTS: Three hundred twenty-four questionnaires were reviewed. The mean age of participants was 46.4 18.6 years (29-68 years). Of the responding pediatricians, 22.5 % worked in hospitals, 87.5 % in health centres and 24.7 % in in private practice. A total of 68.8 % of pediatricians (95 % CI: 63.4-73.8 %) alternated antipyretics. The combination of ibuprofen and acetaminophen was recommended by 96.9 %. The use of alternating antipyretics was positively associated with male sex (OR: 0.535; 95 % CI: 0.296-0.967; p 0.038), with few years' experience (OR: 0.952; 95 % CI: 0.922-0.984, p 0.005), with considering ibuprofen the drug of choice (OR: 2.324; 95 % CI: 1.235-4.372; p 0.009) and with the doctor's recommendation that the antipyretic be readministered in the event of slight increases in temperature (OR: 0.529; 95 % CI: 0.310-0.901; p 0.019). CONCLUSIONS: Despite the lack of scientific evidence to justify the practice, the use of alternating antipyretics is common in the treatment of febrile children. Predictive factors of this practice among pediatricians are male sex, having relatively little experience, considering ibuprofen as the drug of choice and recommending the administration of new doses of antipyretic to control mild fever.

Utilización de la alternancia de antipiréticos en el tratamiento de la fiebre en España / Use of alternating antipyretics in the treatment of fever in Spain

Objetivo: Analizar la frecuencia de utilización de la administración alternante de antitérmicos entre los pediatras españoles, y los factores que determinan este uso. Métodos: Se llevó a cabo una encuesta anónima a pediatras en ejercicio activo. Se recogieron los datos de utilización de antitérmicos. Se realizó un análisis de los factores relacionados con la alternancia de antipiréticos con técnicas multivariantes. Resultados: Se obtuvieron 324 encuestas. La edad media de los participantes fue de 46,4 18,6 años (29-68 años de edad). El 22,5%de los pediatras ejercían en un hospital, el 87,5% en un centro de salud y el 24,7% tenía su consulta privada. El 68,8% (IC 95%, 63,4-73,8%) utilizaban la pauta alternante de antipiréticos, siendo la combinación de ibuprofeno y paracetamol la recomendada por el 96,9%. Se relaciona con la utilización secuencial de antitérmicos el hecho de ser varón (OR, 0,535; IC 95%, 0,296-0,967; p 0,038), con pocos años de experiencia (OR, 0,952; IC 95%, 0,922-0,984; p 0,005), considerar el ibuprofeno como fármaco de primera elección (OR, 2,324; IC 95%, 1,235-4,372; p 0,009) y recomendar una nueva dosis de antitérmico ante leves ascensos de temperatura (OR, 0,529; IC 95%, 0,310-0,901; p 0,019). Conclusiones: A pesar de la falta de evidencia científica que lo justifique, la utilización combinada de antitérmicos es una pauta habitual de tratamiento de la fiebre infantil, siendo factores que predisponen a esta práctica que el pediatra sea varón y con pocos años de ejercicio, que el fármaco utilizado de entrada sea el ibuprofeno, y que se recomiende la utilización de antitérmicos para el tratamiento de fiebre de leve intensidad (AU)

[The effect of trandolapril, in monotherapy and associated with verapamil, on arterial pressure, albuminuria, and metabolic control in hypertensive patients with type 2 diabetes and albuminuria]. / Efecto del trandolapril, en monoterapia y asociado con verapamil, sobre la presión arterial, albuminuria y control metabólico en pacientes hipertensos con diabetes tipo 2 y albuminuria.

The aim of this study was to analyse the effect of the ACE-1, Trandolapril, alone or with Verapamil on blood pressure, albuminuria and metabolic profile in type 2 diabetic patients with hypertension and albuminuria. It was an open multicenter, consecutive and prospective study conducted in 281 patients. There was a four-week wash-out period of antihypertensive drugs, after which we carried out a measurement over a 24-h period of the urinary excretion of albumina (UEA). Blood pressure was recorded after at least 5 minutes of rest in the sitting position at 1 to 3 minute intervals with a mercury sphygmomanometer in good condition. Average BP was obtained from three consecutive readings. Within treatment changes were analysed using descriptive statistics and t-tests on the change from baseline. Analysis of variance, chi-square and Mc Nemar tests were also used. If after 8 weeks of treatment with Trandolapril 2 mg o.q.d. the patients were non-responders (mean blood pressure reduction of 5 mmHg or less) or their blood pressure remained uncontrolled (blood pressure > or = 140/90 mmHg), Verapamil 180 mg o.q.d. was added. Two hundred and thirty patients completed the 12 weeks study. Population included 157 (55.9%) males with an average of 61.7 +/- 9.2 years. Baseline measurements were systolic 165.4 +/- 14.6 and diastolic 94.8 +/- 8.5 mmHg blood pressures, fasting glucose 162.7 +/- 43.9 mg/dL, glycosylated hemoglobin (HbAlc) 6.8 +/- 1.2%, and albuminuria 520.9 +/- 602 mg/day. UEA fell significantly (p < 0.001) after treatment to 177.9 +/- 24.3 mg/day (CI 95%, 129.9 to 225.8). The percent reduction reached 29.6%. Albuminuria was lower than 30 mg/day in 47 patients. Blood pressure was completely controlled in 125 (54%) patients. Glucemia fell significantly (p < 0.001) to 153.2 +/- 42.7 mg/dL, and the HbAlc to 6.5 +/- 1.3% (p = 0.012). In summary, in those diabetic type 2 patients with arterial hypertension and proteinuria, Trandolapril alone or associated with Verapamil significant lowered albuminuria and blood pressure facilitated the control or their metabolic profile.

Análisis de los factores pronósticos de la respuesta antipirética del ibuprofeno / Analysis of prognostic factors for the antipyretic response to ibuprofen

OBJETIVO: Analizar los factores que influyen en la respuesta antitérmica del ibuprofeno. PACIENTES Y MÉTODOS: Niños de entre 1y 10años que acudieron al servicio de urgencias con temperatura superior a 38ºC. Se les administró una dosis de 7mg/kg de ibuprofeno, anotándose después la temperatura a los 30, 60, 90, 120, 180y 240min. Se analizó la influencia de la edad, sexo, peso, superficie corporal, entidad nosológica, administración previa de antitérmicos y asociación de medidas físicas sobre la evolución de la temperatura. RESULTADOS: Se estudiaron 384 niños, con temperatura corporal comprendida entre 38y 42ºC (39,1 ñ 60,6ºC), en el 77,8 por ciento la fiebre duraba más de 6h y el 59,5 por ciento habían recibido al menos un antitérmico. El 93,5 por ciento de los niños redujeron su temperatura hasta 37,5ºC o menos, alcanzándose dicha temperatura en el 80,2 por ciento de los niños entre 1y 2horas después del tratamiento. El 95 por ciento de los pacientes alcanzó un descenso de la temperatura corporal de al menos 1ºC. La temperatura inicial más alta (odds ratio[OR] 0,008; intervalo de confianza [IC] 95 por ciento, 00,14) y la mayor superficie corporal (OR, 0,004; IC 95 por ciento, 00,89) facilitan la consecución de dicho objetivo, mientras que la mayor edad la dificulta (OR, 1,67; IC 95 por ciento, 1,032,7). CONCLUSIÓN: El ibuprofeno es un fármaco muy eficaz en el tratamiento de la fiebre infantil y la magnitud de su efecto antitérmico guarda cierta relación con la edad, el grado de temperatura inicial y la superficie corporal (AU)

Evaluación de la eficacia antipirética y seguridad de dos formulaciones pediátricas de ibuprofeno / Evaluation of the antipyretic safety and accuracy of two pediatric ibuprofen formulations

OBJETIVO: Comparar la eficacia y evaluar la bioequivalencia clínica de dos presentaciones de ibuprofeno para niños, suspensión y gránulos efervescentes, en el tratamiento de la fiebre. MÉTODOS: Ensayo clínico abierto, de distribución aleatoria y multicéntrico. Se administró a niños con pesos superiores a 25kg, que acudieron con temperatura axilar superior a38º C a servicios de urgencias hospitalarios, una dosis de ibuprofeno en suspensión de 7 mg/kg, o una dosis de gránulos efervescentes con la siguiente posología: 200 mg en niños con pesos entre 25 y 40 kg, o 400 mg si pesaban entre 35 y 40 kg y tenían una temperatura axilar superior a 39 ºC, así como en los niños de más de 40 kg. Se tomó la temperatura axilar antes del tratamiento y a los 30, 60, 90, 120, 180 y 240 min, y se registraron posibles efectos adversos. RESULTADOS: Se incluyeron 103 pacientes, 51 recibieron gránulos y 52 suspensión. La temperatura media se redujo en los dos grupos a lo largo del estudio (p < 0,005), sin diferencias entre ellos. Las diferencias medias de temperatura en cada momento del estudio se situó dentro del intervalo de bioequivalencia (60,5ºC). En un caso se alcanzó una temperatura axilar de 35,9 ºC, siendo el único acontecimiento adverso ocurrido. CONCLUSIÓN: Ambas formulaciones se mostraron eficaces en la reducción de la temperatura y pueden considerarse bioequivalentes clínicamente (AU)

[Analysis of prognostic factors for the antipyretic response to ibuprofen]. / Análisis de los factores pronósticos delarespuesta antipirética del ibuprofeno.

AIM: To assess the factors influencing the antipyretic activity of ibuprofen in children. PATIENTS AND METHODS: Children aged between 1 and 10 years attending the emergency department with a temperature of> 38 degrees C were given one dose of ibuprofen (7 mg/kg). Temperature was recorded before and 30, 60, 90, 120, 180 and 240 min after ibuprofen administration. The influence of age, sex, weight, body surface, nosologic entity, previous antipyretic administration, and the association between physical measurements and temperature evolution were assessed. RESULTS: A total of 384 children were studied. Baseline temperatures were between 38 degrees C and 42 degrees C (mean: 39.1 +/- 60.6). Most of the patients (77.8%) had been feverish for more than 6 hours and 59.5% had received antipyretic treatment. In 93.5% of the children temperature was lowered to 37.5 degrees C or less. In 80.2% of the children this temperature was reached 12 hours after treatment. In 95% of ther children a decrease of at least 1 degree C was achieved. Older age (OR 1.67; 95% CI: 1.032.7), smaller body surface (OR 0.004; 95% CI 00.89) and lower baseline temperature (OR 0.008; 95%CI 00.14) were associated with a smaller antipyretic response (decrease in body temperature lower than 1 degree C). CONCLUSIONS: Ibuprofen is effective in the treatment of fever in children. Its effectiveness is related to age, the degree of fever and body surface.

[Flubiprofen vs dipyrone combined with hyoscine: the analgesic efficacy in renal colic]. / Flubiprofeno vs dipirona asociada a hioscina: eficacia analgésica en el cólico nefrítico.

OBJECTIVE: We compared the efficacy of flurbiprofen (NSAID) versus dipirone + hyoscine N-butylbromide in the treatment of nephric colic. METHODS: The study comprised 135 patients, aged 18 to 75 yrs, with intense nephric colic. The patients were observed 60 min after a single IM dose of 150 mg flurbiprofen (n = 67) or 2 gm dipirone + 20 mg hyoscine N-butylbromide. RESULTS: Both treatment modalities were well-tolerated and afforded significant pain relief. Flurbiprofen, however, was faster-acting and superior to dipirone + hyoscine in the overall evaluation of good and excellent therapeutic response rates. CONCLUSION: The results of the study show that IM flurbiprofen is a useful alternative to dipirone + hyoscine N-butylbromide in the treatment of nephric colic.

[The efficacy of injectable flurbiprofen in the symptomatic treatment of biliary colic]. / Eficacia del flurbiprofeno inyectable en el tratamiento sintomático del cólico biliar.

BACKGROUND: To evaluate the efficacy of flurbiprofen (nonsteroidal anti-inflammatory drug) in the treatment of biliary colic pain as compared with the drugs commonly used (analgesics and/or spasmolytics). METHODS: Eighty-four patients aged between 21 and 86 affected by intense pain of simple hepatic colic participated in the study. Following a single intramuscular dose of 150 mg of flurbiprofen (FRI, n = 30), 20 mg of N-hyoscine butylbromide (HBB, n = 25) or 30 mg of pentazocine (PTZ, n = 29) the patients were observed during the 6 hours after administration. RESULTS: The evolution of the pain was significantly better in the patients treated with FRI with differences being detected between the three drugs after 30 minutes of administration. A greater number of adverse reactions were seen among the patients who received PTZ with the differences being statistically significant with the other 2 treatments (p less than 0.02). CONCLUSIONS: Intramuscular flurbiprofen was more effective and generally better tolerated than pentozocine and hyoscine butylbromide.

Theophylline binding to plasma proteins in patients with chronic obstructive pulmonary disease.

The binding of theophylline to plasma proteins was studied in samples from healthy adults at different pH values and drug concentrations and in samples from patients with chronic obstructive pulmonary disease (COPD). Binding determinations were performed by ultrafiltration and drug concentrations were measured by high performance liquid chromatography. Total plasma levels of theophylline did not influence the degree of the binding. The percentage of bound theophylline was positively correlated with pH both in vitro (r = 0.998, p less than 0.005) and in vivo (r = 0.579, p less than 0.005). Mean theophylline binding values in vivo (mean 56.3 +/- 12.5) and in vitro (mean 48.3 +/- 9.4) were significantly different. The increase in theophylline free levels detected in COPD patients was partially dependent on low pH values but the influence of other factors must also be considered. The therapeutic implications of altered theophylline binding are discussed.