Effectiveness of vitamin D supplementation on knee osteoarthritis - A target trial emulation study using data from the Osteoarthritis Initiative cohort.

OBJECTIVE: To assess the real-world effectiveness of vitamin D supplementation in patients with knee osteoarthritis (KOA) by replicating a randomized controlled trial (RCT) design in an observational study. METHOD: This study emulated a target trial using data from the Osteoarthritis Initiative (OAI). Eligible participants were ≥45 years, had symptomatic KOA and did not take vitamin D supplements in the past 30 days. A participant can enter the trial more than once. Participants were included in vitamin D group if they took ≥1,000 IU/day for ≥4 days/week in the past 30 days at the first follow-up visit after baseline. The control group did not use vitamin D in the past 30 days. Optimal propensity score matching at 1:1 ratio was performed. The primary outcome was change in knee pain 2 years after baseline measured by the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC). Secondary outcomes included WOMAC physical function and quantitative joint space width (JSW). Standardized mean difference (SMD) was used to compare the findings with previous RCTs. RESULTS: A total of 236 person-trials in the vitamin D group were pair-matched with a control. Compared to the control group, vitamin D supplementation did not reach significant changes in WOMAC pain (SMD = -0.04, 95%CI [-0.21, 0.13]), physical function and radiographic JSW over 2 years. The SMDs were consistent with the effect sizes reported in previous RCTs. CONCLUSION: Target trial emulation in the OAI cohort demonstrated findings close to published RCTs. This supports the future use of target trial emulation in evaluating other systemic therapies for KOA.

Rotavirus gastroenteritis hospitalizations in provinces with different vaccination coverage rates in Spain, 2013-2018.

BACKGROUND: Rotavirus (RV) vaccines are available in Spain since 2006 but are not included in the National Immunization Program. RV vaccination has reached an intermediate vaccination coverage rate (VCR) but with substantial differences between provinces. The aim of this study was to assess the ratio of RV gastroenteritis (RVGE) admissions to all-cause hospitalizations in children under 5 years of age in areas with different VCR. METHODS: Observational, multicenter, cross-sectional, medical record-based study. All children admitted to the study hospitals with a RVGE confirmed diagnosis during a 5-year period were selected. The annual ratio of RVGE to the total number of all-cause hospitalizations in children < 5 years of age were calculated. The proportion of RVGE hospitalizations were compared in areas with low (< 30%), intermediate (31-59%) and high (> 60%) VCR. RESULTS: From June 2013 to May 2018, data from 1731 RVGE hospitalizations (16.47% of which were nosocomial) were collected from the 12 study hospitals. RVGE hospital admissions accounted for 2.82% (95 CI 2.72-3.00) and 43.84% (95% CI 40.53-47.21) of all-cause and Acute Gastroenteritis (AGE) hospitalizations in children under 5 years of age, respectively. The likelihood of hospitalization due to RVGE was 56% (IC95%, 51-61%) and 27% (IC95%, 18-35%) lower in areas with high and intermediate VCR, respectively, compared to the low VCR areas. CONCLUSIONS: RVGE hospitalization ratios are highly dependent on the RV VCR. Increasing VCR in areas with intermediate and low coverage rates would significantly reduce the severe burden of RVGE that requires hospital management in Spain. Clinical trial registration Not applicable.

Clinical practice update of antifungal prophylaxis in immunocompromised children.

Due to the rise in the number and types of immunosuppressed patients, invasive fungal infections (IFI) are an increasing and major cause of morbidity and mortality in immunocompromised adults and children. There is a broad group of pediatric patients at risk for IFI in whom primary and/or secondary antifungal prophylaxis (AFP) should be considered despite scant evidence. Pediatric groups at risk for IFI includes extremely premature infants in some settings, while in high-risk children with cancer receiving chemotherapy or undergoing haematopoietic stem cell transplantation (HCT), AFP against yeast and moulds is usually recommended. For solid organ transplanted, children, prophylaxis depends on the type of transplant and associated risk factors. In children with primary or acquired immunodeficiency such as HIV or long-term immunosuppressive treatment, AFP depends on the type of immunodeficiency and the degree of immunosuppression. Chronic granulomatous disease is associated with a particular high-risk of IFI and anti-mould prophylaxis is always indicated. In contrast, AFP is not generally recommended in children with long stay in intensive care units. The choice of AFP is limited by the approval of antifungal agents in different age groups and by their pharmacokinetics characteristics. This document aims to review current available information on AFP in children and to provide a comprehensive proposal for each type of patient.

Comparing methods for estimation of heterogeneous treatment effects using observational data from health care databases.

There is growing interest in using routinely collected data from health care databases to study the safety and effectiveness of therapies in "real-world" conditions, as it can provide complementary evidence to that of randomized controlled trials. Causal inference from health care databases is challenging because the data are typically noisy, high dimensional, and most importantly, observational. It requires methods that can estimate heterogeneous treatment effects while controlling for confounding in high dimensions. Bayesian additive regression trees, causal forests, causal boosting, and causal multivariate adaptive regression splines are off-the-shelf methods that have shown good performance for estimation of heterogeneous treatment effects in observational studies of continuous outcomes. However, it is not clear how these methods would perform in health care database studies where outcomes are often binary and rare and data structures are complex. In this study, we evaluate these methods in simulation studies that recapitulate key characteristics of comparative effectiveness studies. We focus on the conditional average effect of a binary treatment on a binary outcome using the conditional risk difference as an estimand. To emulate health care database studies, we propose a simulation design where real covariate and treatment assignment data are used and only outcomes are simulated based on nonparametric models of the real outcomes. We apply this design to 4 published observational studies that used records from 2 major health care databases in the United States. Our results suggest that Bayesian additive regression trees and causal boosting consistently provide low bias in conditional risk difference estimates in the context of health care database studies.

Características de los casos incluidos en el Registro Español de Pacientes con déficit de alfa-1 antitripsina / Profiles of cases included in the Spanish registry of patients with alpha-1 antitrypsin deficiency

No disponible

Citrulina plasmática como marcador de pérdida de masa enterocitaria en la enfermedad celíaca en la infancia / Plasma citrulline as a marker of loss of enterocitary mass in coeliac disease in childhood

Introducción: La citrulina plasmática no está incorporada a las proteínas endógenas ni exógenas y constituye un teórico marcador de la atrofia vellositaria. El objetivo del estudio es relacionar los niveles plasmáticos de citrulina y arginina con la severidad de la afectación de la mucosa intestinal en pacientes celiacos. Material y métodos: Estudio transversal de cohortes en niños entre 16 meses y 14 años: 46 con enfermedad celíaca al diagnóstico; 9 celíacos siguiendo dieta sin gluten y 42 controles. Se determina concentración plasmática de aminoácidos, en mmol/L, y variables clínicas y analíticas asociadas. Resultados: No diferencias estadísticamente significativas en IMC, edad o función renal, con ligero incremento de esteatorrea en celíacos. Citrulina, arginina y glutamina plasmáticas significativamente más bajas en los casos (17,7 μmol/l, 38,7 μmol/l, 479,6 μmol/l respectivamente)que en controles (28,9 μmol/l, 56,2 μmol/l, 563,7μmol/l). Citrulina plasmática significativamente más baja en grados avanzados de atrofia (13,8 μmol/l vs 19,7μmol/l, p < 0,05), no así con el resto de aminoácidos. Discusión: La medida postabsortiva de citrulina plasmática constituye buen marcador de reducción de masa enterocitaria en celíacos con atrofia vellositaria; secundariamente disminución también de arginina. Grados bajos de alteración histológica de la biopsia intestinal son suficientes como para diferenciar su citrulina de los controles y además se puede afirmar que grados altos de lesión histológica tienen menor citrulina plasmática que grados bajos (AU)

Introduction: Plasma citrulline is not incorporated in endogenous or exogenous proteins so it is a theoretical marker of villous atrophy. Our aim was to correlate plasma citrulline levels with severity of villous atrophy inceliac patients. Methods: Observational case-control study longitudinal in children 16 month-old to 14 year-old: 48 with untreated celiac disease, 9 celiac children under gluten free diet and 35 non-celiac healthy children. Plasma amino acids concentration is determined, expressed inμmol/L, and so are other clinical and analytical data. Results: No statistically significative difference found in the referring to BMI, age or renal function. Small increase in fecal fat in celiac children. Citrulline, arginine and glutamine are significantly lower in cases (17.7μmol/l, 38.7 μmol/l, 479.6 μmol/l respectively) than in controls(28.9 μmol/l, 56.2 μmol/l, 563.7 μmol/l). Citrulline levels are significantly lower in the severe degrees of atrophy than in mild ones (13.8 μmol/l vs. 19.7 μmol/l, p <0.05), not happening so with rest of amino acids. Summary: Postabsortive mean of plasma citrulline is a good marker of reduction in enterocyte mass in celiac patients with villous atrophy; secondary reduction in plasma arginine too. Just a small histological alteration in intestinal biopsy is enough to differentiate citrulline incases and controls and besides it can be seen that high levels of atrophy present with lower plasma citrulline (AU)

[Plasma citrulline as a marker of loss of enterocitary mass in coeliac disease in childhood]. / Citrulina plasmática como marcador de pérdida de masa enterocitaria en la enfermedad celíaca en la infancia.

INTRODUCTION: Plasma citrulline is not incorporated in endogenous or exogenous proteins so it is a theoretical marker of villous atrophy. Our aim was to correlate plasma citrulline levels with severity of villous atrophy in celiac patients. METHODS: Observational case-control study longitudinal in children 16 month-old to 14 year-old: 48 with untreated celiac disease, 9 celiac children under gluten free diet and 35 non-celiac healthy children. Plasma amino acids concentration is determined, expressed in µmol/L, and so are other clinical and analytical data. RESULTS: No statistically significative difference found in the referring to BMI, age or renal function. Small increase in fecal fat in celiac children. Citrulline, arginine and glutamine are significantly lower in cases (17.7 µmol/l, 38.7 µmol/l, 479.6 µmol/l respectively) than in controls (28.9 µmol/l, 56.2 µmol/l, 563.7 µmol/l). Citrulline levels are significantly lower in the severe degrees of atrophy than in mild ones (13.8 µmol/l vs. 19.7 µmol/l, p < 0.05), not happening so with rest of amminoacids. SUMMARY: Postabsortive mean of plasma citrulline is a good marker of reduction in enterocyte mass in celiac patients with villous atrophy; secondary reduction in plasma arginine too. Just a small histological alteration in intestinal biopsy is enough to differentiate citrulline in cases and controls and besides it can be seen that high levels of atrophy present with lower plasma citrulline.

Prevalencia, grado de detección, tratamiento y control de la hipertensión arterialen población general. Estudio Hortega / Prevalence, degree of detection, treatment and control of arterial hypertension in the general population. Hortega study

Pocos estudios analizan la epidemiología de la hipertensión arterial (HTA) en población general de 15 a 85 años aplicando los criterios actuales. Sujetos y método. Realizamos un estudio epidemiológico transversal en etapas sucesivas sobre población general de Valladolid (España). En una primera etapa destinada a garantizar la representatividad de muestras menores tomadas al azar, realizamos una encuesta por correo breve sobre una muestra aleatoria de 34.742 personas. En una segunda etapa estudiamos una muestra estratificada de 1.500 individuos mediante una encuesta por correo extensa, y de ellas seleccionamos a un tercio al azar y les hicimos además entrevista en consulta con toma de la presión arterial (PA) mediante un esfigmomanómetro automático Omron-711 validado. Resultados. La prevalencia de HTA (PA 140/90 mmHg) fue del 32 por ciento en la población general y alcanzó el 77 por ciento entre los mayores de 65 años. La prevalencia fue mayor en mujeres y únicamente el 44 por ciento del total de los sujetos se reconocía hipertenso. La prevalencia de HTA sistólica aislada (PAS 140 mmHg y PAD < 90 mmHg) en la muestra de población general fue del 14 por ciento, más común en mujeres a cualquier edad, la de diastólica aislada (PAD 90 mmHg y PAS<140 mmHg) del 5 por ciento y la hipertensión de pulso (PP 65 mmHg ) del 14 por ciento. La prevalencia efectiva de HTA (población con PA 140/90 mmHg tratada o no tratada) fue del 24,7 por ciento. El 71 por ciento de los hipertensos conocidos (14 por ciento del total de hipertensos) estaba en tratamiento antihipertensivo farmacológico, aunque únicamente el 23 por ciento estaba controlado con cifras inferiores a 140/90 mmHg (7,8 por ciento del total de hipertensos).Conclusión. La HTA afecta a un tercio de nuestra población, aunque menos de la mitad son conscientes de ello. Uno de cada 4 adultos padece una HTA sin control efectivo. El grado de control en población general es malo, aunque con una leve tendencia a mejorar y similar al detectado en otros subgrupos de población. Es necesario mejorar la detección y la eficiencia en el control de la HTA conocida y tratada (AU)

Consumo declarado de fármacos antihipertensivos en población general. Estudio Hortega / Reported use of antihypertensive drugs in the general population. Hortega study

El análisis del consumo de fármacos antihipertensivos en población general tiene gran interés por permitirnos analizar los hábitos de prescripción médicos y de consumo por los pacientes; los datos existentes se basan en estimaciones a partir del número de envases vendidos o se han obtenido de cohortes. Desarrollamos una encuesta por correo destinada a conocer de forma directa los antihipertensivos empleados en población general. La prevalencia autodeclarada de hipertensión es del 14,23 por ciento de la población, la mitad de ellos no toma antihipertensivos, uno de cada cuatro tratados lo es con más de un antihipertensivo, que en el 27 por ciento es una asociación comercial. Los hipertensos tratados suponen el 7,5 por ciento de la población mayor de 14 años. Los pacientes hipertensos toman más fármacos/día que la población no hipertensa, el consumo es mayor en mujeres y aumenta con la edad. Uno de cada tres antihipertensivos corresponde a un inhibidor de la enzima de conversión de la angiotensina (IECA), uno de cada cuatro a un diurético o diuréticos asociados, uno de cada cinco a un calcioantagonista y sólo uno de cada quince es un betabloqueante. Captoprilo fue el más utilizado (16,7 por ciento), seguido por amilorida-hidroclorotiazida, enalaprilo, nifedipino, amlodipino, clortalidona y atenolol; estos siete principios suponen algo más de la mitad de los tratamientos empleados. Si suponemos que cada hipertenso toma la dosis habitual media de cada antihipertensivo (AH) cada día, podemos estimar las dosis diarias definidas (DDD), 1.000 habitantes/ día en mayores de 25 años resultarían 144,6 DDD/1.000 habitantes/día, aunque en realidad sabemos que son 110 los hipertensos tratados/1.000 habitantes/día. Comparado con una encuesta directa, la estimación del consumo de antihipertensivos a través de los dispensados, aunque permite estimar el perfil de los antihipertensivos empleados, sobreestima el número de hipertensos tratados si consideramos que los hipertensos son tratados con una DDD; además esos medicamentos vendidos pudieron ser indicados para tratar otros procesos o no ser realmente consumidos (AU)

Effect of chronic and progressive aortic constriction on renal function and structure in rats.

The purpose of this study was to evaluate the functional and structural renal damage observed in aortic-constricted hypertensive rats and to identify their possible relationship with transforming growth factor beta (TGF-beta) expression. Progressive renovascular hypertension was induced by progressive aortic constriction between the two renal arteries. Three months after constriction, the glomerular filtration rate (GFR), effective renal blood flow (ERBF), perfusion pressure (PP), urinary protein excretion (UPE) and urinary electrolyte excretion (U(Na)V and U(K)V) in the kidney above (right kidney, RK) and below the ligature (left kidney, LK) were measured. The cross-sectional corpuscular, capillary tuft and mesangial matrix area and tubulo-interstitial fibrosis were measured in tissue sections stained with Syrius Red using a computer-assisted image analysis system. TGF-beta was detected by immunohistochemistry. The functional parameters were similar in the two kidneys of aortic-constricted hypertensive rats (GFR-RK, 1.33+/-0.08 vs. LK, 1.18+/-0.08 mL/min; ERBF-RK, 9.23+/-1.32 vs. LK, 8.18+/-0.91 mL/min; RVR-RK, 28.3+/-3.9 vs. LK, 21.7+/-3.2 mmHg x min/mL). The RK was subject to a higher PP than the LK (176+/-7 vs. 128+/-5 mmHg, P < 0.05). UPE, U(Na)V, and U(K)V were greater in the RK than in the LK (UPE-RK, 512+/-61 vs. LK, 361+/-38 microg/30 min, P < 0.05; U(Na)V-RK, 0.056+/-0.012 vs. LK, 0.022+/-0.006 mEq/30 min, P < 0.05; UKV-RK, 0.042+/-0.006 vs. LK, 0.029+/-0.003 mEq/30 min, P < 0.05). Morphometric analysis revealed that the RK capillary tuft area and mesangial matrix area were higher than those in the LK. The LK had a higher degree of interstitial fibrosis than the RK. No significant differences in TGF-beta immunostaining were observed between the RK and the LK. In conclusion, the RK (subjected to hypertension) of aortic-constricted hypertensive animals developed glomerular fibrosis, only in the outer glomeruli whereas the LK developed mild interstitial fibrosis. Neither glomerular nor interstitial fibrosis seem to be responsible for the proteinuria observed in both kidneys.

Renal fibrosis in diabetic and aortic-constricted hypertensive rats.

To assess if the renal damage observed in rats with diabetes and hypertension is due to hemodynamic or metabolic changes, a progressive aortic constriction between the two renal arteries has been done in streptozotocin-induced diabetic rats (constriction + diabetes group) and in nondiabetic rats (constriction group). This model allows us to study two kidneys subjected to different perfusion pressure (PP) in the same metabolic environment. One-month-old rats (100-120 g body wt) were subjected to the aortic constriction procedure. Three months after constriction, glomerular filtration rate and renal plasma flow were similar in both kidneys of the two groups. PP was greater in the kidney placed over the ligature [constriction high-pressure kidney (CH) or constriction + diabetic high-pressure kidney (DH)] than in the one placed below the ligature [constriction low pressure (CL) or constriction + diabetic low pressure (DL)]. Proteinuria was higher in the CH than in the CL kidneys (512 +/- 61 vs. 361 +/- 38 microg/30 min, respectively) and much higher in the DH kidney (770 +/- 106 microg/30 min). Renal fibrosis was measured in tissue sections stained with Syrius red using a computer-assisted image analysis system. DH and DL kidneys showed higher corpuscular cross-sectional and capillary tuft areas than the CH and CL ones. The DH kidney showed slight mesangial expansion and thickening of the capillary walls, which were more pronounced in the former. Most renal corpuscles from CH and DH groups were nearly normal in morphology appearance, and only in some instances a slight increment in mesangium was observed. Transforming growth factor-beta1 (TGF-beta1) immunostaining revealed that DH kidneys showed the highest glomerular expression. We concluded that 1) diabetic animals develop glomerular but not interstitial fibrosis to a greater extent than nondiabetic animals and that this lesion principally occurs in the hypertensive kidney (DH), and 2) increased TGF-beta expression is associated with diabetic renal damage.

Inspiratory capacity, dynamic hyperinflation, breathlessness, and exercise performance during the 6-minute-walk test in chronic obstructive pulmonary disease.

Patients with severe chronic obstructive pulmonary disease (COPD) develop dynamic lung hyperinflation (DH) during symptom-limited incremental and constant work exercise with cycle ergometer and treadmill. The increase in end-expiratory lung volume seems to be the best predictor of dyspnea. Quantification of DH is based on the relatively complex use of on-line measurement of inspiratory capacity (IC) from flow volume loops. We reasoned that DH could occur during daily activities such as walking, and that it could be simply measured using the spirometrically determined IC. We studied 72 men with COPD (FEV(1) = 45 +/- 13.3% predicted). IC was measured at rest and after a 6-min walk test. Exertional dyspnea was evaluated using the Borg scale and dyspnea during daily activities with the modified Medical Research Council (MRC) scale. IC decreased significantly from 28.9 +/- 6.7% TLC at rest to 24.1 +/- 6.8% TLC after exercise (p < 0.001). Exertional dyspnea correlated with DeltaIC (r = -0.49, p < 0.00001) and baseline MRC (r = 0.59, p < 0.00001). In many patients with COPD, walking leads to DH that can be easily determined with simple spirometric testing. DH helps explain exercise capacity limitation and breathlessness during simple daily activities.

Effect of chronic NG-nitro-L-arginine methyl ester (L-NAME) on blood pressure and renal function in conscious uninephrectomized spontaneously hypertensive rats.

We have studied during 30 days the effect of a low dose of NG-nitro-L-arginine methyl ester (1 mg.kg-1.day-1 in drinking water) in the presence of D- or L-arginine (1 mg.kg-1.day-1 in drinking water) in comparison with D- or L-arginine alone on blood pressure and renal function in conscious uninephrectomized female spontaneously hypertensive rats. At the end of the study, there was a significant increase in systolic blood pressure in the NG-nitro-L-arginine methyl ester + D-arginine group (307 +/- 6 mmHg (1 mmHg = 133.3 Pa), n = 14, p < 0.05) in comparison with NG-nitro-L-arginine methyl ester + L-arginine (281 +/- 6 mmHg, n = 14), L-arginine (262 +/- 5 mmHg, n = 13), and D-arginine (258 +/- 7 mmHg, n = 12) groups. There were no changes in diuresis, proteinuria, or sodium and potassium excretion between differently treated animals during this study. These results suggest that in uninephrectomized female spontaneously hypertensive rats, after 1 month blockade of NO synthesis with a low dose of NG-nitro-L-arginine methyl ester, vasculature is under tonic control by NO and it is not correlated with renal dysfunction.

Beneficial effect of the long-term treatment with the combination of an ACE inhibitor and a calcium channel blocker on renal injury in rats with 5/6 nephrectomy.

The effects of the addition of a calcium channel blocker, verapamil (20 mg/kg/day) to an ACE inhibitor, trandolapril (0.7 mg/kg/day) in a 6-month treatment on renal insufficiency development in rats with 5/6th nephrectomy, were studied. Every month we measured heart rate and arterial pressure by the tail-cuff method. Renal function studies were performed in metabolic cages. At the end of the study, renal tissue was prepared for light microscope analysis. Renal lesions were assessed by semiquantitative scores in a blind fashion. Corpuscular section area, intraglomerular and tubulointerstitial fibrosis were determined by digital image analysis with a specific software (Fibrosis HR) on syrium red-stained renal sections. Trandolapril markedly increased the survival ratio that after 6 months reached 87% in comparison with 61% in untreated rats. No mortality was observed in rats treated with the combination of verapamil and trandolapril. Trandolapril treatment prevented the development of hypertension. The combination verapamil-trandolapril did not induce further reduction on blood pressure. The untreated group showed a marked proteinuria, that in the trandolapril group showed an important reduction. The verapamil + trandolapril group showed a proteinuria significantly smaller than that of all the other groups. Light microscopy semiquantitative studies of the renal injury showed that the trandolapril and verapamil + trandolapril groups had a marked reduction in glomerular and tubulointerstitial alterations, compared with untreated animals. Quantitative determinations of glomerular and interstitial fibrosis performed on syrium red-stained renal sections demonstrated that fibrosis was reduced when rats when treated with trandolapril and even more with verapamil + trandolapril when they were compared to untreated animals' values. In conclusion, long-term treatment with verapamil given in addition to trandolapril produces additional protection against progressive renal injury associated to subtotal nephrectomy.

Bilateral gluteoplasty for fecal incontinence.

PURPOSE: This study describes our clinical experience with adynamic bilateral gluteoplasty in 20 patients with total fecal incontinence, in whom a sphincter repair had failed (n = 17) or was nonviable. METHODS: Between 1986 and 1995, 12 women and 8 men ranging in age from 15 to 58 (mean, 37) years underwent different techniques of adynamic gluteoplasty. The indications for the operation were congenital anomalies, denervation, or sphincter destruction. Postoperative evaluation was clinical (Pescatori grading; self-evaluation) and manometric. RESULTS: Morbidity was only related to wound infection (n = 7) requiring late reoperations for neosphincter repair (n = 5), anal stenosis (n = 2), and incisional hernia after colostomy closure (n = 1). Two other patients with no complications also had further surgery for tightening of the neosphincter; they had a successful outcome. Of the 17 evaluable patients, 9 (53 percent) achieved normal control or were graded as Pescatori A-1, A-2, B-1, or C-1, 1 (6 percent) as Pescatori C-2, and 7 (41 percent) as Pescatori C-3. Six patients (35 percent) judged their results as excellent, three (18 percent) as good, one (6 percent) as fair, and seven (41 percent) as bad. Eight patients are able to retain 200 ml of water instilled into the rectum for between five minutes and two hours. For the nine patients with better results, the mean +/- standard deviation of the differences between postgluteoplasty and pregluteoplasty anal pressures were 40 +/- 25 mmHg (resting pressure) and 122 +/- 85 mmHg (squeeze pressure). These findings demonstrate a tonic and voluntary activity of the plasty. The author's technique has less morbidity, and excellent or good results were achieved in 67 percent of the patients. Failures were attributable to suture disruption (n = 4), poor muscular contraction (n = 2), and intractable constipation (n = 1). CONCLUSIONS: Adynamic gluteoplasty is efficient for achieving good or very good continence status in a higher proportion of patients than with other adynamic muscle transfer procedures.

Sulbactam-cefoperazona en el tratamiento de la neumonía nosocomial / Sulbactam-cefoperazone in the treatment of the nosocomial pneumonia

Investigadores de 8 centros a nivel nacional evaluaron la eficacia y seguridad de la combinación sulbactan/cefoperazona (SBT/CPZ)m, en un estudio abierto en 51 pacientes hospitalizados (29 M, 22 F), con edades comprendidas entre 12-90 años con el diagnóstico (en base a historia clínica, hallazgos radiológicos y/o bacteriológicos) de neumonía nosocomial (NN). La combinación fue administrada como monoterapia en una dosis diaria de 4,76g (rango 39g) entre 1-14 días (X=9,94 días). De los 51 pacientes, 47 fueron evaluados para eficacia clínica; se obtuvo curación en 41 (87,2 por ciento), falla en 5 (10,6 por ciento) y recaída en 1(2 por ciento). Veintidos pacientes se incluyeron para evaluación de eficacia bacteriológica, ocurriendo erradicación en 19 (86 por ciento) y persistencia en 3 (14 por ciento) siendo estos: K.pneumoniae, P.aeruginosa + E.cloacae y P.aeruginosa + S.coagulasa negativa, los cuales respondieron al agregar amikacina. El 88 por ciento de los gérmenes aislados fueron Gram negativos. Como efecto adverso se reportó dispepsia en un paciente. Cinco pacientes muerieron, dos de ellos relacionados con la infección y tres por otras causas. Los resultados permiten concluir que la combinación SBT/CPZ usada como monoterapia constituye una alternativa apropiada para el tratamiento de neumonía nosocomial

Role of atrial natriuretic factor, hemodynamic changes and renal nerves in the renal effects of intraperitoneal morphine in conscious rats.

The aim of the present study was to investigate the role of renal nerves and atrial natriuretic factor (ANF) in the mechanisms responsible for the diuresis and antinatriuresis induced by morphine in rats in a normal state of hydration. Male Wistar rats weighing 350-400 g were divided into two groups: one group was subjected to bilateral renal denervation, whereas the other consisted of sham-operated controls. The animals were placed in individual metabolic cages, and morphine (1.25, 2.5, 5.0 or 10.0 mg/kg body weight) or vehicle (0.5 ml isotonic saline) was injected intraperitoneally. Urine was collected hourly for 1 h before and 3 h after morphine injection. The lower doses of morphine (1.25 and 2.5 mg/kg body weight) induced a transient increase in urine output (from 1.17+/-0.12 to 2.49+/-0.34 and from 0.78+/-0.08 to 1.71+/-0.18 microl/min, respectively). The diuretic response to these doses was similar in bilaterally denervated rats. Higher doses (5.0 and 10.0 mg/kg body weight) induced a marked but transient reduction in the urinary flow rate during the first hour (from 0.90+/-0.11 to 0.48+/-0.05 and from 1.37+/-0.17 to 0.45+/-0.08 microl/min, respectively), followed by a delayed diuretic effect. The antidiuretic action of morphine was not observed in bilaterally denervated rats. In control rats, morphine induced a dose-dependent decrease in sodium excretion 1 h after administration, an effect that was blunted in the denervated group. The lower morphine doses (1.25 and 2.5 mg/kg body weight) elicited a transient increase in the glomerular filtration rate (GFR) in both control (from 1.23+/-0.12 to 1.67+/-0.17 and from 1.28+/-0.14 to 2.41+/-0.18 ml/min) and bilaterally denervated rats (from 1.29+/-0.14 to 1.66+/-0.17 and from 1.18+/-0.22 to 1.72+/-0.19 ml/min), whereas the higher doses (5.0 and 10.0 mg/kg body weight) produced a marked, transient GFR decrease in the controls (from 1.25+/-0.11 to 0.43+/-0.05 and from 1.13+/-0.17 to 0.47+/-0.08 ml/min) and bilaterally denervated animals (from 1.48+/-0.16 to 0.74+/-0.09 and from 1.22+/-0.15 to 0.73+/-0.06 ml/min), although the reduction was less pronounced with renal denervation. Morphine induced a transient, dose-dependent reduction in blood pressure (from 114+/-1 to 71+/-6 mm Hg at 10.0 mg/kg body weight) and a dose-dependent elevation of plasma ANF. No differences in plasma ANF were observed between control and denervated animals under basal conditions (60+/-7 vs. 42+/-6 pg/ml) or after injection of 2.5 or 5.0 mg/kg of morphine (155+/-11 vs. 167+/-9 and 360+/-9 vs. 401+/-9 pg/ml, respectively). Our data suggest that the renal responses to intraperitoneal morphine administration derive from the integration of several different actions: (1) increased ANF release; (2) decreased arterial pressure; (3) subsequent activation of renal sympathetic activity, and (4) the direct effect of morphine on tubular function.

Renal effects of antihypertensive therapy in uninephrectomized diabetic rats.

Diabetic nephropathy is a major cause of chronic renal failure. The evidence available indicates that renal hemodynamics are altered in clinical and experimental diabetes mellitus. In these circumstances, an increased glomerular filtration rate (GFR) is associated with albuminuria and eventually with glomerulosclerosis. We studied the renal and hemodynamic effects of long-term treatment (5 months) using an angiotensin-converting enzyme inhibitor (trandolapril, 0.7 mg/g b.w. per day) and a calcium antagonist (verapamil, 20 mg/g b.w. per day), and the combination of the two (veratran) at the same dose, on streptozotocin-diabetic uninephrectomized rats. A moderate degree of hyperglycemia (2-4 g/l) was maintained with daily insulin. Mean arterial pressure (MAP) was measured monthly using the tail-cuff method. Determinations were made of urinary protein excretion, creatinine clearance, urinary electrolyte excretion and, at the end of treatment, renal and cardiac hypertrophy. MAP was similar in control and untreated diabetic rats. Trandolapril and veratran reduced MAP whereas verapamil alone had no effect on these animals. All groups showed a slight proteinuria that increased with verapamil treatment. The GFR of diabetic animals was higher than in the control group (mainly the first 2 months), except for veratran group, in which it was similar to the control value. Urinary electrolyte excretion increased in all diabetic groups with no significant differences among them. Veratran induced a protective effect against cardiac hypertrophy. None of the treatments affected renal hypertrophy. It is concluded that in a murine model of diabetes without hypertension or proteinuria, a combination of verapamil and trandolapril prevents hyperfiltration whereas verapamil alone increases proteinuria.

Tobacco smoke and age as risk factors in emphysema. Morphometrical study on the rat.

During ageing, a progressive deterioration in the pulmonary function, which can be accelerated by exposure to tobacco smoke, takes place. The hypothesis that the initial age of exposure to tobacco smoke is a factor of utmost importance in the development of emphysema is proposed. Eighty-six rats, aged nineteen months at the time of sacrifice, were used and were ordered into three groups: the first group consisted of unmanipulated animals; the second, of animals which had been exposed to tobacco smoke from the age of twelve months to the age of nineteen months; and the third, of animals which had been exposed to tobacco smoke from the age of nine months to the age of twelve months. The lungs of the animals were histologically processed for light microscopy and were studied morphometrically by computer. Eleven quantitative variables were quantified and ordered into three groups: variables related with alveolar enlargement; variables related with tissue loss; and variables related with the elastic fibre. The number of animals in which alveolar enlargement and tissue destruction concurred was counted, thus enabling the attributable and relative risks of developing emphysema to be calculated in the two groups of manipulated animals. From the results it is clear that, when compared with the unmanipulated group, the two groups which had been exposed to tobacco smoke displayed an increase in the variables which quantified alveolar enlargement and a decrease in those which measured tissue loss; these results were more significant in the third group (p < 0.001) than in the second (p < 0.05); significant differences were also found between these two groups of animals. The relative risk and attributable risks of developing emphysema were 2.41 and 28.15 respectively in the second group and 3.48 and 34.48 in the third group. Our results lead us to propose that the risk of developing emphysema exists in inverse proportion to the initial age of exposure to tobacco smoke.