Long-term survival in cerebellar glioblastoma multiforme. Case report.

Primary cerebellar glioblastoma multiforme (GBM) is a rare tumor in adults that accounts for just 1% of all cases of GBM. Cerebellar GBMs are not yet completely understood also as far as the prognosis. We report a case of cerebellar GBM in a 27-year-old woman. Magnetic resonance imaging (MRI) showed a 3x3.6 cm-sized, ill-defined, heterogeneously enhancing mass in the left cerebellum. GBM was histologically confirmed following radical surgery. Postoperative radiotherapy with concomitant and adjuvant temozolomide chemotherapy was subsequently administrated. She has no evidence of recurrence and is in good clinical conditions up-to date, three years after surgery.

Erythrocyte sodium-lithium countertransport in non-modulating offspring and essential hypertensive individuals: response to enalapril.

Non-modulators are a subset of essential hypertensive individuals in whom renal hemodynamic and adrenal aldosterone responses to angiotensin II fail to modulate appropriately during high dietary salt intake. The main aim of this study was to investigate the familial aggregation of non-modulation and several erythrocyte Na+ transport systems in normotensive and hypertensive individuals as well as offspring of hypertensive parents. An additional aim was to evaluate the effect of treatment with enalapril on erythrocyte Na+ transport. We studied 15 normotensive subjects (6 males, 27+/-6 years), 14 untreated modulating essential hypertensive subjects (7 males, 38+/-7 years), 12 untreated non-modulating essential hypertensive subjects (7 males, 38+/-6 years), 14 modulating offspring of hypertensive parents (8 males, 25+/-6 years), and 14 non-modulating offspring of hypertensive parents (8 males, 26+/-4 years). Blood pressure was recorded with an oscillometric device and renal plasma flow and glomerular filtration rate by clearances of para-aminohippurate and inulin, respectively. Non-modulating subjects were identified as individuals who failed to increase effective renal plasma flow by 30% and decrease filtration fraction by at least 30% 10 days after changing from a low (20 mmol/d) to a high (250 mmol/d) sodium intake. Erythrocyte Na+ transport was characterized by measurements of the Na+-K+ pump, Na+-Li+ countertransport, Na+-K+-Cl- cotransport, passive Na+ permeability, and Na+ content. After the initial studies, hypertensive individuals were treated with enalapril (20 mg/d P.O.) for 6 months, after which erythrocyte Na+ transport measurements were again made. The main findings were that Na+-Li+ countertransport is increased in non-modulating hypertensive subjects and non-modulating offspring of hypertensive parents, that the increase in blood pressure in response to high salt intake is greater in non-modulating than modulating hypertensive subjects, and that enalapril decreases Na+-Li+ countertransport activity to normal in non-modulating hypertensive subjects. These findings provide support for a possible genetic role in the development of salt sensitivity and suggest that Na+-Li+ countertransport and non-modulation are related phenotypes.

Recovery of erythrocyte Na(+)-K(+)-Cl- cotransport activity by enalapril.

We studied total exchangeable sodium, ion transport activity at maximal rate, and erythrocyte Na+ content in response to angiotensin converting enzyme inhibition in mild-to-moderate essential hypertensive patients with normal renal function. Twenty-five patients (mean age 56 years, range 40-62 years) who had abnormal red blood cell Na(+)-K(+)-Cl- cotransport or red blood cell Li(+)-Na+ countertransport were treated with either enalapril (20 mg daily) or hydrochlorothiazide (50 mg daily) during a 30-day period. During the period of enalapril treatment, Na(+)-K+ pump and Na(+)-K(+)-Cl- cotransport increased significantly from 4,282 +/- 255 to 5,236 +/- 325 mumol/l red blood cell/hr (p less than 0.01) and 166 +/- 21 to 220 +/- 24 mumol/l red blood cell/hr (p less than 0.05), respectively. Mean intracellular Na+ content in erythrocytes decreased from 11.4 +/- 0.40 to 10.0 +/- 0.33 mmol/l (p less than 0.01) and exchangeable Na+ from 39.8 +/- 0.6 mmol/kg to 35.6 +/- 0.6 mmol/kg (p less than 0.001). Sodium reduction correlated with the recovery of Na(+)-K(+)-Cl- cotransport activity (r = -0.65, p less than 0.01). During treatment, systolic and diastolic blood pressures were reduced significantly (p less than 0.01). In 12 patients treated with hydrochlorothiazide, Na(+)-K(+)-Cl- cotransport, Na(+)-K+ pump, Na(+)-Li+ countertransport, and Na+ permeability did not change significantly while Na+ content decreased from 11.7 +/- 0.3 to 10.3 +/- 0.2 mmol/l (p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Long-term evaluation of cilazapril in severe hypertension. Assessment of left ventricular and renal function.

The effect of cilazapril as monotherapy or in combination with hydrochlorothiazide was assessed in 30 severely hypertensive patients, 23 men and seven women, aged 38 to 68 years, with sitting diastolic blood pressure of more than 115 mmHg. Fifteen patients had left ventricular hypertrophy documented by two-dimensional echo-cardiography. Sitting systolic blood pressure was reduced from 175.8 +/- 2.0 to 143.3 +/- 3.0 mmHg within 25 days of therapy (p less than 0.0001); sitting diastolic blood pressure decreased in the same period from 117.0 +/- 1.0 to 87.8 +/- 2.0 mmHg (p less than 0.0001), whereas heart rate remained unchanged. In 19 patients treated for an average of 48 weeks the therapeutic response was maintained during the long-term period. The mean effective dose was cilazapril 10 mg plus hydrochlorothiazide 12.5 to 25 mg in 90 percent of the patients. Left ventricular mass decreased from 357 +/- 17 to 314 +/- 22 g (nine patients; p less than 0.005) and a correlation (Spearman r = 0.57, p less than 0.01) was found between left ventricular mass and sitting systolic blood pressure before and during treatment. Deceleration half time of peak early diastolic inflow velocity decreased significantly from 128 +/- 9 to 108 +/- 7 msec (p less than 0.05). Glomerular filtration rate and renal blood flow remained within normal limits, whereas renal vascular resistance decreased from 0.16 +/- 0.0 to 0.10 +/- 0.0 resistance units (10 patients; p less than 0.01). Cilazapril in combination with hydrochlorothiazide was effective in the treatment of severe hypertension. Left ventricular hypertrophy regression influenced favorably left ventricular diastolic function in some patients, whereas renal hemodynamics were generally not affected by the therapy.

Plasma renin activity levels influence the effect of converting enzyme inhibitors in preserving renal function in hypertension.

OBJECTIVE: To study the effect of treatment with cilazapril versus nifedipine on the glomerular filtration rate (GFR), microalbumin excretion rate (mu Alb) and baseline plasma renin activity (PRA) levels in non-diabetic or diabetic essential hypertension. DESIGN AND METHODS: Thirty-four moderate essential hypertensives and thirty-two type II diabetic hypertensives with currently normal renal function completed the study, receiving treatment with a converting enzyme inhibitor (CEI, 5-10 mg/day cilazapril) or a non-CEI (20-40 mg slow-release nifedipine three times a day) during a 12-month controlled follow-up study. RESULTS: Either treatment induced a similar reduction in blood pressure. Patients with PRA > 3 ng/ml per h treated with cilazapril showed a proportional increase in GFR, whereas in those treated with a non-CEI there was a decline in GFR after 8 and 12 months. Only diabetic patients treated with cilazapril showed a mu Alb reduction associated with a stable GFR. CONCLUSION: PRA predicts the effect of CEI preserving renal function in essential and diabetic hypertension.

Higher urinary albumin excretion is associated with abnormal erythrocyte Na(+)/Li(+) countertransport (SLC) in non-modulating essential hypertensives and offspring of hypertensive parents.

Non-modulating is a highly reproducible type of sodium-sensitive hypertension. The aim of this study was to evaluate in non-modulating individuals the erythrocyte sodium-lithium countertransport (SLC) abnormalities, which have been mentioned as a marker of non-modulation, and the association with increased microalbuminuria, as a marker of an early kidney impairment. We measured erythrocyte SLC in 10 normotensives (NT, 28 +/- 4 years), 20 offspring of hypertensive parents being 10 modulating (MHO, 25 +/- 6 years) and 10 non-modulating (NMHO, 26 +/- 5 years), and 23 essential hypertensives being 12 modulating (MHT, 34 +/- 5 years) and 11 non-modulating (NMHT, 32 +/- 4 years). In all the subjects studied, microalbuminuria was determined by duplicate 24-h urine collection by radioimmunoassay. In non-modulating offspring of hypertensive parents and essential hypertensives. SLC was significantly elevated when compared either with normotensives without family history of hypertension, modulating offspring of hypertensive parents or essential hypertensives (P < 0.025). Likewise, 24-h urinary albumin excretion was found higher in non-modulating individuals (essential hypertensives and offspring of hypertensive parents) than in modulating individuals (P < 0.01). In conclusion, non-modulators with higher SLC countertransport sodium transport abnormalities showed higher elimination of microalbuminuria suggesting that non-modulators may have an increased risk for developing cardiovascular morbidity and kidney impairment even in normotensive subjects with familiarity history of hypertension.

[National study of lipids in coronary patients]. / Estudio nacional de lípidos en coronarios.

Although coronary atherosclerosis is considered to have several etiologic factors there is little doubt that elevated plasmatic cholesterol level is the main one. The present study was carried out because of the lack of information concerning cholesterol, lipoproteins and triglycerides levels in the coronary population in Argentina. Patients were selected on the basis of a demonstrated coronary atherosclerosis, detected either by an abnormal coronary arteriogram or a documented myocardial infarction. Total seric cholesterol (TC), low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C) and triglycerides (TG) were determined in a core laboratory. Blood samples were obtained after a 12 hour fasting period. LDL-C was also calculated by the Friedewald formula. Patients were stratified according to sex, age, having or not myocardial infarction, type (Q or non Q wave) and localization of myocardial infarction. A total of 653 patients were included. The mean values obtained were: TC 227 +/- 1.8 mg/dL; LDL-C 153 +/- 1.8 mg/dL; HDL-C 48 +/- 0.4 mg/dL and TG 180 +/- 3.6 mg/dL (expressed as mean +/- SE). Mean values in the male and female subsets are given in Table 1. In women, TC, LDL-C and HDL-C are significantly higher than in men. Cholesterol values according to age are displayed in Table 3. Young people have higher TC and LDL-C mean values than older ones. Different cholesterol levels were not observed when the coronary population in our study was stratified according to the presence or not of previous myocardial infarction (Table 4).(ABSTRACT TRUNCATED AT 250 WORDS)

[Analysis of antihypertensive effectiveness by means of ambulatory blood pressure monitoring. Usefulness of the Discrete Fourier Transform Model]. / Análisis de la efectividad antihipertensiva mediante el monitoreo ambulatorio de presión arterial. Utilidad del modelo de Transformada de Fourier Discreta.

In order to assess the usefulness of the Discrete Fourier Transform Model (DFT) to evaluate time-course drug effects on hypertensive patients studied with Ambulatory Blood Pressure Monitoring (ABPM) a number of experiments were carried out. A total of 10 mild to moderate hypertensive patients were evaluated under placebo and after 8 weeks of active treatment with Enalapril 20 mg per day using ABPM. Systolic and Diastolic blood pressure (SBP and DBP) were registered every 15 minutes during daytime and every 30 minutes at night. Pressure profiles of each patient were initially smoothed by hourly means. DFT was then applied to these profiles. The minimum number of harmonics necessary to generate a statistically significant fitting of the blood pressure profile, were obtained by residuals analysis (run test and analysis of variance of the mean sum of residual squares with each new harmonic incorporated to the model). A profile of the blood pressure differences (treatment-placebo) with the rough data of each patient was smoothed by hourly means. DFT was applied again on these substraction profiles. To estimate peak and trough drug effects for the blood pressure decrease function, maximum, minimum and inflexion points were calculated defining the following parameters: T peak: time from drug administration to maximum pressure decrease; T late response: time from drug administration to the inflexion point following the last minimum previous to the next dose; BP peak: the maximum blood pressure decrease amplitude; and the slope BP peak/T peak. The stability of the individual circadian rhythm was confirmed for both ABPM controls comparing times of maximum and minimum on the DFT smoothed profiles.(ABSTRACT TRUNCATED AT 250 WORDS)

[Automated ambulatory 24-hour monitoring of blood pressure in hypertensive patients]. / Monitoreo ambulatorio automático de la presión arterial de 24 horas (maapa) en hipertensos.

In order to analyse the 24 h blood pressure pattern, a non-invasive 24 h ABPM was recorded in 18 normotensives (23-44 years) and in 24 untreated essential hypertensives (28-65 years) using a Space-Labs 90202. This device was previously validated with a mercury sphigmomanometer (S) and with intraarterial blood pressure (IA). The correlation coefficient obtained for systolic blood pressure (SBP) between ABPM and IA was 0.89, p less than 0.0001 and between ABPM and S was 0.98, p less than 0.0001. Likewise, a significative correlation for diastolic blood pressure (DBP) was found between ABPM and IA (r = 0.78, p less than 0.0001) and between ABPM and S (r = 0.97, p less than 0.0001). Essential hypertensives showed higher mean values of SBP and DBP than normotensives (p less than 0.01) maintaining a similar circadian pattern. In these patients, the percentages of mean abnormal SBP (greater than 140 mmHg) and DBP (greater than 90 mmHg) readings were greater than 58% and 56% for the 24 h period, and 70% and 77% for the activity period, respectively. On the other hand, in normotensives the percentages of mean abnormal SBP and DBP readings were lower than 10.5% and 5.7% for the 24 h period, and 17.2% and 11.7% during the activity period, respectively. In conclusion, 24 h ABPM enabled us to characterize two well differentiated populations either by mean BP values of the percentages of abnormal readings. Between normotensives and hypertensives an intermediate group of subjects, with normal mean BP values and higher percentages of abnormal BP readings than normotensives remains to be characterized and longitudinally studied in order to evaluate their target organ repercussion.

Gas chromatographic determination of avilamycin total residues in pig tissues, fat, blood, feces, and urine.

A gas chromatographic (GC) procedure is presented for the determination of residues of avilamycin and all its metabolites/conjugates which can be converted to the common moiety dichloroisoeverninic acid (DIA). The method involves alkaline hydrolysis to DIA, cleanup by partitioning with chloroform, acidification of the aqueous phase, and partitioning of DIA into methylene chloride. After methylation of DIA, the product, 3,5-dichloro-4,6-dimethoxy-2-methylbenzoic acid methyl ester, is cleaned up on a silica gel column prior to the final determination by electron capture GC. The method is sensitive to 0.1 mg/kg avilamycin equivalent. Overall average recoveries were 85.4%, with a standard deviation of 9.1% for n = 20. Analyses of feces, urine, tissues, and fat of pigs treated with avilamycin demonstrated that 93% of the administered substance is excreted in feces and urine, within 72 h after treatment, and that no residues (less than 0.01 mg/kg) can be found in the tissues and fat of the animals at any time between 0 and 7 days after treatment with medicated feed.

Effect of cilazapril in hypertensive patients with renal impairment.

The aim of the study was to evaluate the clinical and renal hemodynamic effects of cilazapril in 10 hypertensive patients with moderate-to-severe chronic renal failure (creatinine clearance 14-50 ml/min). After 2 weeks of placebo, cilazapril 0.5 mg/day was given, and the dose was increased up to 5 mg/day if sitting diastolic blood pressure (SDBP) was not normalized (less than or equal to 90 mm Hg). Once a normal SDBP value was achieved, the patients remained on the given dose regimen for 6 months. After this period SDBP decreased from 107 +/- 2 to 95 +/- 2 mm Hg (p less than 0.001). At the end of treatment, glomerular filtration rate (GFR) remained unchanged in five patients, improved in four patients, and slightly decreased in one patient, the slope from baseline being 0.137 and the variation of GFR per unit of GFR at baseline being between -0.20 and 0.47. Likewise, effective renal plasma flow increased not significantly, showing considerable variability. Urinary protein excretion was reduced significantly from 2.51 +/- 0.75 to 0.51 +/- 0.10 g/L (p less than 0.05), suggesting that converting enzyme inhibition may exert a renal protective effect. In conclusion, it appears that cilazapril does not induce functional damage in the kidney of predialysis hypertensives.

Antihypertensive, enzymatic, and hormonal activity of cilazapril, a new angiotensin-converting enzyme inhibitor in patients with mild to moderate essential hypertension.

The antihypertensive activity of cilazapril, a new nonsulfhydryl angiotensin-converting enzyme (ACE) inhibitor was evaluated in 20 outpatients (13 women, 7 men; mean age, 49 +/- 2.4 years) with mild to moderate essential hypertension, by means of an open dose-finding study of 10 weeks' duration. Cilazapril, 0.5 mg/day, was given, and the dose increased up to 10 mg/day if sitting diastolic blood pressure (SDBP) was not normalized (less than or equal to 90 mm Hg). Blood pressure measurements were carried out every 2 weeks before and 2 h after dosing. Predose and 2-h postdose measurements of plasma renin activity (PRA), angiotensin II (AII), plasma aldosterone (PA), and enzyme converting activity (ECA) were performed on the 1st day of active treatment and after 2 weeks of therapy. The SDBP decreased from 107.6 +/- 2 to 97.2 +/- 3 mm Hg 2 h after the initial dose (p less than 0.01). At the same time, ECA was inhibited 84.2 +/- 5% (p less than 0.01), AII decreased from 21.2 +/- 3 to 13.6 +/- 2 pg/ml (p less than 0.05), and PA from 208 +/- 29 to 119 +/- 14 pg/ml (p less than 0.01). After 2 weeks of therapy, ECA remained markedly reduced, by 68 +/- 6%, 24 h after the preceding cilazapril dose (p less than 0.01). The mean SDBP decreased from baseline to the end of treatment by 14.6 +/- 3 mm Hg (p less than 0.01). Cilazapril seems to be an effective antihypertensive drug which exerts potent and long-lasting ACE inhibition.

[Neoadjuvant chemotherapy of infiltrating carcinoma of the bladder: our experience]. / Chemioterapia neoadiuvante nel carcinoma vescicale infiltrante: nostra esperienza.

From January 1987 until October 1989, 96 patients have been treated with radical cystectomy for locally advanced bladder cancer. Nineteen, out of 96 underwent chemotherapy (either M-VAC or M-VEC) before cystectomy. Five had T1G3 bladder tumor. After chemotherapy the results had been the following: 5 complete responses (CR) 26%, 7 partial responses (PR) (37%) and no changes in 7 patients (37%). During the first two courses of chemotherapy, 36 administrations out of 152 scheduled should have not been done because of drug toxicity. The seven patients who had no changes had a drug administration reduced of 41% with respect of a rate of reduction of 12% in the group of patients who had complete response. The urinary diversion after cystectomy were performed with a neobladder according to Reddy in 4 patients, with a colon conduit in 1 patient and with an ileal conduit in 12 patients. All the patients survived the surgery. We did not notice any difference in the follow up after surgery in those patients treated before cystectomy with chemotherapy with respect to the patients who underwent cystectomy without chemotherapy. Despite the fact that by now we can not state any conclusion about the efficacy of neoadiuvant chemotherapy, due both to the short follow up and to the small number of patients treated, we should however perform cystectomy in all the patients after chemotherapy because up to now we have no evidence that a conservative treatment of the bladder after chemotherapy could be safe.

[Toxoplasmic infection-disease in suspected cases and healthy subjects]. / La infezione-malattia toxoplasmica in soggetti sospetti e clinicamente sani.

A short epidemiological presentation of the toxoplasmic infectious disease in our country on suspected cases compared with a clinically healthy group shows the importance of the phenomenon, especially for its various preventative and therapeutic implications.

Analisis de la efectividad antihipertensiva mediante el monitoreo ambulatorio de presion arterial. Utilidad del modelo de Transformada de Fourier Discreta / Analysis of antihypertensive effectiveness by means of ambulatory blood pressure monitoring. Usefulness of the discrete fourier transform model

Se estudiaron 10 pacientes con hipertensión arterial a moderada a quienes se efectuó un monitoreo ambulatorio (MAPA) luego de 30 dias de placebo, y otro al cabo de ocho semanas de tratamiento con una dosis fija de 20 mg de maleato de enalapril. La presión arterial sistólica (PAS) y diastólica (PAD) se registró cada 15 minutos de 07 a 22 hs, y cada 30 minutos de 22 a 07 hs. Los perfiles presores y los perfiles de las diferencias presoras droga-placebo individuales, fueron alisados por los promedios horarios. Luego se aplicó la Transformada de Fourier Discreta (TFD). Se determinó el menor número de armónicas que generan un ajuste estadisticamente significativo por análisis de residuos. En las curvas de diferencias presoras alisadas por TFD, se calcularon máximos, mínimos y puntos de inflexión para determinar: el tiempo de respuesta rápida (intervalo entre toma de la droga y máximo efecto), el tiempo de duración del efecto de la droga (intervalo entre toma de medicación y punto de inflexión, siguiente al último mínimo previo a una nueva dosis) y la pendidente de descenso rápido (cociente entre máximo descenso presor y tiempo de respusta rápida). Dependiendo del paciente, 3 a 5 armónicas en las curvas alisadas por TFD de PAS, PAD y de las diferencias droga-placebo, son suficientes para ajustar los promedios presores horarios. Se confirmó la estabilidad del ritmo circadiano en ambos monitoreos. El efectos se presentó a las 3 hrs (rango: 2 a 5) de toma de dosis; y la duración máxima media del efecto de la medicación fue de 17,6 hs para la PAS y de 18,5 hs para la PAD. Se concluye que las diferencias presoras tratamiento-placebo obtenidas a partir del MAPA y analizadas según el modelo de RFD permiten evaluar los intervalos de tiempo de protección presora asociados a un tratamiento antihipertensivo

Monitoreo ambulatorio automatico de la presion arterial de 24 horas (MAAPA) en hipertensos / Automated ambulatory 24 h monitoring of blood pressure in hypertensive patients

El Maapa es consideraod un método más representativo que la medición casual de la presión arterial (PA) para evaluar el efecto que esta ejerce sobre los órganos blanco. El método Maapa (Space Labs 90202) fue previamente validado con mediciones simultáneas mediante el esfigmomanómetro de mercurio (E) o un catéter intraarterial en arteria radial (IA) en reposo. El coeficiente de correlación para la PA sistólica (PAS) entre Maapa e IA fue de 0,89 (p < 0,0001) y para la diastólica (PAD) de 0,78 (p < 0,0001) y entre Maapa y E fue de 0,98 para la PAS y de 0,97 para la PAD (p < 0,0001). Con el objeto de evaluar el comportamiento de la PA durante las 24 h en actividad habitual, se estudiaron 18 individuos normotensos sin antecedentes familiares de hipertensión arterial (23-44 años) y 24 hipertensos esenciales sin tratamiento (28-65 años). En los hipertensos, el promedio de PAS en 24 h fue de 148,3 ñ 15 y de l54 ñ 12 mmHg en el período de actividad, el porcentaje de valores (límite de confiabilidad al 95%) de PAS por sobre 140 mmHg fue durante las 24 h del 58-73% y entre la 06-21 h del 79-90%, mientras que el promedio de PAD en 24 h 95,8 ñ 13 y en el período de actividad fue de 102,2 ñ 10 mmHg, el porcentaje de los valores de PAD por encima de 90 mmHg fueron en las 24 h de 56-70% y entre las 06-21 h de 77-91%. En los normotensos, el promedio de la PAS en 24 h fue de 120,6 ñ 11 y de 127,5 ñ 7 mmHg de 6 a 21 h, las lecturas de la PAS sobre 140 mmHg fueron de 0-10,5% y 0-17,2%. El promedio de...