Changes in peripheral hemodynamics and vasodilating prostaglandins after high-dose short-term ibuprofen in chronically treated hypertensive patients.

The use of cyclooxygenase inhibitors has been seen to reduce the efficacy of many antihypertensive drugs. However, cyclooxygenase inhibitors are normally non-selective because they affect both vascular tissue, where the endothelial prostanoids exert principally a vasodilatory action, and the kidneys, where they also play an important role in regulating hydroelectrolytic metabolism by redistribution of intraparenchymal flow. To evaluate the relative importance of vascular district in the hypertensive patient, we administered ibuprofen - a drug acting with only a minimal antagonist activity. A group of 20 male hypertensives were randomly allocated, according to a single-blind protocol, to treatment with amlodipine (A, 10 mg/day) or lisinopril (L, 20 mg/day). Blood pressure was significantly reduced after 30 days, with a mean difference of -21.75 mmHg for systolic blood pressure (SBP) (95% confidence interval (Cl): -27.46 to -16.04; P< 0.0001) and -14.15 mmHg for diastolic blood pressure (DBP) (95% Cl: -17.13 to -11.17; P< 0.0001). Brachial artery compliance showed a mean increase of 1.657 x 10(-7) dyn-1 cm(4) (95% Cl: 1.188 to 2.126; P<0.001), and forearm resistances showed a mean decrease of -41.973 mmHg ml(-1)s (95% Cl: -75.479 to -8.467; P = 0.017). Changes in compliance were significantly related to those in SBP (r= -0.546; P= 0.013). The administration of ibuprofen (400 mg, three times a day for 3 days) was accompanied by a slight but significant increase in SBP, but not in brachial artery compliance or forearm resistances. Only SBP was affected, showing a mean increase of 4.25 mmHg (95% Cl: 1.26 to 7.24; P = 0.008). There was also reduced urinary excretion of PGI(2) and TXA(2) metabolites. The mean change in 6-keto-PGF(1 alpha) and 2,3-dinor-6-keto-PGF(1 alpha) was 45.71 ng per g urinary creatinine (uCr) (95% Cl: -0.16 to-91.25; P= 0.049) and -73.17 ng (g uCr)(-1) (95% Cl: -38.81 to -107.53; P<0.001), respectively. The mean decrease in TXA(2) catabolites was highly significant: -39.2 ng (g uCr)(-1) (95% Cl: -18.17 to-60.22; P< 0.001) and -102.87 ng (g uCr)(-1) (95% Cl: -61.86 to -143.88; P< 0.001) for TXB(2) and 2,3-dinor-TXB(2), respectively. Our study highlighted an inverse correlation between changes in blood pressure and those in urinary 2,3-dinor-6-keto-PGF(1alpha) excretion, irrespective of antihypertensive regimen. This suggests that, in the hypertensive patient treated with NSAIDs, inhibition of vascular prostanoid synthesis may play an important role in countering the efficacy of an important vascular tone regulatory mechanism.

Early regression of left ventricular diastolic abnormalities in hypertensive patients treated with nifedipine.

The effects of nifedipine on blood pressure (BP), left ventricular hypertrophy, and diastolic function were evaluated in 14 patients with essential hypertension (EH). All males with a mean age of 44 +/- 6 years (range 35-58 years), and in ten normotensive subjects (control group) aged 32-42 years (mean age 36 +/- 4). A complete echocardiogram (ECHO) was performed in basal conditions after 1 and 6 months of therapy with nifedipine (20-40 mg/day). Left ventricular echocardiograms (LV ECHO, M-mode, two-dimensional guided) were plotted with a simultaneous ECG tracing by means of a computerized system that allows evaluation of the following parameters: LV end-diastolic and systolic diameters (EDD, ESD); variations in LV diameter and volume during the entire cardiac cycle, and the velocities of such variations; end-diastolic thicknesses of the interventricular septum and posterior wall (ST, PWT); LV mass, mass/volume (M/V) index, end-diastolic diameter/thickness (D/Th) index, and LV ejection fraction (EF). Left ventricular volume curves were obtained and the contributions of rapid filling (RF) and atrial systole (AS) to EDV were evaluated. Filling velocities during RF (vRF) and AS (vAS) were estimated, as well as the isovolumic relaxation period (IR). No significant changes were observed in the heart rate. After 1 month of therapy, systolic and diastolic BP were significantly decreased (p less than 0.05). ST and PWT were reduced, with a simultaneous increase in EDD and EDV (p less than 0.01). LV mass was slightly reduced, as was the M/V index. The D/Th index was increased (p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Haemodynamic parameters in hypertensive patients: changes induced by lacidipine and nifedipine.

We conducted a randomly allocated, double-blind study in 16 essential hypertensive patients, eight of whom were treated with nifedipine and eight with lacidipine. The antihypertensive efficacy was evaluated and any modifications to peripheral haemodynamic parameters were observed in the brachial artery by a mechanographic method and B-mode scanner with a 10-MHz probe. Statistically significant reductions in blood pressure from basal values were observed after 1 and 6 months' treatment. Enhanced compliance (P less than 0.005), reduced characteristic impedance (P less than 0.001) and lower peripheral resistances (P less than 0.01) were also noted. Variations in pulse wave velocity and mean blood pressure showed a statistically significant correlation as early as the first month of treatment (P less than 0.01). Our results suggest that therapy with nifedipine and lacidipine allows an improvement in peripheral haemodynamics in hypertensive patients. This response is maintained in chronic treatment, even just before the next dose administration at the end of the longest dose interval.

Regression of cardiac hypertrophy after antihypertensive therapy with nifedipine and captopril.

The effects of two antihypertensive agents, nifedipine (N) and captopril (C), on left ventricular (LV) mass and volume were studied in 16 patients with essential hypertension (8 treated with N and 8 with C for 6 months) by means of a complete M-mode echocardiogram monitored by two-dimensional echocardiography. Both N and C induced a significant reduction in end-diastolic, but not systolic, posterior wall and septum thickness and an increase in end-diastolic volume, but not in end-systolic volume. A significant increase in the contribution of rapid filling together with a simultaneous reduction in the contribution of atrial systole to end diastolic volume were also observed. The reduction in LV wall thickness and mass after both C and N might be attributed to an improvement in diastolic function and to a reduction in wall tension, rather than to an effective regression of LV hypertrophy.

Ceftazidime in patients with severe Pseudomonas infections.

Forty patients suffering from severe Pseudomonas infections (13 urinary tract infections, 8 of which complicated, 16 cases of pneumonia, 3 cases of sepsis, 1 case of sepsis with osteomyelitis, 2 cases of osteomyelitis, 1 case of ophthalmitis, and 4 cases of peritonitis) were treated with ceftazidime (1-6 g/die). Most cases presented with severe underlying conditions associated with, or predisposing to, infection (surgical intervention, neoplasia, immunodepression, etc.). Both microbiological results (38 out of 43 strains eradicated) and clinical outcome (28 infections cured, 10 improved, and only 2 unchanged) proved highly satisfactory. The authors advocate the empirical use of ceftazidime as first-line single-drug therapy in severe hospital acquired infections in high-risk patients.

Accidental poisoning with deadly nightshade berries: a case report.

A case of acute accidental poisoning with deadly nightshade (Atropa belladonna) berries is reported. The patient was an elderly but healthy man who soon recovered. On the one hand, the clinical picture looked similar to that of delirium tremens; on the other, there were myoclonic jerks and signs of extrapyramidal involvement to suggest the onset of subacute dementia. The electroencephalogram findings confirmed those already reported during experimentally induced intoxication after ingestion of atropine in man.

Anderson-Fabry's disease: neuropathological and neurochemical investigation.

A clinical, neuropathological and neurochemical study of a case of Anderson-Fabry's disease is described. The clinical course mainly consisted of repeated ictus with major involvement of the CNS. The neuropathological examination is dominated by severe alterations in the cerebral vessels due to glycolipid deposits on the walls, with reduction or occlusion of the lumen. This is correlated with secondary ischaemic foci scattered throughout the cortex as well as through the white matter. In addition, the cells of the cerebral cortex, thalamus, basal ganglia, amygdala, cerebellar and olivary nuclei show a marked accumulation of lipofuscin. Biochemical examination reveals a threefold increase in galactolipids due to the specific alpha-galactosidase deficiency. Cholesterol is reduced secondarily to ischaemic myelin damage. Glycosaminoglycans uronic acid is increased in cytosol and membrane-bound fractions which could be related to reactive gliosis. Glycoprotein sugars show a decrease in N-acetyl-neuraminic acid and fucose as well as an increase in hexosamines and hexoses in membrane-bound fraction, while in cytosol fraction all sugars are increased. This suggests that the alpha-galactosidase deficiency can alter not only the glycolipid but also the glycoprotein metabolism, resulting in a higher presence of hexosamines and hexoses-rich glycoproteins.

"Thalamic" dementia in herpes encephalitis: clinico-pathological report.

Herpes zoster (HZ) primary affections of the CNS are rare and, in most of the reported patients, are representing variously extended forms of ascending myelitis. Our examination concerns a man who at the age of 37 developed apathy after a feverish episode with iridocyclitis. Six months later an ophthalmic HZ was diagnosed and thenceforth the patient showed a dementia with Korsakow's syndrome, apathy and a right hemipalsy, and diplopia appeared; the later symptoms remitted after steroid therapy. Post-mortem examination revealed a slowly progressive encephalitis with symmetrical impairment of the anterior ventral, medial, and centrum medianum of the thalamus. The HZ origin of the lesions and the relation between their site and the peculiar form of dementia, to be ascribed to the "thalamic" ones, are discussed. A vasculitis process can be hypothesized considering both the symmetrical localisation and the microscopical aspects of the lesions.