Osmotic fragility of erythrocytes, cell deformability and secondary hyperparathyroidism in uremic patients on maintenance hemodialysis.

The possible relationship between erythrocyte (RBC) function and secondary hyperparathyroidism (HPT) was examined in 35 uremic patients on maintenance hemodialysis. Mechanical tests (i.e., osmotic fragility and deformability) were used to assess RBC function. Secondary HPT was evaluated by means of serum biochemistry (parathyroid hormone, calcium, phosphorus, and alkaline phosphatase) and radiographic examinations (X-ray films of the hand skeleton). Sixteen sex and age-matched normal volunteers acted as controls. This study shows that the mechanical properties of RBC were indeed markedly altered in hemodialysis patients when compared with controls. No significant correlations between either the osmotic fragility or the deformability of RBC and the hematochemical changes associated with secondary HPT were found. No differences in RBC function tests were found as far as the activity (alkaline phosphatase) or the severity (X-ray findings) of secondary HPT are concerned. Effective treatment of secondary HPT by either pharmacological means (1,25-dihydroxycholecalciferol) or surgical removal was not associated with consequent improvement in RBC function. These findings clearly speak against secondary HPT as a major cause of RBC dysfunction in uremic patients on maintenance hemodialysis.

Hemodialysis-associated platelet loss: study of the relative contribution of dialyzer membrane composition and geometry.

To evaluate the relative contribution that dialyzer membrane composition and geometry make to hemodialysis-associated platelet loss, the effect of a single dialysis with three different types of dialyzers on platelet count was examined on a cross-over basis in 19 uremic patients on maintenance hemodialysis. Also, the plasma levels of antithrombin-iii before and after dialysis were measured, but no significant variations were found regardless of which dialyzer was in use. Our patients suffered significant platelet loss during cuprophan dialysis, but not polyacrylonitrile dialysis. More than 99% of initial circulating platelets were recovered at the end of polyacrylonitrile dialysis, whereas cuprophan dialysis did leave a significantly lower percentage of circulating platelets (p less than 0.05). The internal comparison of results obtained with the two cuprophan dialyzers used shows no difference as to the dialyzer geometry (flat plate or hollow fiber). This indicates that the membrane composition is the major factor influencing hemodialysis-associated platelet loss. We suggest that patients with low platelet count and/or with risk of bleeding may benefit from polyacrylonitrile dialysis.

[Preliminary clinical and experimental data on a new anti-arrhythmic drug: lorcainide]. / Primi rilievi clinici e sperimentali su un nuovo antiaritmico: la lorcainide.

A first series of personal results in the treatment of arrhythmia with lorcainide is presented. Findings were obtained by recording for 24 hr with Holter and compared with those observed in patients treated with quinidine. An ECG study was also made of the atrial and nodal refractory periods. The conclusion is drawn that lorcainaide possesses an undoubted and protracted anti-arrhythmic effect, and does not exert a significant influence on refractory period values.

[Evaluation of the safety and efficacy of the lisinopril + hydrochlorothiazide and captopril + hydrochlorothiazide combinations in the treatment of essential arterial hypertension]. / Valutazione della sicurezza e dell'efficacia delle associazioni lisinopril + idroclorotiazide e captopril + idroclorotiazide nel trattamento dell'ipertensione arteriosa essenziale.

The aim of this study was to assess the efficacy and tolerability of the combinations of lisinopril (LIS) 20 mg + hydrochlorothiazide (HCTZ) 12.5 mg and captopril (CAP) 50 mg + HCTZ 25 mg in moderately hypertensive patients not adequately controlled by LIS or CAP alone. The study was multicentre (11 centres), open, random and carried out in parallel groups. After two weeks' placebo run in patients were randomly assigned to LIS 10-20 mg/o.d. or CAP 25-50 mg/b.i.d. treatment for 6 weeks. After this, patients with supine diastolic blood pressure (SDBP) greater than 90 mmHg were treated with the combinations LIS 20 mg + HCTZ 12.5 mg/o.d. or CAP 50 mg + HCTZ 25 mg/o.d. for 4 weeks; this dose was doubled if DBP was found to be greater than 90 mmHg after 2 weeks' combined therapy. A total of 175 patients were enrolled (92 females and 83 males) of which 153 completed the study. The LIS + HCTZ association caused a significant reduction of DBP in comparison to the other combined treatment (88.1 +/- 0.7 vs 90.3 +/- 0.7; p = 0.026). The statistical analysis of mean SBP values showed no significant difference between the two groups (144.0 +/- 1.3 vs 146.8 +/- 1.3; p = 0.15). At the end of the study 79.5% of patients treated with LIS + HCTZ presented normal results (DBP less than or equal to 90 mmHg), whereas the percentage of similar results in the comparison group was 72%. The percentage of "responder" patients to therapy (DBP reduced by 10 mmHg or more in relation to basal values) was 96.3% in the LIS + HCTZ group and 86.7% in the CAP + HCTZ group. In the CAP + HCTZ group 0.6% of patients reported adverse reactions, while only 0.3% were observed in the LIS + HCTZ group.

[Capillaroscopy and diabetic microangiopathies]. / Capillaroscopie et microangiopathie diabétique.

Using conjunctival capillaroscopy, the authors studied 40 diabetic patients during glycemic decompensation. The capillaroscopic test, after all metabolic control tests, was repeated 1 and 3 months later and demonstrated improved microcirculation in 10 patients, and proved that therapeutic control is possible during the progression of diabetic microangiopathy.

[Autoimmune neuropathy in monoclonal gammopathy]. / Neuropatie disimmuni in corso di gammopatie monoclonali.

The relationship between polyneuropathies and monoclonal gammopathies is well known even though the pathogenetic hypotheses are controversial. The role of autoantibodies against neural antigens has been recently underlined. 45 patients (29 M and 16 F), affected by multiple myeloma (MM) non-Hodgkin lymphoma (NHL) with paraproteinemia and monoclonal gammopathies of undetermined significance (MGUS)4, underwent an EMG study including SCV, MCV and late responses of several nerves, and a search for serum antibodies against neural antigens by immunoblotting assay. 19 out of 45 pts. tested positive to EMG and 15 out of 45 (10 MM and 5 NHL) showed a serological positivity. Among them 11 were positive to EMG too. The results confirm the hypothesis of a possible pathogenetic role of high-titer autoantibodies against neural antigens in cases of polyneuropathy.

[Subclinical neuropathies and paraproteinemias]. / Neuropatie subcliniche e paraproteinemie.

The relationship between monoclonal gammapathies and peripheral nerve involvement is well known. The pathogenesis of neuropathy has been ascribed to infiltrative, compressive, ischemic or haemorrhagic phenomena, to an amyloid storage or to antibody autoaggression toward neural antigens. Forty-five patients suffering from monoclonal gammapathy of uncertain significance (MGUS), multiple myeloma (MM), MG IgM, were submitted to a neurophysiological examination. 10 pts. were excluded because of neurotoxic drugs, diabetes or alcohol abuse. The investigation included SCV of median, ulnar, and sural n., MCV and F wave of peroneal n., H reflex, and computerized analysis of recruitment pattern. A subclinical neuropathy was found in 11 of 35 pts. (30%) without any neurological symptom. A CTS was found in 4 patients. The high rate of subclinical neuropathy in asymptomatic pts. is underlined by the Authors, while the presence of subclinical neuropathy in cases of MGUS needs further studies.

[Importance of digitalemia for a correct therapeutic attitude using cardioactive glycosides]. / Importanza della digitalemia per una corretta impostazione terapeutica con i glucosidi cardioattivi

Recent advances in the quantitation of plasma or serum levels of cardiac glycosides promise to add a new dimension to pharmacologic studies and to the evaluation of clinical problems involving these drugs. A rapid radioimmunoassay technique has been described for the determination of serum digoxin and beta-metyldigoxin concentration in the range encountered clinically. Patients judged clinically to show digitals toxicity in general had higher levels. A relable estimate of serum digoxin and beta-metyldigoxin concentration, considered in the clinical context, has been found to be useful in arriving at acute management decisions.

[The blood rheological and microcirculatory changes in the hypertensive patient]. / Modificazioni emoreologiche e microcircolatorie nell'iperteso.

The authors examined the microcirculatory system alterations which are present in case of arterial hypertension. These alterations consist of an increase in capillary peripheral resistances and in total blood viscosity, of a reduction in red cell deformability and of a vasomotion alteration. The authors evaluated the opportunities of a therapeutic intervention with hypotensive treatments also affecting the microcirculatory system in hypertensive patients with or without associated diabetes mellitus.

[Blood filterability in cerebral vascular disease]. / La filtrabilita' ematica nelle vasculopatie cerebrali.

The aim of this paper is to test whether an alteration of blood flow in microcirculation and in particular of red cell deformability is present in cerebrovascular insufficiency. To this end we determined by the method proposed by Reid and Dormandy (J. Clin. Pharmacol. 1976, 29, 855) whole-blood filterability in 31 patients with cerebrovascular disease, in 15 clinically healthy subjects and in 99 subjects without clinical evidence of ischemic pathology displaying one or more vascular risk factors. Blood filterability turned out to be significantly lower in cases of cerebrovascular disease than in the controls (p less than 0,001), while data about presence of risk factors in cerebrovascular insufficiency and in controls are almost overlapping. Reduction of blood filterability in cerebrovascular disease may therefore be attributed directly to the risk factors associated to the disease, which can significantly reduce red cell deformability. Further we didn't find any significant correlation between blood filterability and levels of fibrinogen, platelets, triglycerides and cholesterol in blood.

[Blood filterability in peripheral obstructive arterial disease]. / La filtrabilita' ematica nelle arteriopatie ostruttive periferiche.

The aim of this paper is to test whether an alteration of blood flow in microcirculation and in particular of red cell deformability is present in chronic arterial occlusive disease. To this end we determined by the method proposed by Reid and Dormandy (J. Clin. Pharmacol. 1976, 29, 855) whole-blood filterability in 18 patients with peripheral vascular disease, in 15 clinically healthy subjects and in 99 subjects without clinical evidence of ischemic pathology displaying one or more vascular risk factors. Blood filterability turned out to be significantly lower in cases of arterial disease that in the controls (p less than 0,001), and we found a constant reduction of blood filterability with the increase of number of risk factors. Comparison of the results obtained in arteriopatics and in controls displaying risk factors shows that though risk factors have an important impact on blood filterability, their presence alone is not enough to explain the reduction of blood filterability which, risk factors being equal, in vascular disease is always significantly lower than in controls. We also found a significant correlation between levels of fibrinogen and reduction of blood filterability.

[Blood filterability in ischemic heart disease]. / La filtrabilita' ematica nella cardiopatia ischemica.

The aim of this paper is to test whether an alteration of blood flow in microcirculation and in particular of red cell deformability is present in myocardial ischaemia. To this end we determined by the method proposed by Reid and Dormandy (J. Clin. Pharmacol. 1976, 29, 855) whole-blood filterability in 23 patients with myocardial ischaemia, in 15 clinically healthy subjects and in 99 subjects without clinical evidence of ischemic pathology displaying one or more vascular risk factors. Blood filterability turned out to be significantly lower in cases of coronary diseases than in controls (p less than 0,001), while it was lower but not significantly so, than in subjects displaying risk factors. We conclude therefore that the presence of risk factors is enough important to be considered one of the fundamental elements (though non the only one) in causing the reduction of blood-filterability encountered in ischemic cardiopathology.

[Changes in blood filterability induced by risk factors for cardiovascular disease]. / Modificazioni della filtrabilita' ematica indotte dai fattori di rischio per cardiovasculopatie.

Our research was aimed at testing the role of the main cardiovascular risk factors in modifying the blood flow in microcirculation and in particular red cell deformability. To this end we determined by the method proposed by Reid and Dormandy (J. Clin. Pharmacol. 1976, 29, 855) whole-blood filterability in 15 smokers, 18 diabetics, 14 hypertensives, 16 dislipidemics, without clinical evidence of ischemic pathology and with negative vascular pathology anamnesis. In diabetics, hypertensives and dislipidemics blood filterability turned out to be significantly lower (p less than 0,001) that in 15 controls. In smokers it was also lower, although in a less significant way.