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Biomedical subjects

G Gambaro

Publications and source records attributed to G Gambaro.

At least 91 records · Page 5Linked to original sources

Prevention of exercise-induced bronchoconstriction by a new leukotriene antagonist (SK&F 104353). A double-blind study versus disodium cromoglycate and placebo.

The effects of 800 micrograms of inhaled SK&F 104353, a peptidoleukotriene receptor antagonist, and of 20 mg disodium cromoglycate (DSCG) on exercise-induced bronchoconstriction were compared in 18 asthmatic patients. The study was conducted according to a double-blind, crossover, randomized, placebo-controlled design. Two baseline exercise tests were carried out, and pulmonary function tests were done before and at 1, 5, 10, 15, 20, and 30 min after completion of the exercise. Patients showing a 20% or greater decrease in FEV1 in both exercise challenges entered the blinded portion of the study. When placebo was administered before exercise, FEV1 fell to the same extent as during the baseline phase. After SK&F 104353 and DSCG, the bronchoconstriction was attenuated. The mean maximal percentage fall in FEV1 after exercise was 29% after placebo and 20% after SK&F 104353 and DSCG. The differences between the two active treatments did not reach the 5% level of statistical significance, though at 20 min SK&F 104353 showed a more pronounced effect than DSCG. The protective effect suggests an important role of leukotrienes in the pathogenesis of exercise-induced bronchoconstriction.

Adult↗

Idiopathic calcium oxalate nephrolithiasis: a cellular disease.

Physico-chemical, metabolic and hormonal theories regarding the pathogenesis of calcium oxalate nephrolithiasis do not sufficiently explain many features of this disease. The recent findings of an abnormally faster oxalate self-exchange and higher phosphorylation of band 3 in erythrocytes of idiopathic calcium oxalate stone formers suggest the hypothesis that nephrolithiasis may be a cellular disease, characterized by a defect in the function of the anion-exchange. The cellular anomaly seems genetically controlled. Band 3 anion exchanger function seems to be biochemically regulated through modulation of band 3 phosphorylation, which depends on cyclic AMP- and phospholipid-sensitive Ca2+ independent protein kinases. In this light, a reduced glycosaminoglycan concentration in the erythrocyte membranes of stone formers might play a role, as these molecules exert a strong inhibitory effects on band 3 phosphorylation and anion transport in vitro and in vivo. An in vivo trial was performed in which stone formers were administered glycosaminoglycans orally. A reduction in oxalate excretion, and oxalate renal clearance, and a simultaneous correction of the abnormal RBC oxalate flux and band 3 phosphorylation were observed. These data suggest the existence of a link between the erythrocyte abnormality and oxalate transport by the kidney and gut.

Animals↗

Correction of erythrocyte abnormalities in idiopathic calcium-oxalate nephrolithiasis and reduction of urinary oxalate by oral glycosaminoglycans.

Calcium-oxalate nephrolithiasis is associated with a defect in erythrocyte oxalate self-exchange and an abnormal rate of erythrocyte membrane protein phosphorylation. There is evidence that glycosaminoglycans (GAGs) have a regulatory effect on both of these processes. This study tested the hypothesis that modifications of erythrocyte oxalate self-exchange induced by oral GAGs are paralleled by similar changes in overall oxalate metabolism. 40 patients with idiopathic calcium-oxalate nephrolithiasis were treated for 15 days with 60 mg/day of a mixture of GAGs. By day 15 of treatment there were significant reductions from baseline in erythrocyte oxalate self-exchange (mean [SD] 1.67 [1.18] vs 2.59 [1.63] x 10(2) per min; p less than 0.005) and erythrocyte membrane protein phosphorylation (55.8 [7.3] vs 72.9 [6.8] x 10(-3) cpm/mg protein; p less than 0.005), but also in urinary oxalate excretion (0.24 [0.09] vs 0.31 [0.15] mmol/24 h; p less than 0.005). This finding suggests similar changes in both erythrocytes and other cells more important in oxalate handling. The changes had reversed by 15 days after withdrawal of treatment. Acute intravenous administration of GAGs (60 mg) induced a fall in carbon-14-labelled oxalate renal clearance (143 [13] vs 169 [28] ml/min; p less than 0.005), which strongly suggests the participation of the kidney. However, reduced oxalate absorption from the intestine, and even decreased synthesis of oxalate, cannot be ruled out.

Administration, Oral↗

Effects of the oral administration of glycosaminoglycans on cellular abnormalities associated with idiopathic calcium oxalate nephrolithiasis.

Oral administration of mixture of extractive glycosaminoglycans to a group of renal stone formers led to a significant decrease in oxalate self-exchange and in erythrocytes membrane protein phosphorylation traits that are abnormal in the majority of patients with idiopathic calcium nephrolithiasis. The action of glycosaminoglycans at the cellular level is probably due to their modulating activity on certain membrane protein kinases. The proven effect of the glycosaminoglycans opens a new pharmacological approach to the prevention of recurrent nephrolithiasis.

Administration, Oral↗

Bronchodilating activity of broxaterol transdermal patch and its protective effect on bronchial constriction induced by inhaled distilled water mist.

The bronchodilating activity and the ability of broxaterol transdermal patch to inhibit bronchial constriction in response to distilled water mist (UNH2O) inhalation were assessed. The study was performed in 10 asthmatic patients in clinical remission according to a placebo-controlled, double-blind, randomized crossover design. Test medications were broxaterol patch (size = 1.75 cm2; programmed delivery = 105 mcg/h) and a matched placebo patch. A spirometric examination was performed before patch application (at 8:30-9:00 a.m.) and 24 hours later. Immediately afterwards, the UNH2O inhalation test was made, consisting of 3 bronchial exposures lasting 30, 60 and 120 s respectively with 3-minute intervals between challenges. Immediately after each exposure, a spirometric examination and specific airway resistance measurements were made. The results obtained show that broxaterol patch exerts a statistically significant bronchodilating effect and has a better protective effect than placebo patch on UNH2O-induced bronchial constriction. The local tolerability of patches was very good. Slight tremors were observed in some subjects.

Administration, Cutaneous↗

[Traumatic injuries++ of the external genitalia: a case of avulsion of the penile skin].

The Authors report their recent experience about a penis trauma with a subtotal organ skinning. After the literature analysis, the AA. explain the case, with a particular attention to the surgical repairing technique. The surgical outcomes are discussed and it is re-marked the necessity of a precise diagnostic approach and follow up, also to prevent possible unerectional chains.

Dermatologic Surgical Procedures↗

Is hydrochlorothiazide-induced hypocalciuria due to inhibition of prostaglandin E2 synthesis?

1. Since prostaglandin E2 could play a role in idiopathic hypercalciuria, and considering the well-established hypocalciuric action of hydrochlorothiazide, we have evaluated the effect of 15 days' treatment with hydrochlorothiazide in 10 hypercalciuric male stoneformers on urinary Ca2+ and prostaglandin E2, as well as on plasma bicyclo-prostaglandin E2, 25-hydroxyvitamin D, 1,25-dihydroxyvitamin D and parathyroid hormone. 2. In addition to lowering urinary Ca2+ (P less than 0.001), hydrochlorothiazide also promoted a significant fall in urinary prostaglandin E2 (P less than 0.001), plasma bicyclo-prostaglandin E2 (P less than 0.001) and 1,25-dihydroxyvitamin D (P less than 0.01), and an increase in plasma parathyroid hormone (P less than 0.025), whereas plasma 25-hydroxyvitamin D was unchanged. 3. A positive correlation between urinary Ca2+ and prostaglandin E2 was present before (P less than 0.00005), but not after, hydrochlorothiazide. Plasma bicyclo-prostaglandin E2 and plasma 1,25-dihydroxyvitamin D were positively correlated both before (P less than 0.005) and after (P less than 0.005) hydrochlorothiazide, as was also the percentage change in each induced by the drug (P less than 0.05). Furthermore, the changes in plasma 25-hydroxyvitamin D and plasma 1,25-dihydroxyvitamin D after hydrochlorothiazide were negatively correlated (P less than 0.05). 4. It is suggested that a block of prostaglandin E2 synthesis plays a role in the effect of hydrochlorothiazide on Ca2+ metabolism, most probably through an inhibition of 1 alpha-hydroxylase activity.

Adult↗

Glycosaminoglycan content, oxalate self-exchange and protein phosphorylation in erythrocytes of patients with 'idiopathic' calcium oxalate nephrolithiasis.

1. This study was performed to test the hypothesis that glycosaminoglycans may play an important role in the observed abnormalities in oxalate flux seen in patients with calcium oxalate nephrolithiasis. 2. Oxalate flux rate, erythrocyte membrane glycosaminoglycan content, membrane protein phosphorylation and effect of heparan sulphate on erythrocyte oxalate flux in vitro were studied in control subjects and patients with calcium oxalate nephrolithiasis. 3. In comparison with control subjects, renal stone-formers showed a significantly higher oxalate self-exchange, a lower erythrocyte membrane glycosaminoglycan content and a higher membrane phosphorylation rate. In stone-formers, erythrocyte glycosaminoglycan content correlated inversely with both oxalate flux rate and protein phosphorylation. In vitro, heparan sulphate promoted a significant fall in the rate of oxalate self-exchange. 4. These findings support the hypothesis that a lower erythrocyte membrane content of glycosaminoglycans enhances membrane protein phosphorylation, leading to an increased rate of transmembrane oxalate flux.

Adult↗

[Post-radiotherapy complications in malignant tumors of the nasopharynx. Analysis of 141 cases].

This study was aimed at retrospectively analyzing the incidence and severity of the complications occurred in 141 patients affected with nasopharyngeal carcinomas treated with exclusive radiotherapy from 1960 to 1986. The acute complications were analyzed (85/141 grade II-III mucositis which generally came to a complete remission) which occurred during and immediately after radiation treatment. The late damage was then studied which occurred in 74/141 patients (52.5%) and which may worsen patients' quality of life. Finally, the incidence and severity of damage were correlated with some parameters: sex, age, performance status, risk factors (tabagism, alcoholism, diabetes), stage, total dose, fractionation, and processing techniques for treatment planning.

Adolescent↗

High urinary excretion of glycosaminoglycans: a possible marker of glomerular involvement in diabetes.

Many insulin-dependent diabetic patients with albuminuria in the "not at risk range" for diabetic nephropathy present high urinary excretion rates of glycosaminoglycans. A lysine provocative test in these subjects disclosed abnormal urinary excretion of albumin, unlike findings obtained in insulin-dependent diabetic patients with normal urinary excretion rates of glycosaminoglycans. These data support the hypothesis that high urinary excretion of glycosaminoglycans is a marker of glomerular involvement in diabetes mellitus.

Adult↗

Inhaled frusemide is highly effective in preventing ultrasonically nebulised water bronchoconstriction.

A decrease in the osmolarity of the periciliary fluid of central airways is supposed to be the initiating mechanism by which ultrasonically nebulised distilled water (UNH2O) induces bronchoconstriction in asthmatics. It is therefore possible that substances, such as frusemide (F), which, in vitro, interfere with ions and water translocation across the tracheo-bronchial epithelium, can also modify such response. To test this hypothesis, 16 adult asthmatics were challenged with UNH2O after being pretreated with either inhaled F (approximately 28 mg delivered into the mouth) or placebo (the diluent) administered in random order and double-blind by means of a jet nebuliser. F did not modify baseline FEV1 and sRaw but attenuated markedly their changes after UNH2O. Mean max % (95% CI) sRaw increases after placebo and F were 293% (168-419) and 63% (21-104), respectively; mean max % falls in FEV1 were 26% (20-32) and 6% (-1-12). Thus inhaled F is highly effective in preventing UNH2O-induced bronchoconstriction and this unexpected property could have therapeutic implications.

Administration, Inhalation↗

[The role of radiotherapy in the treatment of supraglottic laryngeal tumors. Case reports].

Radiotherapy obtains better results when employed alone, in initial forms (T1-T2), and after surgery, when loco-regional relapse incidence reduces. Personal results in the treatment of laryngeal cancer are reported in 281 patients. One-hundred-forty-seven patients treated with exclusive radiotherapy had 5-year global and NED survival of 32.7% and 26.6%; 5-year NED survival in particular was 78.7% for T1-T2 and 22.9% for T3-T4. Subsequently 52.8% of patients relapsed. One-hundred-thirty-four patients treated with postoperative radiotherapy had a 5-year global and NED survival of 58.8% and 52.1%; relapses were observed in 20.9% of patients, mostly in cases with histological G3 grading or with rupture of the lymph node capsule. The importance of exclusive and postoperative radiotherapy with reference to prognostic factors that are deduced from the histological specimen is underlined.

Adult↗

Computed tomography (CT) in children with herpes simplex encephalitis.

Computed Tomography (CT) scans were obtained from nine infants with herpes simplex virus encephalitis (HSE). The early CT findings were generalized or localized edematous change and a mass effect was also seen in two cases. In the follow-up study two patients showed bilateral gyriform calcification, a rare occurrence in association with intracranial infection. The appearance of multicystic encephalomalacia was evident in one patient 3 months after the onset of disease. It is shown that the CT findings of neonates and young children with HSE are different from those of adults.

Child↗

Effects of imidazole-2-hydroxibenzoate on glycosaminoglycan and albumin urinary excretion in type 1 diabetic patients.

The effect of imidazole-2-hydroxibenzoate on urinary excretion rates of glycosaminoglycans and albumin in 22 insulin-dependent diabetics with albumin excretion rates under 300 mg/day was evaluated in a 165-day double blind crossover study. Unlike placebo, the drug reduced glycosaminoglycan and albumin excretion rates significantly after 40 and 60 days of treatment, and the effects were significantly intercorrelated. Moreover, a parallel reduction in urinary excretion of N-acetyl-beta-D-glucosaminidase was also observed. These pharmacological effects may have a positive impact on the subsequent natural history of diabetic nephropathy.

Acetylglucosaminidase↗

Abnormal erythrocyte charge in diabetes mellitus. Link with microalbuminuria.

The anionic charge on the surface of the erythrocyte and the erythrocyte membrane content of sialic acid and acid glycosaminoglycans (GAGs) were evaluated in insulin-dependent diabetic patients who had albumin excretion rates less than 300 mg/24 h. In these subjects a statistically significant reduction of erythrocyte anionic charge (RBCCh) and GAGs content in erythrocyte ghosts was shown. In view of the demonstration of a negative correlation between RBCCh and albuminuria after a lysine provocative test, these observations support the hypothesis that the onset of microalbuminuria in human diabetes is sustained by an alteration of glomerular charge and consequently of glomerular charge selectivity.

Adolescent↗