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Biomedical subjects

P Ferrari

Publications and source records attributed to P Ferrari.

At least 109 records · Page 6Linked to original sources
PubMed1999

Permanently reduced plasma ionized magnesium among renal transplant recipients on cyclosporine.

Hypomagnesemia is common after kidney transplantation. Until recently, only the determination of total plasma magnesium was possible, whereas the assessment of ionized magnesium has since become practicable. One hundred and nine renal transplant patients on cyclosporine with allografts functioning stably for more than 6 months and plasma creatinine levels of less than 200 micromol/l entered the study. Total and ionized circulating magnesium were assessed among these 109 patients, as well as among 15 renal transplant patients not on cyclosporine and 21 healthy volunteers. Cyclosporine patients showed significantly lower total and ionized circulating magnesium values than the two control groups. Plasma total and ionized magnesium levels were also significantly lower among cyclosporine patients treated concurrently with insulin or oral hypoglycemic agents than among those who were not. No correlation was noted between time after transplantation and plasma magnesium with respect to patients on cyclosporine. In conclusion, the study demonstrates that a large subset of renal transplant patients treated with cyclosporine have permanent deficiencies of ionized and total magnesium. The tendency towards hypomagnesemia is also more pronounced among patients with diabetes mellitus.

Adolescent↗
PubMed1999

Effects of a short-term strength training programme on lymphocyte subsets at rest in elderly humans.

The effects of a short-term strength training programme on resting lymphocyte subsets and stress hormone concentrations were analysed in 32 elderly sedentary subjects. Out of these 32 subjects, 8 women and 8 men [mean age 70.1 (SEM 1.0) years] were randomly assigned to a 8-week strength training programme which consisted of three sets of eight repetitions at 80% of one repetition maximum, for leg press, bilateral leg extension and seated chest press, 3 days a week. The remaining 8 women and 8 men [mean age 70.5 (SEM 0.9) years] served as controls. Absolute counts of lymphocyte subsets (CD20+, CD3+, CD3+CD4+, CD3+CD8+, CD3-CD56+CD16+) were measured with a new technique combining fluorescent microspheres and flow cytometry. In the trained subjects, substantial increases in strength took place in one repetition maximum during the 8-week training period for leg press [from means of 20.7 (SEM 1.0) to 23.6 (SEM 1.0) N x kg(-1) LBM (lean body mass)], chest press [from means of 5.4 (SEM 0.3) to 6.2 (SEM 0.3) N x kg(-1) LBM] and bilateral leg extension [from means of 6.3 (SEM 0.2) to 7.4 (SEM 0.3) N x kg(-1) LBM] movements. Baseline cortisol concentration (P < 0.01), CD20+ cell count (P < 0.05), CD3+ cell count (P < 0.05), and CD4+ cell count (P < 0.01) decreased in both groups secondary to circannual variations between winter and summer. No significant effect of strength training on resting adrenaline, noradrenaline and cortisol concentrations or distributions of lymphocyte subsets at rest was observed. The main finding of this study was to demonstrate that 8-week is too short a duration for a strength training programme to modify counts of lymphocyte subsets at rest in elderly sedentary adults.

Aged↗
PubMed1999

Hypovolemia contributes to the pathogenesis of orthostatic hypotension in patients with diabetes mellitus.

PURPOSE: To investigate whether body sodium content and blood volume contribute to the pathogenesis of orthostatic hypotension in patients with diabetes mellitus. SUBJECTS AND METHODS: Exchangeable sodium, plasma and blood volumes, and catecholamine, renin, and aldosterone levels were assessed in 10 patients with Type II diabetes mellitus who had orthostatic hypotension and control groups of 40 diabetic patients without orthostatic hypotension and 40 normal subjects of similar age and sex. In subgroups, clinical tests of autonomic function and cardiovascular reactivity to norepinephrine and angiotensin II infusions were performed. RESULTS: In diabetic patients with orthostatic hypotension, mean (+/- SD) supine blood pressure was 165/98 +/- 27/12 mm Hg (P <0.05 compared with other groups) and mean upright blood pressure was 90/60 +/- 38/18 mm Hg. Compared with controls, diabetic patients with orthostatic hypotension had a 10% lower blood volume. They also had less exchangeable sodium than patients with diabetes who did not have orthostatic hypotension (P <0.01). Compared with both groups of controls, diabetic patients with orthostatic hypotension had decreased 24-hour urinary norepinephrine excretion and a reduced diastolic blood pressure response to handgrip (P <0.05). Moreover, they displayed reduced products of exchangeable sodium or blood volume and sympathetic function indexes. Cardiovascular pressor reactivity to norepinephrine was enhanced (P <0.01) and beat-to-beat variation decreased (P <0.01) in both groups of diabetic patients. Microvascular complications were more prevalent in the diabetic patients with orthostatic hypotension (90% vs 35%). CONCLUSIONS: Patients who have Type II diabetes mellitus and orthostatic hypotension are hypovolemic and have sympathoadrenal insufficiency; both factors contribute to the pathogenesis of orthostatic hypotension.

Adult↗
PubMed1999

[Molecular genetics of hypertension in the human].

In the general population blood pressure varies along a continuum and is regulated via multiple mechanisms involving many genetic loci and environmental factors. Epidemiological studies suggest that blood pressure variance is attributable to both genetic factors and environmental factors to the same magnitude. The molecular basis for three forms of sever hypertension transmitted on an autosomal basis has been recently elucidated: a) the glucocorticoid-suppressible aldosteronism (GSA), b) the Liddle's syndrome and c) the syndrome of apparent mineralocorticoid excess (AME). GSA is due to expression of a chimeric gene produced by fusion of the 11 beta-hydroxylase promoter with the region encoding the enzyme aldosterone-synthase. Expression of this chimeric gene occurs in the zona fasciculata of the adrenal cortex, under the control of ACTH, and can be suppressed by administration of glucocorticoids. Liddle's syndrome is due to mutations in the beta or gamma chain of the epithelial sodium channel in distal renal tubule cells. The hyperactivity of this channel caused by the mutations results in increased sodium reabsorption, which can be suppressed by administration of amiloride or triamterene. AME is caused by mutations of the 11 beta-hydroxysteroid dehydrogenase type 2 enzyme, an enzyme that metabolises cortisol into its receptor inactive keto-form cortisone, thus protecting the mineralocorticoid receptor from occupation by glucocorticoids. Apart from these rare genetic defects of the extended renin-angiotensin system, there are many susceptibility genes that might increase the risk of hypertension in a given environment. Several studies have demonstrated a link between the angiotensinogen gene and familial hypertension. One variant of angiotensinogen gene is associated with elevated plasma angiotensinogen levels and is more prevalent among hypertensive than among normotensive. This observation shows the relationship between the angiotensinogen genotype, the intermediate phenotype (i.e., plasma angiotensinogen elevation), and the distant phenotype (i.e., blood pressure elevation). The identification of these genes as well as other informative genetic markers distributed along the genome could be used in the search for genetic links between arterial hypertension and a chromosomal locus.

Blood Pressure↗
PubMed1999

[Arterial hypertension and rapidly progressing renal failure].

A case report is presented, which describes a patient with a long history of stable but mild renal insufficiency for several years, who presented with end-stage stage renal disease following a rapid decline of renal function and accelerated hypertension. A renal work-up disclosed severe bilateral renal artery stenoses. A percutaneous transluminal renal angioplasty (PTRA) with stent significantly improved both renal function and hypertension and the patient was still not on dialysis twelve months after the procedure. The epidemiology, prognosis, diagnosis and treatment of the atherosclerotic renovascular disease are discussed. Treatment consists in the revascularization, this can improve not only the hypertension but also the renal function. In patients with end-stage renal disease PTRA can postpone for several months the need for dialysis.

Angioplasty, Balloon↗
PubMed1999

The role of tumour markers in predicting skeletal metastases in breast cancer patients with equivocal bone scintigraphy.

Bone scintigraphy (BS) is commonly performed in the staging and postoperative monitoring of breast cancer. Nevertheless, due to low specificity it often demonstrates hot spots with equivocal interpretation, which may be misleading in the management of these patients. The aim of this study was to assess the value of a serum tumour marker panel in selecting among the patients with equivocal BS those with bone metastases. Between January 1986 and December 1995, 297 breast cancer patients were followed-up after mastectomy with serial determinations of a CEA-TPA-CA15.3 tumour marker panel, BS and liver echography. The tumour marker panel was used to select patients with equivocal BS for examination of suspicious bone areas by further imaging techniques. Up to December 1995, 158 (53%) patients showed an equivocal BS and 47 patients developed bone metastases. In the 158 patients with equivocal BS, prolonged clinical and imaging follow-up over 45 months (mean; range 12-120) was used to ascertain the presence or absence of bone metastases. In these 158 patients the negative predictive value and positive predictive value of the tumour marker panel to predict bone metastases was 97% and 75% respectively. This study shows that in breast cancer patients the CEA-TPA-CA15.3 tumour marker panel has a high value in selecting those patients with bone metastases, or at high risk of developing clinically-evident bone metastases, among the large number of subjects with equivocal BS.

Adult↗
PubMed1999

Responses of total and free insulin-like growth factor-I and insulin-like growth factor binding protein-3 after resistance exercise and training in elderly subjects.

To investigate the effects of an acute bout of exercise on total and free insulin-like growth factor-I and insulin-like growth factor binding protein-3 plasma concentrations, 32 healthy elderly subjects (67-80 years, 16 men) performed a strength test, which consisted of two sets of 12 repetitions at 12-repetition maximum and four sets of 5 repetitions at 5-repetition maximum for horizontal leg press, seated chest press, and bilateral leg extension movements. Ten out of the 32 subjects served as time controls. Blood samples were drawn prior (08.30 h), immediately (10.30 h), and 6 h (16.30 hours) after the strength test in exercising and resting subjects. The 32 subjects were then randomly assigned to habitual physical activity or to an 8-week strength training program. After 8 weeks, both sedentary and trained groups underwent blood samplings under the above-mentioned conditions. The exercising group showed increased total and free insulin-like growth factor-I concentrations immediately (+17.7 and +93.8%, respectively), and 6 h (+7.5 and +31.2%, respectively) after the test, whereas no significant changes in insulin-like growth factor binding protein-3 concentrations were observed in either exercising or resting control groups. Strength training induced no significant changes in baseline insulin-like growth factor-I and insulin-like growth factor binding protein-3 concentrations. Trained and sedentary groups showed similar hormonal response pattern to the strength test, which consisted of increased total and free insulin-like growth factor-I concentrations. The data indicated that strength exercise can induce an early and sustained insulin-like growth factor-I release, in elderly subjects, regardless of their training status.

Aged↗
PubMed1999

Reaction mechanism of phosphoglucosamine mutase from Escherichia coli.

The phosphoglucosamine mutase (GlmM) from Escherichia coli, specifically required for the interconversion of glucosamine-6-phosphate and glucosamine-1-phosphate (an essential step in the pathway for cell-wall peptidoglycan and lipopolysaccharide biosyntheses) was purified to homogeneity and its kinetic properties were investigated. The enzyme was active in a phosphorylated form and catalysed its reaction according to a classical ping-pong bi-bi mechanism. The dephosphorylated and phosphorylated forms of GlmM could be separated by HPLC and coupled MS showed that only one phosphate was covalently linked to the active site of the enzyme. The site of phosphorylation was clearly identified as Ser102 in the 445-amino acid polypeptide. GlmM was also capable of catalysing the interconversion of glucose-1-phosphate and glucose-6-phosphate isomers, although at a much lower (1400-fold) rate. Interestingly, the mutational change of the Ser100 to a threonine residue resulted in a 20-fold increase of the nonspecific phosphoglucomutase activity of GlmM, suggesting that the presence of either a serine or a threonine at this position in the consensus sequence of hexosephosphate mutases could be one of the factors that determines the specificity of these enzymes for either sugar-phosphate or amino sugar-phosphate substrates.

Amino Acid Sequence↗
PubMed1999

Abnormalities in insulin sensitivity, vascular resistance and erythrocyte cation transport are independent genetic traits in familial hypertension.

Several isolated abnormalities have been noted in normotensive members of hypertensive families, including exaggerated forearm vascular resistance (FVR), decreased insulin sensitivity and elevated sodium-lithium (Na/Li) countertransport. No family study has investigated the aforementioned abnormalities concurrently within the same hypertensive families. It is therefore unknown whether these disturbances reflect single or different genetic traits. Thus, we studied cardiovascular reactivity of the forearm vasculature, cellular sodium transport mechanisms and insulin sensitivity concomitantly in normotensive (n = 24) and borderline hypertensive (n = 16) members of hypertensive families, compared with normotensive members (n = 24) of normotensive families. At least one abnormality was noted in 27 (67%) out the 40 subjects with a positive family history of hypertension. Na/Li-countertransport was increased in 15 (37%), FVR was increased in 14 (35%) and insulin sensitivity was decreased in 9 (22%) subjects with familial hypertension. The concomitant occurrence of at least 2 out of the 3 abnormalities mentioned was noted in 9 (22%) out of the 40 subjects with family history of hypertension. Decreased insulin sensitivity, increased basal FVR and increased Na/Li countertransport were concurrently observed in two (5%) subjects. This investigation documents the frequent occurrence of abnormalities such as decreased insulin sensitivity, increased basal FVR and Na/Li-countertransport in subjects with family history of hypertension. The concomitant occurrence of at least two of the mentioned abnormalities being observed in less than one-quarter of the subjects with family history of essential hypertension, it is assumed that insulin sensitivity, basal FVR and Na/Li-countertransport reflect more than one genetic trait predisposing to hypertension.

Adolescent↗
PubMed1999

Detection of human papillomavirus DNA in urinary bladder carcinoma by in situ hybridisation.

AIMS: To investigate the sensitivity of an in situ hybridisation system to detect human papillomavirus (HPV) infection in transitional cell bladder cancer and to evaluate the advantages of analysing multiple biopsies; to examine the correlation between HPV tumour infection detected by in situ hybridisation and the presence of serum anti-HPV antibodies detected by enzyme linked immunosorbent assay (ELISA); and to relate the presence of viral infection to grade, stage, and follow up in cases of bladder cancer. METHODS: The in situ hybridisation technique was used with broad spectrum and type specific (6/11, 16/18, 31/33/35) probes against HPV DNA in formalin fixed, paraffin embedded tissues from 43 cases of bladder cancer. The results were analysed for the presence and type of papillomavirus and correlated with clinicopathological variables. RESULTS: The presence of HPV DNA was identified by the in situ hybridisation technique in 17 of 43 cases of bladder cancer; 12 of these were serum antibody positive and 10 had had multiple biopsies. Fifteen of the cases that were negative for HPV DNA by in situ hybridisation had positive serum serology when tested by ELISA. In 14 cases, the HPV was either types 16/18 or types 31/33/35, both of which carry high oncogenic risk. The stage (p < 0.05) and grade (NS) of the tumour and the outcome on follow up (p < 0.05) were correlated with the presence of HPV infection. CONCLUSIONS: ELISA is not useful in identifying patients with HPV positive bladder cancer, but the use of several probes and multiple biopsies increases the detection rate of HPV in neoplastic tissues. The association between tumour virus infection and high grade/high stage tumours and worse outcome suggests that HPV infection of neoplastic tissue has a negative effect on the behaviour and evolution of transitional cell bladder carcinoma.

Adult↗
PubMed1999

Evidence for an interaction between adducin and Na(+)-K(+)-ATPase: relation to genetic hypertension.

Adducin point mutations are associated with genetic hypertension in Milan hypertensive strain (MHS) rats and in humans. In transfected cells, adducin affects actin cytoskeleton organization and increases the Na(+)-K(+)-pump rate. The present study has investigated whether rat and human adducin polymorphisms differently modulate rat renal Na(+)-K(+)-ATPase in vitro. We report the following. 1) Both rat and human adducins stimulate Na(+)-K(+)-ATPase activity, with apparent affinity in tens of nanomolar concentrations. 2) MHS and Milan normotensive strain (MNS) adducins raise the apparent ATP affinity for Na(+)-K(+)-ATPase. 3) The mechanism of action of adducin appears to involve a selective acceleration of the rate of the conformational change E(2) (K) --> E(1) (Na) or E(2)(K). ATP --> E(1)Na. ATP. 4) Apparent affinities for mutant rat and human adducins are significantly higher than those for wild types. 5) Recombinant human alpha- and beta-adducins stimulate Na(+)-K(+)-ATPase activity, as do the COOH-terminal tails, and the mutant proteins display higher affinities than the wild types. 6) The cytoskeletal protein ankyrin, which is known to bind to Na(+)-K(+)-ATPase, also stimulates enzyme activity, whereas BSA is without effect; the effects of adducin and ankyrin when acting together are not additive. 7) Pig kidney medulla microsomes appear to contain endogenous adducin; in contrast with purified pig kidney Na(+)-K(+)-ATPase, which does not contain adducin, added adducin stimulates the Na(+)-K(+)-ATPase activity of microsomes only about one-half as much as that of purified Na(+)-K(+)-ATPase. Our findings strongly imply the existence of a direct and specific interaction between adducin and Na(+)-K(+)-ATPase in vitro and also suggest the possibility of such an interaction in intact renal membranes.

Animals↗
PubMed1999

Treatment of venous leg ulcers with sulodexide.

Venous ulcers are still today one of the main socioeconomic problems of medical interest in terms of prevalence, morbidity, and costs to the health service. In the past, various studies have been carried out to identify a systemic pharmacologic treatment able to accelerate venous ulcer healing times, but frequently the results have not been satisfactory. The aim of this study was to evaluate the efficacy of sulodexide, a drug with profibrinolytic and antithrombotic activity, in accelerating venous ulcer's healing time. Ninety-four patients (32 men and 62 women), aged 72 years old on average, were randomly distributed between two groups. In the first group ("control group") a standard treatment was applied, which consisted of cleansing by washing with physiological solution and the application of elastic compression with short-extensibility, removable bandages. The second group ("sulodexide group") received the standard treatment plus sulodexide (600 lipoprotein lipase releasing units [LRU] by im route per day for 30 consecutive days, followed by 500 LRU by oral route per day for a further 30 days). After 2 months the venous ulcers were found healed in 15 patients (36%) in the control group and in 30 patients (58%) in the sulodexide group (p = 0.03). The life table showed that the healing times were shorter in the sulodexide group in the first 2 months of treatment. Total healing times amounted to 110 days in the control group and 72 days in the sulodexide group (p = 0.08) and the results were in proportion to the initial severity of the lesion. A significant correlation was noted between ulcer healing times and severity of the initial ulcerous lesion, the duration of the ulcer, and the group the patient belonged to. No correlation was found between age, gender of the patient and the etiology of the ulcer. In conclusion sulodexide was shown effective in the treatment of venous leg ulcers, yielding healing more quickly than the standard treatment.

Aged↗
PubMed1999

Molecular basis of human salt sensitivity: the role of the 11beta-hydroxysteroid dehydrogenase type 2.

Salt-sensitive subjects (SS) increase their blood pressure with increasing salt intake. Because steroid hormones modulate renal sodium retention, we hypothesize that the activity of the 11beta-hydroxysteroid dehydrogenase type 2 (11betaHSD2) enzyme is impaired in SS subjects as compared with salt-resistant (SR) subjects. The 11betaHSD2 enzyme inactivates 11-hydroxy steroids in the kidney, thus protecting the nonselective mineralocorticoid receptor from occupation by glucocorticoids. We performed an association study using a recently identified single AluI polymorphism in exon 3 and a polymorphic microsatellite marker of the HSD11B2 gene in 149 normotensive white males (37 SS and 112 SR). The activity of the enzyme 11betaHSD2 was assessed by determining the urinary ratio of cortisol (THF+5alphaTHF) to cortisone (THE) metabolites by gas chromatography in all the 37 SS subjects and in 37 age- and body habitus-matched SR volunteers. Mean (THF+5alphaTHF)/THE ratio was markedly elevated in SS subjects compared with SR subjects (1.51 +/- 0.34 vs. 1.08 +/- 0.26, P < 0.00001), indicating enhanced access of glucocorticoids to the mineralocorticoid receptor in SS subjects. In 58% of SS subjects this ratio was higher than the maximum levels in SR subjects. The salt-induced elevation in arterial pressure increased with increasing (THF+5alphaTHF)/THE ratio (r2 = 0.51, P < 0.0001). A total of 12 alleles of the polymorphic microsatellite marker were detected. Homozygosity for the allele A7 was higher in SS subjects than in SR subjects (41 vs. 28%, P < 0.005), whereas the occurrence of the allele A7 with allele A8 was lower in SS subjects than in SR subjects (8 vs. 15%, P < 0.03). The prevalence of salt sensitivity was 35% in subjects with allele A7/A7, whereas salt sensitivity was present in only 9% of the subjects with allele A7/A8. The (THF+5alphaTHF)/THE ratio was higher in subjects homozygous for the A7 microsatellite allele as compared with the corresponding control subjects. The prevalence of the AluI allele was 8.0% in SR subjects and 5.4% in SS subjects and did not correlate with blood pressure. The decreased activity of the 11betaHSD2 in SS subjects indicates that this enzyme is involved in salt-sensitive blood pressure response in humans. The association of a polymorphic microsatellite marker of the gene with a reduced 11betaHSD2 activity suggests that variants of the HSD 11B2 gene contribute to enhanced blood pressure response to salt in humans.

11-beta-Hydroxysteroid Dehydrogenases↗
PubMed1999

PST 2238: A new antihypertensive compound that modulates Na,K-ATPase in genetic hypertension.

A genetic alteration in the adducin genes is associated with hypertension and up-regulation of the expression of renal Na, K-ATPase in Milan-hypertensive (MHS) rats, in which increased ouabain-like factor (OLF) levels are also observed. PST 2238, a new antihypertensive compound that antagonizes the pressor effect of ouabain in vivo and normalizes ouabain-dependent up-regulation of the renal Na-K pump, was evaluated for its ability to lower blood pressure and regulate renal Na,K-ATPase activity in MHS genetic hypertension. In this study, we show that PST 2238, given orally at very low doses (1 and 10 microg/kg for 5-6 weeks), reduced the development of hypertension in MHS rats and normalized the increased renal Na,K-ATPase activity and mRNA levels, whereas it did not affect either blood pressure or Na,K-ATPase in Milan-normotensive (MNS) rats. In addition, a similar antihypertensive effect was observed in adult MHS rats after a short-term treatment. In cultured rat renal cells with increased Na-K pump activity at Vmax due to overexpression of the hypertensive variant of adducin, 5 days of incubation with PST 2238 (10(-10-)-10(-9) M) lowered the pump rate to the level of normal wild-type cells, which in turn were not affected by the drug. In conclusion, PST 2238 is a very potent compound that in MHS rats reduces blood pressure and normalizes Na-K pump alterations caused by a genetic alteration of the cytoskeletal adducin. Because adducin gene mutations have been associated with human essential hypertension, it is suggested that PST 2238 may display greater antihypertensive activity in those patients carrying such a genetic alteration.

Androstanols↗
PubMed1999

[Mucinous adenocarcinoma of the ovary in pregnancy].

A clinical case of ovarian adenocarcinoma during pregnancy is reported. The diagnostic and therapeutic problems which may be encountered, are illustrated. The data found in the literature concerning ovarian carcinoma in pregnancy are not so many. Most authors agree for the prosecution of pregnancy, with a careful observation of the patient. Also in this case, with a careful observation, an outcome without risk for the mother and the fetus has been obtained. After one month from birth, the surgical therapy has been completed. The tumoral markers CA 125 and CA 72-4 after birth were normal. After one year from intervention, the patient is good health.

Adult↗