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Biomedical subjects

M Salerno

Publications and source records attributed to M Salerno.

At least 55 records · Page 3Linked to original sources

Target organ damage and non-dipping pattern defined by two sessions of ambulatory blood pressure monitoring in recently diagnosed essential hypertensive patients.

OBJECTIVE: To evaluate in a selected population of patients with a recent diagnosis of hypertension whether a reduced nocturnal fall in blood pressure, confirmed by two 24 h ambulatory blood pressure monitoring (ABPM) sessions is associated with more prominent target organ damage (TOD). METHODS: The study was structured in two phases: in the first, 141 consecutive, recently diagnosed, never-treated essential hypertensives underwent 24 h ABPM twice within 3 weeks; in the second phase, 118 of these patients showing reproducible dipping or non-dipping patterns underwent the following procedures: (1) routine blood chemistry, (2) 24 h urinary collection for microalbuminuria, (3) amydriatic photography of ocular fundi, (4) echocardiography and (5) carotid ultrasonography. RESULTS: The 92 patients with (>10%) night-time fall in systolic blood pressure (SBP) and diastolic blood pressure (DBP) (dippers) in both monitoring sessions were similar for age, gender, body surface area, smoking habit, clinic BP, 24 h and 48 h BP to the 26 patients with a < or = 10% nocturnal fall (non-dippers) in both sessions. The prevalence of left ventricular hypertrophy (LVH) (defined by two criteria: (1) LV mass index > or = 125 g/m2 in both genders; (2) LV mass index > or = 120 and 100 g/m2 in men and women, respectively) and that of carotid intima-media (IM) thickening (IM thickness > or = 0.8 mm) were significantly higher in non-dippers than in dippers (23 versus 5%, P < 0.01; 50 versus 22%, P < 0.05; and 38 versus 18%, P < 0.05, respectively). There were no differences among the two groups in the prevalence of retinal changes and microalbuminuria. The strength of the association of LV mass index with night-time BP was slightly but significantly greater than that with daytime BP. CONCLUSIONS: This study suggests that a blunted reduction in nocturnal BP, persisting over time, may play a pivotal role in the development of some expressions of TOD, such as LVH and IM thickening, during the early phase of essential hypertension, despite similar clinic BP, 24 h and 48 h BP levels observed in non-dippers and dippers.

Adult↗

High prevalence of cardiac and extracardiac target organ damage in refractory hypertension.

OBJECTIVE: Target organ damage (TOD) in chronically treated hypertensives is related to effective blood pressure (BP) control. The aim of this study was to evaluate the prevalence of cardiac and extracardiac TOD in patients with refractory hypertension (RH) compared with well-controlled treated hypertensives (C). METHODS: Fifty-four consecutive patients with RH (57 +/- 10 years), selected according to WHO/ISH guidelines definition, and 51 essential hypertensives (55 +/- 10 years) with satisfactory BP control obtained by association therapy, underwent the following procedures: (1) clinic BP measurement; (2) blood sampling for routine chemistry examinations; (3) 24 h urine collection for microalbuminuria; (4) non-mydriatic retinography; (5) echocardiogram; (6) carotid ultrasonogram. In order to exclude 'office resistance' (defined as clinic BP > 140/90 mmHg and average 24 h BP </= 125/79 mmHg), all patients with RH were subjected to 24-hour ambulatory BP monitoring. RESULTS: Both groups were similar for age, gender, body surface area, smoking habit and duration of hypertension, glucose, creatinine and lipid levels. By definition, clinic BP was significantly higher in RH than C (161 +/- 19/96 +/- 9 versus 127 +/- 6/80 +/- 5 mmHg, respectively, P < 0.01). The increased prevalence of left ventricular hypertrophy (LVH) and carotid intima-media (IM) thickening (40 versus 12%, P < 0.01, according to a non-gender-specific partition value of 125 g/m2; and 36 versus 14%, P < 0.01, according to IM thickness > or =1.0 mm, respectively); a higher prevalence of carotid plaques (65 versus 32%, P < 0.05), a more advanced retinal involvement (grade II and III, 73 and 5% versus 38 and 0%, P < 0.01) and a greater albumin urinary excretion (22 +/- 32 mg/24 h versus 11 +/- 13 mg/24 h, P < 0.01) were found in RH compared to C. CONCLUSIONS: Our study suggests that RH is a clinical condition associated with a high prevalence of TOD at cardiac, macro- and microvascular level and consequently with high absolute cardiovascular risk, which needs a particularly intensive therapeutic approach aimed to normalize BP levels and to induce TOD regression.

Albuminuria↗

Abnormal GH receptor signaling in children with idiopathic short stature.

Peripheral GH insensitivity may underlie idiopathic short stature in children. As the clinical and biochemical hallmarks of partial GH insensitivity have not yet been clearly elucidated, the identification of such patients is still difficult. We integrated functional, biochemical, and molecular studies to define the more reliable marker(s) of GH insensitivity. In particular, we measured GH receptor transducing properties through GH-induced protein tyrosine phosphorylation in patients' peripheral blood mononuclear cells and performed direct sequencing analysis of GH receptor-coding exons. Five of 14 idiopathic short stature patients with low basal IGF-I levels showed low or absent IGF-I increment after 4 d of GH administration. However, a prolonged GH stimulation induced in 3 of them an increase in IGF-I 40% above the baseline value. The IGF-binding protein-3 behavior paralleled that of IGF-I. The 2 GH-unresponsive subjects showed an abnormal tyrosine phosphorylation pattern after GH challenge. Sequence analysis of the GH receptor gene revealed a heterozygous mutation resulting in an Arg to Cys change (R161C) in exon 6 in only 1 patient, who had normal GH receptor responsiveness. Our findings indicate that abnormal GH receptor signaling may underlie idiopathic short stature even in the absence of GH receptor mutations. Thus, combining the 4-d IGF-I generation test and the analysis of GH-induced protein tyrosine phosphorylation is a useful tool to help identify idiopathic short stature patients with partial GH insensitivity.

Adolescent↗

Longitudinal growth, sexual maturation and final height in patients with congenital hypothyroidism detected by neonatal screening.

OBJECTIVE: To evaluate longitudinal growth, pubertal development and final height in patients with congenital hypothyroidism (CH) detected by a neonatal screening programme, and to identify factors potentially affecting growth outcome. PATIENTS: Fifty-five patients (41 females) detected by neonatal screening and followed longitudinally from the time of diagnosis and treatment (25+/-5 days) up to the age of 17+/-0.5 years were evaluated retrospectively. RESULTS: Pubertal development began and progressed normally in both males and females. In boys, a testicular volume of 4 ml was reached at 11.3+/-1.0 years. In girls breast enlargement (B2) occurred at a mean age of 10.3+/-1.2 years and the mean age of menarche was 12.5+/-1.2 years. The onset and the progression of puberty were independent of the aetiology, the severity of CH and the timing of the beginning of treatment. Girls treated with an initial amount of L-thyroxine (L-T4) greater than 8 microg/kg per day showed an earlier onset of puberty (B2 9.4+/-0.9 years; menarche 11.5+/-0.8 years) compared with girls treated with a lower initial dose of L-T4 (B2 10.5+/-1.2 years; menarche 12.6+/-1.2 years; P<0.02). However, both groups attained a similar final height (-0.1+/-1.0 SDS and 0.4+/-1.0 SDS, respectively), which in both cases was above the target height (P=0.03). All the patients in the study attained a mean final height (0.1+/-1.1 SDS) within the normal range for the reference population and above the target height (-0.9+/-0.9 SDS, P<0.0001). No significant relationship was found between final height and severity of CH at diagnosis, initial L-T4 dosage or aetiology of the defect. Patients with ectopic gland, thyroid aplasia or in situ gland attained a similar mean final height (0.1+/-1.1 SDS, 0.5+/-1.0 SDS and -0.5+/-1.0 SDS, respectively), which was in all cases greater than target height (-1.0+/-0.9, -0.6+/-0.8, -0.9+/-0.8 respectively; P<0.05). CONCLUSIONS: Our results suggest that conventional management of children with CH detected by neonatal screening leads to normal sexual development and normal adult height, and that the major factor determining height in these children is familial genetic growth potential.

Body Height↗

Analysis of drug transport kinetics in multidrug-resistant cells: implications for drug action.

Multidrug resistance (MDR) in model systems is known to be conferred by two different integral proteins--the 170-kDa P-glycoprotein (P-gp) and the 190-kDa multidrug resistance-associated protein (MRP1)--that pump drugs out of MDR cells. The intracellular level of a drug, which influences the drug's cytotoxic effect, is a function of the amount of drug transported inside the cell (influx) and the amount of drug expelled from the cell (efflux). One possible pharmacological approach to overcoming drug resistance is the use of specific inhibitors that enhance the cytotoxicity of known antineoplastic agents. Many compounds have been proven to be very efficient in inhibiting P-gp activity, but only some of them can inhibit MRP1. However, the clinical results obtained so far by this approach have been rather disappointing. The other likely approach is based on the design and synthesis of new non-cross-resistant drugs whose physicochemical properties favor the uptake of such drug by resistant cells. Our recent studies have shown that whereas the P-gp- and MRP1-mediated efflux of different anthracycline-based drugs may not differ considerably, their kinetics of uptake do. Thus, the high uptake of drug by cells may lead to concentrations at the cellular target site high enough to achieve the needed cytotoxicity against MDR cells. Therefore, increased drug lipophilicity might be one factor in improving drug cytotoxicity in MDR cells. In vitro studies have shown that idarubicin, an analogue of daunorub cin, is more effective than daunorubicin and doxorubicin against MDR tumor cell lines and that this increased effectiveness is related in part to the increased lipophilicity of idarubicin. Other studies have also confirmed the strong impact of lipophilicity on the uptake and retention of anthracyclines in MDR cells.

Animals↗

Evaluation of target organ damage in arterial hypertension: which role for qualitative funduscopic examination?

BACKGROUND: The objective of this study was to compare the prevalence of quantitative markers of target organ damage, such as echocardiographically documented left ventricular hypertrophy (LVH), carotid structural changes and microalbuminuria with that of retinal abnormalities detected by qualitative funduscopic examination in a large selected population of patients with essential hypertension. METHODS: Eight hundred consecutive untreated (n = 232) and treated (n = 568) hypertensive patients (386 men, 414 women, mean age 52.7 +/- 11.8 years) referred for the first time to our out-patient clinic were included in the study. In order to search for target organ damage, they were submitted to the following procedures: 1) amydriatic retinography, 2) 24-hour urine collection for microalbuminuria, 3) echocardiography, and 4) carotid ultrasonography. Retinal changes were evaluated according to the Keith, Wagener and Barker (KWB) classification by two physicians, who had no knowledge of the patients' characteristics. Microalbuminuria was defined as a urinary albumin excretion > 30 and < 300 mg/24 hours, LVH as a left ventricular mass index > or = 134 g/m2 in men and > or = 110 g/m2 in women; finally carotid plaque was defined as a focal thickening > 1.3 mm. RESULTS: Hypertensive retinopathy was the most frequent (KWB grade I 46%, II 32%, III-IV < 2%) marker of target organ damage, followed by carotid plaques (43%), LVH (22 %, eccentric LVH was the prevalent type and was 1.8 times as frequent as the concentric one) and microalbuminuria (14%). CONCLUSIONS: At variance with the markers of cardiac, macrovascular and renal damage, an extremely high prevalence of retinal abnormalities (narrowings and initial arterio-venous crossings) were found in our population. If, as suggested by the WHO/ISH guidelines, these retinal abnormalities were considered as a reliable marker of target organ damage, then almost all patients would be affected by hypertensive vascular disease. Based on this evidence it is suggested that retinal abnormalities included in funduscopic grades I and II of the KWB classification should not be considered among the criteria for the quantitative detection of target organ damage.

Adult↗

Inhibition of the P-glycoprotein- and multidrug resistance protein-mediated efflux of anthracyclines and calceinacetoxymethyl ester by PAK-104P.

Multidrug resistance phenotype in mammalian cells is often correlated with overexpression of P-glycoprotein or Multidrug Resistance-Associated protein (MRP(1)). Both proteins are energy-dependent drug efflux pumps that efficiently reduce the intracellular accumulation and hence the cytotoxicity of many natural cytotoxins. Overexpression of these transporters by tumor cells is thought to be a significant factor in both intrinsic and acquired resistance to anticancer drugs. Consequently a great deal of interest is focused on identifying chemical agents that can either antagonise drug transport by these proteins or that can inhibit the proliferation of tumors cells despite the expression of these transporters. P-glycoprotein-mediated multidrug resistance is reversed by a variety of compounds, but surprisingly, few agents reverse the MRP(1)-mediated multidrug resistance. However, it has recently been shown that 2-[4-(diphenylmethyl)-1-piperazinyl]ethyl-5-(trans-4,6-dimethyl-1, 3, 2-dioxaphosphorinan-2-yl)-2, 6-dimethyl-4-(3-nitrophenyl)-3-pyridinecarboxylate P oxide (PAK-104P) was able to inhibit the P-glycoprotein and MRP(1)-mediated efflux of several compounds. Understanding of the interactions between transporters and multidrug resistance reversing agents is important in the design of more effective multidrug resistance modulators. We now examined the effect of PAK-104P on Pgp-and MRP1-mediated efflux of three anthracyclines, daunorubicin, pirarubicin, hydroxydoxorubicin and of calcein acetoxymethyl ester and calcein. Our data show that PAK-104P non-competitively inhibits the P-glycoprotein-mediated efflux of anthracycline derivatives and calcein acetoxymethyl ester with an inhibitory constant K(I)=0. 25+/-0.05 microM. PAK-104P also non-competitively inhibits the MRP(1)-mediated efflux of daunorubicin, pirarubicin, hydroxyrubicin, calcein acetoxymethyl ester and calcein. However, surprisingly, in this case the K(I) values obtained were very different ranging from 0.06 for hydroxyrubicin to 10 microM for calcein. These data strongly suggested the existence of two different mechanisms for the inhibition by PAK-104P of the MRP(1)-mediated efflux of molecules: a first mechanism, involving a low-affinity site for PAK-104P, and which would concern molecules such as calcein, cysteinyl leukotriene LCT(4) etc. whose efflux do not depend on glutathione. A second mechanism involving a high-affinity site for PAK-104P and which would concern molecules such as anthracyclines, calcein acetoxymethyl ester whose efflux depends on the presence of glutathione.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

"To better know hypertension": educational meetings for hypertensive patients.

BACKGROUND: Pilot educational meetings were conducted to (1) verify the support of hypertensive patients in this initiative; (2) test the knowledge of patients regularly followed-up in our Hypertension Centre Outpatient Clinic concerning problems related to hypertension; (3) improve patients knowledge about hypertension through a formal teaching session, (4) compare the knowledge of these patients with that of a control group. METHODS: An invitation to participate in an educational program on hypertension was extended to 210 consecutive patients (group I ) followed-up in the outpatient clinic of our Hypertension Centre. Each meeting included four sessions: (1) an interactive phase with electronic devices aimed at evaluating the degree of information about hypertension by means of multiple-choice questionnaires, (2) a traditional teaching session, (3) an interactive phase to assess the compliance to treatment, and (4) a general discussion session. The control group (II) included 144 hypertensive patients referred for the first time to our Hypertension Centre. Before the initial visit the patients were asked to answer a questionnaire identical to that provided to group I during the meetings. RESULTS: The meetings were attended by 183 out of the 210 patients in group I (participation rate = 87%). The answers to the questions were corrected as a percentage ranging from 73.7 to 95.6 in group I and from 43.9 to 74.7 in group II (p < 0.01). The provision of more detailed information about problems in hypertension was associated with better compliance to treatment and blood pressure control. (BP under treatment 138 +/- 14/83 +/- 7 mmHg in group I, 152 +/- 15/91 +/- 11 mmHg in group II; (p < 0.01). CONCLUSIONS: Our data indicate that this type of educational approach is appreciated by patients (participation rate 87%) and that the level of knowledge about hypertension and compliance to treatment are greater in selected patients than in control patients.

Aged↗

Prevalence of target organ damage in treated hypertensive patients: different impact of clinic and ambulatory blood pressure control.

OBJECTIVES: First, to evaluate the prevalence of left ventricular (LV) hypertrophy, LV concentric remodelling and microalbuminuria in a selected sample of treated hypertensive patients with effective and prolonged clinic blood pressure (BP) control (BP < 140/90 mmHg). Second, to compare the prevalence of these markers of organ damage in patients with and without ambulatory BP (ABP) control, defined as average daytime BP < 132/85 mmHg). DESIGN AND METHODS: Fifty-eight consecutive hypertensive patients who attended our hypertension outpatient clinic over a period of 3 months and were regularly followed up by the same medical team were included in the study. Obesity, diabetes mellitus, history or signs of cardiovascular or renal complications and major noncardiovascular diseases were the exclusion criteria from the study. Each patient underwent 24 h ABP monitoring, echocardiography and 24 h urine collection for albumin measurement. RESULTS: The prevalence of LV hypertrophy (LV mass index > 125 g/m2 in both sexes), LV concentric remodelling (relative wall thickness > 0.45) and microalbuminuria (urinary albumin excretion < 300 mg/ 24 h) in this selected group of patients (32 men, 26 women; mean age 53 +/- 9 years; mean clinic BP 122 +/- 9/ 78 +/- 6 mmHg) was markedly low (6.9, 8.6 and 5.1%, respectively). The 26 patients with effective ABP control (group I) were similar to the 32 patients without effective ABP control (group II) in age, gender, body surface area, clinic BP, smoking habit, glucose, cholesterol and creatinine plasma levels. Prevalence of LV hypertrophy, LV concentric remodelling and microalbuminuria was lower in group I than in group II (0 versus 12.9% P< 0.01, 7.7 versus 9.4% NS, 3.8 versus 6.2% NS, respectively). CONCLUSIONS: This study demonstrates that nonobese, nondiabetic hypertensive patients with an effective clinic BP control have a very low prevalence of target organ damage and that LVH is present only in individuals with insufficient ABP control.

Albuminuria↗

Liver abnormalities during growth hormone treatment.

BACKGROUND: Occasional and transient increase in liver enzymes is reported during growth hormone (GH) treatment in girls with Turner syndrome (TS). METHODS: Retrospectively, the specific role of GH treatment on liver and muscular enzymes was evaluated in 78 patients (48 boys; age range 4.0-20.8 years) affected by GH deficiency (GHD) who had been treated with GH for at least 1 year (range: 1-15 years). All patients had normal serum levels of liver and muscular enzymes before GH therapy was started. RESULTS: A clinically asymptomatic and mild increase in serum transaminase levels was observed in 6 of 78 patients with GHD during GH treatment; 3 (3.8%) of the patients showed an isolated, transitory and self-limiting increase in serum liver transaminase levels which was noticed 6 to 12 months after GH treatment was started, and normalized spontaneously within 3 to 6 months, without stopping the therapy. Three additional patients showed a transitory mild increase both in aspartate aminotransferase (AST) and creatine phosphokinase (CK) which also normalized spontaneously within 3 to 6 months. The increase in transaminase levels was not related to the brand of GH preparations nor to the dosage administered. CONCLUSIONS: A mild, transient, self-limiting increase in serum transaminase may occur during GH treatment. Concomitant determination of CK serum levels may quickly differentiate muscular from hepatic hypertransaminasemia. Except for persistent cases, this condition does not generally require further investigations.

Adolescent↗

Adiabatic approximation and parametric stochastic resonance in a bistable system with periodically driven barrier

In this paper we compare the analytical adiabatic exponential approximation and exact numerical description of fluctuation-induced transitions in a "quartic" potential with periodically driven barrier. We show that the adiabatic approximation gives an adequate description of the processes in a wide region of parameter space and the accuracy of the approximation improves with increasing noise intensity. For parameter values outside this region, a different kind of resonant activation, which we call parametric stochastic resonance, is observed.

Journal Article↗

Phase locking effect and current reversals in deterministic underdamped ratchets

We study the transport properties (currents) of deterministic underdamped ratchets in terms of phase locking dynamics. The occurrence of reverse currents is interpreted in terms of different stability properties of the periodic rotating orbits and is shown to exist also in the absence of bifurcations from chaos to periodic motion. We briefly discuss the effects of noise on this phase locked dynamics.

Journal Article↗

Shock wave dynamics in a discrete nonlinear Schrodinger equation with internal losses

Propagation of a shock wave (SW), converting an energy-carrying domain into an empty one, is studied in a discrete version of the normal-dispersion nonlinear Schrodinger equation with viscosity, which may describe, e.g., an array of optical fibers in a weakly lossy medium. It is found that the SW in the discrete model is stable, as well as in its earlier studied continuum counterpart. In a strongly discrete case, the dependence of the SWs velocity upon the amplitude of the energy-carrying background is found to obey a simple linear law, which differs by a value of the proportionality coefficient from a similar law in the continuum model. For the underdamped case, the velocity of the shock wave is found to be vanishing along with the viscosity constant. We argue that the latter feature is universal for long but finite systems, both discrete and continuum. The dependence of the SW's width on the parameters of the system is also discussed.

Journal Article↗

Impact of blood pressure control on prevalence of left ventricular hypertrophy in treated hypertensive patients.

AIM: The aim of the present study was to evaluate (1) the prevalence and patterns of left ventricular hypertrophy (LVH) and (2) the impact of blood pressure (BP) control, assessed by clinical and 24-hour ambulatory BP monitoring (ABPM) criteria on the persistence of LVH in a representative sample of treated patients attending our Hypertension Clinic. METHODS: One hundred consecutive essential hypertensives (61 m/39 f, age 56+/- 9 years) regularly followed up by the same medical team (average period 52 months, 12-156 months) were included in the study and underwent 24-hour ABPM and complete echocardiographic examination. RESULTS: Twenty-eight of the 100 patients were found to have LVH [left ventricular mass index (LVMI) >125 g/m(2) in men and >110 g/m(2) in women]; LVH was eccentric in 20 patients and concentric in the remaining 8. LVMI did not correlate with clinical BP values but only with ABPM values (mean 24 h systolic r = 0.34, p <0.01; diastolic r = 0.37, p <0.01). The prevalence of LVH in patients controlled according to clinical BP criteria (n = 43, BP <140/90 mm Hg) was 19%, in patients controlled according to ABPM criteria (n = 30, BP during daytime <132/85 mm Hg) 17%, and in those controlled with both criteria (n = 16) 6% (p <0. 01). CONCLUSIONS: The results of this study suggest that the eccentric type of LVH is the prevalent pattern in chronically treated patients. The persistence of LVH is significantly dependent on BP levels achieved during treatment; indeed the prevalence of LVH is very low in patients with an optimal BP control, whereas it is elevated (37%) in uncontrolled patients.

Antihypertensive Agents↗

Near final height after GnRH agonist treatment in central precocious puberty.

The impact of treatment of central precocious puberty (CPP) with gonadotropin-releasing hormone agonists (GnRHa) on final height remains controversial. We analyzed the long term results of 23 girls with CPP treated with triptorelin or leuprolide. Their "near final height" (NFH) assessed at a bone age of at least 14 years and expressed as SDS, was compared either with predicted height before treatment (PAH) or with parental height (TH). We also compared NFH of 12 girls treated before 8 years of age (7.0 +/- 0.5 yr) with NFH of 11 girls treated after 8 years old (8.5 +/- 0.3 yr). The NFH of the 23 girls (-0.9 +/- 1.0 SDS) was not different either from PAH (-0.85 +/- 1.5 SDS) or from TH (-0.5 +/0.6 SDS). Earlier treated girls reached a NFH (-0.97 +/- 1.0 SDS) not different from later treated girls (-0.91 +/- 1.0 SDS; p = ns) and both groups reached parental height (NFH - TH = -0.44 +/- 1 and -0.09 +/- 0.83 SDS, respectively). In conclusion, our patients, treated either earlier or later, reached a near final height comparable to predicted height and familial target; however, these results might still improve further because the girls have not yet reached their final adult height.

Body Height↗

Adolescent girls with idiopathic central precocious puberty: typical character traits.

It has been reported that girls at onset of idiopathic central precocious puberty (ICPP) and during treatment have symbiotic character traits. The aim of this study was to investigate the development of character in a group of adolescents. Ten adolescent girls aged 14 years treated for ICPP were evaluated. All the adolescents in the study had a negative body image compared with age-matched controls and expressed a strong inhibition of their femininity. Their poor body image is reflected by their limited self-esteem. These adolescents have not been able to operate a reorganization of their affective life and therefore go through the necessarily slow and painful separation from their family. Symbiotic traits are "hard-wired" into their lives. These results suggest that at ICPP onset, in addition to setting up an educational program for the parents, it is equally important to supply psychological support for the patients in order to gain a better interaction between biological, psychological and cultural influences.

Brain Diseases↗

Exercise training in intermittent claudication.

BACKGROUND: Peripheral arterial occlusive disease (PAOD) at II stage results in a moderate to severe impairment in walking ability. Aim of this study, controlled and randomized, was to evaluate the efficacy of an intensive 4 weeks exercise training in PAOD followed by a six-month period and to analyse the risk factors for atherosclerosis and the site of the lesion for possible predictors of result outcome. METHODS: Patients with PAOD were included in the study (ankle/arm ratio < or = 0.7 and < or = 0.5 after exercise) with initial claudication distance (ICD) < or = 200 m and absolute claudication distance (ACD) < or = 500 m evaluated on a constant-load treadmill test (3 km/hr, 0% slope). Forty patients were randomized (all with antiplatelet therapy): 20 to a supervised walking exercise (mean ICD 121.8 m, ACD 289.7 m) and 20 to a non exercising control group (ICD 111.6 m, ACD 230.1 m). Both groups were tested at 4 weeks (T1) and 6 months (T2). Training group was enrolled in a 4-week supervised training program. RESULTS: In the training group 10% of patients became asymptomatic (>1000 m). At T1 ICD increased 141% (p<0.001) and ACD was with low-pain-claudication >1000 m in 50%, at T2 ICD was 200% (p<0.05) with 70% of asymptomatic for ICD and ACD. Control group has a no significant increase of ICD and ACD at T1 and T2. Only arterial hypertension and intermittent claudication severity emerged as negative predictive factors for the results of training. CONCLUSIONS: Vascular training produces a significant and lasting improvement in walking distance in PAOD.

Aged↗

[Combined treatment of thymoma. State of the art and our experience].

Thymoma is the most common neoplasm of the anterior mediastinum and is frequently associated with paraneoplastic syndromes. Surgery is the first therapeutic option, but in advanced disease a multidisciplinary approach is feasible, because of chemosensitivity and radiosensitivity of the disease. The natural history of thymoma after surgery points to local recurrence. Adjuvant radiotherapy seems to improve local control and survival. Chemotherapy based on cisplatin plus anthracyclines could be performed in advanced and metastatic disease. The optimal sequence of chemotherapy, radiation therapy and surgery is yet to be defined. In our experience, primary chemotherapy seems to give best results in advanced thymoma with good tolerability.

Antineoplastic Combined Chemotherapy Protocols↗