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A Carpi

Publications and source records attributed to A Carpi.

At least 37 records · Page 2Linked to original sources

Large needle aspiration biopsy and galectin-3 determination in selected thyroid nodules with indeterminate FNA-cytology.

Thyroid fine-needle aspiration biopsy (FNA)-cytology is widely used for the preoperative characterisation of thyroid nodules but this task is difficult for follicular lesions, which often remain undefined. We propose a strategy for improving the preoperative characterisation of selected follicular thyroid proliferations, which is based on large needle aspiration biopsy (LNAB) and galectin-3 expression analysis. Eighty-five thyroid specimens were obtained by LNAB (20-gauge needles) from thyroid nodules with indeterminate follicular FNA-cytology. Aspirated material was processed as a tissue microbiopsy to obtain cell blocks for both cyto/histo-morphological evaluation and galectin-3 expression analysis, by using a purified monoclonal antibody to galectin-3 and a biotin-free immunoperoxidase staining method. Preoperative diagnosis was compared to the final histology. LNAB and cell-block technique allow a preliminary distinction between nodules with a homogeneous microfollicular/trabecular structure, as frequently observed in tumours, and lesions with mixed normo-micro-macrofollicular architecture, as observed in goitre. Furthermore, LNAB provides optimal substrates for galectin-3 expression analysis. Among 85 cases tested, 14 galectin-3-positive cases were discovered preoperatively (11 thyroid cancers and three adenomas confirmed at the final histology), whereas galectin-3-negative cases were 71 (one carcinoma and 70 benign proliferations at the final histology). Sensitivity, specificity and diagnostic accuracy of this integrated morphologic and phenotypic diagnostic approach were 91.6, 97.2 and 95.3%, respectively. In conclusion, LNAB plus galectin-3 expression analysis when applied preoperatively to selected thyroid nodules candidate to surgery can potentially reduce unnecessary thyroid resections.

Adult↗

Safety and effects on the lipid and C-reactive protein plasma concentration of the association of ezetimibe plus atorvastatin in renal transplant patients treated by cyclosporine-A: a pilot study.

Ezetimibe (E) is a new cholesterol adsorption inhibitor which prevents the adsorption of dietary and biliary cholesterol by binding to a recently described cholesterol transporter. This pilot study was performed to evaluate the safety and the low-density lipoprotein (LDL)-C and C-reactive protein lowering efficacy of atorvastatin (A) and of the association of A plus E in five renal transplant patients with hypercholesterolemia and mild renal functional impairment receiving cyclosporine-A (CsA). Patients received for three periods, each of 3 weeks, A at a dose of 20 mg/day; A at a dose of 10 mg/day and finally, A 10 mg plus E 10 mg daily. The medications were well-tolerated and no important clinical or laboratory (muscle enzyme, creatinine clearance and CsA concentration) abnormalities were observed throughout the study period. A alone lead to target LDL-C values only in two of five patients and did not significantly reduce the mean CRP values. The combination of E plus A produced the lowest lipid levels and significantly reduced CRP mean values and allowed all patients to attain target levels of LDL-C: total cholesterol decreased from 240 +/- 42 (mean +/- S.D.) to 171 +/- 34 mg/dl, LDL-C from 129 +/- 32 to 87 +/- 21 mg/dl, plasma triglycerides from 330 +/- 54 to 194 +/- 71 mg/dl and CRP from 6.2 +/- 1.9 to 3.9 +/- 2.4 mg/l (P < 0.05 for all). This pilot study suggests that the co-administration of E and A at 10 mg/day in renal transplant patients receiving CsA is well-tolerated and effective in reducing important cardiovascular risk factors.

Aged↗

Spectral analysis of skin blood flowmotion before and after exercise in healthy trained and in sedentary subjects.

Cutaneous blood flowmotion (CBF) can contribute to a reduction in the resistance in skin microvascular networks. The increase of CBF during exercise can improve the capacity of skin microvascular networks to transport and eliminate heat. In order to verify if the physical training could increase the skin blood flowmotion during exercise, we performed spectral analysis of cutaneous forearm laser Doppler signal, before and after acute maximal exercise in 15 healthy trained subjects (TS) and in 15 control sedentary subjects (SS). Within the total spectrum of 0.009 - 2.3 Hz, five frequency intervals of CBF were analysed: 0.009 - 0.02 Hz (endothelial activity), 0.02 - 0.06 Hz (sympathetic activity), 0.06 - 0.2 Hz (vascular myogenic activity), 0.2 - 0.6 Hz (respiratory activity), and 0.6 - 2.3 Hz (heart activity). In basal conditions, no difference between TS and SS was observed in the cutaneous blood perfusion (CBP), expressed in conventional perfusion units (PU), and in the mean value of CBF total spectrum power density (PD), measured in PU/Hz, while the absolute PD of the endothelial and myogenic CBF components was significantly higher (p < 0.05) in TS (0.69 +/- 0.62 PU/Hz and 0.47 +/- 0.43 PU/Hz, respectively) than in SS (0.29 +/- 0.16 PU/Hz and 0.23 +/- 0.16 PU/Hz, respectively). In both TS and SS, acute exercise induced a significant increase of CBP mean value (30.91 +/- 20.28 PU, p < 0.0005 and 16.45 +/- 7.02 PU, p < 0.0005; respectively) and of CBF total spectrum PD (6.65 +/- 4.13 Hz/PU, p < 0.001 and 4.17 +/- 1.86 Hz/PU, p < 0.05; respectively), with a significant difference of these two parameters between the two groups (p < 0.05). After exercise, CBF components regarding endothelial and myogenic activities maintained a higher PD mean value in TS in respect to SS (1.69 +/- 1.34 PU/Hz and 1.59 +/- 0.93 versus 0.91 +/- 0.44 and 0.98 +/- 0.48 PU/Hz respectively, p < 0.05). These findings suggest that physical training is associated with the increase of CBF and particularly on its endothelial and myogenic components in response to exercise. This can favour a greater reduction of resistance in skin microvascular networks during exercise and consequently an increase of its capacity to transport and eliminate heat.

Adult↗

Diazepam administration prevents testosterone decrease and lipofuscin accumulation in testis of mouse exposed to chronic noise stress.

Lipofuscin is an autofluorescent and undegradable material, which accumulates in tissues during ageing and under different types of stress. Among these, oxidative stress represents a major trigger for lipofuscin formation. However, prolonged noise exposure is also an effective stressful stimuli. Diazepam may inhibit lipofuscinogenesis in liver and prevent the noise-induced reduction of the steroidogenesis in the adrenal gland. The aim of the study was to ascertain whether chronic noise exposure causes lipofuscin accumulation in mouse testis, and to evaluate the effects of diazepam administration. Eight-week old mice were either exposed for 6 weeks (6 h day(-1)) to white-noise (group A), or received diazepam (3 mg kg(-1), i.p.) before noise exposures (group B), while a further group was used as control (group C). Light fluorescence and transmission electron microscopy revealed lipofuscin in large amounts in the Leydig cells in mice of group A, which concomitantly had low serum testosterone levels; pre-treatment with diazepam occluded both effects. The present study indicates that: (i) chronic noise exposure causes lipofuscin accumulation at the level of the Leydig cells and a decrease in testosterone; (ii) all these effects are suppressed by pre-treatment with diazepam. As the Leydig cells represent the only cellular type of the interstitial testicular tissue having peripheral benzodiazepine receptors, these results could be explained by the capacity of the peripheral benzodiazepine receptors to prevent reactive oxygen species damage and to increase the resistance of these cells to oxidative stress.

Animals↗

C-reactive protein in patients on chronic hemodialysis with different techniques and different membranes.

In hemodialysis patients, C-reactive protein (CRP), an acute-phase reactant, is a sensitive and independent marker of malnutrition, anemia, and cardiovascular mortality. The aim of the present study was to evaluate CRP levels in plasma samples from long-term hemodialysis patients on different extracorporeal modalities and dialyzed with different membranes, at baseline and after 6 months. Two hundred and forty-seven patients were recruited in eight hospital-based centers. All patients had been on their dialytic modality for at least 3 months and were prospectively followed in their initial dialytic modality for 6 months. Patients were treated with conventional bicarbonate dialysis (N = 127) or hemodiafiltration (N = 120). Patients treated with conventional bicarbonate dialysis were dialyzed with different membranes: Cuprophane (N = 51), low-flux cellulose modified membrane (N = 37) and synthetic membranes (N = 39). Hemodiafiltration was performed in post-dilution mode with polysulfone (N = 66) and polyacrylonitrile (N = 54) membranes. Analysis of baseline CRP values in the clinically stable patients showed that an unexpectedly high proportion (47%) of the patients had CRP values higher than 5 mg/l (upper limit in normal subjects). The mean +/- S.D. CRP values were significantly higher (P < 0.05) in hemodiafiltration with infusion volumes < 10 l per session (14.6+/-3.1 mg/l) than in standard hemodialysis (5.1 +/- 2.1 mg/l) and hemodiafiltration with infusion volumes > 20 l per session (4.9 +/- 2.1 mg/l). These values did not significantly change after 6 months of follow-up. Concerning the membranes, the highest levels of CRP were observed in patients dialyzed with Cuprophane with a significant increase from 15.1 +/- 3.6 to 21.2 +/- 3.1 mg/l after 6 months (P < 0.05); a significant reduction of CRP levels was observed in patients dialyzed with polysulfone in the same follow-up period (from 13.5 +/- 2.9 to 8.1 +/- 2.4 mg/l; P < 0.05). The CRP increase following low volume HDF can be related to back-filtration of bacterial derived contaminants.; moreover, an important effect on CRP of the hemodialysis membrane is observed and new synthetic membranes can be used to decrease these levels.

Acrylic Resins↗

Controversies in diagnostic approaches to the indeterminate follicular thyroid nodule.

In this paper we review the controversies in diagnostic approaches to follicular thyroid nodules with indeterminate cytology. The authors consider some of the controversies surrounding the indeterminate follicular thyroid nodule, including the definition and the postoperative outcome. Among the techniques that may improve preoperative diagnostic accuracy are large needle aspiration biopsy and immunohistochemistry for galectin-3.

Adenocarcinoma, Follicular↗

Skin blood flowmotion response to insulin iontophoresis in normal subjects.

In order to explore the mechanisms directly involved in the insulin vasodilatory activity, we studied skin blood flowmotion by means of spectral analysis of the skin forearm laser Doppler (LD) signal registered before and after iontophoresis of insulin in saline (I.S.) (0.1 ml Humulin R 100 IU/ml diluted 1/10 in 0.9% saline) or pure saline (P.S.) (0.1 ml of 0.9% saline) in twenty normal subjects. Skin LD blood perfusion was also measured in conventional perfusion unit (PU; 1 PU=10 mV). Using a Fast Fourier transform algorithm, power density (PD) of the total flowmotion spectrum, from 0.009 to 1.6 Hz, was measured in PU/Hz. Power density of five skin flowmotion frequency intervals (F.I.) within 0.009-0.02 Hz, 0.02-0.06 Hz, 0.06-0.2 Hz, 0.2-0.6 Hz and 0.6-1.6 Hz (referred to endothelial, sympathetic, myogenic, respiratory and heart activity, respectively) was also measured in PU/Hz. The mean skin LD perfusion increment (expressed as percent change from baseline) was significantly higher after I.S. than after P.S. (P<0.001, ANOVA for repeated measures). Skin flowmotion total spectrum mean PD value significantly increased following iontophoresis of both P.S. (from 1.06+/-0.62 to 1.86+/-0.94 PU/Hz, P<0.005) and I.S. (from 1.07+/-0.92 to 2.39+/-1.73 PU/Hz P<0.00005), however, the mean PD increment was significantly higher after I.S. than after P.S. (1.27+/-0.98 PU/Hz versus 0.69+/-0.67 PU/Hz, P<0.05). Only the flowmotion component referred to myogenic activity showed a percent PD increase from baseline significantly higher in response to I.S. than to P.S. iontophoresis (114.5+/-21.8% versus 58.8+/-17.9%, respectively, P<0.05). These findings show that insulin has a vasodilatory activity on skin microvascular district. The higher increase of total blood flowmotion PD and particularly of the component related to the myogenic activity in response to insulin iontophoresis suggests that the cutaneous vasodilatory activity of insulin is, in part, related to an important action of this hormone on skin microvascular smooth muscle.

Adult↗

Effect of nebivolol on QT dispersion in hypertensive patients with left ventricular hypertrophy.

Hypertensive patients with left ventricular hypertrophy (LVH) have increased QT dispersion, which is considered an early indicator of end-organ damage and a non-invasive marker of risk for clinically important ventricular arrhythmias and cardiac mortality. The purpose of this study was to examine the effect of nebivolol antihypertensive therapy on QT dispersion in hypertensive subjects. Twenty-five subjects (15 men and 10 women, mean age 53.6 +/- 4.5 years) with essential arterial hypertension and mild-to-moderate LVH (blood pressure: 147.2 +/- 6.2/90.6 +/- 3.8 mmHg; left ventricular mass indexed: 149.1 +/- 10.7 g/m(2)) were compared with 25 age-matched healthy control subjects. All the participants underwent a complete clinical examination, including electrocardiogram for QT interval measurements. The QT dispersion was defined as the difference between the longest and the shortest QT interval occurring in the 12-lead electrocardiogram. The QT dispersion was corrected (QTc) with Bazett's formula. Hypertensive subjects were treated with 5 mg daily of nebivolol. The ECG and echocardiogram were repeated after four weeks of treatment. At baseline, hypertensive patients showed QT dispersion (56.9 +/- 6.4 vs. 31.7 +/- 8.4 ms, P < 0.001) and QTc dispersion (58.3 +/- 6.2 vs. 33.2 +/- 7.8 ms, P < 0.001) significantly higher than control subjects. Four-week nebivolol treatment reduced blood pressure from 147.2 +/- 6.2/90.6 +/- 3.6 mmHg to 136.3 +/- 3.1/83.3 +/- 2.5 mmHg (P < 0.0001), and resting heart rate from 75.3 +/- 4.7 to 64.2 +/- 3.0 bpm (P < 0.001), without significant change in left ventricular mass (LVMi: 149.1 +/- 10.7 vs. 151.4 +/- 9.8 g/m(2), ns). Nebivolol-based treatment improved QT dispersion (56.9 +/- 6.4 vs. 40.5 +/- 5.8 ms, P < 0.001) and QTc dispersion (58.3 +/- 6.2 vs. 42.2 +/- 5.6 ms, P < 0.001), which remained higher than in control subjects (P < 0.001 in both cases). The reduction of QT dispersion did not correlate with arterial BP reduction. In conclusion, nebivolol reduced increased QT dispersion in hypertensive subjects after four weeks. This effect, occurred without any change in LVM, did not seem to be related to the blood pressure lowering and could contribute to reduce arrhythmias as well as sudden cardiac death in at-risk hypertensive patients.

Benzopyrans↗

Antihypertensive effect of oral potassium aspartate supplementation in mild to moderate arterial hypertension.

BACKGROUND: Previous studies showed that potassium chloride (48-120 mmol/day) supplementation reduced arterial blood pressure (BP) in hypertensive patients. OBJECTIVES: Our aim was to evaluate the effect of a lower dose of potassium aspartate salt on BP in individuals with essential arterial hypertension. METHODS: One hundred and four patients (65 males, age 53 +/- 12 years) with mild to moderate essential hypertension (systolic/diastolic BP 154.2/96.2 +/- 10.8/5.4 mmHg) were allocated in two comparable groups of 52 to receive or not 30 mmol/day per os of potassium aspartate supplementation for four weeks. Office and 24-h BP, as well as serum and urinary electrolytes, were measured at baseline and at the follow-up visit after four weeks. RESULTS: Office and 24-h BP did not change in the control group, while these values were significantly reduced in the potassium supplementation group. Changes in office (systolic BP: 154.4 +/- 8.2 vs. 142.2 +/- 7.6 mmHg; diastolic BP: 95.0 +/- 5.6 vs. 87.2 +/- 4.3 mmHg, P < 0.001 for both) and 24-h BP (systolic BP: 142.7 +/- 8.2 vs. 134.8 +/- 6.3 mmHg; diastolic BP: 90.8 +/- 4.4 vs. 84.6 +/- 3.8 mmHg, P < 0.001 for both) following potassium supplementation were highly significant. The changes in day time and night time BP were similar. The treated group showed significantly increased potassium serum level and 24-h urinary excretion of potassium (P < 0.01 in both cases) after four weeks, while the untreated group showed no significant changes of the same parameters. Urinary Na/K ratio decreased significantly with potassium supplementation (P < 0.001). In the treated group changes in office (r = 0.58, P < 0.001) and 24-h SBP (r = 0.51, P < 0.001), but not in DBP (r = 0.29 and r = 0.25, n.s.), correlated positively with the urinary Na/K ratio at baseline. CONCLUSIONS: A relatively low supplementation of 30 mmol/day of potassium as aspartate lowered office and 24-h ambulatory BP in subjects with mild to moderate essential hypertension. The antihypertensive effect was sustained throughout the day, and was greater in the patients with high basal urinary Na/K ratio.

Administration, Oral↗

Generalised wavelet analysis of cutaneous flowmotion during post-occlusive reactive hyperaemia in patients with peripheral arterial obstructive disease.

The purpose of the present study was to assess whether the generalised wavelet analysis (GWA) of the leg cutaneous laser Doppler (LD) flowmotion waves recorded during baseline (Bsl) and after skin post-occlusive hyperaemia (POH) can provide information on the leg cutaneous microcirculatory adaptation to stage II peripheral arterial obstructive disease (PAOD). With this aim the flowmotion was characterised in 20 healthy subjects (HS) and 20 stage II PAOD patients by GWA of LDF tracings during Bsl and POH test. The vascular endothelial and smooth muscle function was also evaluated exploring the arm skin vasodilatory response to iontophoretically delivered acetylcholine (Ach) and sodium nitroprusside (SNP) using LD. During Bsl there was no significant difference in leg skin perfusion between HS and PAOD patients (7.3+/-5.6 vs. 5.8+/-2.9 AU, respectively). PAOD patients revealed higher peak powers in the frequency interval of 0.007-0.02 Hz (120+/-82 vs. 85+/-62 AU(2)/Hz; P < 0.05), 0.02-0.06 Hz (116+/-128 vs. 63+/-48 AU(2)/Hz, respectively; P < 0.05) and 0.06-0.2 Hz (39+/-49 vs. 14+/-10 AU(2)/Hz; P < 0.05). These flowmotion frequencies are related to vascular endothelium activity, sympathetic activity and vessel wall myogenic activity, respectively. During POH the mean peak power of the flowmotion waves increased significantly (P < 0.05) in HS respect to Bsl with the only exception of the 0.02-0.06 Hz band. In the PAOD patients, compared to Bsl the amplitude of the flowmotion waves did not significantly change during POH. In addition, the PAOD patients presented an increased time from release to peak-flux (18.25+/-15.5 vs. 2.16+/-1.28 s, respectively; P < 0.05), an increased time from release to recovery of the basal perfusion (90.26+/-39.14 vs. 26.55+/-14.05 s, respectively; P < 0.05) and a lower slope of the POH curve (10+/-15 vs. 54+/-17 degrees , respectively; P < 0.05), compared with HS. The cutaneous arm vasodilatory response to Ach and to SNP was reduced in PAOD patients in comparison with HS (P < 0.001). In conclusion, our findings showed an increased amplitude of the frequency interval 0.007-0.02, 0.02-0.06 and 0.06-0.2 Hz during Bsl in PAOD patients which did not change during the POH test. All data suggest that in stage II PAOD patients the leg skin perfusion is not impaired during Bsl because of a compensatory mechanism related to increased endothelial, myogenic and sympathetic activities. However during reactive hyperaemia these mechanisms appear to be exhausted in accordance with the reduced vasoreactivity to Ach and SNP.

Acetylcholine↗

Inflammatory mediators and eosinophilia in atopic and non-atopic patients with nasal polyposis.

Nasal polyps are characterized by eosinophilic infiltration and presence of inflammatory mediators, such as total IgE, eosinophil cationic protein (ECP) and cytokines. The role of atopy in nasal polyp pathogenesis is still unclear. Therefore, we evaluated serum IgE levels, nasal mucus concentrations of ECP and cytokines and the number of infiltrating eosinophils in nasal tissue of polyps from atopic and non-atopic patients. Samples were obtained from a randomized population of 31 patients with nasal polyposis having endonasal sinus surgery and of 13 control subjects undergone corrective surgery of the nasal septum. On the basis of medical history of allergy, positive skin-prick tests and total IgE levels, patients with polyposis were divided in atopic (n = 13) and non-atopic (n = 18) patients. We determined levels of IgE in blood, ECP and cytokines (IL-4, IL-6, IL-8, IFN-gamma and IL-2) in nasal mucus, and number of infiltrating eosinophils in nasal tissue. The concentrations of total IgE, ECP, IL-4 and IL-8 and eosinophilia were significantly higher in all patients with nasal polyps compared with controls. Inside, all patients with nasal polyposis showed lower levels of IL-6, IFN-gamma and IL-2 compared with controls. The atopic patients showed significant differences when compared with non-atopic patients for the higher concentrations of total IgE (698.80+/-322.24 vs. 279.63+/-234.11; P < 0.0001) and IL-8 (1437.2 pg/ml+/-1250.7 vs. 605.5 pg/ml+/-481.1; P < 0.015). These findings suggest that inflammation still remains the major factor in the etiology of nasal polyposis and show different levels of inflammatory mediators into atopic and non-atopic patients.

Adult↗

Effects of pulsed electromagnetic fields on articular hyaline cartilage: review of experimental and clinical studies.

Osteoarthritis (OA) is the most common disorder of the musculoskeletal system and is a consequence of mechanical and biological events that destabilize tissue homeostasis in articular joints. Controlling chondrocyte death and apoptosis, function, response to anabolic and catabolic stimuli, matrix synthesis or degradation and inflammation is the most important target of potential chondroprotective treatment, aimed to retard or stabilize the progression of OA. Although many drugs or substances have been recently introduced for the treatment of OA, the majority of them relieve pain and increase function, but do not modify the complex pathological processes that occur in these tissues. Pulsed electromagnetic fields (PEMFs) have a number of well-documented physiological effects on cells and tissues including the upregulation of gene expression of members of the transforming growth factor beta super family, the increase in glycosaminoglycan levels, and an anti-inflammatory action. Therefore, there is a strong rationale supporting the in vivo use of biophysical stimulation with PEMFs for the treatment of OA. In the present paper some recent experimental in vitro and in vivo data on the effect of PEMFs on articular cartilage were reviewed. These data strongly support the clinical use of PEMFs in OA patients.

Animals↗

Effect of chronic aerobic exercise on cutaneous microcirculatory flow response to insulin iontophoresis and to ischemia in elderly males.

The aim of this study was to assess whether chronic aerobic exercise can favourably influence the vascular activity of insulin in elderly subjects. We measured in arbitrary units (A. U.) the cutaneous blood flow basally and in response to iontophoresis of insulin, by the means of a Laser Doppler flowmeter, on the right arm of 10 elderly athletes (10 males, aged 65 +/- 6 years) and of 10 sex- and age-matched sedentary subjects. The cutaneous blood flow response to ischemia was also explored in the right leg of the same subjects by means of the same instrument. No significant differences in cutaneous arm and leg blood flow were observed basally between athletes and sedentary subjects (7.25 +/- 2.65 A. U. versus 6.35 +/- 4.04 A. U. and 9.74 +/- 5.11 A. U. versus 9.41 +/- 6.40 A. U., respectively). Cathodal iontophoresis (six poulses of 0.1 mA each for 20 s, with 40-s interval between stimulations) of regular insulin (0.1 ml Humulin R 100 IU/ml diluted 1/10 with 0.9 % saline) induced a significant increase of cutaneous blood flow in both groups (p < 0.01 in athletes, p < 0.01 in sedentary subjects). However the maximal cutaneous blood flow response to insulin was higher in athletes than in sedentary subjects (24.69 +/- 13.34 A. U. versus 14.33 +/- 7.73 A. U., respectively, p < 0.05) as well as the curve of the net blood flux response to insulin iontophoresis (% change from baseline in response to insulin minus % change from baseline in response to saline iontophoresis) (p < 0.001 ANOVA for repeated measures). After ischemia there was a significant increase of leg cutaneous blood flow in both groups (p < 0.001 in athletes and in sedentary subjects) with higher blood flow response in athletes than in sedentary subjects (38.18 +/- 17.08 A. U. versus 26.01 +/- 6.39 A. U., respectively, p < 0.05). The time reached from the release of ischemia to peak-flow was significantly longer in sedentary subjects than in athletes (43.5 +/- 28.5 s versus 20.0 +/- 9.3 s, p < 0.05, respectively). These results suggest that chronic aerobic exercise increases insulin vasodilatory activity and improves endothelial function in elderly subjects.

Aged↗

Histomorphometric bone modifications induced by growth hormone treatment in a rabbit model of short bowel syndrome.

The effects of recombinant human growth hormone (rhGH) on cancellous and cortical bone were investigated in an experimental rabbit model of short bowel syndrome (SBS). Eighteen young male New Zealand rabbits, 2.0 +/- 0.2 kg b.w., were divided into three groups: an SBS Group submitted to a 70% midjejunoileal enterectomy and reanastomosis; an SBS-GH Group undergoing the same surgery and receiving 0.4 mg/kg/day rhGH for 28 days; a Control Group which was sham-operated. Thirty-five days after surgery, all the animals were pharmacologically euthanised and their femurs and L5 vertebrae were used for densitometric and histomorphometric studies. Vertebral and femoral densitometric results showed that the SBS Group presented significantly (P<0.01) lower values (10-25%) than the Control and SBS-GH Groups. Significant differences in the cancellous histomorphometric parameters, namely the trabecular bone area (-7% to 46%), trabecular thickness (-21% to 34%) and trabecular separation (17-32%), were observed between the SBS Group and the other groups. Both the SBS and SBS-GH Groups showed significantly (P<0.05) higher values than the Control Group in terms of cross-sectional area (approximately 24%), cortical area (approximately 20%), and periosteal perimeter (approximately 9%), while medullary area (41%) and endocortical perimeter (18%) were significantly higher (P<0.05) in SBS Group than those of Control Group. The current findings are encouraging and suggest that GH administration in SBS animal model used may improve skeletal tissue remodelling.

Animals↗

New polymers for drug delivery systems in orthopaedics: in vivo biocompatibility evaluation.

The use of biodegradable polymers for drug delivery systems excluded the need for a second operation to remove the carrier. However, the development of an avascular fibrous capsule, reducing drug release, has raised concern about these polymers in terms of tissue-implant reaction. Five novel polymers were evaluated in vivo after implantation in the rat dorsal subcutis and compared to the reference polycaprolactone (PCL). Poly(cyclohexyl-sebacate) (PCS), poly(L-lactide-b-1,5-dioxepan-2-one-b-L-lactide) (PLLA-PDXO-PLLA), two 3-hydroxybutyrate-co-3-hydroxyvalerate copolymers (D400G and D600G), and a poly(organo)phosphazene (POS-PheOEt:Imidazole) specimens were histologically evaluated in terms of the inflammatory tissue thickness and vascular density at 4 and 12 weeks from surgery. The highest values of inflammatory tissue thickness were observed in D600G (P < 0.01), PCS (P < 0.001) and PLLA-PDXO-PLLA (P < 0.001) at 4 weeks, while POP-PheOEt:Imidazole showed the lowest value of inflammatory tissue thickness (P < 0.05) at 12 weeks. D400G, D600G, PLLA-PDXO-PPLA and POP-PheOEt:Imidazole showed higher (P < 0.001) values of vascular density near the implants in comparison to PCL at 4 weeks. Finally, D400G and D600G increased their vessel densities while POP-PheOEt:Imidazole and the synthetic polyester PLLA-PDXO-PLLA presented similar vessel density values during experimental times. These different behaviours to improve neoangiogenesis without severe inflammatory tissue-responses could be further investigated with drugs in order to obtain time-programmable drug delivery systems for musculoskeletal therapy.

Animals↗

Adsorption of cationic antibacterial on collagen-coated titanium implant devices.

Two different cationic antimicrobial molecules, chlorhexidine (CH) and poly(hexamethylenebiguanide) (PH), were adsorbed from aqueous solution to titanium implant devices surface-modified by the covalent coupling of collagen on a polyanionic acrylic acid overlayer. Results show that more antimicrobial was adsorbed on surface modified implants as compared to control titanium devices. Moreover, the kinetic of release was affected by the interaction between the polyanionic overlayer and the cationic antimicrobial, leading to slower kinetic of release in the case of CH and stable adsorption in the case of polycationic PH . These data indicate that biochemically modified collagen coated surfaces could be endowed also by antimicrobial properties, in the spirit of present researches on multifunctional implant surfaces.

Adsorption↗

Skin microcirculation in peripheral arterial obliterative disease.

The important role of microcirculation in the pathophysiology and symptoms of peripheral arterial obliterative disease (PAOD) has been progressively emphasized during the past twenty years, thanks to the use of different non-invasive methods, such as capillaroscopy, laser Doppler (LD) fluxmetry and transcutaneous measurement of oxygen tension (tcPO2). Basally, in the diseased leg of stage II PAOD patients, leg skin perfusion recorded by means of LD fluxmetry is quantitatively normal. However, spectral analysis of skin LD tracing shows an abnormal flowmotion, with increased amplitude of the flowmotion waves related to endothelial, neurogenic and myogenic activities, suggesting a relatively early skin microcirculatory adaptation in this PAOD stage. Following ischemia, an impaired total skin LD hyperemia and a reduced skin capillary nutritional blood flow at capillaroscopy, concomitantly with a reduced increase of flowmotion waves related to endothelial, myogenic and sympathetic activities, have been observed in the diseased leg of stage II PAOD patients. In critical limb ischemia (CLI), a more advanced cutaneous microcirculatory deterioration has been clarified, with a more severely impaired post-ischemic hyperemia, a reduced tcPO2 and a severely perturbed skin flowmotion in the diseased leg. This integrated skin microcirculatory diagnostic approach can be used for a better management of PAOD patients.

Arterial Occlusive Diseases↗

Oral low-dose cyclophosphamide in metastatic hormone refractory prostate cancer (MHRPC).

The chemotherapeutic approach to hormone-refractory metastatic prostate cancer (MHRPC) for a long time included only estramustine. Then, attempts have been made with other various agents as cyclophosphamide, vinblastine, etoposide, taxanes and carboplatinum. Although the new drugs and combinations have increased the response rate of MHRPC, they have had no impact on the natural history of MHRPC, which is about 1 year as median time of survival. After an occasional observation of prolonged response in a patient with MHRPC treated with a very well tolerated oral low-dose of cyclophosphamide, from February 1996 to October 2002, seven more patients with MHRPC and progressive disease were consecutively recruited. Response to treatment was evaluated by conventional radiological procedures and/or serial serum PSA measurements. The decline of PSA value was considered to assess the response consistent with the response guidelines from the prostate specific antigen-working group. All eight studied patients continuously received oral low dose cyclophosphamide until progression or the occurrence of significant toxicity. So far three patients (37.5%) progressed (PD), two (25%) showed PR and the three remaining SD. Response rate was 25%, and clinical benefit occurred in 62.5% of the studied patients. In the five patients with clinical benefit on cyclophosphamide median duration of clinical benefit, PR and SD were 9, 24+ and 8 months, respectively. In these five patients median overall survival times from cyclophosphamide and from the first regimen of chemotherapy were 17 and 33+ months respectively, while in the three patients with PD they were 4 and 13 months. The same interval times in patients with > or =50% decline of serum PSA were 29 and 50.5 months, while in those with <50% decline of the same marker, they were 13 and 32 months, respectively. Grade 2 or 3 neutropenia were observed in all the studied patients. In four (50%) of them pulmonary and urinary infections that were easily cured by the common antibiotics occurred. These data suggest that the metronomic use of cyclophosphamide, given alone, has similar or higher activity with lower toxicity than when administered with other active drugs. So it can be an useful option before or after the use of other single or combined potentially active chemotherapeutic agents.

Administration, Oral↗