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Biomedical subjects

S Giannini

Publications and source records attributed to S Giannini.

At least 37 records · Page 2Linked to original sources

Pleiotropic effects of thiazolidinediones: taking a look beyond antidiabetic activity.

Thiazolidinediones (TZD) [Troglitazone (TRO), Pioglitazone (PGZ), Rosiglitazone, (RGZ)] are a novel class of antidiabetic drugs for patients with Type-2 diabetes mellitus (T2DM) able to decrease blood glucose, working through a reduction of insulin resistance. The family of TZD exerts its effect specifically bound to peroxisome proliferator-activated receptor y (PPARy). This is a member of the nuclear hormone receptor superfamily of ligand-dependent transcription factors, together with PPARalpha and deltabeta. Although PPARgamma is essentially expressed in adipose tissue, it has also been found in endothelial cells, macrophages, vascular smooth muscle cells, glomerular mesangial cells, hepatic stellate cells and in several cancer cell lines. In these cells, the PPARgamma activation by TZD determines modulatory effects on growth factor release, production of cytokine, cell proliferation and migration, extracellular matrix remodeling and control on cell cycle progression and differentiation. In addition, TZD have been shown to have a potent antioxidant effect. This review, taking a quick look beyond the antidiabetic activity of PPARgamma, shows the dramatic ranging of medical implications that the use of TZD could have modulating the PPARgamma activity in several diseases with a strong social impact, such as insulin resistance syndrome, chronic inflammation, atherosclerosis and cancer.

Arteriosclerosis↗

Bone microarchitecture as an important determinant of bone strength.

Structure and microarchitecture are determinant aspects of bone strength and essential elements for the assessment of bone mechanical properties. The main structural determinants of bone mechanical strength include width and porosity in the cortical bone; shape, width, connectivity, and anisotropy in the trabecular bone. There are several methods to assess bone architecture, particularly at the trabecular level. Two different approaches can be identified. The first is based on the use of optical microscopy and on the principles of quantitative histology, which evaluate microarchitecture two-dimensionally. The second applies the most modern diagnostic techniques, employing computed tomography and magnetic resonance to obtain and analyze three-dimensional images. From a clinical point of view, microarchitecture is an interesting aspect to study and define specific patterns, such as glucocorticoid-induced osteoporosis, or to evaluate bone alterations in transplanted patients. Microarchitecture seems to be a determinant of bone fragility independent of bone density. Moreover, bone microarchitecture seems to be important to understand the mechanisms of bone fragility as well as the action of the drugs used to prevent osteoporotic fractures. Several in vivo studies (on animals and humans) showed important findings on the effects of different treatments on microarchitecture. Bisphosphonates and parathyroid hormone seemed to preserve or even improve microarchitecture. These observations can provide an additional interpretation for the anti-fracture effect of drugs from a structural viewpoint. The challenge for the future will be to evaluate bone quality in vivo with the same or better resolution and accuracy than the invasive methods in use today.

Biomechanical Phenomena↗

Effect of age, weight and lifestyle factors on calcaneal quantitative ultrasound in premenopausal women: the ESOPO study.

The objective of this study was to identify the determinants of bone mass as measured by quantitative ultrasound (QUS) in premenopausal women. The study population is part of the "Epidemiological Study On the Prevalence of Osteoporosis" (ESOPO) on risk of the general population of Italy. We report the data on 2727 premenopausal women aged 40-50 years who are still regularly menstruating. Bone stiffness (called simplicity stiffness), which is derived from the values of broadband ultrasound attenuation (BUA) and speed of sound (SoS), was measured by a heel QUS device (Achilles Apparatus, Lunar, Co. USA). The most commonly recognized determinants of bone mass were modelled with stiffness by multiple regression analysis or analysis of variance (ANOVA). Bone stiffness was negatively related to age and number of cigarettes and positively to body weight, body weight at 25 years, height and estimated daily calcium intake. By multiple regression analysis, independent, positive, predictors of bone stiffness were age, weight at 25 years and daily calcium intake. Bone stiffness adjusted for age and body weight at 25 years was positively associated with outdoor activity score and negatively with number of pregnancies, chronic use of any drug, smoking and subjective health status. Bone stiffness was also somewhat (p < 0.015) negatively related to history of prolonged bedrest and thyroxin use. In conclusion, our results indicate that risk factors usually associated in other studies with DXA-BMD in elderly women are also associated with calcaneal bone stiffness, as measured by QUS in premenopausal women. These findings should help to identify premenopausal women at risk and to design an early strategy for osteoporosis prevention based on eliminating modifiable risks.

Adult↗

Cast vs external fixation: a comparative study in elderly osteoporotic distal radial fracture patients.

AIM: This study compared fracture treatment with plaster cast vs external fixation. METHODS: Forty elderly female osteoporotic wrist fracture patients were randomized to be treated with either plaster cast (Group A) or external fixation (Group B). Bone mineral density less than -2.5 T-score was among the inclusion criteria. RESULTS: In Group A, four redisplacements occurred, whereas in Group B there were none (p = 0.005). Horesh score was higher in Group B (p < 0.006) than in Group A. Volar angle deformity (p < 0.0005) and radial angle deformity (p = 0.008) were lower in Group B. CONCLUSIONS: This study shows that external fixation improves stability in elderly osteoporotic wrist fracture patients.

Aged↗

Low-intensity pulsed ultrasound in the conservative treatment of pseudoarthrosis.

AIM: The management of pseudarthrosis remains a challenge. Several in vivo animal and controlled clinical studies have demonstrated that low-intensity pulsed ultrasound can influence fracture healing. METHODS: A prospective longitudinal design was used. Fifteen patients (12 males and 3 females; mean age 35.5+/-12.9, range 18 to 60), all amateur athletes, under treatment for pseudarthrosis at different sites (average fracture age: of 336.6+/-60.1 days) were treated with a single 20 min daily application of low-intensity pulsed ultrasound (frequency 1.5 MHz and intensity 30 mW/cm2). All patients underwent clinical examination and plain radiography at the beginning of treatment and were followed up clinically and radiographically at 4, 8, 12, 16, 20 and 24 weeks until the fracture healed. RESULTS: All fractures healed with a mean healing time of 94.7+/-43.8 days. CONCLUSION: Low-intensity pulsed ultrasound is effective in the management of long standing fracture non-unions. Prospective randomized studies are needed to confirm the value of this modality of treatment.

Adult↗

Definition of a population-specific DXA reference standard in Italian women: the Densitometric Italian Normative Study (DINS).

Osteoporosis is currently defined on the basis of the T-score by dual-energy X-ray absorptiometry (DXA). Despite its limitations, this definition is applied worldwide. However, the normal values provided by manufacturers may not be fully representative of specific local populations. So far, there are no normative data in the Italian population using Hologic densitometers. The Densitometric Italian Normative Study (DINS) is an ongoing multi-center study that aims to establish reference values for bone densitometry with dual-energy X-ray absorptiometry (DXA) in the male and female Italian population. In this paper we report the results of the lumbar vertebrae (L2-L4) and proximal femur in 1,622 women aged 20-79 years. Bone mineral density (BMD) was determined using dual-energy X-ray absorptiometry (DXA) on Hologic bone densitometers (Hologic, Waltham, Mass.). Most of the subjects were examined with a QDR 4500. The BMD of the lumbar vertebrae was virtually constant between 20 and 49 years (test for trend: P=0.66); the BMD values between 20-45 in premenopausal women (mean 1.036; SD 0.109 g/cm(2)) were thus defined as the peak bone mass values, significantly lower compared to the Hologic reference curve (mean 1.079, SD 0.11 g/cm(2)). The mean BMD values of the femoral neck were virtually identical to those of the NHANES study in the first 3 decades; after the age of 50 the BMD values were slightly greater than those of the NHANES subject. The subject classification according to the WHO criteria was similar using the DINS and NHANES reference values for the femur; for the spine, the Hologic reference values classified a larger proportion of women as osteoporotic (21 vs. 16%) or osteopenic (42 vs. 38%) compared to DINS.

Absorptiometry, Photon↗

Dynamic in-vivo tibio-femoral and bearing motions in mobile bearing knee arthroplasty.

To determine the tibio-femoral and bearing motions in well functioning mobile bearing total knee arthroplasties, a quantitative analysis by means of fluoroscopy was carried out during stair ascending, chair rising-sitting and step up-down motor tasks. Femoral and tibial component positions were obtained using a CAD-model-based shape matching technique. Direct measurement of mobile bearing motion was carried out by tracking previously inserted tantalum beads. A relatively small motion of the bearing was observed. The advantage of self-alignment claimed for the mobile bearing arthroplasty seems to be confirmed by subject-specific ranges of motion exhibited by these patients. It has also been demonstrated that these total knee arthroplasties, which are not fully conforming in flexion, provide little constraint to antero-posterior motion, leading to a kinematic pattern very similar to an ACL deficient knee.

Activities of Daily Living↗

Mobile and fixed bearing total knee prosthesis functional comparison during stair climbing.

OBJECTIVE: The purpose of this investigation is to determine the functional performance of the mobile bearing total knee replacement prosthesis as compared to the fixed bearing type total knee replacement prosthesis. DESIGN: Kinematics, kinetics, and electromyography data were gained from 10 patients with mobile bearing and 10 patients with a fixed bearing posterior stabilized Insall Burstein II total knee replacement during ascending and descending stairs. A control group of 10 normal subjects, matched by sex and age, was also analysed. BACKGROUND: No significant biomechanical differences in patients with different total knee replacement designs have been reported from level-walking studies. Slightly better performance of posterior retaining with respect to cruciate sacrificing total knee replacement designs have been claimed from stair climbing studies. Only one study has been conducted regarding mobile versus fixed bearing total knee replacement assessed by gait analysis. This study did not show any biomechanical differences between the two groups. METHODS: Motion analysis was used to quantify the knee kinematics, kinetics, and electromyography (right and left longissimus dorsi, gluteus medius, rectus femoris, biceps femoris, semitendinosus, gastrocnemius and tibialis anterior muscles) during stair ascent and descent. RESULTS: The mobile bearing group demonstrated a reduced knee extensor moment during stair climbing and descending, and a reduced knee adductor moment during stair climbing. When ascending stairs, most of the mobile bearing patients show a peak knee flexion and a peak knee flexion moment at the late stance phase during the double support period. This kinematic and kinetic pattern is absent in normal subject. Both mobile bearing and fixed bearing groups showed abnormal electromyography patterns in both descending and ascending. CONCLUSIONS: During stair climbing, the mobile bearing design demonstrates a different kinematic pattern to the fixed bearing total knee replacement. Lower limb compensatory mechanisms seemed to be adopted particularly by the mobile bearing patients during ascending stairs. RELEVANCE: Total knee replacement patient with mobile bearing design can feel excessive femoro-tibial motion during daily living activities such as stair climbing and descending. Proprioceptive control of this tibio-femoral translation is needed as demonstrated by the lower limb compensatory mechanism. This data suggest that antero-posterior constraint structures (ligamentous or mechanical) are important to obtain reproducible knee kinematics.

Aged↗

Muscle activation pattern and gait biomechanics after total knee replacement.

OBJECTIVE: The aim of this study is to evaluate residual muscle function abnormalities after total knee replacement, with respect to gait kinematics and kinetics. DESIGN: Longitudinal study on a follow-up of up to two years. BACKGROUND: Gait usually presents an excellent improvement after total knee replacement. Nevertheless, some kinematics and kinetics abnormalities persist even after a long period of time and they might have implications in long-term prosthesis failure. Additionally, lower limb muscle activity has not been sufficiently studied in the past directly by means of dynamic EMG. METHODS: Nine patients who had a posterior cruciate sparing total knee replacement design were evaluated by means of clinical assessment and gait analysis at the end of rehabilitation trials at six, twelve and twenty four months. EMG from trunk and lower limb muscles was registered and elaborated through a statistical detector for the on-off timing. RESULTS: Gait analysis showed a slow gait, with a "stiff knee gait pattern" and prolonged muscular co-contractions during stance. CONCLUSIONS: Knee kinematics and kinetics abnormalities during loading acceptance after total knee replacement are associated with co-contractions in muscular activation pattern. RELEVANCE: Gait pattern at two years after total knee replacement is deemed unphysiological, potentially dangerous for the implant duration in time and responsible for residual disability in patients. Muscular behavior during daily activities provides insight into the integration of the prosthetic biomechanics within the muscular-skeletal system. This information is of relevance to improve prosthetic design, rehabilitation programs and knee motor performance.

Aged↗

Botulinum toxin with and without casting in ambulant children with spastic diplegia: a clinical and functional assessment.

This study compared clinical and functional outcomes after treatment with botulinum toxin A (BTX-A) and BTX-A with casting in children with dynamic equinus foot. Ten children (seven males, three females; mean age 6 years 4 months, SD 2 years 7 months; range 4 to 11 years) with mild spastic diplegia and independent walking were divided into two groups: group 1, BTX-A and group 2, BTX-A plus casting. BTX-A was injected in the triceps surae bilaterally at multiple sites while the children were sedated with mask anaesthesia. Dysport toxin was used, 15 to 20 IU/kg in each muscle. Immediately after injection an ankle-foot orthosis was applied to children in group 1 and a cast to children in group 2. Clinical assessment using the Ashworth scale, Gross Motor Function Measure (GMFM), range of movement measurement, and gait analysis was performed before treatment and 1, 4, and 12 months after treatment. Spasticity decreased significantly at 1-month examination in both groups (p = 0.002), at 4-month examinations (Wilcoxon test p = 0.003), and 12 month (p = 0.052) examinations in group 2. GMFM highlighted a significant improvement in group 2 at the 4-month examination (p = 0.052 for standing,p = 0.007 for walking). Gait analysis showed a significant increase in the walking speed in group 2 (p = 0.04). No change was detected in ankle kinematics and kinetics or in muscular activity during the gait cycle. We confirmed that BTX-A reduces spasticity and improves functional performance in standing and walking; association with casting provides more marked and enduring results.

Ankle↗

Histomorphological study of bone response to hydroxyapatite coating on stainless steel.

Bone response to hydroxyapatite coating on stainless steel has not been so extensively tested in animals as it happened for other metallic substrate, like Ti6Al4V. For this reason, authors performed an in vivo histomorphological electron microscopic study of hydroxyapatite coating on duplex stainless steel cylinders, to gather further evidences on the characters of bone apposition at the interface. Sixteen HA-coated cylinders were implanted in the distal femur of New Zealand White rabbits. Comparison with uncoated controls was made. Retrieval steps were at: 4, 8, 26 and 34 weeks. Specimens were analyzed in a Jeol JSM 6301F scanning electron microscope. The response to HA-coated samples has a morphological character of tight apposition between bone and coating. Osteocytic lacunae may be found few microns close to the coating and newly formed bone is extremely interlocked with it so that even an higher magnification electron-microscopy cannot resolve any discontinuity in between. Pictures of physiological bone-turnover are distinguishable at the bone-coating interface; areas of well preserved coating may be present together with areas where local exfoliation or fragmentation has already completely exposed the metallic substrate. On the opposite in uncoated samples, despite a morphological picture of properly formed bone, the largest area of the metal has no direct apposition with it.

Journal Article↗

Importance of radio-guided minimally invasive parathyroidectomy using hand-held gamma probe and low (99m)Tc-MIBI dose. Technical considerations and long-term clinical results.

AIM: (99m)Tc-MIBI radio-guided surgery results, obtained in a group of 141 patients with primary hyperparathyroidism (HPT), are reported. METHODS: All patients were preoperatively evaluated by a single day protocol based on double-tracer parathyroid scintigraphy and neck ultrasound, and then operated by the same surgical team. In 102 patients (72.3%) with a high scan/ultrasound probability of solitary parathyroid adenoma and normal thyroid gland, a minimally invasive radio-guided surgery was planned. In the other 39 patients (27.7%) with scan/ultrasound evidence of multi-glandular disease (n=8) or concomitant nodular goiter (n=31), the intraoperative gamma probe was used during a standard bilateral neck exploration. Intraoperative quick parathyroid hormone (PTH) levels were routinely measured. The minimally invasive radio-guided surgery technique we developed, consisted of: a) injection of a low 37 MBq (99m)Tc-MIBI dose in the operative theatre during anaesthesia induction, b) patient's neck scan with a hand-held gamma probe just before the surgical cut to localize the cutaneous projection of the parathyroid adenoma, c) intraoperative probe detection of the parathyroid adenoma and its removal through a small 2-2.5 cm skin incision. RESULTS: Minimally invasive radio-guided surgery was successfully performed in 99/102 patients (97.0%). The gamma probe was particularly useful in patients with an ectopic parathyroid adenoma in the upper mediastinum (n=11) or to the carotid bifurcation (n=1) or located deep in the neck (n=8). Minimally invasive radio-guided surgery was also obtained in 18/23 patients who had previously undergone thyroid/parathyroid surgery. The mean operative time for minimally invasive radio-guided surgery was 38 min. No major surgical complication was recorded. Conversion to bilateral neck exploration was required in only 3 cases because of intra-operative diagnosis of parathyroid carcinoma (n=2), and persistence of elevated quick PTH levels after removal of the preoperatively visualized parathyroid adenoma (n=1). Among patients treated by standard bilateral neck exploration, the gamma probe was useful in localizing a thymical enlarged parathyroid gland in 1 patient with multi-glandular disease, a parathyroid adenoma located deep in the neck in 4 patients with concomitant nodular goiter and an ectopic parathyroid adenoma to the carotid bifurcation in another. However, in some other patients with a parathyroid adenoma located near to the thyroid, it was difficult to intraoperatively distinguish the parathyroid adenoma from a MIBI avid thyroid nodule. CONCLUSION: It can be concluded that: (a) in primary HPT patients with high scan/ultrasound probability of solitary parathyroid adenoma and normal thyroid gland, the gamma probe appears to be an effective, rapid and safe technique to perform minimally invasive radio-guided surgery; b) a (99m)Tc-MIBI dose as low as 37 MBq appears to be adequate to successfully perform radio-guided surgery; c) the measurement of quick PTH is recommended during minimally invasive radio-guided surgery; d) minimally invasive radio-guided surgery can be performed also in HPT patients with previous parathyroid/thyroid surgery thus limiting surgical trauma; e) with the possible exception of parathyroid adenoma located in ectopic sites or deep in the neck, the gamma probe technique does not seem recommendable in HPT patients with concomitant nodular goiter.

Adult↗

Bone alterations in patients with idiopathic hypercalciuria and calcium nephrolithiasis.

OBJECTIVES: To verify whether alterations in bone density and turnover in patients with calcium nephrolithiasis and hypercalciuria are observable in various subgroups of patients divided according to the pathogenesis of the hypercalciuria. METHODS: Seventy patients with calcium nephrolithiasis and idiopathic hypercalciuria, 19 to 64 years old, were assessed for spine and femur mineral metabolism and bone density using a Dexa evaluation system. After a low calcium diet, the subjects were classified into two groups: fasting hypercalciuria (FH, 39 patients) and absorptive hypercalciuria (AH, 31 patients). RESULTS: Only in the patients with FH was the lumbar spine bone density lower than in the controls (P <0.001). Also, only the patients with FH had higher bone alkaline phosphatase and urinary hydroxyproline levels than the control group (P <0.005 and <0.015, respectively). The blood pH levels were lower, even though within the normal range, in the hypercalciuric patients than in the controls (P <0.01). There was a negative correlation between the urinary hydroxyproline level and lumbar spine and femoral neck density in patients with FH (P <0.001 and <0.005, respectively), and the blood pH correlated positively with the lumbar spine bone density. CONCLUSIONS: Altered bone metabolism and overall bone loss were found only in the patients with FH. Overloading of acid valences, perhaps of dietary origin, could be the pathogenic factor responsible.

Adult↗

High-dose intravenous immunoglobulin in the treatment of acute myocarditis. A case report and review of the literature.

A few reports have suggested the beneficial effect of high-dose intravenous immunoglobulin (IVIG) in the treatment of acute myocarditis and cardiomyopathy. We describe a 49-year-old woman in which acute myocarditis was diagnosed on the basis of clinical and echocardiographic findings. Conventional treatment with captopril and frusemide was administered: intravenous heparin and, subsequently, oral anticoagulants were added because of the appearance of an apical thrombus. On the fifth day of hospitalization, treatment with high-dose (400 mg kg(-1) day(-1)) IVIG was started and prosecuted for 5 days. A dramatic improvement of clinical conditions was observed, with increase of the left ventricular ejection fraction (LVEF) from 30% to 75% within 1 week. One year after the diagnosis the patient is in good health, with steady normal LVEF. The rapid recovery, which was immediately subsequent to the administration of high-dose IVIG, suggests that this kind of treatment has been effective in our patient with acute myocarditis.

Acute Disease↗

Three-dimensional domain swapping in the folded and molten-globule states of cystatins, an amyloid-forming structural superfamily.

Cystatins, an amyloid-forming structural superfamily, form highly stable, domain-swapped dimers at physiological protein concentrations. In chicken cystatin, the active monomer is a kinetic trap en route to dimerization, and any changes in solution conditions or mutations that destabilize the folded state shorten the lifetime of the monomeric form. In such circumstances, amyloidogenesis will start from conditions where a domain-swapped dimer is the most prevalent species. Domain swapping occurs by a rearrangement of loop I, generating the new intermonomer interface between strands 2 and 3. The transition state for dimerization has a high level of hydrophobic group exposure, indicating that gross conformational perturbation is required for domain swapping to occur. Dimerization also occurs when chicken cystatin is in its reduced, molten-globule state, implying that the organization of secondary structure in this state mirrors that in the folded state and that domain swapping is not limited to the folded states of proteins. Although the interface between cystatin-fold units is poorly defined for cystatin A, the dimers are the appropriate size to account for the electron-dense regions in amyloid protofilaments.

Amino Acid Sequence↗

Computer-assisted design of the sagittal shapes of a ligament-compatible total ankle replacement.

The poor results of total ankle replacement have been attributed to the inability of designers to restore adequately the critical mutual function of the ligaments and the articular surfaces. The purpose of this study was to design sagittal shapes of the articular surfaces for a new ankle prosthesis to be compatible with the geometry of the retained ligamentous structures. Several ligament-compatible pairs of articular surfaces were tested using a computerised version of a four-bar linkage model. The kinematics of the ankle when replaced by non-conforming two-component and by fully conforming three-component designs with either flat, concave or convex tibial surfaces were assessed by the model. A ligament-compatible convex-tibia fully-congruent three-component prosthesis showed the best features. The three-component prosthesis allows complete congruence over the entire range of flexion. A convex shape for the tibial arc was preferred because of the better degree of entrapment of the meniscal bearing. A 5 cm convex-tibia arc radius gave 2 mm entrapment together with 9.8 mm of tibial bone cut. Ligament elongation imposed by full congruence of the articular surfaces was less than 0.03% of the original length. The original patterns of joint kinematics and ligament tensioning are closely restored in the joint replaced by the proposed prosthesis.

Ankle Joint↗

Direct measurement of IGF-I and IGFBP-3 in bronchoalveolar lavage fluid from idiopathic pulmonary fibrosis.

Idiopathic pulmonary fibrosis (IPF) is characterized by the rearrangement of extracellular matrix and progressive increase in the amount of fibrotic tissue in the lung. IGF-I is a potent profibrogenic molecule and its bioavailability is dependent on at least 6 binding proteins called IGFBPs. Among these, IGFBP-3 is the most represented in serum and in different connective tissues. The purpose of this study was to identify and characterize IGFBP-3 in bronchoalveolar lavage (BAL) fluids. We studied 11 patients with IPF and 6 normal subjects by performing baseline pulmonary function test and BAL. IGF-I and IGFBP-3 were measured by RIA in BAL and serum. No significant differences were observed between serum IGF-I and IGFBP-3 from IPF patients and normal subjects. Instead, the direct measurement in BAL revealed a significant increase of IGF-I and IGFBP-3 in IPF patients compared to normal subjects. BAL IGF-I and IGFBP-3 concentrations were significantly related to inspiratory vital capacity (IVC) and carbon dioxide partial pressure (PaCO2): the higher the value of IVC and the lower the value of PaCO2, the higher the level of IGF-I and IGFBP-3. In conclusion, IGFBP3 and IGF-I could be important local mediators of IPF. Their direct measurement in BAL in IPF patients could be used as a clinical marker of the disease, since high levels of IGFBP-3 and IGF-I in BAL are associated to the initial phase of the disease.

Aged↗