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Biomedical subjects

Sandro Giannini

Publications and source records attributed to Sandro Giannini.

At least 19 recordsLinked to original sources

Bisphosphonates decrease telomerase activity and hTERT expression in MCF-7 breast cancer cells.

Bisphosphonates are important in the management of tumours with secondary bone involvement. Recent findings have suggested that these drugs also have an effect on primary tumour burden. Telomerase is a cellular ribonucleoprotein reverse transcriptase responsible for elongation of the telomere. Telomerase expression is increased in many cancers. We studied the direct effects of clodronate, alendronate, and pamidronate (from 10(-6) to 10(-4) M) on MCF-7 human breast cancer cell line. In particular, we investigated their effect on viability, proliferation, apoptosis, human telomerase reverse transcriptase expression (h-TERT) by RT-PCR and telomerase activity. Alendronate and pamidronate showed an inhibition of viability (-63 and -35%, respectively; p < 0.0001) and proliferation of cancer cells, while no effect was observed with clodronate. Amino-bisphosphonates induced a significant increase of apoptosis in MCF-7. In addition, they showed a significant decrease in telomerase expression and activity with respect to control and to clodronate.

Alendronate↗

Migration of cemented stem and restrictor after total hip arthroplasty: a radiostereometry study of 25 patients with Lubinus SP II stem.

The aim of this study was to investigate the migration pattern of the Lubinus SP II prosthesis stem. Migration at the stem-cement and at the bone-cement interface was assessed. Twenty-five patients were studied by radiostereometry during a period of 2 years. The migration of the head, of 2 points on the collar, of the stem tip, and also of the cement restrictor, was measured. The collar and the head were found stable at 2 years' follow-up, whereas an anterior migration occurred at the stem tip (median, 0.3 mm; 25th percentile, 0.04 mm; 75th percentile, 1.27 mm). Virtually no subsidence or axial rotation of the stems was observed. An anterior migration of the restrictor marker was also observed, compatible with a rigid sagittal plane rotation of the stem and of the cement mantle about the collar. Therefore, stem tip migration occurred at the bone-cement interface. Key words: total hip arthroplasty, anatomic stem, radiostereometry, subsidence, bone-cement interface.

Aged↗

Secondary hyperparathyroidism is associated with vitamin D receptor polymorphism and bone density after renal transplantation.

Immunosuppresive treatment and secondary hyperparathyroidism (SHPT) are considered among the most important pathogenetic factors for post-renal transplant bone disease. The aim of this study was to investigate the relationships among vitamin D receptor (VDR) gene polymorphism, parathyroid hormone (PTH) levels and bone density in renal transplant recipients. We enrolled 75 patients (50 male and 25 female, mean age 47+/-11 years) who had undergone kidney transplantation 53+/-4 months before. All patients underwent an evaluation of the main biochemical parameters of bone metabolism as well bone densitometry. VDR alleles were typed by a PCR assay based on a polymorphic BsmI restriction site. When patients were categorized according to the VDR genotype (BB, Bb, bb), serum creatinine and the cumulative doses of immunosuppressive drugs were similar across the groups. PTH levels higher than 80 pg/ml were found in 53.6% of the patients, with the highest values being detected in the bb VDR genotype (P<0.05). PTH was significantly correlated to urinary NTx values. Bone density was low in the whole population; however, spinal bone density was lower in the bb subgroup (P<0.02). In the whole population, only PTH (P<0.05) and body mass index (P<0.01) were independent predictors of spinal bone density. Grouping patients by the VDR gene polymorphism, only PTH continued to be an independent predictor of spinal bone density in the bb allele subgroup (R(2) Adj.=0.17). We can conclude that the VDR genotype polymorphism affects bone density of renal transplant recipients via its effects on the severity of SHPT.

Adult↗

Bone disease in primary hypercalciuria.

Primary hypercalciuria (PH) is very often accompanied by some degree of bone demineralization. The most frequent clinical condition in which this association has been observed is calcium nephrolithiasis. In patients affected by this disorder, bone density is very frequently low, and increased susceptibility to fragility fractures is reported. The very poor definition of this bone disease from a histomorphometric point of view is a crucial aspect. At present, the most common finding seems to be a low bone turnover condition. Many factors are involved in the complex relationships between bone loss and PH. Since bone loss was mainly reported in patients with fasting hypercalciuria, a primary alteration in bone metabolism was proposed as a cause of both hypercalciuria and bone demineralization. This hypothesis was strengthened by the observation that some bone resorbing-cytokines, such as interleukin-1 (IL-1), interleukin-6 (IL-6), and tumor nechrosis factor-alpha (TNF-alpha), are high in hypercalciuric patients. An excessive response to the acid load induced by dietary protein intake seems to be an additional factor explaining a primitive alteration of bone. The intestine plays a major role in the clinical course of bone disease in PH. Patients with absorptive hypercalciuria less frequently show bone disease, and a reduction in dietary calcium greatly increases the probability of bone loss in PH subjects. It has recently been reported that greater bone loss is associated with a larger increase in intestinal calcium absorption in PH patients. Considering the absence of parathyroid hormone (PTH) alterations, it was proposed that this is not a compensatory phenomenon, but probably the marker of disturbed cell calcium transport, involving both intestinal and bone tissues. While renal hypercalciuria is rather uncommon, the kidney still seems to play a role in the pathogenesis of bone loss in PH patients, possibly via the effect of mild-to-moderate urinary phosphate loss with secondary hypophosphatemia. In conclusion, bone loss is very common in PH patients. Even if most of the factors involved in this process have been identified, many aspects of this intriguing clinical condition remain to be elucidated.

Animals↗

Surgical treatment of neck hyperextension in myopathies.

Neck hyperextension occurs in relation to several myopathies. It is a progressive increase of lordosis associated with a limitation in flexion of the cervical spine, forcing the patient to assume awkward compensatory postures to maintain balance and level vision. We evaluated operative complications, degree of correction, achievement of a solid arthrodesis, maintenance of the correction, and clinical assessment of seven patients. All had surgery in which the interspinous processes between C2-C7 were opened in a posterior approach and bone graft wedges driven into them to maintain the correction. The mean age of patients at the time of surgical intervention was 16.5 years (range, 10-28 years). The average followup was 10.4 years (range, 2.4-16.5 years). No major surgical complications occurred. After surgery, the average angle between C2-C7 in neutral position had decreased from 50.7 degrees (range, 40 degrees -70 degrees ) to 21.4 (range, 2 degrees -50 degrees ). The range of motion in the C1-C2 joint remained unaffected, whereas it decreased in C2-C7 from 33.5 degrees (range, 15 degrees -64 degrees ) to 1.8 degrees (range, 0 degrees -8 degrees ). A solid arthrodesis was achieved in all patients The followup showed significant clinical improvement of posture in all patients. The operating technique used proved to be safe and effective.

Adolescent↗

Hydroxyapatite-coated external fixation pins.

The aim of this review is to report on studies of hydroxyapatite-coated external fixation pins as a solution to enhance pin fixation. In a highly loaded animal study, three tapered pin types were compared: Type A uncoated, Type B coated with hydroxyapatite and Type C coated with titanium. There was a 13-fold increase in the extraction torque of Type B pins compared with Type A, and a twofold increase compared with Type C pins. Extraction torque was significantly lower compared with the corresponding insertion torque in both Types A (p < 0.001) and C (p = 0.003). Conversely, with the hydroxyapatite-coated pins there was no difference between extraction and insertion torque. In a clinical study of 76 external fixation pins in 19 patients treated with hemicallotasis for osteoarthritis on the medial side of the knee, pin insertion and extraction torque forces were measured. The patients were randomized to be treated with either standard tapered pins or tapered pins coated with hydroxyapatite. Extraction torque of the hydroxyapatite-coated pins was higher than the extraction torque of the standard pins in both cancellous and cortical bone (p < 0.005). In a prospective, randomized clinical study of osteoporotic wrist fractures, extraction torque of the coated pins was higher than with standard pins (p < 0.0001). These studies demonstrate that with the use of hydroxyapatite-coated pins, no deterioration of pin fixation occurs, and that there is no significant pin loosening and infection, regardless of bone type and loading conditions.

Animals↗

Dynamic hip screw compared with external fixation for treatment of osteoporotic pertrochanteric fractures. A prospective, randomized study.

BACKGROUND: Although the use of a sliding hip screw is considered to be the preferred treatment for pertrochanteric femoral fractures, we theorized that external fixation could produce clinical outcomes equal to, if not better than, the outcomes obtained with conventional treatment. Furthermore, because external fixation is minimally invasive, we expected a lower rate of morbidity and a reduced need for blood transfusions. Therefore, we compared the two treatments in a clinical trial of elderly patients with pertrochanteric fracture. METHODS: Forty consecutive elderly female patients who had a pertrochanteric fracture were randomized to be treated with either fixation with a 135 degrees four-hole sliding hip screw (Group A) or an external fixation device with hydroxyapatite-coated pins (Group B). The inclusion criteria were female gender, an age of at least sixty-five years, an AO/OTA type-A1 or A2 fracture, and a bone mineral density T-score of less than -2.5. There were no differences in patient age, fracture type, bone mineral density, comorbidities, length of hospital stay, or quality of reduction between the two groups. RESULTS: The average intraoperative time (and standard deviation) was 64 +/- 6 minutes in Group A and 34 +/- 5 minutes in Group B (p < 0.005). The average number of units of blood transfused postoperatively was 2.0 +/- 0.1 in Group A and none in Group B (p < 0.0001). Group B had less pain five days postoperatively (p < 0.05). Varus collapse of the fracture at six months averaged 6 degrees +/- 8 degrees in Group A and 2 degrees 1 degrees in Group B (p < 0.002). No pin-track infections occurred in Group B. The average Harris hip score at six months was 62 +/- 19 points in Group A and 63 +/- 17 points in Group B. CONCLUSIONS: This study showed that external fixation with hydroxyapatite-coated pins is an effective treatment for this fracture in this patient population. The operative time is brief, the blood loss is minimal, the fixation is adequate, and the reduction is maintained over time.

Aged↗

Effect of oral vitamin D2 yearly bolus on hip fracture risk in elderly women: a community primary prevention study.

BACKGROUND AND AIMS: Vitamin D deficiency is a well-known risk for hip fracture, and vitamin D insufficiency is so frequent in the elderly that population-wide preventive intervention would be useful. The objective of the study was to evaluate the efficacy of vitamin D bolus on hip fracture incidence in elderly women. METHODS: All women aged > 65 years registered at Health District 20 of the Regione Veneto, Italy, were eligible for this quasi-experimental, prospective community intervention study. A vial containing 400,000 IU vitamin D2 (Ostelin 800, Teofarma, Italy) was offered for oral administration to all women in the winters of 2000-2001 and 2001-2002. The only exclusion criteria for treatment were age and gender, and the control group included women who did not participate in the Health District initiative. Analysis of hip fracture incidence was carried out for 4 years, from 1999 to 2002. Patients with incident hip fracture were identified as soon as they were admitted to one of the 3 hospitals of the health district and interviewed regarding their participation in the vitamin D preventive intervention program. In 120 of the women (age range 68-90 years), serum concentrations of 25-OH vitamin D were measured from October to June, both before and 1 and 4 months after vitamin D administration. RESULTS: 23,325 and 24,747 women received the vitamin D bolus during winters 2000-2001 and 2001-2002 respectively, i.e. 45-47% of eligible women. The proportion of women who accepted the bolus declined with advancing age, from 50-55% in women aged 60-70 years to 22-26% in those aged > 90 years. The two-year intervention on the community decreased the incidence of fracture by 10% (p = 0.050) in comparison with the previous two years. The age-adjusted risk reduction (RR) of hip fracture during 2001 and 2002 in women who had received vitamin D, with respect to women who had not, decreased by 17% (p = 0.056) and 25% (p = 0.005) respectively. The RR was considerably greater and statistically significant over both 2001 and 2002 in the cohort aged > 75 years. 25-OH vitamin D concentrations, in the subset of women in whom it was measured, rose significantly (p < 0.0001) by 9 ng/ml over 4 months after administration. CONCLUSION: Despite several obvious limitations due to its nature, this study sufficiently documents that yearly vitamin D bolus supplements, given as primary prevention to elderly Caucasian women, may decrease the incidence of hip fracture. For its probable safety and excellent feasibility and cost-effectiveness, this primary intervention has a great potential for generalisability.

Administration, Oral↗

The stability of the cemented tibial component of total knee arthroplasty: posterior cruciate-retaining versus posterior-stabilized design.

Micromotion of the tibial component in 40 knee arthroplasties for gonarthrosis was studied using Roentgen stereophotogrammetric analysis. The stability of this component was assessed for 2 years' postoperatively. In all arthroplasties, an attempt was made to reconstruct the preoperative posterior slope. Posterior cruciate-retaining (CR) and posterior-stabilized (PS) components showed at 2 years a maximum total point motion of 0.6 +/- 0.4 mm and 0.7 +/- 0.5 mm, respectively. Whereas 92.5% of the implants were determined to be stable, 1 of the CR group and 2 of the PS group displayed migration between the first and the second year of at least 0.2 mm. A negative correlation between subsidence of the tibial component at 2 years of follow-up and the difference between preoperative and postoperative tibial slope was found. Consequently, we suggest that restoring the original posterior slope of the tibial plateau must be a goal of tibial component implantation.

Aged↗

Minimally invasive radioguided parathyroidectomy: an attractive therapeutic option for elderly patients with primary hyperparathyroidism.

BACKGROUND AND AIM: Surgery for primary hyperparathyroidism (PHPT) due to a solitary parathyroid adenoma (PA) is moving from traditional bilateral neck exploration (BNE) towards the use of limited neck exploration. The aim of the present study was to define the efficacy of minimally invasive radioguided surgery (MIRS) in PHPT patients with a high probability of a solitary PA with particular regard to benefits achievable in elderly patients. PATIENTS AND METHODS: The study population included a total of 266 consecutive PHPT patients who had undergone surgery at our centre between September 1999 and February 2003. Preoperative imaging consisted of [Tc]pertechnetate/Tc sestamibi (TcO4/sestamibi) scintigraphy and neck ultrasound obtained in the same session. One hundred and eighty-seven patients from the whole series (75 of whom were older than 65 years) with a high scan/ultrasound probability of a solitary PA, a high PA sestamibi uptake, and a normal thyroid gland were selected for MIRS. The other 79 patients were selected for traditional BNE. The intra-operative technique was based on the injection of a low dose (37 MBq) of sestamibi in the operating theatre a few minutes before the beginning of intervention and on the use of an 11 mm collimated gamma probe. RESULTS: MIRS was successfully performed in 97.8% of all PHPT patients selected for this type of surgery and, in particular, in 100% of the subgroup (n=75) of elderly patients. MIRS required a mean operating time of 35 min and a mean hospital stay of 1.2 days; that is, approximately half of that required for traditional BNE. Moreover, local anaesthesia was successfully performed in 27 patients, 19 of whom were >65 years with concomitant invalidating diseases contraindicating general anaesthesia. No major surgical complications were recorded. Transitory hypocalcaemia was observed in 9% of cases treated with MIRS compared with 27% of patients treated with BNE. CONCLUSION: MIRS can be accurately planned in elderly PHPT patients with a solitary PA on the basis of a TcO4/sestamibi scan and neck ultrasound. MIRS has been proven to be safe and effective in our experience, and allows a significant reduction of operating and recovery time, as well as the possibility of using local anaesthesia, especially in elderly patients with concomitant invalidating diseases.

Adenoma↗

Mobility of the human ankle and the design of total ankle replacement.

Our prior research has shown that currently available total ankle implants fail to restore physiologic ankle mobility. Most of the modern mobile-bearing designs that feature a flat tibial component and a talar component with anatomic curvature in the sagittal plane function nonphysiologically with the natural ligament apparatus. To establish a more natural relationship between the implanted components and the retained ankle ligaments, we have developed a new design. According to our prior research, we suggest that physiologic ankle mobility is reproduced best with a design featuring a spherical convex tibial component, a talar component with radius of curvature in the sagittal plane longer than that of the natural talus, and a fully conforming meniscal component. Our preliminary observations in trial implantation and in a few patients suggest that while reproducing physiologic ankle mobility, the new design is capable of maintaining complete congruence at the two articulating surfaces of the meniscal bearing over the entire motion arc, with the prospect of minimizing wear of this component.

Ankle Joint↗

HA-coated screws decrease the incidence of fixation failure in osteoporotic trochanteric fractures.

This study was done to determine if elderly patients with trochanteric fractures and with osteoporosis could benefit from treatment with a dynamic hip screw fixed with HA-coated AO/ASIF screws. One hundred twenty patients with AO, A1, or A2 trochanteric fractures were selected. Patients were divided into two groups and randomized to receive a 135 degree-four-hole dynamic hip screw fixed with either standard lag and cortical AO/ASIF screws (Group A), or HA-coated lag and cortical AO/ASIF screws (Group B). Lag screw cutout occurred in four patients in Group A, but not in any patients in Group B. In Group A, the femoral neck shaft angle was 134 degrees +/- 5 degrees postoperatively and 127 degrees +/- 12 degrees at 6 months. In Group B, the femoral neck shaft angle was 134 degrees +/- 7 degrees postoperatively and 133 degrees +/- 7 degrees at 6 months. The Harris hip score at 6 months was 60 +/- 25 in Group A and 71 +/- 18 in Group B. The superior results of Group B can be attributed to the increased screw fixation provided by the HA-coated screws. We recommend lag screws coated with HA for dynamic hip screw fixation, especially in osteoporotic bone.

Aged↗

Interdigital neuroma: clinical examination and histopathologic results in 63 cases treated with excision.

Between November 1993 and September 1999, 60 patients (three bilateral) were consecutively treated with excision of interdigital neuroma. The clinical examination was preoperatively performed and a personal interview, physical examination, and routine radiographs were included. A specific clinical rating system was developed. The clinical results were excellent or good in 49 (78%) feet, fair in 12 (19%), and poor in two (3%). Prior to surgery, the clinical evaluation score was an average of 16 points. Postoperative average score was 67 points, with an average improvement of 50 points. Histopathologically, intraneural fibrosis and sclerohyalinosis were observed, as in the interstitium; furthermore, an increase of the elastic fibers in the stroma was also observed. The precise etiology of interdigital neuroma remains obscure.

Adult↗

Operative treatment of osteochondral lesions of the talar dome: current concepts review.

Osteochondral lesions of the talar dome are common problems encountered in orthopaedics. Procedures for the treatment of osteochondral lesions of the talus, including debridement of the joint, shaving of fibrillated cartilage, and resection or perforation of subchondral bone in the last decade, have been performed arthroscopically with very low morbidity. These seem to be inadequate in lesions larger than 1.5 cm(2) and have not been histologically effective in restoring the hyaline cartilage sheath. Osteochondral allografts or autogenous grafts and autologous chondrocyte transplantation have proven to be capable of restoring the articular hyaline cartilage surface, including defects larger than 2 cm(2), although with higher costs and morbidity. In this review, the aforementioned methods of operative treatment are examined and issues that are related to these methods are discussed.

Algorithms↗

The effect of age, weight, and lifestyle factors on calcaneal quantitative ultrasound: the ESOPO study.

Quantitative ultrasound (QUS) techniques have been shown to be as good as bone mineral density (BMD) assessed by dual-energy X-ray absorptiometry (DXA), in predicting fracture risk: QUS technique could increase substantially the accessibility to a reliable bone osteoporosis risk evaluation, but little is know regarding the relationship of QUS to risk factors that have been found to predict DXA-BMD values and this is even more true in men. We studied 6,811 postmenopausal women 40 to 80 years of age and 4,981 men 60-80 years of age representative of the general population of all regions of Italy. All participants were questioned on lifestyle habits and on their medical history. After a physical examination "bone stiffness" (called here for simplicity, stiffness), which is derived from the values of broadband ultrasound attenuation (BUA) and speed of sounds (SoS) was measured by a heel QUS device (Achilles apparatus, Lunar, Madison, USA). The most common recognized determinants of bone mass (either categorical or continuous variables) were modeled with stiffness by multiple regression analysis or ANOVA. Stiffness was strongly related to age and weight. After adjusting for these variables, the women who had taken hormone replacement therapy for more than a year had significantly higher stiffness values. The difference versus nonusers remained significant for up to 20 years-since-menopause (YSM). This effect was so strong that for further analysis these women were excluded. By multivariate analysis, stiffness was then found to be significantly related to recalled body weight at 25 years of age, actual and past cigarettes smoked per day, and dairy calcium intake. Stiffness was also associated with a number of categorial factors adjusted for age, weight, and YSM: prior ovariectomy, history of more than 2 months confined to bed, outdoor physical activity, smoking, chronic use of any drug, and past corticosteroid use. All these categorial and continuous variables predicted stiffness equally in men and women. In conclusion, QUS bone measurements discriminate postmenopausal women according to past use of hormone replacement therapy. Risk factors usually associated to BMD as measured by DXA are also associated to calcaneal bone stiffness as measured by QUS, and most risk factors for osteoporosis usually observed in women are equally applicable to men.

Adrenal Cortex Hormones↗