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Biomedical subjects

Roberto Marcolongo

Publications and source records attributed to Roberto Marcolongo.

At least 19 recordsLinked to original sources

Osteogenic growth peptide effects on primary human osteoblast cultures: potential relevance for the treatment of glucocorticoid-induced osteoporosis.

The osteogenic growth peptide (OGP) is a naturally occurring tetradecapeptide that has attracted considerable clinical interest as a bone anabolic agent and hematopoietic stimulator. In vivo studies on animals have demonstrated that the synthetic peptide OGP (10-14), reproducing the OGP C-terminal active portion [H-Tyr-Gly-Phe-Gly-Gly-OH] increases bone formation, trabecular bone density and fracture healing. In vitro studies performed on cellular systems based on osteoblastic-like cell lines or mouse stromal cells, have demonstrated that OGP (10-14) increases osteoblast proliferation, alkaline phosphatase (ALKP) activity and matrix synthesis and mineralization. In view of a potential application of OGP (10-14) in clinical therapy, we have tested different concentrations of OGP (10-14) on primary human osteoblast (hOB) cultures. We have observed significant increases of hOB proliferation (+35%), ALKP activity (+60%), osteocalcin secretion (+50%), and mineralized nodules formation (+49%). Our experimental model based on mature hOBs was used to investigate if OGP (10-14) could prevent the effects on bone loss induced by sustained glucocorticoid (GC) treatments. A strong decrease in bone formation has been attributed to the effects of GCs on osteoblastogenesis and osteocyte apoptosis, while an increase in bone resorption was due to a transient osteoblastic stimulation, mediated by the OPG/RANKL/RANK system, of osteoclasts recruitment and activation. Moreover, GCs act on hOBs decreasing the release of osteoprotegerin (OPG) a regulator of the RANKL/RANK interaction. Here, we provide evidences that OGP (10-14) inhibits hOB apoptosis induced by an excess of dexamethasone (-48% of apoptotic cells). Furthermore, we show that OGP (10-14) can increase OPG secretion (+20%) and can restore the altered expression of OPG induced by GCs to physiological levels. Our results support the employment of OGP (10-14) in clinical trials addressed to the treatment of different bone remodeling alterations including the GC-induced osteoporosis.

Aged↗

Subcutaneous panniculitis-like T-cell lymphoma misdiagnosed as lupus erythematosus panniculitis.

We report a case of subcutaneous panniculitis-like T-cell lymphoma (SPTCL), associated with macrophage activation syndrome, mimicking a lupus erythematosus panniculitis (LEP). A 29-year-old woman presented with high fever, general malaise, nausea, vomiting, and subcutaneous nodules and ulcerating lesions located on the lower extremities. The histopathology showed an infiltration of the panniculus, mostly involving fat, and periadnexial and perivascular structures consistent with lymphocytic lobular panniculitis (LLP). LLP is a shared feature of LEP and SPTCL. The immunophenotyping of the cell infiltrate was crucial for a correct diagnosis.

Adult↗

A proteomic study on human osteoblastic cells proliferation and differentiation.

Changes in expression profiles for 17 proteins were ascertained in human mature osteoblasts compared to pre-osteoblasts (differentiation markers). A differential approach was used to highlight proteomic changes between human osteosarcoma cells and mature osteoblasts, showing a relative over-expression of 8 proteins (proliferation and tumor indicators), as well as under-expression of proteins also found down-regulated in pre-osteoblasts (specific markers of osteoblast differentiation). Our findings confirmed the differences between cell lines and primary human cell cultures and suggested caution on the use of osteosarcoma to study anti-osteoporotic drugs in humans.

Adult↗

Novel therapeutic agents for bone resorption. Part 1. Synthesis and protonation thermodynamics of poly(amido-amine)s containing bis-phosphonate residues.

Two poly(amido-amine)s (oligoPAM and oligoNER) containing bis-phosphonate residues were obtained by a Michael-type polyaddition of pamidronate and neridronate to 1,4-bis(acryloyl)piperazine. The SEC (size-exclusion chromatography) and the MALDI-TOF (matrix assisted laser desorption ionization) analyses were consistent with the presence of oligomeric species (2-3 kDa) and with a narrow polydispersity index. The thermodynamic results (log Ks, -DeltaH(o) , and DeltaS(o) obtained at 25 degrees C in 0.15 M NaCl) of both the oligomers and the corresponding low molecular weight precursors were in line with a cluster structure formed during the protonation of the basic nitrogen in the pamidronate. The solubility of the oligoNER with a longer aliphatic chain was improved at high pHs, allowing the evaluation of their solution properties. Preliminary biological results show that both the oligomers do not negatively affect the in vitro viability, proliferation, and cellular activity of either normal animal or human osteoblasts.

Bone Resorption↗

Clinical presentation of osteoarthritis in general practice: determinants of pain in Italian patients in the AMICA study.

OBJECTIVE: To assess the clinical characteristics and determinants of pain observed by general practitioners (GPs) in Italian patients with osteoarthritis (OA) of the hand, hip, and knee. METHODS: The 2764 GPs participating in the study were asked to enroll 10 consecutive patients with OA diagnosed according to the American College of Rheumatology (ACR) clinical criteria. To standardize the diagnosis, the GPs received ad hoc training from musculoskeletal system specialists. A questionnaire evaluating demographic data, the clinical characteristics of OA, and previous diagnostic and therapeutic interventions was administered by the GPs. RESULTS: 25,589 evaluable patients were enrolled during a mean period of 2.8 weeks by the GPs: 17,567 women (69%) and 7878 men (31%). The most painful OA joints were the knee in 12,827 patients (54%), the hip in 5645 patients (24%), and the hand in 5467 patients (23%)--percentages calculated on the 23,939 patients for whom this information was available. The weekly incidence of referrals to GPs for OA was higher for women and for knee OA. The median age of the patients was 70 years (range 50 to 104 years) and disease duration was 8.3 +/- 7.10 years. The most frequent comorbidities were hypertension (53%), obesity (22%), osteoporosis (21%), type II diabetes mellitus (15%), and chronic obstructive pulmonary disease (13%). The median pain visual analog scale (VAS) score was higher for women than for men, for hip OA, and for generalized OA (GOA) than for knee and hand OA (P < 0.0001). Intense pain, defined as VAS readings of >60 mm, was increased in women only in the knee (OR = 1.24; 95% CI 1.15 to 1.34) and in GOA (OR = 1.17; 95% CI 1.03 to 1.33). It was also significantly increased in patients older than 70 years (OR = 1.46; 95% CI 1.39 to 1.54), those with a low educational level (OR = 1.44; 95% CI 1.36 to 1.5), a BMI of > or =30 (OR = 1.52; 95% CI 1.42 to 1.61), a disease duration of more than 7 years (OR = 1.60; 95% CI 1.52 to 1.68), comorbidities (OR = 1.61; 95% CI 1.5 to 1.73), and GOA (OR = 2.05; 95% CI 1.91 to 2.19). Manual occupations were associated with highly intense pain only in men. CONCLUSIONS: The results of this study underscore the major impact of OA on care in general practice, the high frequency of OA-associated comorbidities, and the role of different risk factors in OA pain.

Age Distribution↗

Do physicians treat symptomatic osteoarthritis patients properly? Results of the AMICA experience.

OBJECTIVE: The main objective of the AMICA project was to photograph the Italian scenario of osteoarthritis (OA) and its treatment in general and specialty practice. The study was designed to evaluate their prescription modalities to determine whether they matched the recently proposed treatment guidelines for OA (ACR 2000; EULAR 2000; APS 2002). METHODS: The study involved 2764 general practitioners (GPs) and 316 specialists who enrolled a total of 25,589 patients with OA of the hand, knee, and hip. RESULTS: Pharmacological treatment alone was prescribed to 55% of the patients seen by GPs, 25% of those seen by rheumatologists, 8% of those seen by orthopedic surgeons, and 17% of those seen by physical medicine specialists (GPs versus specialists, P < 0.001). Specialists often prescribed a combined pharmacological and nonpharmacological approach (rheumatologists 51%, orthopedic surgeons 66%, physical medicine specialists 76%). Concomitant comorbidities and their treatment do not seem to influence OA prescription modalities except for peptic ulcer and anticoagulant therapy. The presence of peptic ulcer was associated with a reduction in NSAID prescriptions (OR 0.61, CI 0.53 to 0.69) and more frequent use of Coxibs (OR 1.15, CI 1.03 to 1.28) and simple analgesics (OR 1.42; CI 1.26 to 1.61), as well as physical therapy. NSAIDs and Coxibs also were less frequently prescribed if patients were receiving anticoagulant therapy (NSAIDs OR 0.86, CI 0.70 to 1.06; Coxibs: OR 0.77; CI 0.64 to 0.93). Gastroprotective therapy was more frequently used in patients treated with NSAIDs, Coxibs, and analgesics. There was no significant difference in therapies prescribed for patients with hypertension or cardiac disease (myocardial infarction and/or angina pectoris). CONCLUSIONS: The published guidelines appear to be properly used by most of the physicians in terms of the pharmacological approach; however, the increased use of Coxibs has not reduced the amount of prescribed gastroprotection. No specific precautions were observed in the treatment of patients with hypertension or cardiac problems. Nonpharmacological treatments are mainly used in conjunction with medications and did not take into account the findings of evidence-based medicine. Continuing education of GPs and specialists caring for OA patients is essential.

Combined Modality Therapy↗

Prolongation of the corrected QT interval in adult patients with anti-Ro/SSA-positive connective tissue diseases.

OBJECTIVE: Newborns of mothers positive for anti-Ro/SSA autoantibodies may develop a series of electrocardiographic (EKG) disturbances. Prolongation of the corrected QT (QTc) interval was recently reported in a significant proportion of children with maternally acquired anti-Ro/SSA antibodies, with a concomitant disappearance of EKG abnormalities and acquired maternal autoantibodies during the first year, suggesting a direct, reversible electrophysiologic effect of anti-Ro/SSA antibodies on the ventricular repolarization. On this basis, we investigated whether these antibodies may also affect cardiac repolarization in anti-Ro/SSA-positive adult patients with connective tissue diseases. METHODS: Fifty-seven patients with connective tissue diseases were selected: 31 had anti-Ro/SSA antibodies and 26 did not (controls). In all subjects, we analyzed the QTc interval, heart rate variability, and signal-averaged high-resolution EKG recording. RESULTS: Anti-Ro/SSA-positive patients showed a significant prolongation of the mean QTc interval compared with the controls (mean +/- SD 445 +/- 21 versus 419 +/- 17 msec; P = 0.000005). Eighteen of the 31 anti-Ro/SSA-positive patients (58%) and none of the 26 anti-Ro/SSA-negative patients had QTc values above the upper limit of normal (440 msec). Both groups had a reduction in heart rate variability, with a prevalence for the sympathetic nervous system and a high incidence of ventricular late potentials; these values were not significantly different between the 2 groups. CONCLUSION: Adult patients with anti-Ro/SSA-positive connective tissue diseases showed a high prevalence of QTc interval prolongation. This feature, with the concomitant abnormalities in the autonomic tone and ventricular late excitability observed in all patients studied, suggests that anti-Ro/SSA-positive patients may have a particularly high risk of developing life-threatening arrhythmias.

Adult↗

Pregnancy in Wegener's granulomatosis: successful treatment with intravenous immunoglobulin.

We present the case of a women diagnosed with Wegener's disease at the age of 26 years, refractory to corticosteroid and cyclophosphamide therapy. Treatment with intravenous immunoglobulin (IVIg) was started, leading to partial clinical remission of disease. During IVIg treatment she became pregnant. IVIg therapy was continued, the disease went into remission, and after 40 weeks the patient delivered a healthy boy. After 6 months from the delivery, the patient became pregnant again. Now she is at the 22nd week of pregnancy and she is doing very well. This case supports the beneficial effect of IVIg in Wegener's granulomatosis and illustrates its safety and efficacy during pregnancy.

Adult↗

Long-term effects of neridronate on human osteoblastic cell cultures.

UNLABELLED: Bisphosphonates (BPs) are widely used in the treatment of a variety of bone-related diseases, particularly where the bone turnover is skewed in favor of osteolysis. The mechanisms by which BPs reduce bone resorption directly acting on osteoclasts are now largely clarified even at molecular level. Researches concerning the BP's effects on osteoblast have instead shown variable results. Many in vitro studies have reported positive effects on osteoblasts proliferation and mineralization for several BPs; however, the observed effects differ, depending on the variety of different model system that has been used. OBJECTIVES: We have investigated if neridronate, an aminobisphosphonate suitable for pulsatory parenteral administration, could have an effect on human osteoblastic proliferation and differentiation in vitro. METHODS: We have investigated whether prolonged addition of neridronate (from 10(-3) to 10(-11) M) to different human osteoblasts cultures, obtained from 14 different bone specimens, could affect the cells number, the endogenous cellular alkaline phosphatase (ALKP) activity, and the formation of mineralized nodules. RESULTS: Our results show that neridronate does not negatively affect in vitro the viability, proliferation, and cellular activity of normal human osteoblasts even after a long period addition of the drug (20 days) at concentrations equal or lower than 10(-5) mol/l (therapeutic dose). In addition, neridronate seems to enhance the differentiation of cultured osteoblasts in mature bone-forming cells. A maximum increase of alkaline phosphatase activity (+50% after 10 days; P < 0.01) and mineralized nodules (+48% after 20 days; P < 0.05) was observed in cultures treated with neridronate 10(-8) M. CONCLUSIONS: These results encourage the use of neridronate in long-term therapy of demineralizing metabolic bone disorders.

Aged↗

Intermittent treatment of knee osteoarthritis with oral chondroitin sulfate: a one-year, randomized, double-blind, multicenter study versus placebo.

OBJECTIVE: To investigate the efficacy and tolerability of a 3-month duration, twice a-year, intermittent treatment with oral chondroitin sulfate (CS) in knee osteoarthritis (OA) patients. DESIGN: A total of 120 patients with symptomatic knee OA were randomized into two groups receiving either 800mg CS or placebo (PBO) per day for two periods of 3 months during 1 year. Primary efficacy outcome was Lequesne's algo-functional index (AFI); secondary outcome parameters included VAS, walking time, global judgment, and paracetamol consumption. Radiological progression was assessed by automatic measurement of medial femoro-tibial joint space width on weight-bearing X-rays of both knees. Clinical and biological tolerability was assessed. RESULTS: One hundred and ten of 120 patients were included in the ITT analysis. AFI decreased significantly by 36% in the CS group after 1 year as compared to 23% in the PBO group. Similar results were found for the secondary outcomes parameters. Radiological progression at month 12 showed significantly decreased joint space width in the PBO group with no change in the CS group. Tolerability was good with only minor adverse events identically observed in both groups. CONCLUSION: This study provides evidences that oral CS decreased pain and improved knee function. The 3-month intermittent administration of 800mg/day of oral CS twice a year does support the prolonged effect known with symptom-modifying agents for OA. The inhibitory effect of CS on the radiological progression of the medial femoro-tibial joint space narrowing could suggest further evidence of its structure-modifying properties in knee OA.

Acetaminophen↗

Alkaptonuria, ochronosis, and ochronotic arthropathy.

OBJECTIVES: To describe the clinical presentation and course of a relatively large group of Italian adult patients screened for mutation of the homogentisate dioxygenase gene causing alkaptonuria (AKU) and ochronosis, and to review typical and atypical facets of this condition. METHODS: We reviewed the medical records of 9 patients affected by ochronotic arthropathy who were observed in our institutions between 1979 and 2001. All patients were diagnosed as having AKU through a rapid urine test with alkali. Mutation screening was performed by single-strand conformation analysis of all homogentisate dioxygenase exons, followed by sequencing of altered conformers. RESULTS: Our 9 cases had similar clinical features and they reflected those described in the literature: a progressive degenerative arthropathy mainly affecting axial and weight-bearing joints associated with extraarticular manifestation. Musculoskeletal symptoms began in most of our patients around the age of 30 years with back pain and stiffness: involvement of the large peripheral joints usually occurred several years after spinal changes. Ochronotic peripheral arthropathy generally was degenerative, but joint inflammation was observed in some cases; this could be attributed to an inflammatory reaction of the ochronotic shard in the synovial membrane. CONCLUSIONS: Ochronosis is a model of arthropathy with known etiologic factors. Over time, AKU, the genetically determined metabolic defect, leads to the accumulation of pigment and the development of this crippling condition. Most of the clinical findings may be explained by inhibition of collagen crosslinks, but some require additional interpretation. For example, inflammatory features of the ochronotic joint only occur in a minority of cases, and may be attributable to ochronotic shards. Further studies are needed to establish the genotype-phenotype correlation to identify mutations that are predictive of severe disease. For this purpose, the Italian Study Group on Alkaptonuria (www.dfc.unifi.it/aku) is enrolling affected patients in an on-line database to characterize the molecular defects and their relationship to clinical data.

Aged↗

Combination therapy with montelukast and ketotifen for arthritis and rash resulting from idiopathic hypereosinophilic syndrome.

Idiopathic hypereosinophilic syndrome (IHES) is a rare condition of uncertain etiology characterized by marked peripheral blood eosinophilia and organ system dysfunction that cannot be explained by any factor other than the presence of eosinophils or their potentially toxic products. Diagnostic criteria include 1) a sustained eosinophilia greater than 1500/mm for longer than 6 months, 2) absence of other causes of eosinophilia, including parasitic infections and allergic diseases, and 3) multiorgan involvement (ie, lungs, heart, central nervous system, skin, liver, joints). Steroids represent the initial therapeutic approach, although for those patients unresponsive to steroids, cytotoxic chemotherapy should be considered. We describe a case of IHES characterized by polyarticular inflammatory joint involvement, hypereosinophilia, and urticarioid skin manifestations without visceral involvement. Synovial fluid smears as well as pathology of skin lesions and knee synovial membrane confirmed the presence of numerous eosinophils. The patient was successfully treated with a combination therapy of a cysteinyl leukotriene receptor antagonist (montelukast) and ketotifen. Hypereosinophilic syndrome like in this patient is a rare cause of polyarthritis.

Journal Article↗

Effects of high dose methylprednisolone pulse therapy on bone mass and biochemical markers of bone metabolism in patients with active rheumatoid arthritis: a 12-month randomized prospective controlled study.

OBJECTIVE: To study the effects of one year of high dose 6-methylprednisolone pulse therapy (MPPT) on bone mass, seric bone alkaline phosphatase (sBAP), and urinary deoxypyridinoline (uDpyr) in patients with active rheumatoid arthritis (RA), and to compare results with those of patients with active RA treated with oral methylprednisolone (OMP). METHODS: Thirty-one women with active RA were given 1000 mg of MP IV for 3 alternate days, with a mean interval of administration of 76 days (+/- 8.3 SD) for one year (MPPT group). Bone mineral density (BMD) (total body, lumbar spine, and femur neck), plasma levels of sBAP, and urinary concentrations of uDpyr were assessed at the beginning of the treatment and every 3 months until the end of the study. Moreover, erythrocyte sedimentation rate (ESR), Thompson joint score, and early morning stiffness were assessed at study entry and every month. The control group, 31 women with active RA treated with oral MP, was followed in the same way (OMP group). RESULTS: In the MPPT group there was no significant reduction of BMD at any site compared to significant reductions in lumbar BMD at 6 and 12 months and total body BMD and femur neck BMD at 12 months in the OMP group. Also in the OMP group, a significant reduction in the mean sBAP was observed. The mean uDpyr levels were not significantly reduced in either group. CONCLUSION: Our results show that MPPT, compared to continuous therapy with oral corticosteroids, preserves bone mass without modifying the biochemical markers of bone metabolism.

Absorptiometry, Photon↗

Ultrasonographic study of Achilles tendon and plantar fascia in chondrocalcinosis.

OBJECTIVE: To investigate by high frequency grey-scale ultrasonography (US) and power Doppler sonography (PDS) the modality and frequency of involvement of the Achilles tendon and plantar fascia in chondrocalcinosis (CC), and to correlate these findings with clinical complaints and radiographic evidence. METHODS: The heels of 57 consecutive patients with CC were evaluated by US, PDS, and radiography. One control group of 50 consecutive patients with osteoarthritis (OA) without signs of CC was studied in the same way. A second control group of 50 healthy subjects underwent only US/PDS examination. All subjects also underwent clinical assessment. RESULTS: US revealed Achilles tendon calcifications in 57.9% of those with CC, but none in the control groups. Plantar fascia calcifications were observed in 15.8% of CC and in 2% of OA cases, but not in healthy controls. US showed no significant difference in postero-inferior and inferior calcaneal enthesophytosis between subjects with CC (59.6% and 61.4%, respectively) and those with OA (46% and 44%, respectively). Such alterations were also present, in lower percentages, in the healthy controls. Posterior and inferior calcaneal erosions were absent in all groups. Achilles enthesopathy was found in 22.8% of patients with CC (14.9% of heels, with vascular signals in 11.4% of heels on PDS). Deep retrocalcaneal bursitis was found in 10.5% of patients with CC (7% of heels, with vascular signals in 5.2% of heels on PDS). Plantar fasciitis was found in 40.3% of patients with CC (36% of heels, with vascular signals in 2.6% of heels on PDS) and in 14% of OA patients, but not in healthy controls. No significant correlation was found between talalgia or sex of patients and presence of calcifications. A significant correlation was observed between talalgia and Achilles enthesopathy (r = 0.78, p < 0.0001), deep retrocalcaneal bursitis (r = 0.7, p < 0.0001), and plantar fasciitis (r = 0.31, p < 0.001). A significant correlation between talalgia and vascular signals on PDS was observed in Achilles enthesopathy (r = 0.91, p < 0.0001) and deep retrocalcaneal bursitis (r = 0.65, p < 0.0001). The presence of vascular signals on PDS was significantly associated with the presence of tendinous and bursal grey-scale US alterations. Achilles tendon calcifications were 39% sensitive, 100% specific, and 77% accurate for the presence of CC, whereas plantar fascia calcifications were 15% sensitive, 98% specific, and 54% accurate. Excellent agreement was found between US and radiography in detecting Achilles tendon calcifications (k = 0.86), plantar fascia calcifications (k = 0.77), postero-inferior enthesophytosis (k = 0.90), and inferior enthesophytosis (k = 0.83). CONCLUSION: Calcaneal tendon calcifications are frequent and asymptomatic findings in patients with CC, and they have a high specificity for this disease. US shows high agreement with radiography in depicting calcifications and enthesophytosis. Inflammatory changes of the calcaneal soft tissues are frequently observed by US and PDS in patients with chondrocalcinosis.

Achilles Tendon↗