The Role of Circulating Bone Cell Precursors in Fracture Healing

Fracture healing is a complex process that involves several cell types; as a previous report suggested an increase in osteoblast (OB) precursors in peripheral blood during this process, this paper examines the role of circulating bone cell precursors in this process in the light of a prior suggestion that OB precursors are increased. Nine healthy men less than 60 years old with traumatic fractures were enrolled. The parameters circulating OB precursors (osteocalcin+/alkaline phosphatase+/CD15− cells) and osteoclast precursors (CD14+/CD11b+/vitronectin receptor + cells) were measured by flow cytometry; bone formation markers and TGFβ1, by ELISA; and PTH, by RIA in serum on arrival at the emergency department (baseline) and 15 days after fracture. Bone cell precursors behaved differently during healing. TGFβ1 was inversely correlated with OB number, but increased their degree of maturation at baseline. Bone formation markers and TGFβ1 were increased after fracture, whereas PTH was decreased. The TGFβ1 increase was directly correlated with age, whereas age was not correlated with the precursors. In conclusion, we confirm the role of TGFβ1 in fracture healing; and its possible role in the control of pre-OB homeostasis. There was no variation in circulating precursor cells during healing, though the increase in TGFβ1 may suggest increased pre-OB maturation and homing to the injured site.     

Aicardi syndrome with favorable outcome: case report and review

Aicardi syndrome is a congenital disorder characterized by severe psychomotor retardation, corpus callosum agenesis, chorioretinal lacunae, and early-onset infantile spasms. The prognosis is generally poor for children with the classical form. We report a peculiar case of Aicardi syndrome characterized by corpus callosum hypoplasia, brain malformations with subependymal heterotopias, extensive chorioretinal lacunae, seizures, and normal cognitive functions. Therefore, the clinical picture of the syndrome is broader than originally described. Cognitive disorders should not be considered inevitable and the prognosis not ineludibly poor.     

Chitotriosidase activity in the serum of patients with sarcoidosis and pulmonary tuberculosis

BACKGROUND: Human chitotriosidase is a chitinase selectively expressed by activated macrophages. An increase in chitotriosidase activity was previously described by us in the serum and bronchoalveolar lavage of sarcoidosis patients. OBJECTIVE: The aim of the present study was to analyze serum chitotriosidase activity in a larger number of sarcoidosis patients to verify the reported increase with respect to controls and to compare serum chitotriosidase levels in patients with sarcoidosis and tuberculosis, two granulomatous disorders of different etiology. METHODS: Chitotriosidase activity was measured in the serum of 96 sarcoidosis patients, 15 pulmonary tuberculosis patients and 30 healthy controls. RESULTS: We found significantly higher serum chitotriosidase activity in sarcoidosis patients than controls (p < 0.01) and in sarcoidosis patients than tuberculosis patients (p < 0.01), confirming a striking elevation of chitotriosidase activity (>10 times greater than normal) in pulmonary sarcoidosis patients. This is the first time that chitotriosidase activity has been analyzed in the serum of patients with pulmonary tuberculosis; it was found to be significantly lower than in sarcoidosis patients and not significantly greater than in controls. CONCLUSION: Although the mechanisms leading to the increase in chitotriosidase activity in sarcoidosis are still unknown, this enzyme may be specifically involved in the pathogenesis of the disease. Further studies with a greater number of patients are needed to confirm these results and to determine whether chitotriosidase could be a marker with diagnostic or prognostic value in sarcoidosis.     

Levetiracetam monotherapy for children and adolescents with benign rolandic seizures.

To assess the efficacy, tolerability and safety of Levetiracetam (LEV) therapy, we identified 21 (15 male; 6 female) patients with a history of benign epilepsy with centrotemporal spikes (BECTS), with and without secondarily generalization in children and adolescents aged between 5.0 and 12.1 years. LEV was administered as a first drug (number of patients=9) or converted after previous treatment with other AEDs (number of patients=12). The patients were subdivided into two groups: "newly diagnosed" patients and "converted" patients. Patients were followed up for 12 months and all patients were able to continue on LEV treatment. At the end of follow-up (12 months), all patients were seizure free or showed a reduction of seizures >50%. LEV dosage ranged from 1000 to 2500mg/daily. Overall, 100% of patients completed the 12 months study, without any important side effect. Somnolence and irritability occurred in two (9.5%) patients. Our results support findings that LEV monotherapy is effective and well tolerated in children with BECTS. Prospective, large, long-term double-blind studies are needed to confirm these findings.     

Comparison between remnant and red-marrow absorbed dose in thyroid cancer patients submitted to 131I ablative therapy after rh-TSH stimulation versus hypothyroidism induced by L-thyroxine withdrawal

OBJECTIVE: In thyroidectomized patients, increased levels of thyroid stimulating hormone (TSH) are necessary to maximize I uptake. Traditionally, this has been achieved by withdrawing L-thyroxine (L-T4) for 4-6 weeks, inducing hypothyroidism in patients. The availability of a genetically engineered version of the recombinant human TSH (rh-TSH) provides an alternative tool to enhance the TSH serum level without inducing hypothyroidism. In this paper the I remnant and red-marrow doses calculated in differentiated thyroid cancer (DTC) patients pre-treated with rh-TSH are compared to those calculated in patients in hypothyroidism induced by L-T4 withdrawal. METHODS: Forty-six DTC patients, submitted to I ablative therapy, were randomly divided in group A (pre-treated with rh-TSH) and group B (treated after L-T4 withdrawal for 30 days). The red-marrow absorbed dose per unit administered activity and the remnant cumulated activity per unit administered activity were calculated for both groups. RESULTS: The red-marrow dose in 17 rh-TSH treated patients is 0.06+/-0.02 mGy.MBq; that in 14 hypothyroid patients is 0.09+/-0.03 mGy.MBq (two-tailed unpaired t-test P=0.003). The remnant cumulated activity per unit administered activity in 10 rh-TSH treated patients is 0.9+/-0.8 h; that calculated in 21 hypothyroid patients is 1.55+/-1.05 h (two-tailed unpaired t-test P=0.063). This last result is mainly due to the difference between the maximum uptake (U) in rh-TSH (U=0.01+/-0.01) and hypothyroid patients (U=0.03+/-0.02) (two-tailed unpaired t-test P=0.019). CONCLUSION: The rh-TSH pre-treated patients seem to have a lower uptake compared to those in hypothyroidism induced by L-T4 withdrawal. On the other hand their red-marrow absorbed dose seems to be lower.     

Clinical benefit of bone-targeted radiometabolic therapy with 153Sm-EDTMP combined with chemotherapy in patients with metastatic hormone-refractory prostate cancer

Background Bone metastases are responsible for most of the morbidity associated with hormone-refractory prostate cancer (HRPC). ¹⁵³Sm-ethylenediaminetetramethylene phosphonate (¹⁵³Sm-EDTMP) has been approved for palliation of painful skeletal metastases. We retrospectively investigated the possible synergistic effect on survival of ¹⁵³Sm-EDTMP (given to HRPC patients for bone pain palliation) and chemotherapy. Methods Forty-five HRPC patients were evaluated, with a median age of 71 years. The number of metastatic bone sites was ≤10 in 25 patients and >10 in 20 patients. Median serum PSA was 224 ng/ml. Bone pain was mild in 6 patients, moderate in 16, severe in 22 and intolerable in 1. Fifteen patients were only treated with ¹⁵³Sm-EDTMP (group A), while 30 patients also received chemotherapy (estramustine phosphate or mitoxantrone plus prednisone) at variable times: between 3 and 5 months after ¹⁵³Sm-EDTMP (14 patients, group B) or within 1 month after ¹⁵³Sm-EDTMP (16 patients, group C). Results Haematological toxicities observed after either regimen were in general mild, consistent with common observations after either ¹⁵³Sm-EDTMP or chemotherapy, and without any additive adverse effects in the patients receiving both ¹⁵³Sm-EDTMP and chemotherapy. Bone pain palliation to some degree was induced by ¹⁵³Sm-EDTMP in 32/45 patients (71.1%), the proportion of patients with a favourable clinical response being significantly higher in group C than in group A (87.5% vs 53.3%, p = 0.0388). Also in terms of biochemical response (serum PSA levels), patients of group C performed significantly better than patients of group A (p = 0.0235). Overall median survival from the time of administration of ¹⁵³Sm-EDTMP was 15 months in the total cohort of 45 patients, and was significantly longer in group C than in either group B (30 months vs 11 months, p = 0.023) or group A (30 months vs 10 months, p = 0.008). Conclusion The results of this study confirm that ¹⁵³Sm-EDTMP is effective in terms of pain relief and PSA response, with minimal toxicity. When it was administered in combination with chemotherapy, prolonged survival indicated actual clinical benefit, while there were no additive toxicities. These results provide the rationale for future prospective evaluation of combined therapeutic strategies.     

Clinical features of psychogenic non-epileptic seizures in prepubertal and pubertal patients with idiopathic epilepsy

A retrospective multicentre study was performed to analyse psychogenic non-epileptic seizures (PNES) in prepubertal and pubertal patients with idiopathic epilepsy and to determine whether have different clinical characteristics. In this study, we reviewed 36 patients from six neurological referral centres: Department of Pediatrics, Chieti (3 patients); Department of Child Neuropsychiatry, Naples (9 patients); Department of Child Neuropsychiatry, Bologna (8 patients); Department of Neuroscience, Tor Vergata University, Rome (3 patients); Department of Pediatrics, La Sapienza University, Rome (5 patients); and Department of Pediatrics, Siena (8 patients). The population was divided according to Tanner’stages into 14 prepubertal (group I) and 22 pubertal (group II) patients. The two groups were compared on several variables examining the differences between them. The most frequent clinical manifestations in group I were unresponsive events, whereas in group II, motor events were exhibited more significantly. Mood disorders, including major depression, appeared more frequently in pubertal group, but this did not reach a significant difference. Among the psychosocial stressors, fear of rejection and need for attention were the predominant types in the prepubertal patients. The findings of this study reveal some similarities and differences between prepubertal and pubertal patients, which might help to identify predictive factors in patients affected by idiopathic epilepsy who can develop PNES.     

Does Lactoferrin Behave as an Immunohistochemical Oncofetal Marker in Bone and Cartilage Human Neoplasms?

By immunohistochemistry, lactoferrin (LF) has been extensively investigated in human neoplastic tissues; moreover, LF is able to promote bone growth in a murine model. Until now, no systematic studies on human osteocartilagineous fetal samples have been performed in comparison to corresponding neoplastic specimens to verify if LF may represent an oncofetal marker in this field of pathology. By a monoclonal antibody (clone 1A1; Biodesign International; w.d. 1:75) the distribution pattern of LF in bones of 25 human fetal tissues (8–34 gestation weeks), 10 adults (47–82 years) and 30 cartilage as well as 27 bone tumours (9–76 years) was analyzed. LF was encountered in 23/57 cases of osteocartilagineous tumors and namely in 10/10 giant cell tumours, 5/7 osteoid osteomas, 3/3 chondroblastomas, 3/3 chondromyxoid fibromas, 1/1 myeloma, 1/1 adamantinoma. No LF immunoexpression was detected in osteosarcomas, chondrosarcomas, ossifying fibromas, osteochondroma and enchondromas. In embryo-fetal tissues, LF immunoreactivity was localized in mesenchymal cells as well as in chondroblasts at the 8th gestational week and in immature osteocytes and osteoblasts up to the 18th gestation week, with a considerable decrease by the 24th week. No LF expression was found in any bone district since the 30th and up to the 34th week of gestation as well as in corresponding adult samples. Our findings indicate a role for LF as a bone growth regulator in the early phases of the human endochondral ossification, although the hypothesis of LF as oncofetal marker appears questionable in bone tumours.