Multiple diaphyseal sclerosis (Ribbing disease): what about neridronate?

Sclerosing bone disorders are uncommon diseases and represent a diagnostic challenge. Osteocondensation is a bone alteration, involving both acquired and hereditary conditions. Multiple diaphyseal sclerosis (Ribbing disease) is an inherited condition. It is characterized by excessive proliferation of endosteal and periosteal osseous tissue at the diaphyses of long bones, especially of tibias and femurs. The conventional radiology depicts cortical thickening of diaphyses of long bones while bone scintigraphy shows characteristically an abnormal tracer concentration in the involved diaphyses. The magnetic resonance imaging (MRI) examination confirms the presence of sclerosis and reveals bone marrow edema in the diaphyses of the afflicted bones. Due to the lack of knowledge of the pathophysiology, the treatment is empirical with glucocorticoids or bisphosphonates. Concerning bisphosphonates, the literature reports are conflicting. We report the case of a patient that showed lack of response to intravenous neridronate within 1 year of treatment, both in terms of pain and persistence of bone marrow edema at MRI.

Regional differences of vitamin D deficiency in rheumatoid arthritis patients in Italy.

Vitamin D deficiency is very common in patients with rheumatoid arthritis (RA). Aim of this study was to evaluate the prevalence of vitamin D deficiency among the different Italian regions and whether these variations are associated with different severity of the disease. The study includes 581 consecutive RA patients (464 women), not taking vitamin D supplements, from 22 Italian rheumatology centres uniformly distributed across Italy. Together with parameters of disease activity (disease activity score 28), functional impairment (activities of daily living and health assessment questionnaire disability index) and mean sun exposure time, all patients had serum 25-hydroxyvitamin D (25OHD) measured in a centralized laboratory. Vitamin D deficiency (25OHD level <20 ng/mL) was very frequent among RA patients; its prevalence was 60%, 52% and 38% in southern, central and northern Italy, respectively. Mean disease activity and disability scores were worse in southern regions of Italy. These scores were inversely related to 25OHD levels and this correlation remained statistically significant after adjusting for both body mass index (BMI) and sun exposure time. However, disease severity remained significantly higher in southern regions versus central-northern Italy after adjustment also for serum 25OHD levels, age and BMI. In RA Italian patients there are significant regional differences in the prevalence of vitamin D deficiency explained by different BMI, and sun exposure time, and inversely associated with disease activity and disability scores.

[Gitelman syndrome associated with chondrocalcinosis: description of two cases]. / Sindrome di Gitelman associata con condrocalcinosi: descrizione di due casi.

Gitelman syndrome is a rare inherited tubulopathy, characterized by hypomagnesemia, hypokalemia, metabolic alkalosis, hypocalciuria and hyperreninemic hyperaldosteronism. The clinical spectrum is wide and includes: cramps, myalgias, muscle weakness, until episodes of carpo-podalic spasm, tetania, rhabdomyolysis and paralysis. Some cases have been described in literature underlining the association of this condition with chondrocalcinosis, as a typical example of hypomagnesemia-induced crystal deposition disease. The therapy of Gitelman syndrome consists on the administration of defective electrolytes, although not always effective. We describe two cases of Gitelman syndrome associated with chondrocalcinosis showing the wide range of presentation of this clinical condition.

Relative roles of endothelial cell damage and platelet activation in primary Raynaud's phenomenon (RP) and RP secondary to systemic sclerosis.

OBJECTIVE: To evaluate the relative roles of endothelium and platelets in the pathogenesis of primary RP and RP secondary to SSc. METHODS: Endothelial derived ET-1, t-PA, PAI-1, and platelet derived beta-TG, PDGF, TGF-beta were measured in 36 patients with primary RP, 14 patients with RP secondary to SSc and 30 age and sex matched controls. RESULTS: A significative increase of ET-1, t-PA, PAI-1, TGF-beta, and beta-TG were the most relevant changes in patients with RP secondary to SSc with respect to the controls. Less relevant increases of t-PA, PAI-1, PDGF, and beta-TG levels were observed in patients with primary RP vs controls. CONCLUSIONS: These data seem to confirm the involvement of endothelial cells and platelets in the pathogenesis of RP, with mild changes in primary RP and more relevant changes in RP secondary to SSc.

[Somatostatin in peri-arthropathies of the shoulder: clinical effectiveness and tolerability after sub-acromial administration]. / La somatostatina nelle periartropatie della spalla: efficacia clinica e tollerabilità dopo somministrazione subacromiale.

In the last few years, the intra-articular administration of somatostatin, has been used in some diseases regarding rheumatology such as rheumatoid arthritis psoriatic arthritis and osteoarthritis, giving encouraging results. The objective of this study was to asses the efficacy and tolerability of subacromial-injection of somatostatin in 20 patients with painful shoulder. The study consisted of 3 injection administered every 4 days. The results revealed a significant improvement of the pain during active movement as well as joint excursion, and interference with daily activity immediately after the first injection. The good tolerability of the drug and the absence of unwanted side-effects allow us to foresee that the local-administration of somatostatin could be used in painful shoulder notably in those patients in which other drugs are not appropriate.

Hypertrophic osteoarthropathy: endothelium and platelet function.

Hypertrophic osteoarthropathy (HOA) is characterized by finger clubbing, periostosis and arthritis. The pathogenesis of hypertrophic osteoarthropathy is still uncertain. Earlier studies have been focused on the potential role of platelet and endothelium in the pathogenesis of HOA. The aim of this study was to evaluate the circulating levels of endothelin-1 (ET-1), beta-thromboglobulin (beta-TG) and platelet-derived growth factor (PDGF) in 21 HOA patients. The circulating levels of ET-1, beta-TG were significantly higher in HOA patients vs healthy controls, but not vs controls with lung diseases. On the contrary, PDGF was significantly higher in HOA patients vs healthy controls and vs subjects with lung diseases. These findings suggest that "endothelium/platelet unit" may play a role in the pathogenesis of HOA, and PDGF could induce the changes observed in HOA.

Serum levels of insulin in overweight patients with osteoarthritis of the knee.

OBJECTIVE: Obesity is often associated with knee osteoarthritis (OA) and with chronic hyperinsulinemia. The aim of our study was to investigate the relationship between overweight patients and OA of the knee. METHODS: Forty-eight overweight outpatients (40 women and 8 men) were recruited into the study. They were separated into 2 groups: Group 1 patients with OA of the knee and Group 2 subjects without OA of the knee. Serum insulin levels were determined in all patients. RESULTS: Insulin levels were statistically higher in patients with OA (p < 0.01) compared to subjects without OA. CONCLUSION: Our data suggest that insulin may play a role in the pathogenesis of OA of the knee in overweight patients.

[Chondrocalcinosis and diabetes mellitus. The clinico-statistical data]. / Condrocalcinosi e diabete mellito. Rilievi clinico-statistici.

Chondrocalcinosis is an important, common, age-related joint disease. Its characteristic is the deposit of calcium pyrophosphate dihydrate crystals in hyaline and fibrous cartilages. Occasionally, it is a familial disorder; more often, it is a sporadic disease of adults sometimes in association with hormonal and metabolic disorders. The relationship between CC and diabetes mellitus (DM) is disputed. In this study the prevalence of radiographic CC (knee and/or wrist) in 184 DM patients was evaluated. For comparison two matched groups without DM were studied: i) 184 consecutive unselected out-patients seem in Rheumatology Department of Ancona University with X-rays of knee and/or wrist; ii) 184 consecutive unselected outpatients observed in a Radiology Department with X-rays of knee and/or wrist. No statistical difference was found between the prevalence of CC in DM patients vs controls. Moreover 113 CC patients were studied. No statistical difference was observed between the prevalence of DM and impaired glucose tolerance in CC patients vs controls. These results may suggest that there is no relationship between CC and diabetes mellitus, as other studies have recently shown.

Intra-articular injection of somatostatin in knee osteoarthritis: clinical results and IGF-1 serum levels.

Recently somatostatin (SST) intra-articular administration has been used in the treatment of some rheumatoid diseases such as rheumatoid arthritis, psoriatic arthritis and osteoarthritis with encouraging results. The aim of this study was to evaluate the efficacy and tolerability of SST intra-articularly injected, involving 20 patients with knee osteoarthritis. Treatment consisted of 4 injections, administered weekly, each of 750 mcg SST. Additionally, in six of them we evaluated the circulating levels of the insulin-like growth factor (IGF)-1 at the base-line time and then every 7 days (immediately before each dose of SST). The results revealed an improvement in pain and in joint function after intra-articular SST, confirmed by statistical analysis. The circulating levels of IGF-1 did not show significant variations following intra-articular administration of SST. The excellent tolerability and the absence of unwanted side-effects with SST allow us to foresee that intra-articular SST could be used in cases of painful knee osteoarthritis, especially in those patients in which other drugs are not appropriate. Moreover, in the absence of modifications of serum levels of IGF-1, SST could be used in athletes.

Nitrofen-induced diaphragmatic hernias in rats: pulmonary antioxidant enzyme activities.

We developed an experimental rat model of congenital diaphragmatic hernia (CDH) to elucidate the etiology and pathogenesis of this serious congenital anomaly in humans and in particular to study the effects of a short period of artificial ventilation on the CDH lung in relation to antioxidant defense mechanisms. CDH was induced in about 60% of the offspring by maternal exposure to 2,4-dichlorophenyl-p-nitrophenylether (Nitrofen) during pregnancy. This herbicide resembles thyroid hormone in chemical structure. The lungs of fetal rats (d 19, 20, 21, and 22) were examined for protein and DNA content and activity of superoxide dismutase, catalase, and glutathione peroxidase (GPX). The same parameters were assessed in tracheotomized newborn rats after pressure-controlled artificial ventilation with either room air or pure oxygen during a short period of 5 h. In both CDH rats and controls, wet lung weight increased during gestation. At term, CDH rats had significantly lower mean lung weights than controls. Neither group differed in protein and DNA content per mg lung or superoxide dismutase, catalase, and GPX activity before and at birth. After artificial ventilation of neonates with air and pure oxygen, superoxide dismutase activity tended to decrease, whereas catalase activity remained virtually unchanged in the CDH lung. However, GPX activity in the CDH lung was reduced to 80% of initial activity at term after ventilation with air and to 70% with pure oxygen. The present finding of a decline in GPX activity in this animal model after a short period of artificial ventilation may indicate that the CDH rat neonate is at risk to develop oxygen-related lung damage.

The "endothelium/platelet unit" in hypertrophic osteoarthropathy.

Various pathogenetic theories of hypertrophic osteoarthropathy (HOA) have been proposed (neurogenic, hormonal, artero-venous shunts, genetic theory), but none of them is able to satisfactorily explain the genesis of HOA. The hypothesis of a central role of the "endothelium/platelet unit" was recently discussed. Above all, the release of the platelet derived growth-factor (PDGF) contained in platelet granules is particularly interesting. In order to assess the microvascular involvement in HOA we set up a research project whose aims were to evaluate the morphology of the capillary network at the nailfold, the dynamic aspects of microcirculation and in vivo platelet function. Since this study is still in progress, for the time being we present only a few preliminary results.

Stimulated chemiluminescence of polymorphonuclear leukocytes in rheumatoid arthritis: in vivo enhancement by auranofin.

The aim of the study was to investigate the interaction of opsonized zymosan with polymorphonuclear leukocytes (PMNLs) from 26 rheumatoid arthritis patients (six males and 20 females; mean age, 51.88 +/- 11.15 years; range, 33-72 years) and 11 control subjects (two males and nine females; mean age, 56.54 +/- 12.1 years; range, 33-75 years) using a luminol-amplified chemiluminescence (CL). The data obtained suggest that the opsonized zymosan stimulated CL is decreased in untreated rheumatoid patients compared with control subjects. The decreased stimulated CL may be the result of a physico-chemical alteration of the membrane (including decreased membrane fluidity and translocation of receptor sites) induced by free radicals of oxygen and/or by multiple exposures to chemotaxins. Auranofin enhances stimulated CL although the mechanism is not clear. Auranofin could interact with membrane lipids, induce changes in membrane surface charges and increase membrane fluidity. Our results are difficult to compare with those of previous studies, since different assays, and chemoattractants were applied. In addition, the disease activity and medication were also different.

[Chemiluminescence of oxygen radicals. A computerized method for its evaluation]. / La chemiluminescenza dei radicali dell'ossigeno. Un metodo computerizzato per la sua valutazione.

The measurement of oxygen free radicals (O2-) production after polymorphonuclear leukocytes (PMNLs) stimulation may be useful to elucidate the pathogenesis of rheumatic disorders and to assess the efficacy of anti-inflammatory and anti-rheumatoid drugs. The Authors describe a computerized method (with original specific analogic/digital converter and software) which allows a rapid and accurate determination of O2- production and a prompt storage of the data. The Authors, in disagreement with the current opinion, believe that PMNLs activity is more truly expressed by the total amount of emitted energy in a defined interval time than by the peak of emitted energy.