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Biomedical subjects

C Marcelli

Publications and source records attributed to C Marcelli.

At least 55 records · Page 3Linked to original sources

In vivo effects of human recombinant transforming growth factor beta on bone turnover in normal mice.

Reports of the effects of TGF-beta on bone cells are conflicting and controversial. Different cell culture and organ culture models for both osteoblasts and osteoclasts have given different responses. In some the effects are dependent on prostaglandin synthesis, and in others they are prostaglandin independent. To determine the effects of TGF-beta on osteoblasts and osteoclasts in vivo and the role of prostaglandins in mediating these effects, we injected 2.5-5 micrograms TGF-beta into the subcutaneous tissue overlying the calvariae of normal mice for 2-5 days anc compared the morphologic responses in underlying calvarial bone with those in mice injected caused a marked increase in periosteal thickness (fivefold) and cellularity, morphologic changes in osteoblasts, and new mineralized bone formation. These effects were localized to the site of injection and were partially inhibited by concomitant indomethacin treatment. There was a parallel increase in osteoclast numbers in adjacent marrow spaces, and the osteoclasts formed were unusually large. In contrast, no increase in the numbers of osteoclasts was seen in indomethacin-treat animals. These data show that TGF-beta has powerful effects on local bone cell function in vivo and that these effects may be mediated, in part, by prostaglandin generation.

Animals↗

Micro-osteoclast resorption as a characteristic feature of B-cell malignancies other than multiple myeloma.

Multiple myeloma (MM) is characterized by the presence of lytic bone lesion and frequent hypercalcaemia. These are due to an excessive osteoclastic resorption in association with a low bone formation, as demonstrated by bone histomorphometry. Conversely, B-cell malignancies other than MM are rarely associated with lytic bone lesion and/or hypercalcaemia. In this study we have analysed quantitative bone histology in 65 patients with B-cell malignancies other than MM at diagnosis: chronic lymphocytic leukaemia (CLL, n = 20), non-Hodgkin's lymphoma (NHL, n = 25), Waldenström's disease (WD, n = 14), hairy cell leukaemia (HCL, n = 6). Fifty patients presented no clinical evidence of increased bone resorption, including no lytic bone lesions radiologically detectable and/or no hypercalcaemia. 80% of these patients (40/50) had increased bone resorption parameter using quantitative bone histology, including 19/29 (65.5%) patients with CLL or WD and 21/21 (100%) patients with NHL or HCL (P less than 0.01). As a control group, seven patients lacking bone marrow involvement on bone sample presented no excessive bone resorption. However, eight patients presented lytic bone lesions and/or hypercalcaemia. All of these patients had increased resorption parameters with high numbers of osteoclasts per surface trabecular bone (mean = 35.3), as opposed to the patients lacking lytic bone lesions and/or hypercalcaemia (mean = 6.6, n = 28) and to normal individuals (mean +/- SD = 3.8 +/- 1.7 and 6.3 +/- 2.6, respectively before and after 60 years). In all the cases, excessive histologic bone resorption was mediated by mononuclear small osteoclasts (mean osteoclast length +/- SD = 27.3 +/- 4.1 as compared to normal range = 35.0 +/- 1.0, P less than 0.001). In different in vitro models, these small mononuclear osteoclasts are considered as progenitors. These data suggest an abnormal osteoclast differentiation in B-cell malignancies other than MM, probably due to differences in the production of local factors acting on bone remodelling.

Adult↗

Osteoblast stimulation in multiple myeloma lacking lytic bone lesions.

The reasons why some patients with multiple myeloma (MM) do not develop severe bone loss, or even develop sclerotic bone lesions, remain unclear. In order to answer this question at the cellular and tissue level, we evaluated the histological bone condition of 10 patients with MM who never developed lytic bone lesions during the course of their disease (including two patients with sclerotic MM). Myeloma-induced bone changes in the close vicinity of myeloma cells were evaluated by quantitative histology (bone histomorphometry). All 10 patients presented a significantly increased osteoblastic activity. This was associated with an increased bone resorption in seven of the 10 cases. Three patients had a pure osteoblastic presentation. These features were the reverse of the pattern observed in seven patients with lytic bone lesions: increased bone resorption with decreased bone formation. Almost all of these 10 patients showing excessive osteoblastic activity had increased serum bone gla protein levels, a specific marker of bone formation. Finally, 90% of these patients were lambda MM (70% of them were IgG lambda MM), an immunoglobulin subtype previously associated with the sclerotic MM variants. In conclusion, a subset of patients with MM never develop severe bone loss because of the stimulation of osteoblastic activity. These patients belong to the same family as osteosclerotic MM, presenting more frequently the IgG type and lambda subtype.

Aged↗

[Diabetic cheiroarthropathy. Microcirculatory aspects].

Diabetic cheiroarthropathy (DCA) or pseudosclerodermatous hand of the diabetic is characterized by nonpainful limited extension of the proximal metacarpophalangeal and/or interphalangeal joints with spontaneous flexum of the fingers. The mechanism of lesion formation is poorly known but apparently associates neurogenic, vascular and cutaneous phenomena. Fifteen patients with DCA (9 men, 6 women; range 20-74 years) were studied by capillaroscopy, photoplethysmography and skin biopsy. Eleven had type 1 diabetes and 4 type 2 over periods ranging from 1 to 42 years (mean 19.9 years). Diabetic retinopathy was noted 10/15 times, nephropathy 5/15 times and neuropathy of the lower limbs 13/15 times. All patients had at least one of these abnormalities. In capillaroscopy, "Shoal of fish" features of diabetic microangiopathy were found only 4 times, but minor dystrophy was noted in 12 cases. In digital photoplethysmography, a drop in digital systolic pressure or an increase in pulse time was noted in 5 cases. The Hillestad test was less than or equal to 2 in 8 patients. Histological study showed constant dermal collagenous fibrosis in diseased skin, which was also found in normal skin in 6/13 patients. PAS staining showed a thickening of vascular basal membrane 14/15 times in diseased skin and 11/13 times in normal skin. The relation between DCA and microangiopathy is discussed in terms of collagen metabolism abnormalities observed during diabetes.

Adult↗

[Biphotonic absorptiometry of the foot: methodology and application to algodystrophy].

A simple methodology for the evaluation of the bone mineral content of the foot by biphotonic absorptiometry is described. From the study of a test population, a pathological demineralization threshold of 10%, given that the measurement is expressed in g, has been defined at the level of the forepart of the tarsus. This threshold enables the significant distinction between the test population and a population with algodystrophy. Biphotonic absorptiometry seems to provide a quantitative diagnostic argument to complement the radiographical and scintigraphical examinations.

Absorptiometry, Photon↗

Mechanisms of bone destruction in multiple myeloma: the importance of an unbalanced process in determining the severity of lytic bone disease.

In order to clarify the mechanisms involved in the occurrence of lytic bone lesions (BL) in multiple myeloma (MM), we have compared the presenting myeloma-induced histological bone changes of 14 previously untreated MM patients with lytic BL with those of seven MM patients lacking lytic BL at presentation despite similar myeloma cell mass. A major unbalanced bone remodeling (increased bone resorption with normal to low bone formation) was the characteristic feature of patients presenting lytic BL. Furthermore, this unbalanced process was associated with a significant reduction of bone mass. Unexpectedly, a balanced bone remodeling (increase of both bone resorption and bone formation, without bone mass reduction) rather than a true lack of an excessive bone resorption was the usual feature of patients lacking lytic BL. Our current work clearly shows that a majority (72%) of patients with MM present an important unbalanced bone remodeling at diagnosis, leading to bone mass reduction and bone destruction (unbalanced MM). Some patients (20%) retain a balanced bone remodeling with initial absence of bone destruction (balanced MM). Few (8%) patients have pure osteoblastic MM without bone destruction.

Bone Diseases↗

[Diabetic cheiroarthropathy].

Cheiroarthropathy is quite frequent in diabetics, but is only really specific at stage III, which is the most characteristic form. It is all the more frequent as the diabetes is old, but remains unrelated to sex, age and type of diabetes. The stiffening of the joint readily extends to other joints. The patients are moderately alerted in the absence of other associated pathologies: trigger finger, Dupuytren's disease, carpal tunnel syndrome. All these manifestations form the "diabetic hand", of which cheiroarthropathy is only one component. The need for an accurate analysis with the purpose of appropriate treatments, should be emphasized. The angiologic and histopathological study of patients with stage III cheiroarthropathy, enables us to demonstrate moderate abnormalities of the microcirculation, which are quite different from those encountered in sclerodermia. The etiopathogenesis of cheiroarthropathy remains mysterious and is probably related to an alteration of the collagen metabolism. One of the most interesting component is the association between cheiroarthropathy and the micro-angiopathic complications of diabetes mellitus: cheiroarthropathy being the indicator of such diabetes.

Adult↗

[Insufficiency fractures of the sacrum. 5 cases].

Five cases of insufficiency fracture of the sacrum in women aged over 60 are reported. The elements of diagnosis and causative factors are reviewed. In all cases the diagnosis was confirmed by technetium bone scintigraphy and computerized tomography of the sacrum. Bone tissue evaluation in search of a bone-wasting disease, the principal cause of this type of fracture, was conducted in all 5 patients, using photon absorptiometry and/or double energy computerized tomography and histomorphometry. These examinations provided detailed information on disorders of mineralization in the genesis of these insufficiency fractures.

Aged↗

Histologic evidence of an abnormal bone remodeling in B-cell malignancies other than multiple myeloma.

In a prospective study of the quantitative bone changes induced by B-cell cancers other than multiple myeloma (MM), but including chronic lymphocytic leukemia (CLL; n = 8), hairy cell leukemia (HCL; n = 3), and Waldenström disease (WD; n = 7), an abnormal bone remodeling close to malignant cells was found in 80% of the patients. This was observed more frequently in cases of diffuse, but not nodular, bone marrow involvement by tumor cells. More particularly, excessive bone resorption (a major feature of MM) associated with a normal to low bone formation (i.e., uncoupling bone disease) was the most frequent feature and in the same range of that observed in overt MM. However, as opposed to MM, this bone resorption was characteristically mediated by small mononucleated osteoclasts (i.e., microresorption). The same phenomena of abnormal bone remodeling, the uncoupling process, excessive bone resorption, and above all microresorption were confirmed by the detailed bone study of five cases of B-cell cancers other than MM presenting lytic bone lesions and hypercalcemia. The current findings are important for clarifying the biology of these B-cell malignant diseases, and also could be of diagnostic and prognostic value.

Adult↗

[Bone complications during the treatment of osteoporosis with fluor].

Fourteen osteoporotic women who had been under treatment with fluoride (23 mg/day of fluorine ions) for 12 months on average developed periarticular pain in the lower limbs or pelvis, corresponding to 21 fractures due to bone insufficiency. Six of these fractures were revealed only by radionuclide uptake in the painful areas, whereas the remaining 15 fractures, including 2 of the sacrum, were visible at radiography. Four patients had a past history of hyperthyroidism or were in a state of active hyperthyroidism detected by hormonal assays and iliac bone biopsy when the fractures were diagnosed. The decalcification associated with hyperthyroidism facilitates the occurrence of bone insufficiency fractures, as do treatments with high doses of fluoride, inadequate calcium supplement intake (observed in 5 cases) or the presence before treatment of renal impairment or disorders of bone mineralization, sometimes detected only by iliac bone biopsy. Repeated measurements of blood and urinary fluoride levels during treatment make it possible to adjust fluoride dosage, and lower doses (14 mg/day of fluorine ions) might reduce the incidence of the adverse effects of fluoride on bone.

Aged↗

Nonspecific back pain in children. A search for associated factors in 14-year-old schoolchildren.

BACKGROUND: Nonspecific back pain in children is nearly as common as in adults but is associated with a number of age-specific risk factors including female gender, a family history of low back pain, a high level of physical activity, and prolonged sitting. OBJECTIVE: To investigate potential school-related risk factors for back pain in children, most notably schoolbag weight expressed as a percentage of body weight (relative schoolbag weight), whether the schoolbag is carried by hand or by a shoulder harness, how the child travels to and from school, and sitting positions. PATIENTS AND METHODS: 123 eighth-graders, 58 girls and 65 boys, with a mean age of 14 +/- 0.6 years, completed an anonymous self-questionnaire during a school day involving six hours of classes. Their schoolbag was weighed on the same day. RESULTS: Most respondents traveled to and from school in a vehicle (70%), made one trip in each direction each day (75%), and carried their schoolbag by the shoulder harness (92%). The prevalence of back pain on the study day was 27.6%, whereas the cumulative prevalence for the last 12 months was 82.9% with 16.3% of respondents reporting a single episode of pain, 57.7% recurrent pain, and 8.9% chronic pain. A need for a physician visit for back pain was reported in 18.7% of cases, and 14.6% of respondents had missed school and/or sporting activities because of back pain. Female gender was associated with current back pain (odds ratio [OR], 2.7; 95% confidence interval [CI], 1.2-6.1). A relative schoolbag weight of 20% or more was associated with a history of back pain (OR, 3.1; 95% CI, 1.0-9.2), and this effect was larger in children who traveled to and from school on foot and in those who carried their schoolbag in their hand. Sitting on the edge of the chair while completing the questionnaire was significantly associated with a history of a physician visit for back pain (OR, 3.1; 95% CI, 1.0-9.5). Neither handedness nor the position of the questionnaire on the table were significantly associated with back pain in our study population. CONCLUSIONS: The findings from this cross-sectional study indicate a need for a longitudinal prospective study designed to identify etiologic and prognostic factors of back pain in adolescents, with the goal of devising preventive strategies likely to reduce the risk of low back pain in adulthood.

Adolescent↗