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Electrical resistivity of stainless steel AISI 316 L was measured by millisecond pulse-heating in the temperature range from room temperature to the melting point at approximately 1400°C. The measurement results of electrical resistivity as a function of specific enthalpy were combined with results of specific heat capacity measurements by differential scanning calorimetry to obtain the relation between resistivity and temperature. Additionally to electrical resistivity and specific heat capacity, thermal diffusivity, density at room temperature, and thermal expansion were measured. From these results, thermal conductivity was calculated. Using the results of thermal conductivity and electrical resistivity, a Smith-Palmer-plot was drawn. It shows a significant deviation from the Wiedemann-Franz law with the Sommerfeld value due to the lattice component, electron scattering by solute atoms, and other smaller contributions. [ABSTRACT FROM AUTHOR]

Flow-cytometry studies of DNA and RNA content were carried out in acridine orange-stained synovial fluid lymphocytes from 11 patients presenting with classical or definite rheumatoid arthritis. Monoclonal antibodies were used to detect specific T cell surface antigens (OKT3, OKT4, OKT8) and antigens associated with lymphocyte activation (OKIa 1, OKT10). T3 positive cell percentages were comparable to those of normal blood, although T4/T8 ratios were decreased in 4 out of 5 cases, and HLA-DR positive cells increased. Six out of 11 patients showed percentages of dividing cells varying from 2.2 to 7.2% as compared with less than 1% in the other patients and in normal blood. Nondividing cells were characterised by an increase in their RNA content compared with normal blood. A greater increase of RNA content was observed in patients with lower percentages of dividing cells, suggesting a G1/S block. Changes in cellular DNA and/or RNA contents provide a valuable parameter of lymphocyte activation, not necessarily linked to the expression of differentiation antigens by activated cells. [ABSTRACT FROM PUBLISHER]

Association between bacterial endocarditis (BE) and vertebral osteomyelitis (VO) has infrequently been noted. In a retrospective analysis of BE (280 cases) and VO (150 cases) 14 cases were found to have this association. There were 12 males and 2 females, ages ranging from 39 to 72 years, mean age 56·6. Blood cultures were positive for Streptococcus viridans (6 cases). Str. faecalis (4 cases), staphylococcus (2 cases). Gram negative bacteria (1 case). Organism was not isolated in one case. Fever and severe back pain antedate the diagnosis of VO 3·5 and 2·5 months. X rays films of the spine and bone scans (4 cases) revealed lumbar (6 cases) or cervical (4 cases), or dorsal (3 cases) or combined cervical and dorsal (1 case) locations. History of murmur (4 cases) and development of mitral (8 cases) or aortic (4 cases) or combined mitral and aortic (2 cases) insufficiencies were consistent with concomitant BE. Echocardiogram revealed vegetations in 6 out of 9 cases. Patients received antibiotic therapy for 3·5 months. Ten patients were cured with antibiotics only, 4 required valve replacement. One died. Thus age, sex, history of heart disease, valvular involvement, duration of symptoms prior to admission and bacteriological pictures are the same in BE with VO as in BE without VO. Survival rates are also the same early recognition of BE and VO with prompt and prolonged antibiotic therapy may prevent severe haemodynamic or vertebral problems. [ABSTRACT FROM PUBLISHER]

In the Dosing IntraVenous Administration (DIVA) study, IV ibandronate injections (15-30 s duration) provided significantly greater gains in bone mineral density than daily oral ibandronate (P<0.001). Single transiliac bone biopsy was performed in a subgroup of women (n=109/1395) from DIVA to assess the impact of ibandronate on newly formed bone and bone remodeling. Patients received ibandronate IV injections 2 mg every 2 months, 3 mg every 3 months or oral ibandronate 2.5 mg daily, plus oral or IV placebo, as appropriate to maintain blinding. Of the 1395 participants from the DIVA study, 122 were enrolled in the substudy. Qualitative histological analysis was performed on all biopsy cores and 89 cores were considered to be evaluable for quantitative histomorphometry. Following 2 years of ibandronate treatment, trabecular bone maintained its normal lamellar structure with no evidence of woven bone, marrow fibrosis, cellular toxicity, or other qualitative abnormalities. Primary mineralization of new bone remained normal, as indicated by the slightly lower osteoid thickness and osteoid volume, with normal mineral apposition rate compared to healthy, postmenopausal women. Mineralizing surface, osteoid surface, activation frequency and bone formation rate were decreased in all ibandronate-treated groups compared with values from healthy, postmenopausal women. Specifically, the bone formation rate (BFR/BV and BFR/BS) was approximately 5 times lower in the ibandronate-treated (3 mg) group than in healthy, postmenopausal women. Histomorphometric analysis of transiliac bone biopsies demonstrated normal micro-structure of newly formed bone with normal mineralization and reduced remodeling after oral or IV ibandronate.

Oral daily and weekly bisphosphonates represent the current mainstay of treatment for postmenopausal osteoporosis (PMO). However, the inconvenience of frequent dosing is known to negatively affect adherence to therapy in the long term. This has prompted the development of convenient oral bisphosphonate regimens that feature simple, less frequent dosing schedules. Such regimens require high potency agents, which can be given at low effective doses and that also have good tolerability. Ibandronate is a potent, nitrogen-containing bisphosphonate with proven efficacy when given intermittently to estrogen-depleted beagle dogs, rats and cynomolgus monkeys. Clinically, a pivotal prospective study has established that oral ibandronate has significant vertebral fracture efficacy in PMO, whether given daily (2.5 mg) or intermittently (20 mg every other day for 12 doses every 3 months; extended between-dose interval>2 months). Both oral regimens were well tolerated, which is noteworthy as patients with a history of gastrointestinal (GI) disturbance were not specifically excluded. As a result of these findings, a large, multinational, randomized, double-blind study (Monthly Oral iBandronate In LadiEs: MOBILE) is currently exploring the non-inferiority of once-monthly oral ibandronate (100 or 150 mg) to the oral daily ibandronate (2.5 mg) regimen with proven anti-fracture efficacy, in terms of lumbar spine bone mineral density (BMD) change. As with the trials investigating the weekly administration of other bisphosphonates, vertebral fracture efficacy will be inferred if the study demonstrates the non-inferiority of once-monthly ibandronate to the proven oral daily regimen in terms of spinal BMD change. The availability of this once-monthly ibandronate regimen is expected to offer benefits in terms of convenience (by having to follow dosing recommendations once a month vs. once daily or weekly) and potentially tolerability (by reducing the potential for upper GI irritation that can result from frequent, repeated exposure). Greater convenience and tolerability may enhance the therapy adherence and, hence, improve long-term therapeutic outcomes in PMO.

Context: Ibandronate, a potent, nitrogen-containing bisphosphonate developed for intermittent administration in postmenopausal osteoporosis, aims to overcome current adherence issues with daily and weekly oral bisphosphonates through once-monthly oral dosing., Objective: The purpose of this study was to investigate the safety, pharmacodynamics, and pharmacokinetics of once-monthly oral ibandronate., Design: A randomized, 3-month, double-blind, placebo-controlled, phase I study (Monthly Oral Pilot Study) was conducted., Setting: The study was conducted at five clinical trial centers in the United Kingdom and Belgium., Patients or Other Participants: Subjects were postmenopausal women (age, 55-80 yr; > or =3 yr post menopause; n = 144)., Intervention(s): Once-monthly oral ibandronate 50, 100, or 150 mg or placebo was used. After the first cycle, the 50-mg arm was split, with participants continuing on either 50 or 100 mg., Main Outcome Measure(s): Primary outcome measures were safety, serum and urinary C-telopeptide (CTX), and serum ibandronate AUC0-infinity., Results: Once-monthly oral ibandronate was well tolerated, with a similar overall and upper gastrointestinal safety profile to placebo. Once-monthly ibandronate was also highly effective in decreasing bone turnover; substantial reductions from baseline in serum CTX (-56.7% and -40.7% in the 150- and 100-mg arms, respectively; P < 0.001 vs. placebo) and urinary CTX (-54.1% and -34.6%, respectively; P < 0.001 vs. placebo) were observed at d 91 (30 d after the final dose). Analysis of the area under the effect curve (d 1-91) for change from baseline (percent x days) in serum CTX and urinary CTX indicated a dose-response relationship. The AUC0-infinity for ibandronate increased with dose but not in a dose-proportional manner., Conclusions: These findings indicate a potential role for once-monthly oral ibandronate in the treatment of postmenopausal osteoporosis.

Unlabelled: Once-monthly (50/50, 100, and 150 mg) and daily (2.5 mg; 3-year vertebral fracture risk reduction: 52%) oral ibandronate regimens were compared in 1609 women with postmenopausal osteoporosis. At least equivalent efficacy and similar safety and tolerability were shown after 1 year., Introduction: Suboptimal adherence to daily and weekly oral bisphosphonates can potentially compromise therapeutic outcomes in postmenopausal osteoporosis. Although yet to be prospectively shown in osteoporosis, evidence from randomized clinical trials in several other chronic conditions shows that reducing dosing frequency enhances therapeutic adherence. Ibandronate is a new and potent bisphosphonate with antifracture efficacy proven for daily administration and also intermittent administration with a dose-free interval of >2 months. This report presents comparative data on the efficacy and safety of monthly and daily oral ibandronate regimens., Materials and Methods: MOBILE is a 2-year, randomized, double-blind, phase III, noninferiority trial. A total of 1609 women with postmenopausal osteoporosis were assigned to one of four oral ibandronate regimens: 2.5 mg daily, 50 mg/50 mg monthly (single doses, consecutive days), 100 mg monthly, or 150 mg monthly., Results: After 1 year, lumbar spine BMD increased by 3.9%, 4.3%, 4.1%, and 4.9% in the 2.5, 50 /50, 100, and 150 mg arms, respectively. All monthly regimens were proven noninferior, and the 150 mg regimen superior, to the daily regimen. All monthly regimens produced similar hip BMD gains, which were larger than those with the daily regimen. All regimens similarly decreased serum levels of C-telopeptide, a biochemical marker of bone resorption. Compared with the daily regimen, a significantly larger proportion of women receiving the 100 and 150 mg monthly regimens achieved predefined threshold levels for percent change from baseline in lumbar spine (6%) or total hip BMD (3%). All regimens were similarly well tolerated., Conclusions: Monthly ibandronate is at least as effective and well tolerated as the currently approved daily ibandronate regimen in postmenopausal osteoporosis.

The prevention and treatment of glucocorticoid-induced osteoporosis is a major concern for rheumatologists since inflammatory joint disease is among the most common reasons for long-term glucocorticoid therapy. We used a randomized placebo-controlled design to evaluate the efficacy of one-year cyclical etidronate therapy in preventing bone loss in 83 glucocorticoid-treated patients with rheumatoid arthritis, polymyalgia rheumatica, or giant cell arteritis. Glucocorticoid treatment duration was shorter than three months, and the starting dose was greater than 7.5 mg of prednisone-equivalent per day. Etidronate was given according to the standard cyclical schedule, i.e. 400 mg/d for periods of 14 days separated by 76-day intervals during which patients took 500 mg of supplemental calcium per day. The primary evaluation criterion was the change in lumbar spine bone mineral density after one year of etidronate therapy. Bone mineral density decreased by 1.94 +/- 0.61% in the placebo group and increased by 0.86 +/- 0.6% in the etidronate group, yielding a between-group difference of 2.8 +/- 0.86% (P = 0.002). The difference was largest in postmenopausal women (3.38 +/- 1.11%; P = 0.004). At the femoral neck, there was a smaller bone mineral density decrease in the etidronate than in the placebo group, but the difference (1.11 +/- 1.13%) was not statistically significant. The most common side effects were gastrointestinal symptoms and showed no difference between the two groups. Four fractures (including one vertebral fracture) occurred in the placebo group versus two (including one vertebral) in the etidronate group. Etidronate prevents glucocorticoid-induced lumbar spine bone loss in patients with rheumatoid arthritis, polymyalgia rheumatica, or giant cell arteritis.

Rheumatoid arthritis (RA) is an autoimmune disease whose diagnosis was long based solely upon the demonstration of rheumatoid factors (RF) which are IgM antibodies with anti-IgG specificity. The development of modern techniques which are more sensitive and/or detect non-IgM rheumatoid factors has reduced the percentage of presumptive seronegative RA. Immunological studies of the disease also reveal other evidences of polyclonal B-lymphocyte activation: hypergammaglobulinemia, high levels of beta-2-microglobulin and circulating immune complexes, presence of various autoantibodies (anti-collagen, antilymphocyte and, in some instances, anti-nuclear antibodies). These anomalies are found, not only in the blood, but above all in the synovial fluid, which explains the low synovial complement level. The disturbances of cellular immunity cannot yet be used for diagnostic purposes, but suggest that the physiopathologic mechanism of RA involves a decreased T-suppressor lymphocyte activity and/or B-cell unresponsiveness to suppressor influences.

Synovial fluid lymphocytes were studied by cytofluorometry in 11 patients with classical or definite rheumatoid arthritis. This method allowed the study of the cellular cycle after acridine orange staining and of membrane antigens, expressed by normal and/or activated lymphocytes, which were demonstrated by using various monoclonal antibodies (OKT3, OKT4, OKT8, OKIa1, OKT10). The OKT4/OKT8 ratio was decreased in 4 out of 5 cases and the percentage of HLA DR + cells was clearly increased. In 6 out of the 11 patients, the percentage of dividing cells varied from 2.2 to 7.2 and was less than 1 in the others as in normal blood lymphocytes. Increase in cellular RNA content characterized the non dividing cells. The most elevated values of the cellular RNA content were observed in patients who had the smallest percentage of dividing cells, suggesting that the cellular cycle was stopped between the G1 and S phases. Study of the cellular cycle may reveal a lymphocyte activation parameter which could be unrelated to the expression of differentiation membrane antigens.

The authors have endeavoured to determine the place occupied by mast cells in bone tissue from the mode of action on the bone of their secretion products (metachromatic granules, heparin, prostaglandins), from their proliferation in reaction to some bone diseases (secondary mastocytosis) and from the bone lesions associated with systemic mastocytosis. Metachromatic granules are capable of chelating calcium, and heparin and prostaglandins stimulate bone resorption. However, the role of mast cells in bone remodeling through these mechanisms has not yet been demonstrated. Similarly, the significance of mastocytosis secondary to osteomalacia, renal osteodystrophy and ordinary osteoporosis remains hypothetical. Primary bone mastocytosis produces diffuse or circumscribed osteogenic, osteolytic or mixed lesions. While the pathogenesis of osteolytic forms can readily be explained by the actions of heparin and prostaglandins, that of the osteogenic forms is still mysterious. Finally, the histological profile, and even the nosological profile, of mast cell osteoporosis, a diffuse condition recently individualized, remain undetermined.

The authors report a case of ankylosing spondylitis affecting a woman with low-back pains. Although initial X-rays did not show any lesions of the spine, one year later, radiographs prove the existence of multiple lesions mimicking spondylodiscitides and characterized by erosions diffusely involving end-plates of cervical, dorsal and lumbar vertebrae. Surgical biopsy at the lumbar site provides an histological evidence of non specific inflammatory lesions.

HLA-DR antigen distribution was determined by lymphotoxicity on total lymphocytes for locus A.B.C. antigens numbering 14,28 and 7 respectively, and by a search on B lymphocytes for the 12 antigens of locus DR. The normal population included 124 subjects typed for HLA-A.B.C. and 200 subjects typed for HLA-DR. The frequency of alleles was compared to that of the different groups of patients. Significant variations were evaluated by the X2 test, using Woolf's method; the P value obtained was multiplied by the number of antigens looked for (P corrected, or pc). No deviation in frequency was found with the HLA-A.B.C. antigens. Only the DR 4 antigen, present in 23% of the normal population, was increased in proportions that depended on clinical classification: 39.4% (Pc = 0.05) in all patients with giant cell arteritis: 27% (NS) in the 37 polymyalgia rheumatica patients with negative biopsy of the temporal artery; 46.8% (P 0.05) in the 62 patients with Horton's disease presenting either as clinical and histological temporal arteritis (26 cases; DR 4 = 38.5%; NS), or as clinical and/or histological temporal arteritis associated with polymyalgia rheumatica (36 cases; DR 4 = 52.8%; Pc less than 0.005). The frequency of DR 4 antigen in Horton's disease with typical temporal artery biopsy (37 cases) was 46% (Pc = 0.05).

Using an immuno-enzymatic technique, the authors studied the production of anti-collagen I and II auto-antibodies in 171 cases of rheumatoid arthritis (RA), 40 cases of systemic lupus erythematosus (SLE) and 21 cases of overriding syndrome. Cellular immunity to native collagen II was tested in a group of 26 patients with RA and 27 control subjects, by studying the production of LIF (Leukocyte Inhibitory Factor) in response to this antigen. The anti-collagen I and II antibodies are present in 15.2% and 17.5% of RA patients respectively and also in 15% and 15.5% of the SLE patients studied. Anti-collagen I antibodies are associated with RA with extra-articular signs and anti-collagen II antibodies are associated with early RA, but no association could be found with the clinical or radiological course of the disease. Cellular reactivity to collagen II was found in 30% of the cases of RA studied and was associated with the early forms of the disease. Complementary studies on the association of certain HLA antigens with cellular or humoral reactivity to collagen should allow a better approach to the clinical relationships of certain cases of chronic inflammatory rheumatism with anti-collagen auto-immunization.

Twenty patients with classical or proved rheumatoid arthritis were treated with Isoprinosine. 13 patients received a dose of 25 mg/kg/day and 7 received a dose of 50 mg/kg/day, continuously for 2 months and then discontinuously, 5 days every fortnight. The series being treated with 25 mg/kg/day (7 patients) have received treatment for 12 months. No side effects have been observed; the only reason for ceasing treatment was its ineffectiveness (after at least 3 months of administration). The dosage of the associated anti-inflammatory drugs did not need to be increased, but neither was it decreased. The authors conclude that Isoprinosine is largely ineffective clinically, on laboratory tests and in terms of immunology, at least with the therapeutic protocols tested here.

In a study on the frequency of the HLA A, B, C and DR antigens seen in 100 controls and 31 patients with rheumatoid arthritis, the authors found a significant increase in the DR4 antigen in rheumatoid arthritis. (50% as against 25%; X2 = 8,5; 0,04 greater than Pc greater than 0,008; RR = 3,43). The other antigens on loci A, B. C and DR are not altered significantly. However the increase in DR4 which does not seem to be related to the severity of the rheumatoid arthritis, seems to be proportional to the level of rheumatoid factor. The authors review literature on HLA in rheumatoid arthritis and the figures for the antigenic frequency of HLA-DR4 are compared with their own results. The findings are of interest especially from a pathogenic point of view.

Fifteen cases of destructive disco-vertebral lesions discovered in patients with ankylosing spondylitis are reported. The incidence of these lesions was 5.5% and they were unrelated to underlying conditions. Radiologically, they fell into five categories: pseudodystrophic, pseudotuberculous, extensive erosions, bone condensation and isolated narrowing of the intervertebral spaces. From an analysis of these 15 cases and of published data, it would appear that these forms result from different pathogenetic processes: an inflammatory process for the pseudodystrophic and pseudotuberculous forms and for early extensive erosions; a mechanical process for bone condensation and perhaps also (though this is more controversial) for late extensive erosions and isolated intervertebral narrowing.

Articular manifestations occur in approximately 1% of cases of leprosy, sometimes at onset. They consist in a highly inflammatory polyarthritis, fairly similar to that seen in rheumatoid polyarthritis. They often herald a reactive leprous exacerbation and are dependent upon immunologic disturbances in brittle leprosy (mainly lepromatous). Joint pain should be differentiated from neurologic pain resulting from peripheral neuropathy which is often concomitant. Leprosy should be considered among the causes of polyarthritis, especially in immigrants, but also in residents who have travelled to areas where leprosy is endemic.

Systemic lupus erythematosus (SLE) is a polymorphic disease of unknown origin, characterized by many stigmata of autoimmunization which allow a biological diagnosis. Besides non-specific inflammatory disorders, considerable alterations of humoral and cellular immunity are found. The hallmark of the disease is the presence of anti-double-stranded-desoxyribonucleic acid (anti-ds DNA) antibodies, detected by the Farr radioimmunologic method or the crithidia luciliae immunofluorescence technique, both of which are nearly specific for SLE. The clinical significance of other types of anti-nuclear antibodies is unclear. Serial evaluations of antinuclear antibodies, complement fractions, circulating immune complexes, and, above all, immune complexes bound to target organs (kidneys, skin, synovial membranes) are needed to follow the course of the disease. The demonstration of abnormal suppressor T-cell activity has led to current pathogenic hypotheses and ongoing therapeutic trials with immunoregulating drugs.

The authors report their experience in the treatment of metatarsophalangeal arthritis of chronic inflammatory rheumatism by Erbium 169 synoviortheses (112 joints treated) and by infiltrations of triamcinolone hexacetonide (53 joints treated). The steroid appears to have a marked early superiority as it gives 85% good results compared to 61.6% for Erbium 169 after a period of one to three months. However, its results then deteriorate more rapidly and after 6 months, the proportion of good results is greater with the radioactive treatment (64% compared to 46.7%). The authors consider it reasonable to use triamcinolone hexacetonide as the first line treatment as it is easier to manage and less expensive, reserving the radioactive synoviortheses for later with the prospect of more lasting results.

This work is based on a review of 120 peripheral bone metastases of the upper limbs found in the literature and 10 others selected from a personal series of 469 cases of bone metastases. The authors stress the scarcity of these lesions (2%), metastases arising in bones of the forearm are usually part of a widespread osseous involvement, generally of mammary or prostatic origin. Metastases to the bones of the hand are more peculiar: 1) Those from bronchogenic carcinoma account for 50%. 2) Resultant soft tissue necrosis creates swelling, redness, heat and pain, which can mimic acute osteomyelitis. 3) X-rays reveal isolated osteolysis affecting metacarpals, phalanges, or more rarely carpal bones. Distal location of those metastases does not modify therapeutic management amputation is the best effective palliative treatment and must be discussed every time there is a concomitant skin ulceration, or if bone metastasis is unique or if the primary tumor is cured or accessible to treatment.