Remarkable improvement in serum 25-hydroxyvitamin levels among hip fracture patients over a 12-year period: a prospective study in South-eastern Finland.

Hypovitaminosis D is a problem among hip fracture patients. In a 1-year cohort study comprising 245 hip fracture patients (mean age of females 81 years and males 78 years) from south-eastern Finland, the mean 25-hydroxyvitamin D [S-25(OH)D] concentration was 73(SD 31) nmol/L. Vitamin D supplementation has been integrated into our current practice. INTRODUCTION: The objectives of this study are to verify vitamin D levels among hip fracture patients and to compare the results with a similar study conducted in the same two hospitals covering the same geographic area 12 years ago. METHODS: A prospective cohort comprising 245 Caucasian hip fracture patients was enrolled in the study in two acute hospitals in south-eastern Finland (61° N) over a 12-month period in 2015-2016. The S-25(OH)D was measured using 25-hydroxyvitamin D electrochemiluminescence binding assay. The S-25(OH)D concentrations were compared with the corresponding concentrations of a similar cohort analyzed in the same two hospitals 12 years ago. RESULTS: Of the 245 patients, 70% were women with a mean age of 81 (SD 10) years, while the men had a mean age of 78 (SD 12) years (p < 0.01). The total mean S-25(OH)D concentration was 73 (SD 31.3) nmol/L. Regional differences were found: 15% in hospital A and 36% in hospital B had a S-25(OH(D level < 50 nmol/L, and the mean S-25(OH)D level was 79.2 (SD 31.7) nmol/L in hospital A and 62.4 (SD 27.5) nmol/L in hospital B (p < 0.001). No differences were found in S-25(OH)D concentrations by either the place of residence or the time of year. Overall, the percentage of patients with a sufficient vitamin D level (> 50 nmol/L) was remarkably higher in 2015-2016 (77%) than in 2003-2004 (22%). CONCLUSION: Our results indicate that vitamin D supplementation has been widely integrated into our current practice. However, regional differences were found in the S-25(OH)D concentrations for which the reasons are unknown.

Correction to: Remarkable improvement in serum 25-hydroxyvitamin levels among hip fracture patients over a 12-year period: a prospective study in South-eastern Finland.

The presentation of Table 4 was unclear in the original publication. The article has now been corrected in this respect.

Complete restoration of bursa-dependent immune system after transplantation of semiallogeneic stem cells into immunodeficient chicks.

For transplantation of semiallogeneic bursal stem cells into cyclophosphamide-treated 3-day old chicks, two lines of chickens homozygous at the major histocompatibility locus and their F(1) hybrids were used in reciprocal combinations. The semiallogeneic transplantations resulted in a complete restoration of antibody formation to sheep red blood cells (SRBC) and Brucella, of microscopic morphology of bursa fabricii, and of germinal center formation in the spleen. In contrast, allogeneic bursal stem cells were not effective in restoring secondary response to SRBC and germinal center formation, while they were able to reconstitute anti-Brucella responses and bursal morphology. These findings indicate an effective cooperation of donor and host cells leading to a complete restoration of the bursa-dependent lymphoid system, when the donor and recipient share at least one haplotype determining the major histocompatibility antigen complex.

Ontogeny of bursal function in chicken. 3. Immunocompletent cell for humoral immunity.

To study the occurrence of immunocompetent cells directly responsible for antibody production, cells from yolk sac, embryonic liver, bursa of Fabricius, bone marrow, spleen, or thymus were injected together with SRBC and Brucella abortus into 4-day old cyclophosphamide-treated chicks. A second stimulation was given 4 days later, and samples taken 4 days thereafter were used for antibody titrations. During ontogeny, immunocompetent cells appeared in significant numbers first in the spleen for anti-SRBC responses, but in the bursa for anti-Brucella responses. Later these cells were also found in thymus and bone marrow. In the bursa, cells immunocompetent for anti-SRBC response were not encountered in significant numbers. The slight response to SRBC by transferred bursa cells reflects the presence of stem cells and their immediate descendents in the bursa at different stages of development. These findings are compared with the development and maturation of the stem cell responsible for humoral immunity. In the bursa, development of the stem cell population precedes that of immunocompetent cells. The opposite relationship was found in bone marrow, spleen, and thymus where immunocompetent cells were always present some weeks before the appearance of cells capable of achieving a long-lasting reconstitution of bursa-dependent functions. These observations reveal that the bursa seeds out immunocompetent cells during its entire postembryonic development, but does not release the lymphoid stem cell population before this population has matured sufficiently and before the bursa itself, after fulfilling its function, starts to involute.

Association of tumour necrosis factor a, b and c microsatellite polymorphisms with clinical disease activity and induction of remission in early rheumatoid arthritis.

OBJECTIVE: To study the associations of tumor necrosis factor (TNF) a, b and c microsatellite markers with 1) the clinical disease activity and 2) the induction of remissions in patients with early rheumatoid arthritis (RA) treated with two treatment strategies. METHODS: In the FIN-RACo (FINnish Rheumatoid Arthritis Combination therapy) trial of two years, 195 patients with recent-onset RA were randomly assigned to receive either a combination (COMBI) (sulphasalazine, methotrexate, hydroxychloroquine, and prednisolone) or a single (SINGLE) (initially sulphasalazine with or without prednisolone) disease modifying antirheumatic drug (DMARD) therapy. TNF a, b and c microsatellite and HLA-DRB1 typings were carried out in 165 (79 COMBI; 86 SINGLE) study completers. RESULTS: At baseline the 28 joint disease activity scores (DAS28) of the patients positive for TNFa2, a13 or b1 microsatellite markers were significantly higher than in the other patients. In the SINGLE patients the DAS28 improved comparably in patients with (n = 31) or without (n = 53) the TNFb1 marker (NS), while the DAS28 of the TNFb1-positive COMBI patients (n = 22) improved significantly more than that of the TNFb1-negative cases (n = 57) (p = 0.014). Respective 31.8% (7/22) and 28.1% (16/57) of the COMBI patients with or without TNFb1 allele achieved remission at one year. The corresponding figure in SINGLE patients were 0% (0/31) and 20.8% (11/53) (p = 0.006). At two years the remission frequencies in the TNFb1+/TNFb1- patients in the COMBI and SINGLE were 50.0%/38.6% and 9.7%/22.6%, respectively. CONCLUSION: Early TNFb1+ RA patients have more active disease but respond more favourably to COMBI treatment than the patients without this microsatellite allele. The finding may be of clinical relevance for the choice of DMARDs in early RA.

Detection of circulating Yersinia-immunoglobulin complexes by enzyme immunoassay (EIA).

An enzyme immunoassay (EIA) was developed for the detection of Yersinia-immunoglobulin complexes of known Ig class. Immune complexes (ICs) were attached to polystyrene microtiter plates by rabbit anti-human immunoglobulins, and the existence of Yersinia enterocolitica O:3 antigens was demonstrated using Fab fragments of alkaline phosphatase (AP)-conjugated antibody against the same serotype. Simultaneous binding of Yersinia antigens and immunoglobulins was a prerequisite for the detection of ICs. The method will be valuable for research into the immunopathogenetic mechanisms leading to reactive arthritis after Yersinia infection.

Early ontogeny of germinal center formation in the chicken.

Germinal center formation was studied in the spleen of young chickens immunized in ovo and at the time of hatching. When immunization was performed on day 18 in ovo and on the day of hatching, the first germinal centers were observed at 4 days. This is markedly earlier than in unimmunized chickens, where the first germinal centers appear at the age of 10 days or later. Germinal center formation preceded significant antibody production. The possible role of germinal centers in the generation of immunological memory is discussed in the light of these and earlier observations.

Bacteria-Triggered reactive arthritis: implications for antibacterial treatment.

Reactive arthritis (ReA) is definitely caused by an infection. Several observations suggest that the triggering microbe may persist in the tissues of the patient for a prolonged time. The obvious conclusion is to consider antibacterial treatment. In two instances antibacterial agents are of definite value: in the primary and secondary prevention of rheumatic fever and for early eradication of Borrelia burgdorferi in order to prevent development of the arthritis associated with Lyme disease. Altogether, clinical and experimental data exist to indicate that if antibacterial treatment of ReA can be started very early during the pathogenetic process, the disease can be prevented or the prognosis improved. In fully developed ReA, the value of antibacterial agents is less certain. All available evidence indicates that short term antibacterial treatment has no effect on the prognosis and final outcome of ReA, and the results with long term administration of antibacterials are also overall poor. In some instances sulfasalazine appears useful, rather as a result of its antirheumatic effect or influence on an underlying inflammatory bowel disease than its action as an antibacterial agent. Tetracyclines have also been found to have an effect on ReA, but again, this is probably due to their anti-inflammatory action rather than any antibacterial effect.

Allogeneic bone marrow transplantation in multiple myeloma: a report of four cases.

Allogeneic bone marrow transplantation offers a new and promising form for treatment of multiple myeloma incurable with chemotherapy. We present four cases of advanced multiple myeloma given bone marrow transplantation from HLA-identical and MLC-negative sibling donors. One patient had a recurrent plasmacytoma 8 months later and one died 12 days after the transplantation whereas the other two are in good clinical remission 15 and 19 months post-transplantation.

Failure to prevent cytomegalovirus infection by cytomegalovirus hyperimmune plasma: a randomized trial by the Nordic Bone Marrow Transplantation Group.

Bone marrow transplantation recipients who were cytomegalovirus (CMV) seropositive and/or had a CMV seropositive donor were randomized for treatment with CMV hyperimmune plasma (n = 27) or no treatment at all (n = 27). The CMV hyperimmune plasma had neutralization titers greater than 250 and enzyme-linked immunosorbent assay titers greater than 18,000. Plasma (200 mg/kg body weight) was given on four occasions (during 2 days) from day 3 to day 76 after transplantation. Patient characteristics were similar in the two groups. After transplantation, the median CMV titers increased with greater than 100% in the group receiving the CMV plasma and decreased to less than 50% in the controls (p less than 0.01). Asymptomatic CMV infections occurred in 26% of the patients in the plasma group and 33% of the controls. The frequency of patients with symptomatic CMV infections was also the same in the two groups (51% vs 33%). Three patients each in the two groups developed CMV-associated interstitial pneumonitis. Patient survival and causes of death were similar in the two groups. To conclude, no beneficial effect of CMV hyperimmune plasma was seen in patients at high risk of developing CMV infections.

Serologic evidence of Yersinia infection in patients with anterior uveitis.

Anterior uveitis is a common inflammatory eye disease associated with the HLA-B27 phenotype. Bacteriologic cofactors have been implicated in the pathogenesis of several diseases associated with HLA-B27. Using a sensitive enzyme-linked immunosorbent assay, we examined the incidence of previous Yersinia infection in a group of 28 consecutive patients with anterior uveitis. Twelve patients had a significantly increased antibody response to Yersinia, 8 of whom were HLA-B27 positive. Eight patients had IgM antibodies, possibly indicative of recent infection. There were no positive Yersinia serologic findings in our control group of 28 subjects, 13 of whom were HLA-B27 positive. A strong association was found between previous Yersinia infection and the development of anterior uveitis in HLA-B27-positive and HLA-B27-negative patients.

Immunoblot analysis of human IgM, IgG and IgA responses to plasmid-encoded antigens of Yersinia enterocolitica serovar O3.

Human IgM, IgG and IgA responses after infection with Yersinia enterocolitica serovar O3 were studied by immunoblotting sera against whole-cell homogenates of a plasmid-containing strain of Y. enterocolitica O3 and a plasmid-free strain derived from it; each strain was grown in conditions expressive for the plasmid. The antibodies observed were directed against several plasmid-encoded polypeptides. The response against different bacterial components decreased uniformly with time and the persisting antibody production was directed against several epitopes. Strong reactions to the prominent plasmid-specified antigens of mol. wts (10(3] 26, 34, 45 and 52.5 were found more often with IgG-class antibodies than with IgM or IgA; the latter immunoglobulins recognised, respectively, antigens of mol. wt (10(3] 26 and 45 (IgM) and 26, 34 and 52.5 (IgA). Immunoblotting of sera from patients with yersinia-triggered reactive arthritis did not reveal any antigens that were involved additionally or specifically. However, IgA-mediated recognition of certain antigens of mol. wts (10(3] 26, 34 and 52.5 tended to persist longer in the arthritic patients.

Ankylosing spondylitis: current approaches to treatment.

To date there is no definite cure for ankylosing spondylitis. However, modern treatment improves the quality of life and the final outcome for most patients. Patient education and physiotherapy form the basis of treatment. In pharmacotherapy, nonsteroidal anti-inflammatory drugs have a central role. Second-line drugs such as sulfasalazine, immunomodulating agents and other antirheumatic disease-modifying drugs should be applied if the disease is active. Corticosteroids are used mainly intra-articularly. The problem of osteoporosis in ankylosing spondylitis is gaining more interest, and efforts to prevent or treat it will increase. It is critical to make an early diagnosis of ankylosing spondylitis and in active cases start intensive therapy before irreversible damage takes place.

Acute anterior uveitis after yersinia infection.

Twenty-eight cases of acute anterior uveitis in which raised antibody titres indicated yersinia infection as a possible causative factor in the disease were studied retrospectively. In most cases the antibodies belonged to the IgA class; in only 6 patients did the presence of IgM class antibodies indicate recent infection. In half the cases also antibody titres against Chlamydia were raised. The clinical features and course of the disease did not differ from those of acute anterior uveitis due to other causes.

Serum carnitine levels in bone marrow transplant recipients.

This study investigated plasma carnitine levels in patients undergoing allogenic bone marrow transplantation. The patients received fat-based TPN (50% fat, 50% CHO; calorie: nitrogen ratio 125:1) for an average of 33 +/- 7.5 days. TPN was started before transplantation and stopped when patients were able to eat. Caloric needs were estimated using the Harris-Benedict equation; 150% of the estimated BEE was given for the first two weeks after transplantation. The amount of TPN was gradually decreased as patients resumed their oral intake. All patients had low-normal serum carnitine levels before transplantation. There was no significant change in total or free serum carnitine levels during the course of TPN. However, in patients who had symptoms of graft vs. host reaction (GVH), the highest carnitine values during GVH (total 72.3 +/- 6.5 and free 61.2 +/- 12.4 mumol/l) were significantly higher (p < 0.001) than the baseline values (total 27.1 +/- 9.3 and free 24.9 +/- 9.6 mumol/l) or the highest non GVH values after transplantation (total 32.0 +/- 10.7 and free 29.0 +/- 10.7 mumol/l, respectively). The serum triglyceride, total cholesterol, and HDL cholesterol remained within normal range. In conclusion, bone marrow transplant patients receiving fat-based TPN have normal circulating levels of carnitine. GVH reaction caused an increase in the carnitine levels, which was probably due to increased tissue catabolism.

Ten-year follow up study of patients from a Yersinia pseudotuberculosis III outbreak.

A Yersinia pseudotuberculosis serotype III outbreak in 1982 was characterized by a high frequency of post-infectious complications. Ten years later 16 out of the 19 patients originally included in the outbreak were reached for a follow up evaluation. Altogether nine patients suffered from chronic joint symptoms. Four of them were HLA B27-positive. Two of these had ankylosing spondylitis; one with severe erosive polyarthritis and secondary amyloidosis which led to uremia requiring haemodialysis and eventually to death, the other with ankylosis of the lumbar spine and sacroiliitis. None of the patients any longer had detectable anti-Yersinia antibodies. The long-term prognosis of Yersinia-triggered reactive arthritis is discussed.

Yersinia-associated arthritis in rats: effect of 65 kDa heat shock protein, bovine serum albumin and incomplete Freund's adjuvant.

OBJECTIVE: We have previously shown that the microbial load of rats has a significant effect on their susceptibility to Yersinia-associated arthritis. In this study our aim was to see whether mycobacterial 65 kDa heat shock protein (hsp) could induce the same suppressive effect in experimental Yersinia-associated arthritis as has been reported for arthritides induced by adjuvant, pristane, or streptococcal cell walls (SCW). METHODS: Arthritis was induced by the intravenous injection of Yersinia enterocolitica 0:8 into Lewis rats. Hsp, bovine serum albumin (BSA) or NaCl, administered in incomplete Freund's adjuvant (IFA), was given subcutaneously on day -5 or +5 with regard to the bacterial inoculation. RESULTS: Mycobacterial hsp given in IFA on day -5 significantly suppressed the development of arthritis. However, a similar suppression was observed with BSA or NaCl given in IFA. CONCLUSION: These results, together with those known from the effect of microbial load, suggest that susceptibility to Yersinia-associated arthritis is easily affected by external factors.

In vitro lymphoproliferative response to Yersinia: depressed response in arthritic patients years after Yersinia infection.

The persistence of lymphocyte transformation response to Yersinia was studied three to six years after Yersinia infection in subjects who had or had not suffered from reactive arthritis. In persons who had had arthritis, significantly weaker response to Yersinia was found than in those who had recovered without developing arthritis. The same held true also for the response to Klebsiella. These results support and extend our earlier observations of a depressed lymphocyte transformation response to Yersinia during the course of Yersinia arthritis. This phenomenon may be linked to the individual's susceptibility to arthritic complications after Yersinia infection.

HLA frequencies in HLA-B27 negative patients with reactive arthritis.

The purpose of the present work was to find out whether there is an HLA type common to the patients who, in spite of being B27 negative, have developed reactive arthritis (ReA). We compared the HLA-antigens of 25 HLA-B27 negative ReA patients to those of healthy control persons. No statistically significant differences were observed in the HLA-A, B, C, DR and DQ antigen frequencies between the patients and the control group. The frequency of DR4 was slightly lower in the patients than in the controls, although this difference was not statistically significant. On the other hand, 18/25 (72%) of the B27-negative ReA patients experienced a chronic or prolonged course of the disease. These findings indicate that DR4 does not contribute to the chronicity of ReA in the same way that it is known to do in rheumatoid arthritis (RA) or Lyme arthritis. They do not support the hypothesis that some other HLA-antigen, in addition to HLA-B27, could have a predisposing or protective effect in ReA.

Effect of antimicrobial treatment on chronic reactive arthritis.

In a double-blind study comprising 36 patients the effect of a three-month course of ciprofloxacin on chronic reactive arthritis was evaluated. At the end of the follow-up period 6 months after stopping the therapy, arthralgia, pain at movement and morning stiffness had decreased significantly compared to the values before the treatment in the ciprofloxacin group, whereas the Ritchie index and ESR showed a significant decrease in the control group. We conclude that further studies are necessary before the value of prolonged ciprofloxacin treatment of chronic reactive arthritis can be established.