Danish translation and cultural adaptation of the Psoriatic arthritis UnclutteRed screening Evaluation (PURE-4) scale.

OBJECTIVES: Screening tools are needed to help to identify psoriatic arthritis in patients with psoriasis. The Psoriatic arthritis UnclutteRed screening Evaluation (PURE-4) questionnaire was developed for this purpose and has been shown to perform very well. The aim of this study was to translate and culturally adapt the PURE-4 scale into the Danish language. METHOD: The translational process followed the guidelines provided by the Mapi Research Trust, which include the following steps: forward translation, backward translation, cognitive interviews, and proofreading. Following the guidelines helps to maintain the content validity of the questionnaire and secures a translation that is both literally and culturally appropriate for the target population. RESULTS: All four items were modified throughout the translation process, involving mainly minor changes such as the addition of more colloquial words in the Danish version. The new Danish version of PURE-4 was reviewed and approved by the original developers. CONCLUSIONS: A Danish version of the PURE-4 questionnaire was produced. The translation and cultural adaptation of PURE-4 constitute the first step in the validation of the questionnaire in Danish patients with psoriasis.

Enthesitis in a European registry-based cohort of patients with psoriatic arthritis treated with tumour necrosis factor inhibitors: clinical burden, patient-reported outcomes, and treatment response.

OBJECTIVE: To explore the registration of enthesitis among biologic-naïve patients with psoriatic arthritis (PsA) initiating tumour necrosis factor inhibitor (TNFi) treatment across 12 European registries, compare the disease burden and patient-reported outcomes (PROs) between patients with and without enthesitis, and assess the enthesitis treatment response. METHOD: Demographics, clinical characteristics, and PROs at first TNFi (TNFi-1) initiation (baseline) were assessed in patients with PsA, diagnosed by a rheumatologist, with versus without assessment of entheses and between those with versus without enthesitis. Enthesitis scores and resolution frequency were identified at follow-up. RESULTS: Of 10 547 patients in the European Spondyloarthritis (EuroSpA) Research Collaboration Network initiating TNFi, 1357 underwent evaluation for enthesitis. Eight registries included a validated scoring system for enthesitis. At baseline, 874 patients underwent entheses assessment [Maastricht Ankylosing Spondylitis Enthesitis Score (MASES) 485 patients, Spondyloarthritis Research Consortium of Canada (SPARCC) 389 patients]. Enthesitis was detected by MASES in 170/485 (35%, mean score ± sd 3.1 ± 2.4) and by SPARCC in 236/389 (61%, 4 ± 3.4). Achilles enthesitis was most frequent, by both MASES (unilateral/bilateral 28%/9%) and SPARCC (48%/18%). MASES/SPARCC baseline and follow-up scores for TNFi-1 were available for 100/105 patients. Of these, 63 patients (63%) (MASES) and 46 (43.8%) (SPARCC) achieved resolution of enthesitis. The site-specific enthesitis resolution was overall lower at SPARCC sites (peripheral; 63-80%) than at MASES sites (mainly axial; 82-100%) following TNFi-1. Disease activity and PROs were worse in patients with versus without enthesitis. CONCLUSION: Entheseal assessments are only registered in a minority of patients with PsA in routine care. When assessed, enthesitis was common, and a substantial proportion demonstrated resolution following treatment with TNFi-1.

Disease activity-guided tapering of biologics in patients with inflammatory arthritis: a pragmatic, randomized, open-label, equivalence trial.

OBJECTIVE: To evaluate whether disease activity-guided tapering of biologics compared to continuation as usual care enables a substantial dose reduction while disease activity remains equivalent. METHOD: In this pragmatic, randomized, open-label, equivalence trial, adults with rheumatoid arthritis, psoriatic arthritis, or axial spondyloarthritis in low disease activity on stable-dose biologics for ≥ 12 months were randomized 2:1 into either the tapering group, i.e. disease activity-guided prolongation of the biologic dosing interval until flare or withdrawal, or the control group, i.e. maintaince of baseline biologics with a possible small interval increase at the patients request. The co-primary outcome in the intention-to-treat population was met if superiority in ≥ 50% biologic reduction at 18 months was demonstrated and disease activity was equivalent (equivalence margins ± 0.5). RESULTS: Ninety-five patients were randomized to tapering and 47 to control, of whom 37% (35/95) versus 2% (1/47) achieved ≥ 50% biologic reduction at 18 months. The risk difference was statistically significant [35%, 95% confidence interval (CI) 24%-45%], while disease activity remained equivalent [mean difference 0.05, 95% CI -0.12-0.29]. A statistically significant flare risk was observed [tapering 41% (39/95) vs control 21% (10/47), risk difference 20%, 95% CI 4%-35%]; but, only 1% (1/95) and 6% (3/47) had persistent flare and needed to switch to another biological drug. CONCLUSIONS: Disease activity-guided tapering of biologics in patients with inflammatory arthritis enabled one-third to achieve ≥ 50% biologic reduction, while disease activity between groups remained equivalent. Flares were more frequent in the tapering group but were managed with rescue therapy.

Complement C3d is not associated with axial spondyloarthritis and magnetic resonance imaging changes at the sacroiliac joint.

OBJECTIVE: To investigate the associations between complement C3d and inflammatory and structural changes by magnetic resonance imaging (MRI) at the sacroiliac joints (SIJ) suggestive of axial spondyloarthritis, according to the Assessment of SpondyloArthritis international Society (ASAS) criteria, in patients with low back pain. METHOD: This was a cross-sectional study of patients referred to the Spine Centre of Southern Denmark owing to unspecified low back pain (Spines of Southern Denmark cohort). The patients were divided into three groups: group 1: patients fulfilling the ASAS criteria for axial spondyloarthritis (axSpA, n = 96); group 2: patients with either a positive MRI of the SIJ and no spondyloarthritis features, or a negative MRI of the SIJ but positive human leucocyte antigen-B27 and one spondyloarthritis feature (non-axSpA, n = 38); group 3: patients with unspecified low back pain for > 3 months (control group, n = 82). Complement C3d was measured with double-decker rocket immunoelectrophoresis and evaluated in relation to the group division and baseline findings by SIJ MRI. RESULTS: In total, 184 C3d analyses were performed. The mean ± sd level of C3d was 33.8 ± 8.1 AU/mL. There were no differences in C3d levels between the three patient groups, mean values being: axSpA = 34.3 ± 7.9 AU/mL, non-axSpA = 33.5 ± 6.9 AU/mL, and controls = 33.4 ± 9.2 AU/mL. The level of C3d was not related to MRI findings. CONCLUSIONS: In these patients, complement C3d was not associated with active or structural SIJ changes on MRI suggestive of axial spondyloarthritis.

Diagnosing axial spondyloarthritis by multidiciplinary team conference at 3.5 years' follow-up in a cohort of patients with disease features according to the ASAS criteria.

OBJECTIVES: During the past two decades, magnetic resonance imaging (MRI) has increasingly been used diagnostically in axial spondyloarthritis (axSpA), and in 2009 MRI was introduced in the Assessment of SpondyloArthritis Society (ASAS) classification criteria. In clinical practice, there is a risk of overdiagnosis if MRI findings are not related to clinical and biochemical findings. The aim of this study was to provide an estimate of the prevalence of axSpA in a cohort of clinical patients with low back pain and findings suggestive of axSpA according to ASAS through consensus diagnosis at a multi-disciplinary team (MDT) conference, and to describe the performance of the features included in the ASAS criteria. METHOD: Consensus diagnoses of axSpA at MDT conferences were retrospectively established at 3.5 years' follow-up in a cohort of 84 patients, initially referred with disease features according to the ASAS criteria. Patients were examined clinically regarding spondyloarthritis features, and biochemical tests and MRI of the sacroiliac joints and entire spine were performed at baseline and after a mean of 3.5 years. RESULTS: According to the MDT consensus, 25 patients (30%) of the total cohort had axSpA at follow-up; 40% of individuals who fulfilled the ASAS criteria at baseline had axSpA, and 37% at follow-up; 96% of axSpA patients according to the MDT consensus met the ASAS criteria at baseline and 92% at follow-up. CONCLUSION: Approximately one-third of the included patients had axSpA when evaluated at the MDT conference. The ASAS criteria had low predictive value, but high sensitivity at both baseline and follow-up.

Plasma levels of H- and L-ficolin are increased in axial spondyloarthritis: improvement of disease identification.

Axial spondyloarthritis (axSpA) is a chronic inflammatory disease that primarily affects the axial skeleton. A predominance of innate versus adaptive immune responses have been reported in axSpA, indicating a prominent autoinflammatory component of the disease. Little is known about the lectin pathway proteins (LPPs) of the complement system in relation to axSpA. We have investigated LPPs in patients with axSpA and control individuals. Plasma samples were obtained from a cross-sectional cohort of 120 patients with a clinical diagnosis of axSpA and from 144 age- and gender-matched controls. The plasma concentrations of 11 LPPs were measured, using sandwich-type time-resolved immunofluorometric assays in patients and controls, and related to clinical diagnosis and disease activity. Three LPPs [H-ficolin (ficolin-3), L-ficolin (ficolin-2) and collectin liver 1 (CL-L1)] were significantly higher in axSpA patients than in controls (P < 0·0001) and one LPP, collectin kidney 1 (CL-K1), was significantly lower (P < 0·0001). Further, combining H- or L-ficolin concentrations above the 75th percentile of the respective H- or L-ficolin concentration measured in controls with human leucocyte antigen (HLA)-B27 positivity yielded axSpA diagnostic specificities of 99/99% and positive likelihood ratios of 68/62, respectively. H-ficolin and L-ficolin plasma concentrations were found to be elevated in axSpA patients regardless of time since diagnosis. H-ficolin and L-ficolin may represent diagnostic biomarkers for patients with axSpA and should be further evaluated. Our results showed no association between disease activity and the measured LPP concentrations. This result might be due to the cross-sectional design, and should be further investigated.

Structural progression rate decreases over time on serial radiography and magnetic resonance imaging of sacroiliac joints and spine in a five-year follow-up study of patients with ankylosing spondylitis treated with tumour necrosis factor inhibitor.

OBJECTIVE: To investigate temporal changes in structural progression assessed by serial conventional radiography and magnetic resonance imaging (MRI) of the sacroiliac joints (SIJs) and spine in patients with ankylosing spondylitis (AS) treated with tumour necrosis factor (TNF) inhibitor for 5 years. METHOD: Forty-two patients were included and 33 patients were followed for 5 years in a prospective investigator-initiated study. Conventional radiographs were required four times and MRI seven times. The modified Stoke Ankylosing Spondylitis Spinal Score (mSASSS); Spondyloarthritis Research Consortium of Canada (SPARCC) MRI SIJ and Spine Inflammation, and SPARCC MRI SIJ Structural Score (SSS) for Fat, Erosion, Backfill, and Ankylosis; and the Canada-Denmark MRI scores for Spine Inflammation, Fat, Erosion, and New Bone Formation (NBF) were applied. RESULTS: Compared with baseline, MRI Inflammation had decreased significantly at week 22 (spine)/week 46 (SIJ) and thereafter. MRI SIJ Fat (from week 22), SIJ Ankylosis, Spine NBF, and mSASSS had increased significantly at week 46 and thereafter. SIJ Erosion had decreased from year 2. The annual progression rate in mSASSS was significantly higher during weeks 0-46 compared to week 46 to year 3. In multivariate regression analyses, baseline SIJ Inflammation and Backfill were independent predictors of 5 year progression in SIJ Ankylosis. Spine Erosion predicted progression in Spine NBF. Longitudinally, Ankylosing Spondylitis Disease Activity Score, Bath Ankylosing Spondylitis Disease Activity Index, MRI Spine Inflammation, Fat, and Erosion scores were significantly associated with mSASSS. SIJ Inflammation, Fat, Erosion, and Backfill scores were longitudinally associated with SIJ Ankylosis. Structural progression was not associated with body mass index, smoking, or Assessment of SpondyloArthritis international Society Non-Steroidal Anti-Inflammatory Drug Index. CONCLUSION: In a 5 year follow-up study of patients with AS treated with TNF inhibitor, structural progression decreased over time.

No diagnostic utility of antibody patterns against Klebsiella pneumoniae capsular serotypes in patients with axial spondyloarthritis vs. patients with non-specific low back pain: a cross-sectional study.

OBJECTIVES: To investigate whether antibody response patterns against Klebsiella pneumoniae capsular serotypes can discriminate patients with axial spondyloarthritis (axSpA) from patients with non-specific low back pain (LBP). METHOD: Immunoglobulin (Ig)G and IgA antibodies against K. pneumoniae capsular serotypes K2, K26, K36, and K50 were measured, and antibody seropositivity compared between groups and analysed for patient correlation in five different groups: (a) 96 patients fulfilling the Assessment of SpondyloArthritis International Society (ASAS) classification criteria for axSpA; (b) 38 patients with either a positive magnetic resonance imaging (MRI) scan as defined by ASAS or a positive human leucocyte antigen (HLA)-B27 status plus one clinical SpA feature, characterized as 'non-axSpA'; (c) 82 non-specific LBP patients; (d) 40 healthy blood donors and (e) 43 patients with diagnosed ankylosing spondylitis (AS) served as the negative and positive control groups. RESULTS: There was no difference in IgG and IgA seropositivity against all serotypes between the axSpA, non-axSpA, and LBP groups. No significant correlations were found between anti-Klebsiella antibodies and age, gender, HLA-B27, or high-sensitivity C-reactive protein (hsCRP). IgG seropositivity against K50 was more frequent in AS (25.6%) than in axSpA (13.5%, p < 0.05). axSpA patients with radiographic sacroiliitis and AS controls concordantly had the highest frequency of seropositivity for ≥ 2 serotypes (21%). CONCLUSIONS: The antibody patterns against K. pneumoniae serotypes K2, K26, K36, and K50 did not discriminate between early axSpA and non-specific LBP.

The discriminative value of inflammatory back pain in patients with persistent low back pain.

OBJECTIVES: To estimate the prevalence of inflammatory back pain (IBP) characteristics and analyse the discriminative value of IBP relative to axial spondyloarthritis (SpA) according to the Assessment of SpondyloArthritis international Society (ASAS) criteria. METHOD: Patients who had low back pain for > 3 months were selected from a cohort of secondary care patients aged 18-40 years. Data included information on SpA features, human leucocyte antigen (HLA)-B27 typing, C-reactive protein (CRP) level, magnetic resonance imaging (MRI) of the sacroiliac joints, and self-reported IBP questions covering the pain characteristics included in the Calin, Berlin, and ASAS IBP definitions. RESULTS: Of the 759 included patients, 99% [95% confidence interval (CI) 98-100] had at least one IBP characteristic. The prevalence of the single IBP characteristics ranged from 10% (95% CI 7-12) for 'pain worst in the morning' to 79% (95% CI 76-82) for 'morning stiffness'. Two-thirds of the patients (67%, 95% CI 63-70), met at least one of the three IBP definitions. In all, 86 (11%) were classified as 'SpA according to ASAS'. All three IBP definitions were significantly associated with 'SpA according to ASAS'; however, the discriminative value was low, with sensitivity, specificity, and balanced accuracy values of 64, 50, and 57% for Calin, 59, 60, and 60% for Berlin, and 35, 79, and 57% for ASAS IBP definitions, respectively. CONCLUSIONS: In this study population, IBP characteristics were in general common and the discriminative value was low, as IBP could not differentiate patients with SpA according to ASAS criteria from patients with other causes of back pain.

Short-term treatment with growth hormone stimulates osteoblastic and osteoclastic activity in osteopenic postmenopausal women: a dose response study.

To investigate the potential use of growth hormone (GH) in Activate-Depress-Free-Repeat treatment of postmenopausal osteoporosis, we measured changes in serum levels of biochemical markers of bone turnover, insulin-like growth factor-I (IGF-I), calciotropic hormones, and bone mineral density in 40 postmenopausal women with osteopenia (ages 52-73 years) in response to 7 days of treatment with either placebo or GH (0.05, 0.10, or 0.20 IU/kg/day) administered subcutaneously in the evening. GH treatment increased serum osteocalcin (p < 0.01) and C-terminal type-I procollagen propeptide (p < 0.01) and also serum levels of type-I collagen telopeptide (p < 0.001), fasting urinary hydroxyproline/creatinine (p < 0.05), pyridinoline/creatinine (p < 0.05), and deoxypyridinoline/creatinine (p < 0.01) in a dose-dependent fashion. Even the lowest dose of GH tested induced a significant increase in these parameters; however, the effects were transient lasting only 1-2 weeks. In the highest dose group, however, a somewhat prolonged effect (30 days) on serum osteocalcin was observed. Furthermore, GH increased serum levels of IGF-I, insulin, and tri-iodothyronin. No effect on serum 1,25-dihydroxyvitamin D3 or parathyroid hormone could be demonstrated. Adverse effects were mainly related to fluid retention. They were clearly dose-dependent and rapidly reversible. In conclusion, short-term GH treatment stimulates bone formation and bone resorption in postmenopausal women with osteopenia.

Is skeletal responsiveness to thyroid hormone altered in primary osteoporosis or following estrogen replacement therapy?

Hyperthyroidism is characterized by increased bone turnover and resorptive activity. Similar changes in remodeling are seen in osteoporosis. To study the pathogenetic role of thyroid hormone in osteoporosis, we measured concentrations of free and total thyroid hormones and investigated the sensitivity of the skeleton toward thyroid hormones in 14 osteoporotic, 16 estrogen-treated, and 15 normal postmenopausal women with comparable thyroid status. Triiodothyronine (T3, 60 microg/day for 7 days) was administered to the three groups. The skeletal response was assessed by monitoring bone alkaline phosphatase (BAP), osteocalcin (BGP), and pyridinium cross-linked telopeptide domain of type I collagen (ICTP) in serum and urinary excretion of hydroxyproline (OHP), pyridinoline (PYR), and deoxypyridinoline (DPR) at days 0, 8, 15, and 57. Women on estrogen replacement therapy exhibited lower bone turnover than the normal postmenopausal women. Markers of bone formation were reduced by 19-43% and markers of resorption by 22-48%. The osteoporotic women displayed lower bone mass at the lumbar spine and the distal forearm (p < 0.01-0.001), but the levels of biochemical markers of bone formation and resorption were comparable to values obtained in the normal postmenopausal women. T3 stimulation caused significant increases (p values ranging between 0.05-0.001) in all three groups of the resorptive markers: ICTP (47%, 47%, 45%), OHP (29%, 30%, 33%), PYR (43%, 27%, 51%), and DPR (42%, 24%, 59%). Of the formative markers, only BGP increased significantly (32%, 40%, 47%) (p < 0.001). At day 57, however, all three formative markers increased compared with day 15 (p < 0.05-0.001). No significant differences in bone markers were demonstrated between groups. In the osteoporotic group, as the only group, serum calcium increased (p < 0.05) and serum PTH fell (p < 0.05). In conclusion, osteoporosis and estrogen substitution are not characterized by altered concentrations of thyroid hormones or responsiveness to thyroid hormones at the level of individual bone cells; however, altered responses pertaining to PTH and calcium were detected.

Skeletal responsiveness to thyroid hormone is not altered at menopause.

Hyperthyroidism is characterized by increased bone turnover and resorptive activity. Similar changes in remodeling are seen after menopause. To study the role of thyroid hormone in the menopause-related changes in bone metabolism, we investigated thyroid status and the sensitivity of bone to thyroid hormone in 14 premenopausal and 15 early postmenopausal women. Triiodothyronine (T3) was administered to the two groups as 20 micrograms doses three times daily for 7 days. The skeletal response was assessed by monitoring bone alkaline phosphatase (BAP), osteocalcin (BGP), pyridinium crosslinked telopeptide domain of type I collagen (ICTP) in serum and urinary excretion of hydroxyproline (OHP), pyridinoline (PYR), and deoxypyridinoline (DPR) at days 0, 8, 15, and 57. The early postmenopausal women had increased bone turnover as reflected in sBAP (p < 0.05), sBGP (p < 0.05), and uOHP (p < 0.01) when compared with premenopausal controls. T3 stimulation of early postmenopausal and premenopausal women significantly increased the markers of bone resorption: sICTP (56% vs. 44%), uOHP (45% in both groups), and UPYR (83% vs. 17%) without any significant differences between groups. Of the formative markers, only sBGP increased significantly after stimulation (34% vs. 41%), but both sBGP and sBAP displayed significant increases from days 15 to 57. Thus, stimulation with thyroid hormone results in an immediate stimulation of ongoing bone formation and bone resorption, but also initiation of new remodeling which, after 8 weeks, reached the formative phase. PTH decreased (p < 0.01) in both groups but serum calcium and serum phosphate were unaltered. In conclusion, menopause is not characterized by altered levels of thyroid hormones or altered skeletal responsiveness to thyroid hormones.

Bone mass, bone turnover and body composition in former hypothyroid patients receiving replacement therapy.

The aim of the present cross-sectional study was to disclose whether long-term thyroxine replacement therapy (TRT) in primary hypothyroidism causes osteopenia. We compared 36 adult biochemically and clinically euthyroid patients who had received TRT for more than 5 years (mean 13 years) for primary hypothyroidism with 80 sex- and age-matched normal controls. Height, body weight and lean body mass were similar, but the patients had 21% higher fat body mass (p = < 0.01) than their controls. Furthermore, compared to controls the patients had 29% higher serum thyroxine (T4) and 31% higher serum free T4 index (FT4I) levels (p < 0.001), whereas serum triiodothyronine (T3) and FT3I levels were both reduced by 7% (p < 0.05). In the patients, serum TSH was reduced significantly (p < 0.001). No significant differences were observed between patients and normals in regional or total bone mineral content or bone mineral density levels, apart from 20% higher lumbar bone mineral content among the premenopausal patients (p < 0.05). Surprisingly, the mean serum calcium level was slightly elevated (2.38 +/- 0.08 vs 2.33 +/- 0.07 mmol/l, p < 0.001), serum phosphate decreased (1.13 +/- 0.19 vs 1.23 +/- 0.16 mmol/l, p < 0.01) and 24-h renal calcium excretion was reduced by 19% (p < 0.05). No changes were observed in serum magnesium, intact parathyroid hormone or calcitriol. The biochemical markers of bone resorption (serum carboxyterminal telopeptide of type I collagen, renal excretion of hydroxyproline, pyridinoline and deoxypyridinoline) and formation (serum levels of carboxyterminal propeptide of type I procollagen, osteocalcin and total and bone alkaline phosphatase) were similar in the two groups. We conclude that long-term thyroxine replacement therapy in primary hypothyroidism does not exert a negative effect on bone mass or alter bone turnover.

Bone mass, bone turnover, body composition, and calcium homeostasis in former hyperthyroid patients treated by combined medical therapy.

It is still uncertain whether bone mass and bone turnover are completely normalized after treatment of hyperthyroidism. The aim of the present investigation was to determine bone mass, bone turnover, body composition, and calcium homeostasis in former hyperthyroid patients who had been euthyroid for at least 4 years following combined medical therapy. Thirty-nine former hyperthyroid patients and 67 normal sex- and age-matched controls participated. Height, body weight, and body composition were similar in the two groups. All patients were euthyroid. However, serum FT3I (free T3-index) was reduced by 9% (p < 0.01) in the patients compared to controls, serum FT4I was normal, while serum TSH was nonsignificantly reduced by 39%. No significant differences were observed between patients and controls with respect to total or regional bone mineral content (BMC) or density (BMD). The former hyperthyroid patients had slightly higher serum calcium (2.35 +/- 0.06 vs. 2.32 +/- 0.07 mmol/L, p < 0.05) and lower serum phosphate (1.15 +/- 0.15 vs. 1.24 +/- 0.15 mmol/L, p < 0.01) than their controls. Renal excretion of calcium and serum levels of magnesium, 1,25-vitamin D and intact PTH were unchanged. Renal excretion of pyridinoline was increased by 30% (p < 0.05) in the patients, whereas the remaining resorptive markers, renal excretion of hydroxyproline and deoxypyridinoline and serum cross-linked carboxy-terminal teleopeptide of type I collagen (ICTP) were unaltered. Among the formative bone markers the average serum carboxy-terminal propeptide of human type I procollagen (PICP) level was 12% lower (p < 0.05) than in the control group, whereas serum levels of osteocalcin and total and bone alkaline phosphatase were normal. In conclusion, former hyperthyroid patients treated by combined medical therapy have normal bone mineral content and density in spite of minor variations in thyroid hormones and skeletal homeostasis.

Bone mass, bone turnover, calcium homeostasis, and body composition in surgically and radioiodine-treated former hyperthyroid patients.

Untreated hyperthyroidism is characterized by increased bone turnover with loss of bone and bone mineral. The aim of the present investigation was to evaluate the reversibility of these changes by measuring bone mass, bone turnover, and calcium homeostasis in surgically treated former hyperthyroid patients who had been euthyroid for at least 6 years. Sixty euthyroid former hyperthyroid patients and 94 normal sex- and age-matched controls participated. Heights and body weights and composition were similar in the two groups. In the thyroxine substituted patients (n = 27) both serum T4 and serum free T4-index (S-FT4I) were increased (p < 0.001) compared to the normal controls as well as the nonsubstituted patients. In the nonsubstituted patients. In the nonsubstituted patients (n = 33), serum TSH was increased (p < 0.001) compared to the normal controls. No significant differences were observed between substituted and nonsubstituted patients and normal controls with respect to serum T3, serum free T3-index (S-FT3I), or regional or total bone mineral content (BMC) and density (BMD) values. Serum levels of calcium, phosphate, magnesium, intact PTH, and renal excretion of calcium were unchanged. However, serum levels of 1,25-dihydroxy- and 25-hydroxyvitamin D were reduced. Urinary excretion of hydroxyproline was increased by 16% (p < 0.05), but serum cross-linked carboxy-terminal teleopeptide of type I collagen (ICTP) was decreased by 11% (p < 0.01). Urinary excretion of collagen cross-links was normal. Serum levels of osteocalcin, carboxy-terminal propeptide of human type I procollagen (PICP), and total and bone alkaline phosphatase were all normal. In conclusion, surgically treated former hyperthyroid patients have normal bone mass, bone turnover, and calcium homeostasis in spite of minor variations in thyroid hormones and vitamin D metabolites.

Immunochemical determination of amniotic fluid acetylcholinesterase in the antenatal diagnosis of open neural tube defects.

The aims of the studies reviewed were 1) to identify the molecular forms of acetylcholinesterase encountered in amniotic fluid from pregnancies with a normal fetus and those with a fetal open neural tube defect or other fetal malformation and, 2) to raise and characterize antibodies against human acetylcholinesterase and to identify those useful for immunochemical determination of amniotic fluid acetylcholinesterase where there is a fetal open neural tube defect. Eleven monoclonal antibodies and one polyclonal rabbit antibody were evaluated with regard to their clinical usefulness in the antenatal diagnosis of open neural tube defects. One of these, the monoclonal antibody 4F19, preferentially bound acetylcholinesterase from human brain and identified better than the others amniotic fluid samples from pregnancies with a fetal open neural tube defect (I, II). The monoclonal antibody 4F19 was used in an enzyme antigen immunoassay whose performance was found to be similar to that of the polyacrylamide electrophoretic gel test for acetylcholinesterase determination (III). However, the 4F19 enzyme antigen immunoassay is simpler, more rapid and less technically demanding than the gel test, and furthermore, it gives a quantitative result. The 4F19 enzyme antigen immunoassay was also compared with the alpha-fetoprotein test, normally used as the primary test for the antenatal diagnosis of open neural tube defects. The 4F19 enzyme antigen immunoassay performed better than the alpha-fetoprotein test, but the best performance was found for a combination of the two tests (VI). A positive result can be found using the combined tests for conditions other than open neural tube defects, e.g. abdominal wall defects, intrauterine fetal death and other fetal malformations. These conditions can often be discerned by ultrasound examination. However, combining the result of the 4F19 enzyme antigen immunoassay with the result of an enzyme antigen immunoassay for butyrylcholinesterase makes a discrimination between these conditions possible (V). The diagnostic implications of the above procedures are evaluated and specific recommendations concerning their use are given.

Determination of amniotic fluid acetylcholinesterase activity in the antenatal diagnosis of foetal malformations: the first ten years.

The concentration of amniotic fluid acetylcholinesterase activity is elevated in cases of foetal open malformations, the levels being higher in cases of open neural tube defects than in cases of abdominal wall defects. Determination of amniotic fluid acetylcholinesterase activity is an established procedure for the antenatal diagnosis of foetal neural tube defects. Performance data, technical advantages and limitations for three procedures for the determination of acetylcholinesterase activity are reviewed in this paper: an immunoassay, a gel electrophoretic procedure and a spectrophotometric procedure. An immunoassay using the monoclonal antibody 4F19 and the gel electrophoretic procedure show nearly identical diagnostic performances, with detection rates for open spina bifida close to 100% and overall false positive rates of approximately 0.2%. The spectrophotometric procedure is not suitable for the antenatal diagnosis of foetal open neural tube defects and abdominal wall defects. It is possible to distinguish open neural tube defects from abdominal wall defects by determination of the ratio of acetylcholinesterase activity to butyrylcholinesterase activity, either by combining the 4F19 immunoassay with a butyrylcholinesterase immunoassay or by gel electrophoresis followed by densitometry, on samples that display elevated levels of acetylcholinesterase activity.

Alpha-fetoprotein and acetylcholinesterase activity in first- and early second-trimester amniotic fluid.

Normal ranges of amniotic fluid alpha-fetoprotein (AFP) and acetylcholinesterase activity (AChE) are described for gestational weeks 11-14 using rocket gel immunoelectrophoresis for AFP quantitation and a monoclonal antibody (4F19) enzyme antigen immunoassay for AChE activity measurement. The normal ranges were established by the examination of 281 amniotic fluid samples from 281 normal pregnancies. AFP was found to increase from a median level of 14.0 MIU/l at 11 weeks to a maximum at 13 weeks (median = 18.0 MIU/l) (P < 0.05), thereafter falling (not significant). No AChE test result exceeded 4.8 nkat/l. In addition, AFP and AChE values for three cases of fetal malformation, identified by the biochemical analyses of amniotic fluid, are given. These cases included two fetuses with a neural tube defect and one fetus with an abdominal wall defect. Amniocentesis was performed at 10, 11, and 14 weeks, respectively. The AFP and AChE values were all high.