Diagnosis of osteoarthritis in relation to molecular processes in cartilage: comment on the article by Clark et al.
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The interpretation of the electromyogram (EMG) of dynamic contractions might be difficult because the movement per se introduces additional factors that could affect its characteristics. There is a lack of studies concerning the reproducibility of surface EMG registrations during dynamic contractions. The aim was to investigate the during-the-day reproducibility (using intra-class correlation; ICC) of the peak torque (PT) and the EMG variables (without removing the electrodes) of dynamic contractions. Ten healthy subjects performed three sets of 10 dynamic maximum right-knee extensions with a one-hour interval in between, using an isokinetic dynamometer and the PT was determined. EMG signals were recorded from the right vastus lateralis, rectus femoris and vastus medialis muscles using surface electrodes and the mean frequency of the power spectrum (MNF [Hz]) and the signal amplitude (RMS [microV]), were computed. The ability to relax in-between the maximum extensions was calculated as a ratio of the RMS during the passive flexion phase and the RMS during the active extension phase of each contraction cycle: the signal amplitude ratio (SAR). Both PT (ICC = 0.99) and RMS (ICC = 0.83-0.98) had good reproducibility. The reproducibility of MNF was good for all muscles when the mean of contraction nos.: 1-10 was used. Vastus lateralis had the highest ICC among the three muscles. The reproducibility of SAR was generally poor (ICC < 0.60). The present study showed good reproducibility for common EMG variables (MNF and RMS) obtained during maximum isokinetic contractions.
OBJECTIVE: To examine the hypothesis that aggrecan, cartilage oligomeric matrix protein (COMP), and bone sialoprotein (BSP) concentrations in synovial fluid could provide information on variations of progression of joint destruction in rheumatoid arthritis. METHODS: Aggrecan, COMP, and BSP were quantified by enzyme linked immunosorbent assays in longitudinally collected knee joint synovial fluid samples of patients rapidly developing destruction in knees or hips, the "'destructive" group, n = 18, and in patients slowly developing destruction, the "non-destructive" group, n = 25. RESULTS: The aggrecan concentrations decreased from initially high levels (P < < 0.001), and the BSP concentrations increased (P < < 0.001) over time in the destructive group, whereas levels of both markers were low and did not change in the non-destructive group. The COMP levels did not change in any of the groups. The aggrecan concentrations were initially highest in the group developing destructions (P < < 0.001), whereas no difference between the groups was found regarding levels of COMP or BSP in the first sample. CONCLUSIONS: A destructive group was characterised by higher initial aggrecan concentrations and rising BSP concentrations in synovial fluid with time. Quantification of cartilage and bone derived macromolecules contributes to the assessment of extent of tissue destruction and may help in the early identification of patients at risk of rapidly progressing destruction.
Serum concentrations of specific cartilage and bone molecules reflecting tissue turnover were measured in two well-defined patient groups with early rheumatoid arthritis with distinctly different disease outcome to see if early differences in their levels are prognostic of the rate of joint destruction. Compared with a matched normal population, increased concentrations of cartilage oligomeric matrix protein (COMP) were found in all patients who developed rapid hip joint destruction. In contrast, levels of a putative marker of cartilage aggrecan synthesis, the chondroitin sulfate epitope 846, were increased only in patients with slow joint destruction. Levels of bone sialoprotein (BSP) were increased in both groups, as were levels of the C-propeptide of type II procollagen (CPII), a marker of collagen II synthesis. The increased concentrations of the 846 epitope in patients with slow joint destruction suggest increased aggrecan synthesis. The low levels of the 846 epitope in patients with rapid joint destruction, concomitant with elevated levels of CPII, suggest a selective increase in collagen synthesis. The elevated BSP levels indicate an increased bone turnover in both groups. Thus elevated serum levels of COMP may indicate an unfavorable prognosis for rapid joint destruction, whereas elevated 846 epitope indicates a more favorable prognosis.
Cytidine deaminase (CD) is a cytoplasmatic enzyme present predominantly in polymorphonuclear cells (PMNC) in inflamed joints. Lactoferrin is situated in the secondary granules of PMNC and is released by secretory/phagocytic stimuli, whereas CD is released mainly upon cell lysis. To study the release of these molecules in arthritic conditions we measured CD and lactoferrin levels in synovial fluid (SF) drawn from patients with rheumatoid arthritis (RA), crystal pyrophosphate disease (CPPD), psoriatic arthropathy, reactive arthritis, spondylarthropathy, and osteoarthrosis. CD activity was highest in SF from RA and CPPD followed by psoriatic arthropathy, reactive arthritis and spondylarthropathy. Lactoferrin concentrations were highest in CPPD followed by RA, reactive arthritis, psoriatic arthropathy, and spondylarthropathy. Both CD and lactoferrin levels were low in osteoarthrosis SF. Although SF CD activity and lactoferrin levels correlated well in all diagnostic groups, the ratio between CD and lactoferrin was higher for RA, psoriatic arthropathy, and spondylarthropathy compared to reactive arthritis and CPPD. This suggests predominant release by PMNC lysis in the more chronic arthritis groups and more degranulation in the more episodic CPPD and reactive arthritis groups. CD activity and lactoferrin levels correlated significantly with SF cell counts in the RA and psoriatic arthropathy groups.
All cases undergoing neck operation for thyroid or parathyroid disease at Lund University Hospital, Lund, over a 7 year period were examined with indirect laryngoscopy pre- and postoperatively for the determination of the true incidence of operatively induced palsy of the recurrent laryngeal nerves. A total of 1.048 patients were operated; 810 females and 238 males. At 439 operations, bilateral neck exploration was performed; hence, 1.487 nerves were at risk for complications. It was found that immediate postoperative recurrent laryngeal nerve palsy was induced in 72 patients (= 4.8% of nerves at risk). In 44 of these patients, the palsy was temporary and disappeared within 6 months. Therefore, a total of 28 patients developed permanent nerve palsy postoperatively. In 5 of these operations, the nerve was intentionally divided, yielding a true incidence of permanent accidental postoperative nerve palsy of 1.6% of nerves at risk.
In a prospective study, resection of the thyroid gland by means of a linear stapling device was compared with the conventional resection technique in 12 consecutive patients with thyreotoxicosis. The median time for resection of the stapled lobe was shorter than for the conventionally resected right lobe, although the difference was not statistically significant. The median preoperative bleeding during resection of the stapled left lobe was 42 ml (range 15-126 ml), compared with 78 ml (range 34-247 ml) during the conventional resection of the right lobe (P less than 0.05). Median postoperative bleeding was somewhat less from the stapled side compared with the conventionally resected side, but did not reach statistical significance. The study thus demonstrates the feasibility of carrying out resection of the thyroid gland with a linear stapling device. The technique minimizes peroperative bleeding. It could therefore be used in thyroid surgery.
A secretion of parotid saliva in the anaesthetized rat in response to stimulation of the parasympathetic nerve occurs in the presence of atropine and adrenoceptor antagonists, albeit reduced and transient in the face of continuous high-frequency stimulation (40 Hz). In non-atropinized rats prolonged stimulation of the parasympathetic nerve at a high frequency (40 Hz, 40 min), aiming at depletion of the neuronal stores of transmitters thought to be responsible for the non-adrenergic, non-cholinergic (NANC) secretion of parotid saliva, was performed. The magnitude of the secretory response to various stimulation frequencies (0.2-60 Hz) applied to the parasympathetic nerve was assessed before and after the period of high-frequency stimulation. The second time, the frequency-response curve was shifted to the right and, moreover, the initial maximal secretory response was not reached. Control experiments suggested that this reduction in secretory responses could be attributed neither to impaired cholinergic neurotransmission nor to decreased responsiveness of the secretory cells. The secretory responses to parasympathetic nerve stimulation after high-frequency stimulation are thought to be evoked by acetylcholine predominantly. When these responses were compared with (1) those obtained before high-frequency stimulation and thought to be evoked by acetylcholine and non-adrenergic, non-cholinergic transmitters in conjunction and (2) those depending on non-adrenergic, non-cholinergic transmitters only it appears that the non-adrenergic, non-cholinergic transmission contributes to the parasympathetic secretory response at a frequency (0.2 Hz) far below threshold frequency (5 Hz) for the non adrenergic, non-cholinergic evoked secretory response. At frequencies below 20 Hz it appears that acetylcholine and non-adrenergic, non-cholinergic transmitters interact positively thereby enhancing the secretory responses.
Eleven arthritic knee joints in seven patients with rheumatoid arthritis were studied before and after intraarticular injection of a corticosteroid preparation. Extensor muscle torque and quantitative electromyography increased on days 7 and 14 after treatment, indicating that muscle function had been inhibited by synovitis. Clinical signs of synovitis, such as pain, range of motion and knee circumference, also improved. Synovial fluid withdrawal alone improved extensor muscle torque. Joints with instability and/or radiological cartilage involvement also improved.
Cytogenetic investigation of short-term cultures from a parathyroid adenoma revealed a t(1;5)(p22;q32) as the sole clonal chromosomal aberration. Karyotypic abnormalities have not previously been described in this tumor type.
1. The long-term influence of substance P (SP) and vasoactive intestinal peptide (VIP) on rat salivary gland weight was investigated after parasympathetic denervation or on feeding soft food. 2. The parotid gland lost about one-third of its weight within 4-5 days following parasympathetic post-ganglionic denervation or change in dietary regimen, from pellets to liquid diet, thought to reduce nerve reflex activity. 3. Daily i.v. infusions with SP or VIP diminished or largely prevented the fall in parotid gland weight, whereas infusions with pentagastrin, bethanechol and saline had no effect. The infusions were preceded by administration of alpha- and beta-adrenoceptor antagonists; these antagonists were also given to the control animals. 4. The effect of SP and VIP on the parotid gland weight appeared to be related to cell size rather than to cell number, as judged by measurements of RNA and DNA. 5. Observations on the two other major salivary glands underlined the fact that different gland types in the same animal behave differently. Parasympathetic preganglionic denervation (decentralization) lowered the weights of the sublingual and submandibular glands, whereas liquid diet only reduced the weight of the sublingual gland. SP and VIP did not affect the weights of the submandibular glands, but VIP prevented the slight fall in sublingual gland weight induced by liquid diet. 6. The present results suggest a trophic role in rats for SP and VIP on parotid glands and for VIP on sublingual glands. Such an influence may be exerted naturally as a result of their release from nerves containing these peptides around acini.
Rats were fed a liquid diet with the aim of decreasing nervous reflex activity in the parotid glands. In rats killed after 21 days on this diet the glands were atrophied and the total amounts of the neuropeptides, substance P, vasoactive intestinal peptide and calcitonin gene-related peptide, were lower than in control glands.
It is claimed that cytidine deaminase activity reflects local granulocyte turnover or activity in the synovial fluid of patients with rheumatoid arthritis, but cytidine deaminase is not a granulocyte specific enzyme. Lactoferrin is a granulocyte specific protein that is released from the secondary granulae during activation. We measured cytidine deaminase activity and lactoferrin concentrations in 33 rheumatic synovial fluid samples. Cytidine deaminase activity and lactoferrin concentrations correlated closely, indicating that both analyses reflect similar events in the joint-that is, result in their release from granulocytes. Cytidine deaminase activity and granulocyte concentrations correlated less closely, suggesting that there are additional factors besides the cell number which contribute to this release. Joint acidosis may be one such factor, as pH and cytidine deaminase activity correlated inversely. There was no association with synovial fluid proteoglycan concentrations, a marker of cartilage degradation.
We examined immunocytochemically the occurrence of the three peptides calcitonin, calcitonin gene-related peptide (CGRP), and gastrin-releasing peptide (GRP) in medullary carcinoma of the thyroid. We also sought to determine whether the plasma levels of these peptides were increased when stimulated with calcium and pentagastrin in familial medullary carcinoma of the thyroid (MCT). The tumor tissue from all 17 cases examined was found to exhibit calcitonin and CGRP immunoreactivity, and in 15 of the 17 cases the tumor tissue also contained GRP immunoreactivity. In 7 of the cases selected at random, an intravenous injection of calcium carbonate (2 mg/kg body weight) and pentagastrin (0.6 microgram/kg body weight) produced marked elevation in plasma levels of calcitonin but did not significantly alter the plasma levels of CGRP or GRP. We conclude that most MCT tumors contain CGRP and GRP immunoreactive cells but that the plasma levels of CGRP and GRP are not altered on stimulation. This finding is clearly in contrast to the markedly elevated calcitonin levels. Hence, determination of plasma calcitonin levels still seems to be the most appropriate diagnostic test for MCT.
Large dense-cored vesicles (60-100 nm in diameter) have been assessed electron-microscopically in terminal parasympathetic axons at acinar neuro-effector sites in rat parotid glands. Their numbers in control unstimulated glands have been compared with those in the contralateral glands of the same animals after prolonged nerve stimulation. Bilateral postganglionic sympathectomy had been undertaken 4-6 weeks previously to remove adrenergic axons from the glands. Stimulation of the postganglionic parasympathetic nerve to the gland--the auriculotemporal nerve--for 80 min at 40 Hz caused a significant depletion of large dense-cored vesicles from the terminal axons. This depletion corresponded in time and magnitude to the depletion of vasoactive intestinal peptide and substance P from the glands that had been found previously to occur under identical conditions. This adds support to the belief that the neuropeptides are stored in such vesicles and that these vesicles release their contents at neuro-effector sites as a result of propagated impulse formation in the axons.
In parotid, sublingual and submaxillary glands stimulated by continuous intravenous infusion of isoprenaline at various doses for 3 h, the concentrations of the polyamines putrescine, spermidine, spermine and N1-acetylspermidine as well as the activities of ornithine decarboxylase and spermidine/spermine-N1-acetyltransferase were determined. Ornithine decarboxylase is the enzyme that catalyses the formation of putrescine from ornithine. The most striking effect was observed in parotid glands. Here, the beta-adrenergic agonist increased the activity of spermidine/spermine-N1-acetyltransferase markedly, but only slightly (if at all) that of ornithine decarboxylase. It also increased the concentrations of N1-acetylspermidine and putrescine markedly. The result obtained in this gland indicates interconversion of higher polyamines to putrescine.
Polyamines are important for protein synthesis and tissue growth. In rat salivary glands, the activity of ornithine decarboxylase (ODC), the enzyme catalysing the formation of putrescine, and the content of putrescine, spermidine, spermine and N1-acetylspermidine were assayed after parasympathetic or sympathetic nerve stimulation in the presence of various autonomic receptor blockers. Increases in ODC activity occurred on activation of non-adrenergic and non-cholinergic receptors in response to parasympathetic nerve stimulation and on activation of alpha(alpha 1)- as well as of beta(beta 1)-adrenoceptors in response to sympathetic nerve stimulation. Moreover, in parotid glands, a beta(beta 1)-adrenoceptor-mediated inverse pathway for putrescine formation seemed to exist: from spermidine via N1-acetylspermidine.
Patients with serotonin-containing metastatic midgut carcinoid tumours were treated with temporary liver dearterialization (19 patients) or liver embolization (8 patients). After 3, 6 and 12 months the effects of treatment were registered in changes in serotonin in platelet-poor plasma and blood, in urinary 5-HIAA, in tumour extent in the liver and in symptomatic relief. Seventeen patients, who underwent the dearterialization procedure survived the operation, while 2 patients who had a concomitant small bowel resection died of complications. Tumour response was obtained in 8 patients after 6 months and in 9 patients after 12. Stable disease was noted in 5 patients after 6 months and 3 patients after 12 months. Progressive disease was seen in 4 patients. All 19 patients except one exhibited the carcinoid syndrome prior to operation and 11 patients were free from symptoms for at least 12 months postoperatively. The gelatine foam powder liver embolization was performed uneventfully in all 8 patients. Tumour response was obtained in 3 patients at both 3 and 12 months. Stable disease was noted in 5 patients at 3 months and 4 patients at 12 months. Before embolization the patients suffered from the carcinoid syndrome and the treatment resulted in the immediate disappearance of the syndrome in 5 patients. After 12 months one patient was still free from obvious carcinoid symptoms. In one patient the disease aggravated in spite of treatment and he died 5 months after embolization. Thus, temporary liver dearterialization and liver embolization in midgut carcinoid patients resulted in tumour regression and symptomatic relief in 9 out of 19 patients and 3 out of 8 patients respectively. The complication rate was low.