Heat shrinkage of extraocular muscle tendon.

We have designed and employed a bipolar heating device to shorten extraocular muscles. Treatment involves placing the unidirectional heating device on the sclera with the active surface beneath the tendinous portion of the extraocular-muscle. When power is applied, visible tissue shrinkage occurs. Heat-induced extraocular muscle shrinkage was performed on live rhesus monkeys. Two months later, thermal tendinoplasty-treated extraocular muscles were surgically isolated and evaluated for strength. Biopsies were then performed on these muscles. It was our clinical impression that treated tissues retained their strength, while histologic and electron-microscopic evaluation of heat-treated tendon revealed evidence of shrinkage and compaction of collagen bundles. Thermal tendinoplasty may offer a sutureless method of correcting strabismus by shortening and thereby strengthening extraocular muscles.

A single-blind crossover trial of the anti-inflammatory drug sodium meclofenamate and placebo, including an evaluation of hand grip and of lymphocyte responsiveness.

A single-blind crossover trial was carried out in 21 patients with active rheumatoid arthritis to assess the effectiveness and tolerance of sodium meclofenamate (300 mg per day) compared with placebo. After a 1-week washout period patients had two periods of active medication, each of 2 weeks, separated by 1 week on placebo. Morning stiffness, walking speed, pain score, patient impression of response, joint tenderness and power, work and maximum grip strength achieved by hand grip were all improved by sodium meclofenamate and an anti-inflammatory effect of the drug was demonstrated, with some reduction in the swelling of PIP joints. There was no advantage in assessing pain on full movement of the small joints of the hands in addition to direct tenderness. Power, work and rate of grip release achieved during hand grip provided more information about hand function than maximum grip strength alone. Lymphocyte transformation to non-specific mitogens was enhanced by the drug. Twelve patients had some form of gastro intestinal complaint during the study and it is suggested that diarrhoea is likely to prove to be the major limiting factor of acceptance by some patients.

Non-steroidal anti-inflammatory drugs in combination. Experimental observations.

Diflunisal in combinations with oxaprozin, indomethacin and sodium meclofenamate produced significant synergistic suppression of carrageenan-induced oedema of the rat foot-pad. Oxaprozin, benoxaprofen, indomethacin, diflunisal, sodium meclofenamate and auranofin in some paired combinations but not in others were associated with a greater effect than the component drugs used alone. Antagonism was demonstrated with other combinations of these drugs.

Decreased collagen concentration in rat uterine implantation sites compared with non-implantation tissue at days 6-11 of pregnancy.

Collagen concentrations at implantation sites in the rat uterus were found to be significantly decreased compared with concentrations in adjacent non-involved uterine tissue in early pregnancy (75% by Day 11). The decrease in collagen was most marked in primary decidua and was also observed to a lesser extent (20%) in myometrium at the implantation site. There was a decrease of 20% in the concentration of total proteins at Day 7 (as measured by the ninhydrin method) and a slight increase in water content (2%) at Days 6 and 7. The differences in total protein and water content were transient, but the difference in collagen was maintained throughout early pregnancy. The localized changes in collagen content observed in this study, along with previously reported morphological changes in fibrillar and basement-membrane collagens in the uterus, give support to a theory of remodelling in early pregnancy involving simultaneous synthesis and degradation of extracellular proteins during decidualization.

Localization and synthesis of collagen types III and V during remodelling and decidualization in rat uterus.

Uteri of pregnant rats on Days 6, 7 and 8 of pregnancy were studied to determine the histochemical distribution of collagen types III and V and the incorporation of [3H]glycine into fibrillar collagens during the period of embryonic implantation. Types III and V had a similar distribution in the non-decidual stromal region and muscle layers in implantation sites. They were found to have very low levels in the primary decidual tissue on Day 6 and were not detected in developing decidual tissues on Days 7 or 8. Following injection of labelled glycine, collagen was extracted and the specific activity of the collagens determined by fluorography and 3H incorporated into the collagen bands in the gels. It was found that incorporation of label into both types I and III was similar (33.4+/-12.0 and 31.8+/-18.1 cpm microg-1 collagen respectively) but 3.5 times that of type V (7.7+/-5.3 cpm microg-1). These studies suggest that although fibrillar collagens are metabolized or redistributed in the growing decidual tissue, they are incorporated rapidly into the extracellular matrix during remodelling of the outer stroma and muscle tissues.

Temporal changes to uterine collagen types I, III and V in relation to early pregnancy in the rat.

Uterine tissues of pregnant rats were extracted to define any changes to the proportions of collagens types I, III and V. The total concentration of extracted collagen was determined in tissue samples from implant and adjacent non-implant (NI) sites. Extracts were also subjected to polyacrylamide gel electrophoresis (PAGE), immunoblotting and gel densitometry to define the collagen types and to determine their relative proportions. By relating the proportions to the collagen concentrations in the extracts, type I was found to be the predominant collagen in both tissue regions although the concentration in the implant sites was lower than that in the NI sites. The concentration of Type I collagen decreased significantly over the period of observation in both implant and NI sites. Although the concentrations of collagen type III and type V also decreased in the implant sites, they did not alter in the NI sites. The results demonstrate that shortly after the initiation of implantation the uterus responds to the presence of the implanting embryo by decreasing the concentration of all three types of collagen. This indicates that their metabolism may, in part, be regulated by similar mechanisms. Furthermore, it was evident that a decrease in the concentration of collagen type I was initiated in uterine areas that, at the time of sampling, were not directly involved with implantation. During the study, it was found that the alpha 1 chain of collagen type V separated into two distinct bands when run on gels containing 3.8 M urea.(ABSTRACT TRUNCATED AT 250 WORDS)

Subcellular particles in synovial fluids and synovial cells.

Membranous particles of mycoplasma-like appearance (100 to 300 nm in diameter) and non-membranous particles which are viral-like (20 to 80 nm in diameter) were observed in negatively-stained preparations of synovial fluid pellets from patients with rheumatoid arthritis (RA), osteoarthrosis (OA) or psoriatic arthritis (PA). The incidence of positive fluids were: membranous particles--22/28 (RA), 7/11 (OA), 1/3 (PA); non-membranous particles--12/28 (RA), 1/11 (OA), 1/3 (PA). Eight of the RA fluids, one OA and one PA fluid were positive for both types of particle. The observation of an increased frequency of viral-like particles in RA synovial fluids compared to OA and PA fluids is of possible aetiological interest. Viral-like particles were also observed in the nuclei of rheumatoid synovial macrophage syncytia by electron microscopy of ultra-thin sections of cultured cells.

Serum copper and zinc in rheumatoid arthritis and osteoarthritis.

Serum copper, zinc and caeruloplasmin levels were measured in 49 patients with active rheumatoid arthritis, in 33 patients with osteoarthritis and a group of blood donor controls. Serum copper and caeruloplasmin levels in the osteoarthritic patients were significantly higher and serum zinc levels significantly lower than in the blood donor controls. Although these differences could not be accounted for on the basis of age or drug administration neither did they correlate with a radiological grading of disease severity. Copper and caeruloplasmin levels were raised in the rheumatoid group as compared to both osteoarthritic and control groups. These were strong correlations between serum copper, caeruloplasmin, ESR and alpha 1 globulin levels in the rheumatoid patients. Although caeruloplasmin-bound copper accounted for most of the elevation in serum copper levels in the rheumatoid group, the calculated non-caeruloplasmin bound copper level was also elevated in rheumatoid, as compared to osteoarthritic patients. Serum zinc levels in the rheumatoid group were lower than in the control group but not significantly different to those in the osteoarthritic group.

Ibuprofen and diflunisal in rheumatoid arthritis: a double-blind comparative trial.

Both diflunisal (750 mg/day) and ibuprofen (1600 mg/day) were shown to be superior to placebo in the treatment of rheumatoid arthritis in a double-blind cross-over trial. Neither drug affected lymphocyte transformation to plant mitogens. Diflunisal scored better than ibuprofen at the dose levels chosen but the differences did not reach significance.

Electron microscopic autoradiography of 35SO4-labelled material closely associated with collagen fibrils in mammalian synovium and ear cartilage.

Electron microscopic autoradiography of connective tissue obtained from mice and rabbits previously injected with 35SO4 indicated that sulphated proteoglycans are localized on collagen fibrils. Ruthenium Red-positive transverse belts surrounding fibrils near the a-bands were heavily labelled, but fine lateral filaments of Ruthenium Red-positive material were not. These filaments, which interconnect collagen fibrils in a variety of connective tissues may represent linear aggregations of hyaluronic acid, glycoproteins and non-sulphated or long-lived sulphated proteoglycans.

A study of the structural response of wet hyaline cartilage to various loading situations.

A direct view has been obtained of the manner in which the fibrous components components and chondrocytes in hyaline cartilage respond to the application of uniaxial tensile loading and plane-strain compressive loading. A micro-mechanical testing device has been developed which inserts directly into the stage of a high-resolution optical microscope fitted with Nomarski interference contrast and this has permitted simultaneous morphological and mechanical observations to be conducted on articular cartilage maintained in its wet functional condition. Aligned and crimped fibrous arrays surround the deeper chondrocytes and can be observed to undergo well-defined geometric changes with applied stress. It is thought that these arrays may act as displacement or strain sensors transmitting mechanical information from the bulk matrix to their associated cells thus inducing a specific metabolic response. The process of tissue recovery following sustained high levels of compressive loading can also be observed with this experimental technique.

Binding of sodium [195Au]aurothiomalate to Mycoplasma arthritidis.

The binding of sodium [195Au]aurothiomalate (ATM) to whole cells of Mycoplasma arthritidis has been measured within the temperature range of 4 to 53 degrees C. The time course (kinetics) and the effect of varying the total concentration of free ATM in the suspension at 37 degrees C were also measured. The extent of binding at 37 degrees C leveled off after 30 min at approximately 65 nCi of [195Au]ATM per mg of membrane protein. The amount of ATM bound per cell appeared to be directly proportional to the concentration of free ATM in the range of 0.25 to 0.60 muCi of [195Au]ATM per ml. An Arrhenius plot showed two distinct regions with slopes of -0.56 degrees K/mg of protein (5 to 22 degrees C) and -2.78 degrees K/mg of protein (22 to 53 degrees C). The break in the Arrhenius plot corresponds to a temperature known to be related to a sudden change in mycoplasma membrane fluidity. Estimations of Scatchard binding constants and number of binding sites per membrane protein molecule resulted in 0.8 to 1.4 sites per molecule in the intact organisms compared to 1.4 to 1.8 sites in membrane fragments. The latter were purified by repeated washings in phosphate-buffered saline after alkaline lysis of the cells. It is suggested that ATM reacts with available protein sulfhydryl groups in the mycoplasmal membrane.

Preliminary observations on an isolate from synvoial fluid of patients with rheumatoid arthritis.

A very slow-growing micro-organism has been isolated from the synovial fluid of patients suffering from rheumatoid arthritis. This organism exhibits some of the properties of a mycoplasma such as growth in the presence of penicillin, and the requirement of serum and yeast, but generally does not behave like any known species of this group. Colonies resemble some types of T-mycoplasma in morphology and size. Scanning electron microscopy showed that the size of the components of these colonies was exceedingly small.

Morphological and biomechanical studies of rheumatoid pannus and cartilage.

Invasive pannus or granulation tissue was observed in 0.2 mm thick slices of cartilage and adjacent subchondral bone taken from fresh metatarsal and metacarpal heads removed surgically from patients with rheumatoid arthritis. Application of stress to the slices showed "tracking" of pannus or invasive tissue between lacunae and through breaches in the subchondral plate. Softened regions in the cartilage matrix became creased and were easily distinguished from regions of normal consistency. The pannus-matrix interface was not disrupted by stresses as high as 30 g/mm2.

Proximal and distal changes in collagen content of peripheral nerve that follow transection and crush lesions.

Collagen content of rat sciatic nerve was measured 10 weeks after either nerve transection or nerve crush. Nerve transection led to a significant increase in fascicular collagen in nerve segments 2.5 mm proximal and distal to the injury site. Remote from the transection, fascicular collagen was also significantly increased, this effect being most marked distally. Nerve crush by comparison resulted in only a small increase in fascicular collagen, significantly less than after transection. The greater amount of fascicular collagen far distal to the nerve injury could relate to a predominantly caudal endoneurial flow of inflammatory or growth factors. Differences in the amount of fascicular collagen formed after nerve transection compared with nerve crush are clearly due to factors other than axonal degeneration, and may relate to collagen synthesis by denervated Schwann cells or to the severity of the nerve injury.