Clinical determinants of quality of life in Paget's disease of bone.

Paget's disease of bone (PDB) can adversely affect quality of life, but relatively little is known about the clinical predictors of reduced quality of life in patients with the disease. Here, we studied quality of life and its determinants in a large cohort of PDB patients who had been enrolled into the PRISM study, a randomized comparative trial of intensive versus symptomatic treatment for PDB. Health-related quality of life was assessed using the Short-Form 36 (SF36) questionnaire and other validated assessment instruments in 1,324 subjects with PDB. Clinical predictors of quality of life were identified by multivariate regression analysis. The physical summary (mean +/- standard deviation) score of the SF36 was substantially reduced in PDB to 36.3 +/- 11.3 compared with the expected population norm of 50 (P < 0.001). The mental summary score was only slightly reduced, to 48.7 +/- 11.8, in PDB; but this was statistically significant (P < 0.001). Bone pain due to PDB, previous bisphosphonate therapy, and increasing age were identified as negative predictors of the SF36 physical summary score (P < 0.001); but serum levels of total alkaline phosphatase (ALP) did not predict physical summary score. We conclude that PDB has a substantial negative impact on health-related quality of life, which mainly affects physical functioning. The lack of correlation between ALP and quality of life observed in this study emphasizes the importance of addressing quality-of-life issues when treating PDB and not just focussing on response of ALP levels.

Management of Paget's disease of bone.

Paget's disease of bone is a common condition with a strong genetic component, characterized by focal increases in bone turnover, affecting one or more bones throughout the skeleton. Paget's disease can be asymptomatic but is frequently associated with bone pain, bone deformity, pathological fracture, secondary osteoarthritis and deafness. Inhibitors of osteoclastic bone resorption, such as bisphosphonates and calcitonin, suppress bone turnover and improve bone pain in Paget's disease. Many patients also require therapy with analgesics and anti-inflammatory agents, since pain in Paget's disease can arise not only from increased bone turnover but also from complications such as osteoarthritis and nerve compression syndromes, which do not respond well to antiresorptive therapy. Comparative studies have shown that second- and third-generation bisphosphonates, such as tiludronate, alendronate and risedronate, are more effective than etidronate at inhibiting bone turnover in Paget's disease but they have not been found to be significantly more effective in controlling bone pain. Importantly, none of the treatments that are currently available for Paget's disease have been shown to prevent complications such as deafness, fracture or bone deformity, or to alter the natural history of the disease. More research is required to define the long-term effects of antiresorptive treatment on clinical outcomes in Paget's disease, so that clinicians and their patients can make better-informed choices about the risks and benefits of treatment.

Susceptibility of three different strains of juvenile Atlantic halibut (Hippoglossus hippoglossus L.) cultured at two different temperatures to Vibrio anguillarum and temperature effect on antibody response.

Three geographically distinct-reared strains (Canadian, Icelandic, Norwegian) of juvenile Atlantic halibut (Hippoglossus hippoglossus L.) cultured at optimal and super-optimal growth temperatures (12 and 18 degrees C respectively), were challenged with a virulent isolate of Vibrio anguillarum by injection. The halibut were injected intraperitoneally with 100 microl of the bacterial suspension (1 x 10(6) cells per fish). After challenge, temperature and strain-related differences in survival were observed. Canadian and Icelandic halibut cultured at the super-optimal temperature of 18 degrees C were significantly more susceptible to infection than those strains cultured at 12 degrees C. Total mortality at 18 degrees C for the Canadian and Icelandic strains was 56.4 and 61.85% respectively, compared to 32 and 26.6% respectively at 12 degrees C. Norwegian halibut were significantly more resistant to infection with V. anguillarum at 18 degrees C compared to the other strains, with total mortality of 13.3%. There was no significant difference in total mortality of Norwegian halibut at 18 or 12 degrees C (13.3, 25% respectively). The specificity of the antibodies in sera from challenged halibut cultured at 18 degrees C was primarily to LPS. Immunoblots showed the presence of antibodies against O-side chain antigens. This reaction was strongest in sera from the Norwegian halibut strain compared with the Canadian and Icelandic halibut, which suggests that the difference in resistance to challenge may be ascribable to the presence of antibodies to LPS. Specific antibody levels, as measured by ELISA, increased with increasing temperature and strain differences were apparent, however these did not relate to disease resistance.

The effect of temperature on non-specific defence parameters of three strains of juvenile Atlantic halibut (Hippoglossus hippoglossus L.).

The effect of temperature (8, 12, 15 and 18 degrees C) on a variety of non-specific defence and haematological parameters was examined in three geographically distinct reared strains (Canadian, Icelandic, Norwegian) of Atlantic halibut. The results indicate that temperature exerts a considerable influence on some blood parameters (packed cell volume and the percentage population of leucocytes in peripheral blood) and on some humoral parameters (serum lysozyme activity and serum protein levels) of halibut. A high temperature of 18 degrees C caused a decrease in the number of circulating blood cells and an increase in serum lysozyme levels; effects consistent with those reported within the literature for stress. The different strains of halibut exhibited differing responses with respect to differential counts of peripheral blood lymphocytes and thrombocytes, and to serum protein concentrations, serum lysozyme activity, serum iron content, unsaturated iron binding capacity of serum and O2- production by kidney macrophages.

The kinetics of the hypoferraemic response and changes in levels of alternative complement activity in diploid and triploid Atlantic salmon, following injection of lipopolysaccharide.

To study any possible effects of triploidy on the kinetics of the response of two non-specific disease factors, full sibling diploid and triploid Atlantic salmon were injected intraperitoneally with either lipopolysaccharide (1 mg kg(-1) body weight) or saline. Individually marked fish were repetitively blood sampled for up to 19 days. Total serum protein concentrations remained constant throughout the experiment indicating that the sampling regime did not cause haemodilution. The alternative complement pathway activity (measured by the titre of haemolytic activity against rabbit erythrocytes) in the serum of saline injected fish remained constant but in LPS-injected fish it fell to barely detectable levels 2 days after injection, but recovered to pre-treatment levels by about day 5. Triploid fish took slightly longer to reach full recovery levels than diploids. All groups of fish showed a hypoferraemic response, suggesting that the sampling regime was at least partially responsible. However, the response was more rapid and pronounced in the LPS-injected fish. In the latter, serum iron concentrations decreased to very low levels by day 2 post-injection in the diploid fish and by day 3 in the triploid fish. Pre-treatment iron levels were re-established by about 15 days post-injection in all groups. The data show only slight differences between the diploid and triploid fish, but the longer time taken for the triploids to recover complement activity and the slower onset of the hypoferraemic response following injection of LPS, suggest that they may be at a disadvantage compared with their diploid siblings in their defence against bacterial infections.

Rapid reorganization of cortical maps in adult cats following restricted deafferentation in retina.

The retinotopic map in the visual cortex of adult mammals can reorganize in response to a small injury in a restricted region of retina. Although the mechanisms underlying this neural plasticity in adults are not well understood, it is possible that rapid, adaptive alterations in the effectiveness of existing connections play a key role in the reorganization of cortical topography following peripheral deafferentation. In order to test this hypothesis, a small retinal lesion was made in one eye of adult cats and the visual cortex was mapped before and immediately after enucleating the non-lesioned eye. We found that substantial reorganization takes place within hours of enucleation.

Disruption of binocularly correlated signals alters the postnatal development of spatial properties in cat striate cortical neurons.

1. Extracellular single-cell recording techniques were employed to investigate the effects of ocular misalignment on the postnatal development of the spatial response properties of striate cortical neurons. The primary objective of the study was to gain insight into the neural basis of strabismic amblyopia. 2. Two basic rearing strategies were used to study specific aspects of experimental strabismus in developing kittens. In one group, strabismus was optically induced by fitting kittens with goggles that held a 15-diopter base-in prism in front of one eye (MP) or both eyes (BP) between the ages of 4 wk and 4 mo. In the second group, a unilateral esotropia was surgically induced at 3 wks of age either by the simple resection of the lateral rectus muscle tendon (tenotomy) or by a more drastic procedure that involved removing sections of the lateral rectus and superior oblique muscles (myectomy). In addition, the eyelids of the nondeviating eyes of these kittens were sutured closed (ESO/MD). The first rearing paradigm isolated the effects of conflicting visual inputs on neural development, whereas the second procedure isolated the effects of anomalous ocular motility by producing a misalignment without putting the deviated eye at a competitive disadvantage. 3. The recording experiments were conducted when the animals were greater than or equal to 9 mo of age. A total of 445 striate cortical neurons were isolated and quantitatively studied in 17 cats (3 MPs, 3 BPs, 5 ESO/MDs, 3 goggle-reared controls, and 3 normals). In addition, we analyzed the distribution of preferred stimulus orientations of 1,205 single units that had been studied qualitatively in our previous investigation of 42 kittens reared with optically induced strabismus. 4. As expected, the proportion of binocularly driven units was reduced in both MP and BP cats. The great majority of units in ESO/MD animals were exclusively driven or highly dominated by the open deviating eye. 5. Prism-reared animals showed physiological deficits in spatial resolution, contrast sensitivity, contrast gain, and peak firing rate. These effects were manifest in both eyes, although there was always an interocular asymmetry in the deficits observed in the two eyes. In MP animals, the units dominated by the treated eye, which was contralateral to the recording hemisphere, were on the average more severely affected. The interocular asymmetry was smaller in BP cats; however, two of the three BP animals also showed a greater deficit in those units dominated by the contralateral eye.(ABSTRACT TRUNCATED AT 400 WORDS)

Reorganization of retinotopic cortical maps in adult mammals after lesions of the retina.

The organization of the visual cortex has been considered to be highly stable in adult mammals. However, 5 degrees to 10 degrees lesions of the retina in the contralateral eye markedly altered the systematic representations of the retina in primary and secondary visual cortex when matched inputs from the ipsilateral eye were also removed. Cortical neurons that normally have receptive fields in the lesioned region of the retina acquired new receptive fields in portions of the retina surrounding the lesions. The capacity for such changes may be important for normal adjustments of sensory systems to environmental contingencies and for recoveries from brain damage.