Randomised, blinded, placebo controlled trial of doxycycline for chronic seronegative arthritis.

OBJECTIVE: To determine whether long term doxycycline improves symptoms in patients with chronic seronegative or reactive arthritis. METHODS: A randomised, triple blind, controlled clinical trial of three months' treatment with doxycycline or placebo of patients with chronic reactive or seronegative arthritis was conducted. The primary study end points were three month pain and functional status measured by a self administered Arthritis Impact Measurement Scales version 2 (AIMS2) quality of life questionnaire. Secondary end points were pain and functional status at 6-12 months, three month rheumatologist assessed joint count, pain, and arthritis activity, and treatment efficacy in those with previous exposure to chlamydia. RESULTS: Of 60 patients randomly allocated to receive doxycycline or placebo, results from 37 were evaluable at three months. Groups were well balanced for major prognostic variables. Doxycycline had no detectable effect at three months on pain change scores (mean difference 1.5, 95% CI -1.2 to 4.2, p=0.25) or composite functional change scores (mean difference 0.8, 95% CI -5.6 to 7.1, p=0.81). Furthermore, there were no differences in secondary study end points, and no apparent treatment effect in patients with previous chlamydia infection. CONCLUSION: Three months' treatment with doxycycline did not improve pain or functional status in patients with chronic reactive or seronegative arthritis.

Aluminum and acid effects on calcium and phosphorus metabolism in young growing chickens (Gallus gallus domesticus) and mallard ducks (Anas platyrhynchos).

Acidification is associated with increased mortality, reduced growth, and bone abnormalities in birds. Associated with acid deposition is an increase in aluminum availability due to solubilization from soil and other sources. (Conversely, experimental diets containing aluminum sulfate have much reduced pHs.) The present studies compare the effects of two levels of dietary acid (sulfuric acid) (0.122 and 0.56 mol H+ per kg feed; 0.056 and 0.277 mol sulfate per kg feed) and dietary aluminum (aluminum sulfate at 0.1 and 0.5%; sulfate at 0. 056 and 0.277 mol sulfate per kg feed) on bone growth, mineralization, and phosphorous/calcium homeostasis in growing birds (chickens and mallard ducks). Growth was reduced by the high acid (chicken) and aluminum (ducks and chickens) diets. A reduction in bone mineralization was observed in birds receiving aluminum-containing diets [low aluminum diet: decreased tibia ash, calcium, and phosphorus (chickens); high aluminum diet: decreased tibia dry weight, % of ash and mg; ash, calcium (chickens, ducks as % of ash), and phosphorus (chickens mg/duck, % of ash)]. Moreover, plasma concentrations of inorganic phosphate were reduced in chicks on the high aluminum diet. There were also marked decreases in bone growth and mineralization [tibia weight, ash (mg), calcium (mg), phosphorus (mg)] and plasma concentrations of 1,25-dihydroxy vitamin D3 in chicks on the high acid diet compared to those on a control diet. These changes were probably due to reduced feed intake; changes in bone indices being of a greater or similar magnitude in pairfed control. There was little change in bone indices, growth rate or feed consumption in ducklings receiving either the low or high acid diets. It is concluded that aluminum directly adversely affected bone mineralization whereas acid effects are mediated in part by changes in feed consumption.

The reliability of examination for tenderness in patients with myofascial pain, chronic fibromyalgia and controls.

OBJECTIVE: To establish the reliability with which tenderness could be evaluated in patients with chronic myalgias, using dolorimetry and palpation. METHODS: Three blinded examiners using pressure dolorimetry and digital palpation compared 19 paired tender points and 8 paired control points in 4 matched groups of 6 patients with fibromyalgia (FM), myofascial pain, pain controls, and healthy controls. RESULTS: Good interrater and test-retest reliability were found for dolorimetry scores. There were significant differences in tenderness ratings by dolorimetry between the diagnostic groups, with the patients with FM and myofascial pain having the greatest tenderness, the normals having the least tenderness, and the pain controls having tenderness levels midway between the patients with FM or myofascial pain and the normals. In all patients, control points had higher pain thresholds than tender points. One-third of patients with localized pain complaints demonstrated a significant relationship between region of clinical pain complaint and measured tenderness thresholds by dolorimetry. In ratings of tenderness by digital palpation, there was very good intrarater reliability over 26 of 27 paired points, and good interrater reliability at 75% of the points. One-half of patients with localized pain complaints demonstrated a significant relationship between region of clinical pain complaint and number of tender points by palpation. CONCLUSION: Both dolorimetry and palpation are sufficiently reliable to discriminate control patients from patients with myofascial pain and FM, but may not discriminate patients with myofascial pain from those with FM. Neither method appears to correlate well with the location of the clinical pain complaint, regardless of diagnosis.

Monitoring biological effects of polychlorinated dibenzo-p-dioxins, dibenzofurans, and biphenyls in great blue heron chicks (Ardea herodias) in British Columbia.

The Canadian Wildlife Service monitors levels of polychlorinated aromatic hydrocarbons in great blue heron (Ardea herodias) eggs in British Columbia as indicators of environmental contamination. The present project assessed the temporal effects of environmental contamination with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and other polychlorinated dibenzo-p-dioxins (PCDDs), dibenzofurans (PCDFs), and biphenyls (PCBs) on hepatic microsomal ethoxyresorufin O-deethylase (EROD) activities and several morphological parameters in heron hatchlings. Between 1990 and 1992, eggs were collected from two great blue heron colonies in British Columbia that had elevated levels of contamination in 1988: Vancouver in 1990 and 1992, and Crofton in 1991. Biological parameters in the hatchlings and chemical contaminant levels in matched eggs from the same clutch were measured and compared with the findings from the same colonies studied in 1988. Levels of TCDD and other PCDDs and PCDFs had decreased significantly in both colonies since 1988. A concomitant decrease in EROD activity and incidence of chick edema, increase in body weight, and improvement of the reproductive success of the Crofton colony was observed. Body, yolk-free body, stomach, and intestine weights, tibia wet, dry, and ash weights, and tibia length regressed negatively on TCDD level (p < .01; n = 54). Hepatic EROD activity regressed positively on TCDD level (r2 = .49; p = .00005; n = 54). Regression of these parameters on the sum of TCDD toxic equivalents (TEQ) resulted in similar relationships. The reduction in severity of the effects observed in the contaminated colonies in the recent collections, accompanied by the declines in levels of PCDDs and PCDFs, was consistent with the dose-response relationships determined in 1988.

Biological effects of polychlorinated dibenzo-p-dioxins, dibenzofurans, and biphenyls in double-crested cormorant chicks (Phalacrocorax auritus).

The present project assessed the effect of environmental contamination with polychlorinated dibenzo-p-dioxins (PCDDs), dibenzofurans (PCDFs), and biphenyls (PCBs) on hepatic microsomal ethoxyresorufin O-deethylase (EROD) activities and morphological parameters in matched double-crested cormorant (Phalacrocorax auritus) hatchlings from egg clutches chosen for chemical analysis. Double-crested cormorant eggs were collected from five colonies across Canada, with differing levels of contamination. Levels of contamination expressed in sum of 2,3,7,8-tetrachlorodibenzo-p-dioxin-toxic equivalents (TCDD-toxic equivalents or TEQ, ng/kg egg; mean +/- SEM) were: Saskatchewan, 250 +/- 50; Chain Islands, 672 +/- 73; Christy Islet, 276 +/- 14; Crofton, 131, n = 1; and Lake Ontario, 1606 +/- 118. In the hatchlings, hepatic EROD activities (pmol/min/mg protein; mean +/- SEM) were: Saskatchewan, 283 +/- 42; Chain Islands, 516 +/- 98; Christy Islet, 564 +/- 91; Crofton, 391 +/- 52; and Lake Ontario, 2250 +/- 156. Hepatic microsomal EROD activity (pmol/min/mg protein) regressed positively on TEQ (r2 = .69; p < .00005; n = 25). Yolk weight (g) regressed negatively on TEQ (r2 = .44; p = .00005). Wing length (mm) regressed negatively on PCB-169 (r2 = .28; p = .007). Monospecific antibodies raised against rat cytochrome P-450 1A1 recognized a protein in the hepatic microsomes of the double-crested cormorant, and also in those of the great blue heron (Ardea herodias), using immunoblotting. The intensity of the stained band increased with increased EROD activity, supporting the assumption that ethoxyresorufin is a suitable substrate for avian cytochrome P-450 1A1. These results validate the use of avian hepatic microsomal EROD activity as an index of cytochrome P-450 1A1 induction by environmental levels of polychlorinated aromatic hydrocarbons and as a useful screening tool to determine the extent of exposure to such chemicals. Furthermore, the induction of cytochrome P-450 1A1 observed in the cormorant indicates that the Ah receptor-mediated process, by which TCDD and related chemicals exert many of their toxicities, has been activated.

Exercise and soft tissue injury.

Once the almost exclusive domain of the orthopaedic surgeon, sports injuries are now being seen with increasing frequency by other specialists, including rheumatologists. It is therefore important for rheumatologists to be able to diagnose and manage the various musculoskeletal conditions that are associated with physical activity. Soft tissue injuries are a very common cause of morbidity in both competitive and recreational athletes. Most of these conditions are provoked by muscle-tendon overload (or overuse) that is usually the result of excessive training or improper training techniques. However, despite an emerging literature on the natural history of soft tissue overuse syndromes, relatively little is known about the causes, incidence and outcome of many of these injuries. Of the methodologically robust epidemiological studies that have been done, most have focused on habitual distance runners. In this population, it has been reported that the incidence of injury can be as high as 50% or more, and that overtraining and the presence of previous injury are the most significant predictors of future injury. In other popular forms of exercise, such as walking, swimming, cycling, aerobics and racquet sports, injuries are also reported with high frequency but, to date, no prospective studies have examined actual incidences in these populations, and risk factors for injury in these activities remain speculative. Several of the more commonly occurring soft tissue injuries (such as rotator cuff tendinitis, lateral and medial epicondylitis, patellar tendinitis, the iliotibial band friction syndrome, Achilles tendinitis and plantar fasciitis) exemplify the overuse concept and are therefore highlighted in this review. The management of these, and most other, exercise-related soft tissue injuries is directed towards promptly restoring normal function and preventing re-injury.

Comparison of two multiple blood sampling regimens using an indwelling vascular access device for investigations of the hen's ovulatory cycle and calcium metabolism.

The objectives of the present study were to compare the effects of two regimens of serial blood sampling on the concentrations of hormones and ions during the ovulatory cycle of the domestic hen, and to examine the effectiveness of an indwelling vascular access device for repeated collection of blood samples. Single Comb White Leghorn hens were bled every 2 h over a period of 24 to 26 h, either from one oviposition to the next oviposition (OVIP-OVIP), or from 10 h prior to ovulation until the same time 24 h later (AFTN-AFTN). Whole blood was analyzed for ionized calcium concentration. Plasma was analyzed for total calcium, inorganic phosphorus, 1,25-dihydroxycholecalciferol, estradiol-17beta, and progesterone concentrations. The OVIP-OVIP regimen, using oviposition as a reference point, provided more accurate measurements of ionized calcium, inorganic phosphorus, and estradiol-17beta than did the AFTN-AFTN regimen. Either bleeding regimen was suitable for observing the patterns of 1,25-dihydroxycholecalciferol and progesterone concentrations. The decrease in bound calcium concentration observed with both regimens appeared to be an artifact of repeated blood sampling. The chance of a bird laying an egg following her second oviposition was lower following the OVIP-OVIP regimen than the AFTN-AFTN regimen. The vascular access device was a helpful tool in procuring multiple blood samples for measurement of ions and hormones during the ovulatory cycle of the domestic fowl.

Ionic and endocrine characteristics of reproductive failure in calcium-deficient and vitamin D-deficient laying hens.

Whole blood ionized calcium and plasma total calcium, inorganic phosphorus, estradiol-17 beta, progesterone, and 1,25-di-hydroxycholecalciferol concentrations were measured in calcium- or vitamin D-deficient Single Comb White Leghorn hens. Control birds were serially sampled every 2 h for 26 h immediately following oviposition until the next oviposition. Deficient birds, which had ceased laying 10 to 14 days prior to sampling, were sampled at the same times. The control birds had significantly higher mean total and bound plasma calcium and inorganic phosphorus concentrations than the deficient hens. Control and vitamin D-deficient hens had similar mean ionized calcium concentrations. Control hens exhibited a cyclic pattern in ionized calcium and inorganic phosphorus concentrations over the sampling period that was related to shell calcification. Deficient hens showed no changes in ionized calcium concentration during this time. Plasma 1,25-dihydroxycholecalciferol concentrations were significantly higher in the calcium-deficient birds than the control or vitamin D-deficient hens. Mean plasma estradiol-17 beta and progesterone concentrations were consistently higher in the control hens than the deficient hens. Consistent with this observation were decreases in ovary and oviduct weights, which occurred in the nonlaying deficient hens.

Suspected sodium toxicity in hand-reared great blue heron (Ardea herodias) chicks.

Sodium toxicity was suspected in hand-reared great blue heron (Ardea herodias) chicks fed herring frozen in brine (seawater). Affected chicks were lethargic with stiff legs that extended to the posterior, and breathing was labored. Chicks regurgitated food or refused to eat. All chicks that were fed herring exclusively and eight of the 10 chicks fed a mixed diet (herring and salmonids) died, whereas all chicks fed only salmonids survived. Renal lesions ranged from mild to marked generalized nephrosis, which was characterized by degeneration and necrosis of the proximal convoluted tubular epithelium and dilation of the distal convoluted tubules and collecting ducts. These observations suggest that fish frozen in brine is unsuitable food for hand-rearing of young herons.

Aerobic fitness and hormonal responses to prolonged sleep deprivation and sustained mental work.

This study examined the influence of aerobic fitness on the responses of selected hormones to the combined stressors of sleep deprivation (SD) and sustained mental work. Six aerobically high fit (HF) (VO2max greater than 50 ml.kg-1.min-1) and six average fit (AF) (VO2max less than 40 ml.kg-1.min-1) female subjects were subjected to a period of sleep loss of 60 h during which time they performed sustained mental tasks with no physical activity component. Venous blood samples were drawn every 12 h at 1330 hours and 0130 hours and plasmas analyzed for cortisol, growth hormone (hGH), prolactin, thyroxine (T4), triiodothyronine (T3), and reverse-triiodothyronine (rT3). For cortisol, both the HF and AF groups exhibited the normal high-daytime and low-nighttime pattern of secretion, with levels increasing significantly as the duration of SD increased. The normal elevations of hGH and prolactin levels during normal sleep were suppressed during SD. No significant fitness effects were found for cortisol, hGH, and prolactin responses. Plasma levels of T4, T3, and rT3 increased significantly during SD, with highly fit subjects exhibiting higher levels of these hormones than those of average fitness. We suggest that aerobic fitness may influence the peripheral metabolism of T4 during SD, but that aerobic fitness does not influence the regulation of the classical stress hormones during SD.

Comparison of four articular indices for use in clinical trials in rheumatoid arthritis: patient, order and observer variation.

Using a Latin square design, 4 patients were examined by 4 rheumatologists. Joints were scored for tenderness and inflammation. The Ritchie, the index of the American Rheumatism Association (ARA), the Hart modified Ritchie and a simplified Lansbury index were calculated from the raw data. The results suggest that an articular index consisting of a simple count of tender joints (Hart modified Ritchie) or a simple count of tender or swollen joints (ARA index) are the most reproducible with multiple observers. We suggest that these indices would be most appropriate for multicenter clinical trials.

The effect of taurine transport antagonists on cardiac taurine concentration and the incidence of sudden death syndrome in male broiler chickens.

Two experiments were conducted in which 540 day-old male broiler chickens were raised in heated battery brooders to 4 wk of age. Diets contained taurine antagonists to test effects on cardiac taurine content and the incidence of Sudden Death Syndrome (SDS). In Experiment 1 treatments during Weeks 2 to 4 were A) basal diet; B) basal diet supplemented with .25% guanidinoethyl sulfonate (GES) in Week 2 and 1.5% GES in Weeks 3 and 4; and C) basal diet supplemented with .5% GES in Weeks 2 to 4. The taurine content of heart was significantly reduced (P less than .05) with GES supplementation, but no effects on SDS mortality rates were noted. In Experiment 2 birds received diets containing 0. 2.5, or 5% beta-alanine. Supplementation with this compound decreased cardiac taurine concentration to extremely low levels (P less than .05). No significant effects on SDS mortality rates were noted. The results are interpreted as suggesting that taurine does not play a major role in the etiology of SDS.

Dioxin contamination and growth and development in great blue heron embryos.

A great blue heron colony located near a pulp mill in British Columbia failed to fledge young in 1987, with a concurrent sharp increase in polychlorinated dibenzo-p-dioxin (PCDD) and polychlorinated dibenzofuran (PCDF) levels in their eggs. In 1988 we tested the hypothesis that the PCDD and PCDF contamination caused reproductive failure by increasing mortality of the heron embryos in ovo. Pairs of great blue heron eggs were collected from three British Columbia colonies with low, intermediate, and high levels of dioxin contamination: Nicomekl, Vancouver, and Crofton, respectively. One egg of each pair was incubated under laboratory conditions at the University of British Columbia (UBC) while the other egg was analyzed for PCDDs and PCDFs. All incubated eggs were fertile. All eggs from the Nicomekl colony hatched, while 13 of 14 eggs from Vancouver and 12 of 13 eggs from Crofton hatched. Subcutaneous edema was observed in 4 of 12 chicks from Crofton and 2 of 13 chicks from Vancouver. No edema was seen in the chicks from Nicomekl. There was a small, but significant, negative regression of plasma calcium concentration, yolk-free body weight, tibia length, wet, dry, and ash weight, beak length, and kidney and stomach weight of the hatched chicks on the tetrachlorodibenzo-p-dioxin (TCDD) level of the paired eggs. Fewer down follicles were present on the heads of TCDD-contaminated chicks. Hence while dioxins did not cause mortality of the heron embryos in ovo, the depression of growth and the presence of edema are suggestive that dioxins at the levels found in the environment have an adverse effect on the development of great blue heron embryos.

Comparison of polychlorinated dibenzodioxin levels with hepatic mixed-function oxidase induction in great blue herons.

As part of the Canadian Wildlife Service monitoring of great blue herons in British Columbia, eggs were collected from three colonies with low, intermediate, and high levels of PCDD and PCDF contamination: Nicomekl, Vancouver, and Crofton, respectively. One egg from each nest was used for chemical analysis by GC-MS; the others were hatched. Liver microsomes were prepared from the heron chicks and used for determination of cytochrome P-450-dependent activities. No erythromycin N-demethylase activity was found in any sample. Ethoxyresorufin O-dealkylase activity in the Nicomekl group was similar to that in pigeons, a control altricial species. The ethoxyresorufin activity in the herons from the Crofton colony was 2.6-fold higher than in the Nicomekl group. The Vancouver colony was intermediate. No difference among the three heron colonies was found in pentoxyresorufin O-dealkylase activity, although levels were 20-33 times that in the pigeon. Chemical analysis was carried out on paired heron eggs. Vancouver and Crofton eggs contained 13.5 and 21 times the levels of 2,3,7,8-TCDD compared to the Nicomekl group. The Crofton eggs contained higher levels of several other contaminants also. A highly significant correlation (p less than .001) was found between ethoxyresorufin O-dealkylase and 2,3,7,8-TCDD concentrations. The correlation coefficient did not change when ethoxyresorufin O-dealkylase was compared to total chemical contamination using several toxic equivalency factors. Multiple regression analysis resulted in only one predictor variable for ethoxyresorufin O-dealkylase: 2,3,7,8-TCDD.

Moderate exercise and hemodilution during sleep deprivation.

The effect of 52 h of sleep deprivation (SD) upon blood constituents was studied in 12 young women aged 21.5 +/- 0.4 years. Subjects were individually isolated without time cues, performing a sequence of cognitive tasks. Significant decreases in hematocrit (p less than 0.002) and red cell count (p less than 0.04) developed, mainly over the first 28 h of SD, reaching a subsequent plateau or partial recovery. The calculated plasma volume also increased by 10.7 +/- 3.1% at 52 h, with recovery to a 6.9 +/- 3.2% increase the following day. About 1 L of water was retained over the first 30 h of SD, with a subsequent partial elimination of this excess. Plasma albumin and total protein concentrations were largely sustained in the face of the plasma expansion. The plasma pH showed a progressive fall from a baseline value of 7.381 +/- 0.014 to 7.332 +/- 0.006 at 52 h, while plasma bicarbonate decreased from a baseline figure of 31.2 +/- 0.7 to 26-27 mM/L (p less than 0.05). After 8 weeks, all subjects repeated the experiment, with the introduction of 30 min of exercise in the 40th h of wakefulness. Hematocrit and plasma volume changes were similar to those of the first experiment up to the time of exercise, but hematocrit decreased and plasma volume increased after the exercise bout, rather than reaching a plateau. Plasma pH increased with exercise, but returned to the previous low level at 52 h. Any arousing effect of the exercise bout was transient. The plasma expansion reflects metabolic and/or respiratory acidosis, plus possible effects of a prolonged period without recumbency.