Nonvisual photic responsiveness in newly hatched pigeons (Columba livia).

Overt behavioral arousal was elicited by light stimulation in pigeon hatchlings. The sensitivity is not mediated via the retina or by direct stimulation of the brain, but rather it is most likely a dermal sensitivity.

Automated detection of lung nodules in multidetector CT: influence of different reconstruction protocols on performance of a software prototype.

PURPOSE: To evaluate the accuracy of software for computer-aided detection (CAD) of lung nodules using different reconstruction slice thickness protocols in multidetector CT. MATERIALS AND METHODS: Raw image data sets for 15 patients who had undergone 16-row multidetector CT (MDCT) for known pulmonary nodules were reconstructed at a reconstruction thickness of 5.0, 2.0 and 1.0 mm with a reconstruction increment of 1.5, 1.0 and 0.5 mm, respectively. The "Nodule Enhanced Viewing" (NEV) tool of LungCare for computer-aided detection of lung nodules was applied to the reconstructed images. The reconstructed images were also blinded and then evaluated by 2 radiologists (A and B). Data from the evaluating radiologists and CAD was then compared to an independent reference standard established using the consensus of 2 independent experienced chest radiologists. The eligible nodules were grouped according to their size (diameter > 10, 5 - 10, < 5 mm) for assessment. Statistical analysis was performed using the receiver operating characteristic (ROC) curve analysis, t-test and two-rater Cohen's Kappa co-efficient. RESULTS: A total of 103 nodules were included in the reference standard by the consensus panel. The performance of CAD was marginally lower than that of readers at a 5.0-mm reconstruction thickness (AUC = 0.522, 0.517 and 0.497 for A, B and CAD, respectively). In the case of 2.0-mm reconstruction slices, the performance of CAD was better than that of the readers (AUC = 0.524, 0.524 and 0.614 for A, B and CAD, respectively). CAD was found to be significantly superior to radiologists in the case of 1.0-mm reconstruction slices (AUC = 0.537, 0.531 and 0.675 for A, B and CAD, respectively). The sensitivity at a reconstruction thickness of 1.0 mm was determined to be 66.99 %, 68.93 % and 80.58 % for A, B and CAD, respectively. The time required for detection was shortest for CAD at reconstruction slices of 1.0 mm (mean t = 4 min). The performance of radiologists was greatly enhanced when using CAD: sensitivity 91.26 % and 94.17 % for CAD+A and CAD+B, respectively (AUC = 0.889 and 0.917). CAD was most advantageous in the detection of nodules < 10 mm. CONCLUSION: At a 1.0-mm reconstruction thickness, CAD's ability to detect nodules < 10 mm is superior to that of radiologists and its relatively short evaluation time makes it a viable second reader.

Psychological Distress in Out-Patients Assessed for Chronic Pain Compared to Those with Rheumatoid Arthritis.

Background. Patients diagnosed with chronic pain (CP) and rheumatoid arthritis (RA) represent two samples with overlapping symptoms, such as experiencing significant pain. Objectives. To compare the level of psychological distress among patients diagnosed CP attending a specialist pain clinic with those attending a specialist RA clinic. Measures. A cross-sectional study was conducted at an academic specialist chronic pain and rheumatology clinic. Participants. 330 participants included a CP group (n = 167) and a RA group (n = 163) completed a booklet of questionnaires regarding demographic characteristics, duration, and severity of their pain. Psychological and personality variables were compared between the CP and RA participants using a Multivariate Analysis of Covariance (MANCOVA). Results. Level of psychological distress based on the subscales of the DASS (depression, anxiety, and stress), PASS (escape avoidance, cognitive anxiety, fear of pain, and physiological anxiety), and PCS (rumination, magnification, and helplessness) was significantly higher in the CP group compared to the RA group. Categorization of individuals based on DASS severity resulted in significant differences in rates of depression and anxiety symptoms between groups, with a greater number of CP participants displaying more severe depressive and anxiety symptoms. Discussion and Conclusions. This study found greater levels of psychological distress among CP individuals referred to an academic pain clinic when compared to RA patients referred to an academic rheumatology clinic.

Mood, Disability, and Quality of Life among a Subgroup of Rheumatoid Arthritis Individuals with Experiential Avoidance and Anxiety Sensitivity.

Objective. The current study aimed to identify and characterize distinct RA subgroups based on their level of EA and AS and compares the difference among the subgroups in mood, disability, and quality of life. Methods. Individuals with chronic pain for at least 3 months were recruited from an academic rheumatoid clinic. Participants were assessed for demographic, psychosocial, and personality measures. A two-step cluster analysis was conducted to identify distinct subgroups of patients. Differences in clinical outcomes were compared using the Multivariate ANOVA based on cluster membership. Results. From a total of 223 participants, three distinct subgroups were formed based on cluster analysis. Cluster 1 (N = 78) included those with low levels of both EA and AS. Cluster 2 (N = 81) consisted of individuals with moderate levels of EA and low levels AS. Cluster 3 (N = 64) included those with moderate levels of EA and high AS. Compared to those in Cluster 1, those in Cluster 3 had significantly higher levels of mood impairment and disability and lower quality of life (p < 0.05). Significantly lower levels of mood impairment were seen in Cluster 1 compared to Cluster 2 (p < 0.05). However, no significant difference in disability or quality of life was seen between the two groups. Conclusions. The three subgroups differed significantly in levels of impairment in mood, disability, and quality of life. However, levels of EA had a greater impact on disability and quality of life than AS.

Adult Still's disease: manifestations, disease course, and outcome in 62 patients.

Clinical and laboratory manifestations, disease course, outcome, and HLA associations were studied in an inception cohort of 62 subjects with adult Still's disease (ASD) from 5 Canadian universities. Twenty-eight patients (45%) were female and the median age at disease onset was 24 years. In general, the clinical features observed in our patients were identical to those in other published series. However, significantly higher frequencies of sore throat (92%), weight loss (76%), lymphadenopathy (74%), pleuritis (53%), pneumonitis (27%), and abdominal pain (48%) were noted in our patients compared to those in a recent literature review. Liver involvement with hepatomegaly (44%) or abnormal liver function tests (LFTs) (76%) was common and was responsible for the 2 deaths attributed to Still's disease in our series. Severe liver failure always occurred in conjunction with aspirin or NSAID therapy. Therefore, whether or not aspirin or other NSAIDs are used, we recommend close monitoring of LFTs in patients with ASD, especially early in the disease course. Laboratory manifestations were similar to those already reported. Leukocytosis (greater than or equal to 15,000/mm3) was present in 50 patients (81%), a normochromic, normocytic anemia (hemoglobin less than or equal to 10 g/dl) in 42 (68%), and an elevated ESR in all. The mean follow-up of the 62 patients was 70 months (range, 2-163). Twenty-one patients (34%) had a self-limited disease course, 15 (24%) an intermittent course, and 22 (36%) a chronic disease course. Four patients (6%) died, and 2 of these deaths were attributed to Still's disease. For those patients who experienced a recurrence of ASD, the flares were usually of shorter duration and milder in severity than the initial episode. No initiating factor for disease exacerbation was identified in our patients. Although 22 of 62 patients (36%) had a chronic disease course, 52 (90%) were in ARA Functional Class I, and only 4 and 2 patients were in ARA Functional Class II and III, respectively. Patients with Still's disease had higher scores than the controls on the Pain (P less than 0.01) and Physical Disability (P less than 0.05) subscales of Arthritis Impact Measurement Scales health status questionnaire. Joint radiographs performed at the follow-up evaluation disclosed typical carpometacarpal and intercarpal involvement in 16 of 39 patients. In our series, HLA-B17, B18, B35, and DR2 were significantly associated with ASD. Three significant predictors of an unfavorable outcome, either a chronic disease course or a longer time to clinical remission, were identified.(ABSTRACT TRUNCATED AT 400 WORDS)

A controlled study of the long-term prognosis of adult Still's disease.

PURPOSE: To assess the long-term prognosis of patients with adult Still's disease for physical and psychological disability, pain, social functioning, social support, medication use, formal education, occupation, time lost from work, and family income, and to contrast these results with those of same-sex sibling controls. PATIENTS AND METHODS: Patients were recruited from medical center-based cohorts in Pittsburgh and Eastern Canada and from a national survey of rheumatologists. Patients and same-sex sibling controls completed the Health Assessment Questionnaire for physical disability, the psychological and social function domains of the Arthritis Impact Measurement Scales, and the Interpersonal Skills Evaluation List questionnaire for social support, and replied to questions on medication use, formal education, occupation, time lost from work, and family income. RESULTS: One hundred four of 111 eligible adult Still's patients (94%) provided data. They identified 86 same-sex sibling controls, of whom 60 (70%) participated. The mean duration of adult Still's disease was 10 years. Approximately half of patients continued to require medication even 10 years after diagnosis. Patients had significantly higher levels of pain, physical disability, and psychological disability when compared with the controls. However, the levels of pain and physical disability were low compared to patients with other rheumatic diseases. Educational achievement, occupational prestige, social functioning and support, time lost from work, and family income were similar for both patients and controls. CONCLUSIONS: Despite causing disability, pain, and, in many, the need for long-term medication, patients with adult Still's disease are resilient. The disease did not interfere with educational attainment, occupational prestige, social functioning and support, time lost from work, or family income.

Effects of beta 2-agonist- and dexamethasone-treatment on relaxation and regulation of beta-adrenoceptors in human bronchi and lung tissue.

1. Long-term treatment with beta 2-adrenoceptor agonists can lead to a decreased therapeutic efficacy of bronchodilatation in patients with obstructive pulmonary disease. In order to examine whether or not this is due to beta-adrenoceptor desensitization, human bronchial muscle relaxation was studied in isolated bronchial rings after pretreatment with beta 2-adrenoceptor agonists. Additionally, the influence of pretreatment with dexamethasone on desensitization was studied. 2. The effect of beta 2-agonist incubation alone and after coincubation with dexamethasone on density and affinity of beta-adrenoceptors was investigated by radioligand binding experiments. 3. In human isolated bronchi, isoprenaline induces a time- and concentration-dependent beta-adrenoceptor desensitization as judged from maximal reduction in potency by a factor of 7 and reduction of 73 +/- 4% in efficacy of isoprenaline to relax human bronchial smooth muscle. 4. After an incubation period of 60 min with 100 mumol l-1 terbutaline, a significant decline in its relaxing efficacy (81 +/- 8%) and potency (by a factor 5.5) occurred. 5. Incubation with 30 mumol l-1 isoprenaline for 60 min did not impair the maximal effect of a subsequent aminophylline response but led to an increase in potency (factor 4.4). 6. Coincubation of dexamethasone with isoprenaline (120 min; 30 mumol l-1) preserved the effect of isoprenaline on relaxation (129 +/- 15%). 7. In radioligand binding experiments, pretreatment of lung tissue for 60 min with isoprenaline (30 mumol l-1) resulted in a decrease in beta-adrenoceptor binding sites (Bmax) to 64 +/- 1.6% (P < 0.05), while the antagonist affinity (KD) for [3H]-CGP-12177 remained unchanged. 8. In contrast, radioligand binding studies on lung tissue pretreated with either dexamethasone (30 mumol l-1) or isoprenaline (30 mumol l-1) plus dexamethasone (30 mumol l-1) for 120 min did not lead to a significant change of Bmax (160 +/- 22.1% vs 142.3 +/- 28.7%) or KD (5.0 nmol l-1 vs 3.5 nmol l-1) compared to the controls. 9. In conclusion, pretreatment of human bronchi with beta-adrenoceptor agonists leads to functional desensitization and, in lung tissue, to down-regulation of beta-adrenoceptors. This effect can be counteracted by additional administration of dexamethasone. Our model of desensitization has proved useful for the identification of mechanisms of beta-adrenoceptor desensitization and could be relevant for the evaluation of therapeutic strategies to counteract undesirable effects of long-term beta-adrenoceptor stimulation.

Radiologic review: the rheumatoid cervical spine.

We have reviewed the multiplicity of lesions present in the cervical spine in the adult with RA. The clinicoradiographic correlations are presented, and the techniques available for appropriate investigation are suggested. Readily available, conventional radiology provides useful information for the majority of patients. A standardized system of weighting and grading roentgenographic changes would be a welcome area of future research. Myelography and angiography should be considered in every patient before cervical spine surgery. CT evaluation should be reserved for those without a readily appreciable cause for myelopathy and those undergoing cervical surgical procedures.

Work disability evaluation and the fibromyalgia syndrome.

Fibromyalgia syndrome (FMS) is a common and costly cause of work disability. Patients with FMS, nevertheless, encounter considerable difficulties in their assessment of claims for disability payments. Factors that contribute to FMS as an important cause of disability are its high prevalence, the patients' perception of severe discomfort, and poor function. Disability evaluation in FMS is controversial for several reasons including lack of acceptance of the diagnosis, concurrent psychological abnormalities, difficulties in objectifying disability, deficiencies in instruments of evaluation, the uncertain efficacy of treatment, and physician attitudes. Third parties appear to have inappropriate expectations of the physician's role in determining disability. We suggest that the process of disability evaluation be improved by more objective assessments and by the inclusion of other health professionals in assessing disability and necessary retraining. Further research is needed to develop better instruments for measuring disability, to assess the long-term effects of various treatments, and to clarify the contributions of the work place and of compensation in causing or aggravating FMS.

Trauma and fibromyalgia: is there an association and what does it mean?

OBJECTIVES: The primary objective is to review current research with respect to the role of trauma in fibromyalgia (FM). A secondary objective is to hypothesize which steps need to be taken, first to determine whether such an association truly exists, and second to clarify what such an association might mean. METHODS: An extensive literature review was undertaken, including Medline from 1979 to the present. RESULTS: The strongest evidence supporting an association between trauma and FM is a recently published Israeli study in which adults with neck injuries had greater than a 10-fold increased risk of developing FM within 1 year of their injury, compared with adults with lower extremity fractures (P= .001). Several other studies provide a hypothetical construct for such an association. These include studies on (1) postinjury sleep abnormalities; (2) local injury sites as a source of chronic distant regional pain; and (3) the concept of neuroplasticity. There are, however, several primary arguments against such an association: (1) FM may not be a distinct clinical entity; (2) FM may be a psychological, rather than physical, disease; (3) the evidence supporting any association is limited and not definitive; (4) the Israeli study, itself, has some methodological limitations; and (5) other factors may be more important than the injurious event in determining chronic symptoms after an acute injury. CONCLUSIONS: Although there is some evidence supporting an association between trauma and FM, the evidence is not definitive. Further prospective studies are needed to confirm this association and to identify whether trauma has a causal role.

Reconstitution of impaired autologous mixed lymphocyte reactivity in rheumatoid arthritis.

We examined the ability of recombinant IL-2 to reconstitute the autologous mixed lymphocyte reaction (AMLR) defect in peripheral blood mononuclear cells (PBM) from patients with rheumatoid arthritis (RA). Our results revealed an ability to fully reconstitute RA AMLRs with pharmacologic concentrations (100 units/ml), but not physiologic concentrations (10 units/ml) of IL-2. Full reconstitution of RA AMLRs was achieved whether IL-2 was added as the initiation of culture or at 48 or 72 hours prior to termination of the cultures. Impaired IL-2 production was noted throughout the time course of the RA AMLRs. Neither an inhibitor of IL-1 nor IL-2 was detected in AMLR culture supernatants. Moreover, IL-1 in pharmacologic concentrations up to 50 units/ml failed to reconstitute impaired AMLR reactivity. In 2 patients whose AMLRs failed to reconstitute fully with 100 units/ml IL-2, addition of 10 units/ml IL-1 in combination with IL-2 fully reconstituted the AMLR defect. The results may suggest that defective IL-2 generation alone cannot fully account for impaired AMLR reactivity in RA patients.

The efficacy of dexamethasone iontophoresis for the treatment of rheumatoid arthritic knees: a pilot study.

OBJECTIVE: To examine the efficacy of dexamethasone sodium phosphate (DEX) iontophoresis for the treatment of rheumatoid arthritis (RA) of the knee, and to obtain statistical information for a future randomized controlled trial (RCT). METHODS: Ten subjects with RA, ranging in age from 34-75, were randomly assigned to either the experimental or placebo group. Iontophoresis treatments were given to both groups on days 1, 3, and 5. Five subjects in the experimental group received a mixture of 1 ml of DEX (4 mg/ml) and 1 ml of injectable sterile water; those in the placebo group received 2 ml of saline solution. Pain on movement, at rest, and on pressure, active joint count, and active range of motion, were evaluated on days 1, 5, and 20. The patient's global assessment of treatment efficacy was also assessed on days 5 and 20. Mann-Whitney U tests and Friedman two-way analyses of variance were performed for statistical analyses. RESULTS: Pain at rest was found to be statistically different between the two groups (P = 0.0317). Statistical significance was also found over time for pain on movement within the experimental group (P = 0.0224). CONCLUSION: The results suggest that DEX iontophoresis is more effective than placebo in relieving pain at rest and on movement in the RA knee. Based on the study data, a total of 40 subjects will be required for an RCT of a similar nature.

Functional restoration. Returning patients with chronic low back pain to work--revolution or fad?

STUDY DESIGN: A review was performed to assess the basis for functional restoration programs in returning patients with chronic low back pain to work. OBJECTIVE: To review and assess the effectiveness of functional restoration programs in the treatment of chronic low back pain. SUMMARY OF BACKGROUND DATA: Functional restoration programs generally use an aggressive program of physical exercises and psychosocial support with the focus on improving function despite the pain. METHODS: A review was conducted of significant papers presenting results of large clinical trials that used functional restoration programs. RESULTS: Several influential studies have reported statistically significant improvement in return-to-work rates of treated patients. The comparison groups consisted of treatment failures and/or patients refused entry to the programs because of insurers refusal to pay. Selection bias, incomplete follow-up, and inappropriate allocation of compared patients cast doubt on the effectiveness of these functional restoration programs. The only published prospective randomized clinical trial failed to demonstrate the efficacy of a functional restoration program. CONCLUSIONS: Further clinical trials based on sound methodology are needed.

Gold and modulation of the immune response.

The effects of gold on immune responses are reviewed. Gold salts used therapeutically can be followed by a decline in serum immunoglobulin levels, and rheumatoid factor titers in rheumatoid arthritis; in pemphigus there is similarly a drop in anti-epithelial antibody titers. Gold inhibits stimulation of immunoglobulin-secreting cells. Gold inhibits the activation of the classical and alternate complement pathways. Gold compounds inhibit numerous cell-mediated immune responses to various mitogens and antigens. Inhibition may be due to the effect of gold on macrophages acting as helper cell in these reactions. Auranofin is a new oral compound which seems to be particularly potent in its immuno-regulatory actions; it differs from other gold compounds in its pharmacokinetics, and in the nature of its ligand. Gold has also been reported to enhance certain immune reactions. The extent of the immuno-regulatory effects of gold in vivo is unknown, and the relation of these effects to its therapeutic actions remains to be clarified.

Mechanisms of action of disease modifying antirheumatic drugs.

The relationship between the biologic activities of disease modifying antirheumatic drugs (DMARD) and their therapeutic effects are complex. Some DMARD are prodrugs, e.g., azathioprine; others may act in combination with endogenous substances, e.g., D-penicillamine and copper salts. Gold compounds, antimalarials, sulfasalazine, azathioprine and methotrexate affect various phagocytic cell functions. Most DMARD inhibit the immune responses of monocytes and of T and B lymphocytes. Gold, sulfasalazine, D-penicillamine also affect fibroblast and/or endothelial cell proliferation. Many DMARD inhibit responses to, or production of, cytokines. Several DMARD have overlapping biologic effects but differ in their therapeutic efficacy in individual patients for unknown reasons.

Inhibition of lymphocyte responses by gold: modulation by time of drug addition and antigen dose.

Gold sodium thiomalate added to peripheral blood mononuclear (PBM) cell cultures inhibits the mixed leukocyte reaction (MLR), and cell-mediated cytotoxicity (CMC). The addition of GST to MLR was inhibitory only if the compound was added at the beginning of culture; late addition of GST did not inhibit MLR, or CMC. In a different set of experiments the number of stimulating cells added to MLR was varied. The inhibitory effects of GST decreased markedly as the number of stimulating cells added to culture was increased. The effects of gold in vivo may be modulated by a number of immunologically competent cells that are already antigenically stimulated, as well as by the amount of available stimulating antigen.

Inhibitory effects of gold and other drugs on mononuclear cell responses: a comparison.

The effects of gold sodium thiomalate (GST) were compared with those of acetylsalicylic acid (ASA), D-penicillamine (PEN), and methlyprednisolone succinate (MP) on the mixed leukocyte reaction (MLR), and on cell-mediated cytotoxicity (CMC) using mononuclear cells from normal human volunteers. GST and MP inhibited MLR in concentrations readily achieved in the serum, or tissues of patients. ASA showed only a modest effect on MLR, in high concentrations. All drugs inhibited CMC; PEN inhibited CMC at doses of 100 mcg/ml which were no inhibitory in MLR. ASA inhibited CMC at relatively low concentrations. The effects of some of the drugs on MLR and CMC were not consistent. This may be due to the preferential action of the drugs on various immunologically competent cells.

Cells with immunoregulatory function: the human macrophages and the effects of remittive drugs.

Different inhibitory effects on the mixed leukocyte reaction were noted with sodium aurothiomalate (GSTM) and D-penicillamine (D-Pen) depending on the lymphocyte/macrophage ratio of responder cell populations. GSTM and auranofin strongly inhibited oxy radical generation whereas D-Pen had a selective effect.

Improvements in pain responsiveness in patients with fibrositis after successful treatment with amitriptyline.

Thirty-six patients with fibrositis received low dose amitriptyline and placebo in a randomized double blind crossover study lasting 10 weeks. Amitriptyline was associated with significant changes on the outcome measures of pain, tender point sensitivity and patient assessment of well being. Clinically significant improvements for pain and tender point sensitivity and a statistically significant improvement in generalized pain responsiveness were found between patients who reported subjective improvement on amitriptyline and those who felt no change.

Gold therapy in rheumatoid arthritis. Interim report of the Canadian multicenter prospective trial comparing sodium aurothiomalate and auranofin.

One hundred and twelve patients with classical or definite rheumatoid arthritis (RA) were randomly assigned to receive either sodium aurothiomalate (GSTM) or auranofin (AF). Monthly clinical assessments (morning stiffness, grip strength, articular index, pain, quality of life) and concurrent hematological, biochemical, and urine studies were performed to monitor the efficacy/toxicity (E/T) ratio. Ninety-two patients have completed 3 months; 65, 6 months; 47, 9 months; and 30, 12 months. The groups were numerically balanced at each time period. Analysis of the 0-6 month period suggests that both drugs were equally and significantly beneficial after 3 months and that this was maintained at 6 months. Toxicity was as frequent in both groups but more serious in the GSTM group. The main side effects were gastrointestinal (diarrhea) in the AF group and mucocutaneous in the GSTM group. Half of the withdrawals (14 in each group) were because of side effects in the GSTM group and for inadequate therapeutic efficacy in the AF group. This study suggests that after 6 months of treatment the E/T ratio of AF is greater than or equal to that of GSTM. These conclusions will need to be confirmed during the ongoing longer observation period. A significant clinical difference between the 2 drugs is that in a given patient treated with GSTM, the onset of toxicity coincides with a good therapeutic effect. This relationship does not appear to exist during AF treatment.