Monitoring of mitochondrial NADH levels by surface fluorimetry as an indication of ischaemia during hepatic and renal transplantation.
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Animals↗
Biomedical subjects
N Lane
Publications and source records attributed to N Lane.
Validity of self-reported rheumatoid arthritis in elderly women.
OBJECTIVE: To determine the validity of a self-reported physician diagnosis of rheumatoid arthritis (RA) in elderly women. METHODS: Women with self-reported RA were contacted and permission requested to contact their physician. Physicians were mailed a questionnaire requesting information on the subject's arthritic condition. Hand radiographs obtained at study entry were read for changes of RA. RESULTS: The self-reported diagnosis of RA could be confirmed in 26 (21%) individuals. CONCLUSION: The positive predictive value of self-reported RA was low in this cohort. Caution needs to be exercised in the use and interpretation of self-report data concerning arthritic conditions in epidemiologic studies.
Aged↗
The relationship between fibromyalgia and temporomandibular disorders: prevalence and symptom severity.
OBJECTIVE: To determine the prevalence of muscular or myofascial temporomandibular disorders (TMD) in fibromyalgia (FM) and the prevalence of FM in TMD; and to determine which characteristics best distinguish the 2 disorders. METHODS: 39 consecutive patients with TMD seen in a TMD clinic and 60 patients with FM were examined according to Research Diagnostic Criteria (RDC) for TMD and the American College of Rheumatology 1990 Criteria for the Classification of Fibromyalgia. All patients completed the questionnaires of the RDC and a health status instrument that assessed pain, function, sleep disturbance, fatigue, and psychological status (CLINHAQ). RESULTS: A small proportion of patients with TMD (18.4%) also had FM, but most of those with FM (75.0%) satisfied criteria for muscular (myofascial) TMD. Patients with FM had lower pain thresholds and more severe manifestations of all disease measures (e.g., pain, fatigue, sleep, etc.) compared to those with TMD. As might be predicted, they also had more painful body regions. Patients with FM also differed significantly from those with TMD in self-reported work ability and health assessment. The features that best differentiate FM from TMD are functional disability, reports of work difficulty, and general dissatisfaction with health. CONCLUSION: TMD is a local disorder and FM a generalized disorder, and there is less evidence of distress in those with TMD. TMD is a separate disorder from FM, but many patients with FM have TMD symptoms.
Adult↗
Physician-determined patient risk of toxic effects: impact on enrollment and decision making in phase I cancer trials.
BACKGROUND: The conventional phase I trial design yields an estimate of the maximum tolerated dose (MTD) of a new drug defined from treatment toxic effects observed in a small heterogeneous cohort of patients. The MTD is specific for those patients treated in the study and may not be reproducible in another patient series, a limitation known as cohort dependency. PURPOSE: We conducted an opinion survey of phase I investigators in an attempt to characterize physician attitudes and clinical practices regarding assessment of risk of toxic effects in patients. METHODS: A physician opinion survey of scaled multiple choice and open-ended questions was distributed to oncologists (faculty and fellows) at National Cancer Institute (NCI)-funded phase I contract institutions. The target sample was narrowed to these specific institutions because of their experience in conducting various phase I trials. Each NCI-funded phase I contractor received an instruction sheet and 25 surveys and envelopes that were made available to oncologists enrolling patients in phase I trials. RESULTS: Of the 75 surveys distributed, 67 (89%) were returned. Most respondents agreed that unexplained variability in toxicity exists in phase I trials. However, opinion varied considerably among five participating institutions (two-sided P = .001). Informal scoring of patients for toxicity risk prior to treatment was a common practice (85% overall), although the prevalence of this practice varied somewhat among the institutions (two-sided P = .01). Physicians' opinions were mixed regarding the practice of becoming increasingly selective in enrolling patients as the MTD was approached, with strong disagreement noted among institutions (two-sided P = .001). Given background on a hypothetical phase I trial, respondents were asked to rank the usefulness of 27 patient factors for predicting the risk of dose-limiting leukopenia. Eight factors were perceived as strongly informative: Eastern Cooperative Oncology Group performance status of 2 or worse, recent weight loss of more than 10%, multiple bone marrow metastases, two or more prior chemotherapy regimens, history of treatment toxic effects, and prior treatment with carboplatin, mitomycin, or nitrosoureas. CONCLUSIONS: Informal assessment of the risk of toxic effects in a patient was found to be common practice among oncologists who enroll patients on phase I trials, and there was strong agreement on the usefulness of several key patient factors for such assessments. Interestingly, interinstitutional variation in opinions and practices were noted, specifically regarding patient-selection bias. Follow-up studies are required to establish if physician-determined assessments of patient risk are consistent and accurate.
Adult↗
Mechanical and biochemical changes in the superficial zone of articular cartilage in canine experimental osteoarthritis.
The changes in the tensile mechanical properties and biochemical composition of the superficial zone of articular cartilage were examined in a canine model of early osteoarthritis generated by transection of the anterior cruciate ligament. Sixteen weeks following ligament transection, the tensile stiffness of the articular cartilage was decreased by 44% and the ion-induced stress relaxation of the tissue was increased by 57% compared with the contralateral control. Biochemical analyses indicated that the water content of the experimental tissue was increased by 13%, which was reflected as an apparent 37% decrease in the proteoglycan content and a 36% decrease in the collagen content (expressed per wet weight). The hydroxypyridinium crosslink density was decreased in the experimental tissue by 11%. A significant negative correlation was found between the ion-induced stress relaxation and the hydroxypyridinium crosslink density in both control tissue (R = -0.56) and experimental tissue (R = -0.70). No correlation was noted between the tensile stiffness and the biochemical composition of the tissue. These results suggest that, in the superficial zone of articular cartilage, the structure of the tissue may play a more important role than the composition in the determination of its mechanical properties. A major event observed in the model of early osteoarthritis appears to be the disruption and remodeling of the collagen network in the superficial zone of the articular cartilage.
Animals↗
Cancellous bone behavior in hindlimb immobilized rats during and after naproxen treatment.
Temporary immobilization creates bone loss. The purpose of this investigation was to use an agent to protect the skeleton from bone loss bone during temporary immobilization. Eighty-nine 6-month-old retired breeder Sprague-Dawley female rats were used. Animals were randomly divided into six groups of equal numbers. Four groups were given drinking water from day 0, containing naproxen (100 or 200 mg/l). At day 7, half the animals in all groups had their right hindlimb immobilized. At day 49, half the immobilized rats and non-immobilized controls were sacrificed. The remaining rats were remobilized and the drug was stopped. At day 91, all remaining rats were sacrificed. Gastrocnemius and soleus muscle weights were determined. Right tibiae were analyzed for cancellous bone mass, bone structural and bone dynamic variables. At the close of immobilization, bone mass was lower in the right (immobilized) hindlimb of the immobilized group than in the non-immobilized group. Immobilized rats drinking 100 mg/l naproxen water had significantly higher bone mass in their immobilized limbs than did untreated immobilized rats, but all rats drinking 200 mg/l naproxen water had lower bone mass than controls. After 6 weeks of recovery, bone mass in the immobilized limb of untreated formerly immobilized rats improved, but remained below untreated never-immobilized rats. Formerly immobilized rats that had been treated with 100 mg/l naproxen water had normal bone mass after 6 weeks of recovery. Naproxen, an agent that mildly depresses activation frequency, prevents some of the transient bone mass and structural deterioration during temporary immobilization. Such treatment facilitates a more rapid return to normal bone mass, though not to normal structure. The more rapid recovery occurs because the difference from normal is less, not because of more rapid formation in recovering animals.
Analysis of Variance↗
Transient bacteremia due to Mycobacterium avium complex in patients with AIDS.
It is generally assumed that Mycobacterium avium complex (MAC) bacteremia, once it develops, is unremitting. On the basis of this presumption, changes in the level of mycobacteremia are used to gauge therapeutic response. In 7 (12%) of 60 patients enrolled in a prospective trial of MAC bacteremia and AIDS, bacteremia became undetectable before the initiation of antimycobacterial therapy. Patients with transient bacteremia reported fewer and shorter symptoms and survived longer than those with sustained bacteremia (59 vs. 31 weeks; P = .022). There was no difference in the duration of AIDS, CD4+ cell count, hematocrit, or body weight between groups. Two additional patients with transient bacteremia were identified outside this study setting. Despite disappearance of detectable mycobacteremia and subsequent administration of antimycobacterial agent(s), bacteremia once again became detectable in 6 patients 4-45 weeks after their negative pretreatment cultures. Patients with disseminated MAC may have fluctuating levels of mycobacteremia that become undetectable in the absence of antimycobacterial therapy.
AIDS-Related Opportunistic Infections↗
In vivo effects of naproxen on composition, proteoglycan metabolism, and matrix metalloproteinase activities in canine articular cartilage.
Naproxen is a nonsteroidal anti-inflammatory drug commonly used in the clinical treatment of joint disease. In this study, its effect in vivo on the biochemical composition, metabolic activities, and metalloproteinase activities of normal canine articular cartilage was analyzed. The articular cartilage from the knee joints of dogs who had been given naproxen for 4 weeks to maintain a serum level of 40-50 micrograms/ml was examined. Control animals were given a placebo. Treatment with naproxen was not found to change the composition (water, collagen, and proteoglycan) of the articular cartilage. The culture studies of cartilage explants indicated that proteoglycan synthesis rates were unaffected by the treatment with naproxen but that proteoglycan release from the tissue was suppressed. Analysis of the cartilage for matrix metalloproteinase activities showed reduced activity of neutral matrix metalloproteinase by 80%, of collagenase by 40%, and of gelatinase by 87%, with no change in activity of acid metalloproteinase or of tissue inhibitor for metalloproteinase. These findings indicate that in vivo treatment with naproxen has the capacity to modulate catabolic activities in articular cartilage.
Animals↗
The in vivo effects of naproxen on canine experimental osteoarthritic articular cartilage: composition, metalloproteinase activities and metabolism.
A canine experimental model of osteoarthritis (OA), generated by arthroscopic transection of the anterior cruciate ligament (ACL) of the knee, was used to investigate the in vivo effects of the NSAID naproxen on the course of cartilage degeneration. The drug was given at the time of surgery, or from before surgery, and for 16 weeks after surgery. Analysis of the articular cartilage showed the naproxen was able to significantly suppress the decrease in proteoglycan content and metalloproteinase activities. The results indicate that pharmaceutical agents have the potential to modulate the progression of degenerative joint disease.
Animals↗
Precision and accuracy for rat whole body and femur bone mineral determination with dual X-ray absorptiometry.
Precision and accuracy for rat whole body and excised femur bone mineral density (BMD) measurements were evaluated with two dual X-ray absorptiometry (DXA) systems. The 'small subject' mode on the Norland XR-26 (XR), and the 'ultra high resolution mode' on the Hologic QDR-1000/W(QDR) were used for the analysis. The whole body mode was only available on the XR. The lowest precision error for the whole body was found using a scan resolution of 1.0 x 1.0 mm and a scan speed of 15 mm/s. The scan spatial resolution of the femur measurement was approximately eight times higher on the QDR than on the XR. However, the XR allowed analysis of an arbitrary region of interest within the femur, which was not easily done with the QDR. Precision for the total femur measurement on the QDR (0.5-0.9%) was approximately two to four times superior to that of the XR (1.5-4.3%). The difference may be due to the superior scan resolution of the QDR. Bone mineral content and BMD on the QDR significantly declined with an increase of water depth (P < 0.001). No significant change was observed on the XR. Both DXA systems demonstrated an excellent correlation (r > or = 0.98) with ash weight under the scan conditions examined. The optimal scan condition for the excised femur measurement on the XR was obtained with 1.5-2.5 cm of perspex or water and a scan speed of 10 mm/s. For the QDR, we recommend scanning the rat femur with approximately 2.5 cm of perspex or water in terms of precision and accuracy.
Absorptiometry, Photon↗
Synovium-like tissue from loose joint replacement prosthesis: comparison of human material with a canine model.
The formation of synovium-like tissue is a biological response to a loose joint replacement prosthesis. Histological examination of this tissue has shown a synovial lining with a predominance of fibroblasts and macrophages, some multinucleated giant cells, and dispersed particles from the implant. Previous studies have reported elevated interleukin 1 (IL-1), prostaglandin E2 (PGE2), and collagenase in this tissue. We developed a canine model for the loose cemented femoral stem. Tissue harvested from the canine model was compared with human tissue retrieved at revision arthroplasty. Histology showed synovium, similar to that observed around loose human prostheses, adjacent to the canine cement sheath. Cells were isolated from this tissue and incubated in culture medium with or without naproxen for 3 days. Aliquots of the conditioned media were tested in the thymocyte proliferation assay to determine IL-1-like activity. IL-1 beta levels in human cell-conditioned media were analyzed by enzyme-linked immunosorbent assay, and PGE2 levels were measured by radioimmunoassay (RIA) using a PGE2 RIA kit (New England Nuclear). Human tissue contained levels of IL-1 beta in the range of 150 to 7,040 pg/mL and PGE2 levels of 82 to 952 ng/mL. The canine specimens contained IL-1-like activity and significant amounts of PGE2 (76 to 1,720 ng/mL). Naproxen decreased PGE2 levels in vitro. This animal model provides the means to investigate the in vivo and in vitro activity of the synovial cells around loose total joint prostheses.
Adult↗
Long-term effect of naproxen on cancellous bone in ovariectomized rats.
Previous work shows that at 42 d post-ovariectomy (OX) in aged rats, naproxen, a nonsteriodal anti-inflammatory drug (NSAID) prevents cancellous bone loss. The purpose of this study was to evaluate the effects of naproxen on cancellous bone of aged OX and sham-OX rats, at 90 days post-OX. Six-month-old Sprague-Dawley retired breeder female rats underwent either sham-OX (n = 49) or OX (n = 65). Sham-OX rats were randomized into five groups and OX rats into six groups. The first five groups of both were given ad lib access to water containing 0, 4, 10, 25, or 62.5 mg/l of naproxen sodium. The sixth group of OX rats was given water containing 156.25 mg naproxen sodium/l. After ninety days, the rats were killed following in vivo dual calcein labeling. Terminal serum naproxen was measured by HPLC. In the proximal tibial metaphysis, trabecular bone volume, trabecular thickness, trabecular number, mineralizing surface (double label), osteoclast surface, and bone formation rate were measured. Sham-OX and OX rats were compared by t-test of means. Kruskal-Wallis tests and, as necessary, Dunnett's t-tests, were applied separately to the groups of Sham-OX and OX rats. Dose-related serum levels of naproxen up to 9.4 mcg/ml were achieved in the 156.25 mg/ml group. OX rats had significantly lower bone volume, trabecular thickness, and trabecular number than Sham-OX groups (p less than .001). OX rats had significantly higher mineralizing surface, formation rate, and osteoclast surface than sham-OX rats (p less than .001). No differences related to naproxen treatment existed in sham-OX rats. Naproxen treatment producing a serum level of 9.4 mcg/ml reduced bone volume in OX rats consuming water with 156.25 mg/l (p less than .05). At 90 days post-OX, naproxen, at serum levels of 9.4 mcg/ml or less, did not diminish estrogen-depletion cancellous bone loss in rats. Naproxen lacks lasting ability to halt estrogen-depletion bone loss in aged OX rats.
Animals↗
Bone mineral density of the lumbar spine in women with endometriosis.
Young women with endometriosis have reduced cortical and trabecular bone mineral density of the wrist compared with age-matched controls. This conclusion was based on 41 subjects from one geographical location. The purpose of this study was to test this finding in a larger, more geographically diverse population. One hundred women with laparoscopically proven endometriosis were enrolled in this study for the evaluation of the efficacy of nafarelin, a gonadotropin-releasing hormone agonist. Patients were recruited from nine investigators across the United States and Canada, and bone mineral density of the lumbar spine was obtained at baseline, with 6 Hologic QDR (Hologic Inc., Waltham, MA) and a Lunar DPX (Lunar Radiation Corp., Madison, WI) instrument. The age of the women was 30.3 +/- 5.8 years (mean +/- SD); 91% were white. Bone mineral density of the lumbar spine was 1.1 +/- 0.11 g/cm2 (n = 85 Hologic QDR) and 1.2 +/- 0.93 g/cm2 (n = 15 Lunar DPX). Hologic bone mineral density was 104.8 +/- 11.0 and Lunar bone mineral density was 103.4% +/- 7.8% of normal values for age. To conclude, in a population based cross-sectional study of patients with endometriosis, we do not observe low bone mineral density of the lumbar spine by techniques that measure a combination of cortical and trabecular bone.
Adult↗
Bone mineral density of the lumbar spine in endometriosis subjects compared to an age-similar control population.
The purpose of this study was to compare the lumbar bone mineral density (BMD) between women with endometriosis and age-similar controls. Eighty-five women from nine North American centers (mean age, 30.7 yr) with laparoscopically proven endometriosis (study patients) were enrolled in a study of the efficacy of nafarelin, a GnRH agonist. Fifty-two women (mean age, 32 yr) from the Palo Alto area, with regular menstrual cycles and no major medical problems, served as age-similar controls. Both groups were predominantly (greater than 92%) white. The mean BMD of the lumbar spine was 1.1 g/cm2 in both the study subjects and the controls. Study patients were 104.8% and controls were 104.8% of normal values for age. BMD was not significantly different in the two groups. BMD was not correlated with severity or time from diagnosis of endometriosis. BMD was positively correlated with weight (r = 0.28; P less than 0.05) in both groups, with height (r = 0.30; P less than 0.01) in study patients, and marginally with height (r = 0.26; P less than 0.07) in controls. This study showed no difference in BMD between endometriosis patients and age-similar controls; both groups had normal BMD.
Adolescent↗
Effect of naproxen on cancellous bone in ovariectomized rats.
Nonsteroidal anti-inflammatory drugs (NSAIDs) affect bone metabolism in vitro and in vivo. They delay but do not alter the outcome of healing processes in bone. In some bone loss models, they block bone resorption and slow the rate of loss. We studied the effect of naproxen, a potent NSAID, on cancellous bone of the proximal tibial metaphysis of 6-month-old adult female ovariectomized rats. Animals were ovariectomized, divided into groups, and fed standard diets differing only in naproxen content for 42 days. The rats of the groups ate 2.0, 5.5, 12.7, and 32 mg naproxen per kg body weight per day, respectively. Serum levels of naproxen were determined. Bone volume, mineralizing surface, osteoblast activity, osteoclast surface, and bone resorption rate were determined by bone histomorphometric techniques. The rats' dose-related serum naproxen levels ranged from 4 to 28 micrograms/ml. Naproxen inhibited up to 70% of the bone loss occurring after ovariectomy at a serum level of 4 micrograms/ml. We deduced that naproxen blocked bone resorption in ovariectomized rats by slowing osteoclast activity at all doses. In contrast, naproxen slowed bone formation only at serum levels greater than 20 micrograms/ml in ovariectomized rats. These findings may have clinical relevance in helping to prevent postmenopausal bone loss in women.
Animals↗
Tissue changes around loose prostheses. A canine model to investigate the effects of an antiinflammatory agent.
The aseptically loosened prosthesis provided a means for investigating the in vivo and in vitro activity of the cells associated with the loosening process in seven dogs. The cells were isolated and maintained in culture for sufficient periods of time so that their biologic activity could be studied as well as the effect of different agents added to the cells in vivo or in vitro. The biologic response as determined by interleukin-1 and prostaglandin E2 activity paralleled the roentgenographic appearance of loosening and the technetium images and observations made at the time of revision surgery. The correlation between clinical, roentgenographic, histologic, and biochemical loosening indicates that the canine model is suitable for investigating the mechanisms of prosthetic failure. A canine model permits the study of possible nonsurgical therapeutic interventions with the ultimate hope of stopping or slowing the loosening process.
Animals↗
Interface between geriatric and general medicine.
Information about their practice has been obtained from 652 consultant physicians in geriatric medicine representing 203 (78%) of the 259 health districts in the United Kingdom (UK). Joint appointments in general and geriatric medicine are held by 19.6%. Admissions policies included admissions selected by suitability for the department (58%) or on an age-related basis (37%)--the most common cut-off age being 75 years. In only a minority, however, were all medical patients above the designated age accepted. The policy generally applied only as long as empty geriatric beds were available. Integrated service (admitting geriatric and internal medicine patients of all ages to a common pool of beds) was practised in 5% of districts. Only one provided long-term care alone. Specialist interests within or in addition to geriatrics were reported by 26% of whole time and 48% of joint appointees. 'Pure' geriatrics remains the most popular form of practice.
Age Factors↗