Phosphor plate computed radiography: response to variation in mAs at fixed kVp in an animal model. Potential role in neonatal imaging.

Computed digital radiography offers a number of potential advantages over conventional film-screen imaging. To determine the applicability of these to portable neonatal examinations we performed a controlled prospective study comparing conventional 200 speed film-screen with a computed radiography unit in an animal model. Images acceptable for diagnostic purposes were obtained on the digital system over an exposure range many orders of magnitude greater than was possible on the film-screen system. Digital imaging offers potential for elimination of repeat examinations due to suboptimal exposure factors, and for reduction in radiation dose to the patient. We believe that computed digital radiography should be particularly suited to portable neonatal imaging.

Treatment of knee osteoarthritis: relationship of clinical features of joint inflammation to the response to a nonsteroidal antiinflammatory drug or pure analgesic.

Our randomized double blinded comparison of acetaminophen versus analgesic and antiinflammatory doses of ibuprofen in the treatment of 182 subjects with knee osteoarthritis (OA) systematically evaluated soft tissue tenderness and joint swelling. Improvement in these signs of joint inflammation was associated with lessening of disability (p = 0.02), and reduction in rest pain (p = 0.07), but not with the drug treatment regimen. Thus, joint tenderness and swelling, presumptive evidence of synovitis, may not be a priori indications for use of an antiinflammatory drug, or predict greater responsiveness to treatment with an antiinflammatory drug than to a pure analgesic, in symptomatic treatment of patients with knee OA.

Variability in the disposition of ibuprofen enantiomers in osteoarthritis patients.

The pharmacokinetics of the enantiomers of ibuprofen have been investigated following oral administration of 300 or 600 mg of racemic ibuprofen four times daily to 45 patients with osteoarthritis. Fifteen of these patients also received single doses of 300 or 600 mg of racemic ibuprofen. Serum concentrations of R- and S-ibuprofen and urine concentrations of the stereoisomers of ibuprofen and its metabolites were measured by high-performance liquid chromatography. The fraction inverted (F(inv)) of the inactive R- to active S-ibuprofen was estimated by a urinary metabolite method. For the 15 patients in both the chronic and single dose studies, there were no significant differences in the clearance of R-ibuprofen or F(inv). The elimination half-lives of R- and S-ibuprofen were comparable for the single and chronic dosing studies. The area under the curve (AUC) values, 6-h trough concentrations, and average steady state concentrations of the R- and S-enantiomers were statistically different after chronic dosing. Despite considerable variability in the clearances in these patients, e.g., clearance (CL) of R-ibuprofen showed 28-49% CV, much less variability was seen in F(inv) (range 9-19% CV), implying that patients would receive similar effective doses of active S-ibuprofen in spite of large differences in kinetics.

Total skin electron beam radiation therapy for mycosis fungoides.

Forty-nine patients with biopsy-proven mycosis fungoides, Stages I-IV were treated using total skin electron beam irradiation (TSEBI). Total dose ranged from 600 cGy to 3,200 cGy. To evaluate the dose response relationship, patients were retrospectively divided into two groups. In Group I, 18 patients received a dose of 2,000 cGy or less, and in Group II, 31 patients received more than 2,000 cGy. The overall response rate was 87.7% with a 75.7% complete response and 12.2% partial response. Complete response was higher among patients with early stage disease: (Stage IA 1/1, Stage IB 23/35 (92%), Stage IIA 3/4 (75%), Stage IIB 4/8 (50%), Stage III 3/6 (50%), Stage IVA 1/1, Stage IVB 0/1, and unstaged group 2/3 (66.6%)). Patients treated with a higher total dose had a higher overall 5-year survival rate (Group I 38%, Group II 68%), longer median duration of complete response (Group I, 27 months; Group II, 35.3 months), slightly better complete response rate (72.2% for Group I, 77.4% for Group II), and lower recurrence rate (Group I, 94%; Group II, 83.9%) compared to patients with lower total dose. Complications from TSEBI were minimal. Total skin electron beam irradiation is effective in controlling early stage mycosis fungoides; however, a prospective study to evaluate optimum total dose is needed.

Impairment of osteophyte formation in hyperglycemic patients with type II diabetes mellitus and knee osteoarthritis.

OBJECTIVE: Since insulin is a potent growth factor for connective tissue, the present study was designed to investigate whether radiographic features of knee osteoarthritis (OA) in patients with poorly controlled, insulin-resistant type II diabetes mellitus differ from those in nondiabetic controls with knee OA. METHODS: Radiographs from 25 female patients with diabetes and knee OA were compared with those from 48 female controls who were similar with respect to age, weight, and duration of OA symptoms. RESULTS: Although the 2 groups were similar with respect to the frequency and severity of joint space narrowing, subchondral sclerosis, and geodes, osteophytes were less common in the patients with diabetes (P = 0.044), and spurring, when present, tended to be "marked" less often in the diabetic patients than in the controls. CONCLUSION: The data suggest that diminished availability of insulin at the cellular level or diabetic microvascular disease attenuates the chondro- and osteogenesis required for osteophyte formation in the joints of patients with OA.

Neurogenic acceleration of osteoarthrosis. The effects of previous neurectomy of the articular nerves on the development of osteoarthrosis after transection of the anterior cruciate ligament in dogs.

The development of osteoarthrosis in unstable knee joints of dogs after transection of the anterior cruciate ligament is greatly accelerated when the afferent nerve fibers from the ipsilateral hindlimb have been interrupted by dorsal root ganglionectomy before transection. The purpose of the current study was to determine whether partial loss of the afferent fibers from the knee joints of dogs, accomplished by neurectomy of the primary articular nerves before transection of the ligament, also accelerates the development of osteoarthrosis. Osteoarthrosis did not develop in dogs that had had transection of the medial, posterior, and lateral articular nerves to the left knee joint but had an intact anterior cruciate ligament. Osteoarthrosis developed in all dogs that had had transection of the anterior cruciate ligament. However, the osteoarthrotic lesions, as gauged by histological and macroscopic criteria, were more frequent and severe in dogs that had had neurectomy before transection than in those that had intact sensory nerves and an unstable joint (p less than or equal to 0.05). A subchondral fracture occurred in three dogs that had had neurectomy and had an unstable joint but in none of the dogs that had intact sensory nerves and an unstable joint.

Comparative analysis of total knee arthroplasty in two health care delivery systems.

A prospective, concurrent comparison of patients undergoing total knee arthroplasty in two different health care delivery systems was carried out. All patients had osteoarthritis, and received treatment between September 1983 and September 1987 under the supervision of a single staff physician. There were 26 total knee arthroplasties performed at the University Hospital (UH) and 22 performed at the Department of Veterans Affairs Medical Center (VAMC). The average patient age at the UH was 73 years (range, 58-87 years). The corresponding average age at the VAMC was 67 years (range, 56-78 years). Statistically significant differences between the two health care delivery systems were noted in preoperative length of hospital stay (P less than .001), postoperative length of hospital stay (P less than .001), total length of hospital stay (P less than .001), and postoperative knee range of motion at 1 and 2 years. Overall complications in the UH patient group (23% of knees) were lower than the VAMC (68% of the knees) (P = .05). Our university health care delivery system has both short- and long-term patient benefits as compared to the VAMC studied.

Comparison of computerized digital and film-screen radiography: response to variation in imaging kVp.

A controlled prospective study, in an animal model chosen to simulate portable neonatal radiography, was performed to compare the response of the Philips Computed Radiography (CR) system and conventional 200 speed film-screen (FS) to variation in imaging kVp. Acceptable images were obtained on the CR system over a very wide kVp range. In contrast the FS system produced acceptable images over a narrow kVp range. This ability suggests that the CR system should eliminate the need for repeat examinations in cases where a suboptimal kVp setting would have resulted in an unacceptable FS image. CR technology should therefore be ideally suited to portable radiography especially in situations where selection of correct exposure factors is difficult as in the neonatal nursery.

Correlation of serum concentrations of ibuprofen stereoisomers with clinical response in the treatment of hip and knee osteoarthritis.

Stereoselective pharmacokinetic measurements of the active enantiomer, S-ibuprofen, were correlated with clinical response in 45 participants in a randomized double blinded 4 week comparison of ibuprofen, 1200 or 2400 mg/day, for treatment of hip or knee osteoarthritis. Ibuprofen dose correlated with S-ibuprofen area under the serum concentration curve (AUC), trough and average concentration, but not with clinical outcome. AUC of S-ibuprofen correlated with improvement in disability, rest pain and in the physician's global assessment (p = 0.02, 0.08, and 0.10, respectively), and negatively with the subject's weight and creatinine clearance (p = 0.09 and 0.07, respectively). Some individual variation in responsiveness to ibuprofen (and other nonsteroidal antiinflammatory drugs) may be attributed to pharmacokinetic differences.

Predicting post-hospital discharge health care costs.

Patients in this study represented an important group for health services research; their postdischarge costs were high, resulted from readmissions (especially for nonelective reasons), and were incurred by a minority of patients. Moreover, intensive interventions delivered by ambulatory care providers has the potential to reduce overall costs if patients at highest risk for readmission could be identified prospectively (Smith et al., 1988; Weinberger et al., 1988). We developed a model to predict post-hospital discharge costs in these patients using strategies to maximize their predictive capability. Although the model appeared to account for more variance in costs than currently available models in the derivation set, its performance in the validation set, albeit statistically significant, was disappointing. Because we considered a broad array of predictors, expanding the number of patient-oriented variables may not be fruitful. Instead, future research may need to consider more homogenous subgroups of patients in whom specific laboratory tests would have clinical significance; variance in providers' behaviors; and studies in health maintenance organizations, where control over resource utilization may make costs more predictable. Finally, empirically derived models must be tested in an independent sample. Without validating predictive models, the models' ability to predict health care costs may be overestimated.

Digital imaging with a photostimulable phosphor in the chest of newborns.

To evaluate use of a digital photostimulable phosphor imaging system in the neonatal nursery, 150 newborns were divided into three groups of 50. In the first two groups, screen-film and computed radiographs of the chest were obtained at the same radiation exposure; in the third group, computed radiographs were obtained with a 50% dose reduction (half-exposure computed radiographs). All images were blindly evaluated by three readers who scored the quality of visualization of the mediastinum, lung, bone, soft tissues, and endotracheal and nasogastric tubes, and also image density. No statistical differences in visualization of tubes existed among the three groups. Visualization of the mediastinum, lung, bones, and soft tissues was statistically significantly better on computed radiographs than on half-exposure computed radiographs; visualization of the lungs, bones, and soft tissues was statistically significantly better on screen-film radiographs than half-exposure computed radiographs. Image density was statistically better on computed and half-exposure computed radiographs than on screen-film radiographs.

Comparison of an antiinflammatory dose of ibuprofen, an analgesic dose of ibuprofen, and acetaminophen in the treatment of patients with osteoarthritis of the knee.

BACKGROUND: The optimal short-term, symptomatic therapy for osteoarthritis of the knee has not been fully determined. Accordingly, we compared the efficacy of a nonsteroidal antiinflammatory drug, ibuprofen, given in either an antiinflammatory dose (high dose) or an analgesic dose (low dose), with that of acetaminophen, a pure analgesic. METHODS: In a randomized, double-blind trial, 184 patients with chronic knee pain due to osteoarthritis were given either 2400 or 1200 mg of ibuprofen per day or 4000 mg of acetaminophen per day. They were evaluated after a washout period of three to seven days before the beginning of the study, and again after four weeks of treatment. The major measures of outcome included scores on the pain and disability scales of the Stanford Health Assessment Questionnaire (range of possible scores, 0 to 3), scores on the visual-analogue scales for pain at rest and pain while walking, the time needed to walk 50 ft (15 m), and the physician's global assessment of the patient's arthritis. RESULTS: Seventy-eight percent of the patients completed four weeks of therapy. No significant differences were noted among the three treatment groups with respect to failure to complete the trial because of noncompliance or adverse events. All three groups had improvement in all major outcome variables, and the groups did not differ significantly in the magnitude of improvement in most variables. The mean improvement (change) in the scores on the pain scale of the Health Assessment Questionnaire was 0.33 with acetaminophen (95 percent confidence interval, 0.14 to 0.52), 0.30 with the low dose of ibuprofen (95 percent confidence interval, 0.09 to 0.51), and 0.35 with the high dose of ibuprofen (95 percent confidence interval, 0.13 to 0.57). Side effects were minor and similar in all three groups. CONCLUSIONS: In short-term, symptomatic treatment of osteoarthritis of the knee, the efficacy of acetaminophen was similar to that of ibuprofen, whether the latter was administered in an analgesic or an antiinflammatory dose.

Comparison of indium-111 nonspecific polyclonal IgG with indium-111-leukocytes in a canine osteomyelitis model.

Osteomyelitis was surgically produced in the proximal tibia of ten dogs. A sham operation was performed on the other tibia. Early (3 hr) and late (20 hr) imaging was performed 1, 4, 7, 10, and 13 wk later, while the osteomyelitis progressed from acute to chronic. Indium-111-IgG had a significantly greater accumulation at the osteomyelitis site than 111In-leukocytes, both during early (p = 0.001) and late (p = 0.03) imaging, and at each of the weeks studied (p less than 0.001). During early imaging, both agents gave equivalent lesion to background ratios. On the late images, the 111In-leukocytes gave significantly higher lesion-to-background ratios than 111In-IgG (p less than 0.001) and higher ratios than they did during the early images (p less than 0.001). Both agents had greater accumulation in acute osteomyelitis than in chronic osteomyelitis (p less than 0.02). Osteomyelitis in the surgical site can be distinguished from the uptake in the sham surgery site using 111In-leukocytes, but not when using 111In-IgG.

The presence of cartilage matrix glycoprotein in serum as determined by immunolocation analysis is not a sensitive indicator of "early" osteoarthritis of the knee.

Widespread effort is being devoted to the search for a serologic "marker" that could aid in the early diagnosis of osteoarthritis and in following the progression of the disease in response to treatment. It is obvious that such a marker would have its greatest utility in patients with mild or early osteoarthritis. CMGP is a disulfide-bonded 550,000 dalton cartilage matrix glycoprotein with a half-life of only 48 to 72 hours that has been found, through immunolocation analysis, in the serum of dogs with experimentally induced osteoarthritis and in the synovial fluid of patients with osteoarthritis but not other types of arthritis. To determine whether detection of CMGP in serum might be of value in identifying patients with "early" osteoarthritis, we examined serum samples from 26 patients with knee pain who had articular cartilage lesions of osteoarthritis at arthroscopy but whose knee radiographs were normal or showed only mild or moderate osteoarthritis. CMGP was identified by immunolocation analysis with specific antibodies. Eleven patients (42%) were seropositive for CMGP. In two, the degenerative cartilage lesions visualized at arthroscopy were mild (grade 2); in the other nine they were more severe (grade 3 or 4). However, 10 of the 15 seronegative patients also had grade 3 or 4 cartilage degeneration. Thus, this serum assay for CMGP was often negative in this group of patients in the presence of well-defined cartilage degeneration.

Relationship between arthroscopic evidence of cartilage damage and radiographic evidence of joint space narrowing in early osteoarthritis of the knee.

We examined the relationship between articular cartilage degeneration, as visualized arthroscopically, and joint space narrowing (JSN) in standing anteroposterior knee radiographs of 161 patients with chronic knee pain. The majority of these patients had radiographic findings of mild osteoarthritis. Twenty-five (33%) of the 76 patients in the series whose radiographs showed tibiofemoral JSN had grossly normal articular cartilage in both tibiofemoral compartments at arthroscopy (false-positive). The specificity of medial JSN for the presence of medial compartment articular cartilage degeneration was 0.61, i.e., only 61% of patients with normal (grade 0) medial compartment cartilage had a normal medial joint space. Of 22 patients with greater than 50% medial JSN, 9 (41%) had normal articular cartilage in the medial compartment at arthroscopy. Of 6 patients with greater than 50% lateral JSN, 3 (50%) had normal lateral compartment articular cartilage at arthroscopy. Among 36 patients with greater than 25% JSN who had neither medial nor lateral compartment articular cartilage degeneration, JSN was associated with articular cartilage degeneration in the patellofemoral compartment in 8 (22%), with meniscus degeneration in 18 (50%), and with both in 8 (22%). Thus, in these patients with chronic knee pain, radiographic evidence of JSN in the tibiofemoral compartment did not permit confident prediction of the status of the articular cartilage.

A behaviorally effective model for training of general health professionals by a rheumatology team.

This project evaluated a model for inservice arthritis education based in part on principles of applied behavior analysis. Thirty-seven public health nurses (PHN) from 10 rural midwestern counties received instruction about screening and management of patients with arthritis; a random half of counties also received public and physician information interventions designed to increase arthritis referrals to community physicians under specific circumstances. In clinic interviews with patients of PHN showed modest, but significant, increases in 14 of 16 target behaviors attributable to inservice education. Because measured arthritis impact was low in this older adult population, physician referral rates were not affected by either intervention. This model illustrates generalizable behavior modification guidelines that are useful adjuncts to traditional procedures for development of professional arthritis education.

Megaloblastic hematopoiesis in vitro. Interaction of anti-folate receptor antibodies with hematopoietic progenitor cells leads to a proliferative response independent of megaloblastic changes.

We tested the hypothesis that anti-placental folate receptor (PFR) antiserum-mediated effects on hematopoietic progenitor cells in vitro of increased cell proliferation and megaloblastic morphology were independent responses. We determined that (a) purified IgG from anti-PFR antiserum reacted with purified apo- and holo-PFR and specifically immunoprecipitated a single (44-kD) iodinated moiety on cell surfaces of low density mononuclear cells (LDMNC); (b) when retained in culture during in vitro hematopoiesis, anti-PFR IgG (in contrast to PFR-neutralized anti-PFR IgG and nonimmune IgG) consistently led to increased cloning efficiency of colony forming unit-erythroid (CFU-E), burst forming unit-E (BFU-E), CFU-granulocyte macrophage (CFU-GM), and CFU-GEM megakaryocyte (CFU-GEMM), and objectively defined megaloblastic changes in orthochromatic normoblasts from CFU-E- and BFU-E-derived colonies; (c) when anti-PFR antiserum was removed after initial (less than 1 h) incubation with LDMNC, a cell proliferation response was induced, but megaloblastic changes were not evident. (d) Conversely, delay at 4 degrees C for 24 h before long-term plating with antiserum resulted in megaloblastosis without increased cell proliferation; (e) however, 500-fold molar excess extracellular folate concentrations completely abrogated the expected anti-PFR antiserum-induced megaloblastic changes, without altering cell proliferative responses. Thus, although cell proliferative and megaloblastic changes are induced after short-term and prolonged interaction of antibody with folate receptors on hematopoietic progenitors, respectively, they are independent effects.

Synovial inflammation in patients with early osteoarthritis of the knee.

While synovitis is common in advanced osteoarthritis (OA), its prevalence and severity in patients with early or mild OA are uncertain. In our study synovial biopsies from patients with arthroscopic evidence of OA whose radiographs were normal, or showed only mild/moderate changes of OA, were examined to determine the prevalence and severity of lining cell proliferation and mononuclear cell infiltration. Synovitis was present in only 16 of 29 patients (55%) who underwent arthroscopy because of chronic knee pain and were found to have OA; no synovium from 50% of the 22 patients in this group with full thickness cartilage ulceration showed infiltration with mononuclear cells. Similarly, no evidence of synovitis was seen in biopsies from 7 of 14 additional patients with OA who did not have knee pain but who underwent arthroscopy to evaluate joint instability. An association was seen between synovial mononuclear cell infiltration and thickness of the synovial lining cell layer (p less than 0.03), but lining cell hyperplasia was found in samples from only 12% of the patients with OA in our series. The severity of OA cartilage lesions was unrelated to severity of synovitis and no topographic relationship was found between cartilage ulceration and synovitis.

Effects of tiaprofenic acid on the concentration and metabolism of proteoglycans in normal and degenerating canine articular cartilage.

The effects of tiaprofenic acid (TPA), a nonsteroidal antiinflammatory drug with high potency as a cyclooxygenase inhibitor, on the metabolism of normal and degenerating articular cartilage were examined. When present in the culture medium in clinically relevant concentrations encompassing those achieved in synovial fluid of patients treated with the drug, TPA had no significant effects on net proteoglycan synthesis in organ cultures of normal, osteoarthritic or atrophic canine articular cartilage. When fed to dogs for 8 weeks in a daily dose of 100 mg, TPA had no apparent effect on cartilage water content or uronic acid concentration. The suppression of net cartilage proteoglycan synthesis caused by immobilization was not affected by administration of TPA nor did the drug affect the proportion of newly synthesized glycosaminoglycans recovered from the spent culture medium, suggesting that it did not increase proteoglycan catabolism or affect the integrity of the cartilage matrix.

Statistical analysis of epidemiologic data of pregnancy outcomes.

In this paper, a generalized logistic regression model for correlated observations is used to analyze epidemiologic data on the frequency of spontaneous abortion among a group of women office workers. The results are compared to those obtained from the use of the standard logistic regression model that assumes statistical independence among all the pregnancies contributed by one woman. In this example, the correlation among pregnancies from the same woman is fairly small and did not have a substantial impact on the magnitude of estimates of parameters of the model. This is due at least partly to the small average number of pregnancies contributed by each woman.