A comparison of survival of moulded monoblock and modular tibial components of 751 AGC total knee replacements in the treatment of rheumatoid arthritis.

We evaluated the survival of moulded monoblock and modular tibial components of the AGC total knee replacement in patients with rheumatoid arthritis. Between 1985 and 1995, 751 knees with this diagnosis were replaced at our institution. A total of 256 tibial components were of the moulded design and 495 of the modular design. The mean follow-up of the moulded subgroup was 9.6 years (0.5 to 14.7), and that of the modular group 7.0 years (0.1 to 14.7). The groups differed significantly from each other in Larsen grade, cementing of components and patellar resurfacing, but no statistically significant difference between the survival of the components was found (Log rank test, p = 0.91). The cumulative success rate of the moulded group was 96.8% (95% confidence interval 93.6% to 98.4%) at five years and 94.4% (95% confidence interval 90.4% to 96.7%) at ten years, and of the modular group 96.2% (95% confidence interval 94% to 97.6%) and 93.6% (95% confidence interval 89.7% to 96%), respectively. Revision was required in 37 total knee replacements, the main causes were infection, pain, loosening of the tibial component and patellar problems. Survival rates for both components were satisfactory.

Patellar resurfacing reduces pain after TKA for juvenile rheumatoid arthritis.

Influence of patellar resurfacing after knee replacement and the frequency of patella infera and its relation to the postoperative appearance of the knee pain were assessed in patients with juvenile rheumatoid arthritis. Seventy-seven total knee arthroplasties using the AGC prosthesis with nonconstrained components were done on 52 patients with a mean followup of 7.3 years (range, 3-13 years). Anterior knee pain was present in 14 of 30 patients (47%) with an unreplaced patella and in two of 18 patients (11%) with patella resurfacing. The patella was replaced in 18 patients (35%) and in 23 of 77 knees (30%). Neither revision surgery of implanted patellar components nor any later resurfacing of an unreplaced patella were done during the followup. Preoperatively using the Insall-Salvati ratio, the majority of knees (54 of 77) had a low-riding patella. Patella infera occurred commonly in patients with juvenile rheumatoid arthritis. No connection between patella infera and anterior knee pain was found.

Comparison of 99mTc ciprofloxacin, 99mTc white blood cell and three-phase bone imaging in the diagnosis of hip prosthesis infections: improved diagnostic accuracy with extended imaging time.

The purpose of this study was to compare the utility of 99mTc labelled ciprofloxacin (Infecton) imaging with the 99mTc white blood cell and three-phase bone imaging procedures for identifying hip prosthesis infection. We studied 30 symptomatic patients in whom infection was confirmed in eight and excluded in 22 cases based on clinical and microbiological findings. 99mTc ciprofloxacin images were obtained at 1, 4 and 24 h after the injection of the tracer, and the data were compared to those obtained from 99mTc leukocyte and three-phase bone imaging. The 99mTc ciprofloxacin imaging correctly identified all true infections. In 13 (59%) of the non-infected patients, non-specific uptake of 99mTc ciprofloxacin was found in the 1-h and 4-h images, which disappeared, however, in the 24-h images. When the early and late 99mTc ciprofloxacin images were compared, the specificity was found to improve from 41% to 95%, positive predictive value from 38% to 89%, and the diagnostic accuracy from 57% to 97%. The accuracy of the conventional 99mTc leukocyte imaging was 90%. Dynamic bone imaging also yielded abnormal findings in all the infected patients although also in 23% of the non-infected patients. Current data indicate that 99mTc ciprofloxacin is a useful method for confirming hip prosthesis infection. The diagnostic efficiency of this method is improved when the imaging time is extended to 24 h post-injection of the tracer.

Dual Articular Knee in demanding primary and revision replacements in patients with rheumatic diseases.

We report the results of 25 total knee replacements in 24 patients with rheumatoid arthritis (RA) using the Dual Articular Knee prosthesis. There were four primary and 21 revision procedures. The main indication was severe joint instability. In four infected arthroplasties a two-stage revision procedure was used. Four patellar tendon avulsions and one deep infection were encountered. Results were excellent in 18 patients. Dual Articular Knee proved to be favourable in both demanding primary as well as revision arthroplasties in patients with RA.

99m Tc-ciprofloxacin (Infecton) imaging in the diagnosis of knee prosthesis infections.

The purpose of this study was to evaluate the usefulness of 99mTc labelled ciprofloxacin imaging in detecting the presence of infection in patients with symptomatic knee prostheses. Among 16 randomly selected patients of whom seven had infection based on clinical and microbiological findings and nine did not, 99mTc-ciprofloxacin images were obtained at 1, 4 and 24h after the injection of the tracer. While there was some diffuse non-specific accumulation of 99mTc-ciprofloxacin in large synovial joints and in prosthetic knee joints, the infected knee prostheses were found to show more intensive focal uptake, which also extended outside the synovial cavity. The infection related uptake remained visible in the 24h images, whereas non-specific uptake had a fading tendency at this time point. 99mTc-ciprofloxacin imaging showed diagnostic sensitivity of 86% and a specificity of 78% for correctly classifying the presence of infection. The data indicate that 99mTc-ciprofloxacin imaging may be used in the diagnosis of knee prosthesis infections. Infection-related uptake remains visible in the 24h images and is typically found also outside the synovial cavity, which should be noted in the evaluation of the images.

Improved method for detecting knee replacement infections based on extended combined 99mTc-white blood cell/bone imaging.

The purpose of this study was to evaluate whether an extension of the imaging time to 24 h post-injection improves the diagnostic accuracy of technetium-99m-hexamethylpropyleneamine oxime (99mTc-HMPAO) leucocyte imaging in detecting knee replacement infections. Thirty patients were studied, with infection confirmed in eight (27%) and excluded in 22 on the basis of clinical and microbiological findings. Leucocyte imaging was carried out at 2-4 h (routine images) and at 24 h (late images) post-injection. For comparison, bone imaging with technetium-99m-hydroxydiphosphonate (99mTc-HDP) was carried out at arterial, soft tissue and metabolic phases. Late leucocyte imaging was found to be more sensitive (100% vs. 87.5%) and more specific (82% vs. 77%) than routine leucocyte imaging in detecting infections. All the bone imaging methods showed a sensitivity of 100%, whereas the specificity varied from only 5% to 23%. All procedures had high negative predictive values (NPVs) (94 to 100%) for excluding infection. However, the positive predictive value (PPV) was only 28 to 32% for bone imaging and 58% for routine leucocyte imaging, whereas late leucocyte imaging showed a PPV of 67% and a diagnostic accuracy of 87%. The data indicate that late leucocyte imaging may be superior to routine leucocyte imaging for examining patients with symptomatic knee replacements.

Charnley total hip arthroplasty in ankylosing spondylitis: survivorship analysis of 76 patients followed for 8-28 years.

76 consecutive Charnley low friction hip arthroplasties were performed in 54 (37 men) patients with ankylosing spondylitis from 1971 to 1991 in the Rheumatism Foundation Hospital. Their mean age was 40 (16-67) years. They were followed until the end of 1999. The overall prosthesis survival was 80% at 10 years, 66% at 15 years and 62% at 20 years. The survival of the acetabular component was 91%, 77% and 73% at 10, 15 and 20 years and that of the femoral component 82%, 79% and 77%, respectively. We found no significant risk factor that predicted prosthesis survival.

Extended combined 99mTc-white blood cell and bone imaging improves the diagnostic accuracy in the detection of hip replacement infections.

Although the diagnosis of hip prosthesis infection is clinically important, X-ray studies, blood chemistry and synovial fluid aspiration may be unreliable for this purpose. The aim of this study was to evaluate whether extending the time for technetium-99m labelled leucocyte imaging to 24 h post injection improves the accuracy of diagnosis of hip replacement infections. We studied 64 symptomatic patients with hip prostheses. The presence of infections was verified by intraoperative bacterial cultures, and infection was excluded either by negative operative findings or by follow-up for at least 1 year. Leucocyte imaging was done with 99mTc-hexamethylpropylene amine oxime (HMPAO)-labelled leucocytes at 2-4 h (routine images) and at 24 h (late images) after the injection of the leucocytes. In addition, bone imaging was carried out with 99mTc-hydroxydiphosphonate (HDP) at the arterial, soft tissue and metabolic phases. A standardised method was used to compare leucocyte images with bone metabolic images. In this material, there were six confirmed infections. All the bone imaging methods had a sensitivity of 100% in detecting prosthesis infections whereas the specificity varied from only 2% to 82%. Routine leucocyte imaging was less sensitive (50% vs 83%) and less specific (90% vs 100%) than late leucocyte imaging. All tests had a high negative predictive value for excluding infection (95%-100%). However, both bone (10%-38%) and routine leucocyte imaging (33%) showed a poor positive predictive value (PPV), whereas late leucocyte imaging had a PPV of 100% and a diagnostic accuracy of 98%. We conclude that late leucocyte imaging improves the specificity of diagnosis of infected hip prostheses. This type of imaging procedure should be combined with three-phase bone scintigraphy in studies of patients with painful joint replacement.

Survivorship of AGC knee replacement in juvenile chronic arthritis: 13-year follow-up of 77 knees.

This study analyzed the survivorship and results of 77 knee replacements in 52 patients with juvenile chronic arthritis using the nonconstrained Anatomically Graduated Components (AGC; Biomet, Warsaw, IN) prosthesis design. Patients were operated on between the years 1985 and 1995. The mean duration of the general disease was 24 years (range, 10-56 years), and the mean age of the patients at the time of surgery was 33 years (range, 16-64 years). Bone-grafts were installed into 15 knees, custom-made components were used in 5 knees, and cemented fixation in 4 knees. The patella was resurfaced in 23 knees. Clinical follow-up examinations were conducted 3 months, 1 year, 4 years, and 8 years postoperatively. An interview was arranged at the end of 1998, 3 to 13 years after surgery; 2 patients were not reached, and 2 died during the follow-up. Fifty-five of 73 (75%) knees were subjectively excellent, 18 (25%) were fair, and none was poor. Radiolucent lines of 1.0 to 1.5 mm were found under 14 tibial trays but not adjacent to femoral components. No deep infections were detected. One knee was revised 4 years after the implantation. The overall survival was 99% (95% confidence interval, 92-100) at 5 years. We consider these results excellent in this demanding patient material. The nonconstrained AGC prosthesis with cementless fixation proved to be feasible in knee replacement in patients with juvenile chronic arthritis.

RT-PCR from eosinophil-depleted leukocytes without RNA extraction: cell selection using streptavidin PCR tubes.

OBJECTIVES: The major RNase activity of leukocytes has been attributed to eosinophil-derived neurotoxin EDN. Depletion of eosinophils enables RT-PCR from 10(5) leukocytes without RNA extraction. In this study we introduced streptavidin-coated PCR tube strips for the selection of eosinophil-free leukocytes for RT-PCR analysis. DESIGN AND METHODS: Polypropylene 0.2 ml PCR tube strips were coated with streptavidin and biotinylated antibodies against cell surface antigens were attached to the tubes. CD7-positive T-lymphocytes, CD19-positive B-lymphocytes and CD16-positive cells (mainly neutrophils and monocytes) were positively selected by incubating of 1-2 x 10(5) leukocytes in the antibody-coated PCR tubes for 30 min at 23 degrees C. RESULTS: The mean amount of cells bound into a tube was 31,500 (CV25%) T-cells and 8,600 (CV61%) B-cells from 12 blood samples, and 23,600 (CV22%) CD16+ cells from 17 samples. The influence of selected cell lysate on the RT-PCR analysis of Philadelphia chromosome (bcr/abl translocation) from 100 K562 cells was small: 78% (CV28%) of the leukocyte-free signal was obtained in the presence of CD16+ cells or 89% (CV15%) and 99% (CV11%) and in the presence of T-cells and B-cells, respectively. CONCLUSIONS: These results suggest that through the introduction of eosinophil-free cell population into RT-PCR a reproducible method with reasonable leukocyte yield and avoiding RNA extraction was developed.

Charnley low-friction arthroplasty in rheumatoid patients: a survival study up to 20 years.

The survivorship of 1,553 consecutive Charnley low-friction arthroplasties (LFA) in 1,086 patients with rheumatoid arthritis (RA) were analyzed. There were 846 women (1,236 hips) and 240 men (317 hips), with a mean age of 53.1 years (range, 24-77 years; standard deviation, 10.7). A uniform postoperative regimen with protected weight bearing for 2 months (6 months in patients with bone grafting on the acetabular side) was used throughout the whole study. The overall survival with revision as the endpoint was 90.5% (95% confidence interval [CI], 88.7-92.2) at 10 years and 83% (95% CI, 80.3-85.7) at 15 years. The survival of the femoral component was 93.2% (95% CI, 91.8-96.7) and 89.9% (95% CI, 88.0-93.0) at 10 and 15 years, and survival of the acetabulum was 93.6% (95% CI, 92.1-95.1) and 87.1% (95% CI, 84.6-89.5) at 10 and 15 years. The indication for revision was late deep infection in 19 patients (1.2%) and in others aseptic loosening of prosthetic components. Young age, male sex, and secondary reactive amyloidosis impaired significantly the survival of LFA in the RA patients. In all, cemented LFA provided good results, and it can be justified for the treatment of hip destruction in RA.

Major interference from leukocytes in reverse transcription-PCR identified as neurotoxin ribonuclease from eosinophils: detection of residual chronic myelogenous leukemia from cell lysates by use of an eosinophil-depleted cell preparation.

BACKGROUND: The extraction of RNA from leukocytes for reverse transcription-PCR (RT-PCR) is time-consuming and contributes to variation in analysis of the Philadelphia (Ph1) chromosome of chronic myelogenous leukemia (CML) by RT-PCR. To detect residual CML after bone marrow transplantation, mRNA from at least 10(5) leukocytes should be analyzed, but the RNase activity of the cells precludes simple leukocytes lysis as an alternative to RNA extraction. We sought to identify the main source of RNase activity of leukocytes. METHODS: We used a three-step chromatographic process and amino acid sequence analysis. We selected eosinophil-free granulocytes by using a biotinylated CD16 antibody and selected mononuclear cells by fractionating the leukocytes with a Ficoll-Paque(R) density gradient. RESULTS: Chromatography and amino acid sequencing identified eosinophil-derived neurotoxin (EDN) as the main source of leukocyte RNase. Depletion of eosinophils reduced the EDN content of cell lysates by approximately 90%, allowing a signal from a lysate of 50 K562 Ph1-positive cells mixed with 10(5) CD16(+) granulocytes that was equivalent to 77% of the signal in the absence of leukocytes. A similar lysate with mononuclear cells gave a signal equivalent to 53% of that without mononuclear cells. RNA extraction gave a signal equivalent to only 24% of the leukocyte-free control. CONCLUSION: The depletion of eosinophils during the preparation of leukocyte samples for RT-PCR efficiently reduces the risk of mRNA degradation by ribonucleases, enabling RT-PCR analysis directly from cell lysates with a better signal than can be obtained by RNA extraction.

Hip involvement in seropositive rheumatoid arthritis. Survivorship analysis with a 15-year follow-up.

In a prospective survey of recent arthritis 96 patients had erosive and seropositive rheumatoid arthritis (RA). Severe radiological changes in the hipjoint (Larsen grade 3-5) were observed in 31 (32%) and acetabular protrusion in five (5%) patients 15 years after the onset of arthritis. At the end of follow-up Larsen score 0-100 of peripheral joints (p < 0.015), HAQ (p < 0.001), ESR (p < 0.001), and CRP (p < 0.01) were significantly higher in patients with hip joint destruction than in those without. Secondary amyloidosis was found in eight patients with and in three patients without hip involvement (p = 0.002). In survivorship analysis (the Larsen 0-2 grade hips) an overall predicted rate of survival was 80% after 14 years of rheumatoid arthritis. When analyzed according to HLA-B27 the rate of radiological survival for the patients with a positive test was 62% and 87% for the others (p = 0.02). In conclusion, RA patients with high number of destructive peripheral joints (Larsen score) and high ESR or CRP should be carefully monitored due to the increased risk of hip destruction.

Proton NMR spectroscopy of the phospholipids in human uterine smooth muscle and placenta.

The parameters regulating the fluidity of myometrial and placental phospholipids include double bonds, fatty acid chain lenght and the cholesterol/phospholipid ratio. The transformation of these parameters was studied during pregnancy and labor. Myometrial and placental tissue samples were collected from 24 patients: 6 were nonpregnant, 6 early-pregnant, 6 late-pregnant not in labor and 6 in labor. After butanol extraction, tissue cholesterol and lipid phosphorus were determined. Proton NMR spectroscopy of the phospholipids was performed at 500 MHz. The myometrial cholesterol/phospholipid ratio was slightly elevated in pregnant patients not in labor. The uterine muscle of the nonpregnant patients contained more CH=CH groups in the phospholipids than that of the late-pregnant patients. There were 29 more double bonds in placental than in uterine tissue per 100 fatty acid molecules. The average fatty acid chain length varied from 14.0 to 18.8. The placenta has longer fatty acid chains than the uterine smooth muscle. The myometrial carbon chain was shortened on the average by 1.4 and the placental by 1.0 carbon atoms, when the patient went into clinical labor. These findings suggest fluidity changes in myometrial and placental phospholipids during human pregnancy and labor.

Carrageenan-induced changes in spinal nociception and its modulation by the brain stem.

Carrageenan was used to study inflammation-induced changes in spinal nociception and its brain stem modulation in the pentobarbitone-anesthetized rat. Carrageenan was administered intraplantarly into one hindpaw 2 h before the start of electrophysiological single unit recordings of wide-dynamic range (WDR) neurons of the spinal dorsal horn. Carrageenan produced a significant leftward shift in the stimulus-response function for mechanical stimuli, whereas that for noxious heat stimuli was short of statistical significance. Conditioning electrical stimulation in the rostroventromedial medulla (RVM) significantly attenuated noxious heat-evoked, but not mechanically evoked, responses to spinal dorsal horn WDR neurons in the control (contralateral) side. However, in the carrageenan-treated side RVM stimulation had no significant effect on mechanically or noxious heat-evoked responses. Following direct spinal administration of neuropeptide FF (NPFF), noxious heat-evoked responses, but not mechanically evoked responses, were attenuated by RVM-stimulation also in the carrageenan-treated side. This selective NPFF-induced enhancement of brain stem-spinal inhibition was not reversed by naloxone. The results indicate that carrageenan-induced inflammation significantly changes the response properties of spinal nociceptive neurons and their brain stem-spinal modulation. During inflammation, NPFF in the spinal cord produces a submodality-selective potentiation of the antinociceptive effect induced by brain stem-spinal pathways, independent of naloxone-sensitive opioid receptors.

The effect of a selective alpha2-adrenoceptor antagonist on pain behavior of the rat varies, depending on experimental parameters.

Effects of atipamezole, an alpha2-adrenoceptor antagonist, in various acute pain tests were studied in the rat. Atipamezole (at doses > or = 0.1 mg/kg I.P.) and idazoxan, another alpha2-adrenoceptor antagonist (2.5 mg/kg, I.P.), increased licking latency in the hot-plate test. Bilateral administration of atipamezole (10 microg) into the locus coeruleus did not increase licking latency in the hot-plate test. Medetomidine (an alpha2-adrenoceptor agonist; 1-3 mg/kg) or repeated pre-exposures to the testing apparatus reversed the effect of atipamezole (1.5 mg/kg) in the hot-plate test. Atipamezole also increased the latency to mechanically induced licking/biting response at a dose of 1.5 mg/kg, but not at lower doses. In the heat-induced tail-flick test, in contrast, atipamezole at doses of 0.1 and 1.5 mg/kg produced a medetomidine-reversible decrease of response latencies. This facilitation of the tail-flick response disappeared if the intensity of the heat stimulus was high. At a dose range from 0.03 to 1.5 mg/kg atipamezole did not significantly alter the paw withdrawal latency to noxious mechanical stimulation, nor pain behavior in the formalin test. Responses to nociceptive spinal dorsal horn neurons were not modulated by atipamezole (1 mg/kg) in anesthetized spinalized rats. The results indicate that an alpha2-adrenoceptor antagonist may have variable effects in behavioral pain tests, depending on habituation of the experimental animals to the testing conditions, the dose of the drug, the type of behavioral response and the submodality or the intensity of the noxious test stimulus. The atipamezole-induced changes in pain behavior observed in this study may rather be explained due to action on motor expression of pain than due to modulation of nociception.

Involvement of nitric oxide and serotonin in modulation of antinociception and pressor responses evoked by stimulation in the dorsolateral region of the periaqueductal gray matter in the rat.

In rats anaesthetized with alphaxalone/alphadolone, electrical stimulation in the periaqueductal gray matter in the region lying lateral and dorsolateral to the aqueduct produced a pressor response and an increase in the latency of the tail flick response to noxious heat applied to the tail. The antinociception and the pressor response were significantly attenuated following microinjection of 15 nmol 5-hydroxytryptamine at the site of stimulation in the periaqueductal gray matter. Microinjection of an equal volume of 165 mM saline had no effect. The inhibitory effects of 5-hydroxytryptamine were blocked by prior intracerebroventricular administration of 100 microg of the nitric oxide synthase inhibitor L-nitroarginine methyl ester. Neither 5-hydroxytryptamine or L-nitroarginine methyl ester had any effect on resting arterial pressure or on the baseline latency of the tail flick reflex. It is suggested that the inhibitory effects of 5-hydroxytryptamine in the dorsolateral periaqueductal gray matter are normally dependent on the functional integrity of local nitric oxide synthase-containing interneurons. Nitric oxide may act in association with 5-hydroxytryptamine to control the excitability of the aversive system in the midbrain.

Survivorship of the Charnley total hip arthroplasty in juvenile chronic arthritis. A follow-up of 186 cases for 22 years.

Between 1971 and 1991 we performed Charnley low-friction arthroplasty (LFA) on 116 patients (186 hips) with juvenile chronic arthritis (JCA). We have now carried out a survival study, taking endpoints as revision, death or the end of the year 1993. Overall survival was 91.9% at ten years and 83.0% at 15 years. That of the femoral component was 95.6% at ten years and 91.9% at 15 years and of the acetabulum 95.0% and 87.8%, respectively. Only the use of steroids significantly impaired the survival. We therefore recommend the use of Charnley LFA for young patients with JCA requiring total hip replacement.

Role of nitric oxide and serotonin in modulation of the cardiovascular defence response evoked by stimulation in the periaqueductal grey matter in rats.

In rats anaesthetised with alphaxalone/alphadolone, electrical stimulation (10 s trains of 1 ms pulses at 80 Hz, 40-80 microA) in the dorsolateral and lateral periaqueductal grey matter (PAG), the midbrain defence area, evoked a pressor response with tachycardia and vasodilatation in the hindlimb. Microinjection of 200 nl 0.66 mM 5HT, but not 200 nl 165 mM NaCl, at the site of stimulation attenuated the components of the PAG-evoked response by 75-98%. The effect of 5HT was significantly reduced by prior intracerebroventricular injection of 100 microg N-nitro-L-arginine methyl ester (an inhibitor of nitric oxide synthase) but not N-nitro-D-arginine methyl ester. Resting cardiovascular parameters did not change significantly following any of these manipulations. The results suggest that serotonin exerts an inhibitory modulation on the excitability of the midbrain defence area by a mechanism which involves nitric oxide.

Measurement of protein concentration of aqueous humour in vivo: correlation between laser flare measurements and chemical protein determination.

We studied the correlation between laser flare cell meter photon count/ms and actual protein concentration both in vitro and in vivo. Laser flare cell meter measurement of human albumin concentrations of 0 to 10 g/l showed photon counts/ms from 0.3 +/- 0.3 to 78.9 +/- 3.9. There was a statistically highly significant linear correlation between photon count/ms and human albumin concentration (r = 0.98, p = 0.0001). Laser flare cell meter measurements were done on 39 cataract patients with the mean age of 77.9 +/- 6.7 years. Aqueous humour obtained by peroperative paracentesis was analysed for total protein. The mean photon count/ms before pupillary dilatation was 11.93 +/- 6.03. There was a significant linear correlation (r = 0.4, p = 0.019) between the photon count/ms after pupillary dilatation (mean 14.73 +/- 12.9, range 2.6-62.4) and anterior chamber protein concentration (mean 0.62 +/- 0.27, range 0.23-1.3 g/l) with the linear regression formula being y = 0.231 x -1.105 where y = log protein concentration (g/l) and x = log of photon count/ms. Laser flare cell meter photon counts/ms may be converted into an equivalent anterior chamber total protein concentration using this formula.