Adverse Tissue Reactions and Metal Ion Behavior After Small‐Head Metasul Hip Arthroplasty: A Long‐Term Follow‐Up Study

ObjectiveTo investigate the long‐term survivorship, incidence of adverse reactions to metal debris (ARMD), and metal ion behavior in patients who underwent small‐head Metasul metal‐on‐metal (MoM) total hip arthroplasty (THA).MethodsBetween February 1998 and September 2003, a retrospective study was performed on 43 consecutive patients (43 hips) who underwent unilateral cementless Metasul MoM THAs at our institution. Of them, 35 patients (nine males and 26 females) who were available for follow‐up more than 15 years after THA were enrolled in this study and underwent metal artifact reduction sequence magnetic resonance imaging (MARS‐MRI) to identify ARMD. The mean age at surgery of the patients was 59.7 years old (range, 31–83). Clinical and radiographic outcomes were evaluated retrospectively. Clinical examinations were conducted using the Harris Hip Score (HHS). Serum cobalt (Co) and chromium (Cr) ion levels and Co/Cr ratio were assessed at different postoperative periods of <5, 5–10, 11–14, and ≥15 years.ResultsThe mean follow‐up period for the 35 patients included was 18.1 years (range, 15–22). The mean HHS significantly improved from 44.6 ± 11.3 points preoperatively to 89.4 ± 7.9 points at the final follow‐up (P < 0.0001). ARMD was found in 20% of the patients using MARS‐MRI. No signs of stem loosening were found clinically or radiographically, whereas cup loosening and ARMD were observed in three patients (9%), for whom revision THAs were performed. The Kaplan–Meier survival rates with revision for any reason as the endpoint were 90.9% at 5 years, 84.8% at 10 years, 84.8% at 15 years (95% CI, 67.1–93.6), and 70.3% at 20 years (95% CI, 43.6–87.0). The survival rates with revision for ARMD as the endpoint were 100% at 5 years, 96.6% at 10 years, 96.6% at 15 years (95% CI, 77.2–99.7), and 80.1% at 20 years (95% CI, 45.3–95.2). Serum Co ion level peaked at 5–10 years after THA, which was significantly higher than that <5 years; however, it decreased to the initial level after 15 years. In contrast, serum Cr ion level significantly increased at 5–10 years and then remained almost constant. Significant differences in Cr ion levels (1.0 vs 2.0 μg/L, P = 0.024) and Co/Cr ratio (1.3 vs 0.9, P = 0.037) were found between non‐ARMD and ARMD patients at >11 years postoperatively.ConclusionOur results suggest that increased Cr ion levels and decreased Co/Cr ratio may be signs of ARMD in patients who underwent small‐head Metasul MoM THA.     

Viable myocardium identified by reinjection thallium-201 imaging: comparison with regional wall motion and metabolic activity on FDG-PET.

Reinjection thallium-201 scans were performed in 68 patients with coronary artery disease after the routine stress-delayed scans for more accurate identification of new fill-in. Following the stress and 3 hour delayed thallium-201 SPECT scans, 40 MBq (1.1 mCi) was injected at rest, and 10 min later, the reinjection SPECT scan was obtained. To determine whether the reinjection method can aid in identifying ischemic but viable myocardium, the thallium-201 findings were compared with regional wall motion on radionuclide ventriculography in 61 patients and with metabolic activity on positron emission tomography (PET) using F-18 fluorodeoxyglucose (FDG) in 18 patients. The reinjection scan identified new fill-in which had not been shown on the stress-delayed scans in 6 of the 22 patients (27%) or in 29 of the 105 segments (28%). Regional wall motion was preserved more in the segments that exhibited new fill-in after reinjection (wall motion score = 1.64 +/- 1.29) than in those without new fill-in (score = 2.72 +/- 1.04) (p < 0.01). In the comparative study with FDG-PET, persistent FDG uptake was observed in all segments with new fill-in (20/20 segments: 100%); whereas, it was seen in only 7 of the 28 segments (25%) without new fill-in after reinjection (p < 0.05). We concluded that the segments having new fill-in after reinjection may represent ischemic but viable myocardium. Thus, the reinjection thallium-201 scan should be performed to identify ischemic myocardium which occasionally cannot be detected by the routine stress-delayed thallium-201 scans.     

Determination of urinary Tamm-Horsfall protein by ELISA using a maleimide method for enzyme-antibody conjugation

A method for enzyme-antibody conjugation using a new maleimide derivative as coupling reagent has been developed. Since a monomeric conjugate of horseradish peroxidase and Fab' antibody could be readily prepared with high efficiency and reproducibility, the enzyme activity and antigen-binding activity were well preserved and nonspecific staining was greatly reduced. The conjugate is suitable for use in both ELISA procedures and immunohistochemistry. Using both methods we examined the pathophysiological significance of Tamm-Horsfall protein (THP) and the present study describes the ELISA method to quantify urinary THP using the new method with rabbit anti-THP antibody. A low concentration (0.04 M) of urea added to the urine samples increased the linearity of the standard curve and the sensitivity of the assay, permitting the detection of as little as 20 ng/ml THP. Freezing and thawing the urine resulted in variable or lower values of THP concentration. THP concentrations in urine as determined by ELISA were stable for at least one month after -70 degrees C storage, but not after -30 degrees C storage. There was no correlation between THP concentrations in 24 h urine samples and the morning urine of the same patient. These results suggest that it is essential to use fresh or -70 degrees C stored 24 h urine samples with added urea (0.04 M) for the determination of THP concentrations in urine by the present enzyme-antibody conjugation method. The THP concentration in normal 24 h urine of young children was found to be less than 51.8 mg/g Cr.     

Asynchronous filling in ischemic heart disease and hypertrophic cardiomyopathy

A multigated blood-pool study was performed to assess regional and global emptying and filling in 16 patients with hypertrophic cardiomyopathy (HCM), 43 patients with ischemic heart disease (IHD), and 14 controls. The regional volume curve was fitted using second-order harmonics in the Fourier series, while the global left-ventricular volume curve was fitted using third-order harmonics. As asynchronous indices, the standard deviations (SD) in distribution histograms of time to end-systole (TES), time to peak ejection (TPE), and time to peak filling (TPF) were obtained in the left ventricle. In patients with IHD, the TPF-SD was higher (14.4 +/- 11.3 degrees) than the TES-SD (7.8 +/- 5.1 degrees) and TPE-SD (8.1 +/- 5.9 degrees), suggesting the presence of asynchronous filling. In patients with HCM, the TPF-SD was also higher (11.6 +/- 11.1 degrees) than the TES-SD (3.5 +/- 2.4 degrees) and TPE-SD (6.2 +/- 4.4 degrees). The phase delay was localized in the anteroseptal or apical region in all 5 HCM patients with abnormal wall motion, while it corresponded with the region of abnormal wall motion in the patients with IHD. The TPF-SD was inversely correlated with the left-ventricular ejection fraction (r = -0.46), peak filling rate (r = -0.50), and the ratio of peak filling rate to peak ejection rate (r = -0.52), suggesting that asynchronous filling is related to global diastolic disturbance. We conclude that asynchronous filling is often present in patients with IHD and HCM, and that our technique can be used to obtain a quantitative assessment of regional asynchronous emptying and filling in these diseases.     

Inflammatory activity of a trypsin-like protease in the tuberculin reaction sites in guinea pig skin

A trypsin-like protease(s) was found in the extracts from tuberculin reaction sites in the guinea pig skin. Extractable enzyme activities were chronologically paralleled with the gross appearance of the inflammation, and the maximum activity from 24-hour old inflamed sites was about 12 times stronger than that from control skin, suggesting a potential role in the pathogenesis of the delayed hypersensitivity reaction (DHR). The enzyme suitably hydrolyzed t-butyloxycarbonyl-phenylalanyl-seryl-arginine 4-methylcoumaryl-7-amide, and was partially purified by gel filtration. It showed an apparent molecular weight of 700,000 with optimal pH of 9.0-9.5. The activity was inhibited by various serine protease inhibitors but not by thiol or metal protease inhibitors. It was relatively heat-stable. These findings suggest that the protease is similar to a trypsin-like protease from DHR to bovine gamma-globulin. Intradermal injection of the enzyme into normal guinea pigs induced a mixed neutrophil-mononuclear infiltrate. The reaction was reduced in intensity with the diisopropylfluorophosphate-inhibited enzyme preparation. The enzyme did not induce any increased vascular permeability. These findings suggest that the protease may be present generally in the DHR sites and probably participates in the cellular response of DHR.     

Myocardial blood flow and glucose metabolism in patients with myocardial infarction evaluated by positron emission tomography: comparison with left ventriculography

Myocardial positron emission tomography (PET) using N-13-ammonia (NH3) and F-18-fluorodeoxyglucose (FDG) was performed in 16 patients with myocardial infarction to assess myocardial blood flow and glucose utilization. These PET data were also compared by left ventriculography. N-13-ammonia PET study was performed at rest and after supine ergometer exercise as a measure of myocardial blood flow, and the F-18-FDG PET study was performed at rest after more than five hours' fasting as a measure of glucose utilization. The N-13-ammonia PET study revealed hypoperfused regions in 15 of 16 patients (94%) corresponding to the infarct regions identified by electrocardiography and by cardiac catheterization. In 12 of 16 patients (75%) these hypoperfused regions expanded with exercise. FDG uptake was observed in the hypoperfused regions, especially in stress-induced ischemic ones. Increased uptake of FDG was more often observed in patients with mildly hypokinetic wall motion on left ventriculography. However, FDG PET studies demonstrated diffuse uptake of FDG in some of the akinetic and dyskinetic segments.     

Quantitative analysis of regional wall motion by gated myocardial positron emission tomography: validation and comparison with left ventriculography

Electrocardiographically gated positron emission tomography (ECG-gated PET) with [13N] ammonia was used to assess regional myocardial wall motion of left ventricle (LV) based on a nongeometric method in nine healthy volunteers and 16 patients with coronary artery disease (CAD). Three transverse sections (upper, middle, and lower) with 16-mm intervals at end-diastole (ED) and end-systole (ES) were analyzed. The LV wall was divided into eight segments with every 30 degrees from septal wall to lateral wall. Based on circumferential profile analysis, the percent count increase [( ES count - ED count) divided ED count x 100) in each segment was analyzed as an index of regional wall motion. In the study of normal controls, the percent count increase was the lowest (32.9 +/- 7.2%) at septal wall of the lower slice and the highest (72.8 +/- 26.5%) at lateral wall of the upper slice (p less than 0.01). In five normal controls, the percent count increase was compared with the percent systolic wall thickening analyzed by magnetic resonance imaging, and a good correlation was observed (r = 0.84). In the study of patients with CAD, the percent count increase was compared with wall motion assessed by left ventriculography (LVG). The percent count increase significantly decreased as wall motion on LVG worsened. In addition, the value in normal controls tended to be higher than that in the segments with normal wall motion in patients with CAD. Thus, quantitative analysis of regional wall thickening was feasible by ECG-gated PET, which should be useful for combined analysis of regional function, perfusion and metabolism in patients with CAD.     

Deoxyribonuclease treatment prevents blood-borne liver metastasis of cutaneously transplanted tumour cells in mice.

Murine L5178Y-ML cells, when transplanted subcutaneously into the flank of (BALB/c x DBA/2)F1 mice, grew locally and always formed spontaneous metastases in the liver. Even after surgical removal of the primary tumour mass 5 or 7 days after tumour cell inoculation, all mice died due to liver metastases within 18 days. Using this model of tumour metastasis, we examined whether serine protease or deoxyribonuclease I (DNase I) would affect metastasis. Spontaneous liver metastasis of L5178Y-ML cells was enhanced by systemic administration of alpha-chymotrypsin at 3, 4 and 5 days or at 5, 6 and 7 days after tumour cell inoculation. This result was consistent with a previous report on blood-borne lung metastasis. In contrast, systemic administration of DNase I at 3, 4 and 5 days or at 5, 6 and 7 days after tumour cell inoculation inhibited liver metastasis. Neither treatment affected primary tumour growth. An influence of DNase I on tumour cell arrest in the microvasculature of the liver was suggested by scanning electron microscopy. DNase I treatment resulted in a statistically significant prolongation of the survival period, however, the effect was not satisfactory. A more striking anti-metastatic treatment resulting in a greater prolongation of the survival period was achieved by combining surgical removal of the primary tumour mass with DNase I treatment. These results suggest that DNase I could be a potential therapeutic agent used in conjunction with surgery to prevent clinical blood-borne metastasis.