Factors affecting aseptic loosening of 4750 total hip arthroplasties: multivariate survival analysis

Background  

Total hip arthroplasty is a successful surgery, that fails at a rate of approximately 10% at ten years from surgery. Causes for failure are mainly aseptic loosening of one or both components partially due to wear of articular surfaces and partially to design. The present analysis aimed to identify risk factors and quantify their effects on aseptic failure.     

Influences of natural menopause on health complaints: a prospective study of healthy Norwegian women.

As a continuation of a cross-sectional study in 1981 involving a representative sample of 1886 women between 45 and 55 years of age, 200 pre-menopausal subjects were selected randomly to take part in a follow-up study. Eighty-seven single measures covering 26 areas of health complaints which have been associated with the menopause in medical textbooks were investigated. A tentative method for relating health complaints at several time points to menopausal status is proposed. A significant number of women reported an increase in vasomotor complaints, vaginal dryness, heart palpitations and social dysfunction following the menopause, although many reported no change or even a reduction in these complaints. On the other hand, a decrease in headache and breast tenderness was noted. No significant differences were observed between the numbers of women reporting an increase or a decrease respectively on any of the other 69 measures (20 complaints), which included anxiety, depression and irritability. Further analyses indicated that the increase in social dysfunction was caused by hot flushes and sweating. This paper raises a number of issues regarding the methodology of longitudinal studies.     

Anterior lumbar fusion using a hybrid interbody graft

Summary This is a radiographic report of 40 patients (20 men, 20 women) who underwent anterior lumbar interbody fusions (73 levels) utilizing a “hybrid” interbody graft composed of femoral cortical allograft (FCA) bone and iliac crest cancellous autograft bone. The average age at surgery was 38 years (range 17–64 years), and follow-up averaged 1.4 years (range 1.0–2.4 years). Nineteen of the patients had undergone previous lumbar surgery. Thirty-two patients (63 levels) underwent anterior fusion combined with some type of posterior fixation, and eight patients (10 levels) had no posterior fixation. Types of posterior fixation included: for 20 patients (36 levels) Steffee variable screw placement fixation, for 10 patients (23 levels) translaminar facet screws (TFS), for 1 patient (3 levels) Knodt rods and for 1 patient (1 level) facet screws. Based on the persistence of lucent lines at the graft-host interface, three patients (one level each) were felt to have non-unions at their latest follow-ups at 1.4, 1.5 and 2.0 years, respectively. Two of these patients had no posterior fixation, and the other had TFS fixation. The overall fusion rate was 96% (70 of 73 levels). The fusion rate for all levels treated with posterior fixation was 98% compared with 75% for those without fixation. Intervertebral disc heights (IVDH) were measured on all films and corrected for magnification with computer assistance. On average, the IVDH was increased postoperatively but returned to preoperative values at follow-up. IVDH loss was independent of the type of instrumentation used. No complications arose from the use of the hybrid graft. Incorporation of the allograft portion of the graft is slow and was felt to be complete in only 7 of the 73 levels at follow-up. We conclude that the hybrid interbody graft technique is a safe and reliable method for performing anterior lumbar interbody fusions and should be combined with some type of posterior fixation. Long-term follow-up will be required to assess the behaviour of the allograft until incorporation is complete.     

Modulation of pro- and anti-apoptotic genes in lymphocytes exposed to bone cements

The ability of bone cements to modify the apoptotic program in activated immune cells and the mechanisms by which they act were evaluated. Mononuclear cells were collected from healthy individuals, cultured for 4 and 24 h with phytohemoagglutinina-P and cement extracts and then tested to assess: (a) cell viability; (b) early apoptotic events, by Annexin V/propidium iodide staining; and (c) the expression of pro- (p53, c-myc, ICE) and anti-apoptotic (bcl-2) genes. After 4 h three cements were able to increase significantly the percentage of apoptotic cells, while after 24 h no differences were found. The proportion of dead cells was not significantly changed at either culture time. The simultaneous expression of both pro-apoptotic (ICE, c-myc, p53) and antiapoptotic genes (bcl-2) was investigated only with regard to the materials which induced significant changes in apoptosis: two cements induced the p53 expression, while the third down-regulated bcl-2. As apoptosis regulates the balance of immune response, the authors recommend that the interaction between materials and immune cells should be assessed, so that the use of pro-apoptotic materials may be avoided in patients with immune defects.     

Sister chromatid exchanges and ion release in patients wearing fracture fixation devices

The quantification of sister chromatid exchange (SCE) during mitosis is a useful index for evaluating genotoxic effects in subjects occupationally or incidentally exposed to potentially toxic substances. The authors investigated the hypothesis that ions released by corrosion from prosthetic components of fracture fixation devices are associated with change in SCE incidence. In the present study, ten patients with implants were examined, and fifteen subjects with no implants were used as controls. SCE and high frequency cell (HFC) numbers were evaluated in circulating lymphocytes. In addition, nickel (Ni) and chromium (Cr) ion values in the serum were measured because, after iron, these metals are major components of stainless steel. A significant increase in SCE numbers was observed in patients compared to the control population (4.9 +/- 1.3 vs. 3.5 +/- 1.4). Ni concentration was 1.71 +/- 1.49 ng/mL in patients and 0.72 +/- 0.52 ng/mL in control subjects; Cr concentration was, respectively, 1.01 +/- 0.77 ng/mL and 0.19 +/- 0. 27 ng/mL. The increase of serum Cr and Ni was statistically significant. No correlation was found between the increased Cr concentrations and SCE number while Cr ion levels were found to be significantly correlated to HFC. An inverse correlation between Ni level and SCE numbers was observed. Our findings suggest that Cr release by stainless steel implants could have a genotoxic effect; thus it would be useful to carefully monitor implanted subjects with regard to serum ion dosage, SCE analysis, and HFC evaluation. In any case, it would be appropriate to remove the implant when fracture fixation is reached.     

Prediction models for insulin resistance in the polycystic ovary syndrome

Women with the polycystic ovary syndrome (PCOS) have a high prevalence of insulin resistance, with consequent increased risk of metabolic diseases later in life. An early metabolic screening would therefore be of clinical relevance. By using stepwise regression analysis on several variables obtained in 72 women with PCOS, we constructed simple and reliable mathematical models predicting insulin sensitivity, as measured by the euglycaemic hyperinsulinaemic clamp. The normal ranges of insulin sensitivity were calculated from 81 non-hirsute, normally menstruating women with normal ovaries, and similar body mass index (BMI) and age as the women with PCOS. Measured variables included BMI, waist and hip circumferences, truncal-abdominal skin folds, circulating concentrations of gonadotrophins, androgens, sex hormone-binding globulin (SHBG), triglycerides, total cholesterol and cholesterol subfractions, fasting insulin, C-peptide and free fatty acids. The three best prediction models included waist circumference, together with insulin (model I: R(2) = 0.77), serum triglycerides (model II: R(2) = 0.65), and the subscapularis skin fold (model III: R(2) = 0. 64). Using reference limits for insulin sensitivity obtained in the 81 normal pre-menopausal women, the models identify insulin resistant women with PCOS. These simple and inexpensive models are potentially useful in clinical practice as an early screening in women with PCOS.     

Isolation and characterization of wear debris generated in patients wearing polyethylene Hylamer inserts, gamma irradiated in air

Hylamer polyethylene was used in the early 1990s to make hip-joint components. Clinical experience has shown that these components, if sterilized by gamma rays in the presence of oxygen, are easily affected by wear, which then leads to osteolysis. The authors analyzed polyethylene wear particles in seven patients who had received Hylamer polyethylene implants sterilized by gamma rays in air and had suffered prosthetic loosening. The results were compared to those of six controls, who had received traditional polyethylene implants, sterilized by the same method. The frequency distribution of globular and fibrillar particles was similar in both groups (38.5% in Hylamer, 45.2% in controls). The globular particles in the Hylamer samples had a mean area of 0.12 microm2, which was significantly lesser than that of the controls (0.30 microm2). The width of fibrillar particles in the Hylamer samples was significantly lesser than that of the controls. Therefore, the two materials, despite undergoing the same type of sterilization, produced different types of wear, due to their different properties. In conclusion, the difference in the morphology of Hylamer polyethylene wear particles in comparison with PCA might have caused a more intensive biological response, early and massive osteolysis, and therefore, early loosening.     

Wear debris and cytokine production in the interface membrane of loosened prostheses

In this study, thirty-nine patients were examined. All of them suffered from hip joint prostheses loosening and underwent revision surgery. Bioptic samples were collected at the interface between bone and implant either at the stem or cotyle level. Immunohistochemistry was performed to detect IL-1alpha, IL-1beta, IL-6 and TNF, cytokines that directly cause bone resorption and indirectly induce synthesis of other bone resorbing cytokines. Quantitative analysis of the positive cells and correlation with clinical data was performed. It resulted that there is a great variability in positive cells for cytokines according to the harvest site; anyway, cytokines tend to be higher in patients carrying a joint prosthesis with polyethylene acetabular component and it is associated with plastic wear particles, even though there is no direct correlation between wear amount and cytokine levels. There is a statistically significant negative correlation between metal wear and a cytokine (IL-6); cytokines levels do not depend on the implant time to failure and do not correlate with pain score. As expected, cytokines levels tend to be lower in subjects being treated with non-steroidal antiinflammatory drugs. It can be concluded that plastic wear is the factor inducing the highest cytokine levels in the tissues around the prosthesis at the interface; cytokines that are an indicator of osteolysis risk.     

Treatment of Burkitt's/Burkitt-like lymphoma in adolescents and adults: a 20-year experience from the Norwegian Radium Hospital with the use of three successive regimens.

BACKGROUND: Burkitt's/Burkitt-like lymphoma (BL/BLL) are highly aggressive lymphomas mainly affecting children and young adults. We report the results in adolescent and adult patients with the use of three successive regimens. PATIENTS AND METHODS: Forty-nine patients aged 15-70 years admitted to the Norwegian Radium Hospital in the period 1982-2001 with a diagnosis of BL/BLL on histological review and who were given chemotherapy with curative intent are included in this analysis. Up to 1987 patients were given doxorubicin-based chemotherapy supplemented with intravenous and intrathecal methotrexate (MmCHOP). From 1987 to 1994, patients who obtained complete remission upon this regimen were consolidated with high-dose therapy with stem-cell support (MmCHOP + HDT). In 1995 we introduced as frontline therapy the German Berlin-Frankfurt-Munster (BFM) regimen. RESULTS: By intention to treat analyses, the progression-free survival rates for patients who received MmCHOP (n=13), MmCHOP + HDT (n=17) or BFM therapy (n=19) are 30.8%, 70.6% and 73.7%, respectively. In the groups of patients who received either the BFM regimen or MmCHOP + HDT, all patients who obtained complete remission upon induction therapy are continuously disease free. There was no treatment-related death. CONCLUSIONS: BL/BLL in adolescents and adults can successfully be treated with 5-day blocks of intensified chemotherapy such as the BFM regimen or CHOP/methotrexate-based chemotherapy consolidated with high-dose therapy. Using the BFM regimen, continuous remissions are obtained without additional myeloablative chemotherapy.     

RSR13 plus cranial radiation therapy in patients with brain metastases: comparison with the Radiation Therapy Oncology Group Recursive Partitioning Analysis Brain Metastases Database.

PURPOSE: This phase II, open-label, multicenter study assessed the efficacy and safety of the potential radiation enhancer RSR13 plus cranial radiation therapy (RT) in patients with brain metastases. The primary end point was patient survival in comparison with the Radiation Therapy Oncology Group Recursive Partitioning Analysis Brain Metastases Database (RTOG RPA BMD). PATIENTS AND METHODS: Eligibility criteria were age > or = 18 years, Karnofsky performance score > or = 70, and brain metastases with solid tumor histology. Patients received cranial RT, 30 Gy in 10 fractions of 3 Gy each, preceded by RSR13, 50 to 100 mg/kg intravenously over 30 minutes. Univariate and multivariate comparisons of survival and cause of death were made between class II study patients and RTOG BMD patients. RESULTS: Fifty-seven RPA class II patients were enrolled. With a minimum follow-up of 24 months, the median survival time and 1- and 2-year survival rates were 6.4 months, 23%, and 11% for the RSR13-treated patients compared with 4.1 months, 15%, and 3% for the RTOG BMD patients (P =.0174). In an exact-matched case analysis (n = 38), median survival time for RSR13 patients was 7.3 months versus 3.4 months for the RTOG BMD patients (P =.006). There was a 54% reduction in the risk of death for RSR13 patients (P =.0267). RSR13-related adverse events of greater than or equal to grade 3 toxicity that occurred in more than one patient included hypoxia, headache, anemia, fatigue, hypertension, and intracranial hypertension. CONCLUSION: RSR13 plus cranial RT resulted in a significant improvement in survival, as well as a reduction in death due to brain metastases, compared with class II patients in the RTOG BMD.