Thompson Score Research Articles

Brain MRI diffusion-weighted imaging in patients with classical phenylketonuria

The aim of this study was to grade magnetic resonance white matter abnormalities (WMAs) of classical phenylketonuria (cPKU) patients treated from birth and to compare sensitivity and specificity of T2-weighted and diffusion-weighted images (DWI). Twenty early-treated cPKU patients still on a low-phenylalanine diet (12 males; mean age 21.2 years) and 26 normal subjects (ten males; mean age 25.1 years) were enrolled. Typical T2- and diffusion-weighted WMAs were semiquantitatively graded according to Thompson score (TS). Besides, a regional magnetic resonance imaging (MRI) score (mTS) was developed according to extension and intensity of WMAs. Phenylalanine and tyrosine plasma concentrations before performing MRI and the amino acid mean levels collected the year before MRI (Tyr(year) and Phe(year)) were measured. No patient with Phe(year) concentration below 460 mumol/L showed WMAs. In cPKU patients, TS and mTS were significantly higher on DWI than on T2 images (3.50 vs 2.65 and 23.65 vs 15.85, respectively, p < 0.002, Wilcoxon test). All controls were scored 0 on DWI, while in T2 images, TS and mTS were 0.19 and 1.70. DWI evaluated by mTS disclosed a frontotemporal, occipital, and parietal WM progressive involvement. TS and mTS, both on T2 images and on DWI, showed no correlation with tyrosine while they proved to have a strong correlation with phenylalaninemia and an excellent one with Phe(year) levels. Among the different MR sequences, DWI seems to be the most sensitive and reliable in detecting and grading the typical WMAs of cPKU patients.

Increased MMP‐2 activity during intervertebral disc degeneration is correlated to MMP‐14 levels

Intervertebral disc (IVD) degeneration is associated with the increased expression of several matrix metalloproteinases (MMPs), in particular MMP-2. However, little is known about the actual activity of MMP-2 in healthy and degenerated discs, or what mechanisms are involved in its activation. A major activation pathway involves complex formation with MMP-14 and a tissue inhibitor of metalloproteinases-2 (TIMP-2). In a series of 56 human IVDs, obtained at autopsy and graded according to the Thompson score (I-V), we analysed whether MMP-2 activity was increased in different stages of IVD degeneration and to what extent activation was related to the production of MMP-14 and TIMP-2. MMP-2 activation and production were quantified by gelatin zymography. Immunohistochemical staining of MMP-14 and TIMP-2 was quantified with a video overlay-based system. A positive correlation was observed between the amount of active MMP-2 and pro-MMP-2 and degeneration grade (p < 0.001, correlation coefficient (CC) 0.557; and p < 0.001, CC 0.556, respectively). MMP-2 activity correlated positively with MMP-14 and less strongly with TIMP-2 (p = 0.001, CC 0.436; and p = 0.03, CC 0.288, respectively). Moreover, immunopositivity for MMP-14 correlated to degeneration grade (p = 0.002, CC 0.398). IVD degeneration was associated with the activity of MMP-2 and the correlation of its activation with MMP-14 production suggests MMP-14 activates MMP-2 during degeneration. As MMP-14 is capable of activating several other enzymes that are also thought to be involved in IVD degeneration, it may be a key mediator of the degenerative process.

Femoral head injuries: Which treatment strategy can be recommended?

Despite different operative and non-operative treatment regimens, the outcome after femoral head fractures has changed little over the past decades. The initial trauma itself as well as secondary changes such as posttraumatic osteoarthritis, avascular necrosis or heterotopic ossification is often responsible for severe loss of function of the afflicted hip joint. Anatomic reduction of all fracture fragments seems to be a major influencing factor in determining the outcome quality. Eight years ago we inaugurated a new surgical approach for better access and visualisation for the treatment of femoral head fractures, using the "trochanteric flip" (digastric) osteotomy. Thus inspection of the entire hip joint and accurate fragment reduction under direct visual control are possible. After good initial experiences with this operative procedure we changed our standard treatment regimen to this approach in an attempt to achieve the most accurate anatomic reduction of the femoral head in every affected patient. Between 1998 and 2006 we operated on 12 patients with femoral head fractures associated with posterior hip dislocation, using the new surgical approach. Patients were followed for 2-96 months and outcome was documented with the Merle d'Aubigne and Postel score as well as the Thompson and Epstein score. The posttraumatic formation of heterotopic bone was documented with the Brooker score. Retrospective analysis of these 12 patients showed good or excellent results in 10 patients (83.3%). The two patients with poor outcome developed an avascular necrosis of the femoral head and underwent total hip arthroplasty. Periarticular heterotopic ossification was seen in five patients. In four patients this caused a significantly reduced range of motion and was therefore considered as a posttraumatic complication. The two patients with the most severe heterotopic bone formation (Brooker III and IV) had initially sustained multiple injuries including brain injury. Comparing our results with earlier published series including our own before changing the treatment protocol, the data suggest a favorable outcome in patients with trochanteric flip (digastric) osteotomy for the treatment of femoral head fractures.

Demographic factors that influence human disc cell proliferation in vitro

Background context Although previous work has shown that greater age, greater disc degeneration, female gender, and surgical derivation of disc tissue had deleterious effects on cell proliferative potential, relatively little is known about the association between disc cell proliferation in vitro and clinical donor characteristics. Purpose To identify the relationships between donor characteristic and the in vitro proliferative potential of human disc cells from the annulus. Study design/setting Studies were approved by the human subjects Institutional Review Board. Donor data included donor source, ethnicity, age, gender, smoking history, height, weight, number of years of back pain, and Thompson score. Cells cultured from the annulus were tested for proliferation. Patient sample There were two study populations: 1) Comparison Group (32 control donors and 33 control surgical subjects; 60 Caucasians, 5 African-Americans). Cell proliferation, age, Thompson score, height, weight, and smoking history were statistically analyzed for control donors versus control surgical group. No significant differences were present, and these two groups were pooled to form the Comparison Group. 2) Nineteen subjects from the United Arab Emirates who underwent disc surgery. Outcome measures Linear models were fit to the data to determine the best prediction of cell proliferation as the outcome variable; multiple R-squared was used to determine model goodness of fit. Methods Control donor specimens were obtained from the National Cancer Institute Cooperative Human Tissue Network, and control donor surgical specimens from disc surgeries. A standardized cell proliferation assay was used to evaluate monolayer and three-dimensional agarose cell proliferation. Data were expressed as mean cpm[ 3H]-thymidine per microgram deoxyribonucleic acid±SEM. Standard statistical methods used the SAS system for data analysis. Results No differences were present in the Comparison Group versus the Middle Eastern group for mean Thompson score (both averaged grade III), mean age (44.3 vs. 43.0 years, respectively), gender, height, weight, length of time with back pain (1.9 years vs. 2.1 years respectively), or smoking history. Three-dimensional proliferation in agarose was not significantly different for the two groups. Monolayer proliferation, however, was significantly different (17,434±2,929 vs. 6,693±2,103, respectively), p=.019. Linear regression models were fit to the data to determine the best prediction using proliferation as the outcome variable. In the Middle Eastern group, monolayer cell proliferation bore a significant negative correlation to age (p=.02, r=−.32), whereas the Comparison Group showed no such relationship. The following equation was derived to fit these data: Log 10 of proliferation (cpm/μg deoxyribonucleic acid)=10.915–0.7919 (Middle Eastern ethnicity)–0.0296 (Age). The r 2 for this equation is 0.203 (ie, 20.3% of the change in proliferation is explained by age and Middle Eastern ethnicity). Middle Eastern ethnicity and age were significant in this equation (p=.04 and .0003, respectively). Conclusions Studies have shown that familial history, age, and smoking are important risk factors for disc degeneration in Arabic pedigrees. It is interesting that our present findings also point to age and familial history as important significant factors influencing monolayer proliferation. Further research is needed to identify the cellular basis for this influence on cellular proliferative capacity.

Clinical and demographic prognostic indicators for human disc cell proliferation in vitro: pilot study.

Human anulus cells were cultured under control and experimental conditions to study associations between proliferation and clinical-demographic features of subjects from which cells were obtained. Statistical multiple regression analyses were applied to develop mathematic models relating proliferation to age, gender, Thompson score (denoting stage of disc degeneration), and status (control donor [postmortem]; surgical patient). To identify the effect of donor characteristics on proliferative capacities of human disc cells. As therapeutic options for disc degeneration increase, novel biologic options are important future considerations. Little is known about the influence of clinical-demographic features on cell proliferation. Anulus cells were studied in two designs: 1) Cells from 12 individuals were grown in monolayer with 50 ng/mL interleukin growth factor-1 (IGF-I), 100 ng/mL insulin, or control conditions. 2) Cells from nine individuals were grown in three-dimensional culture with 10 ng/mL IGF-I or control conditions. Cell proliferation data and data on age, gender, Thompson score, and status were collected. Standard statistical analyses were used to develop correlation models. Data from monolayer experiments produced significant models fitting proliferation in the presence of low serum, 50 ng/mL IGF-I, or insulin, with age, gender, Thompson score, and status (respective R2: 0.827, 0.680, 0.850). Three-dimensional cultures exposed to 10 ng/mL IGF-I resulted in proliferation that correlated in a significant negative manner with Thompson score (r = -0.798). Clinical-demographic prognostic indicators may help predict levels of proliferation. Greater age, greater disc degeneration, female gender, and surgical derivation had deleterious effects on proliferation potential in this model.

Intertrochanteric osteotomy for posttraumatic arthritis after acetabular fractures.

To evaluate the long-term results of intertrochanteric osteotomies for posttraumatic arthritis after acetabular fractures. Retrospective study of eight patients who underwent a total of ten intertrochanteric osteotomies. Two patients underwent two osteotomies of the same hip. Academic Level I trauma center. Patients who developed posttraumatic hip arthritis after nonoperatively or operatively treated acetabulum fractures. The average age of patients was twenty-nine years (range 16 to 47 years). Patients underwent an intertrochanteric osteotomy to decrease contact pressures on damaged cartilage and to lessen contractures. All intertrochanteric osteotomies at our institution were performed by the senior author (R.K.M.). The Merle d'Aubigné score and the Thompson and Epstein score were determined based on each patient's last follow-up. At an average long-term follow-up of 10.2 years (range 2.5 to 22 years), all eight patients had a significant improvement based on the Merle d'Aubigné score (average increase 5.3 points). Less improvement was observed according to the Thompson and Epstein score, which is consistent with the fact that radiographic appearance is weighted disproportionally in that score. Because most acetabular fracture patients are relatively young, the option of joint replacement for posttraumatic hip arthritis is less than ideal. However, we have observed significant improvement in hip function with a decrease in pain and disability when such patients are treated with an intertochanteric osteotomy.

Anti-apoptotic effects of IGF-1 and PDGF on human intervertebral disc cells in vitro.

Human cells from the anulus were grown in tissue culture in an experimental design to study the anti-apoptotic effect of two selected cytokines. To determine whether two selected cytokines, insulin-like growth factor-1 and platelet-derived growth factor, were effective in decreasing apoptosis in human cells from the anulus grown in culture for 10 days. Previous studies have shown that there is a small cell population in the aging human intervertebral disc. Earlier work from the authors' laboratory suggested that apoptosis (programmed cell death) may be a major contributing factor to the decrease in cell number. A wide variety of inhibitors of apoptosis have now been identified; the present report presents findings on the actions of insulin-like growth factor-1 and platelet-derived growth factor in retarding or preventing apoptosis. Using previously published culture methods, cells from the anulus of 25 subjects (mean age, 41.7 years) were grown in monolayer culture for 10 days and tested under the following conditions: 1) control growth in the presence of 20% fetal bovine serum; 2) positive control conditions promoting the development of apoptosis in the absence of serum; or 3) in dose-response regimes where insulin-like growth factor-1 or platelet-derived growth factor were added in the presence of only 1% fetal bovine serum (necessary for basal cell maintenance). Specimens were derived from 18 lumbar, 9 cervical, and 1 thoracic sites; the average Thompson score was III. Cells were grown on chambered slides and evaluated in situ using the TdT in situ apoptosis detection reaction to identify apoptotic cells. An average of 300 cells were counted in replicate cultures at each dose to determine the incidence of apoptosis; results were analyzed with standard statistical techniques. Cultured cells also were examined with transmission electron microscopy. Serum withdrawal to a 1% level was used as a positive apoptosis control in vitro and resulted in a significantly greater percentage of apoptosis compared with the 20% serum negative control (1.02% +/- 0.34 (28) versus 0.14% +/- 0. 04 (27; mean +/- SEM (n)), P < 0.0001). Exposure to 50 ng/mL insulin-like growth factor-1 significantly reduced the percentage of apoptosis (vs.- 1% serum) to 0.49% +/- 0.26 (P = 0.005); 500 ng/mL was also significantly effective (% apoptosis = 0.09% +/- 0.04 (P = 0.0001). Platelet-derived growth factor at a dose of 100 ng/mL also significantly reduced apoptosis (0.18 +/- 0.11, P = 0.0001). Data demonstrate a significant reduction in the percentage of apoptotic disc cells after exposure to 50-500 ng/mL insulin-like growth factor-1 or exposure to 100 ng/mL platelet-derived growth factor. These findings expand the understanding of the cell biology of the disc cell and show that selected cytokines can retard or prevent programmed cell death in vitro. The administration of these cytokines may have future therapeutic potential in the treatment of disc degeneration.

Validity and reliability of joint indices. A longitudinal study in patients with recent onset rheumatoid arthritis.

This prospective longitudinal study evaluates the validity and reliability of joint indices (JIs) used to measure disease activity in patients with RA. From seven traditional JIs (Ritchie Articular Index (RAI), Modified RAI, Thompson score, 28 JI, 36 JI, total tender and total swollen joints) 37 'new' JIs were computed by considering three different characteristics of joint inflammation, tenderness, swelling and the combination of tenderness and swelling, and by grading for tenderness and/or weighting for surface area of the joints. Several aspects of validity were investigated, the construct (correlation with radiographic damage), correlational (correlation with ESR, general health) and criterion validity (correlation with a Health Assessment Questionnaire, discrimination between high and low disease activity). It was found that the validity and reliability of traditional JIs do not differ substantially. Graded JIs are almost always more valid than ungraded JIs. Weighted JIs are almost always less valid and reliable than unweighted JIs. Therefore no JI proved to be superior for measuring the disease activity under consideration. Taking simplicity into account the 28 JI, not graded and not weighted, was preferable.