Prekallikrein deficiency in a 15-year-old boy with Ménière's disease: a case report.

Congenital prekallikrein deficiency is a rare disorder in which there is an in vitro clotting defect despite absence of bleeding or thrombotic tendency. In this report, a 15-year-old boy with an unexpected markedly prolonged activated partial thrombin time, a normal prothrombin time, and without personal nor familial history of bleeding or thrombosis is presented. Laboratory investigation revealed a severe prekallikrein deficiency. This case highlights the importance of following a diagnostic algorithm to establish the correct diagnosis. Moreover, by selecting appropriate laboratory tests, unnecessary and repeatedly testing can be avoided.

Myelofibrosis patients in Belgium: disease characteristics.

OBJECTIVE: To date, only a small number of epidemiological studies on myelofibrosis have been performed. The current study aimed to characterize the myelofibrosis patient population in Belgium according to pre-defined disease parameters (diagnosis, risk categories, hemoglobin <10 g/dl, spleen size, constitutional symptoms, platelet count, myeloblast count), with a view to obtaining a deeper understanding of the proportion of patients that may benefit from the novel myelofibrosis therapeutic strategies. METHODS: A survey was used to collect data on prevalence and disease parameters on all myelofibrosis patients seen at each of 18 participating hematologic centers in 2011. Aggregated data from all centers were used for analysis. Analyses were descriptive and quantitative. RESULTS: A total of 250 patients with myelofibrosis were captured; of these, 136 (54%) were male and 153 (61%) were over 65 years old. One hundred sixty-five (66%) of myelofibrosis patients had primary myelofibrosis and 85 (34%) had secondary myelofibrosis. One hundred ninety-three myelofibrosis patients (77%) had a palpable spleen. About a third of patients (34%) suffered from constitutional symptoms. Two hundred twenty-two (89%) myelofibrosis patients had platelet count ≧50 000/µl and 201 (80%) had platelet count ≧100 000/µl. Of 250 patients, 85 (34%) had a myeloblast count ≧1%. Six (2%) patients had undergone a splenectomy. Thirteen (5·2%) patients had undergone radiotherapy for splenomegaly. CONCLUSIONS: The results of this survey provide insight into the characteristics of the Belgian myelofibrosis population. They also suggest that a large proportion of these patients could stand to benefit from the therapies currently under development.

Long-term follow-up of the cervical spine with conventional radiographs in patients with rheumatoid arthritis.

OBJECTIVES: To investigate the prevalence of cervical spine damage due to rheumatoid arthritis (RA) in the long term and to investigate which disease-specific factors are related to this damage. METHOD: Patients with early RA from the Nijmegen inception cohort with 6 to 12 years of follow-up were included. Conventional radiographs of the cervical spine were obtained at baseline, 3, 6, 9, and 12 years and scored for erosions of C1 and C2, anterior atlantoaxial subluxation (AAS) and atlantoaxial impaction (AAI). Disease-specific factors, such as disease activity, functionality, and peripheral joint damage, at baseline, 3, 6, and 9 years, were compared between patients with and without cervical spine damage at 9 years. RESULTS: A total of 196 patients were included, of whom 134 had radiographs at 9 years. Cervical spine damage was present in 16% (22/134) of the patients at 9 years. During the total 12 years of follow-up, AAS and erosions of C2 were observed most frequently. Erosions of C1 and AAI were very rare. Patients with cervical spine damage at 9 years had a higher number of erosions of the peripheral joints and failed more disease-modifying anti-rheumatic drugs (DMARDs) at 3, 6, and 9 years. Patients without peripheral erosive disease at 3 years were unlikely to develop cervical spine damage within 9 years of disease duration. CONCLUSIONS: The prevalence of cervical spine damage due to RA was 16% at 9 years. Patients without peripheral erosive disease at 3 years were unlikely to develop cervical spine damage at 9 years.

Monocytes are activated in patients with myelodysplastic syndromes and can contribute to bone marrow failure through CD40-CD40L interactions with T helper cells.

Immune mechanisms have been shown to contribute to the process of myelodysplastic syndromes (MDS)-related bone marrow (BM) failure. The aim of this study was to evaluate the possible contribution of activated monocytes through CD40-CD40L(CD154) interactions with activated T helper cells. We demonstrated in 77 predominantly lower risk MDS patients that the CD40 receptor was expressed significantly higher on monocytes and that CD40L was expressed significantly higher on T helper cells in peripheral blood (PB) and BM. Increased levels of CD40 and CD40L were detected in the same patients. In addition, stimulation of the CD40 receptor on purified PB monocytes led to a significantly higher tumor necrosis factor alpha production in patients. Co-culture of BM mononuclear cells of 21 patients in the presence of a blocking CD40 monoclonal antibody (ch5D12) led to a significant increase in the number of colony-forming units. A correlation was seen between increased CD40 expression on monocytes with patients' age below 60 years and with the cytogenetic abnormality trisomy 8. These results demonstrate that CD40 expression on monocytes may identify a subgroup of MDS patients in whom immune-mediated hematopoietic failure is part of the disease process. As such, the CD40-CD40L-based activation of monocytes might be a target to counteract MDS-related BM failure.

Rofecoxib inhibits heterotopic ossification after total hip arthroplasty.

INTRODUCTION: Nonsteroidal anti-inflammatory drugs (NSAIDs) prevent heterotopic ossification but gastrointestinal complaints are frequently. Selective cyclooxygenase-2 (COX-2) inhibiting NSAID produce less gastrointestinal side effects. PATIENTS AND METHODS: A prospective two-stage study design for phase 2 clinical trials with 42 patients was used to determine if rofecoxib (a COX-2 inhibitor) 50 mg oral for 7 days prevents heterotopic ossification. A cemented primary THA was inserted for osteoarthroses. After 6 months heterotopic bone formation was assessed on AP radiographs using the Brooker classification. RESULTS: No heterotopic ossification was found in 81% of the patients, 19% of the patients had Brooker grade 1 ossification. CONCLUSION: Using a two-stage study design for phase 2 clinical trials, a 7-day treatment of a COX-2 inhibitor (rofecoxib) prevents effectively the formation of heterotopic ossification after cemented primary total hip arthroplasty.

Good outcome and restoration of lordosis after anterior lumbar interbody fusion with additional posterior fixation.

STUDY DESIGN: Fifty-two patients with degenerative disc disease underwent single- or double-level anterior lumbar interbody fusion with SynCage and additional posterior fixation as treatment for degenerative disc disease and were prospectively followed for 4 years. OBJECTIVES: To test the clinical performance of anterior lumbar interbody fusion with SynCage, with emphasis on the safety and efficacy of the surgical procedure and the ability to restore anatomy and fuse the motion segment. SUMMARY OF BACKGROUND DATA: Anterior lumbar interbody fusion using femoral allograft and/or autologous bone has a high complication rate. With cage technology, some of these complications can be avoided. The design characteristics of the SynCage offer advantages in restoring and maintaining intervertebral height and restoration of lumbar lordosis. METHODS: Thirty-three patients underwent single-level and 19 patients double-level anterior lumbar interbody fusion with SynCage and additional posterior fixation (translaminar screws, n = 32 or pedicle screws, n = 10). Radiologic and functional results (VAS and Oswestry score) were evaluated. RESULTS: Intervertebral height was corrected from an average of 8.7 to 17.6 mm. Lordosis of the fused segment was significantly increased (average 10.6 degrees for the fused segment and 8 degrees for lumbosacral lordosis). After 2 years, there was radiologic evidence for fusion in 70 of 71 (98.6%) levels. Functional scores showed a significant improvement in pain and function up to the 2-year follow-up observation. At the 4-year follow-up observation, there was some loss of the initial improvement in VAS and Oswestry scores. Despite this loss, they remained significantly better than the preoperative scores. CONCLUSIONS: Anterior lumbar interbody fusion with SynCage and additional posterior fixation is a safe and effective procedure. Intervertebral height is corrected, and lumbosacral lordosis is restored. An initial improvement in VAS and Oswestry scores is partly lost at the 4-year follow-up observation, but 4-year results are still significantly better than the preoperative scores.

Was isolation of Veillonella from spinal osteomyelitis possible due to poor tissue perfusion?

From a needle biopsy of the body of the 12th thoracic vertebra in a 74-year-old man with spinal osteomyelitis a Veillonella parvula was isolated. The significance of this bacterium as lactic acid indicator has been considered and discussed. Since this strictly anaerobic bacterium mainly uses lactic acid for energy generation, lactic acid must continuously and sufficiently have been produced in or near to the vertebrate body to permit outgrowth of this bacterium. Since neither microbial infections nor tumours could be demonstrated, we finally hypothesised that in this patient poor tissue perfusion has been the primary cause of lactic acid production.

Computed tomography determined femoral torsion is not accurate.

INTRODUCTION: Computed tomography (CT) is considered the method of choice for detecting rotational malalignment of the femur. However, it is unclear how reliable the method is, and what the causes are of potential inaccuracies. MATERIALS AND METHODS: To address these issues three observers measured the CT images of the femur of 76 patients on two separate occasions. The images were made during follow-up of a unilateral femoral shaft fractures. Rotational malalignment was determined by comparing the torsion angle of the injured to the noninjured leg. RESULTS: The pooled intraobserver variance was 3.9 degrees and interobserver variance 4.1 degrees. Of the two measurements of one observer 95% were up to 10.8 degrees different, and between observers 95% of the measurements were up to 15.6 degrees different. CONCLUSIONS: CT measurements of rotational malalignment of the femur are not accurate. This is due principally to the difficulty in defining a line through the axis of the femoral neck. The accuracy can be improved by taking the average of two measurements.

Hydroxyapatite does not improve the outcome of a bipolar hemiarthroplasty.

In a one-surgeon study the clinical and radiographic results of 30 cementless bipolar hip prostheses in 24 patients younger than 55 years were evaluated. Eleven noncoated prostheses (Noncoated Group) and 19 hydroxyapatite-coated prostheses (Hydroxyapatite Group) were compared after a mean followup of 10.4 years. The Harris hip score increased from a preoperative average of 41 points to 76 points at final followup (Noncoated Group, 70 points; Hydroxyapatite Group, 80 points). Thigh or groin pain was present in 15 patients (16 hips) (Noncoated Group, 55%; Hydroxyapatite Group, 53%). Radiographically, subsidence was the major problem at the noncoated prostheses (Noncoated Group, 91%; Hydroxyapatite Group, 5%), whereas osteolysis mainly was seen at the hydroxyapatite-coated prostheses (Noncoated Group, 18%; Hydroxyapatite Group, 89%). The obtained aseptic revision rate of 27% (Noncoated Group, 27%; Hydroxyapatite Group, 26%) is too high to use this implant in young patients. The large amounts of polyethylene wear debris generated by the bipolar system play an important role in this limited success. In the initially well-fixed hydroxyapatite-coated prostheses the sealing effect of a hydroxyapatite coating creates high concentrations of polyethylene in the limited joint space, resulting in massive proximal femoral osteolysis. Consequently, a hydroxyapatite coating introduces a new failure mechanism. Therefore, hydroxyapatite does not improve the outcome of a cementless bipolar hemiarthroplasty in the long-term.

Chondrosarcoma of bone: functional outcome and quality of life.

BACKGROUND AND OBJECTIVES: Outcome studies of chondrosarcoma have so far only reported oncological and functional results. Quality-of-life assessment becomes more important because more long-term survival after treatment of malignant diseases occur. The objective of this study is to analyze functional outcome and quality of life. METHODS: Functional evaluation of the patients was carried out according to the MSTS functional scoring system. For assessment of quality of life, questionnaires were used. RESULTS: Response of the questionnaires sent to 45 disease-free patients was 84%. The mean functional score of these 38 patients was 74% (20-100%). Best functional results were seen after bone graft reconstruction and curettage and cryosurgery with reconstruction. Quality-of-life analysis revealed a mean global health status of 75 (66-84). Furthermore, 24% of the patients experienced severe fatigue. Patients reported more problems with regard to physical functioning and sleep in comparison with healthy controls. No correlation was found between global health status scores and functional scores. CONCLUSIONS: Functional scores depend on the type of treatment with best results after curettage and cryosurgery. Quality-of-life analysis reveals problems on several domains, including fatigue, physical functioning and sleep.

Oncologic and functional results after treatment of giant cell tumors of bone.

Surgical treatment of giant cell tumor of bone has always been a difficult problem because of its local aggressive behavior. Oncologic results and functional outcome are reported here in a retrospective study of 36 patients, treated by various surgical procedures. The average age at the time of diagnosis was 34 years, and the median follow-up period was 7 years. Twenty-three patients were treated by intralesional excision with local adjuvant therapy, and 11 patients by extralesional excision. Two patients received radiotherapy only. Seven local tumor recurrences (30%) were encountered after intralesional procedures, while local tumor control was the rule after extralesional excision. Intralesional excision with local adjuvant therapy resulted in significantly better functional results compared with extralesional excision. Wide excision was associated with a poor functional outcome and marginal excision with a good functional outcome. For the treatment of giant cell tumor of bone, intralesional excision with local adjuvant therapy is recommended because of a good functional outcome. When applying cryosurgery as the local adjuvant, more vigorous freezing may be necessary to improve local tumor control.

Plasma fibrin D-dimer levels correlate with tumour volume, progression rate and survival in patients with metastatic breast cancer.

Plasma levels of D-dimer are elevated in cancer patients. Activation of the extrinsic coagulation system and the fibrinolytic cascade within a tumour is thought to be related with growth, invasion and metastasis. We have investigated the relationship between these markers of fibrin metabolism, standard clinicopathological variables and serum levels of angiogenic cytokines in three cohorts: group A (n=30) consisted of 30 healthy female volunteers, group B (n=23) of consecutive patients with operable breast cancer and group C (n=84) of patients with untreated or progressive metastatic breast cancer. Plasma D-dimers, fibrinogen, IL-6, vascular endothelial growth factor and calculated vascular endothelial growth factor load in platelets are clearly increased in patients with breast cancer. D-dimers were increased in nearly 89% of patients with progressive metastatic disease. The level of D-dimers was positively correlated with tumour load (P<0.0001), number of metastatic sites (P=0.002), progression kinetics (P<0.0001) and the cytokines related to angiogenesis: serum vascular endothelial growth factor (P=0.0016, Spearman correlation=0.285), calculated vascular endothelial growth factor load in platelets (P<0.0001, Spearman correlation=0.37) and serum interleukin-6 (P<0.0001, Spearman correlation=0.59). Similarly increased D-dimer levels were positively correlated with increased fibrinogen levels (P<0.0001, Spearman correlation=0.38). The association between markers of fibrin degradation in patients with progressive breast cancer suggests that the D-dimer level is a clinically important marker for progression and points towards a relation between haemostasis and tumour progression. A role of interleukin-6, by influencing both angiogenesis and haemostasis, is suggested by these observations.

Fibrous dysplasia of bone: management and outcome of 20 cases.

BACKGROUND AND OBJECTIVES: Fibrous dysplasia of bone is difficult to manage because of its variable clinical course with many different methods of treatment reported. Therefore we report on our experience. METHODS: We reviewed a series of 20 patients with 32 lesions included. The average age at the time of diagnosis was 32 years for monostotic disease, 26 years for polyostotic disease, and 3 years for McCune-Albright syndrome. The median follow-up period was 6 years. Functional and radiographic outcomes were scored. RESULTS AND CONCLUSIONS: Monostotic disease mostly presented with a circumscribed lesion and monitoring was often sufficient. Symptomatic circumscribed lesions showed satisfactory outcome when treated with curettage, cryosurgery and bone grafting. Lesions of the extended type were most of all seen in polyostotic disease and eventually needed operative treatment. In case of bony deformity, corrective osteotomies and rigid internal fixation were performed in addition to curettage, cryosurgery, and bone grafting. In polyostotic disease, expected outcomes were good, but in McCune-Albright syndrome, results were uniformly poor. J. Surg. Oncol. 2001;76:157-166.

Intraosseous schwannoma (neurilemmoma) of the cervical spine.

PURPOSE: To report on an extremely rare tumour located in the cervical spine, its treatment and result. Review of the literature. PATIENT: Case report of a 38-year-old woman with an intraosseous schwannoma of the cervical spine. RESULTS: After local curettage no evidence for local recurrence at long-term follow-up.

Scintigraphic evaluation of experimental chronic osteomyelitis.

UNLABELLED: Assessment of disease activity and disease extent in chronic osteomyelitis remains a difficult diagnostic problem. Radiography is not particularly sensitive. Scintigraphic techniques can be more helpful, but the routinely available agents lack specificity (99mTc-methylene diphosphonate [MDP], 67Ga-citrate) or are laborious to prepare (111In-leukocytes). We evaluated the performance of 2 new radiopharmaceuticals, 99mTc-polyethyleneglycol (PEG) liposomes and 99mTc-hydrazinonicotinamide (HYNIC)-immunoglobulin G (IgG), in an experimental model of chronic osteomyelitis. METHODS: Chronic osteomyelitis was induced in rabbits by inserting S. aureus into the right reamed and washed femoral canal. The canal was closed with cement. A sham operation was performed on the left femur. Routine radiographs were obtained immediately after surgery and before scintigraphy. Four weeks after surgery, each rabbit was injected with 37 MBq 99mTc-PEG liposomes, 99mTc-HYNIC-IgG, and 99mTc-MDP on 3 consecutive days and imaged up to 4 (MDP) or 22 (liposomes and IgG) h after injection. On day 4, rabbits received either 18 MBq 111In-granulocytes or 67Ga-citrate and were imaged up to 44 h after injection. Uptake in the infected femur was determined by drawing regions of interest. Ratios of infected-to-sham-operated femur were calculated. After the last image, the rabbits were killed, and the left and right femur were scored for microbiologic and histopathologic evidence of osteomyelitis. RESULTS: 99mTc-PEG liposomes and 99mTc-HYNIC-IgG correctly identified all 6 rabbits with osteomyelitis. 11In-granulocytes and 67Ga-citrate gave equivocal results in 1 infected rabbit. 99mTc-MDP missed 1 case of osteomyelitis. The uptake in the affected region did not differ significantly between the agents, although 99mTc-MDP tended to have higher values (MDP, 4.75 +/- 1.23 percentage injected dose per gram [%ID/g]; 67Ga, 2.05 +/- 0.54 %ID/g; granulocytes, 1.56 +/- 0.83 %ID/g; liposomes, 1.75 +/- 0.76 %ID/g, and IgG, 1.96 +/- 0.27 %ID/g). The ratios of infected-to-normal femur were also not significantly different for the respective radiopharmaceuticals. Radiography visualized only severe osteomyelitis. CONCLUSION: In this rabbit model, 99mTc-PEG liposomes and 99mTc-HYNIC-IgG performed at least as well as 111In-granulocytes and 67Ga-citrate in the localization of chronic osteomyelitis. The ease of preparation, the better image quality, and the lower radiation dose suggest that 99mTc-PEG liposomes and 99mTc-HYNIC-IgG might be suitable alternatives for 67Ga-citrate and 111In-granulocytes in the scintigraphic evaluation of osteomyelitis.

Swelling of hand and forearm caused by Mycobacterium bovis.

A 75-year-old native Dutch farmer presented with a painless swelling of his right hand extending into his forearm, accompanied by general malaise and low grade fever. His medical history revealed coxitis tuberculosa in 1954 and injury of the same hand in 1978. His present swelling appeared to be caused by Mycobacterium bovis, probably due to endogenous reactivation. Whether the mycobacteria reached the hand hematogenously or were directly inoculated at the time of injury of his hand in 1978 remains unclear.

The effectiveness of exercise therapy in patients with osteoarthritis of the hip or knee: a randomized clinical trial.

OBJECTIVE: To determine the effectiveness of exercise therapy in patients with osteoarthritis (OA) of the hip or knee. METHODS: A randomized single blind, clinical trial was conducted in a primary care setting. Patients with hip or knee OA by American College of Rheumatology criteria were selected. Two intervention groups were compared. Both groups received treatment from the patients' general practitioner, including patient education and medication if necessary. The experimental group also received exercise therapy from a physiotherapist in primary care. The treatment period was 12 weeks. The main outcome measures were pain, medication use (nonsteroidal antiinflammatory drugs, NSAID) and observed disability. RESULTS: A total of 201 patients were randomized. Exercise therapy was associated with a reduction of pain in the past week (difference in change -17.0; 95% CI -23.6, -10.4) and observed disability (-0.19; 95% CI -0.38; -0.01). Effect sizes were medium (0.58) and small (0.28), respectively. No effect of exercise therapy was found for the use of NSAID. Additional beneficial effects (p = 0.05) were found for the use of paracetamol (effect size 0.33), global effect as perceived by the patient (effect size 0.68), and muscle strength of the hip (effect size 0.34). CONCLUSION: After 12 weeks, exercise therapy is effective in reducing pain and disability. The size of the effects is medium and small, respectively.

Eosinophilic granuloma of bone: results of treatment with curettage, cryosurgery, and bone grafting.

Intralesional instillation of steroids is currently the first choice of treatment for eosinophilic granuloma of bone. However, some lesions fail to respond or are unsuitable for injection therapy due location, pending pathologic fracture, and soft tissue intrusion. The authors treated six patients with these lesion characteristics using curettage, cryosurgery, and bone grafting. After a mean follow-up of 34.3 months, all lesions healed completely, although one femoral fracture occurred 8 months after the operation. In selected cases of eosinophilic granuloma of bone, a primary surgical treatment seems feasible. The use of cryosurgery as adjuvant treatment extends the surgical margin and is of value in averting local recurrence.

Synovial sarcoma: oncological and functional results.

AIM: To evaluate the oncological and functional result of the treatment of patients with a synovial sarcoma. This paper gives a retrospective review of 20 patients (15 male and five female) treated for synovial sarcoma at the Nijmegen University Hospital, The Netherlands. METHODS: The median age of the patients was 30 years (range: 14-71, mean 37 years). RESULTS: The tumour locations were: lower extremity in 12 patients; upper extremity in three; pelvic and groin region in four; and the retroperitoneal space in one. Surgical stages according to Enneking (Clin Orthop 1986; 204: 9-24) were IIA in five cases; IIB in seven; and IIIB in eight. The surgical margin was intralesional in three cases; marginal in three; wide in six; and radical in six. In one case the surgical margin could not be assessed and one patient was not operated. One patient developed a recurrent tumour and one developed nodal metastases. Eight patients who did not have metastases at the time of diagnosis developed metastase during follow-up. Fourteen patients died of metastatic disease; one patient died of diabetes; one is alive with disease; and four presently do not have evidence of disease. CONCLUSIONS: The outcome was poor, especially due to the occurrence of pulmonary metastases. The functional result according to the MSTS was 100% in four patients; in one the result was 93% because of the scar and venous insufficiency.