Individually fitted sports shoes for overuse injuries among newspaper carriers

OBJECTIVES: The aim of the study was to determine the effectiveness of new, individually fitted sports shoes against overuse injuries to the lower limb among newspaper carriers. METHODS: Patients (N = 176) with lower-limb overuse injuries were randomly assigned to use new, individually adjusted footwear with good shock absorbing properties (test group = 86) or the subjects' own, used footwear (control group = 90). The main outcome measurements were lower-limb pain intensity during walking, as rated on a visual analogue scale (0-100), number of painful days, subjective assessment of global improvement, foot fatigue, number of hyperkeratotic skin lesions and diagnosed overuse injuries, and costs of foot care as compared between the treatment groups. RESULTS: At the 6-month follow-up there was a difference in favor of the test group with respect to lower-limb pain intensity and number of painful days, when compared with the control group. At 1 year, 53% and 33% of the test and control groups, respectively, thought they were better than at the time of the baseline examination (number needed to treat being 5 between the test and control groups). The test subjects had less foot fatigue and fewer hyperkeratotic skin lesions. There was no difference in the number of diagnosed overuse injuries between the groups. During the year of follow-up, the all-inclusive mean costs of foot care were USD 70 and USD 158 in the test and control groups, respectively. CONCLUSIONS: Individually adjusted shock-absorbing shoes offer slight health benefits for lower-limb overuse injuries. Proper shoes may decrease the need to use health care resources.     

The combination of HSV-tk and endostatin gene therapy eradicates orthotopic human renal cell carcinomas in nude mice

BACKGROUND AND METHODS: Gene therapy may offer a new tool for the treatment of renal cell carcinoma (RCC). We have tested a combination of cytotoxic and antiangiogenic gene therapy for wild-type orthotopic human RCC xenografts in nude mice using intratumoral adenovirus-mediated herpes simplex virus thymidine kinase (HSV-tk) and endostatin (ES) gene therapy. In vivo magnetic resonance imaging, morphometry, immunocytochemistry, and survival were used to evaluate the treatment effect. Adenovirus-mediated marker gene transfers (GFP) were used as controls. Results: In vivo transduction efficiency, measured using GFP gene transfer, was 27+/-7%. The combination gene therapy with HSV-tk and ES adenoviruses resulted in a significant antitumor effect (P<.01) compared to single HSV-tk (n.s.) or ES (n.s.). In the survival study, all tumors with single gene therapy using HSV-tk, ES, and marker gene adenoviruses showed progression in magnetic resonance imaging. In contrast, the majority of the tumors in the combination treatment group remained dormant or were eradicated (57%). Survival of these mice equaled healthy nude mice, and was significantly prolonged (P<.0001) compared to HSV-tk (P<.028) and ES (n.s.) groups. Conclusions: It is concluded that the inhibition of angiogenesis using ES gene transfer together with the cytotoxic HSV-tk gene therapy results in a significantly improved treatment effect in RCC compared to the single gene treatments.     

Immunohistochemically detectable bcl-2 expression in metastatic melanoma: association with survival and treatment response

OBJECTIVE: The antiapoptotic protein Bcl-2 is supposed to influence the treatment responsiveness of different malignancies. In the present study the prognostic and predictive significance of Bcl-2 expression for survival and response to an administered therapy was explored in patients with metastatic melanoma. Also, the correlation between Bcl-2 expression and proliferation activity of tumor cells was defined to examine the regulatory role of Bcl-2 in proliferation. MATERIALS AND METHODS: Sixty metastatic melanomas obtained from patients treated with chemoimmunotherapy were examined by immunohistochemistry with anti-Bcl-2 and anti-Ki-67 (MIB-1) antibodies. Proliferation activity was expressed in percentages as MIB-1 index. RESULTS: The presence of Bcl-2 immunoreactivity was associated with a significantly lower MIB-1 index (p = 0.016), and a longer disease-free survival (p = 0.004). The lack of Bcl-2 expression was related to a higher response rate to therapy in comparison to a diffuse and focal pattern of Bcl-2 expression (p = 0.017). Although the presence of Bcl-2 immunoreactivity as such did not correlate with survival after the initiation of chemoimmunotherapy, the focal Bcl-2 expression pattern was strongly associated with a worse prognosis compared to a diffuse expression or a lack of Bcl-2 staining (p < 0.0001). CONCLUSIONS: Our results support the role of Bcl-2 in the regulation of cell proliferation and suggest that an increase of metastatic potential and progression of malignant melanoma is associated with a loss of Bcl-2 expression. The lack of Bcl-2 expression could be a predictor of the response to chemoimmunotherapy, whereas the Bcl-2 expression pattern, possibly indicating the heterogeneity of the tumors, might be a potential prognostic factor for survival after the initiation of therapy.     

Dense innervation in pseudocapsular tissue compared to aneural interface tissue in loose totally replaced hips

BACKGROUND: The function of many inflammatory cells is in part regulated by neuronal cells, which may lead to so-called neurogenic inflammation. Sensory nerves also mediate the pain sensation. METHODS: This immunohistochemical study focused on visualization of C-sensory and sympathetic innervation in the synovial membrane-like interface and pseudocapsular tissue around loosened total hip replacement. RESULTS: The synovial membrane-like interface did not contain C-sensory peptidergic or sympathetic neural structures. Only limited attempts to neural regeneration were detected. In contrast, pseudocapsule expressed dense innervation with strong CPON-ir sympathetic innervation and osteoarthritis also had C-sensory fibers. Intense neural regeneration was seen in these synovial membranes. Surprisingly, stellate and/or highly dendritic fibroblast-like cells in the fibrotic areas in the interface tissue expressed strong immunoreactivity to the neural marker PGP 9.5, ubiquitin carboxyterminal hydrolase. CONCLUSION: Pain related to aseptic loosening cannot arise in the aneural interface membrane. Inflammation in interface/aseptic loosening seems to be driven by non-neurogenic factors, such as foreign bodies and micromovement. Insufficient lysosomal degradation of denatured proteins causes accumulation of ubiquitinated conjugates and enzymes involved in the process. This leads to insufficient degradation of platelet derived growth factor (PDGF)-receptor complex and can contribute to the accumulation of connective tissue in the interface. Failure in ubiquitin mediated proteolysis might support overgrowth of interface tissue and aseptic loosening.     

Genes involved in atherosclerosis

Atherosclerosis is a multifactorial disease that involves several genes and proteins. The purpose of this article is to focus on the arterial wall and to review lipoprotein receptors, growth factors, cytokines, chemokines, matrix metalloproteinases, adhesion molecules, and apoptosis genes and their involvement in atherogenesis.     

Radioimmunodetection and Radioimmunotherapy of Malignant Melanoma: A Review

Radioimmunodetection utilizing monoclonal antibodies to various melanoma-associated surface antigens has been studied by several investigators during the past ten years. In the early trials, antibodies were labeled with ¹³¹I or ¹¹¹In, but now ^99mTc is almost exclusively used because of its more favorable energy for gamma camera imaging. Excellent specificity has been achieved in most studies, whereas sensitivity has been less good. In a recent European multicenter study on 493 patients sensitivity was 79% and specificity 96%. In this largest study on melanoma so far performed many previously unknown metastatic deposits were identified indicating that radioimmunodetection has a role in the management of metastatic disease. The clinical utility of immunoscintigraphy in localization of regional lymph node metastases has been documented in several investigations in recent years, indicating that this method can be used in the preoperative evaluation of patients. Radioimmunodetection has also been successfully used in the differential diagnosis of ocular lesions. However, conclusive evidence of improved patient outcome resulting from the earlier detection of melanoma lesions by immunoscintigraphy is still lacking. Anti-melanoma antibodies labeled with alpha- and beta-emitting isotopes are potential therapeutic agents, but so far there is little clinical experience with radio-immunotherapy of metastatic melanoma.     

Amplification of fgfr4 gene in human breast and gynecological cancers

We have investigated gene amplification of fibroblast growth factor receptor-4 (FGFR4) gene in 30 primary breast tumor samples and 15 gynecological tumor samples. Ten percent of the breast tumors showed 2- to 4-fold amplification. Amplification was found more frequently in estrogen- and progesterone-receptor-positive tumors and in tumors with high lymph-node involvement. Breast tumor samples were also analyzed for the amplification of fgfr3 and erbB2 genes and the chromosome I Iq 13 located genes hst I Iint2lbci1 /sea. erbB2 gene was amplified 2- to 13-fold in 13% of the cases, but no amplification of int2/hst I/be/1/sea amplicon was found. Gynecological tumors were also analyzed for the amplification of fgfr4 and fgfr3 genes and for int2 and hst I oncogenes. Eleven of the 15 gynecological tumors were ovarian neoplasms including 2 benign tumors; the remainder comprised I ovarian metastasis of breast cancer; I endometrial cancer; I uterine leiomyosarcoma and I carcinosarcoma of the fallopian tube. In gynecological tumors, fgfr4 gene was found to be amplified in 2 ovarian tumors. Amplification of hst I was found in I benign ovarian tumor. Thus, the fgfr4 gene may be involved in breast and ovarian tumorigenesis.     

Comparison of radiological findings and microbial aetiology of childhood pneumonia

Sixty-one children were treated in hospital from 1981 to 1982 because of both radiologically and microbiologically verified viral or bacterial pneumonia. The chest radiographs were interpreted by two radiologists, not familiar with the clinical data, on two occasions three years apart, and only those patients with a definite alveolar ( n = 27) or interstitial ( n = 34) pneumonia at both evaluations were included in the present analysis. In addition, all patients had viral ( n = 20), mixed viral-bacterial ( n = 21) or bacterial ( n = 20) infections diagnosed by viral or bacterial antibody or antigen assays. Viral infection alone was seen in 7 (26%), mixed viral-bacterial infection in 8 (30%) and bacterial infection alone in 12 (44%) of the 27 patients with alveolar pneumonia. The respective figures were 13 (38%), 13 (38%) and 8 (24%) for the 34 patients with interstitial pneumonia. C-reactive protein concentration was greater than 40 mg/l (a screening limit for viral and bacterial infections) in 15 (56%) of the patients with alveolar and in 11 (32%) of the patients with interstitial pneumonia. Thus 74% of the patients with alveolar and 62% with interstitial pneumonia had bacterial infection, either alone or as a mixed viral-bacterial infection. Our results suggest that the presence of an alveolar infiltrate in a chest radiograph is a specific but insensitive indicator of bacterial pneumonia. We conclude that patients with alveolar pneumonia should be treated with antibiotics. In patients with interstitial pneumonia, however, both viral and bacterial aetiology are possible. In those, the decision concerning antibiotic treatment should be based on clinical and laboratory findings.