A new surgical treatment of an acute dislocation of the proximal tibiofibular joint

Acute dislocation of the proximal tibiofibular joint is rare, and although most dislocations are treated by closed reduction, open reduction and internal fixation is sometimes required. We present the case of an injury to a professional football player where open reduction and internal fixation with bioabsorbable pins was performed.     

Management of osteoporosis in an orthopaedic department: audit improves practice

Patients presenting with an osteoporosis-related fracture are at increased risk of further fractures. We performed a retrospective survey to determine if elderly patients presenting to the orthopaedic unit at Manchester Royal Infirmary with low energy hip or distal radius fractures were being managed appropriately with regards to assessment, investigation and treatment for possible osteoporosis. The initial survey demonstrated that only 16% of elderly female patients with low energy hip fractures and none of those (0%) with distal radius fractures were started on treatment or referred for further investigations for possible osteoporosis. After changes in our practice, 76% (p < 0.00001) of patients with hip fractures and 81% (p < 0.00001) of those with distal radius fractures were investigated, started on treatment or referred to a consultant physician for the management of osteoporosis.     

Interleukin-10 receptor signaling through STAT-3 regulates the apoptosis of retinal ganglion cells in response to stress

PURPOSE: Interleukin (IL)-10 has recently been shown to promote survival of neurons and glia. The purpose of this report is to investigate whether IL-10 has any role in protecting retinal ganglion cells (RGCs) from death under conditions in which growth factors are removed, or in which oxidative stress is present. Signal transduction pathways that activate IL-10 signaling in RGCs were studied in both stress conditions. METHODS: Effects of various interleukins on the viability of the RGC cell line was determined, and apoptotic cells were quantified. Immunoblot analysis was preformed to identify the IL-10 receptor (IL-10R) and phosphorylated or nonphosphorylated Akt and STAT-3 proteins in RGC extracts. Immunohistochemistry was performed on the rat retinal sections to identify native IL-10R. RESULTS: Apoptosis of RGCs in the absence of growth factors with or without dexamethasone (1 microM) occurred in 68.5% +/- 3.4% and 53.4% +/- 2.6% of cells, respectively, after 96 hours. Addition of IL-10 at a concentration of 50 ng/mL significantly reduced the apoptotic population of RGCs to 28.2% +/- 2.3% in the absence of growth factors with dexamethasone and to 31% +/- 2.7% in the absence of growth factors alone. RGCs as well as native retina expressed functional IL-10R as determined by immunoblot analysis and by the ability of IL-10 to phosphorylate Stat-3. However, IL-10 failed to phosphorylate Akt in these cells. CONCLUSIONS: IL-10 caused a 59% and 42% reduction in the apoptotic population of serum-deprived cells with and without dexamethasone treatment, respectively. These observations establish that activation of IL-10R promotes survival of RGCs and this survival-promoting activity is due to IL-10 signaling through the Stat-3 pathway, which inhibits the cell death and not through the Akt cell survival pathway.     

Management of thalidomide toxicity

Thalidomide has re-emerged as a novel antineoplastic agent with immunomodulatory and antiangiogenic activities. In the early sixties, it was withdrawn from the market after its infamous association with congenital abnormalities that left about 10,000 children affected world-wide. With strict regulations and precautions, thalidomide is now approved by the FDA for the treatment of erythema nodosum leprosum. Its role in cancer therapy is promising, with clinical trials in the past 5 years showing significant activity in multiple myeloma. Several trials are ongoing in other malignancies, such as myelodysplastic syndrome, agnogenic myeloid metaplasia, renal cell carcinoma, and prostate cancer. The major toxicities of thalidomide are birth defects, sensorimotor peripheral neuropathy, somnolence, rash, fatigue, and constipation. Less common side effects include deep venous thrombosis, Stevens-Johnson syndrome, elevated liver enzymes, malaise, and peripheral edema. The incidence and severity of adverse events are related to dose and duration of therapy. Doses of the drug of 200 mg/day or less are usually well tolerated. In this review, we will discuss the incidence and management of the side effects of thalidomide and the precautions and interventions needed to minimize the toxicities of this drug.     

Patterns of service use among persons with schizophrenia and other psychotic disorders

OBJECTIVE: This study assessed 12-month service use patterns among people with psychotic disorders and sought to identify determinants of service use. METHODS: As part of a large two-phase Australian study of psychotic disorders, structured interviews were conducted with a stratified random sample of adults who screened positive for psychosis. Demographic characteristics, social functioning, symptoms, mental health diagnoses, and use of psychiatric and nonpsychiatric services were assessed. Data were analyzed for 858 persons who had an ICD-10 diagnosis of a psychotic disorder and who had been hospitalized for less than six months during the previous year. RESULTS: People with psychotic disorders had high levels of use of health services, both in absolute terms and relative to people with nonpsychotic disorders. Those with psychotic disorders were estimated to have an average of one contact with health services per week. Use of psychiatric inpatient services was associated with parenthood, higher symptom levels, recent attempts at suicide or self-harm, personal disability, medication status, and frequency of alcohol consumption. Services provided by general practitioners (family physicians) were more likely to be obtained by older people, women, people with greater availability of friends, those with fewer negative symptoms, and those whose service needs were unmet by other sources. People who were high users of health services also reported having more contact with a range of non-health agencies. CONCLUSIONS: The predictors of service use accounted for small proportions of the variance in overall use of health services. The role of general practitioners in providing and monitoring treatment programs and other psychosocial interventions needs to be acknowledged and enhanced.     

Screening mammography in women aged 40-49 years

Screening mammography in women aged 40-49 years reduces breast cancer mortality by 16%-18%, and is recommended by various national organizations. However, one must be aware of the recognized limitations of the approach. The actual benefit appears to be small (absolute risk reduction, 0.07%; the number of women who need to be screened to prevent 1 woman from dying of breast cancer, about 1,500-2,500), and there are associated risks and costs with this approach. The medical and scientific communities, in partnership with advocacy groups, must continue to work to improve our breast diagnostic capabilities, especially in younger women. Since this is an emotional and controversial issue, each woman will need to consider, with the aid of her primary caregiver, whether the risks of screening outweigh its potential benefits, and make an informed decision regarding screening.     

Bone marrow angiogenesis in patients achieving complete response after stem cell transplantation for multiple myeloma.

Although most of the initial studies in angiogenesis were done on solid tumors, there is now data suggesting the importance of angiogenesis in hematologic malignancies. We estimated bone marrow microvessel density before autologous stem cell transplantation and at the time of response in 13 patients with myeloma (seven complete and six partial responders) using an immunohistochemical stain for factor VIII-related antigen (von Willebrand factor). Baseline microvessel density was significantly different between bone marrow samples from patients with myeloma and morphologically normal, staging marrows from patients with limited stage Hodgkin's disease, mean (+/- s.d.) 294 (+/-115)/mm2 vs 93 (+/-26/mm2, respectively, P = 0.001. After transplantation, microvessel density continued to be high in myeloma samples compared to samples from control patients with limited stage Hodgkin's disease, mean (+/- s.d.) 230 (+/-68)/mm2, P = 0.003. There was no difference in microvessel density at the time of complete or partial response compared to values prior to transplantation. This report confirms that increased angiogenesis is found in myeloma bone marrow prior to transplantation, and suggests that increased angiogenesis persists even after complete response.     

Clinical significance of the translocation (11;14)(q13;q32) in multiple myeloma

The most common chromosomal translocation in multiple myeloma (MM) is t(11;14)(q13;q32). Here, we describe the clinical characteristics of patients with MM who have this translocation. We have identified 24 patients at our institution who had t(11;14)(q13;q32) as determined by standard cytogenetic analysis (CC). Seven patients had the translocation detected at the time of original diagnosis and 17 at the time of relapse. Median survival in all patients after original diagnosis was 43 months; median survival after the translocation was detected was 11.9 months. Four patients had a clinical diagnosis of plasma cell leukemia. Most patients had an elevated beta2-microglobulin (13/20 had >4 microg/ml). The bone marrow (BM) labeling index (LI) of patients, at the time of translocation detection, was elevated in most (median 1.4%, 17/23 patients had BMLI > or = 1%). Of the 24 patients, 19 (79%) died of disease progression and 5 (21%) were alive with disease at last follow-up. Lytic lesions, bone pain, or compression fractures eventually developed in all patients. Patients with MM who have t(11;14)(q13;q32) detected by standard cytogenetics seem to have an aggressive clinical course.