A bioactive sol-gel glass implant for in vivo gentamicin release. Experimental model in Rabbit.

Biomaterial pieces with osteogenic properties, suitable for use in the treatment of bone defects, were synthesized. The materials, which avoid bone infections, are exclusively composed of gentamicin sulfate and bioactive SiO2-CaO-P2O5 sol-gel glass (synthesized previously), and were manufactured by means of uniaxial and isostatic pressure of the mixed components. After implanting the pieces into rabbit femur, we studied (1) antibiotic release, determining the concentration in proximal and distal bone, liver, kidney, and lung as a function of time, and (2) bone growth as a consequence of the glass reactivity in the biological environment. The results demonstrated that the implants are good carriers for local gentamicin release into the local osseous tissue, where they show excellent biocompatibility and bone integration. Moreover, these implants are able to promote bone growth during the resorption process.     

How can health services effectively meet the health needs of homeless people?

BACKGROUND: Homelessness affects many people in contemporary society with consequences for individuals and the wider community. Homeless people experience poorer levels of general physical and mental health than the general population and there is a substantial international evidence base which documents multiple morbidity. Despite this, they often have problems in obtaining suitable health care. AIM: To critically examine the international literature pertaining to the health care of homeless people and discuss the effectiveness of treatment interventions. DESIGN OF STUDY: Review and synthesis of current evidence. METHOD: Medline (1966-2003), EMBASE (1980-2003), PsycINFO (1985-2003), CINAHL (1982-2003), Web of Science (1981-2003) and the Cochrane Library (Evidence Based Health) databases were reviewed using key terms relating to homelessness, intervention studies, drug misuse, alcohol misuse and mental health. The review was not limited to publications in English. It included searching the internet using key terms, and grey literature was also accessed through discussion with experts. RESULTS: Internationally, there are differing models and services aimed at providing health care for homeless people. Effective interventions for drug dependence include adequate oral opiate maintenance therapy, hepatitis A, B and tetanus immunisation, safer injecting advice and access to needle exchange programmes. There is emerging evidence for the effectiveness of supervised injecting rooms for homeless injecting drug users and for the peer distribution of take home naloxone in reducing drug-related deaths. There is some evidence that assertive outreach programmes for those with mental ill health, supportive programmes to aid those with motivation to address alcohol dependence and informal programmes to promote sexual health can lead to lasting health gain. CONCLUSIONS: As multiple morbidity is common among homeless people, accessible and available primary health care is a pre-requisite for effective health interventions. This requires addressing barriers to provision and multi-agency working so that homeless people can access the full range of health and social care services. There are examples of best practice in the treatment and retention of homeless people in health and social care and such models can inform future provision.     

T cells discriminate between differentially phosphorylated forms of alphaB-crystallin, a major central nervous system myelin antigen

Factors such as developmental stage or physiological and infectious stress may change patterns of post-translational protein modification. In order to determine whether such regulated types of modification may influence T cell responsiveness to self proteins we examined the T cell response of SJL (H-2s) mice to alphaB-crystallin, a small heat shock protein that can exist in differentially phosphorylated forms. Epitope mapping revealed the presence of two T cell epitopes that are presented by I-As. One major epitope including residues 41-56 contains an amino acid residue (Ser45) that can be phosphorylated as the result of aging or stress. Accordingly, T cells from SJL mice discriminate between preparations of alphaB-crystallin that differ in their extent of phosphorylation at the level of whole protein as well as at the level of determinant-specific responses. Phosphorylation at Ser45 does not prevent binding of the peptide 41-56 to I-As and computer-assisted modelling of the peptide-MHC complex suggests that the phosphate group of the bound peptide extends outwards from the peptide-binding cleft and may thus be available for direct contact with TCR. Together, our data provide evidence that stress-inducible phosphorylation of alphaB- crystallin creates neo-determinants for T cells and, therefore, may contribute to the breakdown of peripheral tolerance to this self protein.      

CD4+/CD56+ haematodermic neoplasm: a preculsor haematological neoplasm that frequently first presents in the skin

CD4+/CD56+ hematodermic neoplasm, formerly known as blastic NK cell lymphoma, is an aggressive and rare preculsor hematologic neoplasm recently recognized by the WHO-EORTC classification consensus for cutaneous lymphomas. The neoplasm tends to affect elderly patients, who usually present with skin lesions but often have a disseminated disease, including bone marrow involvement. Although the lesions are composed of cells with a lymphoblast-like morphology and an NK-cell phenotype, exhibiting a CD4+, CD56+ positive immunophenotype, recent studies support a relationship to plasmacytoid dendritic cells. Because of the rarity of this disease, we describe two patients suffering a CD4+/CD56+ hematodermic neoplasm.     

4. BREAST CANCER SCREENING

Mammographic screening reduces breast cancer mortality by 24% in women aged ≥50 years. Women aged 50–53 are invited for their first screen in the National Health Service Breast Screening Programme (NHSBSP), thereafter at three-year intervals until the age of 64. Two-view mammography is offered at the first (prevalent) screening examination and one-view for subsequent (incident) screens. The screening films are sorted into either ‘normal’ or ‘abnormal requiring further assessment’. Assessment is carried out by a specialist multidisciplinary team using the triple approach: clinical examination, imaging and, where appropriate, needle biopsy. Imaging is planned according to the mammographic abnormality – paddle compression view to assess parenchymal distortion, magnification view to assess microcalcification. After confirmation of a suspicious abnormality, needle biopsy is performed. Results of triple assessment are considered together by the multidisciplinary team and further management is planned. There are four likely outcomes: benign/normal, confirmed breast cancer, suspicious but needing diagnostic surgical excision, and diagnostic uncertainty needing early recall for screening.     

DNA adducts, mutant frequencies and mutation spectra in lambda lacZ transgenic mice treated with N-nitrosodimethylamine

Groups of lambda lacZ transgenic mice were treated i.p. with N- nitrosodimethylamine (NDMA) as single doses of 5 mg/kg or 10 mg/kg or as 10 daily doses of 1 mg/kg and changes in DNA N7- or O6-methylguanine or the repair enzyme O6-alkylguanine-DNA alkyltransferase (AGT) were followed for up to 14 days in various tissues. Adduct induction in the liver exceeded by at least one order of magnitude than observed in the next nearest target tissue (lung), and was approximately linearly related to dose, except for O6-methylguanine after the first dose of 1 mg/kg which was lower than expected. Substantial induction of lambda lacZ mutagenesis was observed only in the liver, where the mutant frequency was already maximal within 7 days after 5 mg/kg NDMA and remained unchanged thereafter up to 49 days. Small but marginally significant increases in mutant frequency were consistently observed in the spleen after all three modes of treatment. A lack of proportionality between mutation induction and the administered dose or the corresponding adduct levels was observed, probably reflecting the importance of toxicity-related cell proliferation caused by NDMA at higher doses. Twenty eight days after a dose of 10 mg/kg (causing a 3.6- fold increase in mutant frequency), NDMA was found to increase the frequency of GC-->AT mutations (with a concomitant shift of their preferential location from CpG sites to GpG sites), which made up approximately 60% of the induced mutations. Surprisingly, NDMA also caused a significant increase in deletions of a few (up to 11) base- pairs (22%).      

多孔钽假体治疗早期股骨头坏死的生物力学和临床评价

简介 股骨头坏死是因股骨头血运破坏所导致的一种影响功能的疾病。其主要在年轻人中发病。病因包括酗酒、激素药物应用史、创伤、血液系统病、放射治疗以及气压1-30在美国，估计每年有10,000到30,000例发生。其中5％到10％须用人工关节置换术治疗。对股骨头和软骨下板塌陷前的早期坏死进行手术治疗似更有效。早期阶段，病理改变通常局限于股骨头上方负重部位的楔形坏死区。随着疾病的进展。坏死区将塌陷并在存活骨和坏死骨接合处发生骨折。