Intraocular use of rituximab KITZMANN, A. S; PULIDO, J. S; DIXON, L. E ...
Eye,
12/2007, Letnik:
21, Številka:
12
Journal Article
Recenzirano
Odprti dostop
To evaluate the toxicity of 1 mg of intraocular rituximab and to present a small case-series of patients treated with intravitreal rituximab.
Rituximab (1 mg/0.1 ml) was injected in the vitreous of ...one eye of three Dutch-belted rabbits. Two animals were injected with balanced salt solution as controls. At 1 month the rabbits were killed and the eyes examined by light microscopy. Three patients (five eyes) with intraocular lymphoma were also treated with a 1 mg injection of rituximab.
The treated rabbit eyes and the control eyes showed no light microscopic evidence of ocular toxicity at 1 month following injection. The five human eyes of three patients have shown no evidence of intraocular toxicity with a median follow-up time of 3.6 months (range 2.0-6.4 months). One patient received a total of four injections in the right eye and three injections in the left eye.
Intravitreal rituximab at a dose of 1 mg does not appear to cause toxicity in rabbit eyes and in the five eyes of three patients.
Background
Despite drug and surgical therapies for Parkinson's disease, patients develop progressive disability. It has both motor and non‐motor symptomatology, and their interaction with their ...environment can be very complex. The role of the occupational therapist is to support the patient and help them maintain their usual level of self‐care, work and leisure activities for as long as possible. When it is no longer possible to maintain their usual activities, occupational therapists support individuals in changing and adapting their relationship with their physical and social environment to develop new valued activities and roles.
Objectives
To compare the efficacy and effectiveness of occupational therapy with placebo or no interventions (control group) in patients with Parkinson's disease.
Search methods
Relevant trials were identified by electronic searches of MEDLINE (1966‐April 2007), EMBASE (1974‐2000), CINAHL (1982‐April 2007), Psycinfo (1806‐April 2007), Ovid OLDMEDLINE (1950‐1965), ISI Web of Knowledge (1981‐April 2007), National Library for Health (NLH) (April 2007), Nursing, Midwifery and Allied Health (NMAP) (April 2007), Intute: Medicine (December 2005), Proquest Nursing Journals (PNJ, 1986 ‐ April 2007); rehabilitation databases: AMED (1985‐April 2007), MANTIS (1880‐2000), REHABDATA (1956‐2000), REHADAT (2000), GEROLIT (1979‐2000); English language databases of foreign language research and third world publications: Pascal (1984‐2000), LILACS (1982‐ April 2007), MedCarib (17th Century‐April 2007), JICST‐EPlus (1985‐2000), AIM (1993‐April 2007), IMEMR (1984‐April 2007), grey literature databases: SIGLE (1980‐2000), ISI‐ISTP (1982‐April 2007), DISSABS (1999‐2000), Conference Papers Index (CPI, 1982‐2000) and Aslib Index to Theses (AIT, 1716‐ April 2006), The Cochrane Controlled Trials Register (Issue 2, 2007), the CenterWatch Clinical Trials listing service (April 2007), the metaRegister of Controlled Trials (mRCT, April 2007), Current controlled trials (CCT) (April 2007), ClinicalTrials.gov (April 2007), CRISP (1972‐April 2007), PEDro (April 2007), NIDRR (April 2007) and NRR (April 2007) and the reference lists of identified studies and other reviews were examined.
Selection criteria
Only randomised controlled trials (RCT) were included, however those trials that allowed quasi‐random methods of allocation were allowed.
Data collection and analysis
Data was ed independently by two authors and differences were settled by discussion.
Main results
Two trials were identified with 84 patients in total. Although both trials reported a positive effect from occupational therapy, all of the improvements were small. The trials did not have adequate placebo treatments, used small numbers of patients and the method of randomisation and concealment of allocation was not specified in one trial. These methodological problems could potentially lead to bias from a number of sources reducing the strength of the studies further.
Authors' conclusions
Considering the significant methodological flaws in the studies, the small number of patients examined, and the possibility of publication bias, there is insufficient evidence to support or refute the efficacy of occupational therapy in Parkinson's disease. There is now a consensus as to UK current and best practice in occupational therapy when treating people with Parkinson's disease. We now require large well designed placebo‐controlled RCTs to demonstrate occupational therapy's effectiveness in Parkinson's disease. Outcome measures with particular relevance to patients, carers, occupational therapists and physicians should be chosen and the patients monitored for at least six months to determine the duration of benefit. The trials should be reported using CONSORT guidelines.
Objective: Optimizing treatment and outcomes for people with schizophrenia requires understanding of how evidence-based treatments are utilized. Clozapine is the most effective antipsychotic drug for ...treatment-refractory schizophrenia, but few studies have investigated trends and patterns of its use over time internationally. This study examined the prescription patterns of clozapine and its demographic and clinical correlates in Asia from 2001 to 2009.
Method: Clozapine prescriptions were collected in a sample of 6761 hospitalized schizophrenia patients in nine Asian countries and regions using a standardized protocol and data collection procedure.
Results: Overall, the proportion of patients receiving clozapine prescriptions was stable across the three surveys from 2001 to 2009, ranging from 14.5% to 15.9%. However, the rates and patterns observed within different regions and countries at each survey differed considerably. Clozapine use decreased significantly over time in China, while it increased in Korea and Singapore. Multiple logistic regression analysis revealed that patients taking clozapine were significantly younger, had a higher dose of antipsychotic drugs in chlorpromazine equivalents, were more likely to be female, had fewer extrapyramidal symptoms, and had more negative symptoms, admissions and weight gain in the past month than those not receiving clozapine.
Conclusion: The variability in overall rates and changes in prescription rates over time in these samples suggest that factors other than psychopharmacological principles play an important role in determining the use of clozapine in schizophrenia in Asia.
Endostatin is a cleavage product of collagen XVIII that inhibits tumor angiogenesis and growth. Interferon α2a blocks tumor angiogenesis and causes regression of hemangiomas, but has no effect on ...choroidal neovascularization (CNV). Therefore, inhibitors of tumor angiogenesis do not necessarily inhibit ocular neovascularization. In this study, we used an intravenous injection of adenoviral vectors containing a
sig-mEndo transgene consisting of murine immunoglobulin κ-chain leader sequence coupled to sequence coding for murine endostatin to investigate the effect of high serum levels of endostatin on CNV in mice. Mice injected with a construct in which
sig-mEndo expression was driven by the Rous sarcoma virus promoter had moderately high serum levels of endostatin and significantly smaller CNV lesions at sites of laser-induced rupture of Bruch's membrane than mice injected with null vector. Mice injected with a construct in which
sig-mEndo was driven by the simian cytomegalovirus promoter had ∼10-fold higher endostatin serum levels and had nearly complete prevention of CNV. There was a strong inverse correlation between endostatin serum level and area of CNV. This study provides proof of principle that gene therapy to increase levels of endostatin can prevent the development of CNV and may provide a new treatment for the leading cause of severe loss of vision in patients with age-related macular degeneration.
HER-2/neu (neu-N) transgenic mice, which express the nontransforming rat proto-oncogene, develop spontaneous focal mammary adenocarcinomas beginning at 5-6 months of age. The development and ...histology of these tumors bears a striking resemblance to what is seen in patients with breast cancer. We have characterized the immunological responses to HER-2/neu (neu) in this animal model. neu-positive tumor lines, which were derived from spontaneous tumors that formed in neu-N animals, are highly immunogenic in parental, FVB/N mice. In contrast, a 100-fold lower tumor challenge is sufficient for growth in 100% of transgenic animals. Despite significant tolerance to the transgene, neu-specific immune responses similar to those observed in breast cancer patients can be demonstrated in neu-N mice prior to vaccination. Both cellular and humoral neu-specific responses in transgenic mice can be boosted with neu-specific vaccination, although to a significantly lesser degree than what is observed in FVB/N mice, indicating that the T cells involved are less responsive than in the nontoleragenic parental strain. Using irradiated whole-cell and recombinant vaccinia virus vaccinations we are able to protect neu-N mice from a neu-expressing tumor challenge. T-cell depletion experiments demonstrated that the observed protection is T cell dependent. The vaccine-dependent neu-specific immune response is also sufficient to delay the onset of spontaneous tumor formation in these mice. These data suggest that, despite tolerance to neu in this transgenic model, it is possible to immunize neu-specific T cells to achieve neu-specific tumor rejection in vivo. These transgenic mice provide a spontaneous tumor model for identifying vaccine approaches potent enough to overcome mechanisms of immune tolerance that are likely to exist in patients with cancer.
The decline and disappearance of relatively undisturbed populations of amphibians in several high-altitude regions since the 1970s suggests that they may have suffered a global decline, perhaps with ...a common cause or causes. Houlahan et al. examined means of trends for 936 amphibian populations and concluded that global declines began in the late 1950s, peaked in the 1960s, and have continued at a reduced rate since. Here we re-analyse their data using a method that accounts for the sampling of different populations over different time periods, and find evidence of a mean global decline in monitored populations only in the 1990s. However it is calculated, the global mean not only masks substantial spatial and temporal variation in population trends and sampling effort, but also fails to distinguish between a global decline with global causes and the cumulative effects of local declines with local causes.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Current imaging guidelines recommend that many cancer patients undergo soft-tissue staging by computed tomography (CT) whilst the bones are imaged by skeletal scintigraphy (bone scan). New CT ...technology has now made it feasible, for the first time, to perform a detailed whole-body skeletal CT. This advancement could save patients from having to undergo duplicate investigations. Forty-three patients with known malignancy were investigated for bone metastasis using skeletal scintigraphy and 16-detector multislice CT. Both studies were performed within six weeks of each other. Whole-body images were taken 4 h after injection of 500 Mbq (99m)Tc-MDP using a gamma camera. CT was performed on a 16-detector multislice CT machine from the vertex to the knee. The examinations were reported independently and discordant results were compared at follow-up. Statistical equivalence between the two techniques was tested using the Newcombe-Wilson method within the pre-specified equivalence limits of +/-20%. Scintigraphy detected bone metastases in 14/43 and CT in 13/43 patients. There were seven discordances; four cases were positive on scintigraphy, but negative on CT; three cases were positive on CT and negative on scintigraphy. There was equivalence between scintigraphy and CT in detecting bone metastases within +/-19% equivalence limits. Patients who have undergone full whole-body staging on 16-detector CT may not need additional skeletal scintigraphy. This should shorten the cancer patient's diagnostic pathway.
to explore health-care professionals’ views about safety in maternity services. This paper identifies aspects of care that are less safe than they should be, possible ways to improve safety, and ...potential obstacles to achieving these improvements. This study was part of the King's Fund inquiry into the safety of maternity services in England.
qualitative study with a sample of health-care professionals who work in maternity services and who responded to the call for evidence. Data were collected by questionnaire and analysed using thematic content analysis.
maternity professionals throughout England were invited to take part.
midwives, obstetricians, student midwives, nurses, neonatal nurses, general practitioners, managers, hospital doctors and paediatricians. In total, there were 591 respondents.
participants were asked to respond to open-ended questions identifying aspects of maternity care that were less safe than they should be, potential solutions to improve safety of care, and any barriers to implementing these improvements. Problems described included the increasing social and medical complexity of the pregnant population, low staffing levels, inappropriate skill mix, low staff morale, inadequate training and education, medicalisation of birth, poor management, lack of resources and reconfiguration. Proposed solutions included more staff, better teamwork and skill mix, improved training, more one-to-one care, caseloading, better management, more resources, better guidelines and learning from incidents. Barriers to implementing improvements included stressed staff who were resistant to change, inadequate management/poor staff management relationships and financial restraints.
the responses of maternity professionals convey a deep sense of staff anxiety regarding how the problems they face pose a threat to safety.
policy makers and professional bodies need to take the concerns expressed by staff seriously. Concerted efforts are required to improve maternity services and support maternity professionals.
Nijmegen breakage syndrome The, I
Archives of disease in childhood,
05/2000, Letnik:
82, Številka:
5
Journal Article
Recenzirano
Odprti dostop
BACKGROUND Nijmegen breakage syndrome (NBS) is a rare autosomal recessive disorder. NBS-1, the gene defective in NBS, is located on chromosome 8q21 and has recently been cloned. The gene product, ...nibrin, is a novel protein, which is member of the hMre11/hRad50 protein complex, suggesting that the gene is involved in DNA double strand break repair. AIMS To study the clinical and laboratory features of NBS as well as the genotype–phenotype relation. METHODS Fifty five patients with NBS, included in the NBS registry in Nijmegen were evaluated. The majority of the patients were of eastern European ancestry. Most of them had shown a truncating 5 bp deletion 657–661 delACAAA. Four further truncating mutations have been identified in patients with other distinct haplotypes. RESULTS AND CONCLUSIONS Essential features found in NBS were microcephaly, usually without severe retardation, typical facial appearance, immunodeficiency, chromosomal instability, x ray hypersensitivity, and predisposition to malignancy. In 40% of the patients cancer was noted before the age of 21 years. Important additional features were skin abnormalities, particularly café au lait spots and vitiligo, and congenital malformations, particularly clinodactyly and syndactyly. Congenital malformations, immunodeficiency, radiation hypersensitivity, and cancer predispostion were comprehensible in case of dysfunctioning of DNA repair mechanisms. No specific genotype–phenotype relation could be found. Patients with the same genotype may show different phenotypes and patients with different genotypes may express the same phenotype. Specific mutations did not lead to specific clinical features.
Between 1995 and 1998, marine fish from around the coast of the UK were collected and samples analysed for viral haemorrhagic septicaemia virus (VHSV) using cell culture isolation methods. In 1997 ...and 1998 the samples were also analysed for VHSV by reverse transcription PCR (RT-PCR). A total of 1867 fish of 11 species were tested, but VHSV was isolated on only 1 occasion, from herring Clupea harengus, in 1996. However, despite VHSV not being isolated in 1997 and 1998, in both years samples of herring from the west and south coasts of England produced positive signals in the RT-PCR, and in 1997 cod from the east coast of England also produced positive signals in the RT-PCR. These results are believed to be true indications of the presence of VHSV nucleic acid in the fish. In 1997, birnaviruses from Serogroup B1 were isolated from herring (a previously unrecorded host for the virus) and cod Gadus morhua, and a birnavirus from Serogroup A2 was also isolated from cod. In 1998, an aquareovirus was isolated from haddock Melanogrammus aeglefinus, a previously unrecorded host for the virus.
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