Patents and intellectual property: a salvation for patient-oriented research?
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Biomedical subjects
Publications and source records attributed to J Rees.
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OBJECTIVES: To explore British community pharmacists' views on PAS, including professional responsibility, personal beliefs, changes in law and ethical guidance. DESIGN: Postal questionnaire. SETTING: Great Britain. SUBJECTS: A random sample of 320 registered full-time community pharmacists. RESULTS: The survey yielded a response rate of 56%. The results showed that 70% of pharmacists agreed that it was a patient's right to choose to die, with 57% and 45% agreeing that it was the patient's right to involve his/her doctor in the process and to use prescription medicines, respectively. Forty-nine per cent said that they would knowingly dispense a prescription for use in PAS were it to be legalized and 54% believed it correct to refuse to dispense such a prescription. Although 53% believed it to be their right to know when they were being involved in PAS, 28% did not. Most pharmacists (90%) said that they would wish to see the inclusion of a practice protocol for PAS in the code of ethics of the Royal Pharmaceutical Society of Great Britain (CE-RPSGB) in the event of a change in the law on PAS. In addition, 89% would wish to see PAS included in the Conscience Clause of the CE-RPSGB. Males were found to be significantly less likely to favour PAS than females (p < 0.05), as were those declaring an ethnic/religious background of consideration when dealing with ethical issues in practice compared with their counterparts (p < 0.00005). CONCLUSION: Pharmacists view their professional responsibility in PAS to be more obligatory than a physician's, in having to provide the means for PAS. It is worrying that a proportion of the respondents prefer to remain in ignorance of the true purpose of a prescription for PAS; a finding at odds with current developments within the pharmaceutical profession. A practice protocol for PAS and an extension of the conscience clause should be considered in the event of PAS becoming legal. Such measures would allow the efficient provision of the pharmaceutical service whilst at the same respecting the personal beliefs of those who object to cooperating in the ending of a life.
Neurological complications of cancer are some of the most feared manifestations of malignant disease. Their frequency is increasing with improvements in the treatment of primary systemic disease. This article discusses the approach to patients with neurological complications of cancer and reviews some of the most common causes.
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AIMS: We studied the tissue expression of hepatitis B e antigen (HBeAg) in 29 liver biopsies from 27 HBV carriers. METHODS: HBeAg expression was assessed in relation to HBeAg in serum, precore mutations, HBV DNA levels and liver damage as measured by histology activity index. RESULTS: HBeAg in liver tissue was detected by immunostaining in 6 of 7 patients positive for HBeAg in serum. In patients negative for HBeAg in serum, HBeAg was detected in none of 11 specimens from patients infected exclusively with a precore mutant that disrupts HBeAg synthesis, as compared with 3 of 11 specimens from patients carrying HBV with an intact precore region. These 3 patients all showed high HBV DNA levels in serum and severe liver damage. CONCLUSIONS: Overall, viral replication was strongly associated with the cytoplasmic HBeAg and nuclear HBcAg staining, but not with tissue staining for HBsAg. Because of the close relationship between tissue HBeAg expression and high viral load, the pathogenetic importance of HBeAg remains unclear.
OBJECTIVE: To study the association between anti-ganglioside antibody responses and Guillan-Barré syndrome (GBS) after a recent cytomegalovirus (CMV) infection. METHODS: Enzyme linked immunosorbant assay (ELISA) was undertaken on serum samples from 14 patients with GBS with recent cytomegalovirus (CMV) infection (CMV+GBS) and 12 without (CMV-GBS), 17 patients with other neurological diseases (OND), 11 patients with a recent CMV infection but without neurological involvement, 11 patients with recent Epstein-Barr virus (EBV) infection but without neurological involvement, and 20 normal control (NC) subjects. RESULTS: IgM antibodies were found at 1:100 serum dilution to gangliosides GM2 (six of 14 patients), GM1 (four of 14), GD1a (three of 14) and GD1b (two of 14) in the serum samples of the CMV+GBS patients, but not in those of any of the CMV-GBS patients. IgM antibodies were also found to gangliosides GM1, GD1a, and GD1b in one of 11 OND patients, to ganglioside GM1 in one of 11 non- neurological CMV patients, and to ganglioside GD1b in one of 20 NC subjects. Some patients with EBV infection had IgM antibodies to gangliosides GM1 (five of 11), GM2 (three of 11), and GD1a (two of 11). However, the antibodies to ganglioside GM2 had a low titre, none being positive at 1:200 dilution, whereas five of the CMV+GBS serum samples remained positive at this dilution. CONCLUSION: Antibodies to ganglioside GM2 are often associated with GBS after CMV infection, but their relevance is not known. It is unlikely that CMV infection and anti-ganglioside GM2 antibodies are solely responsible and an additional factor is required to elicit GBS.
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Cytogenetics is considered one of the most valuable prognostic determinants in acute myeloid leukemia (AML). However, many studies on which this assertion is based were limited by relatively small sample sizes or varying treatment approach, leading to conflicting data regarding the prognostic implications of specific cytogenetic abnormalities. The Medical Research Council (MRC) AML 10 trial, which included children and adults up to 55 years of age, not only affords the opportunity to determine the independent prognostic significance of pretreatment cytogenetics in the context of large patient groups receiving comparable therapy, but also to address their impact on the outcome of subsequent transplantation procedures performed in first complete remission (CR). On the basis of response to induction treatment, relapse risk, and overall survival, three prognostic groups could be defined by cytogenetic abnormalities detected at presentation in comparison with the outcome of patients with normal karyotype. AML associated with t(8;21), t(15;17) or inv(16) predicted a relatively favorable outcome. Whereas in patients lacking these favorable changes, the presence of a complex karyotype, -5, del(5q), -7, or abnormalities of 3q defined a group with relatively poor prognosis. The remaining group of patients including those with 11q23 abnormalities, +8, +21, +22, del(9q), del(7q) or other miscellaneous structural or numerical defects not encompassed by the favorable or adverse risk groups were found to have an intermediate prognosis. The presence of additional cytogenetic abnormalities did not modify the outcome of patients with favorable cytogenetics. Subgroup analysis demonstrated that the three cytogenetically defined prognostic groups retained their predictive value in the context of secondary as well as de novo AML, within the pediatric age group and furthermore were found to be a key determinant of outcome from autologous or allogeneic bone marrow transplantation (BMT) in first CR. This study highlights the importance of diagnostic cytogenetics as an independent prognostic factor in AML, providing the framework for a stratified treatment approach of this disease, which has been adopted in the current MRC AML 12 trial.
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OBJECTIVE: Human autoantibodies reacting with protein components of the microtubule organizing center of the cell, the centrosome, are rare and have not been extensively studied. We therefore investigated the number, type, and frequency of autoantibodies reactive with centrosomal proteins in a cohort of human sera. METHODS: To establish the type of autoantibodies found in autoimmune sera reactive with the centrosome, we used a prototype human serum, which was chosen for its intense reactivity with the centrosome throughout the cell cycle, to screen a HeLa complementary DNA (cDNA) (expression) library. Positive cDNA clones were sequenced and classified as encoding either known centrosomal autoantigens, known centrosomal proteins but unknown as human autoantigens, or previously unknown centrosomal antigens. To investigate whether these centrosomal autoantibody classes were characteristic of centrosomal-reactive sera, sera from 21 subjects with centrosomal reactivity by indirect immunofluorescence were characterized by Western blotting for reactivity to recombinant protein from each of the classes of centrosomal antigens. Clinical features were studied by retrospective chart review. RESULTS: In each of the sera, autoantibodies that recognize a group of centrosomal proteins were identified. This group included known centrosomal autoantigens (pericentrin and pericentriolar material 1 [PCM-1]), the human homolog of a known mouse centrosomal protein, ninein, which was previously unknown as a human autoantigen, and a novel centrosomal protein (Cep250). Autoantibodies to PCM-1 were the least common (8 of 21 subjects; 38%) while those to ninein, Cep250, and pericentrin occurred at roughly equal frequencies (17 subjects [81%], 17 subjects [81%], and 19 subjects [90%], respectively). There was no apparent correlation between serum autoantibody reactivity and the clinical diagnosis. CONCLUSION: Each of the autoimmune sera contained autoantibodies that reacted with a group of centrosomal proteins. We found that the centrosomal component ninein, first identified in mice, has a human homolog that is an autoantigen. Also, anticentrosomal sera contained antibodies to previously undetected centrosomal components. One of these novel antigens was identified and was designated Cep250. Thus, a characteristic of sera reactive with the centrosome is that they contain antibodies to a group of centrosomal proteins.
It is notoriously difficult to assess the contribution of the sedative effects of benzodiazepines to the cognitive impairments that they produce. The purpose of the present experiment was to determine whether a similar pattern of cognitive impairment would be seen in conditions when subjects felt equally sleepy as the result of sleep deprivation. The effects of a sedative dose of lorazepam (2.5 mg) in healthy volunteers was therefore compared with the effects of acute sleep deprivation (a night on-call) in a group of junior doctors and the effects of chronically disturbed sleep due to snoring. Lorazepam, acute sleep deprivation, and chronic sleep disturbance all significantly increased subjective sedation. In addition, lorazepam significantly impaired performance in two tests of psychomotor speed and caused significant anterograde amnesia. Semantic and short-term memory were not impaired by lorazepam, nor was there any impairment in executive function. The only deficit found following acute sleep deprivation was in a test of semantic memory, generating examples from a difficult category. The only significant deficit in the group suffering from chronically disturbed sleep, compared with age-matched controls, was in executive function, and there was a nearly significant impairment in sustained attention. These results suggest that, despite the common factor of increased subjective sedation, the profile of cognitive impairment in the two sleep deprivation groups are neither similar to each other nor to that seen following an acute dose of lorazepam.
Hepatic veno-occlusive disease (VOD) of the liver is a common complication following high-dose cytotoxic therapy for bone marrow transplantation (BMT). Liver injury is believed to occur following free radical damage to endothelial cells of the sinusoids and small hepatic veins. Glutathione the main antioxidant of the cytosol becomes depleted following chemotherapy. Animal studies have shown that glutamine infusions can maintain glutathione levels and protect against free radical injury. We present two cases of established VOD successfully treated with intravenous glutamine (as dipeptide) and oral vitamin E. Although both cases have possible confounding factors we believe that these give support to the notion that glutamine/vitamin E may have a role in the prophylaxis and treatment of VOD. Further formal trials are indicated.
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BACKGROUND: Muscle functions to generate force-producing movement and also has a role in proprioception. If ageing compromises these sensorimotor functions of muscle, the ability of older subjects to detect and correct postural sway may be impeded, resulting in impairment of functional performance. METHOD: To see if age-related changes occurred and, if so, what their effects might be. Quadriceps strength, proprioception, postural stability and functional performance were assessed in young (n = 20, mean age 23 years), middle-aged (n = 10, mean age 56 years) and elderly (n = 15, mean age 72 years) subjects. RESULTS: With increasing age there were decreases in quadriceps strength (r = -0.511; P < 0.001), acuity of joint position sense (r = -0.603; P < 0.001) and postural stability (ANOVA < 0.002) during stance conditions which placed a greater reliance on muscle proprioceptors. These changes may decrease postural stability confidence, resulting in impaired performance of common activities of daily living (r = 0.635; P < 0.001). CONCLUSIONS: The age-related deterioration in sensorimotor function of muscle may contribute to the increased fear and frequency of falls in elderly subjects, thereby decreasing independence.
Three-and four-part comminuted fractures of the proximal humerus are difficult and technically demanding to treat. The various treatment methods reported in the literature are reviewed. It is recommended that three-part fractures be treated with open reduction and internal fixation. Four-part fractures in the younger, active patient also can be treated successfully with open reduction and internal fixation. However, in the elderly and in the patient with osteoporosis, a hemiarthroplasty is the treatment of choice. There is a need for universal agreement on a scoring system for measuring outcome in these fractures to allow a meaningful comparison between reported treatment methods.