Why interferon beta 1b was licensed is a mystery.
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Biomedical subjects
Publications and source records attributed to P Harvey.
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Paraffin sections from 29 lung carcinomas (28 primary and 1 metastatic) and 9 pleural malignant mesotheliomas were immunostained with antisera to human hepatocyte growth factor/scatter factor (HGF/SF) and its receptor, met. For HGF/SF, immunoreactivity was demonstrated in all 9 mesotheliomas, 9 of 12 adenocarcinomas, and 7 of 10 squamous cell carcinomas. None of seven cases of small cell anaplastic carcinoma was positive. The adenocarcinomas frequently showed enhanced luminal staining, suggesting possible secretion of HGF/SF, and this pattern of staining was also seen occasionally in bronchial epithelium adjacent to the tumour. Stromal fibroblasts also showed immunoreactivity for HGF/SF in 6/8 cases of mesothelioma but in only 3/12 adenocarcinomas, 1/10 squamous cell carcinomas, and 1/4 small cell anaplastic carcinomas. All tumours stained for met, usually strongly. The staining was mainly cytoplasmic in nature, but some plasma membrane staining was usually evident. Adenocarcinomas showed strong luminal membrane staining, as did adjacent, histologically normal bronchial epithelium. This study demonstrates the presence of HGF/SF and met in most of the tumour types described, particularly mesotheliomas, and suggests that the HGF/SF/met signalling system may play a role in the development of these tumours, either by autocrine or by paracrine mechanisms.
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OBJECTIVE: Previous studies have suggested that geriatric inpatients with chronic schizophrenia manifest profound cognitive impairments. This study investigated how these cognitive impairments resemble those seen in degenerative dementing conditions. METHOD: The neuropsychological battery of the Consortium to Establish a Registry for Alzheimer's Disease (CERAD), widely used to characterize the cognitive deficits of patients with Alzheimer's disease, was used to compare patterns of cognitive impairment in 66 triads of subjects consisting of one elderly patient with Alzheimer's disease, one elderly, institutionalized patient with chronic schizophrenia, and one elderly, cognitively normal comparison subject who were matched on age, gender, and education. For some analyses, the two groups of patients were divided into subgroups according to the degree of their cognitive impairment (mild, moderate, or severe) as determined by their scores on the Mini-Mental State examination. RESULTS: Relative to the comparison subjects, both groups of patients showed cognitive deficits on each of the neuropsychological measures. The schizophrenic patients performed worse than the patients with Alzheimer's disease on tests of naming and constructional praxis but were less impaired on the test of delayed word recall. These differences were consistent across all levels of severity of globally measured cognitive impairment. CONCLUSIONS: Consistent with earlier findings from postmortem studies, these findings suggest that major differences exist in the neurobiologic mechanisms responsible for cognitive impairment in schizophrenia and Alzheimer's disease. Effects directly attributable to social and environmental differences between these two groups of patients may also play a role.
The characteristics of antigen-specific IgG in patients with multiple sclerosis and patients with encephalitis have been compared. Both groups of patients showed antigen-specific oligoclonal bands locally synthesised in the CSF. When the affinity distribution of the antigen-specific IgG was measured there was a marked difference between the two groups. Encephalitis patients had high affinity antibody against the causative antigen. This was consistent with the antibody undergoing affinity maturation as a result of the immune system fighting a primary infection. Multiple sclerosis patients lacked high affinity response. This lack of high affinity antibody was also seen in those encephalitis patients when antigens other than the causative antigen were studied.
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The role of work in debates over welfare reform in the United States is analyzed. Five issues are identified and discussed under this heading, with special emphasis on the question of whether enough jobs exist to make it possible for all able-bodied welfare recipients to find paid employment in the regular labor market. It is argued that there are not enough jobs available--not even low-wage jobs--to make this a reasonable goal, and that neither conservatives nor liberals have faced up to the dilemma posed by this job shortage. International human rights doctrine concerning the availability of work at decent wages is cited in support of the proposition that the government should be held accountable for filling this job gap, not only for welfare recipients but for all other job-seekers as well. The costs of a hypothetical jobs program capable of achieving this goal are assessed, with the surprising result that it might actually save the public money. It is suggested that such a program could constitute an effective alternative to current welfare reform proposals.
OBJECTIVES: To describe the establishment of a violence management team (VMT) to manage patients who exhibit violent behaviour in a general hospital (Flinders Medical Centre), and to review data collected in the first 44 months of operation. METHODS: The VMT consisted of a doctor, a senior nurse and four orderlies. Calls to the team were recorded and audited. Data were collected from patient case notes and supplemented, where necessary, with information from medical and nursing staff. RESULTS: There were 282 calls for the VMT during the study period, most often to patients with organic mental disorders (45%), substance abuse disorders (18%) and personality disorders (15%). In 30% of calls, verbal placation alone was sufficient to manage the patient; however, 62% of patients needed physical restraint (i.e., were physically held by team members) and 53% were administered a sedative medication. CONCLUSIONS: Violent behaviour in patients in a general hospital is an important problem, often caused by organic mental disorders. This, and the need to restrain aggressive patients so that they can receive essential medical care, suggest that such behaviour should be treated as a clinical problem rather than one for security guards or the police. The VMT provides a mechanism for dealing with aggressive patients which ensures good patient management, as well as protecting the health and safety of staff. It is also a monitor for quality assurance purposes, and provides data to determine the causes of patient violence and to implement prevention programs.
Objective measures of communication efficiency were collected twice on 10 schizophrenic patients while they participated in a structured interactive task which has seen considerable use in developmental studies of communication skills. Referential communication and thought disorder were assessed while patients were off and then on neuroleptic medication. While medicated, subjects produced more informative task-related responses. Drug-free subjects produced more unclear references and episodes of bizarre speech. These "interruptive" tendencies appeared to be a problem of dialogue maintenance and attentional focus, which improved with medication.
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Despite successful orthoptic liver transplantation some patients develop a recurrent headache that interferes with their quality of life. To estimate the frequency of this symptom 34 patients who had undergone orthoptic liver transplantation were questioned about the history and character of any headache. Six patients described a recurrent headache typical of migraine only since transplantation. In two patients the pain improved after reduction of cyclosporin dosage and thereby plasma cyclosporin concentration.
The catalytic cycle of lignin peroxidase (LiP, ligninase) isozyme L3 from the white-rot fungus Phlebia radiata was investigated using stopped-flow techniques. Veratryl (3,4-dimethoxybenzyl) alcohol and a lignin model compound, non-phenolic beta-O-4 dimer 1-(3,4-dimethoxyphenyl)-2-(2-methoxyphenoxy)propane-1,3-diol, were used as electron donors. This is the first report on the detailed kinetic analysis of a LiP-catalysed C alpha-C beta bond cleavage of the dimer, representing the major depolymerisation reaction in the lignin polymer. The native enzyme showed a typical heme peroxidase absorbance spectrum with a Soret maximum at 407 nm. Following the reaction with H2O2, the Soret band decreased in absorbance, shifted to 403 nm and then to 421 nm, demonstrating the formation of compound I followed by the formation of compound II, respectively. Similar results have been reported for the LiP from Phanerochaete chrysosporium upon reaction with H2O2. However, compound I of L3 was more stable in the absence of additional electron donors. The second-order rate constant of compound I formation by H2O2 was determined to be 6 x 10(5) M-1 s-1 and was the same at pH 3.0 and 6.0. Compound I was rapidly reduced to compound II and further to native enzyme when either veratryl alcohol or the beta-O-4 dimer was supplied as electron donor and in both cases veratraldehyde appeared as the major product. At pH 6.0, the second-order rate constant for compound II formation was similar with either veratryl alcohol or the beta-O-4 dimer (6.7 x 10(3) and 6.5 x 10(3) M-1 s-1, respectively). At pH 3.0 formation of compound II with either reductant proceeded so rapidly that determination of the respective rate constants was not possible. The results point to identical catalytic cycles of L3 with veratryl alcohol or the beta-O-4 dimer involving both compounds I and II as intermediates and participation of the same veratryl alcohol radical as the most appropriate reductant for compound II. Chemical evidence of such a radical, formed after the initial LiP-catalysed one-electron oxidation of beta-O-4 dimeric lignin models, is presented in a separate article [Lundell, T., Schoemaker, H., Hatakka, A. & Brunow, G. (1993) Holzforschung, in the press]. The catalytic redox-cycle and the oxidation mechanism presented here reconcile seemingly contradictory results obtained in previous studies on LiP kinetics during the last decade.
We describe a case of lymphocytic meningitis following insertion of a porcine dermis implant to repair an operative dural defect. Histology of the excised implant revealed local abscess formation with a granulomatous reaction. Oligoclonal Immunoglobulin G, part of which could be removed by absorbtion with the porcine dermis, was present in the patient's cerebrospinal fluid, and, to a less marked degree, in his serum. The cerebrospinal fluid glucose was markedly depressed. An unusual hypersensitivity reaction to the porcine implant was considered the most likely explanation for this meningitic illness. The patient went on to make a full recovery following excision of the implant.
Four commercial enzyme immunoassays (EIA), namely the Behring Enzygnost EIA (BE-EIA), Abbott IMx, Whittaker CMV STAT Test Kit and Diamedix assay, were evaluated for the detection of CMV IgG. The methods were compared as to sensitivity, specificity, positive and negative predictive values, global agreement, ease of performance and, for a small number of specimens, reproducibility. Discordant results were resolved by using the Gull CMV indirect fluorescent antibody (IFA) method. Our data suggest that all four assays were valuable screening tools for the detection of CMV IgG based on their high sensitivity and high negative predictive value. However, differences were noted in the reproducibility level and in the incidence of false-positive, equivocal and nonspecific results regarding certain tests in particular. In our hands, the Abbott IMx and the BE-EIA ranked high in the performance characteristics for a good screening test, yet the Abbott IMx offers the added advantages of being the easiest to perform and having the most rapid turnaround time.
This population-based case-control study contrasted nutrient intakes of 41 women with cutaneous malignant melanoma to those of 297 women sampled from the same community (Brisbane, Australia). Diet was assessed by a comprehensive food frequency questionnaire. The strong inverse relation we observed between high intakes of polyunsaturated fatty acids and melanoma (P < 0.01) adds sufficient weight to prior findings for this persisting causal hypothesis to be abandoned. A relatively strong association with alcohol was observed: Women drinking 20 g or more (two or more drinks) daily had 2.5 (odds ratio) times the risk of melanoma as nondrinkers (95% confidence interval, 0.87 to 7.4). However, previous data are inconsistent. With regard to potential protective factors, our data fit with prior speculation that antioxidants (beta-carotene and vitamin E), zinc, and iron warrant further investigation. The nonsignificant (P = 0.18) 40% reduction in risk seen for those eating the most fish (> or = 15 g daily versus < 5 g) suggests the effects of marine oils and omega-3 fatty acids may deserve specific attention.
A 36 year old woman presented with a subacute brainstem syndrome. MRI showed a solitary, gadolinium enhancing brainstem mass, which on biopsy showed perivenous inflammation and demyelination compatible with acute disseminated encephalomyelitis.