Tuberculosis in England and Wales. Ethnic origin is more important than social deprivation.
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Biomedical subjects
Publications and source records attributed to M J Doherty.
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This study compared the osteoinductive properties of six different bone graft substitutes: Pyrost, natural coral, Callopat, Surgibone, demineralized Surgibone and demineralized rat bone. The materials were implanted heterotopically, in the abdominal musculature of rats, and the results evaluated histologically at 3 and 6 wk post-implantation. Surprisingly, the results showed that both the demineralized rat bone and demineralized Surgibone were less osteoinductive than might be believed from the literature. Mineralized grafts showed no sign of new bone formation and exhibited variable resorption patterns. A layer of what appeared as dense calcification was seen around the coral implant. The most intense inflammatory reactions were exhibited with the xenografts Surgibone and demineralized Surgibone, indicating persistent immune responses. Coral and Pyrost elicited no marked inflammatory response, and this was attributed to the negligible amounts of protein present in these materials.
SETTING: A retrospective study of tuberculosis notifications in England and Wales published by the Office of Population Censuses and Surveys. OBJECTIVE: To analyse the rise in tuberculosis notifications in England and Wales by different sub groups over the time period 1982-91. DESIGN: The average annual percentage change in tuberculosis notification rates (per 100,000) for the groups were analysed by age, sex, standard region and disease site. RESULTS: The average annual increase in tuberculosis notifications from 1987-91 in females was +2.55 (95% confidence interval [CI] 0.5-4.7); males showed no significant change (-0.6%, 95% CI: -2.9 to +2.7). The increase was greater in younger subjects: 3.2% in females aged 25-44 (95% CI 0.9-5.5) and 4.3% in males aged 15-24 (95% CI 1.7-6.9). Only three standard regions showed an increase: the South East, the West Midlands, Yorkshire and Humberside. This increase was significant only in females from the South East, and was predominantly in non-respiratory tuberculosis. CONCLUSION: The rise in tuberculosis notification rates from 1987-91 has been predominantly in females, in those under 65, has occurred in 3 regions, and predominantly in non-respiratory tuberculosis. The analysis highlights some of the inadequacies of the present notification system for tuberculosis.
A case of obstructive sleep apnoea associated with the Arnold-Chiari malformation is described, in which the loss of pharyngeal sensation seems to have played an important part in the aetiology of the obstruction of the upper airway.
BACKGROUND: Although mortality from tuberculosis has continued to fall in recent years, there has been little change in the case fatality rate for tuberculosis over the same period. This has previously been shown to be due to the increasing proportion of cases of tuberculosis occurring in the elderly. Tuberculosis mortality and case fatality were therefore analysed to determine if this disappointing trend in case fatality rate has occurred from disease in all or only certain sites. METHODS: A retrospective analysis of the tuberculosis mortality and case fatality rates in England and Wales for the period 1972-92 was carried out. The average annual percentage change in tuberculosis was calculated for each disease site and by age group and the results were compared. RESULTS: The analysis showed that, although the mortality rate fell steadily by 5.6% per annum, the case fatality rate decreased by only 0.9% (95% CI -1.7 to -0.1) per annum. The case fatality rate for respiratory and central nervous system disease declined, but no decline in tuberculosis at "other" sites was observed (1.01% (+2.2 to -0.2) for all age groups combined). In the group aged 75 and over, however, the proportion of deaths due to disease at other sites increased by 3.2% (2.2 to 4.3) per annum whilst in the other age groups the mortality rate declined. CONCLUSIONS: This analysis suggests that clinicians may be becoming less able to recognise non-respiratory presentations of tuberculosis, particularly in the elderly, and underlines the need to consider tuberculosis as a diagnosis to avoid delay in treatment.
The drawbacks of freshly harvested autologous bone have resulted in the search for an alternative, capable of supporting osteogenic cell growth. This capability was examined in potential bone graft materials by culturing human osteoblasts on each material. Test materials included rat bone, Surgibone, Ostilit, Biocoral and Tisseel. After 3 days osteoblasts had adhered to all materials, except Ostilit. With increasing time the cells multiplied on the materials, to varying extents. Cell affinity was greatest for rat bone and Tisseel. Fewer cells attached to Biocoral and Surgibone. Thus all the materials, with the exception of Ostilit, were biocompatible for human osteoblasts.
Demineralized human bone used as an autologous bone graft substitute is ethylene oxide sterilized, which is reported to reduce the bone's osteoinductive potential. To determine the minimum sterilization time required and the effect of ethylene oxide on bone's osteoinductive capacity and chemical structure, samples were exposed to ethylene oxide for different times (5-240 min). Results showed that 1 h exposure sterilized the bone (assessed by Attests). This exposure time reduced the bone's osteoinductive potential and caused surface ultrastructural changes. These findings raise questions concerning the suitability of ethylene oxide for sterilizing demineralized human bone.
The advantages and disadvantages of the immunofluorescence and immunoperoxidase techniques and an introductory description of the major variations of the basic immunoperoxidase method are discussed. The ability to identify intermediate filaments, T and B lymphocyte cell markers, S-100 proteins, myelin basic protein, and carcinoembryonic antigen in tissue sections can assist the dermatopathologist in classifying undifferentiated or histologically similar-appearing tumors. A systematic approach to the diagnosis of a majority of these tumors with the use of immunoenzyme staining is provided.
A modified model of conjunctival immediate hypersensitivity in the rat is described. The advantages of this model over previously reported rat models are that it does not require invasive challenges, pre-treatment with mucolytic agents to enhance antigen penetration, or the use of haptens, and is therefore more representative of the mode of allergen challenge seen in human hay fever conjunctivitis. This model has been shown to have both early and late-phase cellular responses but only early phase clinical signs. During the early phase of the response the tarsal region accommodates a massive neutrophil infiltration and the fornix-bulbar region participates to a greater extent during the late-phase reaction, with a significant eosinophil infiltration. The development of this model has allowed us to gain a clearer insight into the mechanisms involved during conjunctival immediate hypersensitivity in the rat; and the simplicity of this model makes it attractive to use in the evaluation of new drug therapies prior to their introduction into human clinical trials.
Derivatives of plasmid pBR322 DNA containing tet mutations were constructed by inserting XhoI linkers at various sites in the tetracycline resistance gene. Monomer plasmids containing either the tet-10 allele located at nucleotide position 23 or the tet-14 allele located at nucleotide position 1267 were used to construct a circular dimer containing one copy of each allele and a circular trimer containing one copy of the tet-10 allele and two copies of the tet-14 allele. Genetic recombination of these plasmid DNAs to produce a functional tetracycline resistance gene could be detected as the production of tetracycline-resistant progeny during the growth of transformants or using a restriction mapping assay which detected the rearrangement of the mutant alleles. The structure of individual tetracycline-resistant recombination products was determined by restriction mapping. This analysis suggested that as many as 70% of the plasmid recombination events in Escherichia coli AB1157 could have involved gene conversion events. The formation of these recombination products was most easily predicted by a model involving figure 8 recombination intermediates and the formation of symmetric regions of heteroduplex. Recombination in JC10287 delta(srlR-recA)304 occurred at 5% of the wild-type frequency and appeared to occur by a similar mechanism. Recombination in JC9604 recA56 recB21 recC22 sbcA23 occurred at 20 times the wild-type frequency and appeared to involve multiple independent recombination events.
Results are presented for two studies of speechreading through the Tadoma method using normal subjects with simulated deafness and blindness. In the first study, subjects received training on the identification of consonant and vowel stimuli through Tadoma. In posttraining tests, an average score of 73% was obtained on a set of 24 consonants presented in CV syllables, and an average score of 82% was obtained on a set of 15 vowels and diphthongs presented in /g/-V-/d/ syllables. An analysis of the confusion matrices derived from the identification tests in terms of of various articulatory/phonological features indicated that the features place, voicing, frication, and round were well-perceived for consonants and round, tense, vertical lip separation, and low, for vowels. In the second study, subjects received training through Tadoma on comprehension of sentences composed of words from a 43-item vocabulary. In tests for which sentence stimuli were repeated until a correct response was obtained, the subjects identified an average of 30% of the words correctly on the first presentation and required an average of roughly four presentations for complete identification of the stimulus.
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The effects of intravenous administration of nedocromil sodium were investigated in active and passive models of conjunctival immediate hypersensitivity in rats. In the active sensitization model, animals were immunized with ovalbumin 21 days prior to ocular instillation of a solution containing ovalbumin. Nedocromil sodium administered prior to antigen challenge significantly inhibited emergence of conjunctival edema and erythema (P < .05) and reduced mast cell degranulation (P < .02). In the passive-sensitization model, the conjunctiva in one eye was injected with ovalbumin antiserum 48 hours prior to intravenous administration of ovalbumin. Nedocromil sodium administered prior to antigen challenge significantly and dose-dependently reduced appearance of the signs of conjunctivitis (P < .01) as well as vascular leakage (P < .05). These data indicate that intravenous nedocromil sodium is effective in animal models of allergic conjunctivitis and may have potential for wider therapeutic application. These data are also consistent with results of clinical studies in which nedocromil sodium relieved symptoms of allergic conjunctivitis and further support a role for nedocromil sodium in the prevention of allergic conjunctivitis.
In order to assess the ability of six potential bone graft substitutes to support the growth of human osteoblasts, these cells were grown in culture and then plated onto fragments of the six materials and cultured for a further period of 15 days. Tests to confirm the osteoblastic phenotype of the cells included spectrophotometric alkaline phosphatase assay; Western blotting of secreted osteocalcin, osteonectin, bone sialoprotein, and collagen type I; and mineralization within the cultures provided with a supplemented medium. Cells were seeded onto the materials in 24-well plates (Nunc, Naperville, IL) at density levels 12,500 cells/cm2 and 25,000 cells/cm2. Specimens were examined after the 15-day culture period by scanning electron microscopy. At a seeding density of 12,500 cells/cm2 results showed that the human osteoblasts had greatest affinities for demineralized rat bone and demineralized Surgibone, whilst few osteoblasts were found attached to Pyrost, Surgibone, or coral. The collagen matrix of Callopat hydrated in the culture media exposing the hydroxyapatite crystals within it, and these became the foci for cell attachment and growth. At a seeding density of 25,000 cells/cm2 the osteoblasts had attached to and proliferated upon the surfaces of all the materials, forming multilayers, with the exception of Surgibone. These experiments demonstrated that all the materials, with the exception of nondemineralized Surgibone, were biocompatible for human osteoblasts.(ABSTRACT TRUNCATED AT 250 WORDS)