A new method of drug application to the nasal passage.
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Biomedical subjects
Publications and source records attributed to I Mackenzie.
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OBJECTIVE: This study sought to investigate the effects of implant dose/volume and surgical resection on survival in a rat glioma brachytherapy model. Two doses were investigated to determine a suitable therapeutic range. METHODS: We performed two experiments. Three treatment groups and one control group of male F-344 rats bearing 9L brain tumors 12 days after tumor inoculation were used in the first experiment. Day 12 tumors were an average of 4 to 6 mm in diameter. Animals treated with brachytherapy received a tumor dose of 80 Gy delivered to a 5.5-mm-radius volume. Total macroscopic tumor removal was achieved by microsurgical techniques. A subsequent experiment compared the survival of tumor-burdened rats treated with an implant dose of 60 Gy delivered to a 5.5-mm-radius volume with a control group. RESULTS: Surgery alone produced an increased life span of 28.6% over control animals treated with sham surgery and dummy seed implants, a statistically significant increase in survival (P = 0.0023, log-rank test). Brachytherapy alone produced the most significant increase in survival over control animals (P = 0.0001, log-rank test; median survival not attained with an implant dose of 80 Gy delivered to a 5.5-mm-radius volume; and P = 0.0001, increased life span 121% with an implant dose of 60 Gy delivered to a 5.5-mm-radius volume). This was not improved by the addition of surgical tumor removal. CONCLUSION: We have demonstrated a relationship between implant dose/volume and survival of tumor-burdened rats in this model that is not improved by the addition of tumor removal. Implications for brain tumor brachytherapy are discussed.
Research in the use of vibrotactile devices has focused predominantly on the vibrotactile receptor system within the skin. There is little research relating to the neural pathways and the central processing of information transmitted to the cortex as a result of vibrotactile stimulation. This pilot study that considers the use of vestibulometric measures in predicting the neural pathways. Three measures of vestibular function were undertaken: saccadic eye movement, smooth pursuit and optokinetic nystagmus. Ten normally hearing adults, with no previous history of vestibular dysfunction, were tested using an ICS computer based vestibular testing system. All subjects were tested in four situations: baseline, wearing vibrotactile device with stimulation, vibrotactile device without stimulation and repeated baseline. Five subjects demonstrated a significant change in vestibular measures, four related to measure of optokinetic nystagmus and two in relation to smooth pursuit. There is a demonstrated difference in vestibular function which supports the need for further investigation.
Since the NHS reforms, health authorities have been purchasing health care and have been advised that public health considerations must inform all NHS activities, and that the Director of Public Health must be supported by a team of qualified support staff. This survey of directors of public health and health authority chief executives in England shows the skills currently available to support health authority purchasing, and the perceived importance of this wide range of skills to the purchasing process. Future models of purchasing will need to ensure access by purchasers to public health and multi-disciplinary advice.
Sensorineural hearing loss, tinnitus, dizziness and ataxia are recognised symptoms associated with Chiari malformations but they are rarely the presenting complaints. Patients with such symptoms are frequently referred to otolaryngologists and audiological physicians. We report a case of a 13-year-old girl who presented complaining of tinnitus and impaired hearing, and was subsequently diagnosed as having a type I Chiari malformation. Pure tone audiogram showed a mild hearing impairment on the left side and the speech audiogram was normal. Auditory brain stem responses and the electronystagmography were abnormal. The patient underwent posterior fossa decompression following which her tinnitus disappeared, the hearing problem recovered and some of the abnormal electrophysiological parameters were corrected.
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Efficient delivery of oxygen is important during hyperbaric oxygen therapy. We compared two systems in common use, and developed a method to ensure that O2 delivery was adequate during treatment. The systems were a demand valve system with an oral-nasal mask, and a continuously ventilated hood. Five groups were studied over two different time periods, and a further trial was undertaken to examine exhaled O2 levels. The results showed that an acceptable Fio2 could be reliably achieved only with the continuously ventilated hood system or when trained staff supervised their colleagues using the demand system. Inasmuch as the oral-nasal mask system is the standard equipment for the North Sea diving industry, this work shows the importance of ensuring that the correct dose of O2 is delivered. The study indicates, however, that identification of the problem does not always allow a complete solution, and that a hood-based system is more reliable.
Information on the prevalence of hearing impairment and related ear pathologies in children in sub-Saharan Africa is scarce. A pilot study for a clinical trial of simple treatments for chronic suppurative otitis media (CSOM) in school children in Kiambu district, Kenya, provided information on the prevalence of hearing impairment and ear pathologies. Five-thousand-three-hundred-sixty-eight children from 57 randomly chosen primary schools in Kiambu district were examined. Simple otoscopy was performed by clinical officers with specialty training in ENT, and hering testing was performed by trained nurses, using a hand held field audiometer. Microbiological specimens were obtained from those children with CSOM. Five-point-six percent of the children had a hearing impairment of > 30 dB HL in one or both ears, with 2.2% having bilateral hearing impairment. Two-point-four percent had at least one perforated tympanic membrane, and 1.1% had CSOM. Eight-point-six percent of the children had wax obstructing the tympanic membrane. There is evidence of a relationship between hearing impairment and both CSOM and wax obstructing the tympanic membrane. The most common organisms found were Pseudomonas spp. (34%), Proteus spp. (34%) and Eschericia coli (19%). These results are comparable with other studies in Africa and indicate a considerable burden of ear disease in Kiambu district, Kenya.
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We investigated the resource available for public health doctors to carry out statutory responsibilities out-of-hours by a postal questionnaire survey of consultants in communicable disease control (CsCDC) in England and Wales. The questionnaire requested details of local District Health Authority (DHA) population profile, major incident and outbreak policies, the background of the CCDC, out-of-hours communication, access and resources, reference materials and medical equipment carried by the public health doctor on duty. The CsCDC from 96% (121/126) DHAs in England and Wales responded. Whilst 85% (101/119) of public health doctors carried policies on infectious disease when on duty, only 28% (32/116) carried policies on dealing with chemical incidents and 25% (28/111) carried the District policy to deal with radiation hazards. Twenty-six per cent (32/121) of public health physicians had no access to their District headquarters. There is a wide variation in the standard of resources available to on-call public health doctors in England and Wales; following Department of Health and Department of the Environment guidance, Health Authorities need to ensure that they have adequate arrangements in the event of any major incident or outbreak.
The amyloid protein precursor (APP) of Alzheimer's disease (AD) is abundantly expressed in platelets, where its primary function remains undetermined. As an integral transmembrane protein, the release of APP from the membrane may be a critical event in AD. We examined the association of APP with human platelet membranes using a combination of alkali treatment and immunoprecipitation of the carboxyl-terminus of APP. Most of the platelet membrane-associated APP (APPMem) with molecular mass of 100 to 130 kD is removed with alkali treatment and is also truncated at the carboxyl-terminus. APPMem is present at least in part on the surface of the platelet. The full-length transmembrane form of APP, as a 140- to 150-kD minor species, is alkali resistant and is also present on the plasma membrane. In contrast, most of the APPMem from brain is full-length (possessing the carboxyl-terminus) with a molecular mass of 105 to 130 kD and is resistant to alkali treatment. Immunoelectron microscopy shows platelet APP to be localized to the alpha-granule. Activation of platelets results in a threefold increase in surface APP detectability. In plasma, the 130-kD APP-reactive band is increased in AD. We find that in the gray platelet syndrome, platelets contain reduced amounts of APP, with a corresponding reduction in plasma APP levels, suggesting that platelets are the major source of plasma APP. Our studies also identify an interaction of APP with platelet membranes which differs from that found in the brain, and raise the possibility of a receptor for APP in platelet membranes. Quantitative differences in the amounts of APPMem in platelets compared with brain also indicate regulation of the pathways that determine the cleavage of APP near its transmembrane domain. These pathways are a therapeutic target in AD, and may be easily amenable to investigation in platelets.
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The parotid glands of 228 Japanese human cadavers were examined to determine the incidence and histological features of accessory parotid glands. The incidence was found to be 56% with no differences between right and left sides or between sexes. Thirty parotid glands and their associated accessory glands were examined histologically: eight of these accessory glands were found to be mixed secretory glands (i.e., containing both serous and mucous acini). Thus, the pattern of differentiation of a significant fraction of accessory glands differs from that of the main parotid gland: it appears that mixed acini, present in the early stages of development, persist into later life, and their presence may be related to tumors developing at these sites.
Various experiments indicate that normal growth and differentiation of murine epithelia in vivo are dependent on dermal influences, and the growth-enhancing effects of various connective tissue elements have also been demonstrated in vitro. Such effects were examined by the in vitro growth of murine epidermis on various substrata (collagen, lens capsule) at the air/medium interface with various connective tissue elements or cells apposed to the undersurface of the supporting matrix. Patterns of epithelial growth, morphology and differentiation were examined by histology, electron microscopy, gel electrophoresis and antibody staining. Growth and differentiation varied with differing substrata but good patterns of growth and morphology, and appropriate expression of cytoplasmic and cell surface differentiation markers, were found only in specimens grown in association with dermal elements. It is concluded that diffusible factors of dermal origin facilitate epithelial growth and differentiation.
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Routine screening for hearing impairment in childhood is now widespread in industrial countries, although there is considerable controversy over the most efficient techniques and procedures. In most developing countries, however, routine screening programmes for hearing impairment do not currently exist. The problems involved in implementing screening programmes in developing and industrial countries are very different, and in selecting screening procedures for a particular population the following factors have to be taken into consideration: the environmental test conditions; the availability of resources for equipment and the training of testers; the local attitudes towards disability; the level of hearing impairment that may cause handicaps; and the major types of pathology causing hearing impairment. We suggest that in developing countries children should be screened at school entry using a simple field audiometer and that the external ear be inspected for the presence of a discharge. There is an urgent need to develop reliable and simple screening procedures for infants and young children; where possible, all children should be screened for severe or significant hearing impairment before the age of 2 years. No screening should, however, be implemented until appropriate follow-up services are available.
OBJECTIVE: To describe the results of human immunodeficiency virus type 1 (HIV-1) antibody testing of blood donations in Australia. DESIGN: Blood transfusion services tabulated the number of HIV-1 antibody tests carried out on blood donations and the number of donations found to be positive, from 1985 to 1990. SETTING: All blood transfusion services in Australia. PARTICIPANTS: All donors of blood in Australia from 1 May 1985 to 31 December 1990. OUTCOME MEASURES: The proportion of blood donations found to have HIV-1 antibody, according to State or Territory, year of donation and, when available, age, sex and donation status (repeat or first-time) of the donor. RESULTS: To the end of December 1990, 5,367,970 donations had been tested for HIV-1 antibody, and 46 were found to have the antibody, giving an overall prevalence rate of 0.86 per 100,000 donations. The highest rate was recorded in New South Wales, followed by Western Australia, and four of eight Australian States and Territories reported no donors with HIV-1 antibody. There has been no clear trend with time, but the rate is about 20% higher for 1989-1990 than for 1985-1986. Of donors found to have HIV-1 antibody, 67% were male and 33% female, and 41% reported no known or potential exposure to HIV-1 other than heterosexual contact. Among blood donors in two major Australian cities, the overall prevalence of HIV antibody was higher in those who were male, younger, and first-time donors. There has been a recent increase in the number of blood donors with HIV-1 antibody who were women reporting heterosexual contact as their only potential exposure. CONCLUSION: The rate of HIV-1 antibody in Australian blood donations remains very low and shows no clear temporal trend, but specific donor characteristics define higher rates of antibody prevalence.
Cells of Candida albicans strain WO-1 and related strains switch frequently and reversibly between a white-colony-forming unit (white phase) and a gray-colony-forming unit (opaque phase). Cells in the budding white phase exhibit the usual smooth round phenotype observed in other C. albicans strains, but cells in the budding opaque phase exhibit a unique elongate shape with surface pimples or protrusions. In this study, it was demonstrated that opaque cells formed hyphae at low to negligible levels in suspension cultures but could be induced to form hyphae at high levels when anchored to the chamber wall of a perfusion chamber or to a monolayer of human skin epithelial cells. Variability in the proportion of hyphae formed between experiments appeared to be due to variability between individual opaque clones. The hyphae formed by opaque cells were morphologically identical to hyphae formed by white cells (i.e., they were devoid of pimples or protrusions and exhibited the same shape and septal locations). They also did not stain with an opaque-specific antiserum which differentially stained opaque budding cells in a punctate fashion. However, when stimulated to form buds, opaque hyphae formed opaque-shaped daughter buds, demonstrating that although they are morphologically similar to hyphae formed by white cells, they are genetically opaque.