Asthma inhalers and subsurface enamel demineralisation: an in situ pilot study.

AIM: The purpose of this pilot study was to identify the subsurface enamel demineralising potential of two possible acidogenic lactose-based powders and their corresponding generic pump inhalers. METHODS: Ten healthy non-asthmatic adults participated in a 5- leg randomised crossover study including a 10% sucrose control. A twice-daily 400 microg dose of inhaler was applied in vitro to a demineralised enamel slab on the buccal flange of a mandibular removable appliance before in situ placement for 14 days each. Lesion parameters were determined using transverse microradiography and digitised image analysis. RESULTS: Minimal demineralisation occurred with sucrose, both pump and one powder inhaler. The remaining powder was associated with remineralisation (p = 0.29). Overall, mean lesion depth increased (p = 0.12). CONCLUSION: Asthma inhalers failed to demonstrate a significant acidogenic/cariogenic effect.     

The Stafford outbreak of Legionnaires' disease

A large outbreak of Legionnaires' disease was associated with Stafford District General Hospital. A total of 68 confirmed cases was treated in hospital and 22 of these patients died. A further 35 patients, 14 of whom were treated at home, were suspected cases of Legionnaires' disease. All these patients had visited the hospital during April 1985. Epidemiological investigations demonstrated that there had been a high risk of acquiring the disease in the out patient department (OPD), but no risk in other parts of the hospital. The epidemic strain of Legionella pneumophila, serogroup 1, subgroup Pontiac 1a was isolated from the cooling water system of one of the air conditioning plants. This plant served several departments of the hospital including the OPD. The water in the cooling tower and a chiller unit which cooled the air entering the OPD were contaminated with legionellae. Bacteriological and engineering investigations showed how the chiller unit could have been contaminated and how an aerosol containing legionellae could have been generated in the U-trap below the chiller unit. These results, together with the epidemiological evidence, suggest that the chiller unit was most likely to have been the major source of the outbreak. Nearly one third of hospital staff had legionella antibodies. These staff were likely to have worked in areas of the hospital ventilated by the contaminated air conditioning plant, but not necessarily the OPD. There was evidence that a small proportion of these staff had a mild legionellosis and that these 'influenza-like' illnesses had been spread over a 5-month period. A possible explanation of this finding is that small amounts of aerosol from cooling tower sources could have entered the air-intake and been distributed throughout the areas of the hospital served by this ventilation system. Legionellae, subsequently found to be of the epidemic strain, had been found in the cooling tower pond in November 1984 and thus it is possible that staff were exposed to low doses of contaminated aerosol over several months. Control measures are described, but it was later apparent that the outbreak had ended before these interventions were introduced. The investigations revealed faults in the design of the ventilation system.     

Community survey of primary dystonia in the city of Kolkata, India.

An epidemiological study on dystonia has not been reported from India. As part of a major study to find out the prevalence of major neurological disorders in the large urban city of Kolkata, Eastern India, we planned to determine the prevalence of primary dystonia. The study design was a cross-sectional study of a sample population obtained through stratified random selection and conducted in a two-stage procedure of screening by a nonprofessional team followed by confirmation of screened positive cases by the study neurologist. A total population of 52,377 was screened, and 29 subjects with dystonia were diagnosed. Out of them 23 subjects had primary dystonias [crude prevalence rate (CPR), 43.91/100,000; 95% confidence interval (CI), 28.41-64.81; age-standardized rates to world standard population, 49.06 (95% CI,31.74-72.41)] and all cases were focal type and predominantly of limb dystonia variety. Mean onset of dystonias were earlier in women (43.5 years) as compared to men (46.6 years). Thus our study on primary dystonia shows higher prevalence when compared with that of many studies globally, predominantly of focal type, earlier onset among women, and more cases of limb dystonias when compared with more prominent blepharospasm and cervical dystonias in western reports.     

Pathological and molecular progression of astrocytomas in a GFAP:12 V-Ha-Ras mouse astrocytoma model

We previously characterized a genetically engineered mouse astrocytoma model with embryonic astrocyte-specific, activated ¹²V-Ha-RAS (GFAP-RAS) transgenesis. The GFAP-RAS line Ras-B8 appears normal at birth, but 50% of mice die by 4 months from low- and high-grade astrocytomas. We examined the development and progression of astrocytomas in the Ras-B8 genetically engineered mouse. At embryonic day 16.5 (E16.5), there were no pathological differences compared to control littermates, aside from transgene expression. Diffuse astroglial hyperplasia was the first distinguishing feature in the 1-week-old Ras-B8 mice; however, these astrocytes were not transformed in vitro or in vivo. From 3 to 8 weeks the incidence of low-grade astrocytomas progressively increased with 85% of 12-week-old mice harboring low- or high-grade astrocytomas, the latter characterized by increased proliferation, nuclear atypia, and angiogenesis. Tp53 mutations were detected in both astrocytoma grades, with high-grade astrocytomas expressing elevated levels of epidermal growth factor receptor and vascular endothelial growth factor, plus decreased levels of PTEN and p16, similar to human astrocytomas. We postulate that expression of ¹²V-Ha-RAS in astroglial precursors induces astroglial hyperplasia, but transformation and subsequent progression requires additional molecular alterations resulting from aberrant activated p21-RAS. Of interest, many of these acquired alterations occur in human astrocytomas, further validating GFAP-RAS as a useful model for studying astrocytoma development and progression.     

Hyperspectral and multispectral bioluminescence optical tomography for small animal imaging

For bioluminescence imaging studies in small animals, it is important to be able to accurately localize the three-dimensional (3D) distribution of the underlying bioluminescent source. The spectrum of light produced by the source that escapes the subject varies with the depth of the emission source because of the wavelength-dependence of the optical properties of tissue. Consequently, multispectral or hyperspectral data acquisition should help in the 3D localization of deep sources. In this paper, we describe a framework for fully 3D bioluminescence tomographic image acquisition and reconstruction that exploits spectral information. We describe regularized tomographic reconstruction techniques that use semi-infinite slab or FEM-based diffusion approximations of photon transport through turbid media. Singular value decomposition analysis was used for data dimensionality reduction and to illustrate the advantage of using hyperspectral rather than achromatic data. Simulation studies in an atlas-mouse geometry indicated that sub-millimeter resolution may be attainable given accurate knowledge of the optical properties of the animal. A fixed arrangement of mirrors and a single CCD camera were used for simultaneous acquisition of multispectral imaging data over most of the surface of the animal. Phantom studies conducted using this system demonstrated our ability to accurately localize deep point-like sources and show that a resolution of 1.5 to 2.2 mm for depths up to 6 mm can be achieved. We also include an in vivo study of a mouse with a brain tumour expressing firefly luciferase. Co-registration of the reconstructed 3D bioluminescent image with magnetic resonance images indicated good anatomical localization of the tumour.     

Role of imprint cytology in the diagnosis of gastrointestinal tract malignancies

Endoscopic biopsies obtained from 275 patients (180 from the upper gastrointestinal tract and 95 from the lower gastrointestinal tract) were studied to compare the accuracy of biopsy imprint cytology and histology in the diagnosis of gastrointestinal lesions, and also to establish the degree of reliability of imprint cytology alone for an early diagnosis of malignancy. Biopsy histology results were found to be correct in 100% cases. Imprint cytology had an overall accuracy of 100%, 96.7%, 95.8% and 95.8% for the diagnosis of malignancies of the oesophagus, stomach, duodenum and colorectum respectively. False negative results were obtained with lymphomas. Regenerative cellular atypia was an important cause for false positive results. It was concluded that imprint cytology can serve as a useful and simple tool for an immediate diagnosis of malignancy. This should be subsequently correlated with histopathology which facilitates exact tumour typing and assessment of tumour invasion.     

The effect of RANTES chemokine genetic variants on early HIV-1 plasma RNA among African American injection drug users

HIV-1 plasma RNA is a prognostic indicator of HIV-1, and increased levels of HIV-1 plasma RNA are associated with rapid progression to AIDS. Because chemokines and chemokine receptors are involved in the binding and entry of HIV-1, possible effects of host genetics on viral RNA levels should be visible in early infection. HIV-1 plasma RNA was measured within 2 years of seroconversion in 198 seroincident injection drug users followed in the AIDS Link to Intravenous Experience cohort. Genetic variants were identified in the chemokine receptors (CCR2, CCR5, and CCR5 promoter) and the chemokine RANTES using TaqMan and restriction fragment length polymorphism assays. Linear regression of RANTES haplotypes on early HIV-1 plasma RNA identified individuals homozygous for the RANTES R1 haplotype as having a lower viral load by almost one-half log10 unit compared with those bearing non-RANTES R1 haplotypes (-0.43, 95% confidence interval: -0.74, -0.12). Genetic variants in RANTES may downregulate RANTES gene expression and increase early HIV-1 plasma RNA. Because RANTES is a critical chemokine and competitively inhibits HIV-1 by binding to its receptor CCR5, treatment to enhance RANTES expression may assist in delaying the progression of AIDS by decreasing the initial viral load.