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Biomedical subjects

F Doherty

Publications and source records attributed to F Doherty.

17 recordsLinked to original sources

Studies on stannous fluoride toothpaste and gel (1). Antimicrobial properties and staining potential in vitro.

Stannous fluoride (SF) in a toothpaste vehicle has the potential to provide anticaries and plaque inhibitory benefits through the fluoride and antimicrobial stannous moieties respectively. Dental staining, however, can occur by precipitation of dietary chromogens onto the tooth surface by stannous ions. These studies in vitro compare the antimicrobial profile and propensity to cause tea staining of a number of stannous fluoride formulations. The formulations used were 2 SF toothpaste products (SF1, SF2), 2 experimental SF plus stannous pyrophosphate toothpastes (SFSP1, SFSP2), a SF gel (G) and a NaF toothpaste (C). Maximum inhibitory dilution values against a range of oral bacteria were determined by agar dilution. Tea staining was measured spectrophotometrically on saliva coated clear acrylic blocks exposed to slurries of the paste or gel. All formulations showed antimicrobial activity with the order of greatest activity downwards being C, SF2, SF1, SFSP1, SFSP2 and G. Tea staining at 10 exposures was in the following descending order of optical density SFSP1, SFSP2, G. C, SF1, SF2, water control. The antimicrobial profile of G was similar to that of SF, whereas that of the other formulations were varied but similar to a detergent profile. The difference in staining suggested considerable variation in availability of stannous ions in the formulations. However, the propensity for stannous ions to stain must be balanced against the stain removal propensity of the contained detergents in the toothpaste formulations. In conclusion, the variation in antimicrobial activity and more particularly staining activity of the formulations suggest the products will vary in activity in vivo.

Anti-Infective Agents, Local↗

Studies on stannous fluoride toothpaste and gel (2). Effects on salivary bacterial counts and plaque regrowth in vivo.

There has been a resurgence of interest in stannous fluoride (SF) products in particular to provide oral hygiene and gingival health benefits. The aim of this study was to assess the persistence of antimicrobial action of a number of SF formulations in the mouth and relate these to plaque inhibitory activity. The formulations were 2 SF toothpastes (SF1, SF2), 2 SF plus stannous pyrophosphate toothpastes (SFSP1, SFSP2), a SF gel (G), a NaF toothpaste (C) and saline (S) as control. Both studies involve 2 different groups of 21 healthy dentate volunteers. The studies were single, blind, randomised, crossover designs balanced for residual effects, with a minimum 2 1/2 day washout period. Salivary bacterial counts were determined before and to 7 h after a single rinse with the formulations. Plaque regrowth from a zero baseline (day 1) was measured by index and area on day 5, after 2x daily rinsing with slurries of the formulations or saline. For bacterial counts, highly significant treatment differences were found. Bacterial counts were variably reduced by all treatments to 30 min then showed a variable rate of return towards baseline. All test agents were significantly better than S at some timepoints. The order for greatest persistence of action downwards was; (1) SFSP2; (2) SFSP1, G, and SF1; (3) SF2; (4) C; (5) S. Highly significant differences in plaque regrowth between treatments were found with similar mean ordering of efficacy as for salivary bacterial counts from most effective downwards namely; (1) SFSP1 and SFSP2; (2) SF1; (3) SF2; G and C; (4) S. The results were consistent with a parallel study measuring tea staining in vitro, whereby formulations causing the most staining produced the greatest persistence of action and plaque inhibitory activity. This suggests the availability of stannous ions was important for the clinical effects. It is concluded that stannous ions can enhance the plaque inhibitory action of toothpaste via a persistent antimicrobial action.

Analysis of Variance↗

Comparative staining in vitro and plaque inhibitory properties in vivo of 0.12% and 0.2% chlorhexidine mouthrinses.

The mere incorporation of an active ingredient in an oral hygiene product does not necessarily guarantee efficacy. As new formulations appear, it would seem prudent to at least screen for activity by comparison with an established product. The aim of this study was to compare a new 0.12% chlorhexidine containing rinse with a well researched 0.2% chlorhexidine rinse product. The rinses were firstly compared in vitro for dietary staining effects and in vivo for plaque inhibition. Both formulations in vitro produced progressive staining of acrylic specimens with increasing passages through a standard tea solution. The clinical investigation was a 3-treatment, randomised, double blind, crossover, 4-day plaque regrowth study, balanced for 1st and 2nd order residual effects and involving 24 volunteers. From a zero plaque baseline, volunteers suspended oral hygiene and rinsed 2 x per day with the allocated rinse. The chlorhexidine doses were 18 mg and 20 mg per rinse for the 0.12% and 0.2% formulations, respectively. Plaque was scored by area and index on day 5. The results showed that the 2 chlorhexidine rinses were similar in efficacy by comparison with the control rinse. These studies in vitro and in vivo indicate that the chlorhexidine in the new preparation is available and active and the product could find use in those preventive applications suggested for other chlorhexidine formulations.

Acrylic Resins↗

Effectiveness of adjunctive irrigation in early periodontitis: multi-center evaluation.

The purpose of this study was to determine the effect of daily water irrigation versus regular oral hygiene alone on gingival and periodontal health in periodontitis patients receiving supportive periodontal treatment. The study also sought to determine if there are enhanced benefits from using an antiplaque zinc sulfate rinse as an irrigant. One hundred fifty-five patients who have had periodontitis and had been treated either surgically or non-surgically completed the 6-month multi-center multi-national study. Patients with at least two 5 mm sites demonstrating bleeding on probing were assigned to 3 equal groups by balanced randomization. In all centers Group A (n = 57) performed regular oral hygiene only, and Group B (n = 58) irrigated with 500 ml water once daily after regular oral hygiene. Group C (n = 40) patients irrigated with a total of 500 ml once daily; following irrigation with 300 ml water, the patients then irrigated with an additional 200 ml with a zinc sulfate solution. The irrigants were diluted to provide the manufacturer's recommended daily dosage. The supragingival irrigation was performed with a commercially available oral irrigator. Bacterial measurements at baseline, 3 months, and 6 months were taken to determine the effect of irrigation on the target organisms and will be reported elsewhere. Gingival index: irrigation with water (Group B) was significantly better than normal oral hygiene (Group A) and irrigation with zinc sulfate (Group C) (P < 0.05) in reducing gingival inflammation. Bleeding on probing: significant reductions in bleeding on probing occurred for water (Group B) compared to normal oral hygiene (Group A) (P < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Ubiquitin and the lysosome system: molecular immunopathology reveals the connection.

Considerable advances in our understanding of the molecular pathology of the major human neurodegenerative diseases have been made by the use of ubiquitin immunocytochemistry. The technique demonstrates that filamentous inclusions and vacuoles contain ubiquitin-protein conjugates. The molecular structure of the filaments and the morphological type of vacuoles is not completely understood but there is evidence that some of the filamentous inclusions contain intermediate filaments and the perinuclear distribution of the vacuoles resemble the distribution of intraneuronal lysosomes. Intermediate filaments and lysosomes are involved in the sequestration and degradation of viral membrane proteins in tissue culture cells. Immunogold electron microscopical and biochemical evidence indicates that ubiquitin-protein conjugates are normally considerably enriched in the lysosomes of fibroblasts relative to all other organelles. Immunogold electron microscopy shows a similar enrichment of ubiquitin-protein conjugates in the dense lysosomes of granulocytic precursor cells in the bone marrow. Filamentous inclusions showing several of the features seen in inclusions in the neurodegenerative diseases are seen in Epstein-Barr virus transformed lymphoblastoid cells. Immunohistochemistry shows that the inclusions contain vimentin intermediate filaments, the latent membrane transforming protein of the virus, ubiquitin-protein conjugates, and a heat-shock protein 70 (hsp 70). Immunohistochemistry and immunogold electron microscopy demonstrate that the latent membrane protein, ubiquitin-protein conjugates and hsp 70 are in lysosomes entwined in an intermediate filament cage centred on the microtubule organising centre. The implications of the combined observations for our understanding of the cell stress response in degenerating neurones and in virally infected cells are discussed.

Heat-Shock Proteins↗

Uterine thickness determination using real-time ultrasonography: a guide for intracavitary brachytherapy in the treatment of endometrial carcinoma.

Two patients with medically inoperable stage I endometrial carcinoma were treated with intracavitary implants alone using Simon capsules, tandems, and ovoids. In both cases, uterine thickness was measured during the implant procedure by realtime ultrasonography. Tumor doses in both patients were then calculated to the midmyometrium and to the serosal surface of the uterus. These estimates, rather than the usual milligram-hours or points A and B, were used to make treatment decisions.

Brachytherapy↗

Ultrasound for diagnosing and preventing malplacement of intrauterine tandems.

Postoperative B-mode ultrasound was used to evaluate final tandem position in 50 consecutive placements (28 patients). In 34% (17 of 50), the tandem was found to be suboptimally positioned; in 24% (12 of 50), it penetrated the myometrium; and in 10% (five of 50), it frankly perforated the uterus. The uterine fundus was the region most commonly perforated, and the anterior myometrium was the site most frequently penetrated. In all cases in which postoperative ultrasound showed malpositioning, the clinical and radiographic assessment indicated proper intracavitary placement. Ultrasound affected clinical management in 42% (21 of 50) of the placements involving 61% (17 of 28) of the patients. To improve tandem placement, we used intraoperative real-time ultrasound to guide 73 consecutive surgical insertions. Ultrasound clearly visualized the procedure, allowing tandems to be positioned with confidence even in the most difficult cases. The immediate feedback from intraoperative ultrasound eliminated malplacements and thus the need for a second anesthesia to reposition the tandem.

Brachytherapy↗

Inclusion bodies in motor cortex and brainstem of patients with motor neurone disease are detected by immunocytochemical localisation of ubiquitin.

Histological sections of cerebral motor cortex, brainstem, and spinal cord from 10 cases of clinically diagnosed motor neurone disease (MND) and 10 control cases were examined by conventional histology and immunocytochemical methods to localise ubiquitin. Intracytoplasmic inclusion bodies were identified in motor neurones of hypoglossal nuclei and appeared specific for MND. Similar inclusions were found in both large pyramidal cells and small neurones in the motor cortex, and were restricted to 4 cases having the amyotrophic lateral sclerosis form of MND with severe degeneration of corticospinal tracts. As reported in earlier studies, cellular inclusion bodies were identified in motor neurones of spinal cord from cases of MND but not in control material. Ubiquitin inclusions in motor neurones appear to be markers for the degenerative process causing neuronal loss in MND and there appears to be a close association between the anatomical location of inclusions and clinical manifestations of disease.

Aged↗

Intermediate filaments and ubiquitin: a new thread in the understanding of chronic neurodegenerative diseases.

We have recently shown that there is a previously unsuspected link between the intracellular inclusions seen in several major chronic human degenerative diseases, including neurodegenerative diseases: the inclusions showing ubiquitin immunoreactivity. The conditions include Parkinson's disease, motor neurone disease, Alzheimer's disease, Pick's disease, and alcoholic liver disease as well as cerebellar astrocytomas and a myopathy. The inclusions found in these diseases are reported to contain intermediate filaments: neurofilaments are associated with Lewy bodies in Parkinson's disease, Pick's bodies in Pick's disease and neurofibrillary tangles in Alzheimer's disease, cytokeratins are found in Mallory bodies in alcoholic liver disease, glial fibrillary acidic proteins and vimentin are found in Rosenthal fibres in astrocytomas, and desmin is found in cytoplasmic bodies in cytoplasmic body myopathy. Therefore five classes of intermediate filaments are found in inclusions which also contain ubiquitin immunoreactivity; we have also shown that ubiquitin immunoreactivity is present in vesicles in some areas of granulovacuolar degeneration in Alzheimer's disease. Protein ubiquitination is considered a signal for extralysosomal protein degradation, (although ubiquitination may have several other important functions). We have recently shown that intermediate filaments are involved in protein sequestration before degradation by lysosomally mediated autophagy: therefore intermediate filament-containing ubiquitinated inclusions may be the hallmarks of cellular attempts to eliminate pathogenic insults by the activation of both extralysosomal and lysosomal mechanisms of intracellular protein degradation. We have recently been able to reproduce, at least in part, some of the clinical observations in tissue culture cells. Ubiquitinated protein conjugates accumulate in lysosomes in fibroblasts treated with the lysosomal cysteine protease inhibitor E-64, which may mimic aspects of granulovacuolar degeneration.

Chronic Disease↗

Intracellular degradative fate of transplanted and microinjected proteins.

The mechanisms of intracellular protein catabolism have not been elucidated in spite of 42 years since Schoenheimer's treatise on "The Dynamic State of Body Constituents". Protein catabolism (cf. Protein Synthesis) involves multiple mechanisms, several of which occur reliably only in cells, not test-tubes. Elucidation of the mechanisms relies on both cell biological and enzymological approaches. Transplantation and microinjection of proteins into target cells, although naturally not without experimental and interpretive difficulties, provide the means of identifying the molecular and cell biological events in intracellular protein degradation. In short, these techniques provide the bioassay system to probe the functions of known catalysts and inhibitors of proteinolysis and provide the means of identifying the currently unknown features of the cytoplasmic surveillance system which present the protein substrates for destruction.

Animals↗

Ultrasound used for assessing the in situ position of intrauterine tandems.

Intracavitary radiation is an integral part of the treatment in many gynecologic cancers. The intrauterine tandem has a well-established role in treating both cervical and endometrial malignancies. The effectiveness of this therapy and its complications are directly related to the proper intracavitary position of the tandem. To date, there has been no objective technique appropriate for routine use in assessing the precise in situ location of these devices, apart from plain abdominal films. As such, little is known about the incidence or types of procedural complications and the sequelae associated with improper tandem placement. Here it is reported that ultrasound is an effective tool for evaluating the in situ position of the intrauterine tandem. Two cases are presented demonstrating important applications of this method.

Aged↗