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[The clinical value of magnetic resonance tomography in cystic space-occupying lesions of the mouth floor].

11 patients with cystic lesions of the floor of the mouth were examined by MR imaging. Coronal slices provided an optimal visualisation of the lesions, but axial and sagittal slices added important information with regard to the exact topographic relationship between tumour and muscles. In particular, the mylohyoid muscle could be defined as a key structure. T1-weighted sequences enabled best visualisation of anatomic details, whereas T2-weighted sequences facilitated the primary diagnosis of cystic lesions. The contrast agent Gd-DTPA did not add information of significant diagnostic value. Our results indicate that MRI allows an exact visualisation of location and extent of cystic lesions and their relationship to surrounding muscles. We conclude that MRI is of high value in planning the operative strategy.

Cysts↗

Elective neck dissection versus observation in stage I squamous cell carcinomas of the tongue and floor of the mouth.

A retrospective study was undertaken of patients with T1N0M0 squamous cell carcinoma of the oral tongue and floor of the mouth who underwent surgical treatment between 1985 and 1995. Evaluation of two groups of patients (neck dissection versus observation) was made according to the management of the neck. Results were obtained regarding the presence of occult metastases, recurrence in the neck, treatment failure, results of salvage treatment, and disease-free survival. Forty-nine patients underwent surgical treatment: 25 resection of primary and 24 resection plus neck dissection. Overall incidence of regional metastases was 24.5%. Eight patients (16%) developed recurrence of the disease. Seven (14%) had regional recurrences (including 1 with distant metastases) and 1(2%) had local recurrence. Twenty-four percent of patients from the resection of primary group developed neck recurrences in comparison with 4% of the resection plus neck dissection group (P = 0.05). Overall salvage rate was 37.5%. Second primary tumors developed in 16% of patients. Patients who underwent elective neck dissection had a 23% higher disease-free survival rate compared with those who underwent resection of the tumor alone (P = 0.03). The findings of this study stress the importance of control of the neck in early oral cancer. Elective neck dissection significantly improved regional control of the disease.

Adult↗

Distribution of mucosal pH on the bucca, tongue, lips and palate. A study in healthy volunteers and patients with lichen planus, Behçet's disease and burning mouth syndrome.

Saliva coating all oral surfaces has a buffering capacity that neutralizes bacterial and cariogenic acids. The aim of our study was to determine the surface pH in different regions of the oral cavity in healthy volunteers and in patients with diseases affecting the oral mucosa. Oral pH was measured with a flat glass electrode on the anterior third of the ventral surface of the tongue, middle hard palate, buccal mucosa and inner lips in 32 healthy volunteers, 12 patients with Behçet's disease, 23 patients with oral lichen planus, and 11 patients with burning mouth syndrome. The present study showed that there was an uneven distribution of oral surface pH. The palate had a higher pH than most other sites in all groups, and in patients with lichen planus, the palate pH was higher than that in healthy controls. Those with dentures had lower pH values in the hard palate than dentate patients. The relatively high pH in the palate region in all patient groups as well as healthy volunteers needs to be further studied to clarify its mechanisms and clinical relevance.

Adult↗

RELATIONSHIP OF DONOR AGE TO IN VITRO PRODUCTION OF FOOT-AND-MOUTH DISEASE VIRUS BY MOUSE KIDNEY CELLS.

Multiplication of foot-and-mouth disease virus (FMDV) was compared in kidney cells from 7- to 35-day-old mice representing various degrees of age resistance to this virus. Three types of cell preparations were used: primary monolayer cultures, suspensions of dispersed cells, and suspensions of minced tissue. Virus multiplication in the two types of cell suspensions was related to the age of the donors both in regard to time when multiplication first became evident and to the amount of virus produced. While adsorption rates were similar in the cells from all age groups, virus multiplication began earlier in cells from younger mice and more virus was produced by these cells than by cells from older animals. There was no significant difference in the virus growth rates in the primary monolayer cultures of cells. The results indicate that kidney cells from mice 7 to 35 days old vary in their ability to produce virus in relation to the degree of susceptibility of the cell donors. After propagation of the cells in primary monolayer cultures, however, this difference no longer exists probably because of cell selection under the cultural conditions.

Aging↗

Electron microscope study of red cell membranes after experimental infection with the virus of foot-and-mouth disease.

Guinea pigs were inoculated with the Vallée O type strain of the virus of foot-and-mouth disease. 42 to 48 hours after inoculation red blood cells washed in saline were found to be infective for normal guinea pigs suggesting that erythrocytes carry virus entities at the height of generalization of the disease. This infection is no longer obtained at 92 hours after inoculation when general symptoms of the disease decline. A replica-transfer technique was developed with which hemolyzed blood smears could be observed under the electron microscope. By direct examination and also shadow-casting with palladium, normal red cell membranes show only a very fine structure on the surface. Rounded masses of high electron density appear in the ghosts between 24 and 72 hours after inoculation with virus. The number and particularly the density of these masses tend to increase from 24 to 42 and 72 hours. In some cases they are disposed preferentially in single lines forming ring figures; in other cases they are distributed at random. At 42 hours after inoculation it was possible to detect dense particles of 20 to 70 mmicro. within the masses. Measurements of 100 masses at 72 hours gave results ranging from 116 to 437 mmicro with a mean diameter of 246 mmicro. Results based on 105 electron micrographs and on thousands of cells demonstrate that practically all red cell membranes contained dense masses 24 to 72 hours after inoculation. 92 hours after inoculation, coinciding with the disappearance of infectivity of the erythrocytes, the masses could no longer be seen and the membranes looked entirely normal. Although the facts reported here may be suggestive of a relationship between the dense masses within the red cell membranes and the presence of virus entities in washed erythrocytes, no definite interpretation of these findings is postulated at present.

Animals↗

Adenovirus-mediated type I interferon expression delays and reduces disease signs in cattle challenged with foot-and-mouth disease virus.

Foot-and-mouth disease (FMD) is an economically important disease of livestock. Eliminating FMD outbreaks in previously disease-free countries often relies on restriction of animal movement and massive slaughter of infected and in-contact susceptible animals. To develop a more effective and humane FMD control strategy, we explored the possibility of using type I interferon (IFN-alpha/beta) as a novel anti-FMD agent. We have demonstrated previously that swine inoculated with replication-defective human adenovirus type 5 (Ad5) vector expressing porcine IFN-alpha (Ad5-PoIFN-alpha) were completely protected from FMD virus (FMDV) challenge. To extend this approach to bovines, we constructed Ad5 vectors that express bovine IFN-alpha or IFN-beta (Ad5-BoIFN-alpha and Ad5-BoIFN-beta). Cells infected with these viruses produced high levels of biologically active BoIFN-alpha/beta, but despite expression in vitro, no detectable IFN-induced biologic activity was found in cattle inoculated with Ad5-BoIFN-alpha. Because PoIFN-alpha inhibits FMDV replication in bovine cells, we evaluated the potential use of PoIFN-alpha against FMD in cattle. In cattle inoculated with Ad5-PoIFN-alpha, the appearance of vesicles was delayed after challenge with FMDV and disease was less severe than in control animals. One Ad5-PoIFN-alpha-inoculated animal never developed clinical disease. Similarly, although all the Ad5-PoIFN-alpha-inoculated animals developed viremia, it was delayed for 1 day as compared with the control group. These results suggest that in vivo expression of PoIFN-alpha partially protected cattle from FMD.

Adenoviridae↗

Immunogenicity of the epitope of the foot-and-mouth disease virus fused with a hepatitis B core protein as expressed in transgenic tobacco.

A novel plant-based vaccine protecting against foot-and-mouth disease (FMD) was developed by inserting the VP21 epitope into the internal region of the hepatitis B virus core antigen gene (HBcAg). The specific sequence of the VP21 epitope is located within the VP1 capsid protein of the FMD virus (FMDV). It spans 21 amino acids located between positions 140 and 160 of the G-H loop. The fusion gene, HBCVP, was inserted into the plant binary vector pBI121 and then transformed into tobacco (Nicotiana tabacum) plants via Agrobacterium tumefaciens strain LBA 4404. The presence of HBCVP in the tobacco genome was confirmed by polymerase chain reaction (PCR); its transcription was verified by reverse transcription-PCR; and the recombinant protein expression was confirmed by Western blot analysis. The results of immunologic microscopic observation demonstrated that recombinant fusion protein HBCVP can form a virus-like particle (VLP) structure in transgenic tobacco leaves. Mice, immunized intraperitoneally with a soluble crude extract of transgenic tobacco leaves, were found to produce specific antibody responses to both HBcAg and FMDV VP1. A virus challenge demonstrated that the immunized mice were highly protected against virulent FMD. This work describes a new way to develop an FMD vaccine from plants that will aid the development of new vaccines using HBcAg fused to the conserved epitopes of other pathogenic antigens.

Agrobacterium tumefaciens↗

Recombinant bivalent vaccine against foot-and-mouth disease virus serotype O/A infection in guinea pig.

In this study, two DNA fragments encoding amino acid (141-160)-(21-140)-(141-160) of the VP1 of FMDV (foot-and-mouth disease virus) serotype O and (138-160)-(21-40)-(138-160) of the serotype A FMDV were chemically synthesized. These two tandem-repeat fragments were ligated and transfected into prokaryotic expression vector pTrcHis A to construct pTH-O-A. The other vector called pTH-O-scIgG-A was constructed similarly only that the two tandem-repeat DNA fragments were linked by the bovine-IgG heavy chain coding sequence. Guinea pigs immunized with the two bivalent vaccines pTH-O-A and pTH-O-scIgG-A showed both specific antibody activity and T cell proliferation responses. FMDV challenge tests showed that 85% and 70% of guinea pigs vaccinated twice with 200 mg of the fusion protein of pTH-O-A were protected from FMDV serotype O and serotype A infection respectively. 70% and 57% of the guinea pigs immunized with the fusion protein of pTH-O-scIgG-A were protected from FMDV serotype O and serotype A infection respectively.

Animals↗

Bacterial adherence in the mouth.

Studies of the adherence of bacteria indigenous to the human mouth have contributed greatly to our understanding of oral bacterial ecology. Bacterial adhesion to teeth and oral epithelial surfaces seems to be indispensable for the formation of dental plaque and for the persistent colonization of mucosal surfaces. The strength of adhesion to various oral surfaces differs widely among oral bacteria and is a major reason for their different intraoral localization. Considerable evidence suggests that the adhesion of different bacteria to the acquired pellicle on teeth or to mucosal surfaces as well as the adhesive processes involved in plaque accumulation entail different, specific interactions that are mediated by receptors on the bacterial cell surface, on the oral surfaces, and on plaque matrix components. Some of these interactions may involve lectin-like binding. Knowledge of the mechanisms by which suspected odontopathogens such as Streptococcus mutans and certain Actinomyces species may adhere to oral surfaces has been discussed. Successful methods for interfering with bacterial adhesion to human oral surfaces have not been developed yet.

Actinomyces↗

Sensory and pain thresholds to orofacial argon laser stimulation in patients with chronic burning mouth syndrome.

OBJECTIVE: Psychophysical assessments of orofacial sensory function were performed in order to investigate neurophysiological aspects of the burning mouth syndrome (BMS). DESIGN: Sensory and pain thresholds to brief argon laser stimulation were determined on six test regions, which included the tip of tongue, the lower lip mucosa and skin, the buccal mucosa, the anterior hard palate, and the dorsum of the hand. SETTING: The experimental examination was performed at the Pain Clinic Unit at the Royal Dental College. PATIENTS: Twenty-three elderly denture-wearing patients diagnosed as suffering from BMS were studied, and a control group included 23 age-, sex-, and denture-matched subjects. The obtained thresholds were compared between groups. RESULTS: Sensory thresholds were significantly higher and ratios between pain and sensory thresholds significantly lower in patients with BMS on all the tested regions. Pain thresholds were significantly elevated on the lower lip skin, the anterior hard palate, and the hand in patients with BMS. At sensory threshold level, a faint pinprick perception was often reported by patients with BMS contrary to a perception of warmth described by control subjects. The intraregional variations in sensory and pain thresholds on the hard palate, the lower lip mucosa, and on the skin were similar in both groups, but differences occurred in sensory thresholds on the tongue in patients with BMS. CONCLUSIONS: The presence of abnormal prepain perceptions and disturbances in the perception of nonnociceptive and nociceptive thermal stimuli applied on both pain-affected and normal regions suggest a perceptual deficit unrelated to specific pathophysiological mechanisms in BMS. However, it appears that a psychological explanation of BMS should be used cautiously, as the present results suggest alterations in sensory function.

Aged↗

Lymphatics of the submandibular space: an anatomic, clinical, and pathologic study with applications to floor-of-mouth carcinoma.

The detection and management of submandibular metastases are fundamental to the treatment of oral carcinoma. Detailed investigation of submandibular lymphatic anatomy and subsite predilection for metastases, as well as a comprehensive method for submandibular space dissection, have been lacking. This thesis explores submandibular lymphatic anatomy through a review of the literature and cadaver dissections. A standardized lymph node nomenclature and submandibular dissection technique are proposed. Also presented is a report on 41 consecutive patients with floor-of-mouth squamous cell carcinoma who were prospectively evaluated and treated. Pretreatment clinical and computed tomography (CT) examinations revealed the detection of submandibular metastases to be more difficult than for the remainder of the neck and not improved by the routine use of CT scanning. Management of the neck was either with surgery, which included complete bilateral level I dissections, or at least 2-year follow-up when left untreated. Overall, 39% of patients manifested submandibular disease. The majority of submandibular metastases in this study measured 1 cm or less and most commonly involved the perivascular (primarily prevascular) nodes followed by the preglandular and, previously ill-defined, deep nodes. These findings are discussed with regard to the rationale for currently used neck dissections.

Adult↗

Metastatic metaplastic carcinoma from a pseudosarcoma (Lane tumor) of the mouth.

A case of polypoid metaplastic carcinoma (Lane tumor) of the mouth is presented. There are well defined zones of transition between the squamous epithelium of the polyp and the stroma. Metastases in the right neck and paratracheal lymph nodes contain areas of cartilaginous and osseous metaplasia as well as squamous epithelial pearls.

Carcinoma↗

Quantities of infectious virus and viral RNA recovered from sheep and cattle experimentally infected with foot-and-mouth disease virus O UK 2001.

The profiles of virus production and excretion have been established for sheep experimentally infected with the UK 2001 strain of foot-and-mouth disease (FMD) virus by inoculation and by direct and intensive contact. Virus replicated rapidly in the inoculated sheep, from which a peak infectivity of airborne virus of 10(4.3) TCID(50) per sheep per 24 h was recovered. Around 24 h later, contact-infected sheep excreted airborne virus maximally. Similar amounts of airborne virus were recovered from cattle. The excretion of virus by the sheep under these conditions fell into three phases. First, a highly infectious period of around 7-8 days. Second, a period of 1-3 days soon afterwards when trace amounts of viral RNA were recovered in nasal and rectal swabs. Third, at 4 weeks after exposure, the demonstration, by tests on oesophageal-pharyngeal samples, that 50% of the sheep were carriers. The implications of the results and the variable role that sheep may play in the epidemiology of FMD are discussed.

Aerosols↗

Comparisons of the complete genomes of Asian, African and European isolates of a recent foot-and-mouth disease virus type O pandemic strain (PanAsia).

During the last 12 years, a strain of foot-and-mouth disease (FMD) virus serotype O, named PanAsia, has spread from India throughout Southern Asia and the Middle East. During 2000, this strain caused outbreaks in the Republic of Korea, Japan, Russia (Primorsky Territory), Mongolia and South Africa (KwaZulu-Natal Province), areas which last experienced FMD outbreaks in 1934, 1908, 1964, 1974 and 1957, respectively. In February 2001, the PanAsia strain spread to the United Kingdom where, in just over 7 months, it caused outbreaks on 2030 farms. From the UK, it quickly spread to the Republic of Ireland, France and the Netherlands. Previous studies that utilized RT-PCR to sequence the VP1-coding region of the RNA genomes of approximately 30 PanAsia isolates demonstrated that the UK virus was most closely related to the virus from South Africa (99.7 % nucleotide identity). To determine if there was an obvious genetic reason for the apparently high level of fitness of this new strain, and to further analyse the relationships between the PanAsia viruses and other FMDVs, complete genomes were amplified using long-range PCR techniques and the PCR products were sequenced, revealing the sequences for the entire genomes of five PanAsia isolates as well as an animal-passaged derivative of one of them. These genomes were compared to two other PanAsia genomes. These analyses revealed that all portions of the genomes of these isolates are highly conserved and provided confirmation of the close relationship between the viruses responsible for the South Africa and UK outbreaks, but failed to identify any genetic characteristic that could account for the unprecedented spread of this strain.

3' Untranslated Regions↗

The implications of virus diversity within the SAT 2 serotype for control of foot-and-mouth disease in sub-Saharan Africa.

SAT 2 is the serotype most often associated with outbreaks of foot-and-mouth disease (FMD) in livestock in southern and western Africa and is the only SAT type to have been recorded outside the African continent in the last decade. Its epidemiology is complicated by the presence of African buffalo (Syncerus caffer), which play an important role in virus maintenance and transmission. To assess the level of genetic complexity of this serotype among viruses associated with both domestic livestock and wildlife, complete VP1 gene sequences of 53 viruses from 17 countries and three different host species were analysed. Phylogenetic analysis revealed eleven virus lineages, differing from each other by at least 20 % in pairwise nucleotide comparisons, four of which fall within the southern African region, two in West Africa and the remaining five in central and East Africa. No evidence of recombination between these lineages was detected, and thus we conclude that these are independently evolving virus lineages which occur primarily in discrete geographical localities in accordance with the FMD virus topotype concept. Applied to the whole phylogeny, rates of nucleotide substitution are significantly different between topotypes, but most individual topotypes evolve in accordance with a molecular clock at an average rate of approximately 0.002 substitutions per site per year. This study provides an indication of the intratypic complexity of the SAT 2 serotype at the continental level and emphasizes the value of molecular characterization of diverse FMD field strains for tracing the origin of outbreaks.

Africa South of the Sahara↗

Induction of an antigen-specific immune response and partial protection of cattle against challenge infection with foot-and-mouth disease virus (FMDV) after lipopeptide vaccination with FMDV-specific B-cell epitopes.

To evaluate the potential of chemically synthesized lipopeptides for vaccination against foot-and-mouth disease (FMD), seven lipopeptides containing the immunostimulating principle of bacterial lipoproteins and linear B-cell epitopes of FMDV strain O(1)Kaufbeuren (O(1)K) were used to immunize cattle (n=7). Animals were vaccinated once and 21 days after immunization animals were infected with the homologous virus. Four animals were protected. After vaccination, as well as after challenge infection, B- and T-cell responses were examined. Sera were tested for virus- and peptide-specific antibodies and showed after vaccination only a weak antibody response. After challenge infection, an increase in antibody titre was obvious but there was no correlation between antibody titre and protection. The reactivity of the cellular immune system was detected by analyses of PBMCs for virus- and peptide-specific T-lymphocytes. With regard to the virus-specific T-lymphocytes, a heterogeneous reactivity could be shown. No correlation between virus-specific T-cell proliferation and protection was found. Obvious was the fact that all protected animals showed after vaccination a strong T-cell response against at least one of the peptides used for immunization. These results suggest a correlation between the onset of an antigen-specific T-cell reaction and protection.

Amino Acid Sequence↗

Extent of reduction of foot-and-mouth disease virus RNA load in oesophageal-pharyngeal fluid after peak levels may be a critical determinant of virus persistence in infected cattle.

To investigate whether foot-and-mouth disease virus (FMDV) RNA loads in oesophageal-pharyngeal fluid (OP-fluid) in the early course of infection is related to the outcome of virus persistence, viral RNA in OP-fluid samples from cattle experimentally infected with FMDV type O was quantitatively analysed by using a quantitative real-time RT-PCR. Viral RNA was detected within 24 h post-infection (p.i.) in all infected animals. Rapid virus replication led to peak levels of viral RNA load by 30-53 h p.i., and then the load declined at various rates. In some animals (n=12, so-called non-carriers) viral RNA became undetectable between 7 and 18 days p.i. In contrast, in persistently infected animals (n=12, so-called carriers) viral RNA persisted in OP-fluid samples at detectable levels beyond 28 days p.i. Analysis of early viral decay/clearance and virus clearance half-life in OP-fluid samples showed that the extent of reduction of viral RNA in OP-fluid samples immediately following peak levels is a critical determinant of the outcome of FMDV persistence.

Animals↗

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