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PubMed1983

Floor of mouth cancer: patient selection and treatment results.

Retrospective review of 126 primarily treated floor of mouth (FOM) cancers was done to study patient selection and to search for more optimum treatment strategies. Small surface lesions were treated by local excision (LE); small lesions invading FOM without lymph nodes were treated by radiation alone (RA), while larger lesions and those with palpable nodes were treated by preoperative irradiation and surgery (R + S). Ultimate control of the FOM cancer and nodes was achieved for 100% of the LE, 71% of the RA, and 75% of the R + S patients. The majority of primary tumor and nodal recurrences developed by 15 months and 35% of the failures were salvaged by additional treatment. Change in treatment strategies are suggested for surface lesions because of a poor rate of initial tumor control (43%), for patients treated by RA because of a high rate of complications (41%), and for patients without palpable lymph nodes who can be successfully treated by elective neck irradiation.

Brachytherapy↗

PubMed2007

Composite reconstruction in advanced cancer of the mouth floor: autogenous frozen-thawed mandibular bone and free flaps.

Mandibular symphyseal resection requires composite reconstructions, often with unsatisfactory morphofunctional results. Seven patients with advanced squamous cell carcinoma of the floor of the mouth underwent block resection with immediate reconstruction, using the removed mandible treated with liquid nitrogen and covered with a free forearm flap. In all cases, the resection was radical and no major postoperative complications occurred. Two patients died in 6 months for distant metastases and regional recurrence. In the other 5 patients, no local recurrence occurred at a mean follow-up of 52 months (36-70). Immediate cosmetic and functional results were good. Of the 5 patients, 4 had late complications requiring further surgery. This technique of bone reimplantation produces no donor site morbidity, perfect immediate morphological result, and is of low cost. The free forearm flap is effective in sealing the oral cavity, though further clinical and experimental studies are necessary to reduce late local complications.

Adult↗

PubMed2005

Introduction and history of foot-and-mouth disease virus.

Foot-and-mouth disease (FMD) has been recognized as a significant epidemic disease threatening the cattle industry since the sixteenth century, and in the late nineteenth century it was shown by Loeffler and Frosch to be caused by a submicroscopic, filterable transmissible agent, smaller than any known bacteria. The agent causing FMD was thus the first virus of vertebrates to be discovered, soon after the discovery of tobacco mosaic virus of plants. It was not until 1920 that a convenient animal model for the study of FMD virus was established by Waldmann and Pape, using guinea-pigs, and with the later development of in vitro cell culture systems for the virus, the chemical and physical properties of FMD virus were elucidated during the remainder of the twentieth century, culminating in 1989 with a complete description of the three-dimensional structure of the virion. FMD virus is classified as a species in the Aphthovirus genus of the family Picornaviridae. The virus is acid labile, and the genome RNA contains a characteristic tract of polyC located about 360 nucleotides from the 5' terminus. Seven main serotypes exist throughout the world, as well as numerous subtypes. The World Reference Laboratory for FMD is located at Pirbright, Surrey, UK and undertakes surveillance of FMD epidemics by serotyping as well as by genotyping isolates of the virus. A major epidemic of FMD occurred in the UK in 2001 and was caused by a virulent strain of FMD virus with origins in Asia. The advantages and some disadvantages of controlling FMD outbreaks by vaccination are discussed.

Animals↗

PubMed1978

Adjvant treatment of tongue and floor of the mouth cancers.

Since January 1974, 95 patients with anterior tongue and floor of the mouth cancers were included in a randomized trial. After stratification according to staging and initial treatment, one-third of the patients received chemotherapy for 2 years (methotrexate 400 mg followed by citrovorum factor 100 mg + bleomycin 60 mg/week, during the first 15 weeks), one-third of the patients received immunotherapy with weekly C. parvum injections during 2 years, while the remaining third did not receive any treatment. If adjuvant treatment seems to delay recurrence it did not significantly decrease the recurrence rate. Survival is also not signigicantly modified by adjuvant treatment and was better for patients with small tumors. Patients who previously received radiotherapy did not benefit from adjuvant therapy.

Antigens, Bacterial↗

PubMed1993

Growth and spread of squamous cell carcinoma of the floor of the mouth.

Forty-eight specimens of carcinoma of the floor of the mouth were analyzed histologically by step serial sections. Five tumors were so-called superficial spreading carcinomas with large fields of cancerous mucosa, while 43 specimens showed advanced vertical growth into adjacent structures. Three different routes of invasion could be defined. The region of the sublingual gland was the main pathway in 23 cases. The space between the intrinsic muscles of the tongue and the genioglossus muscle was the main direction of infiltration for 14 tumors. Only 6 specimens showed direct invasion into the intrinsic tongue muscles. There was a good correlation between tumor thickness and the occurrence of metastases. Twenty-six patients (54%) showed metastases in regional lymph nodes and 13 patients with submandibular metastases already had developed metastases along the jugular vein. Unilateral or bilateral functional neck dissections remained the standard treatment procedure for all cases with depths of invasion over 5 mm. To avoid local tumor recurrences, patterns of invasion have to be considered. Soft tissue structures like the sublingual gland, intrinsic tongue muscles, genioglossus muscle and geniohyoid muscle have to be resected routinely. Management of the mandible should be conservative if radiological and clinical investigations are negative.

Carcinoma, Squamous Cell↗

PubMed1976

[Virus diseases of the mouth mucosa].

In accordance with the system of viral species, viral disorders of the oral mucosa may be classified with regard to their intensity of affection. There are but few viral infections exclusively affecting the oral mucosa like e.g. 1. Glossitis papulosa of Michelson, representing a special form of vaccinia inoculata, 2. Gingivo-stomatitis herpetica and 3. warts of the mucosa or condyloma-like papillomas of the oral mucosa including oral papillomatosis, that, itself shows morphological and clinical similarities to laryngeal papilloma. A second group of disorders mainly affecting the oral mucosa includes the "Aphthoid of Pospischill and Feyrter", Zahorsky's herpangina and other viral infections by the Coxsackie group, like vesicular stomatitis. The 3rd group represents viral infections of other organs in which affection of the oral mucosa is a prerogative, e.g. smallpox, varicella, foot-and-mouth disease and pharyngo-conjunctival fever. A 4th group includes those viral infections of the organs in which co-affection of oral mucosa occurs frequently or once in a while (at occasions). Here, we find eczema vaccinatum, herpes zoster, herpes simplex of the oral mucosa mostly on the hard palate, eczema herpeticatum, post-herpetic Erythema exsudativum multiforme, Mononucleosis infectiosa Pfeiffer, viral flu, German measles, parotitis epidemica, rubeola and ECHO-exanthema. A 5th and last group is made up by viral infections of other organs, in which affection of the oral mucosa hardly occurs at all. This group contains paravaccinal Ecthyma contagiosum, poliomyelitis, viral infection of the city of Marburg and some Arbovirus infections. Relatively few viral disorders never co-exist with lesions on the oral mucosa like e.g. Virus-hepatitis or some viral encephalitides. Groups 1 and 2, most important of all, are presented in detail regarding clinics, diagnostics, differential-diagnosis and therapy. The disorders within the other 3 groups are discussed only regarding their importance in the field of ENT-related symptoms of the oral mucosa. A number of pictures and tables completes important clinical details and give further hints to their differential-diagnosis.

Glossitis↗

PubMedDate not supplied

Cervical node metastases in early squamous cell carcinoma of the floor of the mouth: predictive value of multiple histopathologic parameters.

A semiquantitative assessment of multiple histological parameters was applied retrospectively to 66 patients with stage I and II squamous cell carcinoma of the floor of the mouth to determine if prognostic information relative to cervical node metastases could be obtained. Three parameters relating to the tumor cell population and 5 describing the tumor-host interface were evaluated on a point scale from 1 to 3 with the highest score going to the most threatening characteristic. Twenty of the 66 patients had either occult metastases identified by elective lymphadenectomy (n = 11) or developed metastases to the neck (n = 9). There was no correlation between traditional histological grading as recorded at the time of presentation and the frequency of cervical metastases (p greater than 0.05). Histological reevaluation defined 3 groups of patients with low (less than 14), moderate (14-16), and high scores (greater than 16) with an incidence of cervical metastases of 5/39 (12.8%), 6/17 (35.3%), and 9/10 (90%), respectively (p less than 0.001). The results suggest that microscopic grading could be a useful adjunct to the present TNM staging system in selecting patients likely to benefit from elective treatment of the neck.

Adult↗

PubMed2004

[Palliative surgery in squamous cell carcinoma of the anterior floor of the mouth].

A 62 year old patient presented with a bleeding, incurable squamous cell carcinoma of the anterior floor of the mouth. A curative concept was not possible. After four palliative surgical procedures, a definitive and a palliative radiation therapy and a palliative chemotherapy, the patient remained free of tumor in the head and neck region for 2 years after the initial treatment. Using a combination of palliative procedures, it is possible not only to achieve a full local remission but also to provide a high quality of life.

Carcinoma, Squamous Cell↗

PubMed2000

Masses of the tongue and floor of the mouth: findings on magnetic resonance imaging.

The purpose of this study was to determine the value of MR imaging for the demonstration of masses in the tongue and floor of the mouth. Nine patients were prospectively examined with MR imaging after physical examination. Imaging protocol included T2 and contrast-enhanced and non-contrast-enhanced T1-weighted turbo spin-echo sequences, and the findings were compared with surgical and histopathological results. Histopathological examination revealed four squamous cell carcinomas, one adenoid cystic carcinoma, two tongue abscesses, and one chronic inflammatory change. The other case was diagnosed as hemangioma depending on clinical and imaging findings alone. In cases with squamous cell carcinoma, staging was done on the basis of MR imaging findings, and was found to be T4 in two cases, T3 in one case, and T2 in another. The primary role of MR imaging of the tongue and oropharynx is not to make a tissue diagnosis. Multiple deep biopsies are mandatory for the differentiation of other inflammatory and neoplastic lesions. Magnetic resonance imaging produces coronal and sagittal image planes to assess the volume and spread of the lesion and helps the surgeon determine the direction in which the biopsy should be performed.

Abscess↗

PubMed2003

Genetic and antigenic analysis of two recently circulating genotypes of type A foot-and-mouth disease virus in India: evidence for positive selection in the capsid-coding genes.

We have analyzed isolates of two recently circulating genotypes (genotypes VI and VII) of type A foot-and-mouth disease virus (FMDV) from India. Maximum-likelihood models provided support for the presence of positively selected sites in the capsid-coding (P1) region. Positive selection was detected at a number of amino acid positions behind a background of strong purifying selection. Among the positively selected sites, four were identified at known critical antigenic residues (VP2 79, VP3 59 and 70 and, VP1 83), suggesting that FMDVs are under pressure from the immune system. Two residues (VP2 134 and VP3 59) that are part of the heparan sulfate-binding pocket in subtype A22 FMDV are also inferred to be under positive selection. Antigenic divergence was observed between and within the genotypes in neutralization tests with sera raised against the representative isolates from genotypes VI and VII. The two vaccine strains showed one-way antigenic relationships (r value) of <0.2 with 64% of the isolates, whereas, with genotypes VI and VII an r value of >0.4 was observed with 24% and 64% of the isolates, respectively. No correlation could be deduced from the amino acid substitutions at specific critical residues and lower r values in the field isolates.

Amino Acid Sequence↗

PubMed2003

Development of a novel quantitative real-time RT-PCR assay for the simultaneous detection of all serotypes of foot-and-mouth disease virus.

Foot-and-mouth disease virus (FMDV) spreads extremely fast and the need for rapid and robust diagnostic virus detection systems was obvious during the recent European epidemic. Using a novel real-time RT-PCR system based on primer-probe energy transfer (PriProET) we present here an assay targeting the 3D gene of FMDV. The assay was validated for the efficacy to detect all known FMDV serotypes. The test method was linear over a range of at least 7 orders of magnitude and the detection limit was below the equivalent of 10 genomic copies. Analysing recent African probang samples the method was able to detect FMDV in materials from both cattle and buffalo. When compared to traditional virus cultivation the virus detection sensitivity was similar but the RT-PCR method can provide a laboratory result much faster than virus cultivation. The real-time PCR method confirms the identity of the amplicon by melting point analysis for added specificity and at the same time allows the detection of mutations in the probe region. As such, the described new method is suitable for the robust real-time detection of index cases caused by any serotype of FMDV.

Animals↗

PubMed2003

Molecular phylogeny of leader proteinase gene of type A of Foot-and-mouth disease virus from India.

We previously demonstrated the presence of three genotypes (IV, VI and VII) of type A (subtype A22) of Foot-and-mouth disease virus (FMDV) in India based on 1D gene sequence analysis. In the present study, the leader proteinase (L(pro)) gene sequences of 35 type A FMDV field isolates sampled over a period of 24 years (1977-2000) have been analyzed. Maximum-likelihood (ML) phylogenetic analysis revealed four distinct genetic lineages (A-D), indicating high divergence in L gene of type A FMDV. Lineages A and D correspond to the earlier genotypes IV, and VII, respectively. The genotype VI isolates were divided into two separate lineages (B and C) in the tree with high confidence values (96-99%). One isolate (IND 21/90) showed incongruous grouping between the (1D and L) gene-based analyses, which could be due to intergenotypic recombination. The ML molecular clock hypothesis was easily rejected on the data set studied indicating the absence of clock-like evolution in the L gene. ML codon-substitution models identified positive selection in the amino acid site 194 of C-terminal extension of the Lb(pro) with high posterior probability (>99%). The catalytic triad of the L(pro) at C-51, H-148 and D-163 were conserved across all the Indian isolates studied. Finally, amino acid differences between the lineages have been discussed briefly.

Amino Acid Sequence↗

PubMed2005

Differentiation of foot-and-mouth disease virus infected animals from vaccinated animals using a blocking ELISA based on baculovirus expressed FMDV 3ABC antigen and a 3ABC monoclonal antibody.

A blocking ELISA that differentiated foot-and-mouth disease virus (FMDV) infected animals from vaccinated animals was developed which uses baculovirus expressed FMDV 3ABC non-structural protein as antigen and monoclonal antibody against FMDV 3ABC non-structural protein as capture and detector antibody. Sera from naive, vaccinated and infected cattle, sheep and pigs were examined. The specificity of the test was high. Non-specific reactions observed in particular in sera of cattle and sheep could be removed by filtration and inactivation. Positive reactions were obtained for sera from cattle infected with all seven serotypes of FMDV. The test detected antibodies from days 7 or 9 following experimental infection of non-vaccinated cattle and sheep, and in cattle strong positive reactions persisted for up to 395 days after infection. In vaccinated cattle that became carriers after challenge with homologous FMDV, positive reactions were obtained in all but one case. In some of these cattle the antibody response was detected late in comparison to the non-vaccinated infected cattle. The test gave results that compared favourably with two commercial ELISA's when used to test sera from cattle, pigs and sheep collected after experimental or natural infection. The blocking ELISA based on recombinant FMDV 3ABC antigen and a monoclonal antibody to 3ABC is a promising tool for FMD control and eradication campaigns, where vaccination has been carried out.

Animals↗

PubMed2005

Protective immune response against foot-and-mouth disease virus challenge in guinea pigs vaccinated with recombinant P1 polyprotein expressed in Pichia pastoris.

Vaccination of the susceptible livestock with potent, safe and cost effective vaccine is the primary requirement to control foot-and-mouth disease (FMD) in an endemic country. In this study, an alternative approach was used in which structural protein genes of all the four serotypes of FMDV (O, Asia 1, A22 and C) were expressed separately in methylotrophic yeast Pichia pastoris. The recombinant polyproteins (P1) were characterized by SDS-PAGE and in Western Blot analysis. Partially purified protein was used for immunization in guinea pigs with different adjuvant formulations and immune response studied. Ninety micrograms of the recombinant protein per monovalent dose was used for immunization. A single injection of a monovalent or polyvalent vaccine was given to guinea pigs with various adjuvant combinations viz., Monovalent recombinant protein either adjuvanted with Montanide-ISA50V or Indigenous oil, Monovalent recombinant protein mixed with 1/10th dose of inactivated oil-adjuvanted virus vaccine and Polyvalent recombinant protein with Montanide ISA50V. FMDV specific humoral immune response was observed at about 28th day post vaccination. The immune response as assessed by indirect ELISA and Serum neutralization test titres was found to be 320-640 and 16-32, respectively. When challenged with virulent homologous type 'O' virus, the guinea pigs showed protective C index of 2.01,1.81, 2.56 and 2.48, respectively, with above said adjuvant combinations. The study has shown that yeast-expressed FMDV P1 polyprotein in a single dose could elicit a protective immune response in guinea pigs, and this could be a possible future vaccine candidate in homologous host.

Animals↗

PubMed2005

Phylogeny, genome evolution, and antigenic variability among endemic foot-and-mouth disease virus type A isolates from India.

The capsid-coding (P1) and 3A regions of foot-and-mouth disease virus (FMDV) type A field isolates including two vaccine strains collected during 1977-2000 were analyzed. In the phylogenies, the isolates were distributed into two previously identified genotypes VI and VII, with multiple sub-genotypes that are temporally clustered. Comparison of the antigenic relationships of field isolates with the two vaccine strains (IND 17/77 and IND 490/97) and the reference strains of the genotypes VI (IND 233/99) and VII (IND 40/00) indicated two broad antigenic groups that correlate with the phylogenetic groupings (genotypes VI and VII), and are highly divergent from the vaccine strains. The maximum likelihood method of selection analysis identified a number of amino acid sites within the P1 region to be under weak positive selection. Some of the positively selected sites were mapped at/near the antigenically critical amino acid sites of the P1 region, indicating host immune pressure as one of the important driving force behind the observed genetic and antigenic diversity in FMDV. A small number of selected sites are located in the heparan sulphate-binding pocket of the virus, suggesting a fitness advantage for cell entry of the virus. No positive selection was detected in the 3A dataset.

Amino Acid Sequence↗

PubMed2005

Genetic comparison of large fragment of the 5'untranslated region among foot-and-mouth disease viruses with special reference to serotype Asia1.

Foot-and-mouth disease (FMD), the most economically important disease of cloven-hoofed animals, is endemic in India. Sequence analysis revealed that phylogenetic grouping of type Asia1 field isolates on the basis of the large fragment of the 5'untranslated region (5'LF-UTR) was quite similar to that based on the sequences of the capsid-coding (VP1) region of the same viruses. The existence of two distinct lineages of type Asia1 suggested by the study on the VP1 region was further supported by the detection of a difference in length and predicted secondary structure of the 5'LF-UTR between the two lineages. Sequence variability between the isolates of the two lineages was also observed within the different domains of the internal ribosome entry site (IRES) around conserved motifs like the GNRA,- RAAA,- and the polypyrimidine tract. Certain group and lineage-specific signature nucleotides pertaining to FMDV type Asia1 in the 5'LF-UTR have been identified. The present study shows that the 5'LF-UTR of FMDV serotype Asia1 field isolates are variable in relation to the length and probable secondary structure of the IRES.

5' Untranslated Regions↗

PubMed2005

Genomic and antigenic characterization of viruses from the 1993 Italian foot-and-mouth disease outbreak.

The origin and evolution of the type O foot-and-mouth disease viruses (FMDV) that caused the outbreak occurrence in Italy in 1993, the first episode of the disease in the EU after adoption of a non-vaccination policy in 1991, have been studied by the analysis of sequences encoding three main antigenic sites on the viral capsid proteins. The phylogenetic tree derived from sequences spanning the carboxyterminal end of VP1 showed that these Italian viruses were grouped in the ME-SA topotype, closely related to viruses that circulated previously in the Middle East. The analysis of the nucleotide sequences in VP1, VP2 and VP3 showed a co-circulation during the epizootic of genetic variants, including viruses with amino acid replacements in VP3. For some of the isolates analyzed, values of fixation of nucleotide substitutions per year were observed in the three regions analyzed, ranging from 1.5 to 5.1 x 10(-2). The use of a panel of new monoclonal antibodies raised against an isolate from this outbreak, as well as monoclonal antibodies to FMDV O1-Switzerland 1965, showed differences in the reactivity pattern among some of the Italian isolates analyzed, which were consistent with the co-circulation of antigenic variants. These results support the potential for FMDV diversification in a limited period of time and under epidemiological conditions in which no vaccination campaigns were being implemented.

Animals↗

PubMed2005

Retrospective genetic analysis of SAT-1 type foot-and-mouth disease outbreaks in southern Africa.

In areas where foot-and-mouth disease (FMD) is endemic in wildlife hosts, such as the Kruger National Park (KNP) in South Africa, control measures are in place that ensure that potentially infected antelope and buffalo do not come into close contact with domestic animals. In South Africa several SAT-1 outbreaks occurred nearly simultaneously in cattle and impala between 1971-1981. Phylogenetic analysis based on partial 1D gene nucleotide sequencing indicated that several of these outbreaks were linked and it is probable that disease spread from the intermediary impala antelope host to cattle in close proximity. Evidence was found for the involvement of viruses from a single KNP genotype in precipitating outbreaks in impala over a 10-year period. In addition, several unrelated outbreaks affecting cattle and impala occurred within a single year. Characterisation of outbreak strains from Botswana similarly revealed that a single genotype affected different species over a 10-year period and that transboundary spread of SAT-1 virus occurred on at least one occasion. This retrospective analysis of outbreak strains has clearly demonstrated that FMD control policies that address the role of antelope as intermediaries in disease transmission are crucial as these wildlife species play an important role in disease dissemination.

Africa, Southern↗