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PubMed1998

Comments on a commentary: statistical evaluation of split mouth caries trials.

When results of split mouth caries trials are reported, the most frequently used outcome measures are "effectiveness" and "net gain". In a recent review by Riordan & FitzGerald (Community Dent Oral Epidemiol 1994;22:192-7) of the statistical analysis of data from such trials, the close connection between effectiveness and the traditional epidemiological outcome measure, relative risk, was pointed out and the latter measure was recommended. The confidence intervals for these parameters were, however, incorrect. This note provides valid confidence intervals for net gain, effectiveness and relative risk based on data from split mouth trials and presents examples of the calculations.

Confidence Intervals↗
PubMed2006

Reducing the bias of probing depth and attachment level estimates using random partial-mouth recording.

OBJECTIVES: To evaluate the bias and precision of probing depth (PD) and clinical attachment level (CAL) estimates of random and fixed partial examination methods compared with full-mouth examinations. METHODS: PD and CAL were calculated on six sites for up to 28 teeth (considered to be the gold standard with no bias) and three fixed-site selection methods (FSSMs) that resulted in a partial examination of sites: the Ramfjord method, and the NIDCR methods used in NHANES I, and NHANES 2000. Finally, seven random-site selection methods (RSSMs) were created by sampling the following number of sites: 84, 42, 36, 28, 20, 15, 10 and 6. To compare bias and precision of the methods we calculated percent relative bias and relative error. RESULTS: Estimates of means, standard deviations (SD), relative bias and relative error for RSSMs were almost identical to the full-mouth examination, but SDs increase slightly when fewer than 28 sites were sampled and relative bias and error increase for methods sampling fewer than 20 sites. The FSSMs had very low relative error, but much higher relative bias indicating underestimation. The FSSM with the smallest bias and error was the Ramfjord method, but the Random 36 method had less bias and less relative error. The NHANES 2000 method was the FSSM with the lowest bias and relative error for estimates of Extent Scores (percent of sites > or =3, 4, 5, or 5 mm PD or CAL) but random methods sampling fewer sites performed just as well. Both FSSMs and RSSMs underestimated prevalence, especially prevalence of less frequently occurring conditions, but most RSSMs were less likely to underestimate prevalence than the FSSMs. CONCLUSION: The promise of reducing bias and increasing precision of the estimates support the continued development and examination of RSSMs.

Aged↗
PubMed1990

Degenerative changes in masseter and temporalis muscles in limited mouth opening and TMJ ankylosis.

The masseter and temporalis muscles were studied ultrastructurally in eight cases suffering from restricted mouth opening and TMJ ankylosis. The changes varied from slight degeneration of muscle fibers, such as accumulation of lipid or lipofuscin deposits, Z-band streaming and derangement of myofilaments, in one case to moderate or severe changes of muscle atrophy and necrosis in the remaining seven cases. Nemaline bodies were also observed in one of these seven cases. In addition to these muscle changes neural degeneration especially of myelinated nerves were found in three of the cases studied. The present findings showed that in spite of the diversity of the underlying factors affecting the joint, there was many similarities in the changes observed within the muscle. It is postulated that these degenerative muscle changes probably play an important role in restricted mouth opening and TMJ ankylosis, and that some of these muscle pathology may be the result of neural involvement.

Actin Cytoskeleton↗
PubMed2006

Impact of wearing an intra-oral lubricating device on oral health in dry mouth patients.

OBJECTIVE: To establish whether an intra-oral lubricating device for dry mouth alters the oral environment. DESIGN: A single-blind randomized cross-over study. METHOD: Twenty-nine dentate subjects from the Sjogren's syndrome clinic attended on five occasions at 4-week intervals. They were randomized, having the device fitted on either the second or the fourth visit for the experimental period, whilst using their preferred method of lubrication throughout the rest of the study. The preferred methods of lubrication were either water (group 1, n = 10) or saliva substitute (group 2, n = 9) or sugar-free chewing gum (group 3, n = 10). At each visit microbiological, unstimulated and stimulated saliva samples were collected. Dry mouth score, speech test and periodontal indices were recorded. RESULTS: The water lubrication group (1) had a resting salivary flow greater than lubrication groups (2 and 3) by post-ANOVA contrasts (P < 0.001). The postdevice data also demonstrated a salivary flow greater than lubrication group (3) by post-ANOVA contrasts (P < 0.05). The epithelial cell count using the Spearman correlation was high, possibly reflecting increased viscosity of the saliva (P = 0.044). The speech test indicated that the experimental subjects had difficulty in speaking (P = 0.001). This was slightly easier postdevice wear. Streptococcus mutans (P = 0.009) and Lactobacillus (P = 0.058) increased in the saliva after wearing the device. Salivary flow rate, Candida albicans, oral dryness, speaking and periodontal indices were unchanged. CONCLUSIONS: The oral environment was altered by wearing a lubricating device with an increase in the numbers of Strep. mutans and Lactobacillus. Clinical dryness and speech test correlated with the mean whole salivary flow suggesting a screening method for xerostomia.

Adult↗
PubMed1996

Whole saliva and the diagnosis of Sjögren's syndrome: an evaluation of patients who complain of dry mouth and dry eyes. Part 1: Screening tests.

UNLABELLED: Sjögren's syndrome (SS) is a common autoimmune disorder characterised by generalised desiccation, exocrine hypofunction and serologic abnormalities, More than 90% of the patients are women. OBJECTIVE: To determine if whole saliva could be used to diagnose this disease. SETTING: The study was conducted at the School of Dental Medicine, SUNY, at Stony Brook. PATIENTS: There were 49 subjects (48 F; 1 M), the mean age was 54 +/- 13 years. In order to be admitted into the study, they had to complain of dry mouth and dry eyes. TESTS: Whole saliva was collected by the spitting method. "Screening Tests" were employed to measure the salivary flow rate, pH, buffer capacity; lactobacillus and yeast concentrations. Chemical tests were performed to determine protein, albumin, sodium and amylase activity. Lacrimal dryness was assessed by the Schirmer and Rose-Bengal methods. RESULTS: Based on the sialometric findings, the patients were divided into 3 groups: Group 1: those with abnormally low resting (RFR) and stimulated (SFR) flow rates; Group 2: those with a low RFR but normal SFR; and Group 3: those with normal salivary flow rates. The group 1 patients were unique: their saliva demonstrated a low pH and buffer capacity, high lactobacillus and yeast concentrations, decreased protein output and amylase activity, and elevated albumin and sodium. Moreover, virtually all of them had abnormally low lacrimal flow rates. CONCLUSIONS: The findings suggested that whole saliva could be used to provisionally diagnose SS. Critical to this diagnosis was an abnormally low stimulated whole saliva flow rate. Other requisites included a low resting flow rate, the presence of dry mouth and dry eyes and evidence of lacrimal hypofunction. All of these attributes can easily be obtained by dentists in their clinics.

Adult↗
PubMed1996

Whole saliva and the diagnosis of Sjögren's syndrome: an evaluation of patients who complain of dry mouth and dry eyes. Part 2: Immunologic findings.

UNLABELLED: Sjögren's syndrome (SS) is a multisystem, autoimmune disease characterised by generalised desiccation, exocrine hypofunction and serologic abnormalities. Last year we showed that the antibodies which are quasi-specific for diagnosis of SS, anti SS-A/Ro and anti SS-B/La, were present in the saliva of patients with this disease. OBJECTIVE: To determine their presence in patients who complain of dry mouth and dry eyes. SETTING: The study was conducted at the School of Dental Medicine, SUNY at Stony Brook. PATIENTS: There were 49 patients (Mean Age = 54 +/- 13 years). TESTS: Serum was analysed for the SS and other antibodies with "Western Blot Autoantibody Strips". RESULTS: The findings showed that there was a strong correlation between the presence of the SS antibodies in the serum and the saliva. The SS antibodies were primarily found in the saliva of the patients whose resting and stimulated, whole saliva, flow rates were abnormally low. Antibodies to other autoimmune disease (lupus, scleroderma and mixed connective tissue disease) were also found in whole saliva. CONCLUSIONS: The findings in Part 1 of this study, of patients who had complained of dry mouth and dry eyes, suggest that those patients, who demonstrated low resting and stimulated flow rates and had lacrimal hypofunction, suffered from SS. The observation in this paper, that the whole saliva of these patients contains the SS antibodies, confirms this diagnosis. The data suggest that whole saliva can be used to establish the diagnosis of SS and other autoimmune diseases.

Adult↗
PubMed1997

A reference guide to drugs and dry mouth--2nd edition.

Xerostomia (dry mouth) is an uncomfortable and potentially harmful oral symptom which is usually caused by a decrease in the secretion rate of saliva (salivary gland hypofunction, or SGH). It is more prevalent in the elderly population, primarily due to their increased use of drugs and their susceptibility to disease. Many drugs and drug classes have been linked to xerostomia; the xerogenic effect increases when many drugs are taken concurrently. This Reference Guide to Drugs and Dry Mouth is designed to allow the reader to rapidly identify those pharmacologic agents which have the capacity to induce xerostomia and SGH. Xerogenic drugs can be found in 42 drug categories and 56 sub-categories. A guide to the management of drug-induced SGH and xerostomia is also provided.

Aged↗
PubMed1978

Effect of zinc and other chemical agents on foot-and-mouth-disease virus replication.

Chemical agents reported to inhibit the growth of various ribonucleic acid and deoxyribonucleic acid viruses were tested against foot-and-mouth disease virus in cell culture. These included Zn(2+), aurintricarboxylic acid, polyribocytidylic acid, polyriboinosinic acid, phosphonoacetic acid, and the viral contact inactivator N-methyl isatin beta-thiosemicarbazone alone and with CuSO(4). The most effective agent, Zn(2+), inhibited foot-and-mouth disease virus production in primary calf kidney cells by 1 log unit at 0.05 mM Zn(2+) and completely at 0.50 mM. Zinc was inhibitory even when added late in infection and was nontoxic to uninfected cells as measured by protein and nucleic acid syntheses. Polyacrylamide gel patterns of [(35)S]methionine-labeled, virus-specific proteins showed increasing amounts of higher-molecular-weight material, in accord with reports that Zn(2+) inhibits post-translational cleavages of other picornavirus precursor polypeptides.

Antiviral Agents↗
PubMed1975

Production, isolation, and partial characterization of three foot-and-mouth disease virus temperature-sensitive mutants.

Three high temperature-sensitive (ts) mutants of foot-and-mouth disease virus were characterized by their relative abilities to grow at 33 or 38.5 C, to kill infant mice, to infect guinea pigs, and to produce foot-and-mouth disease in steers. Mutants ts-24 and ts-42 did not grow at 38.5 C; both may have produced considerable quantities of noninfectious virus particles at 33 C. A third mutant, ts-22, appeared "leaky" because it multiplied to a limited extent during prolonged incubation at the nonpermissive temperature. Mutant ts-42 was pathogenic for infant mice, whereas ts-22 and ts-24 were essentially apathogenic. Mice were protected against the lethal effects of the wild-type (wt) virus if injected 1 week earlier with ts-22, apparently as a result of specific antibody development. One-half of the guinea pigs injected with the mutant viruses showed lesion development, but only at the site of injection. Antibody development was also much less than in those animals injected with the wt virus. The onset of FMD in steers was delayed and the severity of the disease was diminished after intradermalingual injection of the mutant viruses.

Animals↗
PubMed1982

Application of RNase T1 one- and two-dimensional analyses to the rapid identification of foot-and-mouth disease viruses.

The analysis of several isolates of foot-and-mouth disease virus by RNase T1 fingerprinting of the 32P-labeled RNA is described. It has been shown that use of the 35S induced RNA instead of the virus particle RNA has two advantages. (i) About 40 times more radioactivity is incorporated into the induced RNA. (ii) The RNA can be prepared much more rapidly, thus increasing the value of the technique in rapid diagnosis. One-dimensional maps, in which the RNase T1 oligonucleotides are separated according to size, have been shown to provide a valuable screening method for distinguishing between viruses. Those viruses giving similar one-dimensional maps also gave similar two-dimensional maps. The value of using the length of the polycytidylic acid tract of foot-and-mouth disease virus as a diagnostic tool is also discussed.

Aphthovirus↗
PubMed1980

Location of the initiation site for protein synthesis on foot-and-mouth disease virus RNA by in vitro translation of defined fragments of the RNA.

An mRNA-dependent reticulocyte lysate has been used to translate foot-and-mouth disease virus RNA in vitro. Polypeptides P16, P20a, and P88, which have been shown to be derived from the 5' end of the RNA by pactamycin mapping experiments with infected cells, were preferentially synthesized in vitro. Removal of VPg, the small protein covalently linked to the 5' end of the genome RNA, had no effect on the translation of the RNA. The two RNA fragments (L and S) produced by specific digestion of the polycytidylic acid [poly(C)] tract with RNase H were also translated in vitro. The L fragment, consisting of RNA to the 3' side of the poly(C) tract and including the polyadenylic acid [poly(A)] tract, directed the synthesis of the same products as those made by full-length RNA. However, no small defined products were produced when the S fragment, which contains the 5' end of the RNA, was translated. These results show that the major initiation site for protein synthesis on foot-and-mouth disease virus RNA is to the 3' side of the poly(C) tract. Furthermore, the use of N-formyl [35S]methionine tRNAfMet as a label for the initiation peptides showed that the major polypeptide labeled in lysates primed with both full-length RNA and the L fragment was P16, i.e., the protein nearest the initiation site for translation as deduced from pactamycin mapping experiments. Fragments of RNA were also translated in vitro. Those containing the poly(C) tract gave products similar to those produced when full-length RNA was translated. The polypeptides synthesized when fragments containing the poly(A) tract were used, however, did not resemble those made from full-length RNA.

Aphthovirus↗
PubMed1969

Inhibition of host cell ribosomal ribonucleic acid methylation by foot-and-mouth disease virus.

A study of protein and ribonucleic acid (RNA) synthesis in cells infected by foot-and-mouth disease virus has indicated possible mechanisms of viral control over host cell metabolism. Foot-and-mouth disease virus infection of baby hamster kidney cells resulted in 50% inhibition of host cell protein synthesis at 180 min postinfection. A viral-induced interference with host cell RNA methylation was observed to be more rapidly inhibited than protein synthesis. To determine the nature of methylation inhibition, the kinetics of several host cell methylated RNA species were examined subsequent to virus infection. Data from sucrose zonal centrifugation and methylated albumin kieselguhr chromatography showed that methylation of nuclear RNA was inhibited 50% at 60 min postinfection. Inhibition of nuclear ribosomal RNA precursors and formation of nascent ribosomes correlated with inhibition kinetics of nuclear RNA methylation. It is suggested that the viral interference with the host nuclear RNA methylation is directly responsible for the observed loss of nascent ribosome formation. Moreover, early in the infectious cycle, methylation inhibition of host cell RNA could, in part, account for the cessation of host protein synthesis.

Animals↗
PubMed1983

Identification of an exposed region of the immunogenic capsid polypeptide VP1 on foot-and-mouth disease virus.

Iodination of intact foot-and-mouth disease virus results in the selective labeling of VP1, substantiating its exposed location on the virion. A comparison of tryptic peptides revealed that a single tyrosine-containing peptide was labeled with iodine on intact or protease-cleaved virus. The labeled peptide from intact and protease-cleaved virus was characterized by molecular weight sizing and sequence analysis. Carboxypeptidase digestion of intact VP1, limited trypsin-cleaved VP1, and VP1 purified from bacterially contaminated tissue cultures yielded carboxyterminal residues of leucine, valine-arginine, and serine-alanine, respectively. The correlation of these findings with previous data on the amino acid sequence derived from nucleotide sequencing of serotypes A12 and O1 of foot-and-mouth disease virus VP1 places the probable exposed antigenic region of VP1 in a serotype-variable region including residues 136 through 144.

Amino Acid Sequence↗
PubMed1984

Epitopes on foot-and-mouth disease virus outer capsid protein VP1 involved in neutralization and cell attachment.

Foot-and-mouth disease virus structural protein VP1 elicits neutralizing and protective antibody and is probably the viral attachment protein which interacts with cellular receptor sites on cultured cells. To study the relationships between epitopes on the molecule related to neutralization and cell attachment, we tested monoclonal antibodies prepared against type A12 virus, isolated A12 VP1, and a CNBr-generated A12 VP1 fragment for neutralization and effect on viral absorption. The antibodies selected for analysis neutralized viral infectivity with varying efficiencies. One group of antibodies caused a high degree of viral aggregation and inhibited the adsorption of virus to cells by 50 to 70%. A second group of antibodies caused little or no viral aggregation but inhibited the adsorption of virus to cells by 80 to 90%. One antibody, which is specific for the intact virion, caused little viral aggregation and had no effect on the binding of virus to specific cellular receptor sites. Thus, at least three antigenic areas on the surface of foot-and-mouth disease virus which were involved in neutralization were demonstrated. One of the antigenic sites appears to have been responsible for interaction with the cellular receptor sites on the surface of susceptible cells.

Animals↗
PubMed1984

Induction of antibody to foot-and-mouth disease virus in presensitized mouse spleen cell cultures.

Cultures of spleen cells from immunized mice were stimulated in vitro by soluble preparations of purified foot-and-mouth disease virus. Virus-specific antibody, as detected by an enzyme-linked immunosorbent assay, was produced by immune spleen cells but not by normal, nonimmune cells. The optimal specific response was obtained with 1 microgram of virus per ml of culture; as the virus concentration was increased, the production of specific antibody was reduced. For very low concentrations of virus (less than 0.01 microgram per culture), there was tentative evidence of suppression of the specific antibody response. The levels of specific antibody induced were dependent on the source and number of plastic-adherent cells present in the cultures. We intend to use this model system to study further the basis of immunity to foot-and-mouth disease virus.

Animals↗
PubMed1985

Capsid intermediates assembled in a foot-and-mouth disease virus genome RNA-programmed cell-free translation system and in infected cells.

Structural protein complexes sedimenting at 140S, 70S (empty capsids), and 14S were isolated from foot-and-mouth disease virus-infected cells. The empty capsids were stable, while 14S complexes were relatively short-lived. Radioimmune binding assays involving the use of neutralizing monoclonal antibodies to six distinct epitopes on type A12 virus and polyclonal antisera to A12 structural proteins demonstrated that native empty capsids were indistinguishable from virus. Infected cell 14S particles possessed all the neutralizing epitopes and reacted with VP2 antiserum. Cell-free structural protein complexes sedimenting at 110S, 60S, and 14S containing capsid proteins VP0, VP3, and VP1 are assembled in a rabbit reticulocyte lysate programmed with foot-and-mouth viral RNA. These structures also contain the six epitopes, and cell-free 14S structures like their in vivo counterparts reacted with VP2 antiserum. Capsid structures from infected cells and the cell-free complexes adsorbed to susceptible cells, and this binding was inhibited, to various degrees, by saturating levels of unlabeled virus. These assays and other biochemical evidence indicate that capsid assembly in the cell-free system resembles viral morphogenesis in infected cells. In addition, epitopes on the virus surface possibly involved in interaction with cellular receptor sites are found early in virion morphogenesis.

Animals↗
PubMed1989

Analysis of neutralizing antigenic sites on the surface of type A12 foot-and-mouth disease virus.

A series of seven neutralizing monoclonal antibodies (nMAbs) directed against type A12 foot-and-mouth disease virus was used to generate neutralization-resistant variants. Both plaque reduction neutralization and microneutralization assays showed that the variants were no longer neutralized by the nMAbs used to generate them, although some of the variants still reacted with the nMAbs at high antibody concentrations. Results of cross-neutralization studies by both plaque reduction neutralization and microneutralization assays suggested the presence of at least one immunodominant antigenic site on the surface of type A12 foot-and-mouth disease virus, along with evidence of a second antigenic site on the viral surface. Two of the variants had reduced virulence in tissue culture as evidenced by their inability to inhibit cellular protein synthesis and a marked reduction in virus-induced cellular morphological alterations. Nucleotide sequencing of the variant genomes placed three epitopes of the major antigenic site on VP1 and the fourth epitope on VP3 and VP1. The one epitope of the minor site appears to reside only on VP1.

Amino Acid Sequence↗
PubMed1990

Functional analysis of the internal translation initiation site of foot-and-mouth disease virus.

Mutagenesis of the large untranslated sequence at the 5' end of the genome of foot-and-mouth disease virus revealed that a region of approximately 450 nucleotides preceding the open reading frame of the viral polyprotein is involved in the regulation of translation initiation at two internal start sites. Variations in two domains of this region reduced the translation efficiency up to 10-fold, whereas an intermediate segment seemed to be less essential. A pyrimidine-rich sequence preceding the start codon was most sensitive in that conversion of single pyrimidine residues to purines decreased the translation efficiency strongly. The data are in agreement with a recently proposed general structural model for the internal ribosome entry site of the cardiovirusaphthovirus subgroup of picornaviruses (E. V. Pilipenko, V. M. Blinov, B. K. Chernov, T. M. Dmitrieva, and V. I. Agol, Nucleic Acids Res. 17:5701-5711, 1989). They suggest, however, that this model represents only a core structure for the internal entry of ribosomes and that foot-and-mouth disease virus and other members of the picornaviruses need additional regulatory RNA elements for efficient translation initiation.

Animals↗