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Biomedical subjects

R C Page

Publications and source records attributed to R C Page.

At least 37 records · Page 2Linked to original sources
PubMed1998

In vivo evaluation of the absorption and gastrointestinal transit of avitriptan in fed and fasted subjects using gamma scintigraphy.

The study was conducted to assess the bioavailability of avitriptan after a standard high fat meal, in relation to gastrointestinal transit. Six healthy male subjects were enrolled in a four-period study with a partial replicate design where each was administered 150-mg avitriptan capsule (i) after an overnight fast, (ii) 5 min after a standard high-fat breakfast, and (iii) 4 hr after a standard high fat breakfast. The treatment administered in Period 3 was repeated in Period 4 to assess intrasubject variations in pharmacokinetics and gastrointestinal (GI) transit. Avitriptan capsules were specially formulated with nonradioactive samarium chloride hexahydrate which was neutron-activated to gamma-emitting samarium before dosing. Serial blood samples were collected for analysis of avitriptan up to 24-hr postdose, and serial scintigraphic images were obtained to assess the plasma concentration-time profile in relation to the GI transit of the avitriptan capsule contents. Bioavailability of avitriptan was reduced when administered in the fed condition but only the decrease in AUC(INF) was statistically significant. Tmax was significantly delayed between the fed conditions and the fasted condition. Qualitative appearance of plasma concentration-time profiles for avitriptan could be related to the manner in which the drug emptied from the stomach. It was also apparent that avitriptan exerted a secondary pharmacologic effect that temporarily suspended gastric emptying in the fasted treatment. Thus, when gastric emptying was interrupted and then resumed, the net result was a double peak in some of the individual plasma concentration profiles. Scintigraphic analysis also demonstrated that upon emptying from the stomach, avitriptan was rapidly absorbed from the upper small intestine. In the fed state, gastric emptying was slow and continuous resulting in extended absorption and a lower occurrence of double peaks. Qualitatively, the intrasubject variability in Cmax and AUC could be explained by the intrasubject variability in gastric emptying in both fasted and fed conditions.

Adult↗
PubMed1998

Antigenic variation and cross-reactivity in Bacteroides forsythus clinical isolates detected by western blot.

Bacteroides forsythus is one of the etiologic agents of destructive periodontal diseases. Determining which antigenic components of the bacterium are recognized in the immune response of periodontitis patients is an important step in assessing strategies for vaccine development. The aim of this study was to identify the major strain-variable and cross-reactive antigens of B. forsythus clinical isolates recognized by serum IgG from patients with early-onset rapidly progressive periodontitis. Ten patient sera with measurable IgG against antigenic components of the species were identified by Western blot. Positive sera were tested by checkerboard ELISA to identify those most responsive to strain-variable antigens in nine clinical isolates and ATCC strain 43037. Correlation analysis of the ELISA data suggested that different subsets of isolates were preferentially recognized by different sera. Western blots revealed that certain sera also recognized major shared components across all the isolates, but preferential recognition of different isolate subsets by different patients was clearly confirmed. To determine if the variable antigens recognized were nonprotein, proteinase K-digested isolates were compared to undigested controls by Western blot. The main strain-variable antigens were proteinase resistant, while proteins at 200 and 210 kDa were identified as the major shared components. Two-dimensional SDS-PAGE revealed that these proteins are the quantitatively dominant heat-modifiable components of the cell envelope. Even though variable antigens are prominent in the immune response of patients, a cross-protective vaccine based on the shared envelope proteins of B. forsythus seems feasible in light of these observations.

Adult↗
PubMed1998

Antigenic components of Actinobacillus actinomycetemcomitans lipopolysaccharide recognized by sera from patients with localized juvenile periodontitis.

The dominant antigen of Actinobacillus actinomycetemcomitans recognized by high-titer sera from patients with localized juvenile periodontitis is the serotype antigen located in the O-side chains of lipopolysaccharide. Whether such sera contain antibodies reactive with other epitopes in lipopolysaccharide, as is the case for patients with rapidly progressive periodontitis, remains unknown. We prepared and characterized by gas liquid chromatography lipopolysaccharide, lipid A, core carbohydrate with no or few O-side chains (core) and high-molecular-mass carbohydrate-rich in O-side chains (oligosaccharide) from A. actinomyce-temcomitans ATCC 43718 (serotype b, Y4). Using enzyme-linked immunosorbent assay (ELISA), sera from 36 patients with localized juvenile periodontitis were surveyed using whole-cell sonicate as plate antigen. The seven highest titer sera were selected for further study. Specific IgG antibody binding was observed to intact lipopolysaccharide and to all the lipopolysaccharide fractions. The mean titers were highest for intact lipopolysaccharide (138.8 ELISA units), and lipid A (122 ELISA units), followed by the core fraction (81 ELISA units) and the oligosaccharide fraction (69.5 ELISA units). ELISA inhibition revealed that the core fraction at a concentration of 10 micrograms/test well inhibited antibody binding to A. actinomycetemcomitans lipopolysaccharide by a mean value of 56.7%. To further characterize antibody binding to the core fraction, ELISA inhibition was performed using as inhibitor the core carbohydrate fraction of the Re mutant of Salmonella minnesota, which is known to contain only alpha-keto-3-deoxyoctonate residues and phosphate. This fraction at 10 micrograms/test well inhibited binding of antibodies from 6 of 7 test sera with a mean value of 49.2%. Thus, sera from patients with localized juvenile periodontitis contain antibodies that bind to the O-side chains of lipopolysaccharide, as has been previously reported, but they also contain antibodies that bind to lipid A and to lipopolysaccharide core polysaccharide epitopes, specifically to alpha-keto-3-deoxyoctonate moieties. The humoral immune response to A. actinomycetemcomitans in patients with localized juvenile periodontitis is more complex than previously reported and is very similar to that of patients with rapidly progressive periodontitis.

Adolescent↗
PubMed1998

Differential proliferation of fibroblasts cultured from hereditary gingival fibromatosis and normal gingiva.

Hereditary gingival fibromatosis (HGF) is an oral condition characterized by the enlargement of the gingiva of both the maxilla and mandible. To study the cell proliferation index of fibroblasts from HGF and normal gingiva (NG), cell cultures from 4 members of the same family with HGF and from 4 healthy patients were established. Our results obtained from 6 different cell proliferation assays clearly showed that the cell proliferation rate was significantly higher in fibroblasts from HGF than from normal gingiva. HGF and control fibroblasts in subconfluent culture densities were typically spindle, but in saturation density HGF cells were shorter than control cells. These data suggest that the higher proliferative index of HGF fibroblasts possibly has a role in the pathogenesis of gingival outgrowth in HGF patients.

Adult↗
PubMed1998

Antigenic variation in Bacteroides forsythus detected by a checkerboard enzyme-linked immunosorbent assay.

Evidence indicating that multiple serotypes of Bacteroides forsythus participate in rapidly progressing periodontal infections has not been reported previously. Our aim was to develop an assay for detecting subsets of B. forsythus clinical isolates which differ in serogroup membership and subsets of patients with immunoglobulin G (IgG) responses which differ in serogroup recognition. A checkerboard enzyme-linked immunosorbent assay (ELISA) was used to assess variation in the IgG binding profiles of 22 clinical isolates in sera from 28 patients with early-onset rapidly progressive periodontitis. To accommodate the maximum number of isolates and sera in a given assay run, a multiplate assay grid with standard 96-well microtest plates was established. Single dilutions of individual sera were placed in rows crossing columns of isolate-coated wells, and antigen-specific IgG immobilized in the wells was measured as ELISA absorbance. Pooled sera and isolates were assayed in parallel to serve as negative controls for variation in IgG binding profiles. Correlation and hierarchical cluster analysis of the absorbance data matrix showed that the isolates could be sorted into at least four clusters based on variations in their IgG binding profiles across different sera. Furthermore, at least two patient clusters were defined by variations in their serum IgG antigen recognition profiles across different isolates. We conclude that multiple serogroups of B. forsythus exist and that different serogroups are dominant in the antibody response of different patients. The method applied here could be used to serologically classify clinical isolates of other species which evoke a serum antibody response in patients.

Adult↗
PubMed1998

The pathobiology of periodontal diseases may affect systemic diseases: inversion of a paradigm.

A new paradigm for the pathobiology of periodontitis is presented, and the manner in which periodontitis may relate to susceptibility for certain systemic diseases such as cardiovascular disease and preterm labor is described. Periodontitis is caused by a small group of Gram-negative bacteria present on the tooth root surfaces as bioffilms. Lipopolysaccharide (LPS) and other substances gain access to the gingival tissues, initiate and perpetuate immunoinflammation, resulting in production of high levels of proinflammatory cytokines. These induce production of matrix metalloproteinases which destroy the connective tissues of the gingiva and periodontal ligament, and prostaglandins which mediate alveolar bone destruction. Periodontitis may enhance susceptibility to systemic diseases in several ways. LPS and viable Gram-negative bacteria from the biofilms and proinflammatory cytokines from the inflamed periodontal tissues may enter the circulation in pathogenic quantities. In addition, periodontitis and certain systemic diseases, such as cardiovascular disease, share risk factors including tobacco smoking, male gender, race/ethnicity, stress, and aging.

Animals↗
PubMed1998

Patients' perceptions of chamba (marijuana) use in Malawi.

This study examines the perceptions of the social aspects, triggers, and effects of chamba (marijuana) use among psychiatric patients at Zomba Mental Hospital in Malawi. Focus groups were used to elicit responses from 44 male and 10 female psychiatric patients about their perceptions of chamba use in Malawi. This study provides insight into these patients' perceptions of the triggers and effects of their chamba use, and it has implications for the development of treatment and prevention programs for chamba users in Malawi.

Adult↗
PubMed1997

An account of the quality of life of patients after treatment for non-functioning pituitary tumours.

OBJECTIVE: Studies assessing quality of life in GH-deficient adults have shown varying results. This may be due to a number of factors including varying causes of GH deficiency, the use of radiotherapy in treatment and patient selection. We aimed to assess whether anterior pituitary hormone deficiency or external pituitary radiotherapy influenced the quality of life of patients with non-functioning pituitary tumours. PATIENTS: We studied 48 patients treated and under follow-up for non-functioning pituitary tumours on standard hormone replacement therapy excluding GH. There were 21 females and 27 males with a mean age of 59 +/- 12 years. We also studied 42 control patients who had undergone mastoid surgery and were followed at least annually. There were 17 females and 25 males with a mean age of 61 +/- 14 years. DESIGN: All patients attended a research clinic and completed the Short Form 36 (SF36) and General Well Being Schedule (GWBS) to assess quality of life. Thyroid function tests, IGF1 and IGFBP3 were measured on all patients. Gonadotrophin and cortisol measurements were made on the patients with pituitary disease where appropriate. RESULTS: IGF1 and IGFBP3 levels were lower in the pituitary patients compared with controls: 104 +/- 98 vs 143 +/- 37 micrograms.l (P < 0.0001) and 2.9 +/- 0.75 vs 3.3 +/- 0.52 mg/l (P < 0.004). There were no significant differences in the quality of life scores between the pituitary patients and the control subjects. There was also no difference in quality of life between pituitary patients with two or more hormone deficiencies (n = 29) compared with controls. Patients who had received radiotherapy (n = 18), when compared with controls, had a decreased mental health score using the SF36 71 +/- 21 vs 81 +/- 17 (P < 0.05) and decreased total GWBS score 70 +/- 20 vs 82 +/- 17 (P < 0.05). Subscore analysis of GWBS showed this to be due to depression and decreased control of emotions. CONCLUSIONS: We found that the quality of life of patients treated and under follow up for non-functioning pituitary tumours was similar to that of patients treated by mastoid surgery and under similar follow up. The pituitary patients deficient in two hormones and thus most likely to be GH deficient were also similar to the controls. These results suggest that adding GH replacement in this patient group may not be routinely indicated for improvement in quality of life and needs careful assessment. Patients who had received radiotherapy were more depressed and anxious than controls. Further investigation into the psychological and psychomotor effects of radiotherapy in this group of patients is required.

Aged↗
PubMed1997

Recognition of antigenic epitopes in lipopolysaccharide and protein from Actinobacillus actinomycetemcomitans by serum antibodies in untreated rapidly progressive periodontitis patients.

Actinobacillus actinomycetemcomitans has been associated with early-onset periodontitis, including the localized juvenile and rapidly progressive forms. The immunodominant antigens of A. actinomycetemcomitans recognized by rapidly progressive periodontitis patients remain unidentified. Sera from 22 patients with rapidly progressive periodontitis and 20 periodontally normal subjects were tested by enzyme-linked immunosorbent assay (ELISA) for immunoglobulin G antibodies to whole-cell sonicate, protein, purified lipopolysaccharide and lipopolysaccharide fractions of A. actinomycetemcomitans. The median titers of rapidly progressive periodontitis patients and control subjects to whole-cell sonicate were 25.0 and 14.5 ELISA units, respectively (not significantly different). Binding of antibody from patient sera occurred to both the lipopolysaccharide and the protein fractions, with greater binding to lipopolysaccharide than to protein. We show for the first time that patient sera contain antibodies that bind specifically to antigenic epitopes in lipid A and in the core carbohydrate of lipopolysaccharide that were previously considered to be inaccessible and unavailable, as well as to epitopes in the O side chains. Sera manifesting antibody titers 2-fold or greater than the median titer for control sera were judged to be seropositive. More patients were seropositive for lipid A than for any of the other antigen preparations studied, and the median titer for patient sera to lipid A but to none of the other purified lipopolysaccharide fractions was significantly elevated relative to control values. Of 22 patients, 10 were seropositive to whole-cell sonicate, 7 to protein, 8 to lipopolysaccharide, 7 to the high-molecular-weight lipopolysaccharide-polysaccharide fraction rich in O side chains, and 16 to lipid A. The core carbohydrate did not adhere to the test plate surface, and this precluded ELISA measurements. However, when the core carbohydrate was used in the ELISA inhibition assay, it reduced antibody binding to lipopolysaccharide-coated plates by up to 45%, thereby demonstrating antibody binding to core carbohydrate. The core carbohydrate fraction from the Re mutant of Salmonella minnesota known to contain no O-side chains also inhibited binding of specific antibody to plates coated with A actinomycetemcomitans lipopolysaccharide. Overall, there was extreme variation in responses among patients to the various antigen preparations, with no single pattern dominating. Lipopolysaccharide and its components appear to be the immunodominant epitopes, since most rapidly progressive periodontitis patients are seropositive for lipopolysaccharide and/or its components and they have titers relative to those for proteins.

Adult↗
PubMed1997

Absence of adult dental anomalies in familial hypophosphatasia.

This paper is a supplemental report on 3 previous publications about a family in which 3 male children manifested gingival recession, alveolar bone resorption and premature exfoliation of their deciduous teeth without apical root resorption and without clinical signs of inflammation. Laboratory blood and urine studies in conjunction with an analysis of periodontal microflora and family pedigrees established a diagnosis of hypophosphatasia in these 3 children, as well as their father, the paternal grandmother and paternal great-uncle. Clinical data also revealed that a son of the paternal great-uncle and his daughter were similarly affected. The family pedigree is consistent with an autosomal dominant mode of transmission. The 3 brothers are now between the ages of 18 and 22 yr and all have complete permanent dentitions. Aside from some periodontal manifestations of prior dentoalveolar trauma, most of the findings of the periodontal assessment are within normal limits. All 3 exhibit moderate to severe caries and some degree of gingival inflammation, but minimal periodontal pathosis.

Adolescent↗
PubMed1997

Risk assessment for periodontal diseases.

Assessment of risk for periodontitis is still in its infancy. Nevertheless, a sufficient amount of dependable information exists to begin using risk assessment in the day to day practice of dentistry. The purpose of this paper is to summarise existing information about risks for periodontitis in a manner that is useful to practitioners. Risks for moderate to severe periodontitis that have been identified include cigarette smoking, advancing age, diabetes mellitus and certain other systemic conditions. These include, osteoporosis and HIV infection and conditions such as irradiation and immunosuppressive drugs that interfere with normal host defences, specific pathogenic bacteria in the subgingival flora, microbial deposits and poor oral hygiene status, bleeding on probing, previous disease experience and severity, and inheritance. Some risks such as pathogenic bacteria in the subgingival flora are strongly linked to causation of the disease while others such as bleeding on probing may indicate enhanced risk for future disease but are not known to be involved in causation and still others such as advancing age may be background factors that enhance susceptibility. While some risks such as cigarette smoking can be modified to lower the level of risk, others such as ageing are immutable and cannot be modified but need to be considered in overall risk assessment. A goal of periodontal diagnosis, treatment planning and therapy is to lower risk for future periodontal deterioration to the maximal extent. One approach to achieving this goal is described.

Aging↗
PubMed1997

Serum antibodies to Porphyromonas gingivalis block the prostaglandin E2 response to lipopolysaccharide by mononuclear cells.

The ability of rabbit and monkey immune sera to neutralize prostaglandin E2 (PGE2) production by human monocytes stimulated with lipopolysaccharide (LPS) was examined. CD14-dependent LPS activation of PGE2 was examined under assay conditions which allowed the comparison of preimmune and immune sera. Serum obtained from rabbits immunized with formalin-fixed Porphyromonas gingivalis cells dramatically reduced the amount of PGE2 produced in response to LPS obtained from three different strains of P. gingivalis but not that from Escherichia coli or Bacteroides fragilis. In addition, a significant reduction in the mean PGE2 level was observed in the presence of sera from immunized but not control monkeys employed in a vaccine trial. Immune serum samples from five of nine immunized monkeys were able to reduce LPS-induced production of PGE2 by greater than 50% compared to that in the corresponding preimmune sera. Immune monkey serum, similar to immune rabbit serum, blocked PGE2 production in response to P. gingivalis LPS but not E. coli LPS. These data demonstrate that immunization with P. gingivalis whole cells can elicit an antibody response that is able to block the PGE2 response to LPS. Neutralization of LPS-mediated inflammatory mediator production may account in part for the observed suppression of alveolar bone loss in immunized monkeys.

Animals↗
PubMed1996

Is macrosomia associated with poor glycaemic control in diabetic pregnancy?

The study aimed to determine the influence of glucose control during pregnancy on the incidence of macrosomia in the infants of mothers with insulin-dependent diabetes. The prevalence of macrosomia was determined in pregnancies of all such women attending the City Hospital Nottingham, between July 1987 and July 1993, where it is policy for diabetic patients to aim during pregnancy for preprandial capillary glucose levels of less than 6.0 mmol I-1, and postprandial glucose levels of less than 8.0 mmol I-1. Macrosomia was defined as a birthweight greater than 90th centile using a computer model which takes into account all the major determinants of birthweight. Twelve of 29 infants were macrosomic, which is greater than expected (p < 0.01). During pregnancy there was no difference in mean seven point glucose profiles between those mothers with normal weight babies and those with macrosomia, but fructosamine levels at booking were significantly higher in the latter 2.5 (1.9-2.9) vs 2.2 (1.2-3.0); p < 0.05. These data confirm other studies and suggest that the incidence of macrosomia may be reduced by tighter control of diabetes at conception and in the first trimester, but to a lesser extent during later pregnancy.

Blood Glucose↗