Short communication: catechol-O-methyltransferase allelic variation in relation to psychological and hormonal indices of stress in children and adolescents with chromosome 22q11.2 deletion syndrome (22q11.2DS).

Chromosome 22q11.2 deletion syndrome (22q11.2DS) is a developmental disorder with high rates of anxiety and psychosis. Catechol-O-methyltransferase (COMT) regulates epinephrine (E), norepinephrine (NE), and dopamine (DA) and is implicated in both anxiety and psychotic disorders. The aim of this study was to determine how COMT variation relates to psychological anxiety and associated stress physiology responsiveness to better understand symptom heterogeneity in people with 22q11.2DS. We examined COMT allelic variation in relation to anxiety and hypothalamic-pituitary-adrenocortical (HPA) and sympathetic-adrenomedullary (SAM) hormonal stress indicators in 30 children and adolescents with 22q11.2DS. Contrary to expectation, individuals with the higher activity COMTval allele had higher anxiety levels versus those with the low activity (COMTmet) allele (p = 0.021; Glass' Δ = 0.69). Anxiety was not correlated with salivary cortisol (CORT) or alpha-amylase (sAA) in either group. Groups did not differ in CORT levels (p = 0.58), but the COMTmet group had higher sAA (p = 0.026; Glass' Δ = 0.67, uncorrected) suggesting greater SAM reactivity but not HPA activity. This suggests that COMT allelic variation may contribute to differences in acute SAM but not slower HPA stress reactivity in those with 22q11.2DS.

Prenatal exposure to maternal disadvantage-related inflammatory biomarkers: associations with neonatal white matter microstructure.

Prenatal exposure to heightened maternal inflammation has been associated with adverse neurodevelopmental outcomes, including atypical brain maturation and psychiatric illness. In mothers experiencing socioeconomic disadvantage, immune activation can be a product of the chronic stress inherent to such environmental hardship. While growing preclinical and clinical evidence has shown links between altered neonatal brain development and increased inflammatory states in utero, the potential mechanism by which socioeconomic disadvantage differentially impacts neural-immune crosstalk remains unclear. In the current study, we investigated associations between socioeconomic disadvantage, gestational inflammation, and neonatal white matter microstructure in 320 mother-infant dyads over-sampled for poverty. We analyzed maternal serum levels of four cytokines (IL-6, IL-8, IL-10, TNF-α) over the course of pregnancy in relation to offspring white matter microstructure and socioeconomic disadvantage. Higher average maternal IL-6 was associated with very low socioeconomic status (SES; INR < 200% poverty line) and lower neonatal corticospinal fractional anisotropy (FA) and lower uncinate axial diffusivity (AD). No other cytokine was associated with SES. Higher average maternal IL-10 was associated with lower FA and higher radial diffusivity (RD) in corpus callosum and corticospinal tracts, higher optic radiation RD, lower uncinate AD, and lower FA in inferior fronto-occipital fasciculus and anterior limb of internal capsule tracts. SES moderated the relationship between average maternal TNF-α levels during gestation and neonatal white matter diffusivity. When these interactions were decomposed, the patterns indicated that this association was significant and positive among very low SES neonates, whereby TNF-α was inversely and significantly associated with inferior cingulum AD. By contrast, among the more advantaged neonates (lower-to-higher SES [INR ≥ 200% poverty line]), TNF-α was positively and significantly associated with superior cingulum AD. Taken together, these findings suggest that the relationship between prenatal cytokine exposure and white matter microstructure differs as a function of SES. These patterns are consistent with a scenario where gestational inflammation's effects on white matter development diverge depending on the availability of foundational resources in utero.

Age-related differences in resting-state functional connectivity from childhood to adolescence.

The human brain is active at rest, and spontaneous fluctuations in functional MRI BOLD signals reveal an intrinsic functional architecture. During childhood and adolescence, functional networks undergo varying patterns of maturation, and measures of functional connectivity within and between networks differ as a function of age. However, many aspects of these developmental patterns (e.g. trajectory shape and directionality) remain unresolved. In the present study, we characterised age-related differences in within- and between-network resting-state functional connectivity (rsFC) and integration (i.e. participation coefficient, PC) in a large cross-sectional sample of children and adolescents (n = 628) aged 8-21 years from the Lifespan Human Connectome Project in Development. We found evidence for both linear and non-linear differences in cortical, subcortical, and cerebellar rsFC, as well as integration, that varied by age. Additionally, we found that sex moderated the relationship between age and putamen integration where males displayed significant age-related increases in putamen PC compared with females. Taken together, these results provide evidence for complex, non-linear differences in some brain systems during development.

Family income buffers the relationship between childhood adverse experiences and putamen volume.

Adverse experiences and family income in childhood have been associated with altered brain development. While there is a large body of research examining these associations, it has primarily used cross-sectional data sources and studied adverse experiences and family income in isolation. However, it is possible that low family income and adverse experiences represent dissociable and potentially interacting profiles of risk. To address this gap in the literature, we examined brain structure as a function of adverse experiences in childhood and family income in 158 youths with up to five waves of MRI data. Specifically, we assessed the interactive effect of these two risk factors on six regions of interest: hippocampus, putamen, amygdala, nucleus accumbens, caudate, and thalamus. Adverse experiences and family income interacted to predict putamen volume (B = 0.086, p = 0.011) but only in participants with family income one standard deviation below the mean (slope estimate = -0.11, p = 0.03). These results suggest that adverse experiences in childhood result in distinct patterns of brain development across the socioeconomic gradient. Given previous findings implicating the role of the putamen in psychopathology-related behaviors, these results emphasize the importance of considering life events and socioeconomic context when evaluating markers of risk. Future research should include interactive effects of environmental exposures and family income to better characterize risk for psychopathology in diverse samples.

Structural Connectivity and Emotion Recognition Impairment in Children and Adolescents with Chromosome 22q11.2 Deletion Syndrome.

Children with chromosome 22q11.2 deletion syndrome (22q11.2DS) exhibit impaired ability to process and understand emotions in others. We measured structural connectivity in children and adolescents with 22q11.2DS (n = 28) and healthy controls (n = 29). Compared to controls, those with 22q11.2DS had poorer social skills and more difficulty recognizing facial emotions. Children with 22q11.2DS also had higher fractional anisotropic diffusion in right amygdala to fusiform gyrus white matter pathways. Right amygdala to fusiform gyrus fractional anisotropy values partially mediated the relationship between 22q11.2DS and social skills, as well as the relationship between 22q11.2DS and emotion recognition accuracy. These findings provide insight into the neural origins of social skills deficits seen in 22q11.2DS and may serve as a biomarker for risk of future psychiatric problems.

Developmental trajectories of cortical thickness by functional brain network: The roles of pubertal timing and socioeconomic status.

The human cerebral cortex undergoes considerable changes during development, with cortical maturation patterns reflecting regional heterogeneity that generally progresses in a posterior-to-anterior fashion. However, the organizing principles that govern cortical development remain unclear. In the current study, we characterized age-related differences in cortical thickness (CT) as a function of sex, pubertal timing, and two dissociable indices of socioeconomic status (i.e., income-to-needs and maternal education) in the context of functional brain network organization, using a cross-sectional sample (n = 789) diverse in race, ethnicity, and socioeconomic status from the Lifespan Human Connectome Project in Development (HCP-D). We found that CT generally followed a linear decline from 5 to 21 years of age, except for three functional networks that displayed nonlinear trajectories. We found no main effect of sex or age by sex interaction for any network. Earlier pubertal timing was associated with reduced mean CT and CT in seven networks. We also found a significant age by maternal education interaction for mean CT across cortex and CT in the dorsal attention network, where higher levels of maternal education were associated with steeper age-related decreases in CT. Taken together, our results suggest that these biological and environmental variations may impact the emerging functional connectome.

Graded Variation in T1w/T2w Ratio during Adolescence: Measurement, Caveats, and Implications for Development of Cortical Myelin.

Adolescence is characterized by the maturation of cortical microstructure and connectivity supporting complex cognition and behavior. Axonal myelination influences brain connectivity during development by enhancing neural signaling speed and inhibiting plasticity. However, the maturational timing of cortical myelination during human adolescence remains poorly understood. Here, we take advantage of recent advances in high-resolution cortical T1w/T2w mapping methods, including principled correction of B1+ transmit field effects, using data from the Human Connectome Project in Development (HCP-D; N = 628, ages 8-21). We characterize microstructural changes relevant to myelination by estimating age-related differences in T1w/T2w throughout the cerebral neocortex from childhood to early adulthood. We apply Bayesian spline models and clustering analysis to demonstrate graded variation in age-dependent cortical T1w/T2w differences that are correlated with the sensorimotor-association (S-A) axis of cortical organization reported by others. In sensorimotor areas, T1w/T2w ratio measures start at high levels at early ages, increase at a fast pace, and decelerate at later ages (18-21). In intermediate multimodal areas along the S-A axis, T1w/T2w starts at intermediate levels and increases linearly at an intermediate pace. In transmodal/paralimbic association areas, T1w/T2w starts at low levels and increases linearly at the slowest pace. These data provide evidence for graded variation of the T1w/T2w ratio along the S-A axis that may reflect cortical myelination changes during adolescence underlying the development of complex information processing and psychological functioning. We discuss the implications of these results as well as caveats in interpreting magnetic resonance imaging (MRI)-based estimates of myelination.SIGNIFICANCE STATEMENT Myelin is a lipid membrane that is essential to healthy brain function. Myelin wraps axons to increase neural signaling speed, enabling complex neuronal functioning underlying learning and cognition. Here, we characterize the developmental timing of myelination across the cerebral cortex during adolescence using a noninvasive proxy measure, T1w/T2w mapping. Our results provide new evidence demonstrating graded variation across the cortex in the timing of T1w/T2w changes during adolescence, with rapid T1w/T2w increases in lower-order sensory areas and gradual T1w/T2w increases in higher-order association areas. This spatial pattern of microstructural brain development closely parallels the sensorimotor-to-association axis of cortical organization and plasticity during ontogeny.

Working Memory Impairments in Chromosome 22q11.2 Deletion Syndrome: The Roles of Anxiety and Stress Physiology.

Stress and anxiety have a negative impact on working memory systems by competing for executive resources and attention. Broad memory deficits, anxiety, and elevated stress have been reported in individuals with chromosome 22q11.2 deletion syndrome (22q11.2DS). We investigated anxiety and physiological stress reactivity in relation to visuospatial working memory impairments in 20 children with 22q11.2DS and 32 typically developing (TD) children ages 7 to 16. Children with 22q11.2DS demonstrated poorer working memory, reduced post-stress respiratory sinus arrhythmia recovery, and overall increased levels of cortisol in comparison to TD children. Anxiety, but not physiological stress responsivity, mediated the relationship between 22q11.2DS diagnosis and visuospatial working memory impairment. Findings indicate that anxiety exacerbates impaired working memory in children with 22q11.2DS.

Identity Distress among Youth Exposed to Natural Disasters: Associations with Level of Exposure, Posttraumatic Stress, and Internalizing Problems.

Identity distress involves intense or prolonged upset or worry about personal identity issues including long-term goals, career choice, friendships, sexual orientation and behavior, religion, values and beliefs, and group loyalties. Research suggests that trauma exposure and subsequent PTSD symptoms may negatively impact identity development and psychological adjustment. However, little is known about their specific associations with identity distress and internalizing problems among disaster-exposed adolescents. The purpose of this study was to examine these relationships in a sample of 325 adolescents (60% female; 89% African American) who experienced a major natural disaster and its aftermath. The results indicated that identity distress was positively associated with age, hurricane exposure, PTSD symptoms, and internalizing problems. Linear regression analyses also showed that identity distress was uniquely associated with internalizing symptoms and that there was an indirect effect of hurricane exposure on identity distress via PTSD symptoms. Finally, PTSD symptoms moderated the link between identity distress and internalizing symptoms, with a significant positive slope found for youth with more PTSD symptoms. Findings were generally consistent with previous work and predictions, and add to the extant knowledge about identity distress by providing data on the linkages between disaster exposure, posttraumatic stress and internalizing problems in adolescents.

Novel subgingival bacterial phylotypes detected using multiple universal polymerase chain reaction primer sets.

INTRODUCTION: Molecular ecological analysis based on 16S rRNA gene sequence analysis is well established for the characterisation of complex bacterial communities. However, 'universal' PCR primers can introduce biases into the analysis of the species composition of clone libraries because of mismatches between the primer and target organism sequences. In this study, three universal primer sets were compared for the analysis of the microflora in subgingival plaque. METHODS: Three subgingival plaque samples were collected from two subjects with localised severe chronic periodontitis. Half of each sample was cultured while DNA was extracted from the remaining half and 16S rDNA amplified with universal primer pairs 27F, 1525R (A); 27F, 1492R (B) and 530F, 1525R (C). Amplified genes were cloned, sequenced and identified by comparison with 16S rRNA databases. RESULTS: 137 taxa were identified among 177 isolates and 417 clones sequenced. Of these, 86 were detected only by the molecular technique whereas 26 were found only by culture. Sequences from 81 taxa did not correspond to those of named species and of these, 38 were not represented in the nucleotide databases. 16S RNA genes for these 38 taxa were sequenced and deposited with GenBank. CONCLUSION: The use of three sets of universal primers allowed the identification of 38 novel bacterial phylotypes. There were marked differences in the composition of the libraries generated by the different primer sets. A combination of molecular and cultural techniques is recommended to maximise the coverage of detection of bacterial taxa in oral samples.

The reproducibility of methods of assessment for cervical dentine hypersensitivity.

BACKGROUND: Many agents and toothpaste formulations have been proposed for treatment of dentine hypersensitivity. However, studies have reported equivocal or contradictory results, potentially related to a lack of clinical efficacy for agents being tested, poor study design or the use of assessment techniques which are unable to distinguish longitudinal changes in dentine hypersensitivity. AIM: To investigate the reproducibility of commonly used measurement protocols for dentine hypersensitivity on single or multiple teeth. In addition, newly-developed controlled air and cold fluid stimuli were investigated. METHODS AND MATERIALS: Standardised pain stimulation techniques were used in 2 investigations with 63 and 42 subjects, respectively. The reproducibility of perceived hypersensitivity before and following stimulation was recorded over time periods of 14 and 2 days, respectively, using visual analogue scales and threshold techniques. RESULTS: Subject demographics resembled those reported in other hypersensitivity investigations. Analysis using several measures of reproducibility indicated that subject-based reproducibility was limited, even when the stimuli were standardised. However, the data are consistent with the findings of investigations on pain assessment in other fields. CONCLUSIONS: The reproducibility of subjects in clinical trials of dentine hypersensitivity may therefore contribute to difficulties in establishing treatment efficacy of agents in clinical trials.

Periodontal health of London women during early pregnancy.

OBJECTIVES: A descriptive cross-sectional study to determine the severity of periodontal disease in early pregnancy and its relation to demographic variables in a South East London population. METHODS: 2,027 pregnant women attending Guy's Hospital for an ultrasound scan at 10 to 14 weeks gestation were assessed. Data were collected via questionnaire and periodontal examination, including plaque and bleeding scores, pocket probing depth and loss of attachment. RESULTS: Mean age was 29.8 years (sd 5.5). Of these, 61.8% were white, 28.5% black, and 9.7% of other ethnic group. A total of 15% reported smoking during pregnancy. The mean number of teeth present was 28 (sd 2) per subject, mean percentage of sites with plaque present was 60.5% (sd 22.6), mean pocket depth was 2.0 mm (sd 0.4), mean loss of attachment was 0.4 mm (sd 0.3), and the mean percentage of sites bleeding on probing was 20.2% (sd 16.3). Linear regression demonstrated that probing depth was related to age, ethnicity, socioeconomic status and plaque score but not to smoking whereas loss of attachment demonstrated relationships with age, smoking status and plaque score but not ethnicity or socioeconomic status. CONCLUSION: There was a relatively high proportion of subjects with deep periodontal pockets in this pregnant population compared to the Adult Dental Health Survey 1998 but with similar levels of loss of attachment and percentage of sites with plaque present. Several demographic factors were associated with the level of periodontal disease in this population.

Contribution of individual drugs to gingival overgrowth in adult and juvenile renal transplant patients treated with multiple therapy.

Drug regimens for transplantation often consist of multiple therapeutic agents and may result in drug-induced gingival overgrowth (DIGO). The aim of this study was to investigate the contribution of individual drugs in renal transplant patients. 147 adults (19-84 years) and 60 juveniles (3-18 years) were scored for DIGO and other clinical variables. Duration of treatment, dosage of drugs per kg body weight and serum cyclosporin levels were recorded. 44% of adults and 27% of children had DIGO. All patients were receiving prednisolone. More adults than children were administered cyclosporin, the reverse was true of azathioprine (p<0.01). Explanatory models were evaluated by stepwise ordinal polynomial logistic regression. Statistically significant explanation (p<0.05) of DIGO was afforded by prednisolone, nifedipine and azathioprine concentrations in adults and by cyclosporin, nifedipine and azathioprine concentrations in juveniles. Prednisolone and azathioprine were inversely related to the degree of DIGO. Plaque and irregularity scores, lip coverage and mouthbreathing status showed significant additional explanation in adults, replacing nifedipine and azathioprine in the final model. Irregularity was additionally explanatory in children, but no other clinical variables. A larger proportion of the variance of DIGO was explained by the available variables in children than in adults (pseudo r2=0.50 versus 0.25). The degree of DIGO in renal transplant patients is influenced by the dosage of a number of individual components of multiple drug therapy independently of the presence of local clinical factors.

The relationship between socio-dental indices of handicap, felt need for dental treatment and dental state in a group of frail and functionally dependent older adults.

The present study was designed to investigate the relationship between self-reported oral handicap as measured by socio-dental indicators and both dental state and felt need for dental treatment in a group of frail and functionally dependent older adults. A total of 263 housebound adults over the age of 60 years were investigated with regard to their self-reported dental handicap using the socio-dental indices derived by Locker (Community Dent Health 1992;9:109-24). Of these, 117 were in long-stay residential facilities, 67 in sheltered housing and 79 in private housing. The majority were female (76%) and the largest age group comprised 81-90-year-olds (44%), while only 8% were in the youngest group of 60-70-year-olds. A high level of handicap was recorded. In the previous 4 weeks, 74% of the group experienced difficulty in chewing, 54% some other functional handicap, 22% oral pain, 72% some incident of discomfort and 30% some social problem related to their oral condition. The socio-dental indices related more to the number of teeth than to age or gender. Ability to chew five index foods was related directly to the number of teeth present (P<0.001) but unless there were more than 20 teeth present, subjects with natural teeth were more dissatisfied with their appearance than those with complete dentures (P=0.002). The 57 subjects (29%) who expressed a desire for treatment had significantly higher handicap scores (P<0.001). Thus the results indicate that there are high levels of oral handicap in frail and functionally dependent older adults that are related to both the number of natural teeth retained and desire for treatment.

Reported dental attendance and perceived barriers to care in frail and functionally dependent older adults.

OBJECTIVES: This study was designed to investigate the reported dental attendance and the perceived barriers to dental care for frail and functionally dependent older adults. DESIGN: A single centre study of a housebound group of more than 60 years of age and their personal carers. SETTING: The study was carried out from a general dental practice in Ware, Hertfordshire, a market town 20 miles north of London. SUBJECTS AND METHODS: A group of 263 housebound adults more than 60 years old were identified. The subjects were living in 5 residential homes, 3 sheltered housing complexes and in private accommodation. The subjects and 115 of their personal carers were interviewed. RESULTS: 93% only attended a dentist when they had problems. The presence of natural teeth, residential status and age were all statistically significant independent explanatory variables for the time since the previous reported dental visit. Lack of perceived need was found to be a barrier to care for 86% of subjects. Cost and lack of suitable transport were also commonly identified. However, the true cost implication to a patient was poorly appreciated especially by those 34% of subjects who cited cost as a barrier. 52% of the whole group, rising with age to 75% of those more than 90 years old, expressed a preference for treatment to be carried out in their own homes. 93% of carers had found difficulty in arranging dental care for their clients but the difficulties were not always the same as the subjects' perceived barriers. Among the carers, younger, regular dental attendees who were paid to care were more likely to see benefit in obtaining dental care for their clients. CONCLUSION: The mechanisms by which these barriers to care may be lowered should be investigated in order to meet the unmet need identified by this study.

Can a workplace preventive programme affect periodontal health?

AIM: To evaluate an oral health awareness campaign in an adult population. DESIGN/SETTING: Four workplaces in north-east London were selected, matched in two pairs and randomly allocated to test and control groups. Completion occurred in 1995. SUBJECTS: 98 volunteer employees in good general health. INTERVENTIONS: Two oral examinations were carried out, six weeks apart. The test group received the programme immediately after baseline examination and the controls after the second visit. MAIN OUTCOME MEASURES: Gingival bleeding on probing (BOP) and probing depths (PD) were measured on each occasion using a controlled pressure probe. RESULTS: The mean percentage of sites with BOP per subject reduced from 56% to 25% in the test group, while remaining static in the control group at 46% to 48%. The mean percentage of sites probing 4 mm and above per subject reduced from 38% to 25% in the test group and from 28% to 25% in the control group. These differences between groups were statistically significant when submitted to analysis of covariance (P < 0.001). CONCLUSIONS: The study showed the clinical effectiveness of a workplace-based oral health awareness campaign, which is ideally suited to the skills and resources of the primary care dental team.

The rôle of a dentine-bonding agent in reducing cervical dentine sensitivity.

This double-blind split-mouth trial with 16 adult patients investigated the ability of a dentine bonding agent (DBA) to reduce cervical dentine sensitivity. Following stimulation of pairs of teeth by conventional tactile and air blast stimuli, together with controlled evaporative and cold fluid stimuli, sensitivity was recorded using tactile threshold, visual-analogue scale (VAS) and short-form McGill pain questionnaire (SFMPQ), prior to and 1 week following treatment with DBA. Prior to assessment, subjects recorded their perceived overall sensitivity using VAS and SFMPQ. Application of each stimulus was separated by 10 min. Sensitivity was recorded by a clinician blinded to the treatment status of each tooth. The control tooth was treated by applying DBA to coronal enamel. Dietary information was collected after the post-treatment assessment. There was a significant (p<0.05) improvement in tactile threshold and air flow and air blast VAS scores, together with reductions in sensitivity to evaporative stimuli when assessed by SFMPQ. Treatment response was not influenced by the subjects' age, gender, diet, use of fluoride-containing or silica-based toothpastes or fluoride mouthwashes, or a history of previous sensitivity treatment. It is concluded that topical application of DBA is an effective way to reduce cervical dentine sensitivity.

The relationship between irregularity of the incisor teeth, plaque, and gingivitis: a study in a group of schoolchildren aged 11-14 years.

The relationship between irregularity of teeth and periodontal disease was investigated in 201 children aged 11-14 years. The upper and lower incisor teeth were assessed for spacing, labio-lingual displacement, and mesiodistal overlap at each of the six contact areas. Plaque and gingivitis were assessed at six sites on each of the four upper and four lower incisor teeth. There was evidence for a direct relationship between the number of contact areas with tooth displacement combined with overlap and the number of sites with gingival redness (R = 0.25, P < 0.001), bleeding (R = 0.18, P < 0.01), and profuse bleeding (R = 0.25, P < 0.001). There was no evidence for a relationship between labio-lingual displacement alone and gingivitis. One-hundred-and-twenty-eight subjects without tooth displacement combined with incisor overlap had, respectively, 34, 15, and 35 per cent fewer sites with redness (P < 0.01), bleeding (P < 0.05), or profuse bleeding (P < 0.01) than the 73 subjects with overlap. The statistical significance of these differences was unaffected by covariate adjustment to take account of the effect on gingivitis of variation in the number of sites with plaque. There was no evidence of a relationship between incisor overlap and amount of plaque in these subjects. The results indicate that overlapping of incisor teeth is directly related to gingivitis and this relationship cannot be explained simply by an effect on oral hygiene.

Clinical assessment of periodontitis in young adults--evaluation of probing depth and partial recording methods.

The present study was carried out to compare the ability of different methods of periodontal assessment to identify those subjects in a population who had suffered the worst periodontal breakdown. Comparisons were made between full mouth approximal attachment loss (CAL) assessment and methods relying on pocket probing depth (PPD) evaluation or on partial recording of CAL or PPD. Both of the latter types of assessment are commonly used in epidemiological surveys. 202 workers at an electronics factory aged between 20 and 40 yr were examined for approximal PPD and CAL, excluding third molars. The data were used to determine which individuals had the worst periodontitis based on CAL at several thresholds. Further analysis was carried out to determine which of these subjects would have been identified on the basis of the presence of deep (> or = 6 mm) pocketing, or by using one of a battery of partial recording subsets. CAL was frequently present in the absence of deep pocketing. A subset made up of four approximal sites around each of the 10 index teeth recommended by the WHO for partial recording (two molars in each quadrant and maxillary right and mandibular left central incisors) and a subset comprising maxillary buccal and mandibular lingual sites ("Pritchard" sites) performed best of the subsets considered in identifying the subjects who had been found by full mouth assessment to have at least one or at least two approximal sites with CAL at thresholds of 2, 3 or 4 mm. It was concluded that measurements of CAL using either of these subsets should reduce problems of under-recording of the prevalence of periodontitis associated with the use of PPDs alone or on CAL assessment at other partial recording subsets.

Passive immunization with monoclonal antibodies against Porphyromonas gingivalis in patients with periodontitis.

Selective inhibition of recolonization of Porphyromonas gingivalis was investigated by topical application of monoclonal antibody (MAb). To select a MAb to P. gingivalis with the potential for recognizing most strains of P. gingivalis, we examined seven MAbs, one of which (MAb 61BG 1.3) recognized all 22 laboratory strains and serotypes of P. gingivalis tested as well as 105 human clinical isolates. A comparative study of the number of P. gingivalis bacteria identified by conventional culture and immunofluorescence with MAb 61BG 1.3 showed a very significant correlation between the two methods (Spearman r = 0.85, P < 0.001). Fourteen patients with periodontitis, who harbored P. gingivalis in their subgingival plaque, were treated by root planing and with metronidazole to suppress any detectable P. gingivalis. In this double-blind study, the patients were then divided randomly into two groups; one was treated with MAb to P. gingivalis, and the other was treated with saline. Each patient had four subgingival applications of 3 micrograms of MAb (or saline) per tooth at 1, 3, 7, and 10 days after P. gingivalis was suppressed. The number of P. gingivalis bacteria was then monitored, and significantly less recolonization of the sites with the most severe periodontitis was found in the MAb-treated patients than in the control patients (P < 0.01). This was evident at 6 and 9 months after the application of MAb, but by 12 months, P. gingivalis, was also found to recolonize these sites in two of the MAb-treated patients. The effect of MAb was specific to P. gingivalis, since the numbers of spirochetes were not significantly different between the two groups. However, no significant difference in any clinical periodontal indices between the immunized and control patients at 6 and 12 months was observed. This is the first demonstration that a putative periodontal pathogen can be selectively prevented from recolonization for up to 9 months in sites with the most severe periodontitis. This strategy could be used to establish directly in humans whether a microorganism is involved in the pathogenesis of periodontitis, by repeated application of the corresponding MAb at about 6-month intervals and by comparing the clinical indices between the MAb-treated and control patients.