Catherine A. Demko

Gender differences in cystic fibrosis: Pseudomonas aeruginosa infection.

The median survival age for females with cystic fibrosis (CF) is approximately 3 years younger than for males. We tested whether earlier acquisition of Pseudomonas aeruginosa (PA) by female CF patients or the greater impact of this organism on their lung disease, or both, contribute to their poorer survival. PA infection status, survival, pulmonary function tests, and chest X-ray scores from patients who were followed at our center for at least 2 years with a minimum of three respiratory cultures per year were analyzed (n = 848). The median age of chronic infection with mucoid PA was 1.7 years earlier in females than in males. Patients infected with mucoid PA had poorer survival, chest X-ray scores, and pulmonary function tests than patients who had either no Pseudomonas species or only the nonmucoid phenotype. Acquisition of mucoid PA was associated with an accelerated rate of decline in pulmonary function. However, the rate of change of pulmonary function after mucoid PA infection was similar for males and females. Moreover, even among patients who had only the mucoid form or only the nonmucoid form, males had better percent predicted forced expiratory volume in 1 sec and better survival. Therefore, factors in addition to earlier acquisition of mucoid PA may contribute to the poorer survival of female CF patients.

Stenotrophomonas maltophilia in cystic fibrosis: Incidence and prevalence

Stenotrophomonas maltophilia (SM) was recovered from 211 of 773 cystic fibrosis (CF) patients followed for at least one year, and seen between 1982 and 1994. Yearly prevalence (5.6% to 8.7%) and incidence rates (1.6% to 5.7%) showed no trends. SM persistence varied greatly and was unlike that of Pseudomonas aeruginosa. Fifty percent of SM‐positive patients had only one positive culture and only 24 (11%) remained chronically infected. Although SM‐positive patients were more likely to be hospitalized than SM‐negative patients, for 55% of SM‐positive patients, acquisition did not appear to follow hospitalization. Of 40 SM‐positive patients who had a CF sibling, only 10 siblings were ever culture positive. When stratified by FEV1, the two‐year survival for SM‐positive with mild/moderate disease (98%) and severe disease (78%) was similar to that of our SM‐negative patients. Five‐year survival was only 40% for SM‐positive patients with initially severe pulmonary status, compared with 72% for the SM‐negative patients. Seventy percent of the original SM isolates were panresistant (susceptible to no more than one antimicrobial agent). Ten years later, panresistance was 84%. Despite our reassuring experience with SM, including lack of sibling concordance, the fact that the majority of our patients had no hospital exposure prior to acquisition, the high incidence of transient infection, and the seemingly unaffected two‐year survival, there are insufficient data to definitively conclude that segregation of these patients would be beneficial. The increasing prevalence of multiply resistant gram‐negative pathogens in CF patients suggests the need for continued caution with any panresistant pathogen. Pediatr Pulmonol. 1998;25:304–308.

Inhibitory effect of cystic fibrosis serum on pseudomonas phagocytosis by rabbit and human alveolar macrophages.

Summary: This report presents experimental observations indicating the presence of an inhibitory activity in cystic fibrosis (CF) serum which impairs phagocytosis of Pseudomonas aeruginosa by rabbit as well as human alveolar macrophages. Of the 49 patient serum samples studied, 40 consistently showed ≥ 60% inhibition, 3 showed no inhibition and 6 were in the range of 20–60% inhibition of Pseudomonas phagocytosis. In parallel studies, the phagocytosis of S. aureus and S. marcescens was found not to be inhibited by CF serum. Mixing of CF serum with normal serum could not overcome the inhibitory effect, indicating the presence of an inhibitory factor rather than the lack of a necessary component. The inhibitory activity is not lost upon exposure of serum to glass, upon freezing the serum once, or upon heating at 56 C for 30 minutes.Speculation: The serum of cystic fibrosis patients selectively inhibits alveolar macrophage function in vitro; the expression of this inhibitory activity in vivo may compromise effective host control of infection. Investigation of the origin, nature and pathophysiologic role of the activity may suggest new approaches to the control of Pseudomonas pulmonary infection.Pultionary infection is a major factor in the morbidity and mortality associated with cystic fibrosis (CF) (6). Pseudomonas, a uhrquitous organism in the environment, is cystic fibrosis (CF) (6). Pseudomonas, a uhrquitous organism in the environment, is usually not pathogenic for healthy individuals. However, individuals with the chronic lung disease of CF are particularly susceptible to opportunistic Pseudomonas aeruginosa infections. The frequency of this organism in CF pulmonary infections is inadequately explained. It is well known that most CF patients have elevated levels of Pseudomonas antibodies in their sera and pulmonary secretions (l2,14). While recently there has been an indication that a lymphocyte unresponsiveness to Pseudomonas may be acquired as the infection progresses (18,19), no other immunologic abnormality has been consistendy observed (5.10). Extrapulmonary infection is extremely rare and sepsis is almost never, seen after the first months of life (22). This unusual susceptibility to Pseudomonas despite apparently normal systemic humoral and cellular immunity. suggests that local pulmonary host defense mechanisms are defective in CF. Several recent studies have indicated that lung defenses can, to a certain extent, function independently of systemic humoral and cell mediated immune systems (9,15,20,21).Lung defenses include mucociliary transport as well as phagocytic cells, lymphocytes, and immunoglobulin secretion. Since mucociliary transport in some CF patients is compromised (5). clearing of the bacteria becomes more dependent on the efficient action of the phagocytic cells. Previous studies in our laboratory (2) and by Biggar, et al. (I) have shown that CF serum impairs phagocytosis of Pseudomonas by rabbit alveolar macrophages. This report presents experimental observations indicating the presence of an inhibitory activity in CF serum which impairs phagocytosis of Pseudomonas by human as well as rabbit alveolar macrophages.

Ultrastructure and function of alveolar macrophages from cystic fibrosis patients

Summary: Alveolar macrophages were isolated from three cystic fibrosis patients, and the structure and function of these cells were compared to that of normal alveolar macrophages. The cystic fibrosis (CF) and normal alveolar macrophages were able to phagocytize Pseudomonas in the presence of normal serum, but cells from both sources had decreased phagocytosis of Pseudomonas in the presence of CF seram. Phagocytosis of Staphylococcus was not inhibited. Ultrastructural studies showed CF macrophages to be morphologically normal, however, in contrast to CF polymorphonuclear cells, they had not been heavily engaged in phagocytosis. The similarities between CF and normal macrophages suggest that the chronic pulmonary infection of CF may be due to an extrinsic factor in an altered lung environment rather than to any intrinsic cellular defect of the alveolar macrophage.Speculation: Functional and morphologic observations indicate that cystic fibrosis alveolar macrophages are not providing an adequate phagocytic defense against Pseudomonas. This defective phagocytosis does not appear to arise from an intrinsic problem with the macrophages, but rather appears to be due to extrinsic factors, i.e.. an altered lung environment together with a substance(s) present in cystic fibrosis serum which selectively inhibit Pseudomonas phagocytosis.

Use of Cone Beam Computed Tomography to Volumetrically Assess Alveolar Cleft Defects—Preliminary Results

PURPOSE The purpose of this study was to determine the utility of cone beam computed tomographic (CBCT) imaging in assessing the volume of alveolar cleft defects in patients undergoing secondary cleft repair. MATERIALS AND METHODS Fourteen patients with unilateral clefts were analyzed in a retrospective study. Preoperative CBCT imaging of patients preparing to undergo secondary repair of alveolar clefts was reviewed. Using anatomic landmarks, 3 measurements were collected from CBCT images for each patient: facial width (FW), facial height (FH), and facial-palatal length (FL). These values were used to calculate the estimated volume (EV) of the cleft and thus the amount of bone graft material that would be needed to fill the defect. RESULTS The overall mean values of FW, FH, and FL were 9.7 ± 3.1, 14.07 ± 2.7, and 5.6 ± 0.8 mm, respectively. Mean EV was 489.0 ± 151.6 mm(3). The single (0.879) and average (0.956) measurements of the intraclass correlation coefficient for FH were very good to excellent. Similar data were observed for FH (single, 0.827; average, 0.935). For FL, a decreasing trend in the mean and variability over the 3 measurement times was reflected in low single (0.305) and moderate average (0.569) intraclass correlation coefficients. CONCLUSIONS CBCT imaging can be used to reliably measure FW, FH, and FL and to calculate the EV of the cleft. These data can be used by oral and maxillofacial surgeons to quantitatively assess the volume of an alveolar cleft and aid in preoperative determination of the amount of bone that will be needed to adequately graft the cleft space. This will also aid in appropriate selection of an autogenous graft donor site before surgery.

Characterizing Traditionally-defined Periodontal Disease in HIV+ Adults

BACKGROUND Results have varied from previous studies examining the level and extent of periodontal disease (PD) in HIV-1 infected (HIV+) adults. These studies used different methodologies to measure and define PD and examined cohorts with divergent characteristics. Inconsistent methodological approaches may have resulted in the underestimation of traditionally-defined PD in HIV+ individuals. OBJECTIVES To characterize the level, extent and predictors (i.e. immunologic, microbiologic, metabolic and behavioral) of PD in an HIV+ cohort during the era of highly active antiretroviral therapy (HAART). STUDY DESIGN Cross-sectional study. SETTING HIV+ adults receiving outpatient care at three major medical clinics in Cleveland, OH. Subjects were seen from May, 2005 to January, 2008. MEASUREMENTS Full-mouth periodontal examinations included periodontal probing depth (PPD), recession (REC) and clinical attachment level (CAL). Subgingival plaque was assessed for DNA levels of Porphyromonas gingivalis (Pg), Tannerella forsythia, and Treponema denticola by real-time DNA PCR assays developed for each pathogen. Rather than using categories, we evaluated PD as three continuous variables based on the percent of teeth with >or=1 site per tooth with PPD >or= 5mm, REC > 0 mm and CAL >or= 4mm. RESULTS Participants included 112 HIV+ adults. Each subject had an average 38% (+/-24%) of their teeth with at least one site of PD >or= 5 mm, 55% (+/-31%) of their teeth with at least one site of REC > 0 mm, and 50% (+/-32%) of their teeth with at least one site of CAL >or= 4 mm. CD4+ T-cell count <200 cells/mm(3) was significantly associated with higher levels of REC and CAL, but not PPD. Greater levels of Pg DNA were associated with PPD, REC and CAL.By regression analysis, CD4+ T-cell count <200 cells /mm3 had approximately twice thedeleterious effect on CAL as did smoking (standardized beta coefficient 0.306 versus 0.164) [corrected]. Annual dental visit compliance remained an independent predictor for lower levels of PD. CONCLUSIONS The level and extent of PD were high in this cohort even though most patients were being treated with HAART. The definition of periodontal disease used and cohort characteristics examined can influence the level of periodontal disease reported in studies of persons with HIV. Traditional periodontal pathogens are associated with PD in this cohort. Those with CD4+ T-cell counts <200 cells/mm(3) are at greater risk for PD. Therefore, earlier HAART initiation may decrease exposure to immunosuppression and reduce PD morbidity. Continuity of dental care remains important for HIV+ patients even when they are being treated with HAART.

Effect of Nadir CD4+ T Cell Count on Clinical Measures of Periodontal Disease in HIV+ Adults before and during Immune Reconstitution on HAART

Background The contribution of HIV-infection to periodontal disease (PD) is poorly understood. We proposed that immunological markers would be associated with improved clinical measures of PD. Methods We performed a longitudinal cohort study of HIV-infected adults who had started highly active antiretroviral therapy (HAART) <2 years. PD was characterized clinically as the percent of teeth with ≥1 site with periodontal probing depth (PPD) ≥5.0mm, recession (REC) >0mm, clinical attachment level (CAL) ≥4.0mm, and bleeding on probing (BOP) at ≥4 sites/tooth and microbiologically as specific periodontopathogen concentration. Linear mixed-effects models were used to assess the associations between immune function and PD. Results Forty (40) subjects with median 2.7 months on HAART and median nadir CD4+ T-cell count of 212 cells/μl completed a median 3 visits. Over 24 months, CD4+ T-cell count increased by a mean 173 cells/µl (p<0.001) and HIV RNA decreased by 0.5 log10 copies/ml (p<0.001); concurrently, PPD, CAL and BOP decreased by a mean 11.7%, 12.1%, and 14.7% respectively (all p<0.001). Lower nadir CD4+ T-cell count was associated with worse baseline REC (-6.72%; p=0.04) and CAL (9.06%; p<0.001). Further, lower nadir CD4+ T-cell count was associated with a greater relative longitudinal improvement in PPD in subjects with higher baseline levels of Porphyromonas gingivalis (p=0.027), and BOP in subjects with higher baseline levels of Porphyromonas gingivalis or Treponema denticola (p=0.001 and p=0.006 respectively). Longitudinal changes from baseline in CD4+ T-cell count and level of HIV RNA were not independently associated with longitudinal changes in any clinical markers of PD. Conclusion Degree of immunosuppression was associated with baseline gingival recession. After HAART initiation, measures of active PD improved most in those with lower nadir CD4+ T-cell counts and higher baseline levels of specific periodontopathogens. Nadir CD4+ T-cell count differentially influences periodontal disease both before and after HAART in HIV-infected adults.

The feasibility, acceptance, and key features of a prevention-focused oral health education program for HIV+ adults

Poor oral health is common in HIV+ adults. We explored the feasibility, acceptance, and key features of a prevention-focused oral health education program for HIV+ adults. This was a pilot substudy of a parent study in which all subjects (n = 112) received a baseline periodontal disease (PD) examination and provider-delivered oral health messages informed by the Information-Motivation-Behavioral Skills (IMB) Model. Forty-one parent study subjects were then eligible for the substudy; of these subjects, a volunteer sample was contacted and interviewed 3–6 months after the baseline visit. At the recall visit, subjects self-reported behavior changes that they had made since the baseline. PD was reassessed using standard clinical assessment guidelines, and results were shared with each subject. At recall, individualized, hands-on oral hygiene coaching was performed and patients provided feedback on this experience. Statistics included frequency distributions, means, and chi-square testing for bivariate analyses. Twenty-two HIV+ adults completed the study. At recall, subjects had modest, but nonsignificant (p > 0.05) clinician-observed improvement in PD. Each subject reported adopting, on average, 3.8 (± 1.5) specific oral health behavior changes at recall. By self-report, subjects attributed most behavior changes (95%) to baseline health messages. Behavior changes were self-reported for increased frequency of flossing (55%) and toothbrushing (50%), enhanced toothbrushing technique (50%), and improved eating habits (32%). As compared to smokers, nonsmokers reported being more optimistic about their oral health (p = 0.024) at recall and were more likely to have reported changing their oral health behaviors (p = 0.009). All subjects self-reported increased knowledge after receiving hands-on oral hygiene coaching performed at the recall visit. In HIV+ adults, IMB-informed oral health messages promoted self-reported behavior change, subjects preferred more interactive, hands-on coaching. We describe a holistic clinical behavior change approach that may provide a helpful framework when creating more rigorously designed IMB-informed studies on this topic.

Simultaneous Detection of Oral Pathogens in Subgingival Plaque and Prostatic Fluid of Men With Periodontal and Prostatic Diseases

BACKGROUND Chronic prostatitis (CPr) and benign prostatic hyperplasia (BPH) are complex inflammatory conditions for which etiologic determinants are still poorly defined. Periodontitis is caused by subgingival colonizing bacteria in the oral cavity. The causal effect of periodontal disease on prostatic inflammation has not been established. The purpose of this study is to isolate oral pathogens from expressed prostatic secretions of patients with periodontal disease and CPr or BPH. METHODS Twenty-four men diagnosed with CPr/BPH participated in the study. A complete periodontal examination consisting of probing depth, bleeding on probing, tooth mobility, gingival index, and plaque index was performed on the men, and prostatic secretion was collected for the study. Dental plaque and prostatic secretion samples were used for analysis of bacterial DNA for Porphyromonas gingivalis (Pg), Prevotella intermedia (Pi), Treponema denticola (Td), and Escherichia coli using reverse transcription-polymerase chain reaction. RESULTS Six patients were diagnosed with severe, seven with moderate, and four with mild chronic periodontitis. Seventeen of 24 (70.8%) of the prostatic secretion samples showed one or more of the studied oral pathogens. Nine of 10 BPH and eight of 14 patients with CPr had at least one oral pathogen in their prostatic secretions. Pg was found in both prostatic secretion and plaque samples in six of 17 (35.3%) patients, Td was found in both samples in seven of 15 (46.7%) patients, and E. coli was found in both samples in three of 15 (20%) patients. Pi was detected in all dental plaque samples but not in the prostatic secretion. CONCLUSION An association between chronic inflammatory prostate and periodontal diseases has been demonstrated by the presence of similar bacterial DNA in both prostatic secretion and subgingival dental plaque from the same individual.

Patient-centered quality of life measures after alloplastic temporomandibular joint replacement surgery

The purpose of this study was to evaluate patient-reported outcome measures of quality of life (QoL) for patients with end-stage temporomandibular joint (TMJ) disease who have undergone TMJ prosthetic replacement. The records of 36 patients who had undergone alloplastic total joint replacement procedures were analyzed. Patients were treated using either TMJ Concepts or Biomet/Lorenz prosthetics. Patients were asked to complete a 12-item TMJ-S-QoL survey, which encompassed questions pertaining to pain, speech, chewing function, and various aspects of social life and mental health. The questions were answered on a 5-point scale. Data were analyzed using the Wilcoxon signed-rank test. Among the 36 patients (six male and 30 female), 18 responded to the survey. Markers of QoL after surgery were compared to the preoperative period. Significant improvements were reported for pain (94.4% of patients), chewing (83.3% of patients), speech (55.6% of patients), anxiety (72.2% of patients), activity (66.7% of patients), recreation (61.1% of patients), and mood (66.7% of patients) (all P<0.05). TMJ prosthetic replacement significantly enhanced QoL among patients suffering from chronic pain, limited range of motion, anxiety, impaired speech, and chewing due to end-stage TMJ disease in this sample of surgical patients.