Robert G. Norman

TNF-α and antibodies to periodontal bacteria discriminate between Alzheimer’s disease patients and normal subjects

The associations of inflammation/immune responses with clinical presentations of Alzheimers disease (AD) remain unclear. We hypothesized that TNF-alpha and elevated antibodies to periodontal bacteria would be greater in AD compared to normal controls (NL) and their combination would aid clinical diagnosis of AD. Plasma TNF-alpha and antibodies against periodontal bacteria were elevated in AD patients compared with NL and independently associated with AD. The number of positive IgG to periodontal bacteria incremented the TNF-alpha classification of clinical AD and NL. This study shows that TNF-alpha and elevated numbers of antibodies against periodontal bacteria associate with AD and contribute to the AD diagnosis.

Late Expression of p53 from a Replicating Adenovirus Improves Tumor Cell Killing and Is More Tumor Cell Specific than Expression of the Adenoviral Death Protein

Gene transfer of p53 induces cell death in most cancer cells, and replication-defective adenoviral vectors expressing p53 are being evaluated in clinical trials. However, low transduction efficiency limits the efficacy of replication-defective vector systems for cancer therapy. The use of replication-competent vectors for gene delivery may have several advantages, holding the potential to multiply and spread the therapeutic agent after infection of only a few cells. However, expression of a transgene may adversely affect viral replication. We have constructed a replicating adenoviral vector (Adp53rc) that expresses high levels of p53 at a late time point in the viral life cycle and also contains a deletion of the adenoviral death protein (ADP). Adp53rc-infected cancer cells demonstrated high levels of p53 expression in parallel with the late expression pattern of the adenoviral fiber protein. p53 expression late in the viral life cycle did not impair effective virus propagation. Survival of several lung cancer cell lines was significantly diminished after infection with Adp53rc, compared with an identical p53-negative control virus. p53 expression also improved virus release and spread. Interestingly, p53 was more cytotoxic than the ADP in cancer cells but less cytotoxic than the ADP in normal cells. In conclusion, late expression of p53 from a replicating virus improves tumor cell killing and viral spread without impairing viral replication. In addition, in combination with a deletion of the ADP, specificity of tumor cell killing is improved.

Periodontal Pathogens and Gestational Diabetes Mellitus

In previous cross-sectional or case-control studies, clinical periodontal disease has been associated with gestational diabetes mellitus. To test the hypothesis that, in comparison with women who do not develop gestational diabetes mellitus, those who do develop it will have had a greater exposure to clinical and other periodontal parameters, we measured clinical, bacteriological (in plaque and cervico-vaginal samples), immunological, and inflammatory mediator parameters 7 weeks before the diagnosis of gestational diabetes mellitus in 265 predominantly Hispanic (83%) women in New York. Twenty-two cases of gestational diabetes mellitus emerged from the cohort (8.3%). When the cases were compared with healthy control individuals, higher pre-pregnancy body mass index (p = 0.004), vaginal levels of Tannerella forsythia (p = 0.01), serum C-reactive protein (p = 0.01), and prior gestational diabetes mellitus (p = 0.006) emerged as risk factors, even though the clinical periodontal disease failed to reach statistical significance (50% in those with gestational diabetes mellitus vs. 37.3% in the healthy group; p = 0.38).

The dental office visit as a potential opportunity for diabetes screening: an analysis using NHANES 2003-2004 data.

OBJECTIVES The bidirectional relationship between periodontitis and diabetes suggests that the dental visit may offer a largely untapped opportunity to screen for undiagnosed diabetes. To better examine this potential opportunity, data from the National Health and Nutrition Examination Survey (NHANES) 2003-2004 were used to determine if a larger proportion of patients with periodontal disease as compared with those without periodontitis would be recommended for screening according to American Diabetes Association (ADA) guidelines. The data were also used to determine whether at-risk individuals with periodontitis visited a dental professional recently, so that they could avail themselves of this opportunity for screening, if offered. METHODS Data to perform these analyses were collected from 2,923 subjects aged 20 and older who reported that they were never told that they had diabetes, had a periodontal examination, and had sufficient data to compute body mass index. Descriptive statistics, t-tests, and chi-square analyses that compared those with and without periodontitis were extrapolated to the US population. RESULTS A total of 62.9 percent of those without periodontitis and 93.4 percent of those with periodontal disease met ADA guidelines for diabetes screening. Of those at-risk with periodontal disease, 33.9 percent had seen a dentist in the past 6 months, 50 percent in the past year, and 60.4 percent in the past 2 years. CONCLUSIONS As almost all individuals with periodontitis would have been recommended for diabetes screening, and many at-risk persons with periodontal disease recently visited a dentist, our data suggest that the dental visit provides an important potential venue for this screening.

Changes in the Geriatric Care Environment Associated with NICHE (Nurses Improving Care for HealthSystem Elders).

The aging of the U.S. population has profound implications for acute care nursing practice. NICHE (Nurses Improving Care for HealthSystem Elders) is the only national nursing program that addresses the needs of the hospitalized older adult. This secondary analysis examines the influence of the NICHE program on nurse perceptions of the geriatric nursing practice environment and quality of geriatric care, as well as geriatric nursing knowledge in a sample comprising 8 acute care hospitals in the United States that administered the Geriatric Institutional Assessment Profile before and after NICHE implementation. Results were compared in a sample of 821 and 942 direct care nurses, respectively. Controlling for hospital and nurse characteristics, both nurse perceptions of the geriatric nursing practice environment (P < .0001) and quality of geriatric care (P =.0004) increased, but not geriatric nursing knowledge (P =.1462), following NICHE implementation. NICHE tools and principles can exert an important influence over the care provided to older adult patients by increasing the organizational support for geriatric nursing.

Comparison of the maintenance of wakefulness test (MWT) to a modified behavioral test (OSLER) in the evaluation of daytime sleepiness

The objectives were to evaluate the correlation between sleep onset as defined by the Oxford sleep resistance (OSLER) test and by simultaneous electroencephalography (EEG) and to determine the correlation between sleep latencies measured by the OSLER test and maintenance of wakefulness test (MWT) performed on the same day. This was a prospective, cross‐sectional study carried out in a tertiary‐care university‐based sleep laboratory. Participants were 11 consecutive subjects presenting to the sleep center with clinical indications for nocturnal polysomnography and MWT. The interventions included MWT and OSLER test. Mean sleep latencies for the OSLER and MWT in each subject were closely correlated (ICC = 0.94, [Intra‐class correlation]P < 0.05). Sleep latency by OSLER and simultaneous measurement of EEG also had excellent agreement (ICC = 0.91) with a bias of −0.97 min. The OSLER test is a practical and reliable tool for evaluating daytime sleepiness when compared with the MWT. No obvious systematic adaptation was seen during sequential OSLER test performance. Given its portability and minimal technical requirements, the OSLER test may be useful for large‐scale applications in the evaluation of daytime wakefulness and vigilance.

Periodontal status of adult patients treated with fixed buccal appliances and removable aligners over one year of active orthodontic therapy

OBJECTIVE To compare the periodontal status of adults treated with fixed buccal orthodontic appliances vs removable orthodontic aligners over 1 year of active therapy. MATERIALS AND METHODS The study population consisted of 42 subjects; 22 treated with fixed buccal orthodontic appliances and 20 treated with removable aligners. Clinical indices recorded included: plaque index (PI), gingival index (GI), bleeding on probing (BOP), and probing pocket depth (PPD). Plaque samples were assessed for hydrolysis of N-benzoyl-DL-arginine-naphthylamide (BANA test). Indices and BANA scores were recorded before treatment and at 6 weeks, 6 months, and 12 months after initiation of orthodontic therapy. RESULTS After 6 weeks, only mean PPD was greater in the fixed buccal orthodontic appliance group. However, after 6 months, the fixed buccal orthodontic appliance group had significantly greater mean PI, PPD, and GI scores and was 5.739 times more likely to have a higher BANA score. After 12 months, the fixed buccal orthodontic appliance group continued to have greater mean PI, GI, and PPD, while a trend was noted for higher BANA scores and BOP. CONCLUSIONS These results suggest treatment with fixed buccal orthodontic appliances is associated with decreased periodontal status and increased levels of periodontopathic bacteria when compared to treatment with removable aligners over the 12-month study duration.

Response to CPAP withdrawal in patients with mild versus severe obstructive sleep apnea/hypopnea syndrome.

BACKGROUND Patients with obstructive sleep apnea/hypopnea syndrome (OSAHS), even those generally compliant with CPAP therapy, often intermittently discontinue CPAP. STUDY OBJECTIVE Examine the impact of CPAP withdrawal on sleep, sleep disordered breathing (SDB), and daytime function in subjects with varying severity of OSAHS. PATIENTS AND INTERVENTIONS Forty-two subjects (26M/16 F) with OSAHS (AHI4% = 45.2 ± 35.5/h pretreatment) on CPAP for 4 months were evaluated on the second night of CPAP withdrawal. Sleep architecture, SDB indices, and subjective/objective daytime function were assessed pretreatment, on CPAP therapy, and after CPAP withdrawal. Comparisons were made between pretreatment and CPAP withdrawal for the entire group, and for subgroups of mild/moderate (AHI4% < 30/h, n = 22) and severe (AHI4% > 30/h, n = 20) SDB. RESULTS Overall, and for mild/moderate subjects, SDB indices returned to pretreatment values on CPAP withdrawal but with fewer apneas and more hypopneas/RERAs. For severe SDB, the event frequency (AI, AHI4%, and RDI) was lower and O2 desaturation was improved on CPAP withdrawal. Across SDB severity, sleep architecture showed lower %REM (15.6% vs 12.9%, P = 0.009) on the CPAP withdrawal compared to pretreatment. Stanford Sleepiness Score, MSLT, and PVT measures were not significantly different between pretreatment and CPAP withdrawal. CONCLUSIONS Over a wide range of SDB severity CPAP withdrawal results in recurrence of SDB, albeit with less severe O2 desaturation. Subjective/objective daytime function returned to pretreatment levels. Sleep architecture changes on CPAP withdrawal (acute SDB) may reflect reduced sleep pressure compared to pretreatment chronic SDB. Our data suggest detrimental effects of even brief withdrawal of CPAP in subjects with both mild and severe OSAHS. CITATION Young LR; Taxin ZH; Norman RG; Walsleben JA; Rapoport DM; Ayappa I. Response to CPAP withdrawal in patients with mild versus severe obstructive sleep apnea/hypopnea syndrome. SLEEP 2013;36(3):405-412.

“Computerized Counseling Reduces HIV-1 Viral Load and Sexual Transmission Risk: Findings from a Randomized Controlled Trial”

Objective:Evaluate a computerized intervention supporting antiretroviral therapy (ART) adherence and HIV transmission prevention. Design:Longitudinal randomized controlled trial. Settings:An academic HIV clinic and a community-based organization in Seattle. Subjects:In a total of 240 HIV-positive adults on ART, 209 completed 9-month follow-up (87% retention). Intervention:Randomization to computerized counseling or assessment only, 4 sessions over 9 months. Main Outcome Measures:HIV-1 viral suppression, and self-reported ART adherence and transmission risks, compared using generalized estimating equations. Results:Overall, intervention participants had reduced viral load: mean 0.17 log10 decline, versus 0.13 increase in controls, P = 0.053, and significant difference in ART adherence baseline to 9 months (P = 0.046). Their sexual transmission risk behaviors decreased (odds ratio = 0.55, P = 0.020), a reduction not seen among controls (odds ratio = 1.1, P = 0.664), and a significant difference in change (P = 0.040). Intervention effect was driven by those most in need; among those with detectable virus at baseline (>30 copies/mL, n = 89), intervention effect was mean 0.60 log10 viral load decline versus 0.15 increase in controls, P = 0.034. ART adherence at the final follow-up was 13 points higher among intervention participants versus controls, P = 0.038. Conclusions:Computerized counseling is promising for integrated ART adherence and safer sex, especially for individuals with problems in these areas. This is the first intervention to report improved ART adherence, viral suppression, and reduced secondary sexual transmission risk behavior.

Effect of Circulatory Congestion on the Components of Pulmonary Diffusing Capacity in Morbid Obesity

Objective: Obese patients without clinically apparent heart disease may have a high output state and elevated total and central blood volumes. Central circulatory congestion should result in elevated pulmonary diffusing capacity (DLCO) and capillary blood volume (Vc) reflecting pulmonary capillary recruitment; however, the effect on membrane diffusion (Dm) is uncertain. We examined DLCO and its partition into Vc and Dm in 13 severely obese subjects (BMI = 51 ± 14 kg/m2) without manifest cardiopulmonary disease before and after surgically induced weight loss.