Periodontal Treatment Reduces Circulating Pro-Inflammatory Cytokine and Chemokine Levels in African American HIV+ Individuals with Virological Suppression.

Introduction: Periodontal Disease (PD), a chronic inflammatory disease, is highly prevalent among Persons Living With HIV (PLWH) and is characterized by microbial symbiosis and oxidative stress. Our hypothesis stipulates that periodontal therapy attenuates systemic inflammatory and bacterial burden while improving periodontal status in PLWH. Methods: Sixteen African Americans (AA) with suppressed HIV viremia on long-term Antiretroviral Therapy (ART) were recruited to this study. Participants were placed into two groups, based on their dental care status: group 1 (In-Care, IC) and group 2 (Out of Care, OC). Periodontal health was investigated at baseline, 3 months, 6 months, and 12 months. Cytokine/chemokines, microbial phyla, and Asymmetric Dimethylarginine (ADMA, a marker for endothelial cell dysfunction) levels were assessed in the serum. Statistical comparisons between groups and at different visits were performed using multiple comparison tests. Results: Across longitudinal visits, periodontal treatment significantly reduced the levels of several cytokines and chemokines. At baseline, the out of care group had significantly higher blood levels of ADMA and actinobacteria than the IC group. Periodontal treatment significantly altered the abundance of circulating genomic bacterial DNA for various phyla in out of care group. Conclusions: Periodontal treatment interventions effectively attenuated circulating pro-inflammatory cytokines and altered microbial translocation, both critical drivers of systemic inflammation in PLWH.

Modeling the Dynamics of the U.S. Healthcare Expenditure Using a Hyperbolastic Function.

In this paper, we investigate the dynamics of the U.S. national healthcare expenditures from 1960 to 2011. The data were obtained from the U.S. Department of Health and Human Services, Center for Medicare and Medicaid Services. The analytical method allows extracting the long-run deterministic trend from the cyclical and the random components. The long-run trend is estimated using six classical growth models and three more recent growth curves called Hyperbolastic growth models of types I, II, and III, denoted by H1, H2, and H3, respectively. The statistical results indicate that the H1 model provides the best fit of the data. The study is complemented by a mathematical analysis of the deterministic long-run component of the national healthcare expenditure (NHE) as modeled by H1. This analysis is performed by examining the behavior of the absolute growth rate (pace of increase curve), the relative growth rate, and the acceleration of the U.S. NHE over the 52-year time frame. To the best of our knowledge, this paper provides the first application of Hyperbolastic models to economics data. This study can be used by researchers and policy makers as a descriptive as well as a predictive tool.

Robust Logistic and Probit Methods for Binary and Multinomial Regression.

In this paper we introduce new robust estimators for the logistic and probit regressions for binary, multinomial, nominal and ordinal data and apply these models to estimate the parameters when outliers or inluential observations are present. Maximum likelihood estimates don't behave well when outliers or inluential observations are present. One remedy is to remove inluential observations from the data and then apply the maximum likelihood technique on the deleted data. Another approach is to employ a robust technique that can handle outliers and inluential observations without removing any observations from the data sets. The robustness of the method is tested using real and simulated data sets.

A New Robust Method for Nonlinear Regression.

BACKGROUND: When outliers are present, the least squares method of nonlinear regression performs poorly. The main purpose of this paper is to provide a robust alternative technique to the Ordinary Least Squares nonlinear regression method. This new robust nonlinear regression method can provide accurate parameter estimates when outliers and/or influential observations are present. METHOD: Real and simulated data for drug concentration and tumor size-metastasis are used to assess the performance of this new estimator. Monte Carlo simulations are performed to evaluate the robustness of our new method in comparison with the Ordinary Least Squares method. RESULTS: In simulated data with outliers, this new estimator of regression parameters seems to outperform the Ordinary Least Squares with respect to bias, mean squared errors, and mean estimated parameters. Two algorithms have been proposed. Additionally and for the sake of computational ease and illustration, a Mathematica program has been provided in the Appendix. CONCLUSION: The accuracy of our robust technique is superior to that of the Ordinary Least Squares. The robustness and simplicity of computations make this new technique more appropriate and useful tool for the analysis of nonlinear regressions.

Oscillabolastic model, a new model for oscillatory dynamics, applied to the analysis of Hes1 gene expression and Ehrlich ascites tumor growth.

This paper introduces a new dynamical model, called the oscillabolastic model, to analyze the dynamical behavior of biomedical data when one observes oscillatory behavior. The proposed oscillabolastic model is sufficiently flexible to represent various types of oscillatory behavior. The oscillabolastic model is applied to two sets of data. The first data set deals with the oscillabolastic modeling of Ehrlich ascites tumor cells and the second one is the oscillabolastic modeling of the mean signal intensity of Hes1 gene expression in response to serum stimulation. A generalized oscillabolastic model is also suggested to accommodate cases in which predictor variables other than time are also involved.

Heavy metals distribution in an Iowa suburban landscape.

This study investigated the degree to which human activities through urbanization influence heavy metal concentrations in a suburban landscape in Ankeny, IA. Residential areas from different years in nine time periods of development were identified from aerial photos. Soil cores were collected from the center of the front yard of 10 randomly selected homes. Cores were subdivided into 0- to 5-, 5- to 10-, and 10- to 20-cm increments from a composite of five cores. The soils were analyzed for organic C, pH, and total Cd, Co, Cr, Cu, Ni, Pb, and Zn. Results showed that organic C increased and pH decreased with time, and that there was a general decreasing trend in heavy metal concentrations from the pre-1939 period until 1983-1990, after which there was a sharp increase in the concentrations of most of the metals. The mean Cu concentration ranged from 21 mg kg(-1) for the pre-1939 time period of development to 14.9 mg kg(-1) for the recent period of development (2003-2005). Nickel concentrations increased significantly with depth with means of 21.3 mg kg(-1) at depth 0 to 5 cm, 22.5 mg kg(-1) at depth 5 to 10 cm, and 23.0 mg kg(-1) at depth 10 to 20 cm. The concentrations of heavy metals were significantly intercorrelated, except Zn, suggesting their coexistence as mineral constituents or common contamination source. The concentrations of Cu and Pb in some locations could be due to anthropogenic inputs or higher organic matter content in soils adjacent to older homes. There appears to have been a source that caused an increase in Cd, Cr, Co, Cu, Pb, and Ni concentrations in soil adjacent to homes built between 1983 and 1990.

Stomal seeding of head and neck cancer by percutaneous endoscopic gastrostomy tube placement.

BACKGROUND: Percutaneous endoscopic gastrostomy (PEG) tubes have replaced nasogastric tubes and Stamm gastrostomy tubes as a preferred means of feeding for patients with head and neck cancers, as recommended by the results of large series. A patient with stomal seeding of squamous cell carcinoma of the upper aerodigestive tract by PEG placement was reported. A review of literature was performed. METHODS: A Medline search of implantation of squamous cell carcinoma from the upper aerodigestive tract to PEG exit site since the introduction of PEG was performed. RESULTS: Two reports of implantation of squamous cell carcinoma of the upper aerodigestive tract to PEG exit site were found. Both patients and our patient were staged T4. CONCLUSIONS: Implantation of squamous cell carcinoma from the upper aerodigestive tract to the PEG exit site is a rare and late complication. Its prevalence is not known. For patients with a significant amount of squamous cell carcinoma in the upper aerodigestive tract, we recommend Stamm gastrostomy over PEG insertion by the pull technique. There is no report of such late complication by the push technique.

Significance of tumor thickness in soft palate carcinoma.

Tumor thickness is an important prognostic factor in tumors outside of the upper aerodigestive tract, such as cutaneous melanoma, colorectal carcinoma, and cervical carcinoma. Some studies have also suggested that tumor thickness may have similar prognostic value in the upper aerodigestive tract. This study examined the relationship between tumor thickness (measured with an ocular micrometer) and nodal disease and that between tumor thickness and survival in 44 patients with soft palate epidermoid carcinoma. There was a significant correlation between tumor thickness and nodal disease. None of the 24 lesions less than or equal to 2.86 mm had cervical adenopathy. All of the 15 lesions greater than or equal to 3.12 mm had palpable adenopathy. Tumor thickness correlated more directly with nodal disease than did T stage. Thicker lesions were associated with poorer survival. Tumor thickness is an important parameter in the head and neck and deserves further study.

Multimodality preoperative treatment for advanced stage IV (MO) cancer of the head and neck.

Sixty-three patients with advanced unresectable squamous cell carcinoma of the head and neck were treated with a combination of chemotherapy, radiation, and surgery. We observed a 75% response to neoadjuvant chemotherapy. The 5-year survival rate for all 63 patients was 20%, and only 3 patients were alive at 8 years. The 5-year survival rate for patients who completed the treatment plan and received chemotherapy, radiation, and surgery was 43% compared with 20% for those who had chemotherapy and radiation but refused surgery. Development of a second primary cancer was the cause of death in 62% of the patients who survived more than 24 months.

Impact of esophageal screening in patients with head and neck cancer.

We have reviewed the records of 1,982 patients who were treated for head and neck cancer or esophageal cancer from 1962 to 1986. Forty-one patients had primary cancer at both sites. Twenty-one cases of these multiple primaries occurred synchronously and twenty were metachronous. The overall incidence of esophageal cancer in our head- and neck-cancer patients was 2.5 per cent and the incidence of head and neck cancer in our esophageal cancer patients was 7.1 per cent. From 1980 to 1986, 574 cases with a diagnosis of head and neck or esophageal cancer were routinely screened for other aerodigestive malignancies at the time of initial diagnosis. From this group, only six patients had simultaneous lesions of the head and neck and esophagus with only one asymptomatic esophageal carcinoma. Median survival of all 41 multiple primary patients after diagnosis of esophageal cancer was 5.3 months. Two- and three-year survivals were 6.7 per cent and 0 per cent, respectively. There was no significant survival difference for lesions diagnosed simultaneously, synchronously, and metachronously before 1980 or after 1980. All patients died with uncontrolled esophageal cancer except for one patient who died of head- and neck-cancer recurrence. Our experience indicates that active screening of head- and neck-cancer patients for simultaneous esophageal cancer has a low yield and there appears to be no survival advantage for these patients compared with those with subsequently diagnosed esophageal tumors.

Rapid development of metastases from basal cell carcinoma presenting as cranial nerve palsies.

A case is reported of metastatic basal cell carcinoma presenting with multiple neurologic deficits 20 months after excision of the primary lesion with good local control. Many features associated with the development of metastasis from basal cell carcinoma were not present in this case.

Lung cancer in patients with head and neck cancer. Incidence and long-term survival.

Of the 3,907 cases of primary head and neck or lung cancer diagnosed between 1961 and 1984, 94 patients were identified with a history of cancer at both sites. The total incidence of lung cancer in our head and neck cancer patients was 5.4 percent. Of the 94 patients, 73 had both cancers diagnosed at our institution. These 73 patients were further analyzed. Squamous cell carcinoma accounted for 63 percent of the lung cancers. Twenty of the lung cancers were synchronous and 47 were metachronous after head and neck cancer. Of the synchronous lung cancers, 50 percent were postoperative stage I, whereas only 11 percent of the metachronous cancers were postoperative stage I. The lung cancer survival rate was significantly better for the synchronous cancer group at 5 years (34 percent) than for the metachronous cancer group (5 percent). The better survival rate was evidently due to the greater proportion of early-stage lung lesions. The relatively large number of advanced-stage lung lesions in the metachronous cancer group suggests that aggressive screening of head and neck cancer patients for lung cancer may detect more metachronous lung cancers at an earlier stage and thus improve the survival rate of these patients.

Relation of thickness of floor of mouth stage I and II cancers to regional metastasis.

We have reviewed the clinical course and histologic findings in 84 patients with stage I and II squamous carcinoma of the mouth floor. We concluded that lesion thickness may offer a useful method for predicting the probability of cervical metastasis in node negative (N0) patients. Moreover, surface area of the lesion did not correlate with subsequent nodal disease, whereas thickness did. Elective node dissection appears to be strongly indicated in any patient with a N0 lesion measuring more than 1.5 mm in thickness.

Management of squamous cell carcinoma of unknown origin in cervical lymph nodes.

Forty-three patients with the diagnosis of metastatic squamous cell carcinoma from unknown primary to the cervical lymph nodes were treated in EOVAMC between 1962-1982. Six of these patients were N1, 19 N2, and 18 N3. Five-year survival was 41 per cent for N1, 15 per cent for N2, and 6 per cent for N3 nodes. There was no significant difference in the treatment failure of those patients treated with unimodality versus multimodality. A subsequent primary was detected in the head and neck in 23 per cent of these patients (10/43), and eight of these patients had received previous radiotherapy. The most common site for these subsequent primaries was hypopharynx. Nine of the 43 patients developed distant metastasis with no correlation to stage of disease or treatment modality. These data show that the survival of these patients correlates with the stage of nodal disease, and that radiotherapy did not decrease the subsequent appearance of the primary lesions.

Cancer of the tonsil. Improved survival with combination therapy.

One hundred seventy-four cases of squamous cell cancer of the tonsil (SCCT) were reviewed. Radiation therapy (RT) alone was used in 81 patients, surgery alone (S) in 19 patients, preoperative RT + S in 49 patients, and chemotherapy [( C] methotrexate plus bleomycin plus cisplatin) in 25 patients. The 5-year survival was 83% in Stage I (n = 21), 72% in Stage II (n = 19), 23% in Stage III (n = 34), and 15% in Stage IV (n = 100). RT and S were equally effective in Stages I and II. In Stage III, the 5-year survival for RT + S was 31% versus 11% for RT alone; and in Stage IV, the respective 3- and 5-year survivals for RT + S were 24% and 15% versus 6% and 0%, respectively, for RT alone. There was an 84% response rate to C, and the patients who completed C + RT + S had 3- and 5-year survival rates of 41.7% and 32%, respectively. Our results indicate that RT + S appears to offer better survival in Stage III and IV SCCT. The high response rate in early survival data seen with C + RT + S suggests a promising role for this approach.

A prospective evaluation of 5-fluorouracil plus cisplatin in advanced squamous-cell cancer of the head and neck.

Recent studies have shown improved efficacy of chemotherapy in patients with advanced squamous-cell cancer of the head and neck. Our purpose was to evaluate prospectively the activity of cisplatin plus 5-fluorouracil (5FU) in 37 patients with advanced stage IV squamous-cell cancer of the head and neck. There were two groups. Group 1 consisted of 19 previously untreated patients with either T4 or N3 disease. They received 100 mg/m2 cisplatin (days 1 and 28) and 120-hour infusion of 1,000 mg/m2/24 hours 5FU (days 1 to 5 and 28 to 32). They subsequently were offered preoperative radiotherapy (RT) and surgery. Group 2 consisted of 18 previously treated patients. They received 5FU and cisplatin in the same dosage every 28 days for either recurrent or metastatic disease. It was found that in group 1 there was an 84% response rate (five complete responses (CR) and 11 partial responses (PR) ). Three of those with PR achieved a CR after RT. Seven patients have had RT plus surgery and are disease free at 8 to 27 month follow-up. Six patients (one CR, five PR) refused surgery and progressed within 4 months. In group 2 there was an 11% response rate after two cycles (two PR), three patients had a minimal response (MR, less than 50% response) and received a mean of four cycles of treatment. Three patients with stable disease received a mean of four cycles of chemotherapy until progression. Two of 11 patients who had received previous chemotherapy plus RT showed an MR; nine of these patients had shown a response to their previous chemotherapy. Only one of 14 patients who had RT plus chemotherapy had a PR, and three had MR. Of five patients who had previous surgery, only one had a PR. All five had received chemotherapy as well. It was concluded that 5FU plus cisplatin is an effective combination in previously untreated patients. In previously treated patients with recurrent disease, there is a substantially lower response rate.

Preoperative intra-arterial infusion chemotherapy for advanced squamous cell carcinoma of the mouth and oropharynx.

Twelve patients with advanced locoregional (Stage III and IV) squamous cell carcinoma of the oral cavity and oropharynx underwent treatment with cisplatin, vinblastine, bleomycin, and 5-fluorouracil, given by intra-arterial infusion, as primary adjuvant therapy, in preparation for radiation therapy and surgery. Responses were observed during or immediately after infusion therapy in 8 of 12 (67%) of patients (1 complete response, 7 partial responses). Infusion chemotherapy was followed by radiation therapy alone in five patients and by radiation and surgery in six patients. The protocol was initiated in August 1981, and six patients are now free of their primary cancer, at 21 to 36 months, whereas six have died with disease. Arterial infusion of a combination of effective antineoplastic agents is a promising method for the preparation of selected patients for radiation therapy and surgery, as it is less likely to produce serious systemic toxicity and it requires a shorter period than systemic neoadjuvant chemotherapy.

Multimodality preoperative treatment for advanced cancer of the head and neck.

Neoadjuvant induction chemotherapy with cisplatin, methotrexate, and bleomycin appears to improve the results of treatment of advanced stage IV head and neck cancer, compared with results in historical control subjects. Patients treated with induction chemotherapy and radiation therapy had a 29 percent overall survival rate at 3 years, which represents approximately a twofold improvement in the survival rate. Patients who were treated with chemotherapy and radiation therapy followed by surgery had more than a threefold increase in the survival rate (49 percent at 3 years), compared with historical data from our institution and elsewhere for such patients [9-11]. Distant metastases developed in 25 percent of the patients, and it thus appears that long-term, effective consolidation and maintenance chemotherapy [12,13] need to be developed for patients who receive combination therapy before surgery for head and neck cancer.