CNS inflammation and bone marrow neuropathy in type 1 diabetes.

By using pseudorabies virus expressing green fluorescence protein, we found that efferent bone marrow-neural connections trace to sympathetic centers of the central nervous system in normal mice. However, this was markedly reduced in type 1 diabetes, suggesting a significant loss of bone marrow innervation. This loss of innervation was associated with a change in hematopoiesis toward generation of more monocytes and an altered diurnal release of monocytes in rodents and patients with type 1 diabetes. In the hypothalamus and granular insular cortex of mice with type 1 diabetes, bone marrow-derived microglia/macrophages were activated and found at a greater density than in controls. Infiltration of CD45(+)/CCR2(+)/GR-1(+)/Iba-1(+) bone marrow-derived monocytes into the hypothalamus could be mitigated by treatment with minocycline, an anti-inflammatory agent capable of crossing the blood-brain barrier. Our studies suggest that targeting central inflammation may facilitate management of microvascular complications.

Racial disparity in oral and pharyngeal cancer in Florida in 1991-2008: mixed trends in stage of diagnosis.

OBJECTIVES: To explore changes in distribution of stage at diagnosis among individuals with oral and pharyngeal cancers over the past two decades and whether the changes differ by race. METHODS: We obtained 1991-2008 cancer incidence data for nine anatomic sites of the oral and pharyngeal structure from the Florida Cancer Data System. These cancers were grouped into oral squamous cell carcinoma (SCC), pharyngeal SCC, and other head and neck cancers. Annual percent change was calculated for each group to characterize trends in age-adjusted cancer incidence over time by race and stage at diagnosis. RESULTS: During 1991-2008, the overall age-adjusted oral SCC incidence was decreasing for both races, with a greater decline observed among Blacks. There was a large drop in incidence of regional-stage diagnoses among Blacks. For pharyngeal SCC, the age-adjusted incidence of localized- and regional-stage diagnoses was increasing for Whites during 1991-2008, with the largest increase in the incidence of regional-stage diagnoses. The percentage of localized-stage diagnoses was increasing for both races for oral SCC. A slight increase in percentage of localized-stage diagnoses was observed for Blacks for pharyngeal SCC, whereas no obvious change was observed among Whites. CONCLUSIONS: Blacks continued to have lower percentages of localized-stage diagnoses than Whites for nearly all sites, but an increasing percentage of localized-stage diagnoses was observed for oral SCC among Blacks. For pharyngeal SCC, the increase in incidence among Whites was accompanied by an increasing percentage of late-stage diagnoses. Coordinated public health approaches with a special emphasis on screening underserved populations are needed.

Trends in incidence of oral and pharyngeal carcinoma in Florida: 1981-2008.

OBJECTIVE: While the overall incidence rates of oral and pharyngeal squamous cell carcinoma (SCC) have decreased in the United States, there is evidence of increasing incidence at selected anatomic sites, particularly among younger adults. The objective of this study was to examine trends in incidence rates of oral and pharyngeal cancers in Florida. METHODS: Using data from the Florida Cancer Data System, we examined the incidence of oral and pharyngeal carcinomas in Florida from 1981 through 2008. Factors of interest included sex, race, and trends over time. Percent change (PC) and annual percent change (APC) were computed to characterize trends over time. RESULTS: A total of 53,648 cases of oral or pharyngeal cancer were identified from 1981 through 2008. Significant increasing trends were observed only for pharyngeal cancers in males, with significant decreasing trends for pharyngeal cancer in females and oral cancer for both sexes. For tonsil and base of tongue cancers, increasing trends were detected for white males only. Further investigation among white males showed that, except for base of tongue cancer in the 20-44 age group, the incidence of both cancers increased across all age groups, with the largest increase for both sites found in the 45-64 age group. CONCLUSIONS: This study supports the finding of increasing incidence of SCC of the tonsil and base of tongue in males, in contrast to decreasing trends for most oral and pharyngeal carcinomas. However, we observed that this increase occurred in white males only and the most dramatic increase occurred in the 45-64 age group.

Otologic and audiologic outcomes with the Furlow and von Langenbeck with intravelar veloplasty palatoplasties in unilateral cleft lip and palate.

OBJECTIVE: Cleft palate increases the risk of chronic middle ear disease and hearing loss. The goal of this report was to determine which of two palate surgeries and which timing of palate surgery were associated with better otologic and audiologic outcomes in children with unilateral cleft lip and palate at 5 to 6 years of age. DESIGN: Subjects were randomly assigned to the von Langenbeck with intravelar veloplasty or Furlow palate repair, to palate surgery at 9 to 12 months or 15 to 18 months of age, and to the Spina or Millard lip repair. SETTING: Centralized, tertiary care craniofacial treatment center. PATIENTS: A total of 673 infants with unilateral cleft lip and palate. INTERVENTIONS: Palate and lip were repaired using established techniques. Serial otoscopic and audiometric evaluations were performed. MAIN OUTCOME MEASURES: Hearing and otoscopic findings at 5 to 6 years old. RESULTS: There were 370 children available for analysis. Hearing and need for tympanostomy tube placement did not differ by palatoplasty, age at palatoplasty, cheiloplasty, or surgeon. Risk of developing cholesteatoma or perforation was higher with Millard cheiloplasty (odds ratio  =  5.1, 95% confidence interval  =  1.44 to 18.11, p  =  .012). Type and age at palatoplasty were not significantly associated with either the rate of developing these sequelae or the rate of achieving bilaterally normal hearing and ear examinations. CONCLUSIONS: Type of palatoplasty did not influence otologic and audiologic outcomes in 5- to 6-year-olds with unilateral cleft lip and palate. The potential influence of lip repair on otologic outcomes warrants further investigation.

Phytoestrogens and coronary microvascular function in women with suspected myocardial ischemia: a report from the Women's Ischemia Syndrome Evaluation (WISE) Study.

AIMS: Soy phytoestrogens are popular, but information on their coronary effects in patients with suspected ischemic heart disease is limited. Accordingly, we investigated the relationship between blood phytoestrogen levels and coronary reactivity in women with suspected myocardial ischemia referred for coronary angiography. METHODS: Coronary flow velocity reserve (CFVR) and volumetric flow reserve (VFR) to adenosine (ADO) and nitroglycerin (NTG) (nonendothelial-dependent responses) and acetylcholine (ACH) (endothelial-dependent response) were assessed in 106 women from the Women's Ischemia Syndrome Evaluation (WISE). Blood phytoestrogen (daidzein and genistein) and estrogen (estradiol) levels were correlated with coronary reactivity measures. RESULTS: Participants were mostly postmenopausal (79%), mean age 56 years, and 24% had obstructive coronary artery disease (CAD) at angiography. Genistein blood levels were negatively correlated with nonendothelial-dependent coronary flow responses. The highest genistein tertile (>6.1 ng/mL) had a CFVR of 2.1 +/- 0.5 (mean +/- SD) and VFRADO of 1.0 +/- 0.6, and both were significantly (p= 0.0001) lower compared with the other genistein tertiles combined. Similar associations were noted for CFVR(NTG) and VFR(NTG) (p = 0.03 and p = 0.01, respectively). The highest genistein tertile was associated with lower CFVR(ACH) compared with the other tertiles (p = 0.03). In multivariable modeling, blood genistein levels were significant independent predictors of coronary flow responses to ADO. There were no significant correlations between coronary reactivity variables and daidzein or endogenous estrogen. CONCLUSIONS: In women with suspected myocardial ischemia, higher genistein blood levels are associated with impaired nonendothelial-dependent and endothelial-dependent coronary microvascular function.

Coronary microvascular reactivity is only partially predicted by atherosclerosis risk factors or coronary artery disease in women evaluated for suspected ischemia: results from the NHLBI Women's Ischemia Syndrome Evaluation (WISE).

BACKGROUND: Altered coronary reactivity is frequent in women with findings of myocardial ischemia without significant obstructive disease. This suggests a defect in coronary microvascular function. The adenosine-related component of this altered reactivity has been described in male and mixed gender populations, while the factors influencing this component of coronary reactivity in symptomatic women have received limited attention. Accordingly, the relationship between adenosine-related microvascular coronary reactivity and risk factors in symptomatic women evaluated for suspected ischemia remains uncertain. HYPOTHESIS: Abnormal coronary microvascular reactivity to adenosine is predicted by atherosclerosis risk factors in women. METHODS: As part of the NHLBI-sponsored Women's Ischemia Syndrome Evaluation (WISE), we investigated the relationship between risk factors and coronary microvascular reactivity as flow velocity reserve to intracoronary adenosine (CFVR(Ado)) in 210 women referred for angiography to evaluate suspected ischemia. RESULTS: Univariate analyses identified associations between CFVR(Ado) and multiple risk conditions; however, after adjusting for age, none remained significant. The best multivariable model using combinations of risk conditions to predict CFVR(Ado) yielded an R2 of only 0.18. CONCLUSIONS: Among women with suspected ischemia, risk factors account for <20% of observed variability in CFVR(Ado). Therefore, other as yet unidentified factors must primarily account for coronary microvascular reactivity to adenosine.

Perceptions of orthognathic surgery patient's change in profile. A five-year follow-up.

OBJECTIVES: To compare pairs of silhouettes generated from presurgical and 5-year postsurgical cephalometric radiographs to evaluate whether orthodontists, oral surgeons, and lay persons perceive changes in profile resulting from orthodontics and mandibular advancement surgical treatment. MATERIALS AND METHODS: A survey-based method of data collection was used to evaluate 15 pairs of silhouettes. These silhouettes included 1 control pair and 14 surgically treated pairs representing mandibular advancements ranging from 0.11 mm to 10.13 mm. Collected data were analyzed to determine whether changes can be perceived and whether these changes were esthetically pleasing. RESULTS: The control silhouette pair was identified by 104 of 127 evaluators. For the 14 surgical treated silhouette pairs, the vast majority of evaluators (N = 127; 53 orthodontists, 32 oral surgeons, and 42 lay persons) were able to identify changes in profile and individual features. At least one group of evaluators was able to perceive significant (P < .05) improvement in the visual analog scale (VAS) score for all these silhouette pairs, except for the pair with 10.13 mm of mandibular advancement. This silhouette pair, which represented the largest mandibular advancement, was perceived to have a significant (P < .05) worsening in the VAS score by the lay person group. There were significant differences among the groups of evaluators. Esthetic improvement in profile was perceived for 13 of 14 surgically treated silhouette pairs. CONCLUSION: In some cases, orthodontists, oral surgeons, and lay persons perceived changes in profile differently.

Mental stress provokes ischemia in coronary artery disease subjects without exercise- or adenosine-induced ischemia.

OBJECTIVES: The purpose of this study was to investigate the possibility that some patients with coronary artery disease (CAD) but negative exercise or chemical stress test results might have mental stress-induced ischemia. The study population consisted solely of those with negative test results. BACKGROUND: Mental stress-induced ischemia has been reported in 20% to 70% of CAD subjects with exercise-induced ischemia. Because mechanisms of exercise and mental stress-induced ischemia may differ, we studied whether mental stress would produce ischemia in a proportion of subjects with CAD who have no inducible ischemia with exercise or pharmacologic tests. METHODS: Twenty-one subjects (14 men, 7 women) with a mean age of 67 years and with a documented history of CAD were studied. All subjects had a recent negative nuclear stress test result (exercise or chemical). Subjects completed a speaking task involving role playing a difficult interpersonal situation. A total of 30 mCi 99mTc-sestamibi was injected at one minute into the speech, and imaging was started 40 min later. A resting image obtained within one week was compared with the stress image. Images were analyzed for number and severity of perfusion defects. The summed difference score based on the difference between summed stress and rest scores was calculated. Severity was assessed using a semiquantitative scoring method from zero to four. RESULTS: Six of 21 (29%) subjects demonstrated reversible ischemia (summed difference score > or =3) with mental stress. No subject had chest pain or electrocardiographic changes during the stressor. Mean systolic and diastolic blood pressure and heart rate all increased between resting and times of peak stress. CONCLUSIONS: Mental stress may produce ischemia in some subjects with CAD and negative exercise or chemical nuclear stress test results.

Abnormal coronary vasomotion as a prognostic indicator of cardiovascular events in women: results from the National Heart, Lung, and Blood Institute-Sponsored Women's Ischemia Syndrome Evaluation (WISE).

BACKGROUND: Coronary vascular dysfunction has been linked to atherosclerosis and adverse cardiovascular outcomes in men, but these relationships have not been firmly established in women. METHODS AND RESULTS: As part of the Women's Ischemia Syndrome Evaluation (WISE) sponsored by the National Heart, Lung, and Blood Institute, 163 women referred for clinically indicated coronary angiography underwent coronary reactivity assessment with quantitative coronary angiography and intracoronary Doppler flow before and after intracoronary administration of acetylcholine, adenosine, and nitroglycerin and were then followed up for clinical outcomes. History of hypertension was present in 61%, dyslipidemia in 54%, diabetes in 26%, and current tobacco use in 21% of women enrolled. Seventy-five percent had no or only mild epicardial coronary artery disease (CAD). Over a median follow-up of 48 months, events occurred in 58 women. On bivariate analysis, women with an event had significantly less change in coronary cross-sectional area (DeltaCSA) in response to acetylcholine (P=0.0006) and nitroglycerin (P=0.04). In addition, women with abnormal coronary dilator response to acetylcholine had less time free from cardiovascular events (P=0.004). In multivariable analysis, after controlling for age, hypertension, diabetes, dyslipidemia, tobacco use, and CAD severity, %DeltaCSA with acetylcholine (P=0.001) independently predicted events. When the outcome was restricted to only death, myocardial infarction, congestive heart failure, and stroke, %DeltaCSA with acetylcholine remained a significant predictor (P=0.006). CONCLUSIONS: In women in this study, impaired coronary vasomotor response to acetylcholine was independently linked to adverse cardiovascular outcomes regardless of CAD severity.