A Randomized Clinical Trial Evaluating rh-FGF-2/ß-TCP in Periodontal Defects.

Biological mediators have been used to enhance periodontal regeneration. The aim of this prospective randomized controlled study was to evaluate the safety and effectiveness of 3 doses of fibroblast growth factor 2 (FGF-2) when combined with a ß-tricalcium phosphate (ß-TCP) scaffold carrier placed in vertical infrabony periodontal defects in adult patients. In this double-blinded, dose-verification, externally monitored clinical study, 88 patients who required surgical intervention to treat a qualifying infrabony periodontal defect were randomized to 1 of 4 treatment groups-ß-TCP alone (control) and 0.1% recombinant human FGF-2 (rh-FGF-2), 0.3% rh-FGF-2, and 0.4% rh-FGF-2 with ß-TCP-following scaling and root planing of the tooth prior to a surgical appointment. Flap surgery was performed with EDTA conditioning of the root prior to device implantation. There were no statistically significant differences in patient demographics and baseline characteristics among the 4 treatment groups. When a composite outcome of gain in clinical attachment of 1.5 mm was used with a linear bone growth of 2.5 mm, a dose response pattern detected a plateau in the 0.3% and 0.4% rh-FGF-2/ß-TCP groups with significant improvements over control and 0.1% rh-FGF-2/ß-TCP groups. The success rate at 6 mo was 71% in the 2 higher-concentration groups, as compared with 45% in the control and lowest treatment groups. Percentage bone fill in the 2 higher-concentration groups was 75% and 71%, compared with 63% and 61% in the control and lowest treatment group. No increases in specific antibody to rh-FGF-2 were detected, and no serious adverse events related to the products were reported. The results from this multicenter trial demonstrated that the treatment of infrabony vertical periodontal defects can be enhanced with the addition of rh-FGF-2/ß-TCP (ClinicalTrials.gov NCT01728844).

Human milk oligosaccharides promote the growth of staphylococci.

Human milk oligosaccharides (HMO), which constitute a major component of human milk, promote the growth of particular bacterial species in the infant's gastrointestinal tract. We hypothesized that HMO also interact with the bacterial communities present in human milk. To test this hypothesis, two experiments were conducted. First, milk samples were collected from healthy women (n = 16); culture-independent analysis of the bacterial communities was performed, HMO content was analyzed, and the relation between these factors was investigated. A positive correlation was observed between the relative abundance of Staphylococcus and total HMO content (r = 0.66). In a follow-up study, we conducted a series of in vitro growth curve experiments utilizing Staphylococcus aureus or Staphylococcus epidermidis and HMO isolated from human milk. HMO exhibited stimulatory effects on bacterial growth under various nutritional conditions. Analysis of culture supernatants from these experiments revealed that HMO did not measurably disappear from the culture medium, indicating that the growth-enhancing effects were not a result of bacterial metabolism of the HMO. Instead, stimulation of growth caused greater utilization of amino acids in minimal medium. Collectively, the data provide evidence that HMO may promote the growth of Staphylococcus species in the lactating mammary gland.

Angiogenic biomarkers and healing of living cellular constructs.

The use of intra-oral soft-tissue-engineered devices has demonstrated potential for oral mucosa regeneration. The aim of this study was to investigate the temporal expression of angiogenic biomarkers during wound healing of soft tissue reconstructive procedures comparing living cellular constructs (LCC) with autogenous free gingival grafts. Forty-four human participants bilaterally lacking sufficient zones of attached keratinized gingiva were randomly assigned to soft tissue surgery plus either LCC or autograft. Wound fluid samples were collected at baseline and weeks 1, 2, 3, and 4 post-operatively and analyzed for a panel of angiogenic biomarkers: angiogenin (ANG), angiostatin (ANT), PDGF-BB, VEGF, FGF-2, IL-8, TIMP-1, TIMP-2, GM-CSF, and IP-10. Results demonstrated a significant increase in expression of ANT, PDGF-BB, VEGF, FGF-2, and IL-8 for the LCC group over the autograft group at the early stages of wound repair. Although angiogenic biomarkers were modestly elevated for the LCC group, no clinical correlation with wound healing was found. This human investigation demonstrates that, during early wound-healing events, expression of angiogenic-related biomarkers is up-regulated in sites treated with LCC compared with autogenous free gingival grafts, which may provide a safe and effective alternative for regenerating intra-oral soft tissues (ClinicalTrials.gov number, NCT01134081).

The effects of soy milk and isoflavone supplements on cognitive performance in healthy, postmenopausal women.

RATIONALE: The decline in estrogen concentrations in women after menopause can contribute to health related changes including impairments in cognition, especially memory. Because of the health concerns related to hormone replacement therapy (HRT), alternative approaches to treat menopausal symptoms, such as nutritional supplements and/or diet containing isoflavones, are of interest. OBJECTIVES: This study investigated whether soy isoflavones (soy milk and supplement) could improve cognitive functioning in healthy, postmenopausal women. PARTICIPANTS, INTERVENTION AND DESIGN: A total of 79 postmenopausal women, 48-65 years of age, completed a double-blind, placebo-controlled trial in which they were randomly assigned to one of three experimental groups: cow's milk and a placebo supplement (control); soy milk and placebo supplement (soy milk, 72 mg isoflavones/day); or cow's milk and isoflavone supplement (isoflavone supplement, 70 mg isoflavones/day). MEASUREMENTS: Cognitive functioning was assessed using various cognitive tasks before the intervention (baseline) and after the intervention (test). RESULTS: In contrast to predictions, soy isoflavones did not improve selective attention (Stroop task), visual long-term memory (pattern recognition), short-term visuospatial memory (Benton Visual Retention Test), or visuo-spatial working memory (color match task). Also, the soy milk group showed a decline in verbal working memory (Digit Ordering Task) compared to the soy supplement and control groups. CONCLUSION: Soy isoflavones consumed as a food or supplement over a 16-week period did not improve or appreciably affect cognitive functioning in healthy, postmenopausal women.

Estimation of conjugated linoleic acid intake by written dietary assessment methodologies underestimates actual intake evaluated by food duplicate methodology.

Conjugated linoleic acids (CLA) are conjugated isomers of linoleic acid, which may promote health with regard to cancer, heart disease, diabetes, bone formation, growth modulation and immunity. The c9,t11 isomer of CLA, rumenic acid (RA), is the major isomer present in the diet. However, dietary intakes of CLA and RA by humans have not been examined rigorously, nor has the relationship between dietary CLA or RA and health (e.g., body composition). Three-day dietary records (DR) were collected from adult men (n = 46) and women (n = 47) and analyzed using a nutrient database modified to contain total CLA and RA. Simultaneously, 3-d food duplicates (FD) were collected to determine analytically individual fatty acid intakes, including those of total CLA and RA. Chronic total CLA and RA intakes were estimated using a semiquantitative food-frequency questionnaire (FFQ). Body composition was estimated using body mass index and percentage of body fat. Total CLA intake was estimated from FD to be 212 +/- 14 and 151 +/- 14 mg/d (mean +/- SEM) for men and women, respectively; RA intake was estimated to be 193 +/- 13 and 140 +/- 14 mg/d for men and women, respectively. In general, CLA and RA intakes estimated by DR and FFQ were significantly lower than those estimated by FD. Body composition was not significantly related to dietary total CLA or RA intake. In conclusion, results suggest that DR and FFQ methodologies are not reliable estimators of individual total CLA and RA intakes and may underestimate total CLA and RA intakes of groups. Intake of total CLA and RA was found to be significantly lower than that suggested previously by others.

Prognosis vs outcome: predicting tooth survival.

The assignment of prognosis is one of the most important functions undertaken in clinical practice, yet there is little evidence to support the current decision-making process. This article will review four articles that evaluate the traditional method of assigning a prognosis and predicting tooth survival. Limitations of the current method of assigning a prognosis are discussed, and models are presented that should allow clinicians to be more confident in their projections.

High-fat dairy product consumption increases delta 9c,11t-18:2 (rumenic acid) and total lipid concentrations of human milk.

Conjugated octadecadienoic acids (18:2, conjugated linoleic acids) have been shown to be anticarcinogenic and may influence growth and nutrient partitioning. The delta 9c,11t-18:2 isomer (rumenic acid, RA) is most common in both food sources and human tissues. To determine if maternal diet can influence milk RA concentration, breastfeeding women (n = 16) were enrolled in a 3-wk crossover study. Women initially consumed minimal amounts of food containing RA during week 1, then were assigned randomly to consume diets rich in high-fat dairy foods (and thus RA) during week 2 or 3. Milk was collected by complete breast expression twice during each experimental week. Current and chronic RA intakes were estimated by 3-d dietary records and food frequency questionnaires, respectively. Estimated chronic RA intakes ranged from 49 to 659 mg/d. Dietary RA intake was greater during the high compared to the low dairy period (291 +/- 75 vs. 15 +/- 24 mg/d, respectively; P < 0.0001). Milk contained more RA during the high than the low dairy period (13.5 +/- 0.1 vs. 8.2 +/- 0.4 mumol/g lipid, respectively; P < 0.0001). Milk lipid concentration was influenced by diet, such that lipid concentration was greater during the high than the low dairy period (46.6 +/- 5.0 vs. 38.3 +/- 1.6 mg/g milk, respectively; P < 0.05). Additionally, multiple regression analyses suggested that body mass index was the primary predictor of milk RA and lipid concentrations. In summary, these data indicate that both lipid and RA concentrations of human milk can be influenced by diet.

Prognosis versus actual outcome. IV. The effectiveness of clinical parameters and IL-1 genotype in accurately predicting prognoses and tooth survival.

BACKGROUND: Recently, a genetic marker (IL-1 genotype) that identifies individuals at higher risk for developing severe periodontal disease was discovered. A subgroup of the population reported on earlier was evaluated to determine if knowledge of the patient's IL-1 genotype would improve accuracy in assignment of prognoses and prediction of tooth loss. METHODS: This subgroup consisted of 42 patients (1,044 teeth) in maintenance care for 14 years; 16 tested IL-1 genotype-positive (IL-1GP). Nine were smokers, and 30 had a history of smoking, with an average of 29.44 pack years. A multiple Cox regression model and Kaplan-Meier survival plots were fit to the subset of patients to evaluate tooth loss. RESULTS: Both IL-1GP and heavy smoking were significantly related to tooth loss. A positive IL-1 genotype increased the risk of tooth loss by 2.7 times, and heavy smoking by 2.9 times. The combined effect of IL-1GP and heavy smoking increased the risk of tooth loss by 7.7 times. The value of clinical parameters traditionally used to assign prognosis was found to be dependent on IL-genotype and smoking status. In the model that included IL-1 genotype and heavy smoking, none of the clinical parameters added significantly to the model for tooth loss while mobility, probing depth, crown-to-root ratio, and percent bone loss added significantly to the model, which included IL-1 genotype in non-smokers. IL-1GP patients and patients who smoked heavily demonstrated a much worse tooth survival rate when compared to IL-1 genotype-negative patients and non-smokers, respectively. CONCLUSIONS: Knowledge of the patient's IL-1 genotype and smoking status will improve the clinician's ability to accurately assign prognosis and predict tooth survival. Clinical implications are as follows. Investigators were unable to judge which patients would be IL-GP or negative based on their clinical presentation or family history of tooth loss due to periodontal disease. Since periodontal diseases are multifactorial, knowledge of the patient's genotype is more important in predicting future risk than explaining past disease. Knowledge of IL-1 genotype status would be important in developing a treatment plan and predicting tooth survival for a new patient who smokes and presents with periodontal disease, especially if restorative care is needed. Knowledge of a maintenance patient's IL-1 status would help target therapy for non-responding areas; one would be less likely to take a "wait and see approach" with IL-1GP patients. IL-1 positive non-smokers can be successfully treated and maintained over long periods of time.

Periodontal plastic surgery.

Most periodontal esthetic procedures can be grouped into one of the following areas: crown lengthening, alveolar ridge preservation/augmentation, soft tissue grafts, and the correction of an open interproximal space. Soft tissue abnormalities, with the exception of the loss of the interproximal papilla, can be resolved predictably, improving esthetics and even creating restorative opportunities. In addition to a discussion of the pretreatment esthetic evaluation, an overview of periodontal plastic surgery procedures is presented, along with an example of the "Periodontal Enhancement Prescription," which facilitates communication between offices.

Safflower oil consumption does not increase plasma conjugated linoleic acid concentrations in humans.

Conjugated linoleic acid (CLA) is a mixture of positional and geometric isomers of linoleic acid (LA) with conjugated double bonds. CLA has anticarcinogenic properties and has been identified in human tissues, dairy products, meats, and certain vegetable oils. A variety of animal products are good sources of CLA, but plant oils contain much less. However, plant oils are a rich source of LA, which may be isomerized to CLA by intestinal microorganisms in humans. To investigate the effect of triacylglycerol-esterified LA consumption on plasma concentrations of esterified CLA in total lipids, a dietary intervention (6 wk) was conducted with six men and six women. During the intervention period a salad dressing containing 21 g safflower oil providing 16 g LA/d was added to the subjects' daily diets. Three-day diet records and fasting blood were obtained initially and during dietary and postdietary intervention periods. Although LA intake increased significantly during the dietary intervention, plasma CLA concentrations were not affected. Plasma total cholesterol and LDL-cholesterol concentrations were significantly lower after addition of safflower oil to the diet. In summary, consumption of triacylglycerol-esterified LA in safflower oil did not increase plasma concentrations of esterified CLA in total lipids.

Leptin is present in human milk and is related to maternal plasma leptin concentration and adiposity.

Leptin is elevated during pregnancy and may be involved in the regulation of milk production in women. Immunoreactive leptin was quantified in human milk by modified radioimmunoassay. Leptin concentration was higher in whole vs. skim milk fractions; however, leptin concentration was not correlated with percentage milk fat. Leptin concentrations in whole and skim milk were correlated with maternal plasma leptin concentrations, maternal body weight, body mass index, and tricep skinfold thickness, but not with plasma insulin concentration. These data provide the first evidence for the presence of leptin in human milk in the range of concentrations found in human plasma and indicate that the concentration of leptin in milk reflects maternal adiposity. Determining the biological role(s) of milk-borne leptin could add to our understanding of neonatal metabolism and the mechanisms underlying the development of body fat and obesity in humans.

Food supplementation during lactation shortens anestrus and elevates gonadotropins in rats.

Breastfeeding delays the resumption of ovulation in women, a phenomenon particularly important in less developed areas. Although human and animal studies indicate that undernutrition extends the period of lactational anestrus, the effect of improving nutritional status during lactation on this time of infecundability, however, is less clear. To assess the effects of food supplementation on duration of lactational anestrus, Sprague-Dawley rats were assigned to one of three dietary groups: 1) control (C), given unrestricted access to diet AIN-76A; 2) food-restricted (FR), fed 50% of the control intake; and 3) food-supplemented (FS), food-restricted until d 0 of lactation and thereafter given unrestricted access to diet AIN-76A. Time to first detectable proestrus was monitored starting on d 10 of lactation. Nursing behaviors and gonadotropin and prolactin concentrations were measured in both intact and ovariectomized dams on d 10, 15 and 20 of lactation; we report these data only on the ovariectomized group, which represents the more appropriate animal model of human reproductive physiology during lactation. Proestrus returned significantly (P < 0.0001) sooner in both FS (18.1 +/- 2.4 d) and C (18.0 +/- 2.9 d) than in FR (28.8 +/- 2.8 d) intact dams. FS rats had higher luteinizing hormone and follicle stimulating hormone concentrations than FR rats (P < 0.0001 for each). Prolactin concentrations were lower on d 20 than on d 10 of lactation for all groups (P < 0.02), but we found no effect of dietary treatment. FS rats spent more time away from their pups (P < 0.05) and experienced less suckling (P < 0.05) than FR rats on d 15 of lactation. These results indicate that food supplementation of previously underfed rats hastens the return of ovulation and is accompanied by alterations in nursing behaviors.

Documentation of second-by-second breastfeeding behaviors using a novel method.

The specific way nursing patterns influence the duration of postpartum amenorrhea is unknown. This may result from the shortcomings of available methods: the daily log and recall. We tested these against a novel method, an event monitor (EM), consisting of a wrist-worn stopwatch that stores events. Exclusively breastfeeding women (n = 11) were assigned randomly to use each of the three methods twice during a 2-week period surrounding Weeks 4, 8, and 12 postpartum. More nursing episodes were recorded with the EM than log during Week 4 (p < 0.03) and Week 8 (p < 0.02). EM captured more episodes than recall during all study periods (p < 0.004). The EM was considered as acceptable and accurate to mothers as the other methods and, therefore, is a useful option for documenting breastfeeding patterns.

Tetracycline fibers plus scaling and root planing versus scaling and root planing alone: similar results after 5 years.

This paper presents 5-year data pertaining to a subgroup of patients from a previous investigation who were treated with scaling and root planing plus tetracycline fibers. The parent study demonstrated that 6 months after therapy, scaling and root planing plus tetracycline fiber therapy was significantly better at reducing probing depth and gaining clinical attachment than scaling and root planing alone. However, the long-term data presented here show a regression from the original gains in clinical attachment levels in the fiber group. Ultimately, the use of fibers provided no significant advantage with regards to probing depth reduction or clinical attachment gain. Within the power of this study, which would have required 1.78 mm of change in clinical attachment to show a difference, there was no significant difference between the treatments at 5 years. This study underscores the need for additional long-term evaluation of this mode of therapy.

Soft tissue augmentation on previously restored root surfaces.

Three cases are presented demonstrating that soft tissue augmentation procedures can be accomplished on previously restored root surfaces. Diagnostic techniques to help determine ideal tooth length are discussed, and clinical examples of how to surgically manage the previously restored root surfaces are presented.

Naloxone administration does not relieve the inhibition of gonadotropin release in food-restricted, lactating rats.

Lactational anovulation is an important factor in determining birth spacing in women living in developing countries. Therefore, a more comprehensive understanding of the mechanisms involved in the relationships among lactation, nutrition and ovulation is important. This study was designed using the food-restricted, lactating rat to examine whether endogenous opioids might be involved in depressing gonadotropin release. Females were mated after 65 d of age and, beginning on d 42 of life, offered food in unrestricted amounts (control) or were food restricted to 50% of what the controls consumed. On d 15 of lactation, dams were injected with either naloxone hydrochloride (3 mg/kg body weight) or saline and killed 0, 15, 30 or 60 min later. Plasma was analyzed for luteinizing hormone, follicle-stimulating hormone and prolactin. Food restriction decreased plasma concentrations of luteinizing hormone and follicle-stimulating hormone (P < 0.005). Naloxone administration marginally influenced follicle stimulating hormone (P < 0.1), but not luteinizing hormone concentration regardless of diet group. The interaction among diet group, drug group and time of killing was significant for plasma prolactin concentration (P < 0.05). Food restriction lowered prolactin concentrations, but this effect was diminished with increasing time after injection of naloxone. Furthermore, the magnitude of the effect of food restriction was lessened and even reversed with treatment of naloxone. These results indicate that endogenous opioids are not the primary mechanism suppressing luteinizing hormone release in food-restricted lactating rats.

Prognosis versus actual outcome. III. The effectiveness of clinical parameters in accurately predicting tooth survival.

Tooth loss for 100 treated periodontal patients (2,509 teeth) under maintenance care was evaluated to determine the effectiveness of commonly taught clinical parameters utilized in the assignment of prognosis in accurately predicting tooth survival. Previous studies in this series evaluated prognosis as a surrogate variable representing the condition of the tooth at a particular point. In this study, survival analysis was used to evaluate the relationship of these common clinical parameters to an actual end point, tooth loss. Robust log rank tests indicated that initial probing depth, initial furcation involvement, initial mobility, initial crown-to-root ratio, and initial root form were all associated with tooth loss. In addition, smoking and increased initial bone loss were both found to be associated with increased risk of tooth loss while fixed abutment status was associated with a decreased risk of tooth loss. A Cox proportional hazards regression model showed that initial probing depth, initial furcation involvement, initial mobility, initial percent bone loss, presence of a parafunctional habit without a biteguard, and smoking were all associated with an increased risk of tooth loss. This model suggests that patients are twice as likely to loose their teeth if there is increasing mobility, if they have a parafunctional habit and do not wear a biteguard, or if they smoke. From these data there does appear to be a relationship between the assigned prognosis and tooth loss. Teeth with worse prognosis have a worse survival rate, but the commonly taught clinical parameters used in the traditional method of assignment of prognosis do not adequately explain that relationship. Furthermore, initial prognosis did not adequately explain the condition of the tooth or accurately predict the tooth's survival. These results seem to indicate that the effect of these clinical parameters on tooth survival is only partially reflected in the assigned prognosis initially, suggesting that perhaps some of the clinical parameters should be weighed more heavily than others when assigning prognosis. Further studies are needed to develop a more accurate method for the assignment of prognosis.