Peroxisome proliferator-activated receptor-(gamma) receptor ligand partially prevents the development of endometrial explants in baboons: a prospective, randomized, placebo-controlled study

A prospective, randomized, placebo-controlled study was conducted in a baboon model to determine if a thiazolidinedione agonist of peroxisome proliferator-activated receptor-gamma, pioglitazone, can impede the development of endometriosis. Endometriosis was induced using laparoscopic, intrapelvic injection of eutopic menstrual endometrium, previously incubated with placebo or pioglitazone for 30 min, in 12 female baboons with a normal pelvis that had undergone at least one menstrual cycle since the time of captivity. At this point, the 12 baboons were randomized into two groups and treated from the day of induction. They received either PBS tablets (n = 6, placebo control, placebo tablets once a day by mouth) or pioglitazone (n = 6, test drug, 7.5 mg by mouth each day). A second and final laparoscopy was performed in the baboons to record the extent of endometriotic lesions between 24 and 42 d after induction (no difference in length of treatment between the two groups, P = 0.38). A videolaparoscopy was performed to document the number and surface area of endometriotic lesions. The surface area and volume of endometriotic lesions were significantly lower in pioglitazone treated baboons than the placebo group (surface area, 48.6 vs. 159.0 mm(2), respectively, P = 0.049; vol, 23.7 vs. 131.8 mm(3), respectively, P = 0.041). The surface area (3.5 vs. 17.8 mm(2), P = 0.017, pioglizatone vs. placebo) and overall number (1.5 vs. 9.5, P = 0.007, pioglizatone vs. placebo) of red lesions were lower in the pioglitazone group. A peroxisome proliferator-activated receptor-gamma ligand, pioglitazone, effectively reduced the initiation of endometriotic disease in the baboon endometriosis model. Using this animal model, we have shown that thiazolidinedione is a promising drug for preventive treatment of endometriosis.

3,4-Dehydrodebrisoquine, a novel debrisoquine metabolite formed from 4-hydroxydebrisoquine that affects the CYP2D6 metabolic ratio

Considerable unexplained intersubject variability in the debrisoquine metabolic ratio (urinary debrisoquine/4-hydroxydebrisoquine) exists within individual CYP2D6 genotypes. We speculated that debrisoquine was converted to as yet undisclosed metabolites. Thirteen healthy young volunteers, nine CYP2D6*1 homozygotes [extensive metabolizers (EMs)] and four CYP2D6*4 homozygotes [poor metabolizers (PMs)] took 12.8 mg of debrisoquine hemisulfate by mouth and collected 0- to 8- and 8- to 24-h urines, which were analyzed by gas chromatography-mass spectrometry (GCMS) before and after treatment with beta-glucuronidase. Authentic 3,4-dehydrodebrisoquine was synthesized and characterized by GCMS, liquid chromatography-tandem mass spectrometry, and (1)H NMR. 3,4-Dehydrodebrisoquine is a novel metabolite of debrisoquine excreted variably in 0- to 24-h urine, both in EMs (3.1-27.6% of dose) and PMs (0-2.1% of dose). This metabolite is produced from 4-hydroxydebrisoquine in vitro by human and rat liver microsomes. A previously unstudied CYP2D6*1 homozygote was administered 10.2 mg of 4-hydroxydebrisoquine orally and also excreted 3,4-dehydrodebrisoquine. EMs excreted 6-hydroxydebrisoquine (0-4.8%) and 8-hydroxydebrisoquine (0-1.3%), but these phenolic metabolites were not detected in PM urine. Debrisoquine and 4-hydroxydebrisoquine glucuronides were excreted in a highly genotype-dependent manner. A microsomal activity that probably does not involve cytochrome P450 participates in the further metabolism of 4-hydroxydebrisoquine, which we speculate may also lead to the formation of 1- and 3-hydroxydebrisoquine and their ring-opened products. In conclusion, this study suggests that the traditional metabolic ratio is not a true measure of the debrisoquine 4-hydroxylation capacity of an individual and thus may, in part, explain the wide intragenotype variation in metabolic ratio.

A 4-year study on clinical characteristics of children hospitalized with rotavirus gastroenteritis

Rotavirus (RV) is a frequent cause of severe gastroenteritis (GE) in children. With the licensure of new RV vaccines, data on the burden of disease are important regarding immunization strategies. We reviewed the medical records of children hospitalized with RV infection in our institution between July 2002 and March 2006. Relevant data were extracted in a standardized fashion from records of hospitalized children with a positive RV antigen test in a stool sample. Severity of disease was graded by the 20-point Vesikari score. Population data were obtained from the Federal Office of Statistics. Six hundred eighty-six RVGE were identified and records of 608 hospitalizations (in 607 children) were available. In 539 (89%) cases, RVGE was the primary reason for hospitalization and 69 (11%) were nosocomial infections; yearly peaks occurred between February and May. Cumulative incidence of RVGE was 26.7/1,000 children <3 years of age. Median age of 539 children (55.6% male) with primary RVGE was 1.4 years and median stay in the hospital for both community acquired and nosocomial RVGE was 4 days (interquartile range 3-5). Thirtypercent and 94% of RV hospitalizations were in children <1 and <3 years of age, respectively. Mean Vesikari score was 15 (range 6-20; 96% >11). Intravenous fluids were administered in 378 (70%) patients, 130 (24%) patients were rehydrated via nasogastral tube, and 31 (5.7%) received rehydration by mouth. RVGE causes a substantial burden in children with an estimated risk for hospitalization due to RVGE of one in 37 children <3 years of age.

Prospective clinical study evaluating the long-time adjunctive use of chlorhexidine after one-stage full-mouth SRP

OBJECTIVES: Scaling and root planing are the causal procedure in the treatment of periodontitis. Many attempts have been made to improve the outcome. The aim of this study was to verify the influence of the extended use of chlorhexidine after one-stage full-mouth (FM) SRP in patients with chronic periodontitis on the clinical outcome after 3 months. METHODS: Eighty-one patients with pockets > or =5 mm were treated by FM. All patients rinsed additionally with 0.2% chlorhexidine (CHX) twice daily over 3 months. Plaque index, bleeding on probing, probing depth (PD) and clinical attachment level (CAL) were recorded at baseline and after 1 and 3 months. RESULTS: In the test group, all variables were significantly improved after 1 and 3 months. Mean reduction of PD and CAL gain was 2.25 +/- 1.08 and 1.67 +/- 1.08 after 1 and 2.99 +/- 1.11 and 2.33 +/- 1.31 after 3 months respectively. CONCLUSIONS: Over 3 months of extended use of CHX mouth rinse after SRP showed slightly but statistically significant better results.

Comparison of the effects of cetylpyridinium chloride with an essential oil mouth rinse on dental plaque and gingivitis - a six-month randomized controlled clinical trial

OBJECTIVE: To compare the effects of an experimental mouth rinse containing 0.07% cetylpyridinium chloride (CPC) (Crest Pro-Health) with those provided by a commercially available mouth rinse containing essential oils (EOs) (Listerine) on dental plaque accumulation and prevention of gingivitis in an unsupervised 6-month randomized clinical trial. MATERIAL AND METHODS: This double-blind, 6-month, parallel group, positively controlled study involved 151 subjects balanced and randomly assigned to either positive control (EO) or experimental (CPC) mouth rinse treatment groups. At baseline, subjects received a dental prophylaxis procedure and began unsupervised rinsing twice a day with 20 ml of their assigned mouthwash for 30 s after brushing their teeth for 1 min. Subjects were assessed for gingivitis and gingival bleeding by the Gingival index (GI) of Löe ; Silness (1963) and plaque by the Silness ; Löe (1964) Plaque index at baseline and after 3 and 6 months of rinsing. At 3 and 6 months, oral soft tissue health was assessed. Microbiological samples were also taken for community profiling by the DNA checkerboard method. RESULTS: Results show that after 3 and 6 months of rinsing, there were no significant differences (p=0.05) between the experimental (CPC) and the positive control mouth rinse treatment groups for overall gingivitis status, gingival bleeding, and plaque accumulation. At 6 months, the covariant (baseline) adjusted mean GI and bleeding sites percentages for the CPC and the EO rinses were 0.52 and 0.53 and 8.7 and 9.3, respectively. Both mouth rinses were well tolerated by the subjects. Microbiological community profiles were similar for the two treatment groups. Statistically, a significant greater reduction in bleeding sites was observed for the CPC rinse versus the EO rinse. CONCLUSION: The essential findings of this study indicated that there was no statistically significant difference in the anti-plaque and anti-gingivitis benefits between the experimental CPC mouth rinse and the positive control EO mouth rinse over a 6-month period.

A systematic review of the effects of full-mouth debridement with and without antiseptics in patients with chronic periodontitis

OBJECTIVES: To assess the clinical and microbiological effects of full-mouth debridement with (FMD) and without the use of antiseptics [full-mouth scaling and root planing (FMSRP)] in comparison with conventional staged debridement (CSD) in patients with chronic periodontitis after at least 6 months. MATERIAL AND METHODS: The search in MEDLINE (PubMed), covering a period of 1975 to October 2007, and hand searching yielded 207 titles. Forty-two abstracts and 17 full-text articles were screened for inclusion. RESULTS: Twelve articles allowed a direct comparison of FMD with CSD, FMSRP with CSD and FMD with FMSRP. Probing pocket depth reductions were significantly greater (0.2 mm) with FMD and FMSRP compared with CSD. Moreover, a modest reduction in BOP (9%) favoured FMD. Likewise, clinical attachment levels were improved by 0.2-0.4 mm in favour of FMD and FMSRP, respectively. In all comparisons, single-rooted teeth and deep pockets benefitted slightly from FMD and FMSRP. Limited differences in the changes of the subgingival microbiota were noted between the treatment modalities. CONCLUSIONS: Despite the significant differences of modest magnitude, FMD or FMSRP do not provide clinically relevant advantages over CSD. Hence, all three treatment modalities may be recommended for debridement in the initial treatment of patients with chronic periodontitis.

Early loading of sandblasted and acid-etched implants: a randomized-controlled double-blind split-mouth study. Five-year results

OBJECTIVES: The aim of the present split-mouth study is to assess the peri-implant conditions around early-loaded sandblasted and acid-etched (SLA) implants, 5 years after abutment connection and to compare, in the same patients, the results obtained with a standard protocol using identical implants with a TPS surface. MATERIAL AND METHODS: Surgical procedure was performed by the same operator and was identical at test (SLA) and control (TPS) sites, in 32 healthy patients. Abutment connection was carried out at 35 N cm 6 weeks postsurgery for test sites and 12 weeks for the controls. Patients were seen regularly, for control and professional cleaning. At 60 months, clinical measures and radiographic bone changes were recorded by the same operator, blind to the type of surface of the implant, on 27 patients, as five patients were lost to follow-up. RESULTS: A total number of 106 implants were examined. No implant was lost. No significant differences were found with respect to the presence of plaque [modified plaque index (mPI) 0.27+/-0.56 vs. 0.32+/-0.54], bleeding on probing (29% vs. 32%), mean pocket depth (3.2+/-1 vs. 3.2+/-1 mm) or mean marginal bone loss (0.32+/-1.04 vs. 0.44+/-1.12 mm) between test and control. Four implants that presented 'spinning' at the time of abutment connection presented no significant differences from the rest of the test sites. CONCLUSION: The results of this prospective study confirm that SLA implants, under defined conditions, are suitable for early loading at 6 weeks in both the mandible and the maxilla. Limited implant spinning, occasionally found at abutment connection, produces no detrimental effect on the clinical outcome when properly handled.

The effect of a tin-containing fluoride mouth rinse on the bond between resin composite and erosively demineralised dentin

OBJECTIVES To evaluate the effect of a tin-containing fluoride (Sn/F) mouth rinse on microtensile bond strength (μTBS) between resin composite and erosively demineralised dentin. MATERIALS AND METHODS Dentin of 120 human molars was erosively demineralised using a 10-day cyclic de- and remineralisation model. For 40 molars, the model comprised erosive demineralisation only; for another 40, the model included treatment with a NaF solution; and for yet another 40, the model included treatment with a Sn/F mouth rinse. In half of these molars (n = 20), the demineralised organic matrix was continuously removed by collagenase. Silicon carbide paper-ground, non-erosively demineralised molars served as control (n = 20). Subsequently, μTBS of Clearfil SE/Filtek Z250 to the dentin was measured, and failure mode was determined. Additionally, surfaces were evaluated using SEM and EDX. RESULTS Compared to the non-erosively demineralised control, erosive demineralisation resulted in significantly lower μTBS regardless of the removal of demineralised organic matrix. Treatment with NaF increased μTBS, but the level of μTBS obtained by the non-erosively demineralised control was only reached when the demineralised organic matrix had been removed. The Sn/F mouth rinse together with removal of demineralised organic matrix led to significantly higher µTBS than did the non-erosively demineralised control. The Sn/F mouth rinse yielded higher μTBS than did the NaF solution. CONCLUSIONS Treatment of erosively demineralised dentin with a NaF solution or a Sn/F mouth rinse increased the bond strength of resin composite. CLINICAL RELEVANCE Bond strength of resin composite to eroded dentin was not negatively influenced by treatment with a tin-containing fluoride mouth rinse.

Clinical outcomes following subgingival application of a novel erythritol powder by means of air polishing in supportive periodontal therapy: a randomized, controlled clinical study

OBJECTIVES The aim of this prospective, randomized, controlled clinical study was to compare the clinical outcomes of the subgingival treatment with erythritol powder by means of an air-polishing (EPAP) device and of scaling and root planing (SRP) during supportive periodontal therapy (SPT). METHOD AND MATERIALS 40 patients enrolled in SPT were randomly assigned to two groups of equal size. Sites had to show signs of inflammation (bleeding on probing [BOP]-positive) and a probing pocket depth (PPD) of ≥ 4 mm, however, without presence of detectable subgingival calculus. During SPT, these sites were treated with EPAP or SRP, respectively. Full mouth and site-specific plaque indices, BOP, PPD, and clinical attachment level (CAL) were recorded at baseline (BL) and at 3 months, whereas the percentage of study sites positive for BOP (BOP+) was considered as primary outcome variable. Additionally, patient comfort using a visual analog scale (VAS) and the time needed to treat per site was evaluated. RESULTS At 3 months, mean BOP level measured 45.1% at test sites and 50.6% at control sites, respectively, without a statistically significant difference between the groups (P > .05). PPD and CAL slightly improved for both groups with comparable mean values at 3 months. Evaluation of patient tolerance showed statistically significantly better values among patients receiving the test treatment (mean VAS [0-10], 1.51) compared to SRP (mean VAS [0-10], 3.66; P = .0012). The treatment of test sites was set to 5 seconds per site. The treatment of control sites, on the other hand, lasted 85 seconds on average. CONCLUSION The new erythritol powder applied with an air-polishing device can be considered a promising modality for repeated instrumentation of residual pockets during SPT. CLINICAL RELEVANCE With regard to clinical outcomes during SPT, similar results can be expected irrespective of the two treatment approaches of hand instrumentation or subgingival application of erythritol powder with an air-polishing device in sites where only biofilm removal is required.

Evaluation of the benefit of emergency vaccination in a foot-and-mouth disease free country with low livestock density

Foot-and-mouth disease (FMD) is highly contagious and one of the most economically devastating diseases of cloven-hoofed animals. Scientific-based preparedness about how to best control the disease in a previously FMD-free country is therefore essential for veterinary services. The present study used a spatial, stochastic epidemic simulation model to compare the effectiveness of emergency vaccination with conventional (non-vaccination) control measures in Switzerland, a low-livestock density country. Model results revealed that emergency vaccination with a radius of 3 km or 10 km around infected premises (IP) did not significantly reduce either the cumulative herd incidence or epidemic duration if started in a small epidemic situation where the number of IPs is still low. However, in a situation where the epidemic has become extensive, both the cumulative herd incidence and epidemic duration are reduced significantly if vaccination were implemented with a radius of 10 km around IPs. The effect of different levels of conventional strategy measures was also explored for the non-vaccination strategy. It was found that a lower compliance level of farmers for movement restrictions and delayed culling of IPs significantly increased both the cumulative IP incidence and epidemic duration. Contingency management should therefore focus mainly on improving conventional strategies, by increasing disease awareness and communication with stakeholders and preparedness of culling teams in countries with a livestock structure similar to Switzerland; however, emergency vaccination should be considered if there are reasons to believe that the epidemic may become extensive, such as when disease detection has been delayed and many IPs are discovered at the beginning of the epidemic.

A patterned abrasion caused by the impact of a cartridge case may simulate an atypical muzzle imprint mark.

In contact shots, the muzzle imprint is an informative finding associated with the entrance wound. It typically mirrors the constructional components being in line with the muzzle or just behind. Under special conditions, other patterned skin marks located near a gunshot entrance wound may give the impression to be part of the muzzle imprint. A potential mechanism causing a patterned pressure abrasion in close proximity to the bullet entrance site is demonstrated on the basis of a suicidal shot to the temple. The skin lesion in question appeared as a ring-shaped excoriation with a diameter corresponding to that of the cartridge case. Two hypotheses concerning the causative mechanism were investigated by test shots: - After being ejected, the cartridge case ricocheted inside a confined space (car cabin in the particular case) and secondarily hit the skin near the gunshot entrance wound. - The ejection of the cartridge case failed so that the case became stuck in the ejection port and its mouth contacted the skin when the body collapsed after being hit.

Evidence for Emergency Vaccination Having Played a Crucial Role to Control the 1965/66 Foot-and-Mouth Disease Outbreak in Switzerland.

Foot-and-mouth disease (FMD) is a highly contagious disease that caused several large outbreaks in Europe in the last century. The last important outbreak in Switzerland took place in 1965/66 and affected more than 900 premises and more than 50,000 animals were slaughtered. Large-scale emergency vaccination of the cattle and pig population has been applied to control the epidemic. In recent years, many studies have used infectious disease models to assess the impact of different disease control measures, including models developed for diseases exotic for the specific region of interest. Often, the absence of real outbreak data makes a validation of such models impossible. This study aimed to evaluate whether a spatial, stochastic simulation model (the Davis Animal Disease Simulation model) can predict the course of a Swiss FMD epidemic based on the available historic input data on population structure, contact rates, epidemiology of the virus, and quality of the vaccine. In addition, the potential outcome of the 1965/66 FMD epidemic without application of vaccination was investigated. Comparing the model outcomes to reality, only the largest 10% of the simulated outbreaks approximated the number of animals being culled. However, the simulation model highly overestimated the number of culled premises. While the outbreak duration could not be well reproduced by the model compared to the 1965/66 epidemic, it was able to accurately estimate the size of the area infected. Without application of vaccination, the model predicted a much higher mean number of culled animals than with vaccination, demonstrating that vaccination was likely crucial in disease control for the Swiss FMD outbreak in 1965/66. The study demonstrated the feasibility to analyze historical outbreak data with modern analytical tools. However, it also confirmed that predicted epidemics from a most carefully parameterized model cannot integrate all eventualities of a real epidemic. Therefore, decision makers need to be aware that infectious disease models are useful tools to support the decision-making process but their results are not equal valuable as real observations and should always be interpreted with caution.