[Biocompatibility of composites--literature review].

Composites are a large family of materials composed of polymer matrices imbedded with different types of fillers. The specific properties achievable with diverse chemical combinations provide for a wide range of implications in many industrial fields. Materials designed for medical use must not only efficiently serve the purpose of their use, but also be biocompatible to the tissues they contact and the body as a whole. Dental composites and their components have been studied intensely to assess their potential local and systemic side effects, to establish biocompatibility, in order to receive the proper conformation allowing their safe clinical use. The purpose of the following paper is to summarize several aspects of research focused on determining cytotoxicity, genotoxicity, carcinogenicity, hypersensitivity, and microbial effects of composite components, in order to ascertain in fact how biocompatible dental composite materials are. Research shows that several chemical components may be released from different types of composites, and are able to cause toxic, allergic, mutagenic and other biological effects. However, because of the small amounts applied and the unique conditions in the oral cavity, the clinical relevance of these findings is questionable. Nevertheless, caution should be taken when using these materials, to avoid possible negative outcomes. Future studies should focus on targeting most toxic components and finding biocompatible alternatives and development of materials with high polymerization efficiency in order to reduce the amount of leachable components.

[A tooth or an implant--literature based decision making].

The common use of dental implants in the daily practice led to a profound change in the available treatment strategies. The option of replacing a diagnosed doubtful tooth with an implant has become widely accepted and often used. The prognosis systems in use today are based on the three major disciplines: endodontics, periodontics and prosthodontics. Combining these three may impair and bias the decision making process and increase the tendency to base it on subjective clinical experience and personal preference. Reading and reviewing the relevant literature gives no clear tool for use. Root canal treatment is considered a highly predictable treatment procedure and a treated tooth is affected mainly by the quality and type of the fabricated restoration and the risk of caries. Periodontal treatment followed by a suitable maintenance regimen will likely allow long term tooth survival. When comparing the success rates of natural teeth rehabilitation versus implant supported restorations, it appears that with implants an additional treatment is demanded along the years. This coincides with the fact that to date there is no consensus regarding the extent of perimplantitis and perimucositis that is to be expected around a restored implant. In addition, a peri implant tissue problem or a failure of a dental implant may prove to be more challenging than a failure of a tooth. It is important to remember that a dental implant is made to substitute a missing tooth and it is a treatment modality with known and clear indications for rehabilitation of an edentulous space. The aim of this paper is to review and discuss the various aspects of whether to maintain a compromised or a doubtful tooth or to prefer a treatment modality using dental implants. In conclusion it is advised here, to incorporate the discussed issues in the decision making process towards the most suitable treatment plan.

[Retention or adhesion?].

One of the reasons for immediate or late failure of restorations is the detachment of the restoration from the tooth. Retention for the restoration could be achieved from axial walls (macromechanical retention) or from adhesion of the restoration to the remaining tooth structure. Adhesion relies on bonding of resin cement to enamel or dentin on one side and to the restorative material on the other side. Bonding to enamel is predictable. Good bonding to dentin is more of a challenge especially with indirect restorations. In those cases the restoration is delivered usually a few days after the tooth was prepared during this time the exposed dentin might be contaminated or damaged. The question is whether you can rely on adhesion when cementing indirect restorations? In order to achieve the maximal bonding strength to dentin, the hybrid layer on the dentin must be built immediately after tooth preparation. This procedure is called Immediate Dentin Sealing. In vitro and clinical studies have shown better performance of restorations cemented following the IDS procedure. The article discusses the rational and the protocol of this procedure. A clinical case is presented as an example for the possibilities following this philosophy.

Stability and surface activity of lactate dehydrogenase in spray-dried trehalose.

The stability of the model protein lactate dehydrogenase (LDH) during spray-drying and also on subsequent dry storage was examined. Trehalose was used as a carrier. The spray-drying temperatures Tinlet and Toutlet have a measurable effect on LDH inactivation. Low Tinlet produced the least process inactivation, but gave a high residual moisture content making the protein's storage stability poor. High Tinlet reduced residual moisture and improved storage stability, but at the cost of high process inactivation. As already found for other systems, addition of a surfactant (in this case polysorbate 80) could ameliorate process inactivation of LDH at Tinlet = 150 degreesC. Surfactant had, however, a deleterious effect on storage stability of LDH, the vital factor being the molar ratio of surfactant/protein in the dried product. By using electron spectroscopy it was shown that LDH has a 10 times higher surface concentration in the dried trehalose particles than expected for a homogeneous distribution. Surface tension measurements at the water/air interface proved that LDH is surface active, although the Gibbs equation appeared to be inapplicable. Calculations of spray-droplet formation time and drying time indicate than the extent of diffusion-driven LDH adsorption to the liquid/air interface is sufficient to account for the measured amount of LDH inactivation during spray-drying. The presence of 0.1% polysorbate 80 to the spray solution prevents LDH from appearing at the surface of the dried particles. As a negative control, the phosphatide Lipoid E 80 does not prevent the appearance of LDH in the surface according to electron spectroscopy and does not therefore prevent LDH inactivation during spray-drying at Tinlet = 150 degreesC.

A non-interventional phase IV Belgian survey to assess the antiviral effectiveness of pegylated interferon-alpha-2b and ribavirin treatment according to the stage of liver fibrosis in previously untreated patients with genotype 1/4/5/6 chronic hepatitis C (PRACTICE).

BACKGROUND AND STUDY AIMS: This was an observational, non-interventional, multicenter, phase IV study, in patients with genotype 1/4/5/6 chronic hepatitis C (CHC). The primary objectives were to evaluate SVR in patients with no or minimal fibrosis (METAVIR F0-F1) versus well established fibrosis (F2-F4), and to estimate response on Weeks 12, 24 and 48 on treatment in previously untreated patients with genotypes 1/4/5/6 CHC. PATIENTS AND METHODS: 538 patients treated with pegylated interferon alfa 2b 1.5 mcg/kg in combination with ribavirin 800-1200 mg/day were enrolled in 55 sites in Belgium and Luxembourg, 505 being considered for the analysis. 40% of the patients were female and 60% male, the average age was 47.5 years, 10.5% were 65 or older. RESULTS: SVR was observed in 35% of the patients, EVR in 68%, of which pEVR in 33% and cEVR in 35%. SVR was observed in 43% of the low fibrosis group (F0, F1) and 30% of the high fibrosis group (F2, F3, F4) (p = 0.005). SVR rates were 34% for genotype 1, 37% for genotype 4, and 47% for genotype 5 (NS). Multivariate analysis showed that EVR and baseline METAVIR score are independent prognostic factors for SVR. CONCLUSIONS: This trial confirms that fibrosis stage and early viral response are the most important key-factors to predict sustained response, suggesting that the earlier patients are treated, the better the outcome. Non-invasive techniques enable us to closely monitor progression of fibrosis, allowing a better selection of patients for antiviral treatment in the DAA-era.

Response of Black African patients with hepatitis C virus genotype 4 to treatment with peg-interferon and ribavirin.

AIM: To compare responses to therapy of Black African (BA) and non-Black African (non- BA) patients with hepatitis C virus genotype 4 (HCV-4) residing in Belgium. METHODS: In this retrospective multicenter study, 473 patients with HCV-4 were selected from databases at 7 Belgian centers; 209 treatment-naive patients (154 BA) had received treatment with peg-interferon (peg-IFN) plus ribavirin (RBV) and were included in the study. RESULTS: There was a greater percentage of female patients in the BA group than in the non- BA group; BA patients were also older, had a greater body mass index, and more frequently had abnormal glucose metabolism. The route of contamination was more frequently unknown in BA than in non-BA patients and BA patients had more HCV-4 subtypes. There were no differences in other demographic factors between the groups. Sustained viral response (SVR) and complete early viral response rates were significantly lower and relapse rates significantly higher in BA than in non-BA patients. There were no differences between groups in rates of dose modification or in drug tolerance. CONCLUSION: In our cohort, treatment-naive BA patients with HCV-4 who were treated with peg-IFN and ribavirin had a much lower SVR rate than treatment-naive non-BA patients with HCV-4 who were treated with peg-IFN and ribavirin, and a higher relapse rate, possibly related to a weaker response to interferon-based therapy. Treatment may need to be adapted in this population.

A randomized, open-label, multicenter study evaluating the efficacy of peginterferon alfa-2a versus interferon alfa-2a, in combination with ribavirin, in naïve and relapsed chronic hepatitis C patients.

BACKGROUND/AIMS: A large multicenter trial to compare the efficacy of peginterferon alfa-2a with interferon alfa-2a, in combination with ribavirin, in chronic hepatitis C patients. Efficacy data for prior relapsers are reported because treatment recommendations for this patient population are not well defined. PATIENTS AND METHODS: This study was a multicenter, prospective, randomized clinical trial. The primary efficacy endpoint was sustained virologic response in naive patients (n = 348) and relapsers (n = 95). RESULTS: Sustained virologic response rates were similar in naïve patients and relapsers, both for non-pegylated and pegylated interferon (respectively 27 and 26% and 54 and 43%). Pegylated interferon given for 48 weeks did not improved the relapse rate: 15.9 and 27.3% for non-pegylated and 16.7 and 30.4% for pegylated interferon, naïve vs relapsers respectively. Stepwise logistic regression analysis revealed a significant association between slow response (detectable HCV RNA at week 12 and undetectable at week 24) and relapse in patients with an end-of-treatment response (55% versus 13% respectively; p = 0.02; odds ratio = 6.07). CONCLUSIONS: This trial confirms the value of using peginterferon alfa-2a in both naïve and relapsed patients and provides support for a more tailored approach to treatment for relapsers and particulary for patients with a slow viral response.

Effectiveness and tolerability of pegylated interferon alfa-2b in combination with ribavirin for treatment of chronic hepatitis C: the PegIntrust study.

BACKGROUND AND STUDY AIMS: Large international clinical trials conducted in the past 5 years rapidly improved the treatment of chronic hepatitis C; however, it is unclear whether the advances seen in clinical trials are being paralleled by similar improvements in routine clinical practice. PegIntrust is a Belgian community-based trial evaluating the sustained virological response. PATIENTS AND METHODS: Observational study of 219 patients receiving pegylated interferon alfa-2b (1.5 microg/kg/wk) and weight-based ribavirin (800-1200 mg/day) for 48 weeks. Primary study end point was sustained virological response (SVR), defined as undetectable HCV RNA 6 months after the completion of treatment. RESULTS: In total, 108 patients (49.3 %) had undetectable HCV RNA at the end of therapy, 91 (41.6%) attaining SVR. Of the 111 patients without an end-of-treatment response, 28 were non-responders, and 21 had virological breakthrough. In total, 134 patients attained early virological response (EVR); 88 (65.7%) of those patients attained SVR. In contrast, 82 (96.5 %) of the 85 patients who did not attain EVR also did not attain SVR. Age, fibrosis score and baseline viral load were identified as important predictors of treatment outcome. The most frequently reported serious adverse events resulting in treatment discontinuation were anemia (n = 10), fatigue/asthenia/malaise (n = 6) and fever (n = 3). CONCLUSION: Our data indicate that treatment of chronic hepatitis C with PEG-IFN alfa-2b plus weight-based ribavirin results in favourable treatment outcomes in a Belgian cohort of patients treated in community-based clinical practice.

Clinical trial: a randomized trial of pegylated-interferon-alpha-2a plus ribavirin with or without amantadine in treatment-naïve or relapsing chronic hepatitis C patients.

BACKGROUND: The combination therapy of pegylated-interferon-alpha2a plus ribavirin is considered as the standard of care for patients with chronic hepatitis C. A sustained viral response is obtained in 40-50% of naïve patients with genotype 1 and in around 80% of naïve patients with genotype 2 or 3. AIM: To assess whether amantadine, added to the conventional combination therapy, could improve the treatment efficacy. METHODS: In all, 630 patients (intent-to-treat population) with chronic hepatitis C were randomized into two groups: 316 patients (treatment group) received pegylated-interferon-alpha2a (180 microg once weekly) plus ribavirin (1000-1200 mg/daily) with amantadine (200 mg/daily); 314 patients (control group) received pegylated-interferon-alpha2a (180 microg once weekly) plus ribavirin (1000-1200 mg/daily) without amantadine. The duration of the treatment was 48 weeks for genotypes 1, 4, 5 and 6, and 24 weeks for genotypes 2 and 3. RESULTS: There was no statistically significant difference between treatments groups for any of the variables tested for. Subgroups of patients likely to take advantage of the addition of amantadine were not identified. CONCLUSIONS: This large study definitely excludes the role of amantadine in addition of conventional combination therapy in the treatment of chronic hepatitis C patients.

Weekly pegylated interferon alpha-2b vs daily interferon a-2b versus standard regimen of interferon a-2b in the treatment of patients with chronic hepatitis C virus infection.

BACKGROUND AND STUDY AIMS: The combination of Pegylated (PEG)interferon alpha-2b and ribavirin is considered to be the standard treatment for naïve chronic hepatitis C patients. Study aims are to evaluate the differences between standard interferon and PEG-interferon by conducting a multi-centre, controlled randomized trial comparing 3 groups. Group A : daily interferon alfa-2b at a dose of 4 MIU + ribavirin, Group B : PEG-interferon alfa-2b at a dose of 100 mcg/week + ribavirin; Group C: interferon alfa-2b at a dose of 3 MIU TIW + ribavirin PATIENTS AND METHODS: Multicentrer, open label study including naïve chronic Hepatitis C Virus patients randomised in three groups with a ratio of 2:2:1. Group A: daily interferon alpha-2b (4 MIU s.c. for patients > 65 kg or 0.06 MIU/kg < 65 kg) and ribavirin, group B: PEG-interferon alpha-2b (100 microg s.c. weekly for patients > 65 kg or 1.5 microg/kg weekly for patients < 65 kg) and ribavirin and group C (reference arm) : interferon alpha-2b (3MIU s.c. TWI) and ribavirin. The duration of the treatment was 48 weeks for all 3 groups, with a 6 month follow-up period. 336 patients were enrolled in the study and included in the intention-to-treat analysis; 78 never started treatment (35 in group A, 28 in group B and 15 in group C): 101 in group A, 98 in group B and 59 in group C. RESULTS: Demographic data, PCR results and reasons for early withdrawal have been statistically analysed. At baseline, the 3 groups did not show any statistical difference regarding age, gender, race, genotypes and METAVIR score. At week 24 on treatment, HCV ribonucleic acid RNA was undetectable in 87% in group A, in 79% in group B and in 69% in group C. At the end of treatment, 73% 74% and 58% respectively, had a negative PCR result. At week 24 of follow-up, these results were 71%, 64% and 48%, respectively. When comparing the efficacy of the daily interferon (+ ribavirin) and the PEG-interferon (+ ribavirin) regimen, no statistical difference was found (p = 0.32). In group A, 38% of drop-outs were due to adverse events compared to 37% in group B and 58% in group C. No statistical differences were observed regarding safety. CONCLUSION: Daily weight based interferon alpha-2b dosing and PEG interferon alpha-2b weighed based dosing once weekly both in combination with Ribavirin offer the same efficacy and safety rates.

Surface composition of spray-dried particles of bovine serum albumin/trehalose/surfactant.

PURPOSE: To characterize via electron spectroscopy for chemical analysis (ESCA) the surface of spray-dried particles of trehalose plus a protein (bovine serum albumin). Additionally, to show how and why the addition of a surfactant reduces protein adsorption, and by this mechanism could reduce protein instability during spray-drying. METHODS: Aqueous solutions of trehalose plus bovine serum albumin (bSA) were spray-dried with increasing concentrations of surfactant. The surface composition of the dried particles was examined using ESCA. RESULTS: The presence of bSA, trehalose, and surfactant could be detected quantitatively in the particle surface. In the absence of surfactant the bSA had a large surface excess concentration (determined via its N atoms). Increasing concentration of polysorbate 80 reduced the surface excess of bSA in a concentration-dependent manner. At high polysorbate 80 concentration (5 mg/ml) the bSA could no longer be detected in solid surface. Using sodium dodecyl sulfate it was shown that the reduction in surface concentration of the protein is accompanied by a simultaneous increase in surface concentration of the surfactant. Neither surfactant fully covers the surface at the point of complete protein exclusion. CONCLUSIONS: ESCA provides a direct, quantitative measure of the surface composition of spray-dried trehalose/protein/surfactant particles. Surfactant reduces protein adsorption at the water/air-interface. This appears to be a result of complex formation with the surfactant within the bulk spray solution.

Effects of antipsychotic and antianxiety drugs on the morphine abstinence syndrome in rats.

The effects of representative antipsychotic and antianxiety drugs on the abstinence syndrome in morphine-dependent rats were compared. Groups of 10 to 22 male albino Sprague-Dawley rats (250-300 g) were individually implanted s.c. with either two 75-mg morphine base pellets or two placebo pellets. After 72 hr, chlorpromazine (CPZ 1,2 and 4 mg/kg), haloperidol (0.2, 0.4 and 0.8 mg/kg), thioridazine (10, 20 and 40 mg/kg), chlordiazepoxide (2,4 and 8 mg/kg), diazepam (DPM, 1, 2 and 4 mg/kg) or vehicle was injected s.c. 55 min before precipitation of abstinence with naloxone (1 mg/kg s.c.). Jumping was exacerbated by CPZ (4 mg/kg), chlordiazepoxide (4 and 8 mg/kg) and DPM (1, 2 and 4 mg/kg); haloperidol and thioridazine had no significant effect on this sign. Weight less over 1 hr was decreased by CPZ (4 mg/kg) and DPM (4 mg/kg). Wet-dog shakes were decreased by all doses of haloperidol but increased by chlordiazepoxide (8 mg/kg) and DPM (1, 2 and 4 mg/kg). CPZ (2 and 4 mg/kg) significantly increased the incidence of teeth chattering. Other abstinence signs were not affected in a dose-related manner. Although the antipsychotic agents each decrease dopamine availability at the postsynaptic receptor, this mechanism alone cannot explain their actions on individual signs of abstinence. Perhaps it is therefore time to question how modifying agents can be meaningfully compared in morphine-abstinent rats.

The parotid and the pancreas. V. Effects of a synthetic prostaglandin analog on parotid gland secretion.

Effects of a synthetic prostaglandin analog--16,16-dimethyl prostaglandin E2 methyl ester (16-diMe-PGE2)--on parotid secretion were evaluated in eight dogs under anesthesia. Graded doses of 16-diMe-PGE2 (0.3, 0.5, 1.0 and 2.5 microgram./kg.) were administered intravenously with the parotid in the resting state or in response to urecholine (intravenous infusion or subcutaneous injections). Profound and prolonged inhibition of volume occurred. Amylase concentration was increased but output was unchanged. Bicarbonate concentration was increased but output was decreased. Nonsteroid inhibitors of endogenous prostaglandin synthesis did not alter these effects. Although these studies do not establish a physiologic role for prostaglandins in the regulation of salivary secretion, they do demonstrate a wide-ranging effect of prostaglandins on the gastrointestinal tract.

Whole gut lavage for colonoscopy--a comparison between two solutions.

The clinical efficacy and patient acceptability of a new solution containing mainly sodium sulfate and polyethylene glycol (solution II) compared with a balanced standard electrolyte solution (solution I) for whole gut lavage prior to colonoscopy were evaluated in 240 ambulatory and hospital patients randomly allocated to receive either of the two solutions. On the basis of the quality and rapidity of the bowel preparation and the good results obtained by clinical and biological parameters, we found that the newly designed solution was superior.

Endoscopic treatment of esophagogastric varices.

We report our current management of variceal bleeding with endoscopic sclerotherapy. We emphasize the importance of resuscitation and of recording at time zero and within the first 72 hours clinical and laboratory indicators, as these influence the management of these patients. Primary sclerotherapy using Histoacryl for active bleeding and Ethoxysclerol for recent bleeding should be performed as soon as the patient is stable hemodynamically. As we have identified factors related to the severity of hemorrhage and of liver failure degree which can predict early failure of sclerotherapy, patients presenting with these findings should be, in the future, referred quickly toward alternative therapies among which non-surgical intrahepatic shunt appears a promising modality.