A novel approach to the use of subgingival controlled-release chlorhexidine delivery in chronic periodontitis: a randomized clinical trial.

BACKGROUND: We aimed to analyze clinical, microbiologic, and serologic effects of chlorhexidine (CHX) chips used as a subgingival controlled-release delivery device before and immediately after scaling and root planing (SRP). METHODS: Twenty-four patients presenting with ≥12 teeth with probing depth (PD) ≥5 mm and bleeding on probing were assigned in test or control groups. After prophylaxis, CHX chips (test) or placebo chips (control) were placed in pockets with PD ≥5 mm. Ten days later, SRP was performed in all teeth with PD ≥4 mm in a single appointment. Immediately after SRP, new chips were inserted in all pockets with PD ≥5 mm. Parameters were assessed at baseline; beginning of SRP; and 1, 3, and 6 months after treatment. Subgingival samples were obtained at baseline; beginning of SRP; and at 1 month after treatment. Periodontal pathogens Aggregatibacter actinomycetemcomitans, Porphyromonas gingivalis, Prevotella intermedia, Tannerella forsythia, and Treponema denticola were analyzed. Serum levels of high sensitive C-reactive and lipopolysaccharide-binding proteins were measured. The changes of the parameters between and within the groups were tested by Mann-Whitney U test (P <0.05). RESULTS: All clinical and serologic parameters improved in both groups over time. There was a significant difference in clinical attachment level (CAL) gain from baseline to 6 months between groups (1.17 mm in the test group versus 0.79 mm in the placebo group) (P <0.05). The treatment with CHX chips showed a greater reduction of the microorganisms of the "red complex" after 1 month (P = 0.02). CONCLUSION: The use of CHX chips before and immediately after SRP improved CAL and reduced the subgingival microorganisms of the red complex in the treatment of chronic periodontitis.

Safety and tolerability of inhaled heparin in idiopathic pulmonary fibrosis.

BACKGROUND: Abnormalities in alveolar coagulation occur in idiopathic pulmonary fibrosis (IPF). Anticoagulants attenuate bleomycin-induced lung fibrosis in animals. In this study, we first examined the pharmacokinetics of inhaled heparin in healthy subjects. Second, we investigated the safety and tolerability of heparin inhalation in IPF patients. METHODS: Coagulation assays were performed in blood and bronchoalveolar lavage fluid samples from 19 healthy volunteers after inhalation of increasing amounts of unfractionated heparin. The acute effects of heparin inhalation on lung function and exercise capacity and the safety and tolerability of chronic heparin inhalation for 28 days were assessed in 20 IPF patients in an open-label exploratory pilot study. RESULTS: In healthy subjects, inhalation of 150,000 IU heparin ("filled dose") significantly increased the partial thromboplastin time and anti-factor Xa activity in blood samples indicating the threshold dose. The local alveolar anticoagulant effect was detectable up to 72 h, and the alveolar half-life was estimated at 28 h. In IPF-patients, no acute deleterious effects on pulmonary function, gas exchange, or exercise capacity were noted after inhalation of the threshold dose. During chronic treatment, where one-fourth of the threshold dose was inhaled every 12 h for 28 days to obtain a steady-state anticoagulant activity in the alveolar space approximating the anticoagulant activity observed after threshold dose inhalation, no heparin-related side effects, such as hemoptysis or heparin-induced antibodies and thrombocytopenia, were detected in any patient, and median lung function values, exercise capacity, and quality of life scores appeared largely unaltered. Three adverse and one serious adverse events were noted; however, the relation of these events to the heparin inhalation was assessed as "unlikely" or "no relation" in each case. CONCLUSIONS: Inhaled heparin appears to be safe and well tolerated in IPF patients. Future clinical trials are required to demonstrate the long-term safety and efficacy of inhaled heparin in IPF.

Randomised prospective study for the effect of therapy on residual beta cell function in type-1 diabetes mellitus [ISRCTN70703138].

BACKGROUND: Newly diagnosed insulin-dependent diabetes mellitus is characterised by a temporary recovery of endogeneous insulin ("remission") after the beginning of medical treatment with subcutaneous insulin injections. Although most diabetologists think, that insulin reserve is related to reduced occurrence of diabetic long-term complications, such as eye, nerve and kidney disease, there is only one prospective controlled clinical study (the DCCT) addressing this question, however as secondary hypothesis. METHODS/DESIGN: Therefore, we composed a trial consisting of two cohorts with two therapeutic options within each cohort (conventional versus intensive therapy) and a three-year follow-up. In one group the patients are randomly assigned to the treatment regimes to test the statistical alternative hypothesis if variable insulin dosage is superior to fixed insulin injection in preserving insulin reserve measured by C-peptide in serum. Another group includes patients who prefer one of the two therapies, decline randomisation, but consent to follow-up. Apart from the determination of insulin reserve as a biological parameter a second primary endpoint was defined as 'therapeutic failure' according to the criteria of the European Association for the Study of Diabetes. Patients pass a training program to help them self-manage diabetes. A standardised protocol is being set up to minimize centre effects and bias of health care providers. Potential patient dependent bias will be investigated by questionnaires measuring psychic coping processes of people with diabetes. Management of visit dates is directly navigated by the database. Automated visit-reminders are mailed to patients and caregivers to optimise the number of visits on schedule. Data quality is regularly monitored and centres are informed on the results of continuous data management.