Clinical safety of enamel matrix derivative (EMDOGAIN®) in the treatment of periodontal defects

Abstract The aim of the present clinical trial was to test tolerability during 2 treatments with EMDOGAIN® in a large number of patients. An open, controlled study design in 10 Swedish specialist clinics was chosen, with a test group of 107 patients treated with EMDOGAIN® in connection with periodontal surgery at 2 surgical test sites per patient. The procedures were performed 2 to 6 weeks apart on one-rooted teeth with at least 4 mm deep intraosseous lesions. A control group of 33 patients underwent flap surgery without EMDOGAIN® at I comparable site. In total 214 test and 33 control surgeries were performed. Serum samples were obtained from test patients for analysis of total and specific antibody levels. 10 of the patients had samples taken before and after the first surgery. 56 other samples were taken after one treatment with EMDOGAIN®, and 63 after 2 treatments. None of the samples, not even from allergy-prone patients after 2 treatments, indicated deviations from established baseline ranges. This indicates that the immunogenic potential of EMDOGAIN® is extremely low when applied in conjunction with periodontal surgery. Comparison between the test and control groups demonstrated the same type and frequency of post-surgical experiences, i.e., reactions caused by the surgical procedure itself. Clinical probing and radiographic evaluation was performed at baseline and 8 months postsurgery. About half of the patients (44 test and 21 control) were also evaluated after 3 years. There was a significant difference between the test and control results at 8 months post surgery. and this difference had increased further at the 3 year follow-up. The 2.5–3 mm increase in attachment and bone level after treatment with EMDOGAIN® was of the same magnitude as seen in the studies with split-mouth design aiming for lest of effectiveness of EMDOGAIN®.     

Canine pancreas and kidney transplantation following total-lymphoid irradiation

The effect of total-lymphoid irradiation on survival of canine pancreas and kidney allografts was studied. TLI had a marked immunosuppressive effect as measured by in vitro immune responses and reduced circulating leukocytes. Despite the changes, median graft survival times for animals treated with 800 cGy (9 days) or 1800 cGy (9.5 days) were not significantly different from untreated control animals (7 days). The addition of low-dose antithymocyte globulin (10 mg/kg/day) on post-transplant days 0, 2, 4, 6, 8, and 10 had no measurable synergistic effect. Similarly, median segmental pancreas allograft survival times after 1700-2200 cGy of TLI treatment (16.5 days) were only marginally longer than those of untreated controls (9 days). The only animal to maintain a graft for greater than 200 days was matched to the donor in mixed lymphocyte culture (MLC). This animal was able to reject a third-party skin graft after 8 days while a graft from the original donor was still surviving after 21 days when the pancreas graft failed from a chronic-type rejection. These results indicate that TLI alone or in combination with ATG will not be predictably effective as a method of prolonging allograft survival. The role of matching major histocompatibility complex antigens in TLI treatment requires clarification.     

Improved long-term bone-implant integration Experiments in transgenic mice overexpressing bovine growth hormone

Several recent studies have investigated the effects of growth hormone (GH) on the healing of fractures and bone ingrowth, but with conflicting results. The negative results may be due to antibody formation against injected GH or because some experimental models are able to prove only positive GH effects. In this study, we wanted to investigate the effect of GH on implant integration in bone. To avoid potential formation of antibodies against injected GH, we used a model with transgenic mice overexpressing bovine GH (bGH).

Titanium implants were inserted in the forehead of the mice. 4 months after insertion, the implants were cut out en bloc with the surrounding bone. The calcified specimens were cut and ground to a thickness of approximately 10m. Histomorphometry demonstrated significantly more direct bone-to-metal contact in the transgenic mice than in the nontransgenic littermates. Our findings indicate that systemic administration of GH in humans may improve implant integration in bone.     

Legionnaires' Disease in Leukaemic Reticuloendotheliosis

At our hospital 15 cases of leukaemic reticuloendotheliosis and 4 cases of Legionnaires' disease have been diagnosed. 3 patients had both diseases. The clinical findings are reported. It is probable that patients with leukaemic reticuloendotheliosis have an increased susceptibility to Legionnaires' disease. Possible reasons for the decreased resistance are discussed.     

Health status measurement in Parkinson's disease: validity of the PDQ-39 and Nottingham Health Profile.

We assessed the feasibility and psychometric properties of two commonly used health status questionnaires in Parkinson's disease (PD): the generic Nottingham Health Profile (NHP) and the disease-specific 39-item Parkinson's disease Questionnaire (PDQ-39), from a cross-sectional postal survey of PD patients (N = 81), using traditional and Rasch measurement methodologies. Overall response rate was 88%. Both questionnaires were found feasible, although the NHP performed less well. The PDQ-39 had fewer floor effects and was better able to separate respondents into distinct groups than the NHP, whereas the latter exhibited less ambiguous dimensionality and better targeting of respondents with non-extreme scores. Reliability and validity indices were similar, and potential differential item functioning by age and gender groups was found for both questionnaires. PDQ-39 response alternatives indicated ambiguity. With few exceptions, questionnaire scales were unable to meet recommended standards fully. While preliminary, this study illustrates the need for thorough evaluation of outcome measures and has implications beyond the questionnaires used here. Although promising, both questionnaires warrant further developmental work and stronger support of measurement validity before they could be considered fully suitable for valid use in PD, in particular in earlier stages of the disease.     

Capsaicin cough sensitivity in allergic asthmatic patients increases during the birch pollen season.

BACKGROUND: A change in neural responsiveness may occur as the result of allergic inflammation in the lower airways as well as in the upper airways. In the lower airways, capsaicin cough sensitivity is known to reflect sensory neural reactivity. OBJECTIVE: The aim of this study was to establish whether allergic inflammation changes airway neural sensory reactivity during prolonged allergen exposure. METHODS: Ten nonsmoking patients with birch pollen-allergic asthma performed a capsaicin inhalation challenge twice, once in the off-pollen season and once during the pollen season. The number of coughs and symptoms induced by capsaicin were recorded and compared with those of healthy control subjects. RESULTS: The response to capsaicin, expressed as number of coughs, increased in a dose-dependent manner during both tests. Before the season, the response was similar to that of healthy control subjects, but during the pollen season, the reactivity was significantly increased. Variations in forced expiratory volume in 1 second were not significant before and after each challenge, and values did not change during the pollen season as compared with the winter season. CONCLUSIONS: Sensory reactivity in allergic asthmatic patients may be increased during prolonged allergen exposure as during the pollen season. This finding suggests that allergic inflammation in the lower and/or upper airways may trigger neurogenic mechanisms of significant clinical importance.     

Periosteal transplantation to the rabbit patella

Autologous periosteal transplantation (without chondrocyte cell transplantation) for treating traumatic articular cartilage defects of the patella gives pain relief in uncontrolled clinical studies. To study the whole transplanted area macroscopically and microscopically, animal studies are motivated. In this pilot study, we reproduce the surgical technique for periosteum transplantation on human patella to a rabbit model. A full-thickness cartilage defect of the whole patella was created in eight adult female rabbits. The defect was treated with autologous periosteal transplantation. After surgery, the rabbits were allowed free activity. This is the difference compared to the treatment in humans, where our group uses CPM for 5 days and non-weight-bearing for 12 weeks. After 21 weeks, there was a diffuse synovitis in all transplanted knees, and in five of eight knees there were signs of osteoarthritis in the patello-femoral joint. Histologically, in three animals, small islands of hyaline cartilage surrounded by fibrocartilage were seen in the transplanted area. In the other five animals, fibrocartilage was the predominant tissue. In contrast to previous experimental studies using a rabbit model, we did not achieve hyaline cartilage resurfacing.     

Pharyngeal swallowing in patients with paresis of the recurrent nerve

Pharyngolaryngeal function during swallowing was investigated cineradiographically in 22 patients with paresis of the recurrent nerve. Nineteen of these patients (86%) had defective closure of the laryngeal vestibule: 10 patients had defective apposition of the corniculate cartilages, (paresis of the oblique cricoarytenoid muscle), 9 patients had defective apposition of the arytenoid cartilages, (paresis of the interarytenoid muscle), 13 patients had defective movement of the epiglottis (paresis of, i.a. the thyrohyoid muscle), 1 patient had defective closure of the subepiglottic portion of the vestibule (paresis of the thyroepiglottic muscle), 2 patients had defective closure of the supraglottic portion of the vestibule (paresis of the superior ventricular segment of the thyroarytenoid muscle). Five patients with immobility of the epiglottis also had paresis of the pharyngeal constrictor musculature indicating paresis of the superior laryngeal nerve. Our investigation has shown that patients with paresis of the recurrent nerve who present with dysphagia with or without aspiration should be examined cineradiographically for pharyngolaryngeal function during swallowing.