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®.     

Oral health of individuals aged 3-80 years in J?nk?ping, Sweden in 1973 and 1983. I. A review of findings on dental care habits and knowledge of oral health

The aim of the present study was to present data from dental care habits and knowledge of oral health in two cross-sectional studies carried out in 1973 and 1983. A random sample of approximately 1000 individuals evenly distributed in the age groups 3, 5, 10, 15, 20, 30, 40, 50, 60 and 70 years was studied for each of these two years. In the 1983-year examination 80 individuals 80 years of age were also included. All subjects were inhabitants of the community of J?nk?ping, Sweden. A questionnaire about dental care habits and knowledge was used in combination with a clinical and radiographical examination. The participants answered 23-101 questions. The same questions were raised in 1973 and 1983. For most age groups more then 80 per cent visited a dentist yearly in 1983. This yearly attendance was higher than that for 1973. In the 20-year-old group 14 per cent of the individuals received dental care in the PDS in 1973 compared to 63 per cent in 1983. The main reason to visit a dentist in 1973 was by the patient's own initiative while in 1983 the appointments were based on the dentist's initiative. The number of subjects that felt discomfort in connection with a visit to the dentist had decreased between 1973 and 1983. Knowledge about the etiology of caries had increased between 1973 and 1983 was not the case for gingivitis and periodontitis. An increase had occurred in toothbrushing frequency and the use of toothpicks and disclosing tablets but this between 1973 and 1983. In 1983, 98 to 93 per cent of the subjects in the age groups 10-30 years had been exposed to topical fluorides. The corresponding figure for 30-year-olds in 1973 was 1 per cent. It is obvious that during the period 1973 to 1983 there has been an increase in dental attendance, knowledge of dental diseases, oral health and the use of preventive measures.     

Dioxin treatment of rats results in increased in vitro induction of sister chromatid exchanges by alpha-naphthoflavone: an animal model for human exposure to halogenated aromatics

Recent reports have shown that alpha-naphthoflavone (alpha-NF) in vivo enhances the sister chromatid exchange (SCE) frequency in lymphocytes from human populations exposed to cigarette smoke or polychlorinated biphenyls and dibenzofurans. In this study, female Sprague-Dawley rats (9-11 weeks old) were administered a single oral dose of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and killed 6 days after treatment. Blood cultures were established with or without alpha-NF. The baseline and alpha-NF-induced SCE frequencies were assessed in lymphocytes after a 72-hr culture period. No effect on the SCE baseline frequency (cultures without alpha-NF) was detected in rats exposed to 0-30 micrograms TCDD/kg. However, the SCE frequencies from cultures incubated in the presence of alpha-NF were significantly higher in lymphocytes from rats treated with TCDD. Moreover, delta SCE values (SCE alpha-NF minus SCE baseline) were significantly higher in lymphocytes from rats treated with TCDD than in controls. A dose-dependent increase in delta SCE values was observed between 0 and 3 micrograms TCDD/kg, followed by a plateau at higher doses. This induction pattern closely resembled the induction of the liver microsomal aryl hydrocarbon hydroxylase activity by TCDD. In contrast to TCDD, phenobarbital treatment of rats (75 mg/kg/day) had no effect on alpha-NF-induced SCE frequencies in lymphocytes. Liver microsomes from TCDD-treated rats metabolized alpha-NF at a rate much faster than that of control microsomes. These studies indicate that TCDD-exposed rats provide a useful model to investigate the mechanism of enhanced in vitro induction of SCE frequency in lymphocytes from humans exposed to toxic halogenated aromatics or cigarette smoke.     

Intravenous or rectal administration of sedatives in outpatient oral surgery

A number of cross-over studies on sedation in outpatient oral surgery investigated the quality of sedation produced by intravenous or rectal administration of diazepam. The sedation methods were equally efficient with a mean dose of 0.24 mg/kg (range 0.1–0.4) for i.v. administration and 0.53 mg/kg (range 0.5–0.6) for rectal administration. Eighty-five percent of the patients preferred surgery under sedation and local anaesthesia to local anaesthesia alone. The patients preferred the session in which they experienced stronger sedation, regardless of the route of administration.     

Healing-in of root analogue titanium implants placed in extraction sockets. An experimental study in the beagle dog.

The aim of these animal experiments was to characterize and evaluate the healing-in of root analogue titanium implants fitting with high precision to the alveolar wall. Four beagle dogs were used in the study. The roots of the 3rd and 4th mandibular premolars in both quadrants of 3 dogs and in 1 quadrant of 1 dog (dog 4) were extracted after hemisection. Each root was machine-copied to 1 titanium analogue. In dog 4, however, 2 titanium analogues were fabricated from each of the 4 extracted roots. This enabled insertion of analogues also into the contralateral sockets obtained by extraction of the corresponding roots immediately before implant installation, which was undertaken 2 weeks after the first extractions. Thus, in all, 32 analogues were implanted in their respective (or contralateral) sockets following ridge incision and elevation of mucoperiosteal flaps. The analogues were carefully covered by the repositioned flaps. In dog 4, 2 analogues from the immediate sockets and 2 from the 2-week sockets were surgically exposed and supplied with titanium crowns after a healing period of 2 months. The healing after implantation was evaluated by clinical, radiographic and histological measures after 2, 12 or 36 months. Two analogues (6%) were lost due to early (during the 1st week) exposure to the oral cavity. Another 2 analogues (6%) were, although not exposed, encapsulated by soft tissue and were easily removed with a surgical forceps. Twenty-eight analogues (88%) were healed-in by contact between bone and implant (osseointegration).(ABSTRACT TRUNCATED AT 250 WORDS)     

Breath-hold duration in man and the diving response induced by face immersion

The objective of this study in 5 selected volunteer subjects was to see whether the circulatory diving response which is elicited by breath holding and by cold water on the face would affect the duration of maximal-effort breath holds. Compared to control measurements (breath holding during resting, breathing with 35 degrees C water on the face) breath holding with the face cooled by 20 degrees C water caused a 12% reduction of heart rate, 6% reduction of cardiac output, 33% reduction in [corrected] forearm blood flow, and 9% rise in mean arterial blood pressure, but there was no difference in breath-hold duration (control and experimental both 94 s). There were also no differences in time of appearance of the first involuntary respiratory efforts during breath holding, in alveolar gas exchange, or in breaking-point alveolar O2 and CO2 tensions. When the diving response was magnified by a brief bout of exercise so that there was a 19% [corrected] reduction in heart rate, 23% reduction in cardiac output, and 48% reduction in forearm blood flow, breath-hold duration was still unaffected by face cooling. Compared to intermittent immersions, continuous exposure of the face to cold water abolished the diving response, probably by a cold adaptation of facial thermal receptors. These results with cooling of the face only are consistent with our earlier finding that there was a negative correlation between the duration of a maximal-effort breath hold and the diving response during whole-body submersion in cold water.     

Mammographic growth rate, DNA ploidy, and S-phase fraction analysis in breast carcinoma. A prognostic evaluation in a screened population.

BACKGROUND. The authors examined prognostic factors in 158 cases of breast carcinoma with known mammographic tumor volume doubling times (DT). METHODS. The tumors were retrospectively reexamined histologically and flow cytometric analysis of DNA ploidy and S-phase fraction (SPF) was performed on archival paraffin-embedded material in each case. Life tables and Cox multivariate analyses were used for statistical evaluation of prognostic factors. RESULTS. In univariate analysis of survival data, clinical and pathologic stage, histologic grade, the presence of axillary lymph node metastases, and SPF were significant prognostic predictors, but mammographic DT and DNA ploidy were not. SPF also contributed prognostic information in the subgroup of carcinoma cases detected by screening. In a Cox multivariate analysis, SPF, the presence of axillary lymph node metastases, and Stage II-III disease (as opposed to Stage I disease) were independent significant predictors of survival. In univariate analyses of distant disease-free survival, clinical and pathologic stage, tumor size, histologic grade, the presence of involved axillary nodes, DT, and SPF all were significant prognostic factors. CONCLUSIONS. SPF, stage, and lymph node status were important prognostic factors in this patient material with predominantly small and node-negative breast carcinomas, whereas DNA ploidy and mammographic DT provided less prognostic information. The prognosis of carcinoma detected during screening did not differ significantly from that of breast carcinoma discovered otherwise in this selected patient group.     

Intermediate and fine cytofilaments in cutaneous and subcutaneous leiomyosarcomas.

The expression of fine and intermediate cytofilaments in 10 cutaneous and seven subcutaneous leiomyosarcomas was studied immunohistochemically. All the tumors contained tumor cells which showed a positive immunoreactivity for desmin in formaldehyde-fixed and paraffin-embedded sections, but none of the seven anti-desmin antibodies used alone produced a distinct positive staining in all the tumors. A lack of correspondence in terms of immunoreactivity between tumor cells and the supposed muscle of origin was observed, especially in the subcutaneous leiomyosarcomas. In all cases, antibodies to muscle-specific and smooth muscle-specific actin were found to produce a positive staining in both the tumors and the supposed muscle of origin. Vimentin was detected in 8/10 cutaneous and 4/7 subcutaneous leiomyosarcomas, while the supposed muscle of origin was positive in 3/10 and 7/7 cases, respectively. Four of the cutaneous and three of the subcutaneous leiomyosarcomas contained tumor cells which stained positively for cytokeratins, while the supposed muscle of origin showed no positivity. It thus appears that a phenotypic shift in terms of vimentin and cytokeratin expression occurs in the tumor cells of cutaneous and subcutaneous leiomyosarcomas compared with the supposed muscle of origin. It is recommended that more than one monoclonal anti-desmin antibody is used to characterize these tumor entities. It is also concluded that the immunoreactivity for muscle-specific actins in superficial leiomyosarcomas is more constant, although less specific, than that of desmin and that the demonstration of the simultaneous expression of muscle-specific actins and desmin is helpful.     

Voltage-Gated calcium channels and nonvoltage-gated calcium uptake pathways in the rat incisor odontoblast plasma membrane

Odontoblasts participate actively in the transport and accumulation of Ca²⁺ ions to the mineralization front during dentinogenesis. These cells are known to carry membrane-bound ATP-driven pumps and Na⁺/Ca²⁺ antiports for Ca²⁺ extrusion, but little is known about Ca²⁺ influx mechanisms into these cells. It has been shown that the administration of Ca²⁺ channel blockers in vivo strongly impairs Ca²⁺ uptake in the mineral phase during dentinogenesis in the rat; the present in vitro study is aimed at further elucidating odontoblast Ca²⁺ uptake mechanisms. Dissected rat incisor odontoblasts exhibited a pronounced fluorescence when incubated with a fluorescently-labeled (STBodipy) dihydropyridine, which is specific for voltage-gated Ca²⁺ channels of the L-type, and this binding was competitively abolished by nifedipine. As assayed by fluorescence spectrometry, odontoblast Ca²⁺ uptake was enhanced by the agonistic dihydropyridine BAYK-8644 (5 μM) as well as by plasma membrane depolarization in a high K⁺ (120 mM) medium. The Ca²⁺ uptake after depolarization was impaired by nifedipine (5 μM). When treated with the Ca²⁺-ATPase inhibitor cyclopiazonic acid (CPA; 10 μM), a nonvoltage-gated uptake of ⁴⁵Ca²⁺ was identified. This uptake was not influenced by nifedipine (20 μM) but was impaired by lanthanum ions (200 μM). A nonvoltage-gated uptake of Mn²⁺ into CPA-treated cells could be traced using the fura-2 quenching technique. This CPA-induced Ca²⁺ flux was not caused by an alteration of the plasma membrane potential, as assayed with di-8-ANEPPS. The results demonstrate that Ca²⁺ flux into dentinogenically active odontoblasts occurs through voltage-gated Ca²⁺ channels of the L-type and by nonvoltage-gated, agonist-sensitive Ca²⁺ uptake pathways. Received: 6 November 1995 / Accepted: 21 February 1996