Clinical relevance of adjunctive minocycline microspheres in patients with chronic periodontitis: secondary analysis of a phase 3 trial.

BACKGROUND: A recent Phase 3 trial demonstrated that adjunctive treatment with minocycline microspheres resulted in significant reductions in patient mean probing depths as compared to scaling and root planing (SRP) alone. The objective of the present study was to evaluate clinical relevance of these changes within the trial using proposed site-based criteria. METHODS: A total of 499 patients with moderate to advanced chronic periodontitis were enrolled in a multi-center trial and randomized to either: 1) SRP alone or 2) SRP plus minocycline microspheres. Subjects received complete probing examinations including the measurement of probing depths at baseline, and 1 and 3 months. Probing depth reductions were tabulated by treatment, examination time, and baseline depths, and inter-group differences were evaluated with logistic regression models for correlated data. RESULTS: Significantly more sites treated with adjunctive minocycline microspheres exhibited probing depths < 5 mm at 1 (P = 0.0009) and 3 (P = 0.01) months as compared to sites treated with SRP alone, both in the overall population and in smokers. In addition, significantly more sites decreased by 1, 2, or 3 mm in the adjunctive minocycline group than in the SRP alone group at 1 and 3 months, both overall as well as in smokers (P < 0.05). CONCLUSION: This secondary analysis indicates that treatment with SRP plus minocycline microspheres is consistently more effective than SRP alone in providing clinically relevant site-based responses in patients with chronic periodontitis.

Toxicity of human adenovirus E4orf4 protein in Saccharomyces cerevisiae results from interactions with the Cdc55 regulatory B subunit of PP2A.

The E4orf4 protein of human adenovirus induces p53-independent apoptosis, a process that may promote cell death and viral spread. When expressed alone, E4orf4 kills transformed cells but not normal human cells. The only clear target of E4orf4 in mammalian cells is the Balpha (B55) subunit of protein phosphatase 2A (PP2A), a member of one of three classes of regulatory B subunits. Here we report the effects of E4orf4 in Saccharomyces cerevisiae, which encodes two PP2A regulatory B subunits, CDC55 and RTS1, that share homology with mammalian B and B' subunits, respectively. E4orf4 expression was found to be toxic in yeast, resulting in the accumulation of cells in G2/M phase that failed to grow upon removal of E4orf4. E4orf4-expressing yeast also displayed an elongated cell morphology similar to cdc55 deletion strains. E4orf4 required CDC55 to elicit its effect, whereas RTS1 was dispensable. The recruitment of the PP2A holoenzyme by E4orf4 was entirely dependent on Cdc55. These studies indicate that E4orf4-induced apoptosis in mammalian cells and cell death in yeast require functional interactions with B-type subunits of PP2A. However, some inhibition of growth by E4orf4 was observed in the cdc55 strain and with an E4orf4 mutant that fails to interact with Cdc55, indicating that E4orf4 may possess a second Cdc55-independent function affecting cell growth.

Short-contact topical tretinoin therapy to stimulate granulation tissue in chronic wounds.

BACKGROUND: The use of retinoids in wound healing is increasing. It has been shown that retinoic acid reverses the inhibitory effects of glucocorticoids on wound healing and accelerates the formation of healthy granulation tissue. Pretreatment with tretinoin before epidermal injury such as chemical peeling and dermabrasion has shown accelerated wound healing. Enhanced healing of full-thickness skin wounds has also been demonstrated in early wound healing studies. However, tretinoin therapy can be quite irritating. OBJECTIVE: Our purpose was to observe the clinical and histologic effects of topical tretinoin solution 0.05% applied directly to the wound beds of chronic leg ulcerations. METHODS: We report on the cases of 5 patients with long-standing leg ulcerations. All were treated with topical tretinoin solution 0.05% applied directly to the wound bed. The tretinoin solution was left in contact with the ulcer bed for a maximum of 10 minutes daily and then rinsed with normal saline. Punch biopsy specimens were obtained from the wound beds at baseline and mid therapy. Standard wound care was continued throughout the study. RESULTS: In this study we found that as early as 1 week after treatment with topical tretinoin solution 0.05%, there was increased granulation tissue first noted at the wound's edge. After 4 weeks of therapy with tretinoin, there was further stimulation of granulation tissue, new vascular tissue, and new collagen formation. CONCLUSION: Short-contact tretinoin therapy is a novel modality in which to treat chronic ulcers and stimulate the formation of granulation tissue.

A multicenter 12-month evaluation of single-tooth implants restored 3 weeks after 1-stage surgery.

The time-intensive, multi-step process of dental implant therapy limits patient acceptance. This 3-year prospective multicenter study sought to determine the safety of an expedited therapy that consisted of loading unsplinted maxillary anterior single-tooth implants 3 weeks after 1-stage surgical placement, and determination of the peri-implant cortical bone and mucosal responses to the expedited procedure. Fifty-two patients missing 1 or 2 maxilliary anterior teeth were enrolled in a study approved by the Institutional Committee on Human Subjects Research and based on strict inclusion and exclusion criteria. Astra Tech ST implants placed in a 1-stage procedure were restored 3 weeks later with ST abutments and a provisional crown (baseline); 7 to 9 weeks later, a porcelain-fused-to-metal or all-ceramic crown was cemented. Radiographic and clinical examinations were made at baseline and at 6 and 12 months. Implant survival was recorded. Cortical bone responses and peri-implant mucosal responses were evaluated. Fifty-eight implants were placed. During the 3-week period after implant placement, 4 patients were dismissed because of smoking cigarettes (a protocol deviation), and 1 patient was excluded because of deviation in loading time. Of the remaining 53 implants, 2 failed before definitive crown cementation. The resultant 96.2% survival rate was independent of implant length, tooth position, and bone quality/quantity. The mean change in marginal bone level was 0.4 mm at 12 months. The number of surfaces with plaque decreased from 3.4% at baseline to 0.5% at 12 months. The surfaces with inflammation also decreased. A mean gain in papilla length of 0.61 mm occurred, and a gain in buccal gingiva (x = 0.34 mm) was observed. A high success rate with positive tissue responses was achieved for maxillary anterior unsplinted single-tooth implants placed in a 1-stage surgery and restored at 3 weeks. This 2-component system is suited to a single-stage, rapid loading protocol for esthetic single-tooth replacement.

Treatment of periodontitis by local administration of minocycline microspheres: a controlled trial.

BACKGROUND: Periodontitis is an inflammatory condition of tooth-supporting tissues that is usually treated by mechanical removal of plaque and microorganisms that adhere to teeth. This treatment, known as scaling and root planing, is not optimally effective. Adjunctive therapy with locally delivered antimicrobials has resulted in improved clinical outcomes such as probing depth reduction. This article reports on the efficacy and safety of locally administered microencapsulated minocycline. METHODS: Seven hundred forty-eight (748) patients with moderate to advanced periodontitis were enrolled in a multi-center trial and randomized to 1 of 3 treatment arms: 1) scaling and root planing (SRP) alone; 2) SRP plus vehicle; or 3) SRP plus minocycline microspheres. The primary outcome measure was probing depth reduction at 9 months. Clinical assessments were performed at baseline and 1, 3, 6, and 9 months. RESULTS: Minocycline microspheres plus scaling and root planing provided substantially more probing depth reduction than either SRP alone or SRP plus vehicle. The difference reached statistical significance after the first month and was maintained throughout the trial. The improved outcome was observed to be independent of patients' smoking status, age, gender, or baseline disease level. There was no difference in the incidence of adverse effects among treatment groups. CONCLUSIONS: Scaling and root planing plus minocycline microspheres is more effective than scaling and root planing alone in reducing probing depths in periodontitis patients.

Performance of screening mammography in organized programs in Canada in 1996. The Database Management Subcommittee to the National Committee for the Canadian Breast Cancer Screening Initiative.

BACKGROUND: The results of randomized trials show that breast cancer screening by mammography reduces breast cancer mortality by up to 40% in women aged 50-69 years. Because of these results, by 1998, 22 countries, including Canada, had established population-based organized screening programs. This paper presents the results of screening mammography in 1996 for 7 provincially organized breast cancer screening programs in Canada. METHODS: Analyses of interim performance indicators for screening mammography have been calculated from data submitted to the Canadian Breast Cancer Screening database. The data set consisted of data from 7 provincial programs and was limited to mammographic screens for women aged 50-69 years (n = 203,303). Screening outcomes and performance indicators were calculated for abnormalities detected by screening mammography only. RESULTS: The abnormal recall rate was 9.5% for first screens and 4.6% for subsequent screens, and the cancer detection rate per 1000 women screened was 6.9 for first screens and 3.8 for subsequent screens. The positive predictive value (i.e., the proportion of women who tested positive by mammography who were found to have breast cancer on screen-initiated diagnostic work-up) increased from 7.2% at the first screen to 8.2% at subsequent screens. Estimated participation rates within organized programs varied from 10.6% to 54.2%, depending on the province. INTERPRETATION: For 1996, organized breast cancer screening programs met or exceeded many of the interim measures used in international programs. It is possible to translate the benefits of breast cancer screening by mammography, as demonstrated in randomized trials, into population-based community programs. Screening mammography through organized programs should increase to allow more comprehensive monitoring in Canada.

Induction of p53-independent apoptosis by the adenovirus E4orf4 protein requires binding to the Balpha subunit of protein phosphatase 2A.

Previous studies have indicated that the E4orf4 protein of human adenovirus type 2 (Ad2) induces p53-independent apoptosis. We believe that this process may play a role in cell death and viral spread at the final stages of productive infection. E4orf4 may also be of therapeutic value in treating some diseases, including cancer, through its ability to induce apoptosis when expressed individually. The only previously identified biochemical function of E4orf4 is its ability to associate with the Balpha subunit of protein phosphatase 2A (PP2A). We have used a genetic approach to determine the role of such interactions in E4orf4-induced cell death. E4orf4 deletion mutants were of only limited value, as all were highly defective. We found that E4orf4 proteins from most if not all adenovirus serotypes induced cell death, and thus point mutations were introduced that converted the majority of highly conserved residues to alanines. Such mutants were used to correlate Balpha-subunit binding, association with PP2A activity, and cell killing following the transfection of appropriate cDNAs into p53-null H1299 or C33A cells. The results indicated that binding of the Balpha subunit is essential for induction of cell death, as every mutant that failed to bind efficiently was totally defective for cell killing. This class of mutations (class I) largely involved residues between amino acids 51 and 89. Almost all E4orf4 mutant proteins that associated with PP2A killed cancer cells at high levels; however, several mutants that associated with significant levels of PP2A were defective for killing (class II). Thus, binding of E4orf4 to PP2A is essential for induction of p53-independent apoptosis, but E4orf4 may possess one or more additional functions required for cell killing.

Selected topics related to occupational exposures.

The auditory and nonauditory effects of noise can be quite profound, affecting approximately 15 to 20 million Americans. As with most occupational toxins, recognition and careful assessment of noise exposure are the foundation on which preventive measures and treatment are based. Dosimeters can measure noise exposure over specific time periods. Pure tone air conduction audiometric monitoring should be performed on an annual basis in workers at risk for significant noise exposure. Occupational infectious disease involves far more than hepatitis and tuberculosis. Periodic fever, dermatologic manifestations and other symptoms peculiar to a specific disease may be important clues to an occupationally related exposure. Whereas strict attention to hand washing and isolation are cornerstones of prevention, use of protective gear is mandated in certain situations. Zoonotic disease, agriculture exposure, water transmission, and biologic contaminants in buildings can be important but subtle exposures sources. Recognition of these infections often depends on the alertness of the primary care giver.

Development and characterization of a bispecific single-chain antibody directed against T cells and ovarian carcinoma.

Bispecific antibodies with specificity for tumor antigen and CD3 have been shown to redirect the cytotoxicity of T cells against relevant tumor. Our objective was to generate single-chain bispecific antibodies (bsSCA) that could retarget mouse cytotoxic T lymphocytes (CTL) to destroy human ovarian carcinoma in a xenogeneic setting. A bsSCA, 2C11 x B43.13, was constructed by genetic engineering and expressed in mammalian cells. Molecular characteristics, binding properties, and ability to retarget CTL were studied. Western blot analysis showed that the product is a 65-kDa protein. Purification of antibodies could be done by single-step affinity chromatography using protein L-agarose with an unoptimized yield of 200 microg/L. BsSCA 2C11 x B43.13 was capable of binding to mouse CD3 and human CA125 as detected by FACS analysis of EL4 and OVCAR Nu3H2 cells, respectively. It could also bridge activated splenic T cells and human ovarian carcinoma as demonstrated by a bridge FACS assay. Redirected mouse CTL could mediate human target cell lysis in a 20-h 51Cr release assay despite that they are xenogeneic. Prolonged incubation of redirected CTL and tumor targets resulted in a dramatic reduction in tumor cell number. CD28 co-stimulation enhanced redirected CTL function in both types of assays. BsSCA 2C11 x B43.13 thus can be used as a preclinical immunotherapeutic model for human ovarian cancer in a xenogeneic setting.

Dose-dependent reduction of apoptosis in nutrient-limited cultures of NS/0 myeloma cells transfected with the E1B-19K adenoviral gene.

It is now well documented that apoptosis represents the prevalent mode of death in lymphoid cultures and occurs spontaneously in late-exponential phase of batch cultures following nutrient exhaustion. In an attempt to enhance the cell survival of these cell lines, we have initially engineered nonproducing NS/0 myeloma cells with a vector expressing the adenoviral E1B-19K protein. NS/0 cells transfected with E1B-19K were found to be more resistant to apoptosis occurring in the late phase of batch culture and under stressful conditions such as cultivation in glutamine-free medium or following heat shock. In this study, we have characterised a number of NS/0 subclones constitutively expressing different levels of E1B-19K, as well as several subclones in which the expression of E1B-19K was regulated by a tetracycline-controllable gene switch. We have found that a threshold E1B-19K level was required in order to achieve protection against apoptosis. The extent of resistance against cell death induced by nutrient deprivation in glutamine-free medium and in the late phase of batch cultures correlated with the level of E1B-19K expression up to an optimal level where further increases in E1B-19K levels did not result in significant additional protection. To assess the effects of E1B-19K on antibody productivity, an apoptosis-resistant NS/0 clone was then transfected with a chimeric antibody construct. Despite their improved viability, the antibody productivity of E1B-19K clones in batch culture was not significantly improved. Moreover, while the use of E1B-19K considerably delayed cell death, cells eventually died by apoptosis. Surprisingly, E1B-19K had no beneficial effect on the efficiency of fusion of NS/0 myelomas and splenocytes for the generation of hybridoma cells. Furthermore, the resulting hybridomas, although expressing E1B-19K at levels comparable to the myeloma parent, were no longer resistant to apoptosis. This indicates that the ability of E1B-19K to prevent apoptosis is not only dose-dependent but also seems to be cell-type dependent.

The hazards of vinyl glove ingestion in the mentally retarded patient with pica: new implications for surgical management.

OBJECTIVE: To report experience with the treatment of complications of vinyl glove ingestion in mentally retarded patients with pica. DESIGN: A retrospective case series. SETTING: Two university-affiliated hospitals. PATIENTS: Five mentally retarded patients, 4 with a history of pica, who were admitted for the management of complications resulting from the ingestion of vinyl gloves. MAIN OUTCOME MEASURES: Type of complication, treatment and operative outcome. FINDINGS: The patients ranged in age from 26 to 46 years. One patient died while awaiting surgical consultation of massive gastrointestinal bleeding from a large gastric ulcer caused by a vinyl glove bezoar (VGB). Four VGBs were removed surgically. Endoscopic removal was difficult or impossible because the gloves had become hardened and matted. CONCLUSIONS: VGB should be considered in institutionalized mentally retarded people with a history of pica when they present with gastrointestinal symptoms. VGBs should be removed directly by laparotomy, gastrotomy or enterotomy. Endoscopic removal is not recommended.

A radiographic evaluation of bone healing around submerged and non-submerged dental implants in beagle dogs.

BACKGROUND: The rehabilitation of the oral cavity with dental implants has become a predictable treatment modality. However, there have been only a few direct comparisons evaluating the submerged and nonsubmerged placement techniques. The purpose of this study was to characterize radiographic peri-implant bone changes following the insertion of submerged and nonsubmerged implants in the beagle dog. METHODS: At the end of the extraction healing phase, 19 submerged and 19 nonsubmerged implants were randomly placed in a split-mouth study design and observed over an 18-week period. For submerged implants, a second stage surgery and transmucosal abutment attachment was performed at week 12. Standardized dental radiographs taken at baseline, week 12, and week 18 were used to measure peri-implant bone changes. The radiographs were analyzed with a simple computer assisted method. RESULTS: A total of 43 standardized radiographs were exposed to evaluate the 38 implants. During the study period, all submerged and nonsubmerged implants demonstrated peri-implant bone loss. At baseline, both submerged and nonsubmerged implants had similar bone levels (P > or = 0.05). When the mean peri-implant bone levels for submerged and nonsubmerged implants were compared from baseline to week 12, nonsubmerged implants had a significantly greater amount and rate of bone resorption than submerged implants (P < or = 0.05). Following week 12, the initially submerged implant had a significantly higher rate and amount of peri-implant bone loss than the nonsubmerged implants (P < or = 0.05). However, by the end of the study period, week 18, both submerged and nonsubmerged implants had comparable bone levels (P > or = 0.05). CONCLUSIONS: The study indicates that, although the temporal patterns of peri-implant bone resorption differed, there were no differences between submerged and nonsubmerged implants in the overall amount and rate of peri-implant bone loss.

The concept of "risk" and the emerging discipline of periodontal medicine.

Dental clinicians intuitively weigh patient risks for developing disease and use that information for making treatment decisions and recommendations. Periodontitis, for instance, is one oral disease with documented risk factors including smoking, specific plaque bacteria and diabetes mellitus. While this link between systemic disease and periodontitis was thought to be unidirectional, mounting evidence in the last decade suggests that the relationship may be bi-directional. Cross sectional and case control studies indicate that periodontitis may confer two and seven-fold elevations in risk for cardiovascular disease and premature low birth weight respectively. While these early studies indicate potential associations between oral and systemic health, they support the central hypothesis that periodontitis triggers both local and systemic host inflammatory responses. Consequently, a new discipline, periodontal medicine, has emerged in dentistry which seeks to further define these interrelationships through scientific inquiry. Ultimately, this new knowledge may prove useful in intervention strategies to reduce patient risks and prevent systemic disease outcomes. This manuscript clarifies the concept of risk, traces the emergence of periodontal medicine and serves as a resource for the oral health professional in assessing and utilizing the current evidence on periodontal-systemic disease connections.

A phase I/II clinical trial to evaluate a combination of recombinant human platelet-derived growth factor-BB and recombinant human insulin-like growth factor-I in patients with periodontal disease.

The primary objective of this study was to assess the safety of recombinant human (rh) platelet-derived growth factor-BB (PDGF-BB) and (rh) insulin-like growth factor-I (IGF-I) when applied to periodontal osseous defects in humans; a secondary objective was to begin to accrue data on the therapeutic dose of these growth factors (GFs) required to stimulate periodontal regeneration. Thirty-eight human subjects possessing bilateral osseous periodontal lesions were assigned to one of two treatment groups in a split-mouth design. Following full-thickness flap reflection, test sites received local application of the therapeutic drug delivered in coded syringes by a "masked" investigator. Two dose levels were tested, 50 micrograms/ml each of rhPDGF-BB and rhIGF-I in a gel vehicle (LD-PDGF/IGF-I) and 150 micrograms/ml each of rhPDGF-BB and rhIGF-I plus vehicle (HD-PDGF/IGF-I). Control treatment consisted of either conventional periodontal flap surgery or surgery plus vehicle. Safety analyses included physical examination, hematology, serum chemistry, urinalysis, antibody titers, and radiographic evaluation of bony changes. The primary therapeutic assessment was bone fill measured at re-entry 6 to 9 months after treatment. No local or systemic safety issues were found as a result of GF administration. No patients developed antibodies to the rhGF proteins. In subjects treated with LD-PDGF/IGF-I, there were no enhancements in periodontal regeneration compared to controls. However, in patients treated with HD-PDGF/IGF-I, statistically significant increases in alveolar bone formation were noted as measured by surgical re-entry 9 months following drug delivery (P < 0.05). This corresponded to an increase of 2.08 mm of new vertical bone height and 42.3% osseous defect fill in the HD-PDGF/IGF-I subjects versus only 0.75 mm and 18.5% gains in new bone height and osseous fill, respectively, in the controls. Furcation lesions, although limited in number, responded most favorably to treatment, with 2.8 mm horizontal osseous fill. The results from this study suggest that the local application of rhPDGF-BB and rhIGF-I to periodontal lesions is safe at the dose levels studied. LD-PDGF/IGF-I did not elicit increased defect fill compared to the control; however, HD-PDGF/IGF-I resulted in a significant promotion in bone regeneration. Additional studies are warranted to more fully characterize the effects of PDGF/IGF-I on periodontal regeneration in humans.

Comparison of healed tissues adjacent to submerged and non-submerged unloaded titanium dental implants. A histometric study in beagle dogs.

This study involved histometry of the healed tissues around submerged and nonsubmerged dental implants in beagle dogs. In a split-mouth design, 19 submerged and 19 nonsubmerged commercially pure titanium implants, titanium plasma-sprayed in the bone anchoring part and smooth in the transmucosal portion, were placed in the mandibles of 6 dogs. Oral hygiene was performed 3 times weekly. After 3 months of healing, transmucosal abutments were inserted in the submerged implants. Six weeks after second stage surgery, the dogs were sacrificed and specimens obtained and processed for histology and histometry. Using a light microscope and a digitizing pad, the distance from implant top to mucosa border (DIM), the extent of epithelial downgrowth (ED), the attachment level, (AL), the length of connective tissue contact (CTC) and the distance of the first coronal alveolar bone contact from the implant top (DIB) were measured at the mesial and distal aspects. Means +/- standard deviations for submerged and nonsubmerged implants were calculated, with the dog being the unit of measure. No statistically significant differences between submerged and nonsubmerged implants were found for DIM, CTC and DIB. However, significant differences were observed for ED and AL. This study in beagle dogs indicates that the apical extension of the peri-implant epithelium is significantly greater and the attachment level significantly lower adjacent to submerged implants with second-stage transmucosal abutments than in nonsubmerged, one-stage implants.

Crevicular fluid osteocalcin and pyridinoline cross-linked carboxyterminal telopeptide of type I collagen (ICTP) as markers of rapid bone turnover in periodontitis. A pilot study in beagle dogs.

The objective of this study was to correlate the levels of 2 putative markers of bone metabolism, namely osteocalcin and pyridinoline cross-linked carboxyterminal telopeptide of type I collagen (ICTP), to the progression of experimental alveolar bone loss in the beagle dog. 36 control sites and 36 experimental sites in 2 beagle dogs were assessed longitudinally at 2-week intervals for gingival crevicular fluid (GCF) osteocalcin and ICTP levels during a 6-month observation period. Analysis of osteocalcin and ICTP in GCF was performed by RIA. During the study, bone-seeking radiopharmaceutical uptake (BSRU) of 99mTc-MDP was assessed monthly; standardized radiographs were taken at 2-week intervals. The results showed osteocalcin and ICTP levels in GCF increased significantly (p < 0.05) by 2 weeks following initiation of disease. This increase preceded significant increases in BSRU by 2 weeks and radiographic evidence of bone loss by 4 weeks. BSRU was significantly elevated (p < 0.05) at experimental sites as compared to controls at 4 and 8 weeks post-disease initiation. Osteocalcin in GCF peaked 8 and 10 weeks after ligature placement in experimental sites at levels nearly 10-fold greater than contralateral paired control sites. ICTP levels in GCF remained elevated throughout the entire disease progression phase. Following the removal of ligatures, both GCF osteocalcin and ICTP levels dropped precipitously approaching control values. Osteocalcin revealed overall a positive predictive value (PPV) and negative predictive value (NPV) for future bone loss during disease progression of 0.87 and 0.34, respectively, while ICTP showed both high PPV and NPV of 0.87 and 0.91 respectively. Results from this study in the dog model indicate that osteocalcin and especially ICTP relate to indices of active periodontal bony destruction and suggest that these molecules may serve as predictive markers for future alveolar bone loss.

Longitudinal radiographic study of crestal bone levels adjacent to non-submerged dental implants.

To investigate changes in alveolar crestal bone levels adjacent to dental implants prior to and after functional loading, dental radiographs of 103 implants from consecutively treated patients were taken at four time-points: immediately after surgical insertion, at 3-6 months after surgery, at 12 months, and at 24 months after surgery. A computer-assisted method was used to measure the percent of bone change (%BC) relative to the shoulder-apex length of the implants at mesial and distal sites. Differences in the mean rates of %BC between the pre-loading period (3-6 months post-surgery) and the post-loading periods PLP1 and PLP2 (6-12 months and 12-24 months post-surgery, respectively) were evaluated. Rates of % BC during PRE, PLP1, and PLP2 were also determined for locations (maxilla or mandible) and types (screw or press-fit). Significantly higher rates of % bone loss per month were found for all implants during PRE compared with PLP1 and PLP2, and during PLP1 compared with PLP2. During PRE, maxillary implants had a significantly higher rate of bone loss compared with mandibular implants. During PLP1, mandibular implants showed some further loss, whereas maxillary implants exhibited a small but significant gain. No significant difference was found during PLP2. Bone loss adjacent to press-fit implants was significantly higher than that adjacent to the screw type during PRE, while no difference was found during the post-loading periods.

Chloroprene and isoprene: cytogenetic studies in mice.

Groups of male B6C3F1 mice (n = 15) were exposed for 6 h per day to ambient air, to chloroprene (12, 32, 80, 200 p.p.m.) or to isoprene (438, 1750 and 7000 p.p.m.) on 12 days. These compounds are the 2-chloro and the 2-methyl analogues, respectively, of 1,3-butadiene, a genotoxic and carcinogenic chemical in B6C3F1 mice. Exposure to chloroprene resulted in a 100% incidence of mortality among the mice exposed to 200 p.p.m. At concentrations of 80 p.p.m. and below, chloroprene neither induced a significant increase in chromosomal aberrations (CA), sister chromatid exchanges (SCE) or micronucleated erythrocytes, nor significantly altered the rate of erythropoiesis or of bone marrow cellular proliferation kinetics. However, the mitotic index (MI) in the bone marrow of chloroprene-exposed mice was significantly increased. Under similar conditions, exposure to isoprene induced significant increases at all concentrations in the frequency of SCE in bone marrow cells and in the levels of micronucleated polychromatic erythrocytes (PCE) and of micronucleated normochromatic erythrocytes in peripheral blood. In addition, a significant lengthening of the bone marrow average generation time and a significant decrease in the percentage of circulating PCE was detected. However, exposure to isoprene did not induce in bone marrow a significant increase in the frequency of CA nor did the exposure significantly alter the MI. The dose-response curves for SCE and micronuclei induction were non-linear, appearing to saturate at 438 and 1750 p.p.m., respectively. These results suggest that, similarly to butadiene, inhaled isoprene can be expected to induce tumors at multiple sites in B6C3F1 mice.(ABSTRACT TRUNCATED AT 250 WORDS)