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Biomedical subjects

T H Howell

Publications and source records attributed to T H Howell.

At least 19 recordsLinked to original sources
PubMed2000

The effect of interleukin-11 on the progression of ligature-induced periodontal disease in the beagle dog.

BACKGROUND: The rate of progression of periodontal disease is dependent on the complex regulatory interactions between bacteria and the immune modulators of the host response. The purpose of this investigation was to determine if recombinant human interleukin-11 (rhIL-11), known to downregulate several inflammatory modulators, has the ability in subcutaneous administration to reduce the rate and/or extent of periodontal attachment loss and radiographic bone loss in a ligature-induced periodontal disease beagle dog model. METHODS: Twenty 18-month-old female beagle dogs were brought to optimal periodontal health over a 2-week period. Periodontal disease was induced by placing 2.0 silk ligatures around the mandibular first molar and premolar teeth. The dogs were divided into 3 treatment groups and one control group. The 3 treatment groups received subcutaneous injections of either 15, 30, or 80 microg/kg of rhIL-11 in saline buffer twice a week. The placebo group received buffer only subcutaneously twice a week. The gingival health of each animal was measured by recording the presence or absence of gingival inflammation, plaque, and bleeding upon probing. Attachment levels and bone height were also measured. Treatment administration and clinical and radiographic evaluations were performed in a masked fashion. RESULTS: At week 8, the placebo group had 3.89 mm of attachment loss and 73.8% radiographic bone remaining. The 15 microg/kg group had 1.99 mm attachment loss and 89.5% bone remaining; the 30 microg/kg group had 0.84 mm attachment loss and 92.5% bone remaining; and the 80 microg/kg group had 1.05 mm attachment loss and 85.5% bone remaining. All 3 treatment groups lost significantly less attachment and retained significantly more bone than did the placebo group. CONCLUSIONS: The study indicates that subcutaneous injections of rhIL-11 were able to slow the progression of attachment and radiographic alveolar bone loss in a ligature-induced beagle dog model.

Alveolar Bone Loss↗
PubMed1998

The effect of different diagnostic thresholds on incidence of disease progression.

Detection of periodontal disease progression occurs when a predetermined threshold of attachment loss is exceeded during longitudinal monitoring. The incidence of disease progression in a population may be dependent on the method and threshold utilized to identify significant changes in attachment level measurements. The aim of this study was to investigate the effect of utilizing different methods and thresholds on the incidence of disease progression in an untreated periodontitis population. The relationship between baseline clinical parameters and disease progression was also examined. A total of 411 interproximal sites in 46 individuals were monitored monthly over a 6-month period. Disease progression was determined by the cumulative sum (CUSUM) method and by the absolute change in relative attachment level between months 0 and 6 utilizing 3 different thresholds for attachment level change (0.58 mm, 1.16 mm, and 1.74 mm) based upon examiner repeatability using an automated probe. Utilizing the CUSUM method, 49 of 411 sites (11.9%) demonstrated attachment loss over the 6-month observation period. When attachment level changes > or = 0.58 mm, > or = 1.16 mm, and > or = 1.74 mm were used to identify disease progression, the percentage of sites exhibiting deterioration were 19.5%, 8.8%, and 2.9%, respectively. These results demonstrate that the apparent incidence of disease progression was dependent on the method and threshold utilized to detect progressive sites. When utilizing the CUSUM and 0.58 mm thresholds a significant (P < 0.05), but weak relationship (r = -0.26) was observed between baseline relative attachment level measurements and sites exhibiting disease progression. This finding suggests that sites with significant but relatively less attachment loss may be more likely to experience further breakdown compared to sites with a history of greater periodontal destruction.

Analysis of Variance↗
PubMed1997

Enantiospecific inhibition of ligature-induced periodontitis in beagles with topical (S)-ketoprofen.

Systemic and topical administration of non-steroidal anti-inflammatory drugs (NSAIDs) has been shown to reduce periodontal disease progression in both animal models and human subjects. Our present research focuses on single enantiomers of these agents to examine whether enantiospecific therapy will be efficacious in slowing periodontitis. The purpose of this study was to evaluate the inhibitory effects of (S)-ketoprofen on experimentally induced alveolar bone loss in beagle dogs. 16, 18-month-old, female beagles were brought to optimal periodontal health over a 2-week pretreatment period. Experimental periodontitis was then induced by placing silk ligatures around premolar and molar teeth and by instituting a soft, plaque-promoting diet. At baseline, animals were randomized to 1 of 4 groups, consisting of 2x daily administration of (1) placebo dentifrice, (2) 0.3% (S)-ketoprofen dentifrice, (3) 3.0% (S)-ketoprofen dentifrice, or (4) 10.0 mg (S)-ketoprofen capsules (p.o.) over a 60 day treatment period. Standardized, periapical radiographs exposed at days 1 and 60 were analyzed by computer-assisted digital radiography in order to assess the rate of alveolar bone loss. Secondary outcomes included technetium 99m-tin-diphosphonate (99mTc-Sn-MDP) uptake and the gingival index. At baseline, no differences were observed among the groups for linear bone height or 99mTc-Sn-MDP uptake ratios. From days 1 to 60, cohorts differed significantly in terms of bone loss rates (p < 0.001). In particular, beagles treated with systemic or topical (S)-ketoprofen (0.3% or 3.0% dentifrices) exhibited significantly lower mean rates of bone loss compared to placebo treated beagles (p < 0.05). Group differences in mean radiopharmaceutical uptake ratio changes approached significance (ANOVA, p = 0.07), where animals treated with topical 0.3% (S)-ketoprofen demonstrated a reduction and other groups demonstrated elevations over the 60-day dosing period. Treatment cohorts did differ significantly with respect to changes in mean gingival indices (p < 0.05). Animals treated with 0.3% or 3.0% (S)-ketoprofen dentifrice exhibited significantly reduced elevations in gingival index scores as compared to placebo treated animals. These data provide evidence that enantiospecific therapy with (S)-ketoprofen, topically or systemically delivered, may alter the progression of periodontal disease in the beagle dog model.

Alveolar Bone Loss↗
PubMed1997

Comparison of manual and automated probing in an untreated periodontitis population.

Diagnosis of periodontal disease progression involves recording two probing attachment level measurements over an adequate time interval. A diagnostic instrument which exhibits less measurement variability allows for increased sensitivity and earlier disease detection. Traditionally, a manual probe with an occlusal stent of the cementoenamel junction (CEJ) as a reference landmark has been the method of choice. Automated probes that use an occlusal disk as the reference landmark have been developed as an alternative means of measure. The aim of this study was to compare the variability of these two probing methods. Four hundred eleven (411) interproximal sites in 46 untreated periodontitis patients were monitored by a single examiner over a 6-month period. Each site was measured on a monthly basis, first with an automated probe (AP) followed by a manual probe (MP) in combination with a custom-fabricated acrylic stent. Measurement variability of the two probing methods was also compared over a 7-day interval. The AP measurements were significantly more variable than the MP measurements (P < 0.001) when considering the variability between two passes at the same visit. Over the 6-month period, the MP measurements demonstrated significantly more variability than the AP measurements (P < 0.001). It was also noted that MP measurements exhibited more variability at sites with frequent bleeding during the 6 months of the study (P = 0.006). The results of this study demonstrate that AP may have less variability of attachment level measurements over a 6-month period and may be less influenced by local inflammatory changes. However, future comparison studies should include multiple examiners to reduce examiner bias and should alternate the probing method to reduce bias created by local tissue changes from multiple probings.

Adult↗
PubMed1997

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.

Administration, Topical↗
PubMed1997

A feasibility study evaluating rhBMP-2/absorbable collagen sponge device for local alveolar ridge preservation or augmentation.

This two-center human clinical trial evaluated recombinant human bone morphogenetic protein-2 delivered in an absorbable collagen sponge (rhBMP-2/ACS) for either alveolar ridge preservation after tooth extraction or augmentation of localized osseous defects. This 24-month study comprised two parts: a 4-month acute safety and bone induction period (Part I) followed by a 20-month, osseointegration, functional restoration, and long-term safety evaluation (Part II). The primary objective of Part I, discussed in this article, was to evaluate the short-term safety and technical feasibility of the rhBMP-2 device implantation. Twelve patients (six preservation and six augmentation) were enrolled in the investigation. Patient safety was monitored by oral examinations, radiographs, and the collection of blood samples to measure serum chemistries, hematology, and potential antibody formation. Technical feasibility was evaluated by collecting information relating to the handling properties of the rhBMP-2/ACS device. The ability of various evaluative tools to measure the bone-inducing activity of the rhBMP-2/ACS device was also assessed. The clinical results suggested that rhBMP-2/ACS was well tolerated locally and systemically, with no serious adverse events. The device was found to be easily handled and adapted to the ridge and extraction socket. Using direct measurements, all sites demonstrated firmness and fullness to palpation at 4 weeks; however, a loss of volume was noted in some treatment areas between 4 and 8 weeks. Augmentation of the alveolar ridge was not observed in the patients as assessed by the evaluation techniques. This trial indicated that the use of rhBMP-2/ACS to preserve alveolar ridge after tooth extraction or augmentation of localized defects is safe and feasible. Bone fill was observed in all alveolar sockets filled with the rhBMP-2 device.

Absorption↗
PubMed1996

Polypeptide growth factors for periodontal regeneration.

The regeneration of periodontal attachment apparatus is particularly difficult to achieve, primarily because of the presence of many different kinds of tissue that must be restored to produce a functional unit. Traditional methods aimed at regenerating the periodontium have limited indications, and their results are not predictable. Recently, investigators have begun to understand the cellular processes necessary for repair and regeneration of periodontal tissues. Proteins called growth factors have been identified that coordinate these cellular events. The growth factors that may contribute to periodontal regeneration include platelet-derived growth factor, insulin-like growth factor, transforming growth factor-beta, and bone morphogenetic proteins. In vitro studies have demonstrated the positive effects of these factors on a number of cell types essential for periodontal regeneration. For instance, it has been shown that platelet-derived and insulin-like growth factors promote proliferation of osteoblasts an periodontal ligament cell-derived fibroblasts. Animal models have also been used to verify that growth factors can enhance regeneration in vivo following periodontal disease and as an adjunct to implant placement. In the future, human clinical trials will be required to identify the ideal growth factors, their proper doses, and the most suitable carrier system for them.

Animals↗
PubMed1994

Inhibition of peri-implant bone loss with the nonsteroidal anti-inflammatory drug flurbiprofen in beagle dogs. A preliminary study.

There is increasing interest in how pathways of tissue destruction around dental implants are similar as for teeth and how these pathways can be modulated to slow loss of supporting bone. The purposes of this study were to develop a short-term animal model to study the effect of the nonsteroidal anti-inflammatory drug flurbiprofen, on slowing the rate of induced peri-implant bone resorption. A total of 20 cylindrical titanium implants were placed in 2 beagle dogs using a low-trauma surgical technique. During the 3-month healing period without functional loading of the implants, daily oral hygiene was performed to maintain a Gingival Index of 0 to 0.5. At completion of the healing period, a baseline evaluation was performed which included the uptake of the bone-seeking radiopharmaceutical (BSRU) 99mtechnetium-tin-diphosphonate (99mTc-Sn-MDP) in peri-implant bone and standardized radiographs. Peri-implantitis was induced with 4-0 silk ligatures, cessation of oral hygiene and soft diet. One beagle was given 0.02 mg/kg of flurbiprofen by mouth; the other received a placebo. BSRU and radiographic height of bone were remeasured to calculate the rate of bone loss during the 60-day treatment period. The percent rate of bone loss during the study period was calculated from the radiographs using a computer-assisted method. The radiopharmaceutical uptake for the flurbiprofen-treated implants remained unchanged. However, BSRU for placebo-treated implants was significantly increased from baseline.(ABSTRACT TRUNCATED AT 250 WORDS)

Alveolar Bone Loss↗
PubMed1993

New technologies for the diagnosis of periodontal disease.

Historically the initial onset of periodontal disease in an individual was considered slow but continuously progressive over time. It was inferred that an individual would experience progressive destruction of the attachment structures until edentulous. However, several studies in the early 1970s contested the traditional concept of continuous disease progression. These studies suggested that periodontal disease progressed by recurrent acute episodes. In specific individuals, the loss of attachment was faster than the concept of slowly progressing disease. There were also sites in patients that progressed slower (or not at all) than anticipated on the basis of radiographic and clinical history of previous disease progression. These findings clearly indicated the need to explore the nature of periodontal disease progression and to institute a major effort into innovative methods to diagnose periodontal diseases. Dentists and researchers could more effectively prevent and treat periodontal disease and relate pertinent research findings to specific disease initiation and progression.

Alveolar Bone Loss↗
PubMed1993

The effect of a mouthrinse based on nisin, a bacteriocin, on developing plaque and gingivitis in beagle dogs.

The aim of this study was to evaluate the effect of nisin, an antimicrobial peptide, on the development of plaque and gingivitis in beagle dogs when compared with 0.12% chlorhexidine and a placebo. 16 female beagle dogs 1 year of age were brought to optimum gingival health by scaling, root planing and polishing. At the conclusion of the pretreatment phase, the dogs were divided into 4 groups for the application of the test agents and were placed on a plaque promoting diet of Purina Dog Chow softened with water. Test agents included 100 micrograms/ml nisin and 300 micrograms/ml nisin formulated in a vehicle containing 1 mM NaEDTA; negative control comprised of exactly the same formulation but omitting nisin; and 0.12% chlorhexidine as Peridex. Throughout the treatment period, formulations were applied 2x daily to premolar teeth in each quadrant for 1 min using a Monojet syringe. The development of plaque and gingivitis was monitored at 15, 27, 39, 53, 74 and 88 days during the treatment phase using standard measurements of gingival index, plaque index, stain index and bleeding to probing. Throughout the treatment phase, plaque accumulation increased in all groups, but the rate of plaque build-up was less in groups treated with either nisin or chlorhexidine formulations compared with the placebo treated group. The gingival index of dogs in all groups increased throughout the study period. However, from day 27 onward, the groups receiving nisin had lower gingival index scores than did the placebo group.(ABSTRACT TRUNCATED AT 250 WORDS)

Analysis of Variance↗
PubMed1993

Nonsteroidal antiinflammatory drugs as inhibitors of periodontal disease progression.

Recent interest in the control and modulation of periodontal disease has focused on the potential benefits of blocking the host response mechanisms involved in the progression of the disease. In addition to recent advances in the identification and control of etiologic bacteria, investigators have indicated promising results using nonsteroidal antiinflammatory drugs (NSAIDs) as inhibitors of the inflammatory destruction in periodontal disease. This article examines research efforts over the last 20 years describing the role of prostaglandins in periodontal disease and the effect of NSAIDs on the progression of gingival inflammation and alveolar bone loss.

Alveolar Bone Loss↗
PubMed1993

Blocking periodontal disease progression with anti-inflammatory agents.

Recent advances in the identification of specific immuno-inflammatory pathways of periodontal disease have encouraged investigators to attempt to modulate some of these host responses in an attempt to slow the periodontal disease process. Some of the best known mediators of these immuno-inflammatory pathways are prostaglandins. The action of prostaglandins can be inhibited through the use of non-steroidal anti-inflammatory drugs (NSAIDs). This review examines research over the last two decades during which the effect of several NSAIDs on the progression of gingival inflammation and alveolar bone loss was explored.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1992

Effects of NSAIDs on beagle crevicular cyclooxygenase metabolites and periodontal bone loss.

This investigation focuses on the changes in the concentrations of cyclooxygenase (CO) products present within the crevicular fluid in naturally-progressing periodontitis in the beagle and the effects of various non-steroidal anti-inflammatory drugs (NSAIDs) on these metabolite levels and disease progression. Six groups of 5-6 beagles with periodontitis were followed for 6 months to determine the pretreatment rate of radiographic bone loss. At baseline, groups of animals were placed on soft chow to promote disease progression. Groups were treated with either placebo, three different formulations of systemic ibuprofen, systemic naproxen or topical flurbiprofen. During the 6-month treatment phase, crevicular fluid (CF) samples and radiographs were taken at regular intervals. Radioimmunoassay of CF samples from untreated animals demonstrated a steady increase in prostaglandin E2 (PGE2) over baseline values. At 1 month, CF-PGE2 levels increased 2-fold over baseline and, by 6 months, had reached a 5- to 6-fold elevation. Crevicular fluid thromboxane B2 (CF-TxB2) levels rapidly reached a 4- to 5-fold peak over baseline at 1 month and subsequently dropped to a 2-fold elevation for the remainder of the study. The rate of bone loss (BLOSS) in untreated animals increased 38% during the 6-month period, as compared to baseline pretreatment BLOSS rates. Overall, there was a significant depression in the CF levels of both PGE2 and TxB2 in all NSAID-treated groups. All NSAID treatments significantly retarded BLOSS, ranging from 21.0-36.9% of the control BLOSS rate. Furthermore, CO activation represents a major regulatory step in bone destruction and may thereby serve as an important site for pharmacological modulation.

Administration, Oral↗
PubMed1991

Effect of the NSAID piroxicam, topically administered, on the development of gingivitis in beagle dogs.

A single-blind investigation was designed to study the effects of piroxicam in preventing gingival inflammation and plaque formation in beagle dogs. Twelve 1-year-old beagles were brought to optimum oral hygiene and gingival health. Thereafter, they were fed a moist plaque-promoting diet and were divided into three groups. The first group received daily administration of 1.0 ml placebo gel (methylcellulose) painted on the teeth. The second group received 1.0 ml of gel containing 2 mg/ml piroxicam and the third group received 1.0 ml liquid containing 2 mg/ml of piroxicam. Placebo and test solutions were applied daily, and dogs were examined biweekly for evaluation of plaque accumulation, gingival inflammation, bleeding upon gentle probing and tooth staining. Data were analyzed using the Krushkal-Wallis test. Over the treatment period, plaque accumulation was substantial in all three groups and was not significantly different between the three groups. By week 2, the gingival index in the piroxicam-treated dogs was significantly lower than that of the placebo-treated group and remained so throughout the study, with the exception of wk 6 and 12 in the topical gel-treated group. Mean percent bleeding sites were also significantly less in the piroxicam-treated groups than in the control dogs. Staining of the teeth increased for all groups over the 16-wk treatment period. These data indicate that piroxicam can significantly inhibit the development of gingival inflammation in beagle dogs.

Administration, Topical↗
PubMed1991

Inhibition of alveolar bone loss in beagles with the NSAID naproxen.

The non-steroidal anti-inflammatory drug(NSAID) naproxen was studied in 11 beagle dogs over a 13-month period to determine its effect on the progression of periodontitis. Following a 6-month pretreatment period, 5 dogs received naproxen daily at a dosage of 2.0 mg/kg for 1 month, then 0.2 mg/kg for 6 months. Six control dogs received a gelatin capsule daily as placebo. Standardized radiographs were used to measure the rate of bone loss during the pretreatment and treatment periods. In the control dogs, the rate of bone loss was seen to increase during the treatment period although the increase was not statistically significant. In dogs treated daily with naproxen, the rate of bone loss in the treatment period was significantly less at 4 months of treatment; however, at 7 months the difference, though lower than pretreatment rate, was not significant. When the percent change in rate of bone loss during the overall 7-month treatment period was compared with pretreatment rate, the control dogs demonstrated a 38% increase in rate of bone loss during the treatment period contrasting with a 61% decrease in bone loss rate in naproxen-treated dogs. The data indicate that the non-steroidal anti-inflammatory drug naproxen can significantly inhibit alveolar bone loss in beagles. At 4 months of treatment the rate of bone loss in the naproxen-treated dogs was significantly less than pretreatment, but at 7 months of treatment the rate was no longer statistically significantly less than baseline. This probably reflects a dose response to naproxen treatment for, after 30 days of the treatment period, the naproxen dosage was reduced 10-fold due to tolerance by the beagle.

Alveolar Bone Loss↗
PubMed1991

The effects of short-term application of a combination of platelet-derived and insulin-like growth factors on periodontal wound healing.

Polypeptide growth factors are a class of potent natural biologic mediators which regulate many of the activities of wound healing including cell proliferation, migration, and metabolism. Platelet-derived growth factor (PDGF) and insulin-like growth factor-I (IGF-I) have been shown to regulate DNA and protein synthesis in bone cells in vitro and to interact synergistically to enhance soft tissue wound healing in vivo. We have hypothesized that the combination of PDGF and IGF-I may, therefore, enhance regeneration of both the soft and hard tissue components of the periodontium. To test this hypothesis we performed conventional periodontal surgery on all 4 quadrants of the mouth of 13 beagle dogs with naturally occurring periodontal disease. Following flap reflection, degranulation, and root planing, all premolar teeth in 2 quadrants of each dog received a combination of 3 micrograms of recombinant PDGF-B and IGF-I in a methylcellulose gel, while the premolar teeth in the contralateral quadrants received the gel alone. Teeth in 4 additional animals also received 125I-PDGF or 125I-IGF-I in the treated sites. The clearance rate of the 125I-labeled protein, changes in local bone metabolism, and amount of new bone and cementum with inserting collagen fibers were measured. The clearance studies revealed that the half-life of the factors at the site of application was 3.0 hours for IGF-I and to 4.2 hours for PDGF-B. Greater than 96% of the radio-labeled proteins was cleared by 96 hours and no radioactivity was detected 2 weeks after application. There was a significant (P less than 0.01) 2-fold increase in uptake of the bone-seeking radiopharmaceutical Technetium 99-MDP at 2 and 4 weeks in growth factor treated sites compared to controls, indicating that there was increased metabolic activity within the bone at these sites. Computer-aided histologic analyses of biopsies obtained at 2 and 5 weeks post-operatively revealed a significant (P less than 0.01), 5 to 10 fold increase in new bone and cementum in PDGF-B/IGF-I treated sites at both time points compared to controls receiving the placebo gel. The height and total area of new bone continued to increase from 2 to 5 weeks. The new bone underwent a normal maturation process as judged by histologic appearance. A physiologic periodontal ligament space was also formed between the new bone and new cementum. There was no increase in ankylosis in the treated sites.(ABSTRACT TRUNCATED AT 400 WORDS)

Alveolar Bone Loss↗