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S Froum

Publications and source records attributed to S Froum.

12 recordsLinked to original sources

Crystal structure of an angiogenesis inhibitor bound to the FGF receptor tyrosine kinase domain.

Angiogenesis, the sprouting of new blood vessels from pre-existing ones, is an essential physiological process in development, yet also plays a major role in the progression of human diseases such as diabetic retinopathy, atherosclerosis and cancer. The effects of the most potent angiogenic factors, vascular endothelial growth factor (VEGF), angiopoietin and fibroblast growth factor (FGF) are mediated through cell surface receptors that possess intrinsic protein tyrosine kinase activity. In this report, we describe a synthetic compound of the pyrido[2,3-d]pyrimidine class, designated PD 173074, that selectively inhibits the tyrosine kinase activities of the FGF and VEGF receptors. We show that systemic administration of PD 173074 in mice can effectively block angiogenesis induced by either FGF or VEGF with no apparent toxicity. To elucidate the determinants of selectivity, we have determined the crystal structure of PD 173074 in complex with the tyrosine kinase domain of FGF receptor 1 at 2.5 A resolution. A high degree of surface complementarity between PD 173074 and the hydrophobic, ATP-binding pocket of FGF receptor 1 underlies the potency and selectivity of this inhibitor. PD 173074 is thus a promising candidate for a therapeutic angiogenesis inhibitor to be used in the treatment of cancer and other diseases whose progression is dependent upon new blood vessel formation.

3T3 Cells

The use of transitional implants for immediate fixed temporary prostheses in cases of implant restorations.

While the original Brånemark implant protocol has continued to evolve, the avoidance of implant loading during osseointegration remains a prerequisite with all implant systems. Immediately loaded transitional implants have recently been developed to support the fabrication of a fixed provisional prosthesis that provides implant patients with improved aesthetics and function during the osseointegration period. In this manner, osseointegration can occur free from prosthetic and transmucosal loads. This article describes the use of transitional implants and presents a classification of three different case types.

Aged

Replacement therapy.

HTR Synthetic Bone's user friendly properties include: Hydrophilicity: holds clot and prevents its breakdown. Negative electric charge: adheres to bone and implant. Doesn't seem to get infected: less than one percent. Can graft to its surface: antibiotics or bone growth proteins for a slow timely release into adjacent areas. Does not require a barrier membrane with its use. Regenerating bone adheres to and is in direct contact with the HTR material. Has ability to attract the immature mesenchymal cell of the marrow that differentiate to osteoblasts: it is more than filler. Results in regeneration of bone three to four times as dense as bone regenerated by a barrier membrane/or as found in most normal dental alveolus.

Adult

Human intrabony lesion responses to debridement, porous hydroxyapatite implants and teflon barrier membranes. 7 histologic case reports.

7 vertical lesions at 7 teeth in 3 adults with severe periodontitis were treated using open surgical debridement, porous hydroxyapatite grafts and placement of a barrier membrane. Roots were notched at both gingival margins and deepest visible calculus. Flaps were sutured coronally and patients were placed on 0.12% chlorohexidine gluconate twice daily for 2 weeks, post-surgery. Patients returned frequently for plaque control until block removal at 16 to 28 weeks post-surgery. 1 additional block was harvested after 28 weeks. The latter site received root planing only and closed by epithelial adhesion. In the 7 experimental sites, clinical responses were uneventful, and gain in clinical closure varied from 1.7 to 5.0 mm (average = 3.6 mm). Histologically, 2 sites exhibited closure by a long junctional epithelium. The remaining 5 sites showed gingival recession to be apical to the calculus notch or the calculus notch to be epithelialized. However, apical to the notch and within the osseous crater, cellular cementum deposition was marked as was increased bone mass. The increase in bone mass was the result of osteogenesis within the surrounding graft particles which often fused with osseous seams of the crater. A functionally-oriented PDL was seen usually at these sites.

Adult

Human suprabony healing responses following root demineralization and coronal flap anchorage. Histologic responses in 7 sites.

6 suprabony pockets in 2 adult patients were treated with debridement and citric acid root demineralization. Following these procedures, coronal positioning of the marginal flaps was performed at 2 sites. At 4 sites, the marginal flaps were sutured coronally using orthodontic brackets as anchors. At 1 additional site, root debridement only was performed and the margin was placed at about crestal level. Prior to root planing, all roots were notched both at the level of the gingival margin and the most apically positioned calculus. Blocks were harvested 7 and 18 weeks postsurgery and prepared for histologic analysis. Clinical results showed a gain in probing attachment in both coronally positioned sites (average = 1.8 mm) and coronally anchored sites (average = 4.5 mm). The additional debrided-only site showed a gain in probing attachment of 0.1 mm. Histologically, new cementum with functionally inserted fibers was seen within the calculus notch in all coronally anchored sites. This new attachment was associated with crestal osteogenesis. In the 2 coronally positioned and root demineralized sites, new attachment was seen within the calculus notch in 1 out of the 2 specimens evaluated. Within the limits of the evidence presented, coronal anchorage of flaps enhanced probing attachment and new attachment when used in conjunction with root demineralization.

Antacids

Histologic healing responses in human vertical lesions following the use of osseous allografts and barrier membranes.

4 vertical lesions at 3 teeth in 2 volunteer adults with severe periodontitis were treated by open surgical debridement, osseous allografts and barrier membranes. Roots were notched at both gingival margins and the deepest visible calculus and flaps were sutured coronally. Patients were placed on 0.12% chlorhexidine gluconate 2x daily post-surgery, and blocks were harvested 5 to 6 weeks after surgery. No abnormal clinical responses were noted during the observation period. In the 4 sites, the average preoperative pocket depth was 9.4 mm; the post-operative pocket depth averaged 4.9 mm, recession averaged 0.9 mm and gain in clinical closure averaged 3.6 mm. Histologically, new cementum measured coronally-apically at the treated sites varied from 0.0 mm to 1.7 mm, with an average of 1.1 mm. Osseous remodelling and crestal osteogenesis were seen in association with cementogenesis. The newly deposited cementum showed insertion of functional oriented fibers. New attachment was present within 2 out of 4 calculus notches in this sample.

Adult

Human histologic responses to guided tissue regenerative techniques in intrabony lesions. Case reports on 9 sites.

9 sites of 8 teeth in 5 adults with severe periodontitis were treated by open surgical debridement followed by placement of 1 of 2 Teflon barrier membranes. Teeth were notched at both gingival margins and deepest visible calculus on the root. Barrier membranes were placed apical to alveolar crest and coronal to gingival notch. Flaps were sutured coronally and patients were placed on 1.2% chlorohexodine gluconate twice daily for 2 weeks, post-surgery. Subsequent to suture removal, patients returned for frequent plaque control until block removal. In order to observe early healing responses, 6 sites were harvested 5 to 8 weeks after surgical treatment. 3 additional sites were removed 14, 22 and 30 weeks respectively after surgical treatment. Histologically, new cementum was seen in a linear direction along root surfaces in 6 out of 9 sites (length of cementum = 0.5 to 1.7 mm). 3 sites showed no evidence of new attachment. At sites of cementogenesis, functionally-oriented fibers were inserted. The osseous seams opposite the new attachment often demonstrated osteogenesis. Regenerative responses were seen with both types of teflon membranes and were present as early as 5 weeks after surgery.

Adult

Human intraosseous healing responses to the placement of tricalcium phosphate ceramic implants. II. 13 to 18 months.

Five intrabony lesions in a 40-year-old healthy, white female patient suffering with severe periodontitis were removed en bloc, 13 to 18 months after flap debridement and graft placement. At the time of debridement, the position of the gingival margin and the most apically located calculus were notched in the root to serve as reference points. All lesions received tricalcium phosphate ceramic implants, and the lesions healed uneventfully. The sites were professionally cleaned frequently during the experimental period. At the time of block removal, clinical measurements demonstrated gingival recession (average = 2.6 mm) and a gain in clinical closure (average = 2.3 mm). Histologic evaluation of step serial sections of these blocks showed limited presence of graft particles. The particles were surrounded by dense connective tissue. They did not induce inflammation, nor did they appear to enhance osteogenesis or cementogenesis. Closure of lesions was essentially done by a long junctional epithelium adhesion and limited evidence of new connective tissue--root attachment. In the 18-month specimen, active root resorption was seen immediately apical to the junctional epithelium at a site demonstrating significant inflammation in some sections. Fibrils apparently arising from the resorbing dentinal wall were seen in these sections. Serial sections of this site showed cellular cementum and functional fiber attachment at the resorption sites. These variations in resorption/repair/regeneration within the same surgical site were seen 18 months postsurgery and thus may reflect local tissue responses to inflammatory fluctuations rather than surgical sequellae.

Adult

Histological evaluation of human intraosseous healing responses to the placement of tricalcium phosphate ceramic implants. I. Three to eight months.

Eight intrabony lesions in four patients were removed en bloc 3 to 8 months after periodontal flap debridement. At the time of debridement, the position of the gingival margin and the most apically located calculus were notched to serve as reference points. All lesions received "Synthograft" implants and lesions healed uneventfully. Even though these were severely involved periodontal sites, clinical measurements at time of block removal demonstrated gingival recession (average = 2.9 mm) and a gain in clinical closure (average = 2.6 mm). Histologically, graft particles were present in each specimen. They were walled off by collagen and did not appear to enhance new attachment nor did they induce an inflammatory infiltrate. Thus, they seemed to act as nonirritating fillers. Microscopically, closure of the lesions demonstrated repair with limited evidence of new connective tissue attachment. Histologic expression of the clinical gain in closure was the result of closure by long epithelial adhesion (long junctional epithelium) and possible linkage of dentinal collagen with gingival fibers at areas of dentinal resorption. These variations in closure were often seen within the same clinical site.

Alveolar Process