Prosthodontic treatment, patient response, and the need for maintenance of complete implant-supported overdentures: an appraisal of 5 years of prospective study.

The prosthodontic methods and outcomes of treating 127 patients in nine centres over a period of 5 years is described. The benefits perceived by patients and the changes induced in the denture-bearing tissues and temporomandibular joints are reported. To sustain effective treatment outcomes, the levels of maintenance needed by the overdentures are contrasted for restoration of the edentulous mandibles and maxillae.

A 5-year prospective multicenter follow-up report on overdentures supported by osseointegrated implants.

This report presents the results of a 5-year prospective multicenter study including nine centers worldwide. A total of 30 patients received 117 Brånemark implants in the maxillae, and 103 patients received 393 implants in the mandibles. According to the protocol, all integrated maxillary implants were to be loaded; however, only two of four mandibular implants were planned for support of the overdentures, leaving the remaining implants covered by mucosa as backup for possible implant failures. Thirty-five patients (26.3%) who were provided with 127 implants (24.9%) were withdrawn from the study. Six patients treated in the maxilla lost all their implants and resumed wearing complete dentures. The cumulative success rates for implants and for overdentures supported by two implants in the edentulous mandible were 94.5% and 100%, respectively. The corresponding cumulative success rates for implants and for overdentures supported by an optimal number of implants in the maxilla were 72.4% and 77.9%, respectively. Significantly better jawbone characteristics at the time of implant surgery were considered to contribute to the better cumulative success rates in the mandibles. Mean marginal bone loss was 0.8 mm (SD 0.8) and 0.5 mm (SD 0.8) for loaded implants during a 5-year period of time in the maxillae and mandibles, respectively. Measurements of the clinical height of the abutment cylinders indicated a mean recession (0.2 mm) of peri-implant mucosa during the follow-up period in the mandibles. Conversely, hyperplasia was observed in the maxillae.

Distribution of load in an oral prosthesis system: an in vitro study.

Although the long-term success of osseointegrated endosseous implants for the support of fixed dental prostheses has been reported, the increasingly routine and widespread use of implant-supported prostheses has led to problems associated with their structural integrity. To assess the service life of the components of the prosthetic system, a knowledge of the loads transmitted through the system is needed. This paper reports in vitro findings for forces and bending moments transmitted through the abutments from a fixed dental prosthesis to its supporting implants. The results have been compared to previous theoretical analyses that generally overestimate the maximum tensile forces. The effect of the length of distal cantilevers and of missing gold screws as the result of loosening or fracture is also considered. It is proposed that bending moments may play a larger role in failures than previously believed.

Synthesis and biological characterisation of a series of iberiotoxin analogues.

We report here the synthesis of iberiotoxin (IbTX), a 37-amino acid peptide containing three disulfide bridges, and a series of mono-looped analogues. All syntheses were conducted using Fmoc chemistry. Synthesis of IbTX gave a product which was indistinguishable from a reference sample in both its physico-chemical properties and its biological activity. A series of three mono-looped analogues, in which four of the six cysteines were replaced by alanine, were synthesised to give [Ala7,13,28,33]-IbTX, [Ala13,17,33,35]-IbTX and [Ala7,17,28,35]-IbTX. Oxidation of the linear form of [Ala7,17,28,35]-IbTX to form the Cys13 to Cys33 disulfide bridge proceeded more slowly than that of the other two analogues. None of these analogues was biologically active, indicating that no single loop is the mediator of channel blocking activity.

Factors related to success and failure rates at 3-year follow-up in a multicenter study of overdentures supported by Brånemark implants.

An international prospective study of Brånemark implants retaining overdentures was conducted at nine clinical centers. One hundred thirty-three subjects were recruited in a 12-month period and provided with 510 implants, 117 of which were in maxillae and 393 were in mandibles. This study reports the 3-year follow-up status of 120 overdentures and 444 implants. There were 11 overdenture failures (9.2%). Maxillary overdenture failure rates (27.6%) were nearly nine times greater than mandibular overdenture failure rates (3.3%). Maxillary overdenture treatment was less successful than previously reported fixed implant-supported restorations. However, their mandibular counterparts had success rates slightly higher than those reported for fixed implant-supported restorations. At 3 years, 150 implants remained submerged and 66 implants had been withdrawn because the subjects discontinued study participation. Eleven mandibular and 29 maxillary implants had failed and had been removed from 21 subjects. Logistic regression with forward model selection indicated that one two-way interaction was significantly related to implant failure. At highest risk were the subjects who possessed dental arches with bone quantity E and bone quality 4. Subjects with one implant failure were likely to have more than one failure. The Generalized Estimating Equation was used to adjust for the cluster effect in this population because multiple implants (2 to 6) were placed and evaluated in each of the 133 subjects.

Tightening characteristics for screwed joints in osseointegrated dental implants.

The significance of tightening abutment screws and gold cylinders to osseointegrated fixtures with the correct torque is demonstrated, and a simple relationship between applied torque and screw preload is derived by use of mechanical engineering principles. The principles of a number of tightening methods are outlined and assessments made of their accuracy. The difference between optimum and design torque is highlighted. The necessity and means of achieving optimum torque to ensure a reliable joint in clinical practice is discussed.

The synthesis and use of pp60src-related peptides and phosphopeptides as substrates for enzymatic phosphorylation studies.

A series of peptides and phosphopeptides corresponding to the auto-phosphorylation site of pp60src, -Asn-Glu-Tyr416-Thr-Ala-, were prepared by either Boc/solution or Fmoc/solid phase peptide synthesis and used as substrates to study their enzymatic phosphorylation by various casein kinases. The Tyr(P)-containing peptide, Asn-Glu-Tyr(P)-Thr-Ala, was prepared by the use of Fmoc-Tyr(PO3Bzl2)-OH in Fmoc/solid phase peptide synthesis followed by acidolytic treatment of the peptide-resin with 5% anisole/CF3CO2H. Both Asn-Glu-Tyr-Thr-Ala and Asn-Glu-Ser(P)-Thr-Ala were prepared by the Boc/solution phase peptide synthesis and employed hydrogenolytic deprotection of the protected peptides. Enzymatic phosphorylation studies established that (A) the Tyr residue acted as an unusual positive determinant for directing phosphorylation to the Thr-residue, (B) the rate of Thr-phosphorylation was markedly facilitated by a change from the Tyr-residue to the Tyr(P)-residue, and (C) a Ser(P)-residue was as effective as the Tyr(P)-residue in facilitating Thr-phosphorylation. A subsequent structure-function study using Asn-Glu-Phe-Thr-Ala, Asn-Glu-Tyr(Me)-Thr-Ala (prepared by Fmoc/solid phase peptide synthesis) and Asn-Glu-Cha-Thr-Ala (prepared by hydrogenation of Asn-Glu-Tyr-Thr-Ala) established that the rate of Thr-phosphorylation was influenced by the extent of hydrophobic-hydrophobic interactions by the aralkyl side-chain group (either aromatic or aliphatic) of the 416-residue with casein kinase-2; the rate of Thr-phosphorylation being decreased by the introduction of methyl or hydroxyl groups at the 4-position of the aromatic group (i.e. Tyr(Me) and Tyr respectively) but enhanced by the introduction of the hydrophilic phosphate group (i.e. as Tyr(P)).

Chemical synthesis of an O-phosphorylated tyrosine analogue of human angiotensin II, [Tyr(P)4] angiotensin II, and its vasoconstrictor effect in intact sheep.

The derivative N alpha-fluorenylmethoxy-carbonyl-O-dimethylphosphono-L-tyrosi ne was utilized in continuous-flow solid-phase synthesis to prepare the O-phosphotyrosine analogue of human angiotensin II, [Tyr(P)4] angiotensin II. Side-chain deprotection, including the removal of the methyl phosphate groups, as well as cleavage of the peptide from the solid support was achieved with 1 M trimethylsilyl-bromide-thioanisole in trifluoroacetic acid. Overall yield of purified peptide was 46%. The pressor response in intact sheep to graded infusions of the synthetic [Tyr(P)4] angiotensin II showed it to have similar potency to the native angiotensin II. However, a prolonged, elevated mean arterial pressure was observed following cessation of the infusion.

A multicenter study of overdentures supported by Brånemark implants.

Nine clinical centers participated in a prospective study of overdentures supported by Brånemark implants in the maxilla or mandible. The study initially comprised 133 patients provided with 117 implants placed in the maxilla and 393 implants placed in the mandible. The preliminary results indicate a success rate in the mandible comparable with the reports on fixed prostheses. Conversely, overdenture treatment in the maxilla seems to be less favorable than previous reports of fixed restorations. The differences between the fixed and the present overdentures in the maxilla were mainly based on differences in patient selection and bone quality. A total of 32 implants was mobile and removed and another 29 implants were lost to follow-up because of patient dropout up to the first annual checkup after denture placement. A higher implant failure rate occurred in the maxilla. Mucosal reactions were also more unfavorable around implants placed in the maxilla.

Theoretical analysis of the fatigue life of fixture screws in osseointegrated dental implants.

Metal fatigue failure of the gold screw used to retain a fixed prosthesis to Brånemark osseointegrated fixtures/abutments has been analyzed theoretically. Mechanical engineering principles show the importance of appropriate preload being applied through the gold screw to the gold cylinder and abutment. The significance of the screw design and necessity of applying the correct torque to achieve a long fatigue life for the screw are also described. The consequence of misalignment of a gold cylinder to an abutment is discussed.

Phosphorylation of src-phosphopeptides by casein kinases-1 and -2: favourable effect of phosphotyrosine.

The synthetic phosphotyrosyl tridecapeptide H-Arg-Leu-Ile-Glu-Asp-Asn-Glu-Tyr(P)-Thr-Ala-Arg-Gln-Gly-OH, reproducing a major phosphoacceptor site of protein tyrosine kinases of the src-family, can be phosphorylated at Thr-9 by both casein kinases -1 and -2. Its shorter derivative H-Asn-Glu-Tyr(P)-Thr-Ala-OH is not affected by casein kinase-1 while representing a substrate as good as the tridecapeptide for casein kinase-2. The unphosphorylated analogue H-Asn-Glu-Tyr-Thr-Ala-OH, however, is a much poorer substrate, and no significant phosphorylation could be observed of its O-methyl ether derivative H-Asn-Glu-Tyr(Me)-Thr-Ala-OMe. These data on one side corroborate the concept that casein kinase-1 recognizes residues located on the C-terminal edge of acidic stretches, providing, on the other, the evidence that phosphotyrosyl side chains can act as specificity determinants for casein kinase-2.

Synthetic fragments of beta-casein as model substrates for liver and mammary gland casein kinases.

The octapeptide Glu-Ser-Leu-Ser-Ser-Ser-Glu-Glu, corresponding to the 14-21 sequence of bovine beta-casein A2 and 11 shorter and/or modified derivatives were synthesized and used as model substrates for three casein kinases: rat liver casein kinases 2 and 1 and a casein kinase isolated from the golgi-enriched fraction of lactating mammary gland (GEF-casein kinase). Casein kinase-2 readily phosphorylates the octapeptide at its Ser-4 residue with a Vmax value comparable to those obtained with protein substrates and Km values of 85 microM and 11 microM in the absence and presence of polylysine, respectively. These are the most favourable kinetic parameters reported so far with peptide substrates of casein kinase-2. Stepwise shortening of the octapeptide from its N terminus promotes both a gradual decrease of Vmax and an increase of Km, this being especially dramatic in passing from the hexapeptide Leu-Ser-Ser-Ser-Glu-Glu (Km 210 microM) to the pentapeptide Ser-Ser-Ser-Glu-Glu (Km 2630 microM). The tetrapeptide Ser-Ser-Glu-Glu is the shortest derivative still phosphorylated by casein kinase-2, albeit very slowly, and the tripeptides Ser-Glu-Glu and Glu-Leu-Ser were not substrates at all. Furthermore, the pentapeptide Ser-Ser-Ser-Glu-Glu was found to be a better substrate than Ser-Ser-Ala-Glu-Glu, Ser-Ala-Ser-Glu-Glu and Ser-Ala-Ala-Glu-Glu by virtue of its lower Km value. These data, while confirming that the motif Ser-Xaa-Xaa-Glu is specifically recognized by casein kinase-2, strongly suggest that additional local structural features can improve the phosphorylation efficiency of serine-containing peptides which are devoid of the large acidic clusters recurrent in many phosphorylation sites of casein kinase 2. In particular, predictive structural analysis as well as NMR and C18 reverse-phase HPLC elution profile data support the hypothesis that a beta-turn conformation is responsible for the remarkable suitability of the octapeptide Glu-Ser-Leu-Ser-Ser-Ser-Glu-Glu and some of its shorter derivatives to phosphorylation mediated by casein kinase-2. While neither the peptide Glu-Ser-Leu-Ser-Ser-Ser-Glu-Glu nor any of its derivatives were affected by casein kinase-1, a rapid phosphorylation of the octapeptide by GEF-casein kinase at Ser-5 (not Ser-4) was obtained.(ABSTRACT TRUNCATED AT 400 WORDS)

Partially dephosphorylated phosphopeptide AcSer(P)-Ser(P)-Ser(P) is an excellent substrate for casein kinase-2.

The synthetic phosphopeptide AcSer(P)-Ser(P)-Ser(P), reproducing a recurrent feature of casein and other phosphoproteins, once partially dephosphorylated by acid phosphatase, serves as an efficient substrate for casein kinase-2. Previous dephosphorylation beyond 30% hinders subsequent phosphorylation and the entirely dephosphorylated peptide is not a substrate at all. The kinetic constants of the partially dephosphorylated phosphopeptide are much more favourable than those of the synthetic peptides SEEEAA, SSEE and SEE, the latter one being totally inert. Optimal phosphorylation occurs at pH values that ensure complete ionization of the phosphoseryl side chains. These data provide incontrovertible demonstration that phosphoserine can replace carboxylic amino acids as specificity determinant for CK-2, being more effective than glutamic acid itself.

Inhibition of intestinal citrulline synthesis causes severe growth retardation in rats.

delta-N-(phosphonacetyl)-L-ornithine (PALO) is a powerful and specific inhibitor of ornithine transcarbamylase (1), but it does not readily enter intact cells and therefore does not inhibit citrulline synthesis in intact liver or intestine. We have used the glycylglycine derivative of PALO (Gly-Gly-PALO) to evaluate the importance of intestinal citrulline synthesis in supplying arginine for growth. We have shown that the peptide derivative of PALO is selectively taken up by gut cells via the peptide permease and is released intracellularly as the free inhibitor. When administered in drinking water to 6-wk-old rat pups on an arginine-deficient diet, serum citrulline was reduced from 85 +/- 4.2 to 44 +/- 2.2 microM and arginine from 240.1 +/- 19.0 to 52.1 +/- 4.1 microM. Ornithine increased from 100 +/- 6.2 to 273.5 +/- 21.3 microM. Addition of 0.1 mM Gly-Gly-PALO to drinking water caused a rapid and complete inhibition of growth in rats on arginine-deficient diets, and this growth inhibition could be partially prevented by simultaneous administration of 1% (wt/wt) arginine to the diet and completely prevented with 1% (wt/wt) citrulline. The specificity of the effects of Gly-Gly-PALO on intestinal citrulline synthesis was shown by the inability of the drug to be taken up or to inhibit citrulline synthesis in isolated rat hepatocytes, and the oral administration of the drug had no effect on serum ammonia concentrations. The relative importance of endogenous synthesis of arginine compared with dietary arginine for growth was shown by the ability of Gly-Gly-PALO to inhibit the growth of rats maintained on standard laboratory chow containing normal levels of arginine.

Using commercial application' software. Integrating clinic office practices.

Automation of clinic business office practices has often been accomplished by the use of the procedures obtained from the provider of automated services. With the availability of the microcomputer and the commercially available business application software, the desired automated procedures may be obtained by discretionary use of the products. By describing the integration and the operational use of business application software within a multiphysician specialty clinic, the author highlights both the problems encountered and the benefits achieved.

Phytol degradation by marine bacteria.

Microbial degradation of phytol is often proposed to be the primary source of the acyclic isoprenoid acids observed in sediments, yet only a limited number of these acids have been found in bacterial cultures grown on phytol. This study reports detailed capillary gas chromatography and gas chromatography-mass spectrometry analyses of the products resulting from growth of marine bacteria on phytol as the sole carbon source. We examined two strains of bacteria which were able to oxidize phytol to phytenic acid but were unable to further degrade phytol. The third isolate studied converted phytol to a mixture of five saturated isoprenoid acids. The C(17) isoprenoid acid produced was of particular interest, since its genesis from phytol would have involved several unusual intermediates. It is suggested that this acid is produced by bacterial metabolism of the C(18) isoprenoid ketone (produced from phytol abiologically under oxic conditions) and that its abundance is thus a sensitive indicator of sedimentary depositional conditions.

Normal-phase HPLC analysis of microbial carotenoids and neutral lipids.

A facile, reproducible HPLC procedure for the analysis of algal and bacterial carotenoids has been developed. By selection of appropriate detection wavelengths, it is possible to determine wavelength ratios that typify selected carotenoids and permit rapid distinction between coeluting pigments with different numbers of conjugated double bonds. The concurrent isolation of individual neutral lipid classes with the carotenoid analysis is also demonstrated.