Early Onset Rapidly Progressive Osteoarthritis of the Hip in a Young Athlete.

We report and discuss a very rare case of early-stage rapidly progressive osteoarthritis (RPO) in a 33-year-old female athlete. The etiopathology of RPO remained unclear, although in this case mechanical overloading due to constant joint overuse appeared to be the only significant contributing factor to the very early development of RPO. Key words: rapidly progressive osteoarthritis, rapid destructive arthrosis, hip arthrosis, total hip arthroplasty, athlete, osteoarthritis.

Bilateral mandibular distraction in adult dogs with an epiperiosteal distractor.

We tested the function and efficiency of a new intraoral, bone-borne distraction device for mandibular lengthening, and the effect of bilateral transsection of the inferior alveolar arteries on osteogenesis in adult dogs. Nine adult Beagles had bilateral complete mandibular osteotomies and epiperiosteal placement of the distractor. After 7 days, the mandibles were distracted at 1 x 1mm/day, 1 x 0.5 mm/day or 2 x 0.25 mm/day for 15 or 30 days, respectively. Hemimandibles were harvested after 1, 14, or 42 days consolidation and evaluated clinically, radiographically and histologically. The mean distraction achieved was 11 mm (range 4-16 mm). New bone formation and clinical stability increased with increasing consolidation time and was independent of the distraction protocol used. Osteogenesis at the distal and proximal mandibular fragments did not differ. In 10/18 distraction sites, wound dehiscences compromised osteogenesis. The new epiperiosteal distractor permitted successful distraction osteogenesis despite complete bilateral osteotomy with section of the medullary vessels in adult dogs.

Extracellular carbonic anhydrase activity facilitates lactic acid transport in rat skeletal muscle fibres.

1. In skeletal muscle an extracellular sarcolemmal carbonic anhydrase (CA) has been demonstrated. We speculate that this CA accelerates the interstitial CO2/HCO3- buffer system so that H+ ions can be rapidly delivered or buffered in the interstitial fluid. Because > 80 % of the lactate which crosses the sarcolemmal membrane is transported by the H+-lactate cotransporter, we examined the contributions of extracellular and intracellular CA to lactic acid transport, using ion-selective microelectrodes for measurements of intracellular pH (pHi) and fibre surface pH (pHs) in rat extensor digitorum longus (EDL) and soleus fibres. 2. Muscle fibres were exposed to 20 mM sodium lactate in the absence and presence of the CA inhibitors benzolamide (BZ), acetazolamide (AZ), chlorzolamide (CZ) and ethoxzolamide (EZ). The initial slopes (dpHs/dt, dpHi/dt) and the amplitudes (DeltapHs, DeltapHi) of pH changes were quantified. From dpHi/dt, DeltapHi and the total buffer factor (BFtot) the lactate fluxes (mM min-1) and intracellular lactate concentrations ([lactate]i) were estimated. 3. BFtot was obtained as the sum of the non-HCO3- buffer factor (BFnon-HCO3) and the HCO3- buffer factor (BFHCO3). BFnon-HCO3 was 35 +/- 4 mM pH-1 for the EDL (n = 14) and 86 /- 16 mM pH-1 for the soleus (n = 14). 4. In soleus, 10 mM cinnamate inhibited lactate influx by 44 % and efflux by 30 %; in EDL, it inhibited lactate influx by 37 % and efflux by 20 %. Cinnamate decreased [lactate]i, in soleus by 36 % and in EDL by 45 %. In soleus, 1 mM DIDS reduced lactate influx by 18 % and efflux by 16 %. In EDL, DIDS lowered the influx by 27 % but had almost no effect on efflux. DIDS reduced [lactate]i by 20 % in soleus and by 26 % in EDL. 5. BZ (0.01 mM) and AZ (0.1 mM), which inhibit only the extracellular sarcolemmal CA, led to a significant increase in dpHs/dt and pHs by about 40 %-150 % in soleus and EDL. BZ and AZ inhibited the influx and efflux of lactate by 25 %-50 % and reduced [lactate]i by about 40 %. The membrane-permeable CA inhibitors CZ (0.5 mM) and EZ (0.1 mM), which inhibit the extracellular as well as the intracellular CAs, exerted no greater effects than the poorly permeable inhibitors BZ and AZ did. 6. In soleus, 10 mM cinnamate inhibited the lactate influx by 47 %. Addition of 0.01 mM BZ led to a further inhibition by only 10 %. BZ alone reduced the influx by 37 %. 7. BZ (0.01 mM) had no influence on the Km value of the lactate transport, but led to a decrease in maximal transport rate (Vmax). In EDL, BZ reduced Vmax by 50 % and in soleus by about 25 %. 8. We conclude that the extracellular sarcolemmal CA plays an important role in lactic acid transport, while internal CA has no effect, a difference most likely attributable to the high internal vs. low extracellular BF(non-HCO3). The fact that the effects of cinnamate and BZ are not additive indicates that the two inhibitors act at distinct sites on the same transport pathway for lactic acid.

Donor site morbidity after microvascular fibula transfer.

The free microvascular fibula and soft tissue transfer has become a widely used method to reconstruct the head and neck region. Only few reports focus on the donor site morbidity of purely mandibular reconstructions. On the basis of the hospital charts, a standardized patient interview and a standardized physical examination, the present study evaluates the early and late donor site morbidity in 42 mostly oncologic patients after an average follow-up interval of 34 months. Of these, 16 patients (38.1%) exhibited complicated wound healing that did not correlate with the patient's age, sex, type of transplant, use of a skin graft, result of preoperative angiography, rate of postoperative mobilization or the incidence of late donor site morbidity. At the time of follow-up examination, about one-fourth of the patients reported discomfort, pain or swelling. Objective findings included sensory deficits in 76.3%, motor deficits in 39.5% and reduced strength in 44.7% of the patients. Even though objectively measured morbidity exceeded subjectively perceived morbidity, it can be concluded that there is significant early and late donor site morbidity, which should be considered when opting for a fibula graft. Patients should be informed accordingly.

[Effect of bFGF on regeneration of distracted mandibles after radiation]. / Einfluss von bFGF auf die Regeneration von distrahierten Unterkiefern nach Radiatio.

The potential of distraction osteogenesis in mandibular reconstruction has been limited by its questionable efficacy in previously irradiated bone. The possible osteogenetic effect of recombinant human basic fibroblast growth factor (bFGF) on lengthening of irradiated mandibles was investigated in beagle dogs. We studied nine adult dogs which underwent a full course of external beam radiation therapy (60 Gy/30 fractions). Six months after completion of radiotherapy, the molars were extracted bilaterally followed by bone lengthening of the mandible using an intraoral device. On postoperative day 3 and 7 we injected 10 micrograms bFGF into the osteotomy site of each right hemimandible. The left sides were used as controls. The time course in ossification of the distracted area was evaluated at 2, 4, and 6 weeks after completion of bone lengthening. The radiographs of the newly formed bone tissue were measured by digital image analysis. Corresponding to the radiographic findings, the histological examination of the removed jaws showed an earlier and more intensive bone formation in the treated side after 2, 4, and 6 weeks compared to the control side. We conclude that bFGF promotes the ossification of distracted mandibles after radiation therapy in dogs.

Agonist-induced long-term desensitization of the human prostacyclin receptor.

Phosphorylation of the human prostacyclin (PGI(2)) receptor (hIP-R) by diacylglycerol-regulated protein kinase C (PKC) has been reported to be responsible for its rapid desensitization in HEK293 cells. In this study we demonstrate, that human fibroblasts reveal a much slower hIP-R desensitization kinetics, which was neither affected by stimulation nor inhibition of PKC by either phorbol 12-myristate-13-acetate or GF-109203X suggesting a different cellular mechanism. Although agonist-promoted sequestration of a C-terminally green fluorescent protein-tagged hIP-R was demonstrated, it did not account for the long-term desensitization. Concanavalin A did not abolish, but accelerated receptor desensitization kinetics. Resensitization of hIP-R involved receptor recycling and/or de novo synthesis of receptor protein, depending on the duration of prior desensitization. This is the first study investigating the mechanisms of hIP-R desensitization in intact human cells naturally expressing hIP-R. Our data suggest, that a hitherto unknown mechanism of hIP-R long-term desensitization, which is independent of receptor phosphorylation by conventional and novel type PKC isoforms or endocytosis, is a key event in regulating the cellular responsiveness to PGI(2).

Versatility of vascularized fibula and soft tissue graft in the reconstruction of the mandibulofacial region.

The anatomical region "laterodorsal calf" with the fibula, the flexor muscles and the overlying skin served by the peroneal vessels, is a suitable donor region particularly for combined microsurgical transfer of bone and soft tissue. In a five and a half year period, 59 reconstructions, 39 (66%) with and 20 (34%) without soft tissue transfer, were performed. The versatility and the functional and esthetic results after osseous, osteocutaneous, osteomuscular and osteomyocutaneous tissue transfer are presented.

Preservation of Gi coupling of a chimeric EP3/I-type prostaglandin (IP) receptor.

For the EP3 subtype of prostaglandin E receptors, different C-terminal splice variants are known, which are coupled to distinct heterotrimeric GTP-binding proteins (G-proteins). To test the hypothesis that the C-terminal domain is essential for the G-protein-coupling specificity of the EP3 receptor, we exchanged the carboxyl-terminal tail of a porcine Gi-coupled EP3 receptor isoform for the corresponding C-terminal part of a Gs-coupled prostaglandin receptor. The porcine EP3 receptor was truncated at a lysine (K350) residue at the end of the seventh transmembrane region, representing the splicing site of the different EP3 receptor isoforms. The wild-type C-terminus (37 amino acids) was substituted by the C-terminal tail (89 amino acids) of the human I-type prostaglandin receptor (hIP-R). The G-protein coupling of the resulting chimeric receptor protein was studied in transfected Chinese hamster ovary (CHO) cells. Stimulation of the chimeric receptor protein with the EP3 receptor-specific agonist M&B 28.767 did not increase adenosine 3',5'-cyclic monophosphate (cAMP) formation but did reduce the forskolin-stimulated cAMP formation, indicating Gi coupling. Furthermore, the chimeric receptor did not show constitutive activity as demonstrated for the C-terminally truncated EP3 receptor. Thus, coupling specificity of the EP3 receptor is not exclusively mediated by the carboxyl-terminal tail, and constitutive activity of a C-terminally truncated EP3 receptor can be suppressed by the hIP-R C-terminus.

Tolerance development to antimitogenic actions of prostacyclin but not of prostaglandin E1 in coronary artery smooth muscle cells.

This study compares the antimitogenic effects of iloprost and prostaglandin E1 on platelet-derived growth factor-BB stimulated DNA synthesis ([3H]thymidine incorporation) in bovine coronary artery smooth muscle cells. When added 20-24 h after stimulation with platelet-derived growth factor-BB (20 ng/ml), both iloprost and prostaglandin E1, concentration-dependently (IC50 3-5 nM) inhibited DNA synthesis. However, when added together with the growth factor (0-24 h), the inhibition of DNA synthesis by iloprost was markedly attenuated, indicating tolerance development. In contrast, no tolerance to antimitogenic effects of prostaglandin E1 or forskolin were observed. When added to iloprost-tolerant cells, both prostaglandin E1 and forskolin, still inhibited DNA synthesis. There was no evidence for transcriptional down-regulation of prostacyclin receptor gene by iloprost. The data demonstrate a tolerance development to antimitogenic actions of prostacyclin but not of prostaglandin E1 and suggest that the receptors, mediating the antiproliferative actions of these prostaglandins, may be different.

Antimitogenic effects of vasodilatory prostaglandins in coronary artery smooth muscle cells.

Vasodilatory prostaglandins (PGI2, PGE2, PGE1) are known inhibitors of proliferation of vascular smooth muscle cells (SMC) after stimulation with mitogenic factors. However, endogenous prostaglandins do not prevent SMC proliferation subsequent to vessel injury in vivo. Since vascular cells produce large amounts of antiproliferative prostaglandins, especially subsequent to COX-2 expression, insufficient vascular PGI2 formation is not likely to explain the failure of endogenous prostaglandins to prevent excessive SMC growth. In this paper we demonstrate a rapid development of tolerance to PGI2 in SMC, resulting in diminished antiproliferative activity. These findings may not only be relevant for the control of SMC growth by endogenously synthesized prostaglandins but also for clinical use of PGI2 mimetics.

A randomized clinical trial of two basic removable partial denture designs. Part II: Comparisons of masticatory scores.

STATEMENT OF PROBLEM: There is no known data on the functional efficacy of different removable partial denture designs. PURPOSE: This randomized clinical trial compared the masticatory performance of two commonly used designs in 118 patients who needed a unilateral or bilateral mandibular partial denture. MATERIAL AND METHODS: One half of the patients received a partial denture with distal occlusal rests and cast circumferential clasps and the other half a partial denture with mesial rests and I-bar cast clasps. The left side, right side, and swallowing threshold masticatory tests were made with peanuts and carrots before treatment and 16 weeks after the prosthesis insertion (baseline) and thereafter at 6, 18, 36, and 60 months. RESULTS: Masticatory scores at entry were higher in the circumferential design group, but the only significant (p < 0.05) difference was found in the right side carrot performance. Both groups realized significant improvements (p < 0.001) in all performance scores with partial dentures. Mean improvements of 24.7 with peanuts and 35.8 with carrots in the right side performance scores and 19.0 in the swallowing threshold score with peanuts in the bar design group were significantly higher (p = 0.017) than the respective mean improvements of 15.9, 21.4, and 5.6 in the circumferential design group. However, no significant differences were found between the two groups for any of the 10 performance scores at baseline. CONCLUSIONS: Despite some performance differences at entry, the mean performance scores for the two groups became similar at baseline and at subsequent intervals.

Veterans Administration Cooperative Dental Implant Study--comparisons between fixed partial dentures supported by blade-vent implants and removable partial dentures. Part V: Comparisons of pretreatment and posttreatment dietary intakes.

PROBLEM: Good scientific evidence is lacking on the impact of improvement in masticatory function after prosthodontic restoration of missing teeth. PURPOSE: This study compares 1-week dietary intakes of 218 healthy, male patients, 111 patients restored with mandibular unilateral or bilateral distal base extension removable partial dentures and 107 patients with fixed partial dentures. MATERIAL AND METHODS: Dietary logs recorded before the initiation of treatment and 6-months after the baseline period after partial denture treatment were analyzed for 30 nutritional variables of food intakes including total calories, fats, carbohydrates, proteins, fiber, and a number of vitamins and minerals. RESULTS: Both before and after treatment, intakes of various nutrients were more than 25% above or below the RDAs for approximately half of the patients in both groups. No significant differences were observed between the mean scores of the two groups for any of the 30 variables either before or after treatment. However, beneficial treatment effects were seen in subsets of patients with low and high caloric intakes at entry. Both treatments increased the intakes of calories and 27 nutrients in the low caloric group and decreased the intakes of calories and 27 nutrients in the high caloric group. The decreases in the caloric intake and eight nutrients, including total protein, fat, carbohydrates, and cholesterol, were significantly greater (p < 0.05) in the fixed partial denture group than those in the removable partial denture group. CONCLUSIONS: These beneficial effects of partial dentures, if verified by other studies, may have profound clinical implications for the undernourished and obese patients.

A randomized clinical trial of two basic removable partial denture designs. Part I: Comparisons of five-year success rates and periodontal health.

A randomized clinical trial was undertaken to compare the effectiveness of two partial denture designs, one with I-bar (bar) and the other with circumferential retainers (circumferential), in 134 patients with Kennedy class I and class II edentulous conditions. A total of 30 partial dentures were considered failures, five because of abutment failures and 25 because of the lack of removable partial denture use for eating. The 5-year success rate of 71.3% for the circumferential design did not differ significantly from the 76.6% for the bar design (p > 0.05). There were no discernible changes in the nine periodontal health components of abutment teeth with either of the two designs after 60 months. The results indicate that the two designs do not differ significantly in terms of success rates, maintenance care, and effects on abutment teeth. A well-constructed removable partial denture of either design, supported by favorable abutments and accompanied by a regular recall program offers a satisfactory treatment modality.

Enhancement of reporter gene de novo methylation by DNA fragments from the alpha-fetoprotein control region.

The 5'-upstream region of the rat alpha-fetoprotein (AFP) gene strongly increased de novo methylation of an adjacent chloramphenicol acetyltransferase (CAT) gene upon transfection into F9 mouse embryonal carcinoma cells. The same effect was exerted by a distal 775-base pair (bp) fragment and by 300- and 1-kb fragments preceding the transcriptional start site, but not by other parts of the control region. Further division of the larger, strongly active fragments resulted in a gradual decrease of methylation and clonal variation in the methylation patterns. The effect of the 775-bp fragment did not depend on its orientation. It was ablated by insertion of the mouse metallothionein I promoter between the AFP gene fragment and the CAT gene, but not by its insertion upstream of the AFP gene fragment. Two fragments from the AFP control region increasing methylation contained B1 and B2 small interspersed repetitive elements, respectively. B1 and B2 sequences of different origin also acted strongly to increase methylation. These findings support the idea that mammalian genes contain specific sequences involved in regulating their methylation. The effects of these sequences appear to be exerted in cis, to be dependent on proximity, but not on orientation, and to require an optimal size of 500-700 bp. Small retrotransposon sequences within such elements may be particularly effective in attracting de novo methylation.

Highly efficient transactivation by the yeast Kluyveromyces lactis transcription factor LAC9 and its inhibition by the negative regulator GAL80 in mammalian cells.

Expression of the LAC9 gene from the yeast Kluyveromyces lactis in HepG2 human hepatoblastoma cells efficiently induced luciferase expression from reporter plasmids containing the four LAC9 binding sites from the K. lactis GAL1-GAL10 gene linked to a basal promoter. Induction was approximately 100fold and was dependent on the presence of the UAS sequence and an intact reading frame in the LAC9 gene. Additional cotransfection of constructs expressing the K. lactis GAL80 gene reduced luciferase activity by up to 98%. This inhibition was not affected by addition of 14mM galactose to the medium. No further yeast-specific factors appear necessary for efficient inhibition of LAC9 by GAL80, but additional gene products may be required for activation by galactose.

Comparisons of tactile thresholds between implant-supported fixed partial dentures and removable partial dentures.

This study compared the tactile sensitivity of splinted abutment and denture teeth of 16 fixed partial dentures (FPD) supported by blade implants and 16 removable partial dentures (RPD) in patients with Kennedy Class I and Class II edentulous conditions. No significant differences were noted between the tactile thresholds of the natural abutment teeth and artificial teeth in the FPD and RPD groups. The splinted abutment teeth required 45.4 g, or 5.4 to 5.8 times higher occlusal loads than did those needed for the comparable nonsplinted teeth, to detect the stimulus. A further increase of 54% in thresholds with the FPD and over 100% with the placement of the RPD indicated the superiority of the RPD in terms of load distribution as a result of the cross-arch splinting and mucosal support. Moderate positive correlations (r = 0.37 to 0.46; P < .05) between tactile thresholds and masticatory performance were found, signifying that reduced tactile perception was not responsible for the incomplete restoration of the masticatory function with RPDs or FPDs but might be contributing to increased masticatory performance within both treatment groups.

De novo methylation of transfected CAT gene plasmid constructs in F9 mouse embryonal carcinoma cells.

To study the formation of DNA methylation patterns, plasmids containing promoters of different strengths in front of the bacterial chloramphenicol acetyltransferase reporter gene were transfected into F9 mouse embryonal carcinoma cells. Methylation of the integrated plasmids as well as copy numbers and activities of the reporter gene were determined for individual cell clones. The methylation pattern of the integrated plasmids was found to be determined by properties of the DNA sequence itself. In contrast, the specific methylation patterns were invariant with respect to integration site, copy number and arrangement of the integrates; methylation did also not correlate with transcriptional activity of the different promoters. Certain promoter regions may therefore contain signals recognized by the de novo methylation activity in embryonal carcinoma cells.