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From Wolff's law to the Utah paradigm: insights about bone physiology and its clinical applications.

Efforts to understand our anatomy and physiology can involve four often overlapping phases. We study what occurs, then how, then ask why, and then seek clinical applications. In that regard, in 1960 views, bone's effector cells (osteoblasts and osteoclasts) worked chiefly to maintain homeostasis under the control of nonmechanical agents, and that physiology had little to do with anatomy, biomechanics, tissue-level things, muscle, and other clinical applications. But it seems later-discovered tissue-level mechanisms and functions (including biomechanical ones, plus muscle) are the true key players in bone physiology, and homeostasis ranks below the mechanical functions. Adding that information to earlier views led to the Utah paradigm of skeletal physiology that combines varied anatomical, clinical, pathological, and basic science evidence and ideas. While it explains in a general way how strong muscles make strong bones and chronically weak muscles make weak ones, and while many anatomists know about the physiology that fact depends on, poor interdisciplinary communication left people in many other specialties unaware of it and its applications. Those applications concern 1.) healing of fractures, osteotomies, and arthrodeses; 2.) criteria that distinguish mechanically competent from incompetent bones; 3.) design criteria that should let load-bearing implants endure; 4.) how to increase bone strength during growth, and how to maintain it afterwards on earth and in microgravity situations in space; 5.) how and why healthy women only lose bone next to marrow during menopause; 6.) why normal bone functions can cause osteopenias; 7.) why whole-bone strength and bone health are different matters; 8.) why falls can cause metaphyseal and diaphyseal fractures of the radius in children, but mainly metaphyseal fractures of that bone in aged adults; 9.) which methods could best evaluate whole-bone strength, "osteopenias" and "osteoporoses"; 10.) and why most "osteoporoses" should not have bone-genetic causes and some could have extraosseous genetic causes. Clinical specialties that currently require this information include orthopaedics, endocrinology, radiology, rheumatology, pediatrics, neurology, nutrition, dentistry, and physical, space and sports medicine. Basic science specialties include absorptiometry, anatomy, anthropology, biochemistry, biomechanics, biophysics, genetics, histology, pathology, pharmacology, and cell and molecular biology. This article reviews our present general understanding of this new bone physiology and some of its clinical applications and implications. It must leave to other times, places, and people the resolution of questions about that new physiology, and to understand the many devils that should lie in its details. (Thompson D'Arcy, 1917).

Adult↗

[Preliminary experience of video-mediastinoscopy in clinical application].

OBJECTIVE: To determine the value of video-mediastinoscopy in clinical application. METHODS: The clinical data of 54 patients receiving video-mediastinoscopy were reviewed retrospectively. This operation consisted of cervical mediastinoscopy in 44 patients, parasternal mediastinoscopy in 6, and combined procedures in 4. Of these patients, 18 underwent video-mediastinoscopy for the evaluation of undifferentiated mediastinal disease. Thirty-six patients with suspected lung cancer showed enlarged mediastinal lymph nodes radiographically in the chest and underwent video-mediastinoscopy. RESULTS: Seventeen of 18 patients with undetermined mediastinal diseases had a definitive pathologic diagnosis, with an accuracy of 94.4% (17/18). In the 36 patients with suspected lung cancer, 22 were positive, and 14 negative. In the negative patients who underwent thoracotomy with resection, mediastinal lymph nodes revealed no evidence of metastasis. There were no postoperative complication and deaths. CONCLUSION: Video-mediastinoscopy as a highly effective and safe procedure could be used in the diagnosis and staging of thoracic diseases.

Adolescent↗

[Clinical application of drug delivery system of anti-cancer drugs--the pharmacokinetics and clinical results].

Pharmacokinetic study of anticancer drug is essential for clinical application of cancer chemotherapy. In this paper, the relationship between pharmacokinetics and clinical results was described in addition, the treatment of peritonitis carcinomatosa with mitomycin C adsorbed to activated carbon particles, intraarterial infusion chemotherapy with anticancer drugs suspended in Lipiodol and 5-FU suppository for rectal carcinomas were described. Also monoclonal antibody as a carrier of anticancer drug was mentioned and its problems was discussed from the aspect of pharmacokinetics of antibody-drug conjugate.

Antibodies, Monoclonal↗

Sterilization, toxicity, biocompatibility and clinical applications of polylactic acid/polyglycolic acid copolymers.

This is a review of salient studies of sterilization, toxicity, biocompatibility, clinical applications and current work in the field of orthopaedics, using implants made of polylactic acid (PLA), polyglycolic acid (PGA) and their copolymers. The intrinsic nature of these biomaterials renders them suitable for applications where temporally slow releases of bioactive agents in situ may be required. They are also desirable as fixation devices of bone, because they can virtually eliminate osteopenia associated with stress shielding or additional surgery. The majority of currently available sterilization techniques are not suitable for these thermoplastic materials and it may be desirable to develop new sterilization standards, which can account for the special character of PLA-PGA materials. Biocompatibility and toxicity studies suggest that, overall, PLA-PGA biomaterials may be suitable for orthopaedic applications, although certain problems, especially pertaining to reduction in cell proliferation, have been reported. Clinical applications are also promising, albeit not without problems usually associated with transient tissue inflammation. The future of these materials appears bright, especially in soft tissues. They may be used to address the exceedingly complex problem of osteochondral repair, but also as a means to enhance fixation and repair processes in tendons and ligaments.

Animals↗

A sensitive method for detecting Porphyromonas gingivalis by polymerase chain reaction and its possible clinical application.

BACKGROUND: It is useful for the clinical diagnosis of periodontitis to monitor the colonization of periodontopathic bacteria in periodontal pockets. In this study, we attempted to establish and possibly identify the clinical application of a sensitive method to detect Porphyromonas gingivalis (P.g.), one of the putative periodontopathic bacteria related to chronic periodontitis. METHODS: Genomic DNA extracted from cultured P.g. 381 and clinically isolated subgingival plaque samples were used as a template of polymerase chain reaction (PCR). We designed primers to amplify the genomic DNA coding 40 kDa outer membrane protein (OMP), one of the unique proteins to all strains of P.g. The efficiency and specificity of amplification were evaluated by agarose gel electrophoresis and subsequent Southern hybridization with a digoxygenin-labeled oligonucleotide probe. RESULTS: Fewer than 100 P.g. bacterial cells in the specimen were reproducibly detected by PCR-hybridization assay. This PCR-hybridization assay was at least 100 times more sensitive than the conventional indirect immunofluorescence assay (IIF). Furthermore, the imaging analysis showed that there is a linear correlation between the strength of the signal and the cell number of P.g. from which the template DNA was extracted semiquantitatively. It is noteworthy that the PCR assay could also be applied to detect P.g. from clinical plaque samples and that it was approximately 100 times more sensitive than a conventional IIF assay. CONCLUSION: The PCR assay established in this study can be a powerful tool to detect P.g. in periodontal pockets and monitor the colonization and/or recolonization of P.g. at the very early phase.

Bacterial Outer Membrane Proteins↗

A pancreatic oncofetal antigen: its partial purification and clinical application.

Studies on the purification, characterization and clinical application of pancreatic oncofetal antigen were reported. This antigen was purified from fetal pancreas, and migrated in the beta-region on electrophoresis. Its molecular weight was about 80 x 10(4) daltons on gel filtration with a Sephacryl S-300. This antigen is clearly different from other oncofetal antigens such as alfafetoprotein, carcinoembryonic antigen or ferritin. Clinically, this pancreatic oncofetal antigen was positive in sera of 68.4% of the patients with pancreatic cancer. However, elevated level of this antigen was also observed in the sera of some patients with biliary tract cancer, colon cancer or gastric cancer. The antigen was also found in pancreatic juice obtained from patients with pancreatic cancer in almost the same incidence as in their sera. It is suggested that a pancreatic oncofetal antigen assay of sera and pancreatic juice in combination with other oncofetal antigens is valuable for the diagnosis and monitoring the clinical course of pancreatic cancer.

Antigens, Neoplasm↗

[The clinical application of porcelain laminate veneers].

After a brief review of the literature in the laminate veneers the clinical application is described. The appropriate case selection is mentioned in relation to the function of the Stomatognathic System. The clinical application of the method follows, where the preparation of the teeth, the impression technique and the cementation of the laminate veneers with the new resin systems is described. It is concluded that porcelain laminate veneers could be used successfully as an alternative in the aesthetic restoration of the anterior teeth.

Cementation↗

[Factors affecting clinical application of sex therapy for erectile dysfunction].

OBJECTIVE: To discuss the factors that affect the clinical application of sex therapy for erectile dysfunction (ED). METHODS: Urological researchers recommended free sex therapy to ED patients and their partners in the outpatient department and studied the factors affecting the patients of Medicaid their partnersology, acceptance of sex therapy by interview and observation. RESULTS: Many patients refused sex therapy. Only 11 pairs of volunteers underwent it, of whom 5 pairs gave up halfway, 1 pair were stopped by the therapist due to the breakup of their marriage, and merely 5 pairs accomplished the whole course. Among the 5 pairs of quitters, 2 pairs thought of their problem as organic and turned to drug therapy, 1 pair withdrew because the patient's girlfriend broke up with him, 1 pair gave up because they lived in another city too far away from the clinic, and the other pair discontinued because they could not spare the time from their work. CONCLUSIONS: Many factors affect the clinical application of sex therapy for ED in China. Apart from the shortage of qualified professional sex therapists, some factors from the patients and their partners are at work, such as stress of work, lack of time, home location, education background, relationship between the patient and his partner, attitude to sex therapy, and so on.

Adolescent↗

[4 years' experience with a balloon-expandable endoprosthesis. Experimental and clinical application].

During a 4-year period of clinical application of the balloon-expandable Palmaz stent, a randomized trial comparing stent implantation and traditional balloon angioplasty of iliac arteries in arterial occlusive disease was started. The first long-term results, recorded after 2 years, indicate statistically significant differences in the complication rate (after stenting 2/62 and after angioplasty 5/69) and patency (greater than or equal to 70% of original lumen size upon stent implantation or balloon inflation: 95% after stenting and 72% after angioplasty). Clinical improvement after 2 years was 89% after stenting and 70% after angioplasty. Parallel to the clinical trials, experimental canine artery stenting was performed to evaluate differences in the long-term patency of stents exposed to restricted flow. Significant differences in neointimal healing were found between normally perfused stents and stents with artificially reduced flow: during the total observation period of 6 months the neointimal height was up to 200% higher in flow-restricted stents, while the histological composition of the neointima was the same as with normally perfused stents.

Angioplasty, Balloon↗

[The evaluation of color for the clinical application of thinner porcelain laminate restoration].

OBJECTIVE: The aim of this study was to evaluate the clinical application of the thinner porcelain laminate restoration, which is initiated in the West China College of Stomatology, Sichuan University. METHODS: The color of 51 ceramic veneers was evaluated using the chromatic instrument and visual observation. RESULTS: Among factors affecting the clinical results of the porcelain laminate, the hue of ceramic materials and bond composites played a more important role than the dentition. The brightness of ceramic materials and bond composites were closely correlated with the whole restoration brightness. There was also a close correlation between the brightness and the bond composite. CONCLUSION: Satisfactory restoration results can be achieved by clinical application of thinner porcelain laminate.

Adult↗

The lumbrical muscle flap: anatomic study and clinical application.

This article describes the anatomy and clinical application of the lumbrical muscle flap. Anatomic and radiologic studies were performed in 20 fresh human cadaver hands injected with latex-lead-oxide solution. Only the 2 radial lumbrical muscles were found suitable for flap transposition. The vascular supply of the first and second lumbrical muscles is from branches originating in the superficial palmar arch and from the common palmar digital artery, respectively. The dominant branches invariably enter the muscle bellies at the junction of their proximal and middle thirds. Pedicled on these vessels, the lumbrical muscles can be transposed to reach the entire palm, up to the wrist flexion crease. The clinical use of the first and second lumbrical muscle flaps in 2 patients demonstrated the value of these flaps for coverage of the median nerve and its palmar branches.

Cadaver↗

Clinical application of forced oscillation.

This review summarizes current clinical use of the forced oscillation technique (FOT) for analysis of lung function. It presents an intuitive approach to FOT pattern recognition for interpretation of results in human subjects, and the view that FOT is now well established and, clinically, eminently useful in patients with airflow obstruction. The focus of this review is on findings that relate directly to clinical utility, with less emphasis on theoretical mechanisms. The major thrust for clinical application of FOT derives from a number of European clinical research centers. Farre and Navajas and their colleagues in Barcelona, Harf and the Lorinos and their coworkers in Paris, Peslin and Duvivier and their coworkers in Vandoeuvre-les-Nancy, Pride and coworkers in London, and Van de Woestijne, Clement, Demedts, Landser, Van Noord, and their colleagues in Leuven have essentially been responsible for clinical development of FOT over the past 25 years. Publishing space does not permit an exhaustive listing of the many contributions of these investigators, but it is intended that the present review will provide a useful infrastructure from which the reader may progress to other research citations as desired.

Airway Resistance↗

Current clinical applications of omega-6 and omega-3 fatty acids.

BACKGROUND: Recent years have brought a resurgence of research interest in fatty acids, with studied fields running the gamut of human disease. This movement has run in parallel with an increased interest in using nutrition modalities as therapeutic measures, as opposed to their conventional role as energy sources. The aim of this manuscript is to provide a basic review of current clinical applications of omega-6 and omega-3 fatty acids, with a particular focus on the latter. METHODS: A selective review of the voluminous literature, including randomized controlled trials, meta-analyses, population studies, and case reports, was used to compile data and identify trends in pertinent clinical applications of fatty acid therapy. CONCLUSIONS: There are a myriad of disorders and maladies that seem to benefit from fatty acid supplementation, specifically omega-3 fatty acids. It has clearly been shown that omega-3 fatty acid supplementation provides a protective benefit in heart disease, and in particular sudden cardiac death. Rheumatoid arthritis (RA) is another disease entity that has been proven to benefit from this nutrition intervention, with improvement in symptoms and diminished nonsteroidal antiinflammatory drug (NSAID) usage. In addition, many psychiatric disorders, particularly schizophrenia and major depressive disorder (MDD), have shown positive results when supplementation has been used as an adjunct to standard pharmacotherapy. The remainder of clinical applications for omega-3 fatty acids requires further investigation. Specifically, according to preliminary clinical evidence, parenteral administration of fatty acids warrants further study.

Animals↗

Human factors engineering for clinical applications.

This position paper advocates the necessity for promoting a Human Factors Engineering (HFE) approach to new clinical applications in the medical informatics domain. We first describe the negative consequences of NOT using HFE methods for such sensitive applications as medication Computerized Physicians Order Entry systems. We then describe rapidly the HF technology and how it would apply to the healthcare domain. The specific and complex problem of the necessary re-engineering of existing applications is then addressed. We conclude on the mandatory cooperative characteristic of any practical HFE project for designing or re-engineering safety-sensitive clinical applications.

Ergonomics↗

A ported, proximally-cemented femoral stem for total hip arthroplasty. Development and clinical application.

We describe the development and early clinical application of a ported, proximally-cemented titanium stem for cemented total hip arthroplasty. PMMA bone cement is delivered to the proximal femur under pressure after the stem has been positioned within the femoral canal. A mid-stem cement occluder contains the cement to the proximal stem only. A tapered body is incorporated in the design of the stem to reduce the structural stiffness and hence the degree of stress shielding within the reconstructed joint. We performed preclinical studies to measure the reduction in porosity and the pressurisation achieved. The porosity, as measured by the void percentage within the cured cement mantle, was reduced by more than 50% and there was an almost threefold increase in the mean pressure. Mechanical testing of the stem, using a three-point bend test, showed that the addition of cement injection ports on the anterior and posterior sides of the body of the proximal stem did not reduce its strength. Finite-element analysis indicated that, compared with a fully-cemented conventional stem, there was no change in the stresses within the cement mantle. In a series of 40 proximally-cemented stems followed for up to six years (mean 51 months) the mean Harris hip score was 91, and 85% of patients had good or excellent results. There was excellent pain relief, an increased level of activity and good patient satisfaction. One mechanical failure of the stem required revision at three years after implantation. The early results indicate that the clinical performance was equal to that achieved with other modern cemented stems. Radiological evaluation showed excellent results with no evidence of stress shielding. Further follow-up will determine if long-term stress shielding is reduced and if revision is made easier by the absence of a distal cement mantle.

Adult↗

[Basic research and clinical application of cartilage-derived retinoic acid-sensitive protein].

OBJECTIVE: To know the basic research and the clinical application of cartilage-derived retinoic acid-sensitive protein (CD-RAP) in orthopedic and in other clinical fields. METHODS: The literature related to CD-RAP in basic research and clinical application were extensively reviewed. RESULTS: CD-RAP, as a protein, which is cartilage-specific, could be a marker of the joint diseases. It also can be used to monitor metastasis of melanoma. CONCLUSION: CD-RAP test provides a new way to study repair of cartilage and metastasis of melanoma.

Biomarkers↗

Evolution and clinical application of a rapid chemosensitivity assay.

The clinical usefulness of the soft agar colony-formation assay of in vitro chemosensitivity developed by Hamburger and Salmon is limited by long turnaround time (2-3 weeks), low success rate for small specimens, and clumping artifacts that can lead to erroneous predictions of resistance (false-negative errors). An improved technique was developed for measuring in vitro growth by incorporation of tritiated thymidine that can be performed in 5 days. With this rapid assay, 819 tumors were processed, with an overall success rate of 59.3%. This result compared favorably to the overall success rate of 58.2% for 1591 colony-formation assays because more small specimens could be submitted for the rapid assay. Melanoma and ovarian cancer specimens grew particularly well (76% and 75% successful, respectfully). Sixty-five correlations of in vitro and in vivo responses are available to date. None of 30 tumors, predicted to be resistant in vitro responded to chemotherapy clinically. Patients whose tumors were predicted to be sensitive in vitro had a 43% clinical response rate. The assay appears to be particularly accurate for predicting clinical resistance to chemotherapy, possibly because clumping artifacts do not occur in this system and peak achievable plasma concentrations of chemotherapeutic agents can be used. Optimal in vitro drug concentrations and culture conditions are still being defined, and improved success rates are being seen with more recent specimens. The introduction of this technique underscores the fact that in vitro chemosensitivity tests must continuously evolve to maximize their clinical application.

Antineoplastic Agents↗

Selective removal of low density lipoproteins (LDL) by precipitation at low pH: first clinical application of the HELP system.

The first clinical application of a new extracorporeal procedure (HELP) for the selective elimination of low-density lipoproteins by heparin precipitation at acid pH is described. Plasma, obtained by filtration of whole blood through a 0.2 mu filter, is continuously mixed with an equal volume of an acetate buffer (pH 4.85) containing heparin. After removal of the precipitated heparin complex by filtration, excess heparin is adsorbed to a specially developed filter and the clear plasma filtrate is subject to bicarbonate dialysis/ultrafiltration to restore physiologic pH and remove excess fluid. The calculated efficiency for the elimination of low-density lipoproteins from plasma by HELP is 100% and is therefore comparable to conventional plasmapheresis. The HELP system shows a high degree of specificity with over 80% of total protein being returned to the patient. Over 130 treatment procedures have now been performed. Patient compliance and acceptance have been excellent and no major complications have been observed.

Adult↗