Effects of strength training on muscle cellular outcomes in prostate cancer patients on androgen deprivation therapy.

Androgen deprivation therapy (ADT) improves life expectancy in prostate cancer (PCa) patients, but is associated with adverse effects on muscle mass. Here, we investigated the effects of strength training during ADT on muscle fiber cross-sectional area (CSA) and regulators of muscle mass. PCa patients on ADT were randomized to 16 weeks of strength training (STG) (n = 12) or a control group (CG; n = 11). Muscle biopsies were obtained from m. vastus lateralis and analyzed by immunohistochemistry and western blot. Muscle fiber CSA increased with strength training (898 µm(2) , P = 0.04), with the only significant increase observed in type II fibers (1076 µm(2) , P = 0.03). There was a trend toward a difference in mean change between groups myonuclei number (0.33 nuclei/fiber, P = 0.06), with the only significant increase observed in type I fibers, which decreased the myonuclear domain size of type I fibers (P = 0.05). Satellite cell numbers and the content of androgen receptor and myostatin remained unchanged. Sixteen weeks of strength training during ADT increased type II fiber CSA and reduced myonuclear domain in type I fibers in PCa patients. The increased number of satellite cells normally seen following strength training was not observed.

High rate of revision and a high incidence of radiolucent lines around Metasul metal-on-metal total hip replacements: results from a randomised controlled trial of three bearings after seven years.

A total of 397 hips were randomised to receive Metasul metal-on-metal (MoM), metal-on-conventional polyethylene (MoP) or ceramic-on-polyethylene (CoP) bearings using a cemented triple-tapered polished femoral component (MS-30). There were 129 MoM hips in 123 patients (39 male and 84 female, mean age 63.3 years (40.7 to 72.9)), 137 MoP hips in 127 patients (39 male and 88 female, mean age 62.8 years (24.5 to 72.7)) and 131 CoP hips in 124 patients (51 male and 73 female, mean age 63.9 years (30.6 to 73.8)). All acetabular components were cemented Weber polyethylene components with the appropriate inlay for the MoM articulation. Clinical evaluation was undertaken using the Harris hip score (HHS) and radiological assessments were made at two, five and seven years. The HHS and radiological analysis were available for 341 hips after seven years. The MoM group had the lowest mean HHS (p = 0.124), a higher rate of revision (p < 0.001) and a higher incidence of radiolucent lines in unrevised hips (p < 0.001). In all, 12 revisions had been performed in 12 patients: eight in the MoM group (four for infection, four for aseptic loosening, three in the MoP group (one each of infection, dislocation and pain) and one in the CoP group (infection). Our findings reveal no advantage to the MoM bearing and identified a higher revision rate and a greater incidence of radiolucent lines than with the other articulations. We recommend that patients with a 28 mm Metasul MoM bearing be followed carefully.

A lactoferrin-derived peptide (PXL01) for the reduction of adhesion formation in flexor tendon surgery: an experimental study in rabbits.

Injuries to flexor tendons can lead to loss of finger function after healing due to adhesion formation. The aim of this study was to assess the efficacy and safety of the new peptide, PXL01, in the prevention of peritendinous adhesions. The effect of a single intraoperative administration of PXL01 in sodium hyaluronate on mobility of the affected digit after surgery was assessed in a rabbit model by measuring total active motion, metatarsophalangeal-claw distance and resistance to bending the digits. Load-to-failure testing was done in the same specimens to assess tendon healing. The results demonstrated that a single application of PXL01 in sodium hyaluronate significantly improved mobility of the treated digits compared with the digits in which the same surgery was carried out but no treatment was provided. No negative effects on tendon healing were observed in connection with the treatment.

Growth factor and protease expression during different phases of healing after rabbit deep flexor tendon repair.

The purpose of the study was to contribute to the mapping of molecular events during flexor tendon healing, in particular the growth factors insulin-like growth factor-1 (IGF-1), vascular endothelial growth factor (VEGF) and nerve growth factor (NGF), matrix metalloproteinases (MMP-3 and MMP-13) and their inhibitors (tissue inhibitors of metalloproteinases, TIMP-1 and TIMP-3, and the protease cathepsin K. In a rabbit model of flexor tendon injury, the mRNA expression for the growth factors, MMPs and TIMPs were measured in tendon and tendon sheath tissue at several time points (3, 6, 21, and 42 days) representing different phases of the healing process. We found that MMP-13 remained increased during the study period, whereas MMP-3 returned to normal levels within the first week after injury. TIMP-3 was down-regulated in the tendon sheaths. Cathepsin K was up-regulated in tendons and sheaths after injury. NGF was present in both tendons and sheaths, but unaltered. IGF-1 exhibited a late increase in the tendons, while VEGF was down-regulated at the later time points. In conclusion, we have demonstrated the presence of NGF in flexor tendons. MMP-13 expression appears to play a more protracted role in flexor tendon healing than MMP-3. The relatively low levels of endogenous IGF-1 and VEGF mRNA following injury support their potential beneficial role as exogenous modulators to optimize tendon healing and strength without increasing adhesion formation.

The Charnley stem: clinical, radiological and survival data after 11-14 years.

BACKGROUND: The Charnley stem provides good outcome for 10 years, but several studies find deteriorating results thereafter. However, study populations, techniques and data analysis vary widely. We have studied 240 Charnley stems in a homogeneous group of patients providing clinical, radiological and survival data after 11-14 years. HYPOTHESIS: The clinical and radiological outcome of the Charnley stem is not as good than previously thought. PATIENTS AND METHODS: Five surgeons implanted 240 femoral stems in a community hospital in Norway using antibiotic impregnated cement and third generation cementing techniques. The Charnley stems were implanted with a Charnley cup in 120 cases and an uncemented hemispherical cup (Duraloc) in 120 cases. The mean age of the patients was 65.5 years and the mean Body Mass Index (BMI) was 26.8. All patients received low molecular weight heparin and antibiotic prophylaxis. Patients were assessed after 10 years by means of Harris Hip Score (HHS)and radiographic evaluation. Implant survival studies were performed after 11-14 years. RESULTS: One hundred and fifty-eight patients were available for clinical and radiographic evaluation after 10 years. HHS improved from 48.4 (95% CI: 46.6-50,2) preoperatively to 87.9 (95%CI: 86.6-89.3) after 6 months and 87.6 (95% CI: 85.3-89.8) at 10 years. Thirty-one stems had been revised, the reasons for revision were loosening (21), infection (five), instability (four) and late perisprosthetic fracture (one). Forty-one stems had one or more signs of loosening.Stem survival was 83.6% using any revisions as end point, and mean estimated stem survival was 12.7 years (12.2-13.3 years). DISCUSSION: Other studies report survival at mid-term from 83-96%. Our results are in the low-end. Even though our rate of infection was high (2%), the main cause of the poor results is aseptic loosening. We do not know the reason for this high-rate of loosening. As we believe that our technique is adequate and patient population average, we suspect that this rate of loosening is a characteristic of the implant. Results from this prospective cohort study add to the evidence that the Charnley stem should not be used hip arthroplasty unless patient life expectancy is less than 10 years.

No differences in outcomes between cemented and uncemented acetabular components after 12-14 years: results from a randomized controlled trial comparing Duraloc with Charnley cups.

BACKGROUND: Even though there are multiple studies documenting the outcome of the Charnley low-friction arthroplasty as well as abundant studies on uncemented arthroplasties, there is a dearth of comparative studies of the uncemented acetabular component and a cemented component. In this study we aimed to document the long-term clinical and radiographic outcome as well as component survival in a randomized controlled trial. MATERIALS AND METHODS: Two hundred fifteen patients (240 hips) were randomly allocated to receive a cemented Charnley cup or uncemented Duraloc 1200 cup. All patients received cemented Charnley stems and were evaluated clinically and radiographically after 6 months, and 2, 5, and 10 years. RESULTS: Harris Hip Scores improved from 48.3 [95% confidence interval (CI) 45.0-51.6] to 90.2 [95% CI 87.9-92.6] in the Charnley group and from 49.3 [95% CI 86.9-91.3] in the Duraloc group at 6 months. After 10 years, the Charnley group's Harris Hip Score was 89.8 [95% confidence interval (CI) 87.0-92.6], and the Duraloc group's score was 87.3 (95% CI 84.1-90.6). In the radiographic analysis after 10 years, there was no statistical difference in the prevalence of radiographic signs of loosening. Nine cups were revised in the Charnley group, and five cups were removed in the Duraloc group. The difference was not statistically significant. There was no statistical difference between the cups when aseptic loosening was the end-point, nor in survival analyses. CONCLUSIONS: There is no statistically significant difference in clinical or radiological outcome between the Charnley cup and the Duraloc after 10 years, and no difference in implant survival after 12-14 years. The uncemented Duraloc cup is as good as the cemented Charnley cup after 10 years.

The inflammatory response and hyaluronan synthases in the rabbit flexor tendon and tendon sheath following injury.

Using a rabbit model of flexor tendon injury, mRNA levels for a subset of relevant molecules involved in inflammatory and fibrotic processes were assessed by reverse transcriptase-polymerase chain reaction 3, 6, 12 and 24 days after injury. Increased levels of COX-2, IL-1beta, MMP-13 and TIMP-1 mRNA were detected in both tendon and tendon sheath following injury, with each molecule exhibiting tissue and time-dependent changes. MMP-13 and TIMP-1 mRNA levels were markedly upregulated in both tissues, whereas COX-2 and IL-1beta predominantly increased in tendon. Both hyaluronan synthase (HAS) 2 and 3 exhibited increases in mRNA levels in tendon tissue after injury, HAS 2 being more pronounced. These findings support the concept that healing in the flexor tendon and the sheath involve different molecular events and that each tissue may require unique modifications if healing is to be enhanced and adhesions reduced.

Assessment of mRNA levels for matrix molecules and TGF- beta1 in rabbit flexor and peroneus tendons reveals regional differences in steady-state expression.

This study analysed the differences on a molecular level between two segments of the deep flexor tendon, and compared the intrasynovial flexor tendon with the tendon sheath and the extrasynovial peroneus tendon in a rabbit model. The TRIspin method of RNA extraction was combined with the reverse transcription polymerase chain reaction to assess mRNA levels in the tissue segments. Significant differences were detected for all genes studied. mRNA levels for aggrecan, biglycan and collagen III were significantly higher in the fibrocartilaginous proximal segment of the flexor tendon. Collagen I was higher in the flexor tendon than the sheath and the peroneus tendon, and TGF-beta1 was significantly lower in the peroneus tendon. This study demonstrates differences at the mRNA level between different segments of tendon, indicating that the tendon tissue may be adapted to its environment.

Hyaluronic acid modulates cell proliferation unequally in intrasynovial and extrasynovial rabbit tendons in vitro.

As tendons differ in biochemical composition and cellular capacities, we have compared dose response effects of hyaluronic acid on cell proliferation and synthesis of matrix components in intermediate and proximal segments of intrasynovial deep flexor tendons and extrasynovial peroneus rabbit tendons in vitro. Compared with matched control tendons, hyaluronic acid inhibited cell proliferation in intermediate and proximal intrasynovial flexor tendon segments at the concentrations of 0.1-2.0 mg/ml and 0.5-2.0 mg/ml respectively, but in extrasynovial tendon segments only at the concentration of 0.5 mg/ml. Hyaluronic acid did not affect synthesis of proteoglycan, collagen and non-collagen protein in either type of tendon. These results show that hyaluronic acid modulates cell proliferation unequally in intra- and extrasynovial tendons without affecting the synthesis of matrix components in the two types of tendons, indicating differential hyaluronic acid sensitivity and a possible mechanism of action.

Tendon repair--cellular activities in rabbit deep flexor tendons and surrounding synovial sheaths and the effects of hyaluronan: an experimental study in vivo and in vitro.

One deep flexor tendon and its surrounding sheath of each hindpaw of 48 rabbits were transected and repaired in order to investigate the abilities of rabbit flexor tendons and synovial sheaths to synthesize DNA and matrix components during healing and to study the effects of hyaluronan (HA). After repair, HA or saline was injected between the tendon and the sheath. Short-term culture and labeling in vitro were used up to 6 weeks after surgery to determine synthesis of DNA, proteoglycan, collagen, and noncollagen protein. Within tendon repair sites, the rate of cell proliferation increased and reached a maximum 5 days after surgery; within repaired synovial sheaths, the rate immediately decreased. In the healing tendons, the rate of collagen synthesis decreased and the rate of noncollagen protein synthesis remained unchanged. The opposite results were found within the healing synovial sheaths. HA did not affect the rate of cell proliferation or matrix synthesis in healing tendons or surrounding sheaths. These results show that cellular activities differ between tendons and synovial sheaths during healing and that those activities may not be affected by HA.

Detection of psoriasis-associated antigen pso p27 in sarcoidosis bronchoalveolar lavage fluid using monoclonal antibodies.

Sarcoidosis is a multisystem granulomatous disorder of unknown etiology, predominantly affecting the lung. The increased concentration of pulmonary lymphocytes with specific receptors in subgroups of sarcoidosis patients suggests a local specific immune response. pso p27, a psoriatic scale antigen linked to the pathogenesis of psoriasis, was previously found in BAL cells, serum, and Kveim-Siltzback test in sarcoidosis. With an enzyme-linked immunoassay based on murine monoclonal antibodies, we analyzed BAL fluid from 21 patients with pulmonary sarcoidosis. Eleven (52%) of the patients have detectable levels of pso p27 antigen. No antigen is detected in the BAL fluid from five healthy, nonsmoking controls. Serum concentrations of pso p27 shows no significant difference between the two groups, but three of the sarcoidosis patients have detectable levels of the antigen. Mean concentration of pso p27 is >100 fold higher in BAL fluid than in serum from the sarcoidosis patients. This strongly suggests local pulmonary production of pso p27 antigen.

Division of flexor tendons causes progressive degradation of tendon matrix in rabbits.

Deep flexor tendons of 30 rabbits were divided at the ankle level. The effects of unloading on the synthesis and content of matrix components, the synthesis of DNA, and dry weight were investigated. The ability of the tendons to synthesize collagen during short-term culture and the contents of matrix components decreased inversely to the time of unloading. 12 weeks following division, the fibrocartilagnious segments had lost 2/5 of their dry weight, 2/3 of proteoglycan and 1/3 of collagen and non-collagen protein content. Less pronounced losses were observed in the non-fibrocartilaginous segments. A transient increase in cell proliferation in both types of segments was found. These findings indicate that divided flexor tendons undergo a progressive degradation, degradation, which may have implications for delayed suture of deep flexor tendon injuries.

Effects of hyaluronan on cell proliferation and collagen synthesis: a study of rabbit flexor tendons in vitro.

Hyaluronan (HA), a high-molecular-weight polysaccharide, has been suggested to play a possible role during the early stages of healing of a variety of connective tissues and when topically applied to decrease the formation of adhesions following tendon surgery. As the mechanisms of HA actions are still being discussed, this study was designed to assess the effects of HA on cell proliferation and synthesis of matrix components of deep flexor tendons in a well-defined culture system. Cell proliferation, measured as the radioactive 3H-thymidine uptake by cultured segments of rabbit flexor tendons, was inhibited by the addition of HA to the culture medium. HA of molecular weight 0.5 x 10(6) inhibited the uptake significantly at concentrations within the range of 0.1-2.0 mg/mL, HA of molecular weight 1.6 x 10(6) at 0.5-2.0 mg/mL, and HA of molecular weight 3.6 x 10(6) at 1.0-2.0 mg/mL, as compared to matched control groups. At the concentration of 2 mg/mL, HA of the molecular weights of 0.5, 0.8, 1.6, and 3.6 x 10(6) equally inhibited cell proliferation. No effect on synthesis of matrix components, measured as the radioactive incorporation of 35S-sulfate, 3H-hydroxyproline, and 3H-proline by cultured segments of rabbit flexor tendons, was observed. These findings show that exogenously applied HA may act as a modulator of flexor tendon fibroblast proliferation, indicating a possible mechanism for antiadhesive effects following administration after flexor tendon surgery.

Total hip arthroplasty with Boneloc: loosening in 102/157 cases after 0.5-3 years.

We report the outcome of 177 consecutive primary Charnley total hip arthroplasties inserted with Boneloc cement between November 1991 and November 1993. There were 107 women and 70 men. The mean age at the time of the operation was 71 years. 11 patients (13 hips) died during the follow-up period and 3 patients were too weak to attend a follow-up examination. Of the 161 remaining hips, 4 had been revised because of deep infection. The mean follow-up time for the remaining 157 hips was 2 (0.5-3) years. 24 hips had been revised and 6 are waiting for revision because of stem loosening. Of the remaining 127 hips, 72 showed radiographic signs of stem loosening and 2 hips were probably loose. Osteolysis was seen around the femoral component in 56 hips.

Evaluation of implementation of a cholesterol management program in physicians' offices.

This article describes an evaluation of the implementation of a cholesterol management program in family physicians' offices as part of the Physician-Based Nutrition Program to Lower Coronary Heart Disease Risk (PBNP). The evaluation, conducted through a partnership evaluation model, used multiple case study methodology and combined the use of quantitative and qualitative methods. Data sources included office staff reports and interviews, records of contacts with study personnel, patient care data, and patient telephone interviews. Data from these sources revealed gradual program implementation and considerable variation in practitioner and clinic involvement in cholesterol management. Clinic staff reported that the support provided by PBNP in the form of training, operations materials, patient education materials and ongoing assistance was very useful. This formative evaluation has implications for refinement of the PBNP and for other prevention programs in primary care settings. It demonstrates the feasibility and acceptability of a systems approach to physicians, cholesterol/nutrition educators and clinic support staff. It also suggests ways in which researchers and clinicians can implement and evaluate health care innovations.

Patient perceptions about the influence of cholesterol on heart disease.

National surveys have shown that adults need to known more about their own blood cholesterol levels and about specific methods for lowering blood cholesterol. We examine patient perceptions of cholesterol and heart disease after their participation in a cholesterol management program designed for the primary care setting. We counseled 221 patients and successfully interviewed 179 by telephone four weeks after their initial dietary counseling visit. Nine of 10 patients could report their cholesterol level, and 98% of patients could appropriately label it as borderline-high or high-risk. Ninety-seven percent of the patients could give one valid reason why cholesterol was important to their health. Many patients knew specific dietary recommendations from counselors. Patients positively reviewed counseling and the cholesterol management program. A large percentage of patients had already made changes in diet and eating habits at the time of the interview. Total cholesterol measurements showed a mean reduction of 8.5% postcounseling.

Type I procollagen gene expression in normal and early healing of the medial collateral and anterior cruciate ligaments in rabbits: an in situ hybridization study.

The purpose of this study was to compare the levels of procollagen type I messenger RNA (mRNA) in normal and healing medial collateral ligament (MCL) and anterior cruciate ligament (ACL) in a rabbit model. Our method of injury involved a surgical model with identical partial lacerations in the midsubstance of the MCL and ACL. Paraffin sections of normal ligaments, and ligaments 3, 7, 14, and 28 days postlaceration were studied by in situ hybridization to compare and follow the level of type I procollagen mRNA in the two ligaments. A complementary DNA (cDNA) probe corresponding to alpha 1(I) procollagen mRNA was labeled with [32P]d-CTP. After hybridization, autoradiography, and staining of the sections, the level of procollagen mRNA was assessed by microscopic examination. A higher level of procollagen mRNA was consistently detected in normal MCL than in normal ACL, suggesting higher collagen synthetic activity in the MCL. At the injury sites of the MCL and ACL, the levels of type I procollagen mRNA increased at all post-laceration periods, reaching its highest level at 14 days postsurgery. The MCL healing site had a considerably higher level of procollagen mRNA than the ACL healing site (i.e., injury site) at all postoperative intervals. The results demonstrate that procollagen mRNA levels in MCL tissue are higher than those in ACL tissue under normal conditions, as well as in response to injury. The differences in the procollagen mRNA levels of MCL and ACL may reflect the synthesis of collagen in these tissues, and may contribute to the differences in their healing capacities.

The early effect of high molecular weight hyaluronan (hyaluronic acid) on anterior cruciate ligament healing: an experimental study in rabbits.

The purpose of this study was to assess, morphologically and biochemically, the effect of hyaluronan (HA) on the early repair process of the anterior cruciate ligament (ACL). Following partial bilateral laceration in the midsubstance of the cruciate ligament, a single dose of HA (MW of 3.6 x 10(6] was injected in one knee and saline in the contralateral knee. Postsurgery, the rabbits were allowed normal (nonimmobilized) cage activity, and were killed after 4 (n = 11) and 12 (n = 10) weeks. The ligaments were evaluated by gross morphology and graded according to the degree of repair. We used grades 1,2, and 3 for uncovered, partially covered, and totally covered lacerations, respectively. Five of the HA-treated ligaments at each time studied were completely covered, compared to 0 at 4 weeks, and 1 at 12 weeks in the saline group. Paired evaluations of the lacerated ACLs showed that the HA-treated ligaments received a healing grade higher than the ligaments exposed to saline in 14 of the 21 animals. In the remaining animals, there was no difference between the sides. The repaired tissue of the ACLs was also examined by light and electron microscopy. When compared qualitatively with saline controls, HA-treated ligaments exhibited a more pronounced repair, with an increased angiogenesis and less inflammatory response. Biochemical analysis demonstrated a mean higher value of type III collagen in the HA-treated injured ACL than in saline-treated injured ACL (13.4 +/- 1.1% and 11.0 +/- 0.8%, respectively). This increased synthesis of type III collagen in the HA-treated injured ACL was statistically higher (p less than 0.05) when compared to the saline-treated injured ACL.

Hyaluronan in flexor tendon repair.

This study assesses the effect of a preparation of hyaluronan (hyaluronic acid) applied topically at the time of flexor tendon repair in a well-established model. The hypothesis is that hyaluronic acid applied topically at the time of flexor tendon repair will decrease adhesions, and will improve clinically the gliding function of the repaired flexor tendon. After transection and repair of the second and fifth flexor tendons of the left forepaw of four mongrel dogs, the second flexor tendon was treated with hyaluronic acid of molecular weight 3.6 x 10(6) daltons applied topically between the synovial sheath and the repair site. The left forepaws were completely immobilized for 5 weeks to optimize the formation of adhesion ingrowth. After death, the repaired tendons and sheaths were removed en bloc, fixed, and dissected. Gross inspection and histologic evaluation of all tendons showed that the quality and quantity of adhesions from the wound repair to the synovial sheath appeared to have been consistently affected by hyaluronan. Hyaluronic acid had a beneficial effect on both the repair site and synovial sheath by decreasing the peripheral inflammatory response and promoting a contact healing process via epitenon and endotenon cell involvement in the repair process.