Mohammad Tezval

Prognostic reliability of the Hawkins sign in fractures of the talus.

Objective: To determine the prognostic reliability, sensitivity, and specificity of the Hawkins sign. The Hawkins sign is a subchondral radiolucent band in the talar dome that is indicative of viability at 6 to 8 weeks after a talus fracture. It is visible in the anterior-posterior view, but seldom appears on lateral radiographs. Design: Retrospective study. Setting: University hospital. Patients and Methods: Between January 1995 and December 2000, a total of 41 patients (13 female, 28 male) with displaced talar fractures were operated on in our hospital. Thirty-four patients with a mean age of 35 years (range 12-60) were followed for more than 36 months (range 36-52). The prognostic reliability of the Hawkins sign was studied in 31 of these patients using a two-by-two table. The Ankle-Hindfoot scale of the American Orthopaedic Foot and Ankle Society (AOFAS) was used as an outcome measure. Results: No Hawkins sign was found in the five patients who developed avascular necrosis (AVN) of the talus. In the remaining 26 patients who did not develop AVN, a positive (full) Hawkins sign was observed 11 times, a partially positive Hawkins sign 4 times, and a negative Hawkins sign 11 times. The Hawkins sign thus showed a sensitivity of 100% and a specificity of 57.7%. The Hawkins sign (if present) appeared between the 6th and the 9th week after trauma. Mean [range] AOFAS scores were: Pain, 31 [10-40] out of 40; Function, 39 [14-50] out of 50; and Alignment, 7 [0-10] out of 10. The clinical results were satisfactory. Conclusion: The Hawkins sign is a good indicator of talus vascularity following fracture. If a full or partial positive Hawkins sign is detected, it is unlikely that AVN will develop at a later stage after injury.

Comparison of the phytohormones genistein, resveratrol and 8-prenylnaringenin as agents for preventing osteoporosis

As the average age of society increases, identifying and preventing osteoporosis becomes more important. According to the results of the Womens Health Initiative study, substitution of estradiol is not recommended in hormone replacement therapy (HRT), although phytoestrogens might be a safe alternative. In this study, the osteoprotective effects of genistein (Gen), resveratrol (Res) and 8-prenylnaringenin (8PN) were evaluated by analysing bone biomechanical strength and bone mineral density. After ovariectomy, 88 female rats received soy-free food (C), and according to their grouping, were fed estradiol (E), GEN, RES or 8PN for 12 weeks. The phytohormones were given in two dosages. To analyse the osteoprotective effects of the tested substances, bone biomechanical properties and bone mineral density (BMD) were evaluated on the upper tibial metaphysis. Bone biomechanical properties were significantly improved after treatment with E (F (max): 90.6 N) and 8PN (85.0 N) compared to GEN (76.0 N), RES (72.6 N) and C (76.6 N). Bone biomechanical properties with 8PN (yL: 55.7 N) supplementation reached a level similar to that seen after E (49.3 N) supplementation. Treatment with GEN (38.5 N) was not as effective as E and 8PN, but demonstrated improved biomechanical properties compared to C (40.1 N) and RES (36.3 N). E (Cn.Dn. 217 mg/cm (3)) and 8PN (165 mg/cm3) showed superior results in the analysis of bone mineral density compared to C (112 mg/cm (3)). GEN (164 mg/cm (3)) also demonstrated superior results, though not as good as E and 8PN. RES (124 mg/cm (3)) revealed no effect on bone density. Treatment with 8PN resulted in very good biomechanical properties and showed an increased BMD. GEN had a smaller effect on bone biomechanical strength, while RES did not have an effect on bone biomechanical strength or BMD. Therefore, 8PN might be a safe alternative for HRT, but further studies are needed.

Urinary tract injuries in patients with multiple trauma

This article mainly reviews urinary tract injuries in patients with multiple trauma. Approximately 10% of all traumatic injuries resulting from an external force will involve the genitourinary system. The article discusses mechanisms of injury, diagnosis, and therapeutical approaches for renal, ureteral, bladder, and urethral trauma. Due to the complexity of such injuries—despite several attempts to provide a standard strategy in trauma patients with urinary tract involvement—an individual and patient-specific-therapeutic approach is mandatory in most cases. However, the availability of classified guidelines may help the surgeon to reach the most accurate decision. Because of the similarity of American and European guidelines on urological trauma, this article adapts injury severity scales and classification from the American Association for the Surgery of Trauma.

Whole body vibration during fracture healing intensifies the effects of estradiol and raloxifene in estrogen-deficient rats

Current osteoporosis therapies aim to delay bone destruction and have additional anabolic effects. While they have demonstrated some positive effects on bone healing, more progress is needed in this area. This study used the well-known osteoporotic agents estrogen (E) and raloxifene (R) in conjunction with biomechanical whole body vibration (WBV) at a frequency of 70 Hz twice daily for six weeks to stimulate bone healing. Eighty-four 3-month old female Sprague-Dawley rats (12 per group) were bilaterally ovariectomized to develop osteopenia within eight weeks. Osteotomy of the metaphyseal tibiae was performed and fracture healing was then studied using mechanical tests, histomorphometry, computed tomography (μCT), and gene analysis. We found that E and R improved the structure of osteopenic bones as did WBV alone, although significant levels for WBV were seldom reached. Combination treatments significantly enhanced stiffness (R+WBV; p<0.05), endosteal bone (R+WBV; p<0.01), and trabecular density (E+WBV; p<0.05, R+WBV; p<0.05). In addition, the expression of osteoclast-specific Trap was significantly reduced after treatment with E, R, or their combination with WBV (p<0.01). The effects were additive and not inhibitory, leading us to conclude that the combined applications of WBV with E or R may improve the healing of osteopenic bones. The therapies studied are all currently approved for human use, suggesting ready applicability to clinical practice. To better understand the effects of WBV on osteopenic bones, the ideal vibration regime will require further study.

Impact of 4-methylbenzylidene camphor, daidzein, and estrogen on intact and osteotomized bone in osteopenic rats

The study investigated the influence of 4-methylbenzylidene camphor (4-MBC), daidzein, and estradiol-17β-benzoate (E(2)) on either intact or osteotomized cancellous bone in ovariectomized (Ovx) rats. Three-month old Ovx rats were fed with soy-free (SF) diet over 8 weeks; thereafter, bilateral transverse metaphyseal osteotomy of tibia was performed and rats were divided into groups: rats fed with SF diet and SF diet supplemented with 4-MBC (200 mg), daidzein (50 mg), or E(2) (0.4 mg) per kilogram body weight. After 5 or 10 weeks, computed tomographical, biomechanical, histological, and ashing analyses were performed in lumbar spine and tibia of 12 rats from each group. 4-MBC and E(2) improved bone parameters in lumbar spine and tibia, were not favorable for osteotomy healing, and decreased serum osteocalcin level. However, daidzein improved bone parameters to a lesser extent and facilitated osteotomy healing. For lumbar spine, the bone mineral density was 338±9, 346±5, 361±6, and 360±5 mg/cm(3) in SF, daidzein, 4-MBC, and E(2), respectively, after 10 weeks. For tibia, the yield load was 98±5, 114±3, 90±2, and 52±4 N in SF, daidzein, 4-MBC, and E(2), respectively, after 10 weeks. Serum daidzein was 54±6 ng/ml in daidzein group and equol was not detected. Alp and Igf1 genes were down-regulated in callus after daidzein and E(2) compared with 4-MBC (week 5). The response of bone tissue and serum markers of bone metabolism could be ordered: daidzein<4-MBC<E(2). Treatments were more effective after 5 vs 10 weeks. In SF group, bone structure was impaired after 5 weeks and improved after 10 weeks probably due to adaptation mechanisms to osteoporosis. In conclusion, it is conceivable that 4-MBC may improve bone tissue in osteoporotic organisms; osteoporotic patients with fractures could benefit from daidzein treatment.

Influence of intermittent administration of parathyroid hormone on muscle tissue and bone healing in orchiectomized rats or controls.

Influence of human parathyroid hormone (hPTH 1-34) on muscle and bone healing was studied in either orchiectomized (Orx at 8 months of age) or sham-operated male rats. Eleven-month-old Sprague-Dawley rats underwent bilateral transverse metaphyseal osteotomy of tibia and were divided into four groups (n=12): 1) sham-vehicle, 2) sham group-PTH everyday, 3) Orx-vehicle, 4) Orx-PTH everyday, and 5) Orx-PTH every other day. PTH dosage was 40  μg/kg body weight. After 5 weeks, fiber cross-sectional area, capillary density, and enzyme activity (lactate dehydrogenase, citrate synthase, and complex I) were measured in soleus (MS), gastrocnemius (MG), and longissimus (ML) muscles; tibiae were analyzed by computed tomographical, histological, and gene expression analyses. The effect of PTH in all rats was increased serum osteocalcin, cortical and callus densities and callus area. In sham rats capillary density was increased in limb muscles (MS: 1.3-1.7, MG: 1.2-1.4 capillaries/fiber), and rate of osseous bridging of osteotomy was enhanced (67-100%). In Orx rats serum creatine kinase was decreased (6670-2847 U/l), and bone genes (Igf-1, osteoprotegerin, and receptor activator of nuclear factor kB ligand) were up-regulated. Cross-sectional area, enzyme activity, food intake, weight of body, visceral organs, adipose tissue, MG, and MS were not affected by PTH. PTH had a favorable effect on muscle capillary density and improved bone healing being more effective in sham rats and having no adverse systemic effect. The effect was less if PTH was applied every other day. The findings may show up trends for therapeutic treatment of male patients.

Effect of daidzein, 4-methylbenzylidene camphor or estrogen on gastrocnemius muscle of osteoporotic rats undergoing tibia healing period

The effect of daidzein (D), 4-methylbenzylidene camphor (4-MBC) or estradiol-17beta-benzoate (E(2)) on muscle of osteoporotic rats during fracture healing was studied. After performing a metaphyseal tibia osteotomy in 96 osteoporotic 5-month-old female Sprague-Dawley rats, they received daily 50 mg D, 200 mg 4-MBC or 0.4 mg E(2) per kg body weight, or soy free (SF) diet up to 36 and 72 days. Mitochondrial activity, fiber area, and capillary density were analyzed in M. gastrocnemius. Osseous callus bridging of fracture was observed in half of the rats after 36 days. By day 72, fracture was healed in most of the animals. State 3 mitochondrial respiration significantly enhanced in E(2), 4-MBC and D groups versus SF after 36 days (30, 32 and 32 vs 23 pmol O(2)/s per mg). It declined after 72 days, however, in E(2) group it was still at a higher level versus SF (25, 23 and 21 vs 20 pmol O(2)/s per mg). Size of fast oxidative glycolytic (FOG) and fast glycolytic (FG) fibers, capillary density did not differ significantly between the groups, however, at day 36 an increase in D and 4-MBC groups was detectable. FOG diameter was 64, 66, 68, and 58 microm and FG diameter was 88, 98, 95, and 89 microm in SF, D, 4-MBC, and E(2) groups. The ratio of capillaries to muscle fiber was 1.1, 1.4, 1.3, and 1.1 in SF, D, 4-MBC and E(2) groups by day 36. D and 4-MBC react similar to estrogen thereby improving oxidative cell metabolism in severe osteoporotic rats. The level of mitochondrial activity was higher, though no significant morphological differences could be shown.

Changes in the histomorphometric and biomechanical properties of the proximal femur of ovariectomized rat after treatment with the phytoestrogens genistein and equol.

The isoflavonoids found in soy have attracted great interest as dietary phytoestrogens that might be effective for postmenopausal hormone replacement therapy. Special attention has been devoted to the hormonal effects of various isoflavonoids, like genistein (GEN) and daidzeins (DAID) potent metabolite, equol (EQ). Here we aimed to investigate the short-term effects of genistein and equol on the proximal femur of ovariectomized (OVX) rats. Forty-eight, 3-month-old female Sprague-Dawley rats were ovarectomized; after eight weeks the bilateral osteotomy and osteosynthesis (OS) of their tibiae was performed and the rats were randomly divided into the following four groups: OVX control group (C), treated with estradiol-17beta (E2) -benzoate (E; daily intake 0.086 mg/d per animal), genistein (GEN; daily intake 12.7 mg/d per animal) and equol (EQ; daily intake 4.65 mg/d per animal). At 5 weeks postoperatively (OS), the breaking test was performed on the trochanteric region of femur. Additionally, histomorphometric assessment, and trabecular and cortical bone microstructure analyses were performed. The relative gain of body weight (BW) in the EQ (24 %) group was significantly (p < 0.05) lower than in the C (33 %) and GEN (30 %) groups. After treatment for 5 weeks, the maximal load (F(max)) and yield load (yL) were higher (p < 0.05 for the weight-adapted results) in the E (188.4 N resp. 113.1 N) and EQ (177.3 N resp. 112 N) groups as compared to C (162.8 N resp. 109.1 N) and GEN (165.7 N resp. 108.8 N). In the histomorphometric tests the E- (trabecular area (Tb.Ar) = 74.93 %, trabecular nodes/mm(2) (N.Nd/mm(2)) = 48.65) and EQ-treated (Tb.Ar = 63.13 %, N.Nd/mm(2) = 43.72) animals showed significant improvement with regard to Tb.Ar and trabecular connectivity (N.Nd./mm(2)) in comparison to C (Tb.Ar = 46.84, N.Nd/mm(2) = 31.86) and GEN (Tb.Ar = 48.22 %, N.Nd/mm(2) = 34.15). There were no differences in relative cortical width (Ct.Wi) among the four groups. The treatment with EQ resulted in improved biomechanical and histomorphometric properties as compared to the treatment with GEN. Thus, of the studied substances, EQ seems to be a possible alternative to hormone replacement therapy, but further studies are needed.

Evaluation of twelve vibration regimes applied to improve spine properties in ovariectomized rats

While whole-body vibration (WBV) has recently been introduced as a non-pharmacological therapy for osteoporosis, studies have shown that it has no significant effect on the lumbar spine in older women. However, the vibration protocols differed among studies, and the major factor influencing the outcomes is unclear. The intention of the present study was to evaluate the effect of WBV—vertical (v) or horizontal (h) and of different frequencies and application regimes (1 × or 2 ×/d)—on lumbar spine properties in ovariectomized rats (Ovx). Three experiments were conducted. Thirteen-week old female Sprague–Dawley rats were Ovx or left intact (Non-Ovx). After eight weeks, all of the rats underwent metaphyseal osteotomy of the tibiae. Five days later, the rats were divided into six groups (n = 15): 1) intact, 2) Ovx, and 3–6) Ovx exposed to WBV. In Experiment 1, groups 3–6 underwent 35 Hz-v, 50 Hz-v, 70 Hz-v, and 90 Hz-v, respectively. In Experiment 2, groups 3–6 underwent 30 Hz-h, 50 Hz-h, 70 Hz-h, and 90 Hz-h, respectively. In Experiment 3, groups 3–6 underwent 35 Hz-v, 70 Hz-v, 35 Hz-h, and 70 Hz-h, respectively. Vibration exposure was 15 min 1 ×/d in Experiment 1 and 2 and 2 ×/d in Experiment 3 for up to 30 days. Vertebral bodies were used in micro-computed tomography, biomechanical, ashing, and gene expression analyses. Vertical vibrations applied once a day favorably affected bone volume fraction (BV/TV) and Ca2 +/PO43 − and decreased Rankl gene expression. When applied twice a day, v-vibrations diminished mineral content. Horizontal vibrations (1 ×/d) reduced Ca2 +/PO43 − ratio and Opg mRNA level, whereas h-vibration (2 ×/d) normalized OC serum levels. Many of the other measured parameters did not reveal any significant differences between the vibrated groups and the untreated Ovx group. The effect of ovariectomy was confirmed by atrophied uterus, impaired biomechanical properties, and bone mineral density and BV/TV of the vertebral body. The findings of the present study indicate that application frequency rate and direction of vibration might influence spine response differently. However, we were unable to find any clearly beneficial or harmful effect of vibration regimes on the osteopenic lumbar spine in rats.

Effects of 8-Prenylnaringenin and Whole-Body Vibration Therapy on a Rat Model of Osteopenia

Background. 8-Prenylnaringenin (8-PN) is the phytoestrogen with the highest affinity for estrogen receptor-α (ER-α), which is required to maintain BMD. The osteoprotective properties of 8-PN have been demonstrated previously in tibiae. We used a rat osteopenia model to perform the first investigation of 8-PN with whole-body vertical vibration (WBVV). Study Design. Ovariectomy was performed on 52 of 64 Sprague-Dawley rats. Five weeks after ovariectomy, one group received daily injections (sc) of 8-PN (1.77 mg/kg) for 10 weeks; a second group was treated with both 8-PN and WBVV (twice a day, 15 min, 35 Hz, amplitude 0.47 mm). Other groups received either only WBVV or no treatment. Methods. The rats were sacrificed 15 weeks after ovariectomy. Lumbar vertebrae and femora were removed for biomechanical and morphological assessment. Results. 8-PN at a cancer-safe dose did not cause fundamental improvements in osteoporotic bones. Treatment with 8-PN caused a slight increase in uterine wet weight. Combined therapy using WBVV and 8-PN showed no significant improvements in bone structure and biomechanical properties. Conclusion. We cannot confirm the osteoprotective effects of 8-PN at a cancer-safe dose in primary affected osteoporotic bones. Higher concentrations of 8-PN are not advisable for safety reasons. Adjunctive therapy with WBVV demonstrates no convincing effects on bones.