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PubMed2002

The assessment of nociceptive and non-nociceptive skin sensitivity in the Japanese quail (Coturnix japonica).

We evaluated the efficacy of two nociceptive tests, the hot water (HWT) and the foot pressure tests (FPT), and one non-nociceptive test (Semmes-Weinstein test, SWT) in assessing skin sensitivity in conscious Japanese quail. All stimuli elicited a reflex-like, strongly reproducible response. Responses in the HWT and FPT were identified as typical nocifensive flight-fight behavior. In untreated birds, these responses occurred at temperatures and forces described previously as noxious. In the SWT, two responses were observed: a slight ruffling of the cloacal gland feathers due to the stimulation of the cloacal gland, and a brief extension of the limbs due to the stimulation of the ilium or pectoral apterium. These reactions occurred at intensities recognized as innocuous. Morphine significantly altered the response latency and threshold in the HWT and FPT, but had no effect in the SWT. However, the SWT response threshold was significantly increased by local application of xylocaine. Taken together, the pattern of the responses, the intensities and the effects of morphine and xylocaine allowed to distinguish between nociceptive and non-nociceptive tests. They also demonstrate the efficacy of these tests to evaluate skin sensitivity in quail and to assess its modulation by chemical factors that affect somatosensory processes.

Analgesics↗
PubMed2003

Dental implants in reconstructed jaws: implant longevity and peri-implant tissue outcomes.

PURPOSE: The study aimed to evaluate the clinical status and survival of dental implants inserted in reconstructed jaws, with particular reference to the peri-implant tissues. MATERIALS AND METHODS: We conducted a clinical follow-up study based on 29 rehabilitated patients after oral tumor surgery, who received autogenous bone grafts from the ilium and endosseous implants (14 maxillary and 15 mandibular cases; 140 implants) for functional jaw reconstruction between 1988 and 1999. Clinical records of the patients were reviewed retrospectively. Clinical parameters of plaque index, probing pocket depth, and bleeding on probing were assessed around the implants and control teeth at 4 locations (mesiobuccal, distobuccal, mesiolingual, and distolingual). Implant mobility was assessed clinically and objectively using a Periotest (Gulden; Siemens, Bensheim, Germany) equipment for those implants supporting removable prostheses. Radiographically, the proportion of implant length remained osseointegrated was measured. RESULTS: With a mean follow-up time of 50 months, 90.7% of the 140 implants placed were functional in supporting dental prostheses; 4.3% of implants failed in osseointegration and the remaining 5.0% implants were osseointegrated but nonfunctional. A total of 493 sites of 127 functional implants and 392 sites of 98 control teeth were assessed. No significant difference was found between the implants and control teeth parameters, except on the probing pocket depth. The mean peri-implant probing depth was 3.5 mm, and 52.7% of the measured sites were 3 mm or less. More than one third of the implants (35.9%) presented with increased probing depth (> or =4 mm), and this was significantly higher than in the control teeth (P <.001, chi(2) test). Bleeding on probing was found in 19.3% of the measured peri-implant sites, corresponding to 42.2% of the dental implants. Of the implants, 28.9% were completely free from plaque and 9.4% show visible plaque accumulation. Mobility assessment was feasible on 32 implants and no mobility was detected. Radiographically, the mean implant length remained in bone was 81.1%, with 82.6% in the maxilla and 79.4% in the mandible. Implant survival rate calculated using the Kaplan-Meier method was 86.9% for 5 years. Based on the defined criteria, the success rate of implants placed in reconstructed jaws in this study was 90.7%. CONCLUSION: Endosseous implants can be successfully placed in reconstructed jaws for oral rehabilitation with maintenance of reasonable health status of the peri-implant tissues in the long-term.

Adolescent↗
PubMed1996

Autologous bone grafts and endosseous implants: complementary techniques.

PURPOSE: This article describes predictable techniques to augment contour- or height-deficient edentulous alveolar processes with autologous bone grafts for simultaneous or secondary placement of endosseous implants. METHODS: Augmentation bone grafts harvested from the ilium and mandible were used to reverse alveolar atrophy of the maxilla and mandible. Endosseous implants were either placed simultaneously with the graft or 6 to 9 months after grafting. Implant success was calculated only after an implant-supported prosthesis was in function for a minimum of 12 months. RESULTS: One hundred twenty-nine autologous bone grafts were placed in 99 patients. This included 70 grafts in the maxillary sinus, 32 onlay grafts, 14 veneer grafts, 9 saddle grafts, and 4 inlay grafts. Of these, 117 (90.7%) were successful. A total of 364 implants were placed in the grafted areas, 134 at the time of grafting and 230 6 to 9 months after grafting to allow time for osseous healing and remodeling. Three hundred twenty (87.9%) of the 364 implants placed in grafted areas were successful; 112 (83.6%) of the implants placed at the time of bone grafting and 208 (90.4%) of the implants placed secondarily in consolidated grafts. A total of 51 implants were placed in non-grafted areas in the same group of patients. Of these, 49 (96%) were successful. CONCLUSION: Autologous bone grafts can be used successfully to improve the ability to place endosseous implants. The successful placement of implants in autologous grafts is more predictable when the implants are placed secondarily, 6 to 9 months after bone grafting. Failure of individual implants does not imply failure of the bone graft. In most instances when implants failed to osseointegrate, enough bone graft remains to allow subsequent successful implant placement 6 to 9 months later.

Adolescent↗
PubMed1997

Reconstruction of mandibular continuity defects in dogs using poly (L-lactide) mesh and autogenic particulate cancellous bone and marrow: preliminary report.

PURPOSE: This study evaluated the reconstruction of continuity defects in the canine mandible using a poly [L-lactide] (PLLA) mesh tray and particulate cancellous bone and marrow (PCBM). MATERIALS AND METHODS: Eight adult dogs were divided into two groups of four dogs each. In group A, each dog had a tray fixed with stainless steel wires on each side of the mandibular stumps with the concave surface of the tray attached to the inferior border of the mandible (U-fixation). In group B, the concave surface was attached to the superior border (inverted U-fixation). Each tray was filled with PCBM from the ilium. After the operation, the dogs were radiographed, and specimens were examined histologically at 3-, 6-, and 12-month intervals. RESULTS: All of group A showed good clinical healing and the continuity of the mandibular bone was regained within 3 months postoperatively. However, fibrous tissue had invaded through the area above the tray, resulting in a poorly shaped alveolar ridges. In group B, the dogs showed good bony regeneration with well-shaped alveolar ridges. However, two animals in this group had partial exposure of the PLLA mesh tray into the oral cavity. CONCLUSION: It is suggested that a combination of the PLLA mesh and PCBM grafts might be a useful technique for functional reconstruction of the jaw bone, specifically using method A (U-fixation) as a technique to reconstruct continuity defects of the mandible, and method B (inverted, U-fixation) as a promising method for alveolar reconstruction to make wearing dentures possible.

Animals↗
PubMed1976

Cancellous bone grafting with collagen stents.

Surgical defects were created in the superior border of the mandible in five mongrel dogs and filled with particulate cancellous bone taken from the ilium and held in place with a bovine collagen stent. New bone formation was studied radiographically, histologically, and by intravital tetracycline labeling. The stent was adequate to maintain the bone particles in position and was well-tolerated by the tissues. The length of survival of the collagen stent was related to the degree of tanning.

Animals↗
PubMed2001

Extracorporeal irradiation for malignant bone tumors.

PURPOSE: Extracorporeal irradiation (ECI) has been used selectively in the management of primary malignant bone tumors since 1996. We report our techniques for ECI and the short-term oncologic and orthopedic outcomes. METHODS AND MATERIALS: Sixteen patients with primary malignant bone tumors were treated with ECI from 1996 to 2000. The median age was 14 years. The histologic diagnoses were Ewing's sarcoma (11), osteosarcoma (4) and chondrosarcoma (1). The treated sites were femur (7), tibia (4), humerus (2), ilium (2), and sacrum (1). Following induction chemotherapy in Ewing's sarcomas and osteosarcoma, en bloc resection of the tumor and tumor-bearing bone was performed. A single dose of 50 Gy was delivered to the bone extracorporeally using either a linear accelerator (9 cases) or a blood product irradiator (7 cases). The orthopedic outcome was recorded using a standard functional scale. RESULTS: At a median follow-up of 19.5 months, there were no cases of local recurrence or graft failure. One patient required amputation due to chronic osteomyelitis. For the 10 patients with follow-up greater than 18 months, the functional outcomes were graded good to excellent. CONCLUSION: The short-term oncologic and orthopedic results are encouraging and suggest that ECI provides a good alternative for reconstruction in limb conservative surgery in selected patients. This technique should only be used in a multidisciplinary setting, where careful follow-up is available to assess the long-term outcomes.

Adolescent↗
PubMed2003

Radiotherapy in the management of giant cell tumor of bone.

PURPOSE: To evaluate the outcomes of patients with giant cell tumor of bone (GCTB) treated with radiotherapy (RT) with or without surgical resection. METHODS AND MATERIALS: We performed a retrospective review of the records from 25 consecutive patients with pathologically confirmed GCTB who had undergone RT between 1956 and 2000. RESULTS: Patients ranged in age from 11 to 69 years (median 32); 16 were female and 9 were male. The anatomic distribution of lesions was as follows: cervical spine, 3; temporal bone, 1; thoracic or lumbar spine, 9; sacrum, 8; ilium, 1, and humerus, radius, and thumb metacarpal, 1 each. Tumors ranged in size from 2 to 20 cm (median 9.5) at their maximal dimension. Thirteen patients had been referred for RT for primary GCTB and 12 had been referred with locally recurrent disease after having undergone one or more other treatments. Fourteen patients had undergone RT for gross disease, and the remaining 11 had been treated with RT after gross total resection. In 10 of these 11 patients, the treatment margins were positive or uncertain. Radiation doses ranged from 25 to 65 Gy (median 46). At a median follow-up of 8.8 years (range 0.67-34), 7 patients had developed isolated local recurrence, 2 had developed isolated distant recurrence, and 3 had developed both. The actuarial 5-year overall and disease-free survival rate was 91% and 58%, respectively, and the actuarial 5-year local control and distant metastasis-free survival rate was 62% and 81%, respectively. Univariate analysis suggested that treatment for recurrent disease correlated with a lower disease-free survival rate (83% vs. 33%, p = 0.06), distant metastasis-free survival rate (100% vs. 64%, p = 0.08), and local control rate (83% vs. 42%, p = 0.08) at 5 years. Of the 12 cases of recurrence, 7 were ultimately successfully treated with additional salvage therapy. In 4 of these patients, salvage therapy included interferon-alpha 2b. CONCLUSION: RT should be considered an adjuvant to surgery or as alternative therapy in cases of GCTB that are unresectable or in which excision would result in substantial functional deficits. When RT is used as primary therapy, the rate of local control seems to be satisfactory. In heavily pretreated patients, however, RT delivered as it was in this series can result in poor local control, and alternative therapies should be considered.

Adolescent↗
PubMed1991

Management of potentially infected complex hand injuries.

Fifteen patients with contaminated, and thus potentially infected, hand injuries were treated. All had segmental bone loss: six metacarpals, three proximal phalanges, three middle phalanges, and three joint injuries. The treatment was based on the simultaneous primary application of external minifixators and antibiotic-loaded bone cement beads and completed by early bone grafting. This external fixation and internal antibiotic treatment has synergic effect both mechanically and biologically. Thus potentially infected fresh injuries were treated in exactly the same way as an established osteomyelitis. Although there were a few minor wound problems and superficial pin tract infections, there were no deep infections, and no bone grafts were lost. All of the patients were grafted with autologous bone taken from the ilium within 7 to 8 days. Rehabilitation time was markedly decreased by this method, and all of the patients returned to work within 8 months.

Adult↗
PubMed1985

Functional latissimus dorsi island pedicle musculocutaneous flap to restore finger function.

Functional latissimus dorsi island pedicle musculocutaneous flaps were used to restore flexion or extension of the wrist and digits in four clinical cases. By retaining the fascial origin of the latissimus dorsi from the posterior crest of the ilium, the entire muscle was transferred without dividing its neurovascular pedicle and microneurovascular anastomoses. Its facial origin successfully reached the finger flexor or extensor muscles of the forearm. The latissimus dorsi muscle was sutured to the digital flexor tendons in three patients and connected to the extensor tendons in one patient. All transfers restored active finger flexion or extension.

Adult↗
PubMed1986

The impact of modern cement techniques on acetabular fixation in cemented total hip replacement.

A radiographic study was performed to assess acetabular fixation in 78 total hip replacements performed between 1971 and 1980. In 1979, the technique of acetabular component insertion was modified to include water-pik lavage, preservation of subchondral bone of the acetabulum during reaming, multiple fixation holes in the pubis ischium and ilium, and devices that improve pressurization of the cement into the cancellous bone surfaces. The impact of these techniques was studied. A cumulative radiolucency score was calculated for each acetabulum from 5-year follow-up radiographs, and the mean cup radiolucency scores for two chronologic groups were compared using the t-test for independent samples. No significant differences in patient age, weight, or sex, type of prosthesis, or approach used was found between groups. The acetabular components inserted between 1979 and 1980 had significantly lower cup radiolucency scores than those inserted between 1971 and 1978, at 5-year follow-up evaluation. Modern cement technique may be responsible for significantly enhanced durability of acetabular fixation in cemented total hip replacement.

Acetabulum↗
PubMed1988

Combined anterior and posterior approach to the hip joint in reconstructive and complex arthroplasty.

The combined anterior and posterior approach permits access to the front and back of the hip joint for reconstruction and complex arthroplasty, usually without osteotomy of the greater trochanter, with minimal muscle release. There is ease of access to the anterior and posterior capsule, which can be resected under direct vision, thus permitting accurate hemostasis. The entire acetabular rim is exposed for bone grafting as required. The authors review the useful standard approaches and illustrate the combination of the anterior and posterior approaches through a straight lateral incision. Concomitant exploration of the sciatic nerve is demonstrated, as is the osteotomy of the trochanter performed when the ilium superior to the acetabulum must be reconstructed. The utility and limitations of the operation is illustrated by representative cases. This extensive procedure usually can prevent neurologic and vascular compromise and allows excellent observation of the skeletal structures for accurate component alignment.

Aged↗
PubMed1996

Acetabular revision using a bone-ingrowth total hip component in patients who have acetabular bone stock deficiency.

The clinical and radiologic results of acetabular revision using a porous titanium-mesh metal-backed acetabular component fixed to the pelvis with screws were studied in 30 consecutive patients (32 hips) who had moderate or severe acetabular bone loss. All of the acetabula were classified as type III or IV according to the American Association of Orthopaedic Surgeons' acetabular grading system. Particulate autologous or allogenic bone-graft was used in 75% of the reconstructions. The mean follow-up period was 69 months (range, 46-109 months). Three acetabular components (9%) were rerevised for aseptic loosening at an average of 64 months, including one patient who had a primary diagnosis of radiation necrosis of the ilium. The average Harris hip score for the remaining 29 hips rose from 46 to 81. The radiologic failure rate was 3% (1 of 29 unrevised hips) for a total failure rate of 12%. No pelvic osteolysis was seen with this implant. Revision of acetabula that have moderate or severe bone deficiency by a bone-ingrowth acetabular component fixed with screws and bone-graft appears to be successful in restoring bone stock and providing a stable, pain-free reconstruction.

Acetabulum↗
PubMed1998

An in vitro study of a new design of acetabular cement pressurizer.

Aseptic loosening of the acetabular component remains one of the limiting factors in the long-term success of total hip arthroplasty. Cement pressurization has been shown to improve fixation. A new pressurizer has been designed that seals around the rim of the acetabulum and covers the transverse ligament notch with a flap. The results of in vitro testing of this device are presented and compared with those of pressure generated by insertion of an acetabular cup. The pressurizer allowed sustained, uniform cement pressurization. Peak pressures with the new pressurizer were 180 kPa at both the iliac region of the rim and the pole of an instrumented model acetabulum, compared with 55 kPa at the rim and 120 kPa at the pole on cup insertion. Pressures were maintained in the range of 80-90 kPa. The flap was effective in preventing cement leakage from the notch, and pressures were higher than when the flap was absent. Cup insertion alone gave only transient pressurization, substantially less near the rim of the acetabulum than at the pole. Peripheral pressurization may be significant in producing secure local fixation at the rim of the acetabulum, in particular in the region of the ilium (Charnley zone 1), where radiolucencies are most commonly observed and where stresses in the implanted acetabulum are highest. Improved rim fixation may also play a role in preventing the ingress of wear debris.

Acetabulum↗
PubMed1992

Value of conformal planning in the radiotherapy of soft tissue sarcoma.

The late complications and subsequent limb function seen following treatment of extremity sarcoma are related to the radiation dose used and the volume of tissue irradiated. The potential value of the use of 3D-planning and conformal blocking has been studied in 11 patients with lower limb sarcoma. Tumour, target and normal tissue volumes were reconstructed in 3D following a CT planning scan. Dose calculations were performed for conventional and conformal plans, using customized blocks with a margin of 6 mm around the target volume. No compromise of target dosimetry was permitted. The volumes of tissue receiving 50%, 80% and 90% of the prescribed dose were compared using cumulative volume dose histograms. The treatment volume was reduced in all patients, and by greater than 20% in four of five with thigh tumours. The mean volume of muscle outside the target volume which was irradiated to the 50% isodose was 4.2 litres. The volume irradiated to 90% or greater isodose was reduced by greater than 30% in five of eight patients with thigh and lower leg tumours. Similarly, the volumes of femur, tibia/fibula and ilium were reduced by 38%, 18% and 14% respectively by conformal blocking. Considerable sparing was achieved in the volumes of pelvic contents irradiated, including gonads and rectum. This simple, but time consuming, technique can achieve major reductions in normal tissue irradiation with potential improvements in limb function. To confirm its value and safety, prospective randomized trials must be performed and similar advances in patient immobilization and treatment verification are essential.

Humans↗
PubMed2001

On biomechanical properties of the sacroiliac joint in purebred dogs.

Relative to the Yorkshire Terriers and Maltese dogs the mean expected sacroiliac joint load was calculated to be 1.4-1.6 times higher in other small breeds and 1.7-2.7 times higher in large breeds. The statistically significantly different (p < 0.01, p < 0.001) and mechanically less efficient inclination angles of the wings of the sacrum in adult large breeds (especially German Shepherd Dogs) suggest even higher forces acting on their sacroiliac ligaments. Unlike the case in small breeds, the sacral auricular surface was concave in large dogs to improve interlocking between sacrum and ilium and to reduce craniocaudal translation. An additional ossification center forming the ventral aspect of the transverse process of the second sacral vertebra was present in large breeds, occasionally in midsized and small, but never in toy breeds. This and the relationship between age and inclination angles of the wings of the sacrum in juvenile specimens indicate an affection of the three-dimensional modeling of the wings of the sacrum by formative stimuli such as body weight and locomotion.

Aging↗
PubMed2003

Insufficiency fracture. A survey of 60 cases and review of the literature.

UNLABELLED: We report findings on the site, risk factors and imaging of insufficiency fractures (IF) in 60 patients admitted to our department between 1989 and 1997. RESULTS: Fifty-five women (mean age 72.5 years) and five men (mean age 59 years) had 91 fractures, accounting for 0.32% of admissions. Fractures occurred most commonly in the pelvic girdle (30.7%, 28/91) and in the sacrum (29.6%, 27/91). In eight patients fractures of the sacrum were associated with fractures of the pelvic girdle. The next most common sites of occurrence were the tibia (16.5%, 15/91: 11 transverse, four longitudinal) and the femoral neck (9.9%, 9/91). There were three subchondral fractures of the femoral head, three fractures of the femoral diaphysis (two longitudinal, one transversal), two of the astragalus, and one each of the ilium, perone, calcaneum and sternum. Thirty patients had osteoporosis: six had received fluoride treatment and five had corticosteroids. Other risk factors were rheumatoid arthritis (4), osteomalacia (4), corticosteroid treatment (4), and hyperparathyroidism (1). Radiography showed a fracture line or osteocondensation in 65% (39/60) of cases. Scintigraphy was positive in 87.5% of cases (21/24), showing a fracture line (15) or a callus (6). Bone computed tomography (CT) scan was positive in 98.1% (54/55) of cases. IF occurs in elderly women with osteoporosis and most commonly in the pelvis. CONCLUSIONS: Since radiologic signs are inconstant, scintigraphy is the choice procedure.

Aged↗
PubMed2000

Structural and cellular changes during bone growth in healthy children.

Normal postnatal bone growth is essential for the health of adults as well as children but has never been studied histologically in human subjects. Accordingly, we analyzed iliac bone histomorphometric data from 58 healthy white subjects, aged 1.5-23 years, 33 females and 25 males, of whom 48 had undergone double tetracycline labeling. The results were compared with similar data from 109 healthy white women, aged 20-76 years, including both young adult reference ranges and regressions on age. There was a significant increase with age in core width, with corresponding increases in both cortical width and cancellous width. In cancellous bone there were increases in bone volume and trabecular thickness, but not trabecular number, wall thickness, interstitial thickness, and inferred erosion depth. Mineral apposition rates declined on the periosteal envelope and on all subdivisions of the endosteal envelope. Because of the concomitant increase in wall thickness, active osteoblast lifespan increased substantially. Bone formation rate was almost eight times higher on the outer than on the inner periosteum, and more than four times higher on the inner than on the outer endocortical surface. On the cancellous surface, bone formation rate and activation frequency declined in accordance with a fifth order polynomial that matched previously published biochemical indices of bone turnover. The analysis suggested the following conclusions: (1) Between 2 and 20 years the ilium grows in width by periosteal apposition (3.8 mm) and endocortical resorption (3.2 mm) on the outer cortex, and net periosteal resorption (0.4 mm) and net endocortical formation (1.0 mm) on the inner cortex. (2) Cortical width increases from 0.52 mm at age 2 years to 1.14 mm by age 20 years. To attain adult values there must be further endocortical apposition of 0.25 mm by age 30 years, at a time when cancellous bone mass is declining. (3) Lateral modeling drift of the outer cortex enlarges the marrow cavity; the new trabeculae filling this space arise from unresorbed cortical bone and represent cortical cancelization; (4) Lateral modeling drift of the inner cortex encroaches on the marrow cavity; some trabeculae are incorporated into the expanding cortex by compaction. (5) The net addition of 37 microm of new bone on each side of a trabecular plate results from a <5% difference between wall thickness and erosion depth and between bone formation and bone resorption rates; these small differences on the same surface are characteristic of bone remodeling. (6) Because the amount of bone added by each cycle of remodeling is so small, the rate of bone remodeling during growth must be high to accomplish the necessary trabecular hypertrophy.

Adolescent↗
PubMed2000

A physical, chemical, and mechanical study of lumbar vertebrae from normal, ovariectomized, and nandrolone decanoate-treated cynomolgus monkeys (Macaca fascicularis).

Ovariectomized cynomolgus monkeys have previously been investigated as a nonhuman primate model of postmenopausal osteoporosis (Jerome et al., Bone Miner 9:527-540; 1994). In the present study, Fourier transform infrared microspectroscopy (FTIRM) was used to verify that differences in bone mineral quality and quantity in the vertebrae of mature intact (INT) and ovariectomized (ovx) monkeys were analogous to those seen in osteoporotic and nondiseased human bones. FTIRM spectra were acquired from 15 trabeculae per vertebra from three ovx and three INT adult monkeys (mean age 8 years). These spectra were compared with those of both trabecular and previously reported osteonal bone obtained from 3 "normal" and 11 postmenopausal osteoporotic human subjects. While variations in the mineral:matrix ratio (mineral content), carbonate:phosphate ratio, and crystallinity are typical for trabecular bone from iliac crests of normal human subjects, the values of these parameters were relatively static for trabecular bone from postmenopausal osteoporotic human subjects. In general, trabecular bone from postmenopausal osteoporotic human subjects exhibited decreased mineral content (1.0 +/- 0.5 vs. 2.9 +/- 0.6), increased crystallinity, and increased carbonate:phosphate relative to controls. Similarly, trabecular bone from ovariectomized monkeys exhibited lower mineral content (5.8 +/- 0.2) compared with the INT group (6.2 +/- 0.2; p </= 0.05) and contained larger/more perfect apatite crystals (increased crystallinity) with increased carbonate:phosphate ratios. Variations in absolute values were attributable to site differences (ilium vs. vertebrae). To appreciate the importance of mineral properties on mechanical properties, compression testing was performed using cores of monkey L-3 and L-4 vertebral bodies from a separate group of monkeys. Treating monkeys with the anabolic steroid nandrolone decanoate (ND) immediately after ovariectomy and for the next 24 months (ND group), or beginning 12 months after ovariectomy (dND group), increased the ultimate stress compared with an ovx treatment group, despite large interanimal variations in bone architecture and mechanical properties. These data support the hypothesis that ovariectomized adult monkeys are an excellent model for postmenopausal osteoporosis, and can be used for the evaluation of therapeutic modalities.

Animals↗