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PubMed2004

Comparison between two experimental protocols to promote osteoporosis in the maxilla and proximal tibia of female rats.

The effects of two experimental protocols (ovariectomy associated or not with a low calcium diet) used to promote osteoporosis in the rat maxilla and proximal tibia were compared 5 and 11 weeks after surgery. Female Wistar rats were ovariectomized or sham-operated. Half of the ovariectomized rats were fed a low Ca++ diet (ovx*) and the remaining ovariectomized (ovx) and sham animals received a standard chow. At sacrifice, the proximal metaphysis was excised from the tibia and the molars were extracted from the hemi-maxilla. Dry (60 degrees C overnight) and ash (700 degrees C/14 h) weights were measured and the ashes were used for Ca++ measurement by means of a colorimetric method. After 5 weeks, ovx caused no alteration while ovx* decreased proximal metaphysis (17%) and maxilla (35%) bone mass. After 11 weeks, ovx caused a 14% bone mass reduction in the proximal metaphysis but not in the maxilla, while ovx* caused a comparable bone mass reduction (30%) in both bone segments. Calcium concentration was not altered in any experimental condition. The results show that estrogen deficiency is insufficient to cause maxillary osteoporosis in rats over an 11-week period and a long-term ovariectomy is needed to exert deleterious effect on proximal metaphysis bone mass. When a low Ca++ diet is associated with estrogen deficiency, however, a relatively precocious harmful effect is observed, twice as pronounced in the maxilla than in the proximal metaphysis. On a long-term basis, ovariectomy associated with a low Ca++ diet seems to be equally injurious to both proximal metaphysis and maxilla.

Alveolar Bone Loss↗

PubMed2000

Normal osteoconduction and repair in and around submerged highly bisphosphonate-complexed hydroxyapatite implants in rat tibiae.

BACKGROUND: Ceramic hydroxyapatite implants have been used in dentistry for their unique compatibility with alveolar bone. Recently it was reported that bisphosphonates may be beneficial in preventing alveolar bone destruction associated with natural and experimental periodontal disease. Furthermore, bisphosphonate does prevent resorption of alveolar bone following mucoperiosteal flap surgery. We undertook a preliminary study evaluating the effects of highly bisphosphonate-complexed hydroxyapatite implants on osteoconduction and repair in rat tibiae. METHODS: Porous hydroxyapatite implants were pre-incubated in 10(-2)M bisphosphonate solutions at pH 3.49 and pH 7.32. The implants had a diameter of 2.1 mm and a height of 2 mm and adsorbed 115 microg bisphosphonate in vitro. Bisphosphonate/hydroxyapatite implants and plain hydroxyapatite implants were inserted in opposite tibial metaphyses of 35 rats. The measurement errors for the mineral density (MD) of the implants and the proximal trabecular mineral bone density (TD) were estimated by peripheral computed tomography and the bone mineral density (BMD) measurement error by dual x-ray absorptiometry. RESULTS: The measurement errors for the MD of the implants and the TD by peripheral computed tomography were 0.81% and 1.96%, respectively ex vivo. The BMD measurement error estimated by dual x-ray absorptiometry was 0.51% ex vivo. TD and BMD for bisphosphonate/hydroxyapatite implants were insignificantly higher compared to plain hydroxyapatite implants. Bisphosphonate/hydroxyapatite pre-incubated at pH 7.32 were found to be nondegradable implants, while bisphosphonate/hydroxyapatite (pH 3.49) implants were slowly degradable and lost a significant 5% of their density. Histologically, all bisphosphonate/hydroxyapatite implants appeared to be fully integrated and effective as bone replacement material in rat tibial bone. They exhibited vascularization and osteoconduction of tibial bone growth along and inside their porous structure. CONCLUSIONS: Our study suggests that normal osteoconduction and repair occurred in and around the highly bisphosphonate-complexed hydroxyapatite implants in rat tibiae.

Absorptiometry, Photon↗

PubMed1993

Bone changes associated with intraosseous hypertension in the caprine tibia.

We investigated the effects of increased intraosseous pressure on new-bone formation in the proximal metaphysis of the caprine tibia. Intraosseous hypertension was produced by obstruction of venous outflow by ligation of the popliteal vein draining the proximal aspect of the tibia and occlusion of the medullary space with bone cement (groups 1 and 2). After the obstruction of venous outflow (day 0), the intraosseous pressure measured at the proximal tibial metaphysis increased significantly from a mean of 15.5 millimeters of mercury before the obstruction to a mean of 28.7 millimeters of mercury in groups 1 and 2. In group 1, obstruction of venous outflow was combined with intraosseous infusion of autogenous whole blood under pressure to maintain the intraosseous pressure between thirty and forty-five millimeters of mercury during days 0 through 5. The time for venous drainage was still prolonged and intraosseous pressures were still increased on days 5 and 10 (means, 26.8 and 26.2 millimeters of mercury, respectively) in groups 1 and 2. The intraosseous hypertension produced in group 1 was associated with a significant increase in periosteal (138 per cent), endocortical (369 per cent), and cancellous new-bone formation (889 per cent) at the tibial metaphysis compared with control values. Osseous necrosis within the metaphysis was not observed.

Animals↗

PubMed1999

Malignant tumor of the distal part of the femur or the proximal part of the tibia: endoprosthetic replacement or rotationplasty. Functional outcome and quality-of-life measurements.

BACKGROUND: The present study was performed to determine whether there is a difference, with regard to functional outcome and quality of life, between endoprosthetic replacement and rotationplasty for the treatment of malignant tumors of the distal part of the femur or the proximal part of the tibia. METHODS: Sixty-seven patients, between the ages of eleven and twenty-four years at the time of the diagnosis, had a malignant tumor of the distal part of the femur or the proximal part of the tibia. A rotationplasty was performed in thirty-three patients, and an endoprosthetic replacement was done in thirty-four patients. The median duration of follow-up was six years and one month (range, two years to sixteen years and two months). The scale developed by the Musculoskeletal Tumor Society was used to evaluate the functional results. Quality-of-life issues were assessed with the questionnaire developed by the European Organization for Research and Treatment of Cancer. RESULTS: The patients who had had a rotationplasty had a mean functional score, according to the system of the Musculoskeletal Tumor Society, of 24 points, and the patients who had had an endoprosthetic replacement had a mean score of 25 points. This difference was not found to be significant, with the numbers available (p = 0.47). Only one patient who had had a rotationplasty used an assistive device when walking long distances, whereas six patients who had had an endoprosthetic replacement used an assistive device. This difference was significant (p<0.001). The quality-of-life questionnaire revealed that the patients who had had a rotationplasty could participate in hobbies such as carpentry and sports as well as in other daily activities to a significantly greater degree than those who had had an endoprosthetic replacement (p = 0.001). Restriction in daily activities due to pain was significantly less common in the group that had had a rotationplasty than it was in the group that had had an endoprosthetic replacement (p = 0.047). CONCLUSIONS: Rotationplasty was not associated with any disadvantages with regard to function or quality of life in comparison with endoprosthetic replacement. It is possible that the psychosocial outcome is influenced by the fact that patients who have a rotationplasty know that additional operative intervention is not usually necessary. Despite good functional and quality-of-life results, the cosmetic appearance may be the most serious disadvantage of rotationplasty. The decision to perform this procedure must be made on a case-by-case basis.

Adolescent↗

PubMed1999

Distraction osteogenesis for lengthening of the tibia in patients who have limb-length discrepancy or short stature.

BACKGROUND: This study was performed to determine the safety and effectiveness of lengthening of the tibia, in patients who have a limb-length discrepancy or a short stature, with use of distraction osteogenesis, a technique based on the principle of distracting the callus that is formed after a subperiosteal osteotomy of the proximal portion of the diaphysis of a long bone. METHODS: A total of 230 tibial lengthening procedures were done in 150 patients. Seventy procedures were performed because of a limb-length discrepancy, which was secondary to trauma (thirty limbs), congenital fibular hemimelia (twenty-six), poliomyelitis (ten), or infection (four). The remaining 160 procedures were performed because of a short stature, which was secondary to achondroplasia (fifty-eight limbs), Turner syndrome (thirty-four), an idiopathic etiology (twenty-two), hypochondroplasia (twenty), achondroplasia (ten), Ellis-van Creveld syndrome (six), rickets (four), or adrenogenital syndrome, Laron syndrome, or pseudoachondroplasia (two limbs each). The age of the patients at the time of the operation was 18.4+/-6.2 years (average and standard deviation), with a range of six to forty-one years. The procedures were performed according to one of three protocols. In Group A (ninety procedures), an Orthofix telescopic fixator and a variable number of screws were used and the tibiofibular syndesmosis was not stabilized; in Group B (ninety-six procedures), an Orthofix reconstruction system was used, the syndesmosis was stabilized, and a tenotomy of the Achilles tendon was performed; and in Group C (forty-four procedures), an Orthofix Garches lengthening device was used, the syndesmosis was stabilized, and a tenotomy of the Achilles tendon was performed. RESULTS: At the time of the latest follow-up (average, five years; range, two to seven years), the average gain in length after the seventy procedures performed because of a limb-length discrepancy was 4.0+/-1.98 centimeters (range, 2.5 to 9.5 centimeters), or 14 percent (range, 7 to 45 percent). The average gain in length after the 160 procedures that were performed because of a short stature was 7.8+/-2.28 centimeters (range, 2.5 to fifteen centimeters), or 33 percent (range, 10 to 78 percent). Ten (14 percent) of the seventy procedures performed because of a limb-length discrepancy and forty-six (29 percent) of the 160 performed because of a short stature were associated with a complication. There was only one permanent sequela in the entire series. CONCLUSIONS: Although the three operative protocols resulted in similar healing indices, the rates of complications differed significantly among the groups (p<0.0001). Group C (the Garches device) had the lowest rate of complications (7 percent). It is important to be aware of potential complications as well as the need for additional procedures in order to avoid predictable problems. These procedures include percutaneous tenotomy of the Achilles tendon and fixation of the distal segment of the fibula to the tibia to maintain the integrity of the tibiotalar articulation and the alignment of the foot.

Achilles Tendon↗

PubMed2006

Ultrasound measurements of torsions in the tibia and femur.

BACKGROUND: The purpose of the present study was to determine the validity and reliability of using ultrasound to measure tibial and femoral torsion. METHODS: In vitro ultrasound measurements of torsion in 118 matched dried tibiae and femora were compared with direct anatomical measurements with use of simple regression. The second part of the study involved repeated in vivo ultrasound measurements made on twenty adult limbs to determine the clinical reliability of our methods. RESULTS: The in vitro ultrasound measurements of femoral and tibial torsion were significantly related to the anatomical measurements (p < 0.001 for both). The inter-rater correlation coefficients between three examiners were 0.84 for both the tibial and femoral measurements, and the intra-rater correlation coefficients ranged from 0.86 to 0.98. The in vivo measurements were similar to the in vitro measurements, and the intra-rater correlation coefficients for repeated measures were 0.91 and 0.93 for femoral and tibial torsion, respectively. CONCLUSIONS: Ultrasound is a viable tool for measuring torsion of the tibia and femur. In order to minimize measurement errors, the ultrasound measurement should be used to calculate the predicted value of torsion with use of the regression equation.

Adult↗

PubMed1991

Fibrous dysplasia vs adamantinoma of the tibia: differentiation based on discriminant analysis of clinical and plain film findings.

Differentiation between benign fibrous dysplasia and malignant adamantinoma of the tibia is challenging because of the impact the diagnosis has on the choice of treatment (none or extensive surgery). The histologic and pathologic similarities of the lesions and the controversial relationship between fibrous dysplasia, osteofibrous dysplasia, and adamantinoma complicate the matter. We found a large overlap of histologic features in lesions considered either fibrous dysplasia or osteofibrous dysplasia on the basis of the radiologic findings. The purpose of this study was to determine the value of the plain radiograph of the lower leg in combination with clinical findings to differentiate the benign from the malignant condition. The clinical symptoms, radiographs, and histologic slides of 46 patients with fibrous dysplasia and 22 with adamantinoma in the tibia were reviewed retrospectively. In only one of 12 patients with radiologic or histologic characteristics of osteofibrous dysplasia were both radiologic and histologic criteria for the diagnosis present. A linear discriminant analysis was performed on six clinical (age, spontaneous pain, pain after trauma, swelling only, pain and swelling, and bowing deformity) and 25 radiologic signs. Fibrous dysplasia and its variant osteofibrous dysplasia could be identified correctly in 87% (40 of 46 patients) and adamantinoma in 95% (21 of 22 patients) by using the patient's age and four radiologic signs. When results from the discriminant analysis of a randomized subgroup of patients (32) were used on the other subgroup (36 patients), fibrous dysplasia was correctly identified in 84% (21 of 25) and adamantinoma in 82% (nine of 11). Fibrous dysplasia is more prevalent than adamantinoma in a young patient, when radiographs show a ground-glass appearance and anterior bowing and when there is no multilayered periosteal reaction and moth-eaten destruction. When radiologic signs and the patient's age are combined, fibrous dysplasia and adamantinoma can be discriminated in a high percentage of patients.

Adolescent↗

PubMed2005

[Reconstruction of the infected war defects of the tibia: a fragment elongation according to the Ilizarov technique].

INTRODUCTION/AIM: The treatment of tibia defects complicated with chronic osteomyelitis is difficult, often requiring one or more surgical interventions with prolonged periods of functional incapacity. METHODS: We treated 20 patients with tibia defects, who had been wounded during the war operations in the former Yugoslavia, complicated with chronic osteomyelitis by applying the Ilizarov apparatus. In 10 patients with the average defect of 4.7 cm, interfragmentary diastasis of 1.5 cm, and 3.1 cm of shortening we applied the bilocal synchronous compressive - distractive method (BSCD). In the remaining 10 patients with average defect of 6.4 cm, interfragmentary diastasis of 5.5 cm, and 1.6 cm of shortening we applied bilocal alternating distractive - compressive osteosynthesis (BADC). RESULTS: The average followup was 93 months. In the group A, the average distraction index was 10.6, maturation index 39.8, and external fixation index 52.5. In the group B, the average distraction index was 11.7, maturation index 47.1, and external fixation index 60.1. The average time from the application to the apparatus removing was in the group A 6.5 months, and in the group B 11.9 months. There were 27 complications: 11 problems, 8 disturbs, and 8 true complications. Pin-track inflammation of the soft tissue was noted most frequently (6 patients). CONCLUSIONS: One stage of repairing inflamation and the restitution of defect in lower leg tissue was the advantage of this type of treatment. All of the patients recovered. There was not any bad result, either in osteal or in functional outcome.

Adult↗

PubMed2001

Effects of guided bone regeneration with non-resorbable and bioabsorbable barrier membranes on osseointegration around hydroxyapatite-coated and uncoated threaded titanium dental implants placed into a surgically-created dehiscence type defect in rabbit tibia: a pilot study.

The purpose of this study was to evaluate the effects of guided bone regeneration (GBR) with either a non-resorbable (ePTFE) or bioabsorbable barrier membrane (RSLT) on osseointegration and extent of bone formation around hydroxyapatite-coated (HA) and uncoated threaded titanium (Ti) dental implants placed into surgically-created dehiscence type defects in rabbit tibia. A dehiscence type bone defect, approximately 3 mm in width and height was surgically created on the outer surface of the bone in each tibia of 9 rabbits. For the conventional group, either a HA or a Ti implant was then placed at this site. After the same procedure was performed as in the conventional group, the implant site of the GBR group was covered with either an ePTFE or a RSLT. After 4 months, the rabbits were sacrificed. Specimens were prepared and examined histometrically. It was found that the mean percentage of osseointegration tended to increase in HA compared to Ti implants, both with and without membranes. There was a tendency that the extent of newly regenerated bone was higher in the GBR group than that in the conventional group.

Absorbable Implants↗

PubMed2006

In vitro mechanical evaluation of torsional loading in simulated canine tibiae for a novel hourglass-shaped interlocking nail with a self-tapping tapered locking design.

OBJECTIVE: To describe a novel interlocking nail (ILN) and locking system and compare the torsional properties of constructs implanted with the novel ILN or a standard 8-mm ILN (ILN8) by use of a gap-fracture model. SAMPLE POPULATION: 8 synthetic specimens modeled from canine tibiae. PROCEDURES: An hourglass-shaped ILN featuring a tapered locking mechanism was designed. A synthetic bone model was custom-made to represent canine tibiae with a 50-mm comminuted diaphyseal fracture. Specimens were repaired by use of a novel ILN or an ILN8 with screws. Specimens were loaded for torsional measurements. Construct compliance and angular deformation were compared. RESULTS: Compliance of the ILN8 was significantly smaller than that of the novel ILN. Mean +/- SD maximum angular deformation of the ILN8 construct (23.12 +/- 0.65 degrees) was significantly greater, compared with that of the novel ILN construct (9.45 +/- 0.22 degrees). Mean construct slack for the ILN8 group was 15.15 +/- 0.63 degrees, whereas no slack was detected for the novel ILN construct. Mean angular deformation for the ILN8 construct once slack was overcome was significantly less, compared with that of the novel ILN construct. CONCLUSIONS AND CLINICAL RELEVANCE: Analysis of results of this study suggests that engineering of the locking mechanism enabled the novel hourglass-shaped ILN system to eliminate torsional instability associated with the use of current ILNs. Considering the potential deleterious effect of torsional deformation on bone healing, the novel ILN may represent a biomechanically more effective fixation method, compared with current ILNs, for the treatment of comminuted diaphyseal fractures.

Animals↗

PubMed2006

Cartilage-derived biomarkers and lipid mediators of inflammation in horses with osteochondritis dissecans of the distal intermediate ridge of the tibia.

OBJECTIVE: To assess whether reported alterations in metabolism of cartilage matrix in young (0 to 24 months old) horses with osteochondritis dissecans (OCD) may also be found in older (24 to 48 months old) horses with clinical signs of OCD and to investigate the role of eicosanoids in initiating these clinical signs. SAMPLE POPULATION: Synovial fluid was collected from 38 tarsocrural joints of 24 warmblood horses with (22 joints of 16 horses) or without (16 joints of 8 horses) clinical signs and a radiographic diagnosis of OCD of the distal intermediate ridge of the tibia. PROCEDURES: Turnover of type II collagen was investigated by use of specific immunoassays for synthesis (carboxypropeptide of type II collagen [CPII]) and degradation (collagenase-cleaved fragments of type II collagen [C2C]) products. Furthermore, glycosaminoglycan (GAG), leukotriene (LT) B(4), cysteinyl LTs, and prostaglandin (PG) E(2) concentrations were determined, and concentrations in joints with OCD were compared with those in joints without OCD. RESULTS: Concentrations of CPII, C2C, and GAG did not differ significantly between affected and nonaffected joints. Fluid from joints with OCD had significantly higher LTB(4) and PGE(2) concentrations than did fluids from nonaffected joints. CONCLUSIONS AND CLINICAL RELEVANCE: Altered collagen or proteoglycan turnover was not detected in 24- to 48-month-old horses at the time they developed clinical signs of OCD of the distal intermediate ridge of the tibia. However, increased concentrations of LTB(4) and PGE(2) in fluid of joints with OCD implicate these mediators in the initiation of clinical signs of OCD.

Animals↗

PubMed2000

Effects of long-term treatment with caffeine on the ultrastructure of the golden hamster parathyroid gland and tibia.

The ultrastructure of the parathyroid gland and the SEM appearances of the tibia were studied in hamsters with and without administration of caffeine. Caffeine was treated orally each day at either 2.5 mg (low dose) or 10 mg (high dose) per 100 g body weight for a period of 17 or 32 days. Statistical analysis showed no significant differences among all groups examined regarding the serum calcium level. Transmission electron microscopy of the parathyroid gland revealed that the volume densities occupied by the mitochondria, Golgi complexes and rough endoplasmic reticulum of caffeine-treated groups were found significantly higher when compared with controls. The number of secretory granules observed close to the cell membrane per total amount of these granules revealed significant increase in all caffeine-treated animals. The bone mineral content (BMC) values were closely related to body weight. In the high dose caffeine-treated hamsters increment of the mean BMC and body weight values was significantly lower than those of the controls after 32 days. In the scanning electron microscopic studies of the tibia, no alteration in the morphometric parameters was demonstrated. It is considered that the synthesis and release of parathyroid hormone is stimulated following caffeine consumption. Our data suggest that although chronic administration of caffeine in the hamster may slightly increase bone turnover as evidenced by the BMC decrease, bone morphometry was not altered. Thus the osteoporotic changes were not proved in this study.

Animals↗

PubMedDate not supplied

Hyperthermic treatment of canine tibia through RF inductive heating of an intramedullary nail: a new experimental approach to hyperthermia for metastatic bone tumours.

Although the incidence of metastatic bone tumours is recently increasing, the local control rate of conventional treatment modalities is not satisfactory. If an intramedullary nail for the fixation of a weakened bone with metastatic lesions can be used as a heat-generating material for hyperthermia, the treatment result is expected to improve. This new approach to hyperthermic treatment of bone tumours has been investigated in a canine tibia. An intramedullary nail made of stainless steel was put into a medullary canal of a canine tibia. The leg was exposed to an alternating magnetic field of 100 kHz in the frequency and 100 Oe in the maximum intensity. The nail was inductively heated for 60 min. The temperature of the nail > 50 degrees C and the cancellous bone 5 mm from the nail was heated to a therapeutic temperature, 42.5 degrees C. After a bone labelling with tetracycline and calcein, the dogs were killed 2, 4 and 12 weeks after the heating. The area of osteonecrosis was evaluated by fluorescence microscopy analysis. The heated cancellous bone around the nail showed osteonecrosis in 2 weeks after the treatment, but it recovered completely in 12 weeks. This experiment has demonstrated the heating capability of the new hyperthermic technique and minimal toxicity to the bone, and suggests the clinical application to metastatic bone tumours.

Animals↗

PubMed1982

Resonance of the human tibia. Method, reproducibility and effect of transection.

Driving point impedance technique was used for in vivo determination of the lowest frequency of resonance (Fa) in the human tibia. Optimum conditions for measurement were investigated. The precision of the method was 4.7 per cent and the greatest source of variation was the positioning of the leg and muscular tension. Fa was investigatyed during transection of the human tibia post-mortem and was found to decrease as stiffness was reduced by the transection. Accordingly Fa was decreased in four patients with crural fractures. The experiments indicate that the method can be used for the determination of fracture healing.

Biophysical Phenomena↗

PubMed1983

Resection arthroplasty of the proximal tibia.

Custom made total arthroplasty of the knee with resection of the upper third of the tibia was performed in two cases. The follow-up results showed good function 1 year later. The procedure is recommended in benign as well as selected malignant tumors of the proximal tibia.

Adult↗

PubMed1983

The stress-protecting effect of metal plates on the intact rabbit tibia.

The purpose of the present study was to find the extent of stress-protection by a steel plate (45 X 5 X 1 mm) on the rabbit tibia. The animals were sacrificed after 6, 12 and 18 weeks. The median strength after plate application was 84, 73 and 72%, respectively. The elastic stiffness of plated bones was also reduced, while the deformation at fracture showed no significant reduction. The mineral content in the bone segment previously covered by a plate was measured by photon absorptiometry; it was reduced after 12 and 18 weeks. The stress-protecting effect caused by this thin steel plate was less pronounced than that previously reported by groups using more rigid plates on rabbit tibiae. The stress-protecting effect increased up to 12 weeks, but subsequently no further increase occurred.

Animals↗

PubMed1985

Vascular reactions during electrical stimulation. Vital microscopy of the hamster cheek pouch and the rabbit tibia.

Vital microscopy during electrical stimulation was performed in the hamster cheek pouch and the rabbit tibia. Stimulation with DC of 5,20 or 50 microA or AC of 20 microA was demonstrated to cause macromolecular capillary leakage as evidenced by FITC-dextran fluorescence and histological demonstration of extravasated white blood cells. It was further demonstrated that the vascular leakage was blocked by administration of indomethacin. Pulsed electromagnetical fields did not visibly affect the vascular permeability within 3 h. As the same DC electrical stimulator has been demonstrated to increase the osteogenic capacity in similar titanium implants in the rabbit tibia, it is suggested that the observation of macromolecular leakage may predict a positive osteogenic response.

Animals↗

PubMed1995

Nonviable injuries of the tibia.

Management of severe open fractures and non-viable injuries of the tibia remain both difficult and controversial. The orthopedist must carefully assess the injured limb in order to determine whether it should be salvaged or amputated. The difficult operative procedure requires thorough knowledge of microsurgical techniques necessary to repair vascular and neural injury. Over a 10 year period, 13 patients with non-viable, open fractures of the tibia underwent limb salvaging attempts using identical treatment protocol. 5 of the 13 limbs were salvaged, while 8 limbs were later amputated, because of either failure of revascularization or severe infection. 2 patients died; one with good circulation in the limb because of a massive pulmonary embolism 5 days postoperatively and the other because of severe septicemia 13 days postoperatively.

Adolescent↗