Systemic over-secretion of growth hormone in transgenic mice results in a specific pattern of skeletal modeling and adaptation.

The effects of growth hormone (GH) over-secretion on bone modeling and remodeling in transgenic mice were investigated using systematic and hierarchical methods. The results showed that continual systemic stimulation of GH over-secretion in mice resulted in an initial increase in bone mass, but its bone quality was not comparable with that of the littermate controls. Further continual over-stimulation of GH resulted in an increase in bone resorption leading to thinner cortices with inferior tissue mechanical properties. Three biological mechanisms following GH over-production are formulated to explain the observed results: GH over-secretion stimulated the production of inferior bone matrices, i.e., woven bone and cartilage, in addition to the production of normal lamellar bone; the increased bone formation stimulated by GH was followed by an exaggerated bone resorption process, resulting in cortical tissue with inferior mechanical properties; and a cortical shift occurred following GH over-stimulation that appeared to be caused by the combined effects of GH over-secretion and a variation in mechanical stimuli in the metallothionein-1 growth hormone regulating hormone transgenic mice. An "Optimal Strain Environment" model is proposed to help explain the observed results. From the results of the present and previous studies, we believe that the primary goal of bone adaptation to a biological perturbation, at least in mice, is to ensure proper mechanical function by maintaining structural integrity. In the process of maintaining a targeted whole bone structural integrity, the mechanical integrity of tissue may be sacrificed.

Local expression of human growth hormone in bone results in impaired mechanical integrity in the skeletal tissue of transgenic mice.

The effect of local production of human growth hormone on murine cortical bone was investigated using a transgenic mouse model. Femora and humeri from human growth hormone transgenic mice and littermate control mice were obtained, and the geometrical, biomechanical, compositional, and histomorphometric properties of all specimens were determined. The goals were to investigate the effects of local expression of human growth hormone on skeletal integrity, including the functional geometry of long bone and its related structural and mechanical behavior, as well as tissue composition and integrity. As expected, local production of human growth hormone by osteoblasts indeed resulted in longer femora with significantly greater mid-diaphyseal cross-sectional geometry in the transgenic mice (16% increase in cross-sectional area and 29% increase in bending moments of inertia). However, the significant increase in geometry was not associated with a proportional increase in bending stiffness and other structural properties, which suggested that the mechanical properties of the cortical bone tissue may have been inferior. Microspecimen bending tests verified this prediction, given that transgenic cortical bone tissue had significantly lower apparent elastic modulus and ultimate strength (52 and 68%, respectively, of control values). These defects in the whole bone structural and tissue mechanical properties of transgenic specimens were associated with a smaller fraction of ash, larger fractions of woven bone and cartilage islands, and greater porosity in the mid-diaphyseal cortices. These results suggest that local production of human growth hormone by osteoblasts is indeed anabolic for bone, but at the expense of bone tissue integrity.

Lidocaine-induced CNS toxicity--a case report.

Lidocaine is the first local anesthetic of the amide type to be introduced to clinical practice. It is a versatile drug and in anesthesia, is the most commonly used local anesthetic because of its aptness of potency, rapid onset, moderate duration of action and topical activity. It is relatively safe and useful in many other clinical settings. Unfortunately, systemic intoxication and psychotic reaction associated with its use often occur because of its popularity and wider safety margin, for which guide in use is often ignored and overdose becomes commonplace. Moreover, due to its universality in use seldom reports have recently dealt with lidocaine, particularly regarding its toxic reaction. Here, we present a case of lidocaine intoxication occurring during circumcision for a reviewal of the problem. A healthy young male, weighing 65 kg, underwent circumcision for phimosis under penile block with 2% lidocaine which totaled 600 mg. Twenty minutes after injection the patient developed headache, tinnitus, visual and auditory disturbances. Muscle twitching over the mouth angles, trismus and rigidity of extremities were also noted. Later in the course he became restless, agitative, hallucinative, talkative, and verbose with repetitious words. The whole course of the disorder lasted about 5 h. It was believed that lidocaine-induced CNS intoxication, manifested by psychotic reaction broke out. Treatment with thiopental was not very impressive. Also, we took this opportunity to discuss and review the toxic reaction associated with the use of lidocaine, its risk factors, mechanism, treatment and prevention. The complicated associations of lidocaine-induced CNS toxic reaction with central control of behavior and the neurotransmitter systems (adrenergic, dopaminergic and serotonin) were also touched.

Neuromuscular interactions between succinylcholine and esmolol in the rat.

To study the neuromuscular interactions between succinylcholine (Sch) and esmolol, we determined the dose-response relationship of Sch and the neuromuscular actions of the 3xED90 dose of Sch, both prior to and following esmolol pretreatment. Twenty rats were anaesthetized with urethane. Train-of-four stimulation was applied every 12 s to the sciatic nerve, and the electromyogram (EMG) of the tibialis anterior muscle was measured. The results showed that the potency of Sch decreased with esmolol pretreatment. The ED50 of Sch increased significantly, from 191 ug/kg to 227 ug/kg after esmolol infusion, p < 0.05. The duration of EMG depression achieved by the 3xED90 dose of Sch decreased significantly with esmolol pretreatment (12 min vs 14 min p < 0.05), and also the onset time was significantly longer (43 sec vs 28 sec, p < 0.05). There were no significant difference between groups with regard to the maximal block or recovery index. The results of two methods of study demonstrated that the pharmacological interaction between Sch and esmolol is antagonistic instead of potentiating.

Torsional stiffness of three spine constructs for thoracic scoliosis.

The standard two-rod thoracic scoliosis construct is bulky in the thin, young patient. A single-rod construct with hooks at every level was developed. Five calf spines were tested measuring angular displacement before and after instrumentation using three scoliosis constructs: a standard two-rod construct, a single-rod construct, and a single-rod construct with crossover hooks. Rotational displacements and stiffness were compared. There was no statistical difference in rotational displacement or stiffness among the three constructs. All three constructs were significantly stiffer in torsion than the uninstrumented control. The single-rod construct and the crossover construct may offer the spine surgeon additional options in instrumenting thoracic scoliosis, if our preliminary studies are verified by others.

Harvest of patellar tendon (bone-tendon-bone) autograft for ACL reconstruction significantly alters surface strain in the human patella.

The purpose of this study was to measure the effect of bone-patellar tendon-bone autograft harvest for anterior cruciate ligament (ACL) reconstruction on the surface strain of the human patella. Through progressive removal of bone from the patella, three different defect shapes as well as the intact patella were tested in each of seven knees. Maximum principal strain and corresponding principal direction were determined from each of three gages around the defect for the four conditions (intact plus three defect shapes). There were no statistically significant differences in overall average surface strain between any of the defect shapes. Following graft harvest, overall average strain (all three defects combined) increased in the patella both medial (15 percent increase) and lateral (34 percent increase) to the defect, while decreasing in the region directly proximal (22 percent decrease) to the harvest site compared to the intact patella. A statistically significant 7.5 deg shift of principal direction from longitudinal toward a more transverse (lateral-superior to medial-inferior) direction was observed in the medial region when a shallow-dome defect was made. We conclude that removal of a bone block from the anterior, inferior part of the patella induces a significant redistribution of the surface strain. This results in greater local strain adjacent to the upper border of the bone block increasing the risk for patella fracture. This effect may be of importance in various complications known to occur after ACL reconstruction.

Comparison of preoperative and postoperative iliohypogastric ilioinguinal nerve block for pediatric herniorrhaphy patients.

The purpose of this study was to compare the effects of preoperative and postoperative iliohypogastric ilioinguinal nerve block (IINB) performed on 30 pediatric patients having elective unilateral herniorrhaphy for postoperative pain control and to discuss the theory of post-injury hypersensitivity of the nerves system. The patients were assigned into two groups (A = 15, B = 15) randomly. Both groups were given GA during the surgical procedure except that group A received IINB 15 minutes prior to skin incision and group B immediately after skin closure. The local anesthetic used was 0.25% bupivacaine and the dosage was 1 mg/Kg. The heart rate, BP, and anesthetic concentration (halothane) were recorded during the procedure and postoperative pain was assessed by using the modification of the Children's Hospital of Eastern Ontario Pain Scale (CHEOPS) behavior pain score which were taken at 1 hr, 3 hr (POR), 6 hr, and 24 hr (ward) postoperatively. Group A had less pain at 1 hr and 3 hr than group B postoperatively and is statistically significant. There was no statistically significant in pain score at 6 hr and 24 hr between the two groups.

Sacroepidural analgesia for post-operative pain relief in children.

For evaluation of the practicality of epidural analgesia for alleviation of post-operative pain, 66 class I or II patients with age ranging from 6 months to 12 years undergoing elective surgical procedures below the lower abdomen were enrolled for study during the period from January to April 1989. Before termination of general anesthesia a single dose of 0.25% bupivacaine, respectively at 0.25 mL/kg (Ideal body weight), 0.5 mL/kg, 0.75 mL/kg, 1.0 mL/kg and 1.25 mL/kg was given sacroepidurally to 5 groups of patients. Our results showed that for surgery below the lower abdomen a dose at 1.0 mL/kg was sufficient to suffice the need for relief of post-operative pain. At this dosage it achieved a neural block up to T8-T6 and provided with an analgesia that could last 6.0 +/- 2.1 hours. During the entire course there were no untoward effects such as hypotension, bradycardia, vomiting and shivering to come about. Therefore, sacroepidural analgesia with 0.25% bupivacaine at fitting single dose is safe and feasible in children as far as relief of post-operative pain for procedures below the lower abdomen is concerned.