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Biomedical subjects

T L Greene

Publications and source records attributed to T L Greene.

At least 19 recordsLinked to original sources

Benzodiazepine receptor antagonists modulate the actions of ethanol in alcohol-preferring and -nonpreferring rats.

The pyrazoloquinoline CGS 8216 (2-phenylpyrazolo-[4,3-c]-quinolin-3 (5H)-one, 0.05-2 mg/kg) and the beta-carboline ZK 93426 (ethyl-5-isopropyl-4-methyl-beta-carboline-3-carboxylate, 1-10 mg/kg) benzodiazepine receptor antagonists were evaluated for their capacity to modulate the behavioral actions of ethanol in alcohol preferring and -nonpreferring rats. When alcohol-preferring rats were presented with a two-bottle choice test between ethanol (10% v/v) and a saccharin (0.0125% g/v) solution, both antagonists dose-dependently reduced intake of ethanol by 35-92% of control levels on day 1 at the initial 15 min interval of the 4 h limited access. Saccharin drinking was suppressed only with the highest doses. CGS 8216 (0.25 mg/kg) and ZK 93426 (4 mg/kg) unmasked the anxiolytic effects of a hypnotic ethanol dose (1.5 g/kg ethanol) on the plus maze test in alcohol-preferring rats, but potentiated the ethanol-induced suppression in alcohol-nonpreferring rats. CGS 8216 (0.25 mg/kg) and ZK 93426 (4 mg/kg) attenuated the ethanol (0.5 and 1.5 g/kg)-induced suppression in the open field in alcohol-nonpreferring rats; however, CGS 8216 potentiated the depressant effects of the lower ethanol dose (0.5 g/kg) in alcohol-preferring rats. These findings provide evidence that benzodiazepine receptor antagonists may differentially modulate the behavioral actions of ethanol in alcohol-preferring and-nonpreferring rats. It is possible that the qualitative pharmacodynamic differences seen in the present study may be related to selective breeding for alcohol preference. The findings indicate the potential for development of receptor specific ligands devoid of toxic effects which may be useful in the treatment of alcohol abuse and alcoholism.

Alcohol Drinking↗

Synovial chondromatosis of the distal radioulnar joint: a case report.

The most definitive method for confirming the diagnosis of synovial chondromatosis is the identification of cartilaginous metaplasia within the synovium on histologic examination. In advanced stages of the disease, plain radiographs and magnetic resonance imaging (MRI) scans demonstrate calcified and cartilaginous bodies, respectively, but in earlier stages, plain radiographic findings may be normal and MRI scans may reveal only nonspecific increased fluid. Although rare in the wrist, synovial chondromatosis must be considered in the differential diagnosis in a patient presenting with pain and swelling of the distal radioulnar joint. Surgical exploration of the joint and synovectomy, alone or in combination with removal of loose bodies, is the recommended treatment.

Adult↗

Effects of the benzodiazepine inverse agonist RO19-4603 alone and in combination with the benzodiazepine receptor antagonists flumazenil, ZK 93426 and CGS 8216, on ethanol intake in alcohol-preferring (P) rats.

The present study investigated dose dependence and time course effects of the benzodiazepine (BDZ) partial inverse agonist, RO19-4603 (0.005-0.30 mg/kg) alone, and in combination with the BDZ receptor antagonists flumazenil, ZK 93426, and CGS 8216 (20 mg/kg) in selectively bred alcohol-preferring (P) rats provided a two-bottle choice test between ethanol (EtOH) (10% v/v), and a palatable saccharin (0.0125% g/v) solution. A single dose of RO19-4603 as low as 0.009 mg/kg selectively reduced EtOH drinking during the initial 15 min of a 4 h access to 19-0% of control levels on day 1. The 0.08, 0.15 and 0.30 mg/kg doses of RO19-4603 significantly reduced total EtOH intake in the 4 h access period to 57-45% of controls on day 1. On day 2, no RO19-4603 injections were given; however, six of the seven doses of RO19-4603 (0.009, 0.02, 0.04, 0.08, 0.15, and 0.30 mg/kg) continued to reduce EtOH intake to 42-3% of control levels at the initial 15 min interval, while the 0.005, 0.009, 0.08, and 0.30 mg/kg doses reduced total 4 h EtOH intake to 60-42% of controls. Saccharin intake was either not altered by RO19-4603 or showed increases during the initial 15 min intervals and the total 4 h sessions on days 1 and 2. Food intake was also unaffected by RO19-4603. The CGS 8216, but neither flumazenil nor ZK 93426, reliably reversed the RO19-4603-induced suppression of EtOH intake on days 1 and 2. That certain BDZ inverse agonists can attenuate motivated behavior for EtOH reinforcement over a prolonged time course may provide a possible therapeutic approach to reducing EtOH consumption associated with alcoholism.

Alcohol Drinking↗

Benzodiazepine receptor ligands with different intrinsic efficacies alter ethanol intake in alcohol-nonpreferring (NP) rats.

Benzodiazepine (BDZ) receptor ligands with varying intrinsic efficacies [RO19-4603, 0.02-0.15 mg/kg; FG 7142 1-16 mg/kg; DMCM, 1-8 mg/kg; RO16-6028 (bretazenil), 8-32 mg/kg] in modulating GABAergic activity were examined for the ability to alter palatability-induced ethanol (EtOH) intake in the alcohol-nonpreferring (NP) line of rats. NP rats on a 22-hour fluid-deprivation schedule were given 2-hour daily access to a 10% (v/v) EtOH/3% (g/v) polycose solution and water. Average EtOH intake was 2.1 +/- 0.2 g/kg/2 hours, and water intake was 17.1 +/- 0.9 ml/2 hours. During the initial 15 minutes of the 2-hour session, RO19-4603, the imidazothienodiazepine partial inverse agonist reduced EtOH intake to 19% of control values at 0.04 mg/kg and completely suppressed drinking of the EtOH solution at 0.15 mg/kg. Twenty-four-hour postdrug administration, the 0.08-mg/kg dose of RO19-4603 completely suppressed drinking of the EtOH solution at the 60-minute interval, and the 0.15-mg/kg dose reduced intake to 20% of control levels at the 15-minute interval. FG 7142, the partial beta-carboline inverse agonist reduced EtOH drinking at the 60-minute interval with the 1-mg/kg dose, and the 16-mg/kg dose reduced water intake at the 15-minute interval. DMCM, the full beta-carboline inverse agonist, significantly reduced water intake at 15 minutes (4 and 8 mg/kg), and the same doses caused a substantial increase in EtOH drinking at the 120-minute interval. The anxiolytic agent bretazenil (16 and 32 mg/kg) increased EtOH consumption during the initial 15 minutes to 270% to 425% of control levels, and water intake increased by the end of the 2-hour session to as much as 210% of control following administration of the 32-mg/kg dose. These findings support existing evidence suggesting that BDZ receptor ligands may modify neuronal processes that mediate some reinforcing and/or aversive properties of alcohol. They further demonstrate a potential importance of the GABAA-BDZ receptor complex in mediating palatability- (environmentally) induced EtOH drinking even in rats selectively bred for low alcohol preference.

Analysis of Variance↗

Preliminary soft tissue distraction in congenital forearm deficiency.

Four patients (five limbs) were treated with preliminary soft tissue distraction using an Orthofix external distractor. The patient's ages ranged from 6 months to 14 years. Forearm deficiencies treated included partial absence of the radius (one patient), radial aplasia (two patients, three limbs), and partial absence of the ulna (one patient). Soft tissue distraction (mean, 55 days) was continued in radial deficiency until the hand could be passively centralized without residual radial deviation, allowing centralization to be accomplished through a single mid-dorsal incision. Mean measurement of distraction for the radial deficiencies was 1 cm. In the ulnar deficiency, soft tissue distraction was carried out until the cut radius was distal to the partially absent ulna (98 days) allowing for the creation of a one-bone forearm using the entire radius. Distraction (1 mm/day) was done by the children's parents with no distractor removed because of patient intolerance. All radial deficiency limbs remained centralized at a mean followup period of 14 months.

Adolescent↗

Effects of the benzodiazepine inverse agonist RO19-4603 on the maintenance of tolerance to a single dose of ethanol.

The time course of the novel benzodiazepine inverse agonist, RO19--4603 (0.075 or 0.150 mg/kg) in antagonizing the depressant effects of ethanol (EtOH) (0.50, 1.0 and 1.5 g/kg) and the development of tolerance on locomotor behaviors (e.g., ambulatory count, total distance and stereotypy count) were investigated in Sprague-Dawley rats given EtOH injections spaced at 24-hr intervals. A single dose of RO19--4603 prevented the development of tolerance to the 0.50- and 1.0-g/kg EtOH doses 24-hr post-RO19--4603 administration on most locomotor behaviors. On Day 1, the 0.150-mg/kg RO19--4603 dose prevented the reduction of motor behaviors after the 1.0- and 1.5-g/kg EtOH doses, whereas the 0.075-mg/kg RO19--4603 dose prevented the reduction of motor behaviors only after the 1.5-g/kg EtOH dose. The 0.075- and 0.150-mg/kg RO19--4603 doses also prevented the EtOH-induced reduction of motor behaviors after the 1.5-g/kg EtOH dose 24-hr post-RO19--4603 administration. RO19--4603 was without effect on activity when given alone. These data suggest that the motor impairing effects of EtOH and the development of tolerance to them may involve gamma-aminobutyric acidA-benzodiazepine receptor mechanisms that when occupied, even briefly by certain benzodiazepine inverse agonists, produce long-lasting effects on locomotion and tolerance.

Animals↗

Ossification and pseudoepiphysis formation in the "nonepiphyseal" end of bones of the hands and feet.

Metacarpals, metatarsals, and phalanges were studied to assess the developmental morphology of "secondary" ossification in the "nonepiphyseal" ends of these bones as well as the formation of the pseudoepiphysis as an epiphyseal ossification variant. Both direct ossification extension from the metaphysis into the epiphysis and pseudoepiphysis formation preceded, and continued to be more mature than, formation and expansion of the "classic" epiphyseal (secondary) ossification center at the opposite end of each specific bone. Direct metaphyseal to epiphyseal ossification usually started centrally and expanded hemispherically, replacing both physeal and epiphyseal cartilage simultaneously. In contrast, when remnants of "physis" were retained, while juxtaposed epiphyseal cartilage was replaced, a pseudoepiphysis formed. There were three basic patterns of pseudoepiphysis formation. First, a central osseous bridge extended from the metaphysis across the "physis" into the epiphysis and subsequently expanded to create a mushroom-like osseous structure. In the second pattern a peripheral osseous bridge formed, creating either an osseous ring or an eccentric bridge between the metaphysis and the epiphysis. In the third pattern, multiple bridging occurred. In each situation the associated remnant "physis" lacked typical cell columns and was incapable of significantly contributing to the postnatal longitudinal growth of the involved bone. Pseudoepiphyses were well formed by 4-5 years and coalesced with the rest of the bone months of years before skeletal maturation was attained at the opposite epiphyseal end, which ossified in the typical pattern (i.e., formation of a secondary center de novo completely within the cartilaginous epiphysis). This process may also affect the development and appearance of ossification within the longitudinal epiphyseal bracket ("delta phalanx").

Adolescent↗

Computed analyses of the pathomechanics of scaphoid waist nonunions.

The computed tomography scans of both the injured and the normal wrists of nine patients with a scaphoid nonunion of 5 to 120 months' duration were used to create three-dimensional computer models. When the computer images of the normal and the contralateral fractured scaphoids were superimposed, it was possible to calculate the volume of bone that was lost as a result of the injury and its failure to heal, as well as the angular relationship of the fracture components to one another. The amount of the scaphoid bone that was lost varied from 6% to 15% of bone volume and did not show a linear correlation with the duration of the nonunion. The configuration of the missing bone was consistent and exhibited a prismatic shape whose base is quadrilateral and faces palmarly. The proximal scaphoid fracture component is extended, radially deviated, and supinated in relation to its distal fracture component. The consistent fracture deformity and the configuration of the bony defect in the scaphoid waist nonunions should be helpful in the understanding and treatment of the condition.

Adult↗

Digital subtraction arthrography of the wrist.

Digital subtraction arthrography of the wrist was used to identify abnormalities in eighty-six (60 per cent) of 139 patients during a fifteen-month period. Multiple abnormalities were noted in thirty-four (25 per cent) of the wrists. The clinical signs and symptoms in the eighty-six wrists did not always correlate with the defects that were seen on the arthrograms. Three of five patients who had an isolated tear of the scapholunate ligament, six of thirteen who had an isolated tear of the lunotriquetral ligament, and seven of nineteen who had an isolated tear of the triangular fibrocartilage complex also had signs and symptoms on the opposite side of the wrist. Many of the lesions that were seen on arthrography may have been serendipitous, degenerative, or unrelated to a specific injury. There was a high prevalence of positive ulnar variance in patients who had at least one ulnar abnormality. Capsular tears, most often seen on the radiovolar aspect of the wrist, were best outlined by contrast medium injected into the radiocarpal joint. The arthroscopic findings differed from the arthrographic findings in five of the twenty patients in whom both studies were done. The three-compartment technique of injection is a valuable diagnostic tool. Injections of contrast medium into the distal radio-ulnar joint outlined five of thirteen tears of the triangular fibrocartilage complex that were not seen after injection into the radiocarpal joint. Of the eleven tears that were seen after injection into the radiocarpal joint, five were not seen when contrast medium was injected into the distal radio-ulnar joint.

Adolescent↗

Work in progress: postarthrography computed tomography of the wrist: evaluation of the triangular fibrocartilage complex.

This report reviews a work in progress evaluating the use of postarthrography computed tomography (CT) of the wrist in assessing triangular fibrocartilage complex abnormalities. Twenty-two triangular fibrocartilage complex perforations in 119 patients were identified with both multiple compartment arthrography and postarthrography CT. To obtain a double contrast image of the triangular fibrocartilage complex, the postarthrography CT examinations were performed after multiple compartment arthrography and the injection of air into the radiocarpal compartment. The site of triangular fibrocartilage complex perforation could be identified (radial versus peripheral) as could degenerative changes and internal derangements such as chondrocalcinosis. We did not, however, find any information not provided by arthrography that would have changed the course of management. At this time there is no clinical role for postarthrography CT in the evaluation of triangular fibrocartilage complex derangements.

Arthrography↗

Composite wiring of metacarpal and phalangeal fractures.

Composite wiring techniques using various configurations of Kirschner pins and stainless steel wire sutures have been applied to the treatment of 63 fractures of the long bones of the hand. The secure fixation achieved allowed active motion within 1 week of operation. Thirty-three metacarpal fractures achieved a final mean total active motion of 256 degrees (standard deviation 13.4) (normal total active motion -260 degrees). Twenty-one phalangeal fractures achieved a mean total active motion of 215 degrees (standard deviation, 46 degrees). There were no instances of infection, malunion, nonunion, loss of reduction, or tendon rupture in the 63 fractures that were treated.

Adolescent↗

Advanced imaging of the wrist.

In an effort to improve the radiologist's contribution to the evaluation of the painful wrist, the authors have studied the usefulness of a variety of imaging techniques. Preliminary results of these studies, including: 173 conventional CT, 80 3-D CT, 119 postarthrography CT, 138 multiple compartment digital subtraction arthrography and 55 MRI examinations, are reported, and technical aspects of the examinations are described.

Diagnostic Imaging↗

CT of the wrist for the evaluation of traumatic injuries.

Computed tomography (CT) of the wrist can help evaluate many types of posttraumatic injuries, particularly bony trauma. Most wrist fractures can be diagnosed with routine radiography, but problematic cases and complicated healing fractures can be difficult to evaluate with conventional radiography. CT provides improved contrast resolution and multiplanar imaging. The results of complex healing fractures and fusion procedures can be facilitated with CT. Even in the face of advanced osteoporosis CT can delineate bone edges and detect small areas of bony fusion. The degree of bone graft assimilation can be determined with CT. Unlike conventional radiography, metal fixation pins and cast material do not obviate diagnostic exams with CT. Certain posttraumatic complications such as distal radioulnar joint incongruity and hypertrophy of Lister's tubercle can be detected with axial CT images. Complicated cases of retained foreign bodies can be evaluated with CT. The high-contrast resolution of CT allows precise localization of foreign bodies and can define anatomic relationships to adjacent vital structures such as joints, tendons, and carpal tunnel. Postarthrography CT of the wrist is an investigational tool that permits direct visualization of the triangular fibrocartilage complex (TFCC). Complete and partial tears of the TFCC can be evaluated with postarthrography CT. Ulnar capsular tears and disruptions of interosseous ligaments can also be evaluated with this technique. The exact role of postarthrography CT of the wrist, however, is uncertain at this point. Three-dimensional CT is receiving increasing interest and may eventually help the understanding of wrist pathomechanics and kinematics. In summary, CT of the wrist can be instrumental in evaluating complicated posttraumatic injuries of the wrist and has certain advantages over routine radiography.

Humans↗

Mathematical analysis of computed carpal models.

The computed carpal models from digital computed tomography (CT) data obtained in this study compare favorably to natural anatomy. A new application of algebraic analysis of this data provides mathematical markers from which to calculate the position and orientation of each carpal bone. When the origin of the spatial coordinates of a carpal bone is transferred to the centroid of the bone, the data can be treated as three-dimensional pattern vectors describing its surface. It is then possible to calculate vectors that are the principal axes of the geometry. These axes provided references that were used to calculate position and orientation of the carpal bones in three wrist specimens. Comparisons of volumes, surface areas, and sizes and proportions of five computed images of each carpal bone from two of these wrists demonstrate the reliability of the technique. The analysis of CT scans of ceramics with known boundaries allows an estimation of its accuracy. The technique is well suited to the future study of normal wrist kinematics and pathological conditions.

Carpal Bones↗

Fractures of the body of the trapezium.

Fractures of the body of the trapezium are uncommon. Ten such cases are reported. They may be associated with other carpal or metacarpal fractures and may require special radiographic views for diagnosis. There does not appear to be a consistent mechanism of injury. A classification system is proposed based on the five fracture configurations identified. Open reduction with internal fixation of the displaced articular surface is preferred.

Adolescent↗

Heel reconstruction with the deep circumflex iliac artery osteocutaneous flap.

A patient with extensive loss of bone and soft tissue from the right heel is presented. The defect was reconstructed using an osteocutaneous flap based on the deep circumflex iliac vessels. Indications for this procedure include extensive loss of bone and soft tissue precluding the use of local flaps. A 30-month period has elapsed since her reconstruction. A single ulcer developed 13 months postoperatively that healed after flap revision. We feel that tailoring the flap to minimize redundancy at the initial operation, subsequent tissue excision if necessary, and reinnervation augment durability of the flap.

Child↗