Contrast media and radiopharmaceutical agents: regulatory issues.
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Biomedical subjects
Publications and source records attributed to J T Watson.
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Twenty-seven patients with 28 aseptic nonunions were treated with reamed intramedullary (IM) nailing of the tibia and were followed for at least 1 year postoperatively. The management protocol called for a radiolucent operating room table with the limb draped free and manual manipulation of the nonunion with a preference for closed nailing. Nail interlocking was used when residual axial or rotational instability was observed after nail insertion. Iliac crest bone grafting was performed on all patients requiring open nailing. Closed nailing, using the described technique, was accomplished in 20 cases; open nailing was necessary in eight. Although operative time and total blood loss were significantly increased with open nailing, time to union was similar in the two groups. Twenty-seven nonunions healed. The lone persistent nonunion responded to bone grafting, leaving the nail in situ. One infection occurred, which responded to debridement, drainage, and long-term antibiotic therapy without requiring nail removal. Acceptable bony alignment was attained in all patients. Functional results were excellent. This method is recommended for all tibial nonunions amenable to IM nail stabilization. A history of prior acute infection and/or excessive shortening due to bone loss constitute the relative contraindications.
A retrospective review of 202 closed Weber B bimalleolar or bimalleolar equivalent ankle fractures treated using open reduction and internal fixation (ORIF) from January 1, 1991, through January 1, 1994 was completed at our institution. A total of 105 ankles (52%) were treated using ORIF within 5 days of injury (early group), with a mean 1.5 days from injury to surgery. A total of 97 ankles (48%) were treated after 5 days (delayed group), with a mean of 13.6 days from injury to surgery. Operative time, length of hospital stay, postoperative range of motion, adequacy of reduction, wound and other complications, and other sequelae were compared between the two groups. No significant difference in range of motion at latest follow-up or in operative time was evident between the groups. Minor wound complications were present in 4.8% of the early group compared with 6.2% in the delayed group. No deep infections or osteomyelitis were present in either group. Anatomic reductions were present in 89% and poor reductions (> 2 mm displacement) in 1% of those ankles treated within 5 days versus 83% anatomic reductions and 3% poor reductions in those treated after 5 days. The differences in wound complications and anatomic reductions between groups was not statistically significant. There was a significantly longer median hospital stay in the early (3 days) versus delayed groups (2 days). We conclude that the results and complications of early versus delayed treatment is not significantly different, except for a shorter median hospital stay in the delayed group. Delayed ORIF is an acceptable alternative when soft-tissue swelling, fracture blisters, or abrasions are present that offer an undesirable environment for surgical incisions. Using contemporary, a traumatic techniques, delayed surgery can provide anatomic reduction with minimal complications in severe ankle fractures.
Twenty consecutive multiply injured patients who had a total of twenty-two fractures of the femoral shaft were managed with intramedullary nailing without reaming. A retrograde technique through the intercondylar notch of the knee was used. All patients were followed for at least one year or until union of the fracture. The operative time for the nailing averaged seventy-five minutes (range, thirty-five to 105 minutes). Union of the fracture occurred at an average of fifteen weeks. There were three non-unions and one rotational malunion. There were no infections, and no nail or screw failed. Normal motion of the knee was regained by all patients, except one who had had an ipsilateral dislocation of the knee. On the basis of these preliminary results, we concluded that retrograde nailing is a safe and effective technique for multiply injured patients. The apparently higher prevalence of non-union compared with that reported with antegrade nailing with reaming warrants additional study.
The mechanical integrity of tibial bone treated by distraction osteogenesis (callotasis) using an Orthofix external fixator was evaluated in a group of 6 dogs. Diaphyseal corticotomies were performed on Day 0. Distraction was begun on Day 8, at a rate of 0.33 mm every 8 hours. On Day 34, the Orthofix frame was locked. On Day 56, the frames were removed and the dogs were euthanized. Radiographs were taken weekly to assess regenerate bone formation and extent of tibial bone lengthening, which averaged 12 mm (range, 5-20 mm). One dog showed incomplete bony union that was attributed to pin loosening. Torsional testing of lengthened and contralateral control tibiae resulted in spiral diaphyseal fractures. Five of 6 lengthened tibiae bones fractured within the diaphysis, but outside the regenerate area, suggesting that the strength of the lengthened segment exceeded that of the original diaphysis which was exposed to stress shielding by the external fixator. These observations have led to a method to test and evaluate lengthened bone at the time of frame removal and to monitor the effectiveness of this type of technique.
Fifty open tibial fractures with circumferential cortical bone loss were reviewed. Prospective treatment protocols included fracture stabilization with repeated irrigation and debridement followed by wound coverage. Bony stabilization was accomplished using external fixators, small diameter unreamed interlocking nails, and, in rare instances, plate fixation. Bone graft procedures included posterolateral bone graft, elevation of the free flap or direct anterolateral grafting, bone transport techniques, and free vascularized fibula transfer. Average followup was 18 months (range, 9-40 months). The index graft procedure was used in 30 patients (60%) for fracture healing. The rate of union was 98%, with an average total treatment time of 42.4 weeks (range, 23-80 weeks). Malunion was more likely to develop in patients treated with external fixation and posterolateral bone graft (p = 0.007). Intramedullary nails with direct bone grafting had shorter times to union and shorter total treatment times. The use of free vascular fibular transfers in acute injuries was not successful. Good results were obtained with bone transport techniques. Developing a healthy soft tissue envelope before reconstruction of these injuries is important. Techniques of reconstruction had no correlation to the development of nonunion or infection. They were valuable in determining malunion and total treatment time. These data confirm that carefully staged reconstruction leads to successful outcomes.
Pyomyositis appears to be increasing in prevalence in temperate climates, and often the orthopaedist is integral in the decision making and care of these patients. This is the first reported case of spontaneous bacterial pyomyositis involving the obturator internus muscle. Deep pelvic infections involving the psoas, iliacus, piriformis, and obturator internus can be a significant cause of morbidity and mortality. The infection subsequently may exit the pelvis, and conceivably may progress to a septic hip, bursitis, or lower extremity cellulitis. Improvements in noninvasive imaging such as ultrasound, computed tomography, and magnetic resonance imaging have produced finer resolution of tissue planes. Because of the pathology's deep location within the pelvis of the patient described here, all 3 tests were integral in the surgical planning, exposure, and proper diagnosis. Although 95% of pyomyositis cases are caused by Staphylococcus aureus, cases of pyomyositis with negative cultures have been described. Consideration should be made of disseminated Neisseria gonorrhoeae in sexually active individuals, and cultures should include Thayer-Martin agar to decrease the likelihood of a false-negative culture result.
Fourteen fractures (8 open, 6 closed) were treated with small-diameter interlocking tibial nails and observed for at least 1 year. Radiographs were obtained to monitor the maintenance of reduction and fracture healing. The treating orthopaedic surgeon was blinded to the results of ultrasound studies, which were obtained at 2-week intervals for 10 weeks postoperatively and read by a radiologist who was blinded to the clinical and radiographic progress. Ultrasound correctly predicted fracture healing in all 9 fractures that subsequently progressed to fracture union. Of the 5 fractures that did not heal and required secondary procedures, ultrasound predicted delayed healing in 4 fractures. Overall, ultrasound was able to predict fracture healing before it was radiographically evident. Ultrasound may provide important prognostic information concerning tibial fracture healing after treatment using interlocking nails without reaming. Additional study is warranted.
STUDY DESIGN: The terminal event in disc space narrowing and facet subluxation of the lumbar spine can produce clinical symptoms of spinal stenosis. Reversal of this process via distraction was performed on ten cadaveric motion segments with documented stenosis. METHODS: Computerized tomography and caliperic methods for the measurement of canal and foraminal areas were calculated in each segment after 5 and 10 mm of symmetrical distraction. Measurements were done in a blinded manner verified with orthographic software and statistical analysis. RESULTS: Decompression of foraminal space was statistically significant in 7 of 10 cadaveric specimens after 5 mm of distraction and 9 of 10 specimens after 10 mm of distraction. Minimal yet insignificant improvement in stenotic canal area was evident with distraction. CONCLUSION: The presence of posterior vertebral osteophytes was associated uniformly with poor improvement of space available in both stenotic canal and foramen.
The one-step ethyl chloroformate derivatization of amino acids in an aqueous medium is extended with the use of a variety of alkyl chloroformate reagents. This provides a new and convenient procedure for preparing esters with different alkoxy groups. A new mechanism for esterification during chloroformate derivatization is proposed based on the formation of an intermediate mixed carboxylic-carbonic acid anhydride followed by the exchange with an alcohol. Among the different reagents investigated, isobutyl chloroformate derivatized amino acids were found to provide more sensitivity for analyses by GC-flame ionization detection and GC-MS relative to derivatives prepared by other alkyl chloroformates.
In adult Xenopus laevis, innervation of the vocal organ is more robust in males than in females. This sex difference originates during tadpole development; at stage 56, when the gonads first differentiate, the number of axons entering the larynx is the same in the sexes, but by stage 62, innervation is greater in males. To determine if androgen secretion establishes sex differences in axon number, we treated tadpoles with antiandrogen or androgen beginning at stage 48 or 54 and counted laryngeal nerve axons at stage 62 using electron microscopy. When male tadpoles were treated with the antiandrogen hydroxyflutamide, axon numbers were reduced to female-typical values; axon numbers in females were unaffected by antiandrogen treatment. When female tadpoles were treated with the androgen DHT (dihydrotestosterone), axon numbers were increased to male-like values. These findings suggest that endogenous androgen secretion during late tadpole stages in males is required for the sexual differentiation of laryngeal innervation observed from stage 62 on. Because androgen treatment and laryngeal innervation affect myogenesis in postmetamorphic frogs, numbers of laryngeal dilator muscle fibers were determined for hormonally manipulated tadpoles. At stage 62, vehicle-treated males had more laryngeal axons than females; laryngeal muscle fiber numbers did not, however, differ in the sexes. Both male and female tadpoles, treated from stage 54 with DHT, had more muscle fibers at stage 62 than vehicle-treated controls. Thus, while endogenous androgen secretion during late tadpole stages is subthreshold for the establishment of masculinized muscle fiber numbers, laryngeal myogenesis is androgen sensitive at this time and can be increased by suprathreshold provision of exogenous DHT. A subgroup of tadpoles, DHT treated from stage 54 to 62, was allowed to survive, untreated, until postmetamorphic stage 2 (PM2: 5 months after metamorphosis is complete). Androgen treatment between tadpole stages 54 and 62 does not prevent the ontogenetic decrease in axon numbers characteristic of laryngeal development. In addition, the elevation in stage 62 axon numbers produced by DHT-treatment at late tadpole stages was not associated with elevated numbers of laryngeal muscle fibers at PM2. Juvenile males normally maintain elevated axon numbers (relative to final adult values) through PM2 and the presence of these additional axons may result from--rather than contribute directly to--laryngeal muscle fiber addition.
A series of 44 fractures of the tibia requiring operative stabilization were treated using an intraoperative external transfixion pin frame to correct angular deformity and maintain length in preparation for intramedullary (IM) nailing, eliminating the need for a fracture table. The technique requires a radiolucent operating room table; the injured extremity is draped free. A transfixion pin is inserted in the os calcis. Rotational deformity is manually corrected. Using fluoroscopic control, a second transfixion pin is inserted at a location just distal and parallel to the proximal tibial articular surface, paralleling the horizontal plane of the first pin. The transfixion pins are connected with carbon fiber rods, creating a rectangular frame. Manual fracture reduction is followed by "fine tuning" with compressor/distractor clamps as needed. Alternatively, for added reduction force, the carbon fiber rod on the concave side of the angular deformity may be replaced with the AO/ASIF universal distractor. IM nailing is then performed in the usual fashion. In this series, an acceptable reduction was obtained in all cases. This technique shortens setup time, provides complete access to the distal part of the tibia, and allows free manipulation of the limb, thereby facilitating nail insertion and placement of distal locking screws. Use of medial and lateral bars prevents the angular deformity often created or exacerbated with the use of the universal distractor alone. This technique is recommended for IM nailing of all fractures of the tibia that would otherwise require use of the fracture table or universal distractor.
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High-energy tibial plateau fractures are often the result of blunt trauma. In addition to extensive bony injuries, soft-tissue problems are very common. Preoperative planning for surgical repair of these injuries is invaluable. Contemporary internal fixation techniques using ligamentotaxis, percutaneous fixation, and antiglide techniques provide the basis for internal fixation of these injuries. When extensive comminution and damaged soft tissues prohibit their use, the circular external fixator provides an excellent option for management of these complex injuries. Whether internal or external fixation techniques are used, appropriate management of the soft tissues is also a factor in the successful management of these severe injuries to the knee.
Derivatization of amino acids by using ethyl chloroformate-ethanol-pyridine provides volatile products, N-ethoxycarbonyl amino acid ethyl esters (ECEEs), which are easily amenable to GC or GC-MS analysis. MS behavior of these compounds under electron-impact has been studied. The fragments observed in the spectra facilitate recognition of commonly occurring protein amino acids and characterization of unknown analogues.
Fast atom bombardment collisionally activated dissociation tandem mass spectrometry (FAB CAD MS/MS) of a disulfide-containing peptide, [2-D-penicillamine, 5-D-penicillamine]- enkephalin ([Pen]-enkephalin), is described. Unlike those of most other disulfide-containing peptides investigated, CAD of the native, unreduced protonated molecule of [Pen]-enkephalin yields a relatively large number of fragment ions. Most of the peaks in the CAD spectrum represent fragmentations of the peptide backbone with 'unsymmetric' cleavage of the disulfide bond with charge retention on the N-terminus; the fragment ions generally do not contain a sulfur atom or a disulfide group. The CAD spectrum of the N-terminal ethyl-triphenylphosphonium derivative, on the other hand, shows few fragment ions and is dominated by the single peak at m/z 523. This dominant ion also results from 'unsymmetric' cleavage and corresponds to the analogous protonated species (m/z 235) in the spectrum of the underivatized peptide. The chemical method of charge localization by triphenylphosphonium derivative formation at one end of the peptide is shown to be useful for investigating fragmentation mechanisms in FAB CAD MS/MS. Comparison of the CAD spectra of derivatized and underivatized [Pen]-enkephalin suggests that charge-remote fragmentation plays a significant role in the high-energy dissociation of this disulfide-bonded peptide.
In Xenopus laevis, the sexual differentiation of the neuromuscular system responsible for courtship song is controlled by testicular androgen secretion. To explore the sensitivity of this system to androgenic stimulation, male and female frogs were gonadectomized and given testis transplants at seven different developmental stages between the end of metamorphosis and adulthood, grown to sexual maturity, and the laryngeal muscle fibers and motor axons were counted. Muscle fiber and axon numbers in males were not affected by the testicular transplant at any stage. In females, testicular transplants at all developmental stages increased muscle fiber numbers in adulthood. Values attained were, however, significantly less than those of adult intact or testis-transplanted males. Testis transplantation increased laryngeal axon numbers in females to levels equivalent to those of intact males; this effect was obtained at every stage of postmetamorphic development including adulthood. To further explore androgen regulation in adults, males and females were gonadectomized and implanted with silicone tubes containing testosterone propionate for 1.5-3 years and laryngeal muscle fibers and axon numbers compared to those of gonadectomized or sham-operated adult controls. Neither treatment with exogenous androgen nor gonadectomy had any effect on laryngeal muscle fiber or axon number in either males or females; values did not differ from those of sham-operated controls. We conclude that testicular secretions can induce laryngeal muscle fiber and axon addition in females throughout postmetamorphic life. This degree of plasticity, exhibited after the period when adult values are normally attained, stands in contrast to the effects of administration of synthetic androgen and suggests that the degree of plasticity in adult females may be underestimated if exogenous hormones rather than testicular transplants are provided.
In view of the complications of general, spinal, and caudal anaesthesia for inguinal hernia repair in high-risk neonates, an evaluation of lumbar epidural anaesthesia (LEA) was undertaken to assess its technical feasibility, effectiveness and incidence of complications. In 18 consecutive cases, gestational age 26 +/- 2.6 wk, birth weight 877 +/- 310 g, 16 (89%) had bronchopulmonary dysplasia and 12 (67%) were oxygen-dependent at the time of surgery. Using a standard loss of resistance technique and a 4.0 cm 20 G epidural needle, the epidural space was positively identified on the first attempt in 16 (89%), and on the second attempt in 2 patients (11%). Reflux of 0.9% saline used to identify the epidural space was blood tinged in two cases. Epidural analgesia was achieved in all cases with bupivacaine 0.25% with and without 1:200,000 epinephrine, 0.75 ml.kg-1 for the first two cases, and subsequently 1.0 ml.kg-1. In 15 patients (83%), good operating conditions were achieved with epidural analgesia alone. Inhalational anaesthesia supplementation was necessary in three cases (17%). In the first two patients, the level of analgesia (T8) was insufficient to control the response to traction on the hernial sac. In one infant, analgesic to T4, whose surgery was inadvertently delayed for four hours, inhalation anaesthesia was needed to control restlessness rather than pain. Ten infants were analgesic to T2, four to T4, two to T6 and two to T8. Intraoperative periodic breathing was seen in seven infants (39%), four with oxyhaemoglobin desaturation to 75%, and two to 85%. All responded to increased FIO2.(ABSTRACT TRUNCATED AT 250 WORDS)