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Biomedical subjects

D A Spiegel

Publications and source records attributed to D A Spiegel.

At least 19 recordsLinked to original sources

Congenital longitudinal deficiency of the tibia.

We performed a clinical and radiographic review of 15 patients (19 limbs) with longitudinal deficiency of the tibia treated between 1981 and 2001. Ten limbs with Kalamchi type I deficiencies were managed by through-knee amputation. Five type II deficiencies were treated by foot ablation and tibiofibular synostosis, either at the same time or staged, but prosthetic problems may arise from varus alignment and prominence of the proximal fibula. Patients with type III deficiencies (four cases) were treated by foot ablation. Prosthetic problems relating to proximal or distal tibiofibular instability may necessitate additional surgical intervention.

Abnormalities, Multiple↗

An expeditious approach toward the total synthesis of CP-263,114.

[reaction: see text] Assembly of the carbocyclic core of CP-263,114 has been accomplished efficiently and in high yield. Key steps include a phenolic oxidation/intramolecular Diels-Alder sequence, tandem radical cyclization, and the late-stage fragmentation of a densely functionalized isotwistane skeleton.

Cyclization↗

Anterior vertebral screw strain with and without solid interspace support.

STUDY DESIGN: This in vitro biomechanical study examines segmental anterior vertebral screw strain and solid rod construct stiffness with and without the addition of multilevel, threaded cortical bone dowels in a bovine model. OBJECTIVE: To determine whether strain at the bone-screw interface is higher at the end levels during physiologic range loading, and whether solid interspace support decreases segmental strain on the implant. SUMMARY OF BACKGROUND DATA: Anterior instrumentation provides greater correction and preserves distal motion segments. However, nonunion and implant failure are observed more frequently than with posterior segmental instrumentation, and when observed, loss of fixation occurs at the end levels. METHODS: Eight calf spines underwent mechanical testing in the following sequence: 1) intact condition, 2) anterior release with anterior solid rod and bicortical rib grafts, and 3) anterior release with anterior solid rod and threaded cortical bone dowels (L2-L5). Instrumented vertebral screws were used to assess strain within the vertebral body by the near cortex, whereas an anterior extensometer spanning the instrumented segments was used to measure segmental displacements to calculate construct stiffness. The protocol included axial compression (-400 N), right lateral bending (4 Nm (Newton-meter), away from the implant), and left lateral bending (4 Nm, toward the implant). Statistical analysis included a one-way analysis of variance and a Student-Newman-Keuls post hoc test. A pilot study was performed using four additional specimens loaded for 4000 cycles to investigate macroscopic loosening after fatigue loading. RESULTS: In lateral bending toward the implant, the strain was higher at both end levels, with no differences between the rib and dowel reconstructions. The stiffness values were greater than the intact values for both groups. In lateral bending away from the implant, the strain also was higher at both end screws, and the dowel group had less strain at these levels than the rib group. Both groups were stiffer than the intact condition, and the dowel group was stiffer than the rib group. Axial compressive strain also was higher at the end levels, but this difference did not reach statistical significance. The rib group did not reach intact stiffness values, whereas the dowel group was stiffer than the intact condition. The fatigue study showed gross loosening at one or both end levels in all cases. CONCLUSIONS: Higher strain was observed at the bone-screw interface in both end screws of an anterior solid rod construct during lateral bending, which correlates with the clinically observed failure location. This suggests that physiologic range loading may predispose to failure at the end levels. Disc space augmentation with solid implants increased construct stiffness in all three load paths and decreased strain at the end levels in lateral bending away from the implant. Future implant modifications should achieve better fixation at the end screws, and the current model provides a means to compare different strategies to decrease strain at these levels.

Animals↗

Congenital vertebral anomalies in ischiopagus and pyopagus conjoined twins.

A review of clinical records and radiographs revealed that five of 10 patients with conjoined twinning (three of six ischiopagus and two of two pyopagus twins) had congenital vertebral anomalies including hemivertebrae (3), multiple thoracic anomalies (1), right hemisacral agenesis (1), and three lumbar vertebra (1). No mirror image anomalies were identified, and different regions of the spine were involved in the two cases in which both twins had anomalies. Coexisting visceral and musculoskeletal anomalies included dextrocardia (3), atrial septal defect (1), congenital vertical talus (2), Sprengel's deformity (1), and multiple unilateral foot anomalies (1). Hip subluxation or dislocation was seen in five of eight ischiopagus or pyopagus twins after separation and required femoral and pelvic osteotomies. Lumbar scoliosis not associated with congenital vertebral anomalies was seen in two ischiopagus twins. These observations suggest an association between ischiopagus and pyopagus conjoined twins and congenital vertebral anomalies, and their coexistence is explained best by a nonspecific teratogenic insult during early embryogenesis.

Humans↗

Augmentation of an anterior solid rod construct with threaded cortical bone dowels. A biomechanical study.

STUDY DESIGN: This static, nondestructive, in vitro biomechanical study examines anterior solid rod construct stiffness following the addition of multilevel, threaded cortical bone dowels in a bovine model. A comparison is made with a clinically relevant posterior construct with and without an anterior release. OBJECTIVES: To determine if the addition of solid, multilevel disc space implants will increase construct rigidity, while maintaining or enhancing anterior column length. SUMMARY OF BACKGROUND DATA: Anterior instrumentation for thoracolumbar and lumbar scoliosis has achieved greater correction and preserved distal motion segments; however, kyphosis over the instrumented segments and nonunion have been observed more frequently than with posterior segmental spinal instrumentation. METHOD: Fifteen calf spines underwent mechanical testing. Group A (n = 7) included anterior constructs: 1) intact, 2) anterior release/rod/rib graft (L2-L5), and 3) anterior release/rod/dowels (L2-L5). Group B (n = 8) included posterior constructs: 1) intact, 2) posterior rod without anterior release (T13-L5), 3) posterior rod (T13-L5)/anterior release/rib graft (L2-L5). The protocol included axial compression (-600 N), axial rotation (+7 Nm), flexion/extension (+7.5 Nm), and lateral bending (+7.5 Nm). An anterior extensometer measured segmental displacements to calculate construct stiffness. Lateral radiographs evaluated alignment for the anterior constructs. Statistical analysis involved a one way analysis of variance (ANOVA) and a Student-Newman-Keuls post hoc test. RESULTS: All reconstructions restored stiffness to intact values with the exception of the dowels alone in axial rotation. The rod/dowel construct was stiffer than all other groups in axial compression, flexion/extension, and lateral bending, with the exception of the posterior rod without discectomy, which was superior in flexion and statistically similar in extension, lateral bending, and axial rotation. The anterior construct with rib graft was equivalent to the posterior construct with rib graft in all modes of testing. The dowels created greater lordosis than the bicortical rib grafts. CONCLUSIONS: Disc space augmentation increased stiffness except in axial rotation, in which values were restored to the intact level. Stiffness was superior to a clinically relevant posterior instrumentation comparison group following anterior release, and was equivalent to a posterior construct without anterior release except in anterior flexion. In addition, the implants enhanced lordosis. Increased rigidity should improve rates of arthrodesis, while maintenance of sagittal alignment may prevent pathologic compensatory curves in adjacent spinal segments. Further research is required to determine the optimal method of achieving structural interspace support.

Animals↗

Cognitive-behavioral therapy helps prevent relapse and recurrence of panic disorder following alprazolam discontinuation: a long-term follow-up of the Peoria and Dartmouth studies.

The present research evaluated patients from 2 previous studies (1 conducted in Peoria, the other at Dartmouth) during a 2- to 5-year posttreatment period. Results showed that 75% of the Peoria sample and 76% of the Dartmouth sample were able to discontinue alprazolam therapy, remain abstinent of any type of treatment for panic disorder, and maintain their acute-treatment clinical gains over this follow-up period. The degree to which patients' anxiety sensitivity declined during treatment predicted relapse versus survival during the 1st 6 months of follow-up, when most relapses occurred. Implications of these findings for benzodiazepine discontinuation, combined pharmacotherapy and psychotherapy, and relapse prevention in panic disorder are discussed.

Alprazolam↗

Psychological strategies for discontinuing benzodiazepine treatment.

Successful discontinuation of therapeutic drugs requires patients to negotiate two potentially difficult phases. First, they must complete the drug discontinuation procedure itself, which may entail coping with rebound and withdrawal symptoms as well as anxiety due to stopping a treatment on which they depend psychologically. Second, they must maintain drug abstinence over time, despite possible exacerbations or recurrences of the disorder that the drug was treating. For optimal success, interventions aimed at assisting patients to discontinue drug use must address both of those tasks. Patients' ability to discontinue benzodiazepines seems to be strongly influenced by cognitive appraisals of the threat represented by symptoms and of their own competence to cope with it without medication. For problems of that kind, cognitive and behavioral techniques such as those developed for the treatment of panic disorder may be especially well-suited. Currently, the most successful approaches to benzodiazepine discontinuation include the following components: (1) assisting with initial drug discontinuation, educating patients about benzodiazepine dependence and withdrawal, and about the kinds of symptoms that can emerge as the drug dose is decreased, combined with a flexible drug taper conducted in supportive collaboration with the patient; and (2) dealing with exacerbations of the illness, and providing disorder-specific cognitive-behavioral treatment as an alternative to the resumption of pharmacotherapy. It seems to be crucial that the drug taper be completed before psychological treatment concludes.

Anti-Anxiety Agents↗

Panic control treatment and its applications.

Panic Control Treatment (PCT) is a widely used, empirically validated cognitive-behavioral treatment for panic disorder. Initially developed for the treatment of panic disorder with limited agoraphobic avoidance, PCT more recently has been finding broader applications. It has been used as an aid to pharmacotherapy discontinuation in panic disorder; in the treatment of panic attacks associated with other disorders such as schizophrenia; and, in combination with a situational exposure component, in the treatment of patients with moderate to severe agoraphobia. The authors critically review the evidence for the clinical efficacy of PCT and recent work directed at further enhancing the long-term efficacy and cost-effectiveness of treatment.

Benzodiazepines↗

Efficacy studies of alprazolam in panic disorder.

Alprazolam was the first pharmacological agent to be approved for the treatment of panic disorder. In seeking that approval, the Upjohn Company conducted the earliest large, multicenter drug trials in panic disorder, involving nearly 1,700 patients in 14 countries. The administrative and quality assurance procedures developed for those studies have become a model for subsequent research. Despite this history, the efficacy of alprazolam for panic disorder has been contested. This article summarizes the published multicenter data from the perspective of the assessment criteria recommended by Shear and Maser (1994) and presents comparative findings from the Philadelphia maintenance study and the London/Toronto study of alprazolam and exposure therapy. Data on relapse following treatment discontinuation are also reviewed.

Alprazolam↗

Benzodiazepines and exposure-based cognitive behavior therapies for panic disorder: conclusions from combined treatment trials.

OBJECTIVE: Concurrent use of benzodiazepines and psychotherapy for panic disorder is a prevalent but highly controversial practice. Although there are many rationales for that approach, critics contend that benzodiazepines foster drug abuse and dependence and undermine psychosocial treatments in various ways. The authors examine that controversy in the light of recent empirical findings and offer some tentative conclusions and recommendations. METHOD: Data from studies combining benzodiazepines and the leading psychosocial treatment for panic disorder, exposure-based cognitive behavior therapy, are reviewed, and their application to clinical practice is discussed. RESULTS: The strongest support for combined treatment is for the addition of cognitive behavior therapy to pharmacotherapy for patients with agoraphobia and for those whose benzodiazepine treatment is being discontinued. The greatest problem with combined treatment is relapse after drug discontinuance. CONCLUSIONS: Combined treatment may be advantageous for some patients, but it must be carefully designed to avoid potential problems. Suggestions for that are given.

Agoraphobia↗

An open trial of fluvoxamine therapy for panic disorder complicated by depression.

BACKGROUND: The efficacy of fluvoxamine in the treatment of panic disorder complicated by depression was investigated in an 8-week, single-group, open-label, flexible-dose trial. METHOD: Seventeen patients having a principal diagnosis of panic disorder and scoring 16 or more on the 17-item Hamilton Rating Scale for Depression were treated with fluvoxamine at a mean final dose of 213 mg/ day. Outcome was assessed on measures of panic attacks, general and anticipatory anxiety, agoraphobic avoidance, depression, disability, and fear of anxiety symptoms. RESULTS: Subjects improved on all measures except agoraphobic avoidance. Thirteen either chose to remain on fluvoxamine treatment after the study ended or resumed taking it after a brief period without medication or on another medication. CONCLUSION: Fluvoxamine appears to be effective in this population.

Adult↗

Metastatic melanoma to the spine. Demographics, risk factors, and prognosis in 114 patients.

STUDY DESIGN: One-hundred-fourteen patients with metastatic melanoma of the spine were retrospectively reviewed. OBJECTIVE: The goal was to define the demographics, risk factors, and prognosis for this population. SUMMARY OF BACKGROUND DATA: The incidence of melanoma is increasing faster than any other cancer. Therefore, orthopedic and neurologic surgeons will be increasingly confronted by patients with spinal metastases from melanoma. However, the demographics, risk factors, and prognosis remain unclear. METHODS: From 7010 consecutive patients with melanoma, 114 were identified with clinically or radiographically evident spinal metastases. A comparison was made between these patients and the remainder of the population with melanoma seen at our institution using contingency table analysis with statistical significance determined by a chi-squared test. Survival data were represented by Kaplan-Meier curves, and log-rank testing was used for statistical comparisons. RESULTS: Risk factors associated with the development of these metastases included primary lesions that were ulcerated, deeper than 0.76 mm, or of Clark level II, or located on the trunk or mucosal surfaces. The median survival time for all patients was 86 days, but this was reduced in patients with more than one metastatic site in addition to the spine. CONCLUSION: The prognosis for most patients with spinal metastases from melanoma is dismal. However, patients with metastatic disease limited to the spine and one other organ may survive for a relatively prolonged time and may be candidates for surgical intervention directed toward symptomatic relief.

Adult↗

Predictors of alprazolam discontinuation with and without cognitive behavior therapy in panic disorder.

OBJECTIVE: In a previous paper the authors reported survival data for 20 panic disorder patients whose therapeutic doses of alprazolam were tapered by one of two methods: slow, flexible drug taper with supportive medical management or the same taper procedure carried out concurrently with cognitive behavior therapy. This report is an analysis of predictors of drug discontinuation success in that study. In addition, between-group comparisons of clinical measures at follow-up are presented. METHOD: The subjects in the previous study (10 in each group) were assessed blindly at baseline, 2 weeks after completion of drug taper, and at 3- and 6-month follow-up. Potential predictors of drug discontinuation success were tested by using logistic regression. Between-group differences in symptom severity at 3-month follow-up were examined by using analyses of covariance. RESULTS: Thirteen subjects (nine receiving alprazolam plus cognitive behavior therapy and four receiving alprazolam only) completed the drug taper on schedule and were still medication free at follow-up. A single variable--baseline-to-posttaper change in anxiety sensitivity--predicted drug status at follow-up in 85% of the cases. At follow-up, subjects in the combined-treatment group were significantly more improved on measures of anxiety, depression, catastrophic thinking related to anxiety, perception of emotional control, and disability than subjects in the drug-only group. CONCLUSIONS: Across groups, reduction in the fear of anxiety symptoms was the best predictor of patients' ability to achieve and maintain drug abstinence. Some implications of that finding for the pharmacotherapy of panic disorder are discussed.

Adult↗

Does cognitive behavior therapy assist slow-taper alprazolam discontinuation in panic disorder?

OBJECTIVE: The authors investigated whether cognitive behavioral treatment could facilitate discontinuation of alprazolam therapy and maintenance of drug abstinence among panic disorder patients treated with alprazolam doses sufficient to suppress spontaneous panic attacks. METHOD: Twenty-one outpatients who met DSM-III-R criteria for panic disorder with mild to severe agoraphobia were made panic-free with alprazolam (mean dose = 2.2 mg/day) and were then randomly assigned to receive either supportive drug maintenance and slow, flexible drug taper or an identical medication treatment plus 12 weeks of concurrent, individual cognitive behavioral treatment. Taper in the combined treatment group was sequenced to conclude before cognitive behavioral treatment ended. RESULTS: Twenty subjects completed the study. There was no significant difference between groups in the rate of alprazolam discontinuation (80% and 90%, respectively, in the alprazolam-only group and the combined treatment group). However, during the 6-month follow-up period, half of the subjects who discontinued alprazolam without cognitive behavior therapy, but none of those who were given cognitive behavior therapy, relapsed and resumed alprazolam treatment. CONCLUSIONS: Cognitive behavioral treatment administered in parallel with alprazolam maintenance and taper was effective in preventing relapse after drug discontinuation. The results warrant further research on the thoughtful integration of these two therapeutic modalities.

Adult↗

Recovery following stretch injury to the sciatic nerve of the rat: an in vivo study.

Stretch injuries to peripheral nerves are often associated with poor recovery, which may relate to both the character and the extent of structural alterations in the nerve trunk. Previous biomechanical studies have provided insight into such structural changes; however most of these investigations have involved the testing of specimens after removal from the body. This investigation presents an in vivo model of nerve stretch injury and correlates functional recovery with different regions of the stress-strain relationship described in previous biomechanical studies. Functional recovery was measured for 8 weeks using the Sciatic Functional Index of de Medinaceli. Nerves stretched prior to reaching mechanical failure demonstrated excellent recovery within 2 to 3 weeks, with acute histologic features including variable amounts of degenerating axons. Nerves stretched through the point of mechanical failure were permanently deformed, with widespread degeneration and ruptures in the epineurium and perineurium. Despite these severe pathologic changes, a significant degree of recovery was observed by the end of the study period. These results suggest that if continuity is preserved, a substantial amount of recovery is possible following severe nerve stretch lesions in the rat. Preservation of continuity may create an optimal alignment for regenerating neurons.

Animals↗