Bucindolol, a beta-adrenoceptor blocker with vasodilatory action: its effect in systemic hypertension.

Bucindolol is a newly developed, nonselective beta-adrenergic blocking agent with intrinsic sympathomimetic activity and direct vasodilator properties. In 14 patients with mild to moderate essential hypertension, the effects of bucindolol, hydrochlorothiazide and their combination on blood pressure (BP), heart rate (HR) and parameters of the renin-aldosterone system were compared with those after placebo. Bucindolol's antihypertensive effect was evident within the first hour after drug administration, maximal at 2 to 3 hours, and lasted for as long as 12 hours. Compared with placebo values (108 +/- 5 mm Hg), both bucindolol (97 +/- 9 mm Hg) and hydrochlorothiazide (99 +/- 10 mm Hg) alone significantly and comparably reduced the 12-hour averaged standing diastolic BP, with the combination resulting in approximately additive effects (91 +/- 9 mm Hg). Although bucindolol alone did not affect HR, it attenuated the hydrochlorothiazide-induced increase in HR. There was a tendency for bucindolol to decrease plasma renin activity. Except for transient postural hypotension in 2 patients, bucindolol was well tolerated.

Effect of intravenous carbenicillin, cefoxitin and cefamandole on ADP-induced platelet aggregation and shape change.

The effect of a large daily dose of i.v. carbenicillin, cefoxitin and cefamandole on platelet aggregation with adenosine diphosphate (ADP) and the effect of carbenicillin on ADP induced shape change were evaluated. Six volunteers received carbenicillin 100 mg/kg every 4 hours. Three of them also received cefoxitin 3 gm every 6 hours and cefamandole 2 gm every 4 hours. All treatments were separated by 14 days. Prior to treatment, as well as 1 and 24 hours after the last dose of antibiotic, citrated platelet-rich plasma was tested for the extent of aggregation at a series of ADP concentrations. As previously reported by several groups, carbenicillin decreased the sensitivity of platelets in their aggregation response to ADP. Thus, the concentration of ADP needed to obtain 50% of maximal aggregation response was increased 3.5 +/- 1.7 (S.D.) fold. In addition, when measured separately, the sensitivity of platelets in their shape change response to ADP was decreased to a similar degree. The concentration of ADP needed to produce 50% of maximal shape change response was 2.8 +/- 1.6 (S.D.) fold higher after carbenicillin treatment. The results are in accordance with previous in vitro studies suggesting that carbenicillin interferes with the initial phase of platelet activation. Cefoxitin and cefamandole had no apparent effect on platelet aggregation.

Relationship of morphine-induced miosis to plasma concentration in normal subjects.

The relationship between morphine plasma concentration and pupil diameter was evaluated 2-10 h following intravenous administration of morphine sulfate (10 mg). Seven healthy male volunteers received 10 mg of morphine intravenously following pretreatment for 4 d with either cimetidine (300 mg po four times a day) or placebo in a single blind, balanced crossover study. Pupil diameters were measured directly from contact prints using calipers and a photographed millimeter scale. Cimetidine pretreatment had no significant effect on pupil size either before or after morphine administration or on morphine pharmacokinetics. The relationship between morphine plasma concentration (2-10 h postdose) and pupil diameter was evaluated from the pooled data from both morphine treatment periods by perpendicular least-square regression. In each individual, a strong relationship existed between morphine plasma concentrations and pupil diameter (r = -0.76 to -0.91; p less than 0.05). Weaker correlations for both pupil diameter (r = -0.65; p less than 0.0001) and the absolute change in pupil diameter from baseline (r = 0.72; p less than 0.0001) for the grouped data probably reflect intersubject variation in morphine sensitivity. Thus, the miotic response to an intravenous dose of morphine varies in proportion to morphine plasma concentration.

Minimally invasive anterior retroperitoneal approach to the lumbar spine. Emphasis on the lateral BAK.

STUDY DESIGN: Eighteen patients with lumbar instability from fractures, postlaminectomy syndrome, or infection were treated prospectively with minimally invasive retroperitoneal lumbar fusions. OBJECTIVES: To determine if interbody Bagby and Kuslich fusion cages and femoral allograft bone dowels can be inserted in a transverse direction via a lateral endoscopic retroperitoneal approach to achieve spinal stability. SUMMARY OF BACKGROUND DATA: Endoscopic spinal approaches have been used to achieve lower lumbar fusion when instrumentation is placed through a laparoscopic, transperitoneal route. However, complications of using this approach include postoperative intra-abdominal adhesions, retrograde ejaculation, great vessel injury, and implant migration. This study is the first clinical series investigating the use of the lateral retroperitoneal minimally invasive approach for lumbar fusions from L1 to L5. METHODS: Eighteen patients underwent anterior interbody decompression and/or stabilization via endoscopic retroperitoneal approaches. In most cases, three 12-mm portals were used. Two parallel transverse interbody cages restored the neuroforaminal height and the desired amount of lumbar lordosis was achieved by inserting a larger anterior cage, distraction plug, or bone dowel. RESULTS: The overall morbidity of the procedure was lower than that associated with traditional "open" retroperitoneal or laparotomy techniques, with a mean length of hospital stay of 2.9 days (range, outpatient procedure to 5 days). The mean estimated intraoperative blood loss was 205 cc (range, 25-1000 cc). There were no cases of implant migration, significant subsidence, or pseudoarthrosis at mean follow-up examination of 24.3 months (range, 12-40 months) after surgery. CONCLUSIONS: This preliminary study of 18 patients illustrates that endoscopic techniques can be applied effectively through a retroperitoneal approach with the patient in the lateral position. Unlike the patients who had undergone transperitoneal procedures described in previous reports, in these preliminary 18 patients, there were no cases of retrograde ejaculation, injury to the great vessels, or implant migration.

The incidence of complications in endoscopic anterior thoracolumbar spinal reconstructive surgery. A prospective multicenter study comprising the first 100 consecutive cases.

STUDY DESIGN: A prospective multicenter study on 100 consecutive surgical procedures. OBJECTIVES: A prospective multicenter study was performed to evaluate the early perioperative complications in 100 endoscopic spinal procedures--78 video-assisted thoracic surgical procedures and 22 laparoscopic lumbar instrumentation and fusion procedures. SUMMARY OF BACKGROUND DATA: Endoscopic procedures have been widely applied in general surgery for appendectomy, cholecystectomy, liver resection, Nissen fundoplication, colon resection, and hernia repairs. Video-assisted thoracic surgery is widely used for pleural biopsy, lung resection, and sympathectomy. This is the first large series to date investigating the safety and potential complications using endoscopic surgery for anterior decompression or fusion of the thoracolumbar spine. METHODS: Video-assisted thoracic surgical procedures included multilevel anterior thoracic releases for deformity, 27 patients; anterior thoracic discectomies with spinal canal decompression, 41 patients; pyogenic vertebral osteomyelitis decompression, 2 patients; and vertebral corpectomy for neurologic decompression, 8 patients. Mean operative time was 2 hours, 34 minutes (range, 45 minutes to 6 hours), and mean length of stay was 4.97 days (range, 2-21 days). Anterior laparoscopic interbody stabilization and fusion at L4-5 or L5-S1 was performed in 22 patients. The mean operative time was 4 hours, 17 minutes (range, 2 hours, 40 minutes to 9 hours), and the mean length of stay was 5.6 days (range, 1-23 days). RESULTS: The most common video-assisted thoracic surgical complications were transient intercostal neuralgia (six patients) and atelectasis (five patients). The most common laparoscopic complication was bone graft donor site infection (two patients). There were two endoscopic cases that were converted to open procedures, one for extensive pleural adhesions and one for a common iliac vein laceration. CONCLUSIONS: The endoscopic spinal approaches proved to be safe operative procedures in 100 consecutive cases. There were no permanent iatrogenic neurologic injuries and no deep spinal infections.

Osteogenic protein versus autologous interbody arthrodesis in the sheep thoracic spine. A comparative endoscopic study using the Bagby and Kuslich interbody fusion device.

STUDY DESIGN: Using an in vivo interbody arthrodesis model, the efficacy of the Bagby and Kuslich (BAK) device packed with recombinant human osteogenic protein-1 (rhOP-1) was evaluated. OBJECTIVES: To compare the efficacy of osteogenic protein with that of autograft for interbody arthrodesis, with fusion success based on biomechanical, histologic, and radiographic analyses. SUMMARY OF BACKGROUND DATA: The use of recombinant human bone morphogenetic proteins (rhBMPs) as osteoinductive bone graft substitutes or expanders has recently gained considerable research interest, particularly when applied in posterolateral arthrodesis. However, whether these results can be extrapolated to a successful interbody spinal arthrodesis remains uncertain. METHODS: Twelve sheep underwent a multilevel thoracic spinal decompression by thoracoscopic approach. Three noncontiguous destabilization sites (T5-T6, T7-T8, T9-T10) were prepared and randomly treated as follows. Control group treatments were nonsurgical, destabilization alone, and empty BAK. Experimental groups were treated with autograft alone, BAK device packed with autograft, or BAK device packed with rhOP-1. Four months after surgery, interbody fusion status was quantified by biomechanical testing, computed tomography, microradiography, and histomorphometry. RESULTS: Results of biomechanical analysis showed statistically higher segmental stiffness levels when comparing the control and experimental groups with four of the five testing methods (P < 0.05). Computed tomography and microradiography characterized destabilization alone as producing one fusion in six preparations; the empty BAK, two in six;, autograft alone, four in eight; BAK with autograft, five in eight; and BAK with rhOP-1 group, six in eight-all evidenced by woven trabecular bone spanning the fusion sites. Histomorphometry yielded significantly more trabecular bone formation at the fusion sites in the three experimental groups than in the two control groups (P < 0.05). CONCLUSIONS: Interbody spinal fusions showing biomechanical and histomorphometric equivalency to autologous fusions have been achieved with rhOP-1. The functional unit stability and histologic osteointegration evidenced by the BAK/rhOP-1 complex shows this interbody arthrodesis technique to be a viable alternative toconventional autologous iliac crest, thereby obviating the need for an iliac crest donor site and associated patient morbidity.

Video-assisted thoracoscopic surgery versus open thoracotomy for anterior thoracic spinal fusion. A comparative radiographic, biomechanical, and histologic analysis in a sheep model.

STUDY DESIGN: In this in vivo investigation, a sheep model was used to compare the efficacy of a video-assisted thoracoscopic approach and a traditional thoracotomy in promoting a successful interbody spinal arthrodesis. OBJECTIVES: To compare the incidence of successful anterior spinal arthrodesis among three stabilization techniques-iliac crest, Bagby and Kuslich device, and Z-plate--performed using a video-assisted thoracoscopic approach and conventional open thoracotomy approaches. SUMMARY OF BACKGROUND DATA: A clinical outcome study on open versus endoscopic spinal fusion is not yet available. Moreover, no basic scientific investigations have been conducted to determine whether the success of an endoscopic arthrodesis is comparable to that of a conventional open procedure. METHODS: Fourteen Western Crossbred sheep underwent three identical destabilization procedures at T5-T6, T7-T8, and T9-T10, in which the anterior and middle osteoligamentous columns of the spine were resected, followed by three randomized reconstruction procedures using iliac autograft alone, and Z-plate stabilization with iliac autograft. In seven sheep, the entire destabilization-reconstruction procedure was performed using a video-assisted thoracoscopic surgical approach. In the remaining seven, the procedure was performed by conventional open thoracotomy. RESULTS: Histomorphometric and biomechanical evaluation demonstrated that the video-assisted thoracoscopic approach and open thoracotomy arthrodesis had comparable bone formation and biomechanical properties (P > 0.05). However, the Z-plate fusions, as a group, demonstrated increased flexion-extension stiffness properties and trabecular bone formation compared with the autograft and Bagby and Kuslich device fusions (P < 0.05). CONCLUSIONS: Thoracic interbody spinal fusions performed by thoracoscopy have demonstrated histologic, biomechanical, and radiographic equivalence to those performed by a thoracotomy approach. However, in the endoscopy group, intraoperative complications causing longer operative times, higher estimated blood loss, and increased animal morbidity indicated a substantial learning curve associated with the adoption of this surgical technique.

Revision strategies for salvaging or improving failed cylindrical cages.

STUDY DESIGN: This is a review of 20 patients who experienced failure of threaded interbody fusion cages and underwent surgical correction. OBJECTIVE: To review the causes and possible treatment strategies for failed cylindrical cages. SUMMARY OF BACKGROUND DATA: Intraoperative complications have been described in the past; however, management of the postoperative patient with failure of interbody fusion devices has not been described. METHODS: In 20 patients with failed threaded titanium fusion cages (18 Bagby and Kuslich Devices [BAK; Sulzer-Spine Tech, Minneapolis, MN], 2 Ray Threaded Fusion Cages [Ray TFC; Surgical Dynamics, Norwalk, CT) who underwent revision surgery, all had failure before successful arthrodesis was achieved. Eight of the original titanium cages had been inserted anteriorly (7 laparoscopically), and 12 had been inserted for posterior interbody lumbar fusion. Before the revision surgery, five of the implants were thought to be solid by the referring surgeon, but pseudarthrosis was clearly present in all. In addition, 14 other explanted BAK devices were subjected to undecalcified histologic preparation, quantitative histomorphometry, and histopathologic analysis. RESULTS: The average length of time before revision surgery (implant duration) was 31.8 weeks (range, 1-156 weeks). The most common revision procedure was posterior exploration of the symptomatic nerve root with foraminotomy for unrecognized lateral recess stenosis (11 cases) or excision of iatrogenically herniated intervertebral disc fragments (4 cases). However, four cages inserted through posterior exposure during an interbody lumbar fusion procedure had to be removed because of migration into the spinal canal. In nine cases posterior pedicle screw instrumentation was necessary in addition to posterolateral fusion using iliac crest bone grafting. CONCLUSIONS: All 20 cages failed because of surgical technique rather than an intrinsic defect in fusion cage technology. The factors associated with failure of the original insertion procedure were failure to achieve adequate distraction of the anulus fibrosis; undersized cages, especially when placed through the posterior interbody lumbar fusion approach; cerebrospinal fluid leakage or pseudomeningocele; Type 2 diabetes mellitus; the use of local bone graft rather than iliac crest inside the cage; anterior insertion in an excessively lateral position resulting in symptoms of a far lateral disc herniation; and failure to identify the spinal midline during an anterior approach.

Minimally invasive surgical techniques to treat spine infections.

Minimally invasive techniques including closed laparoscopy and thoracoscopy as well as video-assisted procedures using limited open incisions provide an excellent alternative for treating vertebral osteomyelitis and tuberculous infections in the thoracic and lumbar spine. The traditional principles of surgical debridement and a stable interbody fusion are unchanged when applying endoscopic techniques. In the future, the spinal endoscopist will have available a larger selection of endoscopic instruments, more sophisticated video technology, and the development of anterior instrumentation systems to allow for rigid internal fixation. These advances, along with the surgeon's endoscopic experience and refined techniques, will further establish minimally invasive surgical techniques in the field of spinal surgery.

Anterior thoracic corpectomy for spinal cord decompression performed endoscopically.

A prospective study was undertaken during the past 3 years to investigate the effectiveness of thoracoscopic corpectomy--endoscopic removal of the vertebral body in 15 cases (8 for pathologic fractures for tumors, 5 for traumatic fractures and 2 for infections). The average age of the patients was 53.2 years (range 28-85 years). The vertebral levels of corpectomy ranged from T3 to L1. The mean operating time was 211 min (range 83-450 min) and the mean estimated blood loss was 890 ml (range 150-2,800 ml). The postoperative morbidity appeared to be more favorable than with open thoracotomy [Alband OW, Corkill G. Thoracic disk herniation: treatment and prognosis. Spine 1979; 4:41-6; Landreneau RJ, Hazelrigg SR, Mack NJ. Postoperative pain-related morbidity: video-assisted thoracic surgery versus thoracotomy. Ann Thorac Surg (in press); McAfee PC. Complications of anterior approaches to the thoracolumbar spine: emphasis on Kaneda instrumentation. Clin Orthop 1994;306:110-9; McAfee PC, Bohlman HH, Yuan HA. Anterior decompression of traumatic thoracolumbar fractures with incomplete neurological deficit using a retroperitoneal approach. J Bone Joint Surg [Am] 1985;67: 89-104; Regan JJ, Mack MJ, Picetti GD, Guyer RD, Hochschuler SH, Rashbaum RF. A comparison of video-assisted thoracoscopic surgery (VATS) with open thoracotomy in thoracic spinal surgery. Today's Ther Trends 1994;11: 203-18.] because the mean chest tube duration was 1.22 days (range 1-3 days), the mean length of time in the intensive care unit was 2 days (range 1-4 days), and the mean length of total hospitalization was 6.5 days (range 2-12 days). Overall, the ability to visualize the anterior surface of the dura during corpectomy was better endoscopically than with open thoracotomy techniques--improved magnification, the ability of the operative assistant to see and therefore suction more efficiently, and the perspective of visualization was improved. It was possible to place the 30 degrees angled endoscope within the defect left by the resected vertebral body and look directly posteriorly at the dura, visualizing the epidural vessels and dural pulsations at close range. The limiting factor in wide application of the technique is the absence of a commercially available internal fixation system that can be applied endoscopically.

Cimetidine does not alter morphine disposition in man.

1 The pharmacokinetic parameters of morphine were determined in a crossover fashion following 4 days pretreatment with cimetidine, 300 mg every 6 h, or placebo. 2 Cimetidine had no apparent effect on the mean morphine plasma clearance, volume of distribution, AUC or half-life (P greater than 0.05; power greater than 0.80). 3 Cimetidine had no apparent effect on the magnitude or duration of morphine induced miosis. 4 The absence of a demonstrable effect on the pharmacokinetics of a drug with a high extraction ratio such as morphine suggests that cimetidine did not significantly reduce hepatic blood flow in ambulant normal volunteers.