Ultrastructural study of the short-term effects of chymopapain on the intervertebral disc.

The initial effects of chymopapain, a chemonucleolytic agent, on the intervertebral disc of dogs were studied by light and electron microscopic techniques. Fragments of nucleus pulposus and annulus fibrosis were incubated with chymopapain up to 24 h in vitro. Proteoglycans and matrix proteins were rapidly removed, while collagen fibers remained intact up to 24 h. For several hours, most cells remained normal in appearance with only slight swelling and an increased number of vacuoles. After exposure to the protease for 24 h cells in both the annulus and nucleus showed extensive membrane damage and some were necrotic, but many survived relatively intact. These results suggest that, similar to the results of the digestion of cartilage with other proteases, the cells of the disc can survive brief chymopapain exposure during chemonucleolysis procedures and could serve as a source for regenerating tissue. The nature of the regeneration may depend on the extracellular scaffold that remains and the nutrition available to tissue as well as the age and biomechanical state of the disc. As for clinical significance, chemonucleolysis is an important nonsurgical alternative for treating prolapsed disc. The cells of nucleus and annulus can survive short-term exposure to treatment, and thus be responsible for partial regeneration of the tissue. This regeneration may be important in preventing long-term degenerative disease in the facet joints caused by increased pressure due to decreased disc height.

Cellular contribution of bone graft to fusion.

Although a number of studies have examined the fate of graft-derived cells during the process of fusion, there remains no consensus regarding their exact contribution to bone formation within the fusion mass. We developed two chimeric mouse isograft fusion models that allowed us to track the fate of graft cells within the host fusion bed. Cortical/cancellous bone graft (1:1 ratio of pelvic to vertebral body bone) from male mice was placed between (a) the tibia and fibula or (b) the coccygeal spine transverse processes of syngeneic female hosts. Both models were characterized histologically and histochemically. Graft-derived cells were then identified by fluorescent in situ hybridization for Y-chromosome sequences present in only the graft (male) cells. When the fusion mass was healing but not yet fused (at 1 and 2 weeks), numerous graft-derived cells were observed throughout the fusion site. The predominant graft-derived cell types included chondrocytes, osteoblasts, and fibroblasts. Chondrocytes arose from precursor cells in the graft de novo. as cartilage was not transplanted during the surgical procedure. By the time a mature fusion mass had formed (at 6 weeks), graft-derived cells persisted as osteocytes within the cortical rim surrounding the fusion mass. These osteocytes likely differentiated from graft-derived precursors that had directly formed bone, because transplanted osteocytes within cortical bone graft fragments were noted to rarely survive even at 1 and 2 weeks. Collectively, our results demonstrate for the first time that bone graft contributes cells that, in conjunction with host cells, directly form bone within the fusion mass during all phases of fusion rather than just the early phases.

Successful management of miliary tuberculosis after renal transplantation.

Miliary tuberculosis is the most lethal form of tubercular disease. If dissemination of tubercle bacilli occurs without therapy, death is almost certain. The importance of establishing an etiologic diagnosis as promptly as possible in patients receiving immunosuppressive therapy is self-explanatory. The presence of a life-threatening infection in these patients requires aggressive antimicrobial therapy and discontinuation of the immunosuppressive drugs until the infectious process is under control; the presence of an impaired immunologic response is responsible for the life-threatening infection and the lack of an acute rejection reaction.

Treatment of severe spondylolisthesis by anterior and posterior reduction and stabilization. A long-term follow-up study.

Twenty-two consecutive unselected patients who had severe spondylolisthesis were treated by a first-stage posterior decompression (Gill procedure) and a posterolateral arthrodesis, followed by halo-skeletal traction, and then by a second-stage anterior interbody arthrodesis, followed by immobilization in a cast. Nineteen patients had complete clinical and radiographic evaluation, with an average follow-up of five years (range, two to seven and one-half years). The slip angle averaged 71 degrees preoperatively, was corrected to an average of 31 degrees by reduction, and averaged 28 degrees at follow-up. The average preoperative percentage of slippage (98 per cent) did not change substantially. A pseudarthrosis developed in four patients, all of whom had a reoperation. The neurological deficits that had been present in ten patients preoperatively had completely resolved in all but one at follow-up. One patient had a cauda equina syndrome and two patients had a neuropathy of the root of the fifth lumbar nerve as a result of the reduction; complete recovery occurred in two patients and partial recovery, in one. Alignment in the sagittal plane was restored in seventeen patients, and the back pain and radicular symptoms were relieved in all patients except one who had had those symptoms preoperatively.

Staged salvage reconstruction of grade-IV and V spondylolisthesis.

Sixteen patients who had Grade-IV or V spondylolisthesis underwent a staged reconstruction for the salvage of a failed result of previous procedures. The indications for operation were incapacitating pain, radicular pain, pseudoclaudication, or the inability to stand upright. All patients had shown progression of the deformity after the previous surgery. At an average length of follow-up of fifty-two months, all patients had resumed normal activities and were free of the pain and symptoms of spinal stenosis. The complications included delayed union in six patients and a traumatic pseudarthrosis in one patient. In all of these patients a solid fusion was obtained after additional surgery. In five patients, neuropathy of the fifth lumbar-nerve root developed after surgery; it resolved in three patients. From this work, it is concluded that staged reconstructive surgery is feasible in patients who have Grade-IV or V spondylolisthesis with incapacitating pain and deformity that interfere with normal function. The benefits outweighed the risks in this very select group of patients.

One-stage anterior and posterior hemivertebral resection and arthrodesis for congenital scoliosis.

Seven children who had congenital scoliosis due to a single, fully segmented lumbar hemivertebra were treated with single-stage anterior and posterior vertebral resection and arthrodesis. The scoliosis averaged 47 degrees preoperatively, 14 degrees postoperatively, and 15 degrees (approximately 70 per cent correction) after an average follow-up of 45.6 months. Four patients had thoracolumbar kyphosis preoperatively, and it remained unchanged at the most recent follow-up examination. Postoperatively, a cast was worn for twelve to sixteen weeks, after which a brace was applied. There were no neurological deficits, infections, deaths, or pseudarthroses. The combined procedure was well tolerated and, in the limited period of follow-up, the congenital scoliosis did not progress.

Results of spinal arthrodesis with pedicle screw-plate fixation.

Sixty-one patients were followed for an average of thirty months (range, twenty-four to thirty-five months) after arthrodesis of the lumbar or lumbosacral spine with pedicle screw-plate fixation for painful degenerative arthritis, spondylolisthesis, or pseudarthrosis. The patients rated the clinical result according to an analog scale. Most patients reported a marked decrease in pain and an increase in function, and two-thirds were able to work full time. The result of the operation was regarded as a clinical failure if the patient considered it so, if an additional operation had been done, or if the functional and pain scores were not good (that is, if the patient was not able to work full time and the rating for pain was more than 5 of 10 points). Seventeen (28 per cent) of the patients were considered to have a clinical failure, with the lowest rate (20 per cent) for patients who had painful degenerative arthritis and the highest rate (47 per cent) for patients who had had a pseudarthrosis before the operation. The rate of fusion was 90 per cent in patients who had painful degenerative disease, 93 per cent in patients who had spondylolisthesis, and 65 per cent in patients who had had a pseudarthrosis preoperatively.

Congenital thoracic lordosis.

The rare spinal deformity of congenital thoracic lordosis is illustrated in five patients. Often this deformity is progressive and may cause severe pulmonary deficits and death. In the two patients most recently treated, early spine fusion (one anterior and one posterior) showed promising results--halting of the progression of deformity and even some amelioration of the lordosis. In two patients in whom active attempts were made to correct the lordosis, the complications were severe--one patient died and quadriparesis developed in the other.

Management of severe spondylolisthesis in children and adolescents.

Forty-three patients with a fifth lumbar-first sacral spondylolisthesis of 50 per cent or greater were reviewed. Four had been treated non-operatively; eleven, by arthrodesis; eighteen, by decompression and arthrodesis; and ten, by reduction and arthrodesis. The angle of slipping (measurement of the kyphotic relationship of the fifth lumbar to the first sacral vertebra) was found to be as important a measurement as the percentage of slipping in measuring instability and progression of slipping. Hamstring tightness did not correlate with neural deficit. Arthrodesis alone, even in the presence of minor neural deficits, tight hamstrings, or both, gave relief of pain and resolution of neural deficits and tight hamstrings. Our experience with a limited number of patients suggests that management by postoperative extension casts may achieve a significant reduction in percentage of slipping and in angle of slipping. Progression of the spondylolisthesis may occur following a solid arthrodesis.

Chymopapain, chemonucleolysis, and nucleus pulposus regeneration.

UNLABELLED: In the adult mongrel dog, in vivo injection of chymopapain into the intervertebral disc resulted in disc-space narrowing at two weeks, with a complete loss of proteoglycan (as indicated by safranin-O staining) from the nucleus pulposus, the cartilaginous end-plates, and the annulus fibrosus. As demonstrated by [35S]sulphate-labeling and proteoglycan isolation, the nucleus pulposus retained the ability to synthesize proteoglycans, but these were degraded by endogenous proteolytic activity. Three months after chymopapain treatment the intervertebral disc showed an increase in height. There was a return of intense safranin-O staining in the annulus and the cartilaginous end-plates, and very prominently in the nucleus. The proteoglycans that were present were recovered as aggregates, with the proteoglycan monomer being slightly larger than in the controls. Six months after chymopapain treatment the intervertebral disc had increased further in height, and normal histology had been restored. The chemical composition and physical properties of the proteoglycans that were isolated from the nucleus pulposus were essentially the same as those from the controls. These observations suggest that the nucleus can regenerate following the injection of chymopapain. CLINICAL RELEVANCE: Our observations demonstrate that chymopapain has a profound but reversible effect on the intervertebral disc. The radiographic narrowing of the intervertebral disc following chymopapain injection correlates with the loss of proteoglycan content and structure. The restoration of normal disc height following chymopapain injection is explained by reconstitution of the intervertebral disc with normal proteoglycans. In experimental animals, chemonucleolysis with chymopapain appears to be less likely than surgical excision to permanently alter the biochemistry of the nucleus pulposus.

Management of pseudarthrosis after arthrodesis of the spine for idiopathic scoliosis.

Sixty-three first, second, or third-time repairs of one or more pseudarthroses were done in fifty-one patients who had had an arthrodesis for idiopathic scoliosis. Forty-five of the patients were female and six were male. The average age was 30.2 years. The indications for the sixty-three repairs were pain (twenty-five repairs), progression of the curve (sixteen), both pain and progression of the curve (twelve), and radiographic changes only (ten). Failure of the implant was identified before 27 per cent of the sixty-three procedures. The pseudarthroses were diagnosed an average of 2.8 years after the initial arthrodeses. Sixty-eight per cent of the defects were visible on plain radiographs preoperatively and 32 per cent were identified at operation. During the time between the original arthrodeses and the repairs of the pseudarthroses, the scolioses increased by a mean of 7 degrees and the kyphoses, by a mean of 10 degrees. Harrington distraction was the most commonly used instrumentation (twenty-six [41 per cent] of the sixty-three procedures), and autogenous iliac bone was the most commonly used material for the graft (thirty-three [52 per cent] of the procedures).

Scheuermann's kyphosis. Results of surgical treatment by posterior spine arthrodesis in twenty-two patients.

Twenty-two patients with Scheuermann's kyphosis were treated with correction, Harrington instrumentation (in twenty-one), and posterior spine fusion. This procedure relieved pain and corrected deformity in all patients but loss of correction of 5 degrees or more occurred in sixteen of the twenty-two patients, including all those whose initial kyphosis was greater than 70 degrees. The incidence of complications was so high that this procedure should ordinarily be performed only for disabling pain or spinal cord compression.

Congenital kyphosis due to defects of anterior segmentation.

Twenty-seven patients with Type-II congenital kyphosis (failure of anterior vertebral segmentation) all had progression of the kyphosis which varied in magnitude. The average rate of progression was 5 degrees per year. Pain due to compensatory lumbar hyperlordosis (eight patients) and objectionable deformity (fifteen patients) were the most frequent complaints. Unlike patients with Type-I kyphosis (failure of vertebral formation), paraplegia did not occur and associated congenital anomalies were infrequent (three of the twenty-seven patients). Spontaneous ossification of the anterior part of seemingly normal intervertebral discs leading to bar formation and progression of deformity occurred in five patients. A Milwaukee brace had little effect on this fixed kyphotic deformity in the six patients in whom the brace was used. Early recognition and spine fusion are the recommended treatment. Posterior fusion is sufficient in young children with progressive deformity, whereas combined two-stage anterior and posterior fusion with osteotomy of the anterior bar is recommended in children with severe deformity.

Surgical treatment of adult scoliosis. A review of two hundred and twenty-two cases.

We evaluated the cases of 222 patients older than twenty years in whom scoliosis was the primary diagnosis. No patient had had prior surgical treatment. The diagnoses were idiopathic scoliosis in 160 patients, paralytic scoliosis in forty-four, and congenital scoliosis in eleven, and there were miscellaneous diagnoses in seven patients. The average age of the patients when first seen was 30.7 years. The indications for operation were pain, progression of the curve, magnitude of the curve, and cardiopulmonary symptoms. Preoperative traction, including halo-femoral traction, did not result in increased correction when compared with the initial supine side-bending roentgenogram. A one-stage fusion was performed in 174 patients and multiple-stage procedures, in forty-eight patients. At an average follow-up of 3.6 years the average loss of correction was 6.2 degrees, 68 per cent of the patients were free of pain, and a solid fusion had been obtained in all but six patients. Complications developed in 53 per cent of the patients, the most common problems being pseudarthrosis, urinary tract infection, wound infection, instrumentation problems, a pulmonary disorder, and loss of lumbar lordosis. Paraplegia occurred in one patient. The over-all mortality rate was 1.4 per cent. Complications increased with age, and the highest mortality rate was in patients with congenital scoliosis who had cor pulmonale.

Post-traumatic kyphosis. A review of forty-eight surgically treated patients.

We reviewed the cases of forty-eight patients who were treated surgically for symptomatic post-traumatic kyphosis of the thoracic or lumbar spine six months or longer after the initial injury. Presenting signs and symptoms included pain in 94 per cent, progression of kyphosis in 46 per cent, instability in 36 per cent, and increasing neural deficit in 27 per cent. Twenty-four patients had had a prior laminectomy. Posterior fusion (sixteen patients) and combined anterior and posterior fusion (twenty patients) always resulted in primary fusion. Anterior fusion alone was attempted in twelve patients, but failed in six. The average final correction of the deformity was 26 per cent. Pain was reduced significantly in 31 per cent of the patients and was relieved completely in 67 per cent. Fourteen of the forty-eight patients also had an anterior decompression, of whom five were neurologically improved, four were unchanged or stabilized, and four were immediately worse after operation. One patient was neurologically stable for twenty-three months postoperatively and then deteriorated again. No patients were neurologically improved following posterolateral decompression or repeat exploratory laminectomy.

Total hip arthroplasty with cement after renal transplantation. Long-term results.

Fifty patients with osteonecrosis following a renal transplantation were managed with a total of seventy-six total hip arthroplasties with cement between 1972 and 1982 at the University of Minnesota. The minimum duration of follow-up was ten years. With use of Kaplan-Meier survivorship analysis, with revision for any reason as the end point, the over-all rate of survival of the implants in all patients was 91 +/- 7 per cent (mean and two standard errors of the mean, 95 per cent confidence interval) at five years and 78 +/- 11 per cent at ten years. The prostheses in the patients who were more than forty years old had a rate of survival of 87 +/- 18 per cent and 72 +/- 30 per cent at five and ten years, respectively, compared with 92 +/- 7 per cent and 80 +/- 12 per cent for the patients who were less than forty years old. The acetabular components had a 94 +/- 6 per cent rate of survival at five years and an 86 +/- 9 per cent rate at ten years. The femoral components had a 97 +/- 4 per cent rate at five years and an 87 +/- 9 per cent rate at ten years. We concluded that the results of total hip arthroplasty with cement after renal transplantation are satisfactory and are comparable with those for patients of similar age who have not had a renal transplantation.(ABSTRACT TRUNCATED AT 250 WORDS)

Reconstructive surgery in the adult for failed scoliosis fusion.

Fifty-nine adult patients were examined who had undergone previous spine surgery for scoliosis but in whom pain (78 per cent), loss of correction (68 per cent), or dyspnea (36 per cent) subsequently developed. Twenty-six patients had idiopathic scoliosis, twenty-five had paralytic scoliosis secondary to poliomyelitis, and eight had scoliosis secondary to miscellaneous etiologies. A one-stage reconstructive procedure was performed in sixteen patients and a two-stage procedure, in forty-three patients. The two-stage procedure consisted of exposure of the spine and multiple osteotomies, followed by two weeks of halofemoral traction to obtain correction. The spine fusion was then extended, using Harrington instrumentation to maintain correction. At an average follow-up of 3.3 years there was reduction of pain in 67 per cent of the patients and a solid fusion in all but two. The complication rate was high (71 per cent), the most important complications being pseudarthrosis, wound infection, urinary tract infections, loss of lumbar lordosis, and pressure sores. The mortality rate was 3.4 per cent. No patient became paraplegic at the initial surgical procedure and early recognition and treatment of pseudarthrosis will reduce the number of patients requiring this salvage operation.

The surgical management of patients with Scheuermann's disease: a review of twenty-four cases managed by combined anterior and posterior spine fusion.

Twenty-four patients with Scheuermann's kyphosis underwent correction of the deformity through a combined anterior and posterior spine fusion. All patients had a solid arthrodesis and most were relieved of their preoperative pain. Deformity was improved in all patients. Significant loss of correction did not occur in the fusion area but it did occur below the posterior arthrodesis in five patients.

The selection of fusion levels in thoracic idiopathic scoliosis.

From the material and data reviewed in our study of 405 patients, it appears that postoperative correction of the thoracic spine approximately equals the correction noted on preoperative side-bending roentgenograms. Selective thoracic fusion can be safely performed on a Type-II curve of less than 80 degrees, but care must be taken to use the vertebra that is neutral and stable so that the lower level of the fusion is centered over the sacrum. The lumbar curve spontaneously corrects to balance the thoracic curve when selective thoracic fusion is performed and the lower level of fusion is properly selected. In Type-III, IV, and V thoracic curves the lower level of fusion should be centered over the sacrum to achieve a balanced, stable spine.

Harrington instrumentation and spine fusion for unstable fractures and fracture-dislocations of the thoracic and lumbar spine.

Of forty patients with unstable fractures and fracture-dislocations of the thoracic or lumbar spine treated with Harrington instrumentation and spine fusion, thirty-five had a neural deficit (twenty-three with incomplete or cauda equina lesions and twelve with complete lesions). Laminectomy or posterolateral decompression was performed prior to instrumentation and fusion in twenty-three patients and at the time of stabilization, in thirteen. Solid fusion was obtained in all but one patient. Back pain persisted in four. No patient had residual spinal deformity. Twenty-one patients with incomplete or cauda equina lesions regained some neural function, while all twelve with complete lesions remained unchanged. The advantages of this technique include effective stabilization of the spine, early mobilization and rehabilitation, and prevention of late deformity.