Paul K. Jones

Radiculopathy and Myelopathy at Segments Adjacent to the Site of a Previous Anterior Cervical Arthrodesis

BACKGROUND We studied the incidence, prevalence, and radiographic progression of symptomatic adjacent-segment disease, which we defined as the development of new radiculopathy or myelopathy referable to a motion segment adjacent to the site of a previous anterior arthrodesis of the cervical spine. METHODS A consecutive series of 374 patients who had a total of 409 anterior cervical arthrodeses for the treatment of cervical spondylosis with radiculopathy or myelopathy, or both, were followed for a maximum of twenty-one years after the operation. The annual incidence of symptomatic adjacent-segment disease was defined as the percentage of patients who had been disease-free at the start of a given year of follow-up in whom new disease developed during that year. The prevalence was defined as the percentage of all patients in whom symptomatic adjacent-segment disease developed within a given period of follow-up. The natural history of the disease was predicted with use of a Kaplan-Meier survivorship analysis. The hypothesis that new disease at an adjacent level is more likely to develop following a multilevel arthrodesis than it is following a single-level arthrodesis was tested with logistic regression. RESULTS Symptomatic adjacent-segment disease occurred at a relatively constant incidence of 2.9 percent per year (range, 0.0 to 4.8 percent per year) during the ten years after the operation. Survivorship analysis predicted that 25.6 percent of the patients (95 percent confidence interval, 20 to 32 percent) who had an anterior cervical arthrodesis would have new disease at an adjacent level within ten years after the operation. There were highly significant differences among the motion segments with regard to the likelihood of symptomatic adjacent-segment disease (p<0.0001); the greatest risk was at the interspaces between the fifth and sixth and between the sixth and seventh cervical vertebrae. Contrary to our hypothesis, we found that the risk of new disease at an adjacent level was significantly lower following a multilevel arthrodesis than it was following a single-level arthrodesis (p<0.001). More than two-thirds of all patients in whom the new disease developed had failure of nonoperative management and needed additional operative procedures. CONCLUSIONS Symptomatic adjacent-segment disease may affect more than one-fourth of all patients within ten years after an anterior cervical arthrodesis. A single-level arthrodesis involving the fifth or sixth cervical vertebra and preexisting radiographic evidence of degeneration at adjacent levels appear to be the greatest risk factors for new disease. Therefore, we believe that all degenerated segments causing radiculopathy or myelopathy should be included in an anterior cervical arthrodesis. Although our findings suggest that symptomatic adjacent-segment disease is the result of progressive spondylosis, patients should be informed of the substantial possibility that new disease will develop at an adjacent level over the long term.

Mitochondrial Abnormalities in Alzheimer's Disease

Mitochondria from persons with Alzheimers disease (AD) differ from those of age-matched control subjects. Differences in mitochondrial morphology and function are well documented, and are not brain-limited. Some of these differences are present during all stages of AD, and are even seen in individuals who are without AD symptoms and signs but who have an increased risk of developing AD. This chapter considers the status of mitochondria in AD subjects, the potential basis for AD subject mitochondrial perturbations, and the implications of these perturbations. Data from multiple lines of investigation, including epidemiologic, biochemical, molecular, and cytoplasmic hybrid studies, are reviewed. The possibility that mitochondria could potentially constitute a reasonable AD therapeutic target is discussed, as are several potential mitochondrial medicine treatment strategies.

Anterior Cervical Decompression and Arthrodesis for the Treatment of Cervical Spondylotic Myelopathy. Two to Seventeen-Year Follow-up*

We reviewed the cases of 108 patients with cervical spondylotic myelopathy who had been managed with anterior decompression and arthrodesis at our institution. Operative treatment consisted of anterior discectomy, partial corpectomy, or subtotal corpectomy at one level or more, followed by placement of autogenous bone graft from the iliac crest or the fibula. At the latest follow-up examination, thirty-eight of the eighty-two patients who had had a preoperative gait abnormality had a normal gait, thirty-three had an improvement in gait, six had no change, four had improvement and later deterioration, and one had a worse gait abnormality. Of the eighty-seven patients who had had a preoperative motor deficit, fifty-four had complete recovery; twenty-six, partial recovery; six, no change; and one had a worse deficit. The average grade according to the system of Nurick improved from 2.4 preoperatively to 1.2 (range, 0.0 to 5.0) postoperatively. A pseudarthrosis developed in sixteen patients, thirteen of whom had had a multilevel discectomy. Only one of thirty-eight arthrodeses that had been performed with use of a fibular strut graft was followed by a non-union. An unsatisfactory outcome with respect to pain was significantly associated with pseudarthrosis (p < 0.001). The development of complications other than non-union was associated with a history of one previous operative procedure or more (p = 0.005). Recurrent myelopathy was rare, but when it occurred it was associated with a pseudarthrosis or stenosis at a new level. The strongest predictive factor for recovery from myelopathy was the severity of the myelopathy before the operative intervention—that is, better preoperative neurological function was associated with a better neurological outcome. Anterior decompression and arthrodesis with autogenous bone-grafting can be performed safely, and is associated with a high rate of neurological recovery, functional improvement, and pain relief, in patients who have cervical spondylotic myelopathy.

Impaired cell-mediated immunity in patients with classic hemophilia

THREE cases of Pneumocystis carinii pneumonia, two of which were fatal, have recently been observed in patients with severe classic hemophilia who had been treated with lyophilized preparations of ...

Microtubule Reduction in Alzheimer's Disease and Aging Is Independent of τ Filament Formation

Biochemical studies show that phosphorylated tau, like that found in paired helical filaments (PHFs), does not promote microtubule assembly leading to the view that PHF formation leads to microtubule deficiency in Alzheimers disease (AD). However, although this issue is one of the most important aspects to further understanding the cell biology of AD, no quantitative examination of microtubule diminution in AD and its relationship with PHFs has been performed. To examine this issue directly, we undertook a morphometric study of brain biopsy specimens from AD and control cases. Ultrastructural analysis of neurons was performed to compare the microtubule assembly state in neurons of diseased and control cases and to examine the effect of PHF accumulation. We found that both number and total length of microtubules were significantly and selectively reduced in pyramidal neurons from AD in comparison to control cases (P = 0.000004) but that this decrement in microtubule density was surprisingly unrelated to PHFs (P = 0.8). Further, we found a significant age-dependent decrease in microtubule density with aging in the control cases (P = 0.016). These findings suggest that reduction in microtubule assembly is not dependent on tau abnormalities of AD and aging.

Increased incidence of thromboembolism in stage IV breast cancer patients treated with a five‐drug chemotherapy regimen

We report an incidence of thrombosis of 17.6% in 159 patients treated with a five‐drug chemotherapy regimen (cyclophosphamide, methotrexate, 5‐fluorouracil, vincristine, and prednisone) for Stage IV breast carcinoma. Chi‐squared analysis of risk factors for thrombosis (ambulatory status, obesity, family history, smoking, diabetes mellitus, hypertension, liver dysfunction, thrombocytosis, and previous endocrine therapy) showed no difference between the patients who had a thromboembolic event and those who did not. Statistical analysis revealed that a significantly higher incidence of thrombosis occurred during the chemotherapy regimen than when off this regimen (P < 0.05). Detailed coagulation studies done prospectively on 10 patients receiving the five‐drug chemotherapy regimen compared with 10 control patients showed a significantly elevated Factor VIII antigen:activity ratio in the group receiving the chemotherapy regimen compared with the control group and normals. These results implicate the chemotherapeutic regimen in the pathogenesis of the increased incidence of thrombosis. The pathophysiology of thrombosis in settings such as this awaits better in vitro tests defining the “hypercoagulable state.”

Robinson anterior cervical fusion : comparison of the standard and modified techniques

In 1990 the authors modified the Robinson anterior cervical interbody fusion technique by burring the endplates to expose subchondral bone. The authors compared 31 patients having the standard technique and 29 patients having the modified technique to evaluate 1) setting of the bone graft, 2) kyphotic angulation, 3) pseudarthrosis rate, and 4) pain outcome. In the standard Robinson fusion technique, the average loss of height across the fused segments was 0.8 mm and the average increase in kyphosis 4.9 degrees. Values for the modified technique were 1.9 mm and 3.1 degrees, respectively. The change in height was statistically significant (P = .01), as was the difference in angulation (P = .028), though the latter was in the opposite direction predicted. The pseudarthrosis rate using the modified technique decreased to 4.4% per level. Pain outcome for the two groups was equivalent. Burring of the endplates for anterior cervical interbody arthrodesis results in a detectable but not clinically important amount of graft settling with a higher success rate for arthrodesis.

Sustained personal autonomy: A measure of successful aging

Objectives: This study addresses the following question: What characteristics of urban, noninstitutionalized elders predict which individuals are most likely to remain independent of personal assistance during a 2-year observation period? Methods: A population-based sample of 602 noninstitutionalized urban residents aged 70 and older was followed for 2 years. Results: Ninety-eight of the 487 survivors remained independent. Factors associated with sustained independence were relatively younger age, male gender, fewer medical conditions, good physical function, and nonsmoking. The attitudes “favors family or self over agency assistance” and “does not expect filial obligation” were also independently associated. Discussion: The results are consistent with previous studies of successful aging and showthat attitudes expressed at baseline favoring personal independence are associated with sustained autonomy during a period of at least 2 years.

Does cost information availability reduce physician test usage? A randomized clinical trial with unexpected findings.

Four similar teams of physicians associated with similar inpatient units and randomly assigned patients were used to study the effect of providing physicians with cost information about their use of lab tests and x-rays. Two teams received information about lab test costs, and two teams received x-ray test costs. Test usage fell during the experimental conditions and continued to fall after the experimental period ended in teams in which there was an interested leader.

Bacterial polysaccharide immune globulin for prophylaxis of acute otitis media in high-risk children

We evaluated the prevention of recurrences of acute otitis media (AOM) by bacterial polysaccharide immune globulin (BPIG), a hyperimmune human immune globulin prepared by immunizing donors with bacterial polysaccharide vaccines. We used a randomized, stratified, double-blind, placebo-controlled design. Children < or = 24 months of age with 1 to 3 prior episodes of AOM received BPIG, 0.5 ml/kg, or saline placebo intramuscularly at entry and 30 days later. During the 120-day follow-up period, AOM was diagnosed by using clinical criteria and was confirmed with tympanocentesis and culture of the middle ear exudates. Eighty-eight episodes of AOM were observed in 76 patients who completed the study. The incidence of AOM during the entire 120-day study period was similar in BPIG and placebo recipients. Pneumococcal AOM was significantly less frequent in BPIG recipients (0.21 episode per patient) than in placebo recipients (0.45 episode per patient; p = 0.05). Time spent free of AOM was significantly prolonged in recipients of BPIG, in comparison with placebo recipients (51 vs 35 days; p = 0.034). This study demonstrated that circulating antibody, even without stimulation of specific local immunity, may prevent infection of the middle ear. The use of immune globulin preparations for longer periods or at a higher dosage might decrease the incidence of recurrent AOM in otitis-prone children, and deserves further evaluation.