PubMed HealthSearch

Biomedical subjects

R D Fraser

Publications and source records attributed to R D Fraser.

At least 19 recordsLinked to original sources

Economic impact of HIV infection and coronary heart disease in immigrants to Canada.

OBJECTIVE: To compare the direct health care costs of illnesses associated with the human immunodeficiency virus (HIV) and of coronary heart disease (CHD) in immigrants to Canada. DESIGN: Comparative cost analysis. PARTICIPANTS: All people who immigrated to Canada in 1988. The numbers with HIV infection and CHD were estimated from country-specific HIV seroprevalence data and national CHD mortality statistics and data from the Framingham study. Health care costs, projected over the 10 years after immigration, were calculated on the basis of data from the Hospital Medical Records Institute and provincial fee schedules. RESULTS: Of the 161,929 immigrants in 1988, 484 were estimated to be HIV positive. The total cost of treatment of HIV-related illnesses from 1989 to 1998 (discounted at 3%) would be $18.5 million: $17.1 million would be spent on the outpatient and inpatient care of the HIV-positive immigrants, $1.0 million on care of the subsequently infected sexual partners and $0.4 million on care of the HIV-positive children born to seropositive immigrant women. In comparison, CHD would develop in 2558 immigrants during the same 10-year period. The total CHD costs would be $21.6 million: $8.4 million would be spent on treating myocardial infarction, $3.2 million on coronary artery bypass grafting, $1.6 million on pacemaker insertion and $8.4 million on treating other CHD events. CONCLUSIONS: The economic impact of HIV infection in immigrants to Canada is similar to that of CHD. This comparison identifies an important shortcoming in current immigration policy: economic considerations can be arbitrarily applied to certain diseases, thereby discriminating against specific groups of immigrants.

Adult

A longitudinal study of the matrix changes induced in the intervertebral disc by surgical damage to the annulus fibrosus.

A 5 x 5-mm anterolateral incision was made in the annulus fibrosus (AF) of lumbar discs of 16 sheep; four animals of similar age not operated on were used as controls. The experimental animals were sacrificed 2, 4, 6, 8, 12, and 18 months postoperatively (PO), and the incised and adjacent lumbar discs were collected. Discs were dissected into four zones: AF (zones 1 and 2) and nucleus pulposus (NP) (zones 3 and 4) corresponding to the half of the AF in which the cut was made and its opposite half, and the complementary halves of the NP. Each zone was analyzed for moisture, proteoglycan (PG), collagen, and noncollagenous protein (NCP) content. The PG extractability, aggregation, and hydrodynamic size were also examined. The NP of injured discs showed a significant loss of PGs and collagen 8 months PO, but NCP levels increased. In the incised discs, PG aggregation initially declined but recovered to within control values 6-8 months PO. The NP of discs adjacent to the incised disc also showed time-dependent changes in matrix components that included loss of collagen and PG; however, the AF matrix remained essentially uneffected. Double immunodiffusion studies indicated that a sizeable proportion of the NCPs present in the injured discs (but not the adjacent lumbar discs) were derived from serum.

Animals

Role of the capsulo-ligamentous structures in rotation and combined flexion-rotation of the lumbar spine.

We carried out experiments on whole cadaveric lumbar spines in order to determine the role that each of the capsulo-ligamentous structures play in axial rotation in the neutral position and in the flexed position. Eight specimens were first tested intact, then after division of all the apophyseal joint capsules between L1 and the sacrum. Another five specimens were also first tested intact, then after division of the supra- and interspinous ligaments and yellow ligament, and finally after cutting the posterior longitudinal ligament and posterior annulus at each level as well. The results show that there is considerable variation in the axial rotation of the lumbar vertebrae within the same spine and across different spines. The apophyseal joint capsules limit rotation both in neutral and flexed positions. In flexion, the amplitude of rotation in the lumbar spine is reduced. Of the capsulo-ligamentous structures, it is the posterior annulus and the posterior longitudinal ligament that seem to play the more important role in limiting axial rotation while the spine is flexed.

Adult

Assessment of outcome in patients with low-back pain.

The Low-Back Outcome Score has been devised as a new and accurate rating system for patients with low-back pain. Thirteen factors, such as pain, employment, sporting ability, rest required, and activities of daily living, were included; subjective opinion was excluded. Pain and active pursuits were weighted. Presentation of the score as a questionnaire, excluding examination findings, eliminated both interobserver variation and observer variation with time. The score was applied retrospectively in a follow-up study of conservatively treated patients and was found to be more comprehensive and more discriminating than the Oswestry Disability Score, the Waddell Disability Rating, or the Waddell Physical Impairment Rating. The Low-Back Outcome Score is recommended for further evaluation in future prospective studies in low-back pain.

Back Pain

Chymopapain. A 10-year, double-blind study.

Sixty patients with sciatica from lumbar intervertebral disc herniation were entered into a double-blind study. Following a randomized schedule, 30 patients were treated with intradiscal chymopapain and 30 patients with intradiscal normal saline. At 10 years, with the patients still unaware of the treatment given, 80% of the chymopapain patients regarded the injection to be successful, compared with 34% for the saline group (P = 0.0006). Laminectomy was required in 20% of the chymopapain patients, compared with 47% of the saline patients (P = 0.028). Seventy-seven percent of the chymopapain group was assessed by a blinded independent observer to be at least moderately improved, compared with 38% for the saline group (P = 0.004). The results of this double-blind study at 10 years demonstrate a sustained therapeutic effect of chymopapain in the treatment of patients with sciatica from lumbar intervertebral disc prolapse.

Adult

Changes in endplate vascularity after an outer anulus tear in the sheep.

In 31 2-year-old sheep, a 5-mm deep cut was made parallel to the end plates in the left anterolateral anulus fibrosus of 3 randomly selected lumbar intervertebral discs. At 2 months, the area of the end plate occupied by blood vessels on the left (operated) side had increased significantly (P less than 0.05) in the cranial end plate to 9.94%, and to 9.39% in the caudal end plate, compared with nonoperated values of 5.17% (cranial) and 5.87% (caudal). One year after operation, these elevated values had diminished significantly (P less than 0.05) to 7.92% (cranial) and 7.13% (caudal), and continued to decline progressively to 7.48% (cranial) and 6.88% (caudal) by 2 years. In contrast, no significant differences were found on the right (nonoperated) side of the discs. Thus, there was an early proliferation of vascular channels in the end plate in the vicinity of the experimental anular lesion, but not on the nonoperated side of the same disc. Thereafter, the end plate vascularity progressively diminished toward a normal level.

Animals

A modified muscle-splitting approach to the lumbosacral spine.

A modification of a previously reported extraperitoneal approach to the lumbosacral spine is described. The external oblique muscle is split in line with its fibers. The anterior and posterior layers of the rectus sheath are divided vertically medial to the semilunaris without splitting the internal oblique and underlying transversalis abdominus muscles. This allows an extensile retroperitoneal approach suitable for exposure of both the mid-lumbar and lumbosacral spine. There have been no complications of this approach with its use in over 50 patients undergoing anterior lumbar interbody fusion.

Abdominal Muscles

MRI and discography of annular tears and intervertebral disc degeneration. A prospective clinical comparison.

We attempted to correlate the findings of MRI and discography in patients with low back pain, examining 108 lumbar intervertebral discs in 33 consecutive patients. MRI results were assessed from the intensity and shape of the signal obtained from the central part of the disc. Discography was classified according to the pattern of contrast material, the pressure accepted and the pain reproduced. All discs which were abnormal on MRI had altered patterns on discography, but 18 of the 60 discs with normal MRI had abnormal discograms. Of 39 asymptomatic discs, 33 had normal MRI signals and 24 had normal discograms. None of the 15 discs showing severe degeneration on MRI sustained high levels of intradiscal pressure, but only six of the 60 discs giving normal MRI had low pressure. With current techniques, discography is more accurate than MRI for the detection of annular pathology: a normal MRI does not exclude significant changes in the peripheral structure of the intervertebral disc which can produce low back pain.

Adult

Annular tears and disc degeneration in the lumbar spine. A post-mortem study of 135 discs.

We studied 135 lumbar discs from 27 spines removed post-mortem from subjects of an average age of 31.5 years. Defects of the annulus fibrosus were classified as peripheral, circumferential or radiating; the nucleus pulposus as normal, moderately or severely degenerate. Peripheral tears were more frequent in the anterior annulus, except in the L5-S1 disc. Circumferential tears were equally distributed between the anterior and the posterior annulus. Almost all the radiating tears were in the posterior annulus, and closely related to the presence of severe nuclear degeneration. Histology suggested that peripheral tears were due to trauma rather than biochemical degradation, and that they developed independently of nuclear degeneration. The association of peripheral annular lesions with low back pain is uncertain but our study suggests that they may have a role in the pathogenesis of discogenic pain.

Adolescent

Radiologic interpretation of lumbar vertebral rotation.

The different parts of the lumbar pedicle were identified on an anteroposterior (AP) radiograph to determine reliable reference points to be used to quantify vertebral rotation. Standard AP radiographs were taken of dry lumbar vertebrae with 5 degrees increments in rotation in the transverse plane, ranging from 0 degrees to 30 degrees both to left and right. Identical sets of radiographs were taken with radiopaque markers around the middle and in the anterior and posterior parts of the pedicles. The anatomic center of the pedicle was found to lie slightly more lateral than the center of the pedicle halo. The inferior edge of the pedicle corresponded with the anterior part of the pedicle and the superior edge, with the posterior part.

Humans

Comparison of eight psychometric instruments in unselected patients with back pain.

A comparative evaluation of eight psychometric instruments was made in 274 patients who were currently suffering or previously had suffered from low-back pain. The specificity and sensitivity values for detection of psychological disturbance were calculated and optimum cutoff scores determined for each test. The influence of current pain, social group, compensation, migrant status, and unemployment on the accuracy of each test were evaluated. The Pain Drawing, the Inappropriate Symptoms, the Inappropriate Signs, and the Illness Behavior Questionnaire were found to be least discriminating. The Modified Somatic Perception Questionnaire, the Hospital Anxiety Scale, the Hospital Depression Scale, and the Zung Depression Scale were the most accurate and least affected by the factors examined. The combination of the Modified Somatic Perception Questionnaire and the Zung Depression Scale yielded specificities and sensitivities of 91% and 84% for men and 96% and 85% for women, respectively. This combination is recommended for the assessment of psychological disturbance in patients with low-back pain.

Back Pain

HIV antibody screening among immigrants: a cost-benefit analysis.

To assess the economic impact of HIV (human immunodeficiency virus) antibody screening among potential immigrants on Canada's health care system we estimated the costs and benefits of such screening among the 160 135 immigrants who entered Canada in 1988 using the in-hospital costs of treating AIDS (acquired immune deficiency syndrome) over the 10 years after immigration. This economic model was based on current international HIV seroprevalence data, Canadian immigration statistics and estimates of disease progression. Between 343 and 862 of the immigrants were estimated to have been HIV seropositive; with the use of the enzyme-linked immunosorbent assay and the Western blot technique 310 to 780 of them would have been correctly identified as being seropositive, and 33 to 82 would have been incorrectly classified as being seronegative. Another 16 would have been falsely classified as being seropositive. There would have been 151 to 379 cases of AIDS from 1988 to 1998 among the immigrants identified as being HIV-positive. The estimated total cost of screening would have been $3.3 to $3.4 million. The in-hospital costs of treating HIV-infected immigrants in whom AIDS developed between 1989 and 1998 would have been $5.0 to $17.1 million. Accordingly, screening would have saved $1.7 to $13.7 million over the 10 years after immigration. However, we do not advocate screening on the basis of economic analysis alone and acknowledge that any policy regarding such screening must also incorporate social, legal and ethical considerations.

Acquired Immunodeficiency Syndrome

1990 Volvo Award in experimental studies. Anulus tears and intervertebral disc degeneration. An experimental study using an animal model.

An animal model was developed to test the hypothesis that discrete peripheral tears within the anulus lead to secondary degenerative changes in other disc components. In 21 adult sheep, a cut was made in the left anterolateral anulus of three randomly selected lumbar discs. The cut was parallel and adjacent to the inferior end-plate, and had a controlled depth of 5 mm. This left the inner third of the anulus and the nucleus pulposus intact and closely reproduced the rim Lear lesion described by Schmorl. Animals were randomly allocated to different groups in relation to the length of time interval between operation and death, varying from 1 to 18 months. At death, the lumbar spine was cut into individual joint units and each disc sectioned into six parasagittal slabs. After observation of the slabs under the dissecting microscope, two of the six slabs, the one containing the anulus lesion and a contralateral, were processed for histology. The results of this study suggest that, despite the great care taken at operation to ensure that the inner anulus was left intact, progressive failure of the inner anulus was seen in all sheep and occurred in the majority of discs between 4 and 12 months after the operation. Although the outermost anulus showed the ability to heal, the defect induced by the cut led initially to deformation and bulging of the collagen bundles, and eventually to inner extension of the tear and complete failure. These findings suggest that discrete tears of the outer anulus may have a role in the formation of concentric clefts and in accelerating the development of radiating clefts. Peripheral tears of the anulus fibrosus therefore may play an important role in the degeneration of the intervertebral joint complex.

Animals

Molecular structure of the cell-attachment protein of reovirus: correlation of computer-processed electron micrographs with sequence-based predictions.

The receptor-recognition interaction that initiates reovirus infection is mediated by the sigma 1 protein, located at the vertices of the icosahedral virion. We have applied computer-based image-averaging techniques to electron micrographs of negatively stained preparations of sigma 1 purified from virions (serotype 2 Jones). Combining these results with inferences based on the amino acid sequence has led to a molecular model in which the overall folding of the chains is described; its conformation embodies motifs, coiled-coil alpha-helices and nodular multichain elements rich in beta-sheets, previously detected in the corresponding proteins of other viruses, but with some novel variations. Sigma 1 is a filamentous lollipop-shaped molecule with an overall length of approximately 48 nm; it has a flexible "tail," approximately 40 nm long by 4 to 6 nm wide, terminating at its distal end in a globular "head," approximately 9.5 nm in diameter. The purified protein is a tetramer (4 by 50 kilodaltons) consisting of two similarly oriented dimers bonded side by side and in register. For each chain, a cluster of hydrophobic residues at its amino terminus resides at the proximal end of the tail; next, an alpha-helical domain (residues 25 to 172) participates in a two-chained coiled coil, 22 nm long, with two such coiled coils pairing laterally to form the proximal half of the tail. The remainder of the tail (residues 173 to approximately 316) is less uniform in width and is expected to be rich in beta-sheet; the interdimer bonding is evidently sustained through this portion of the molecule. Finally, the globular head consists of the carboxy-terminal domains (which contain the receptor-binding sites) folded into compact globular conformations; in appropriate side views, the head is resolved into two subunits, presumably contributed by the respective dimers. This model for how the four sigma 1 polypeptide chains are threaded in parallel through the fiber is supported by the observed match between an empirical curvature profile, which identifies the locations of relatively flexible sites along the tail, and the flexibility profile predicted on the basis of the model. Appraisal of the interactions that stabilize the coiled coils suggests that (i) the alpha-helices are individually only marginally stable, a property that may be of significance with regard to the retracted conformation in which sigma 1 is accommodated in the intact virion, and (ii) the predominant interactions between the two coiled coils are likely to involve hydrogen bonding between patches of uncharged residues.

Amino Acid Sequence

Discitis after discography. The role of prophylactic antibiotics.

Discitis after discography is due to bacterial penetration into the intervertebral disc by a contaminated needle and has an incidence of 1% to 4%. We have examined the prophylactic role of cephazolin administered at the time of discography. An experimental study in sheep using radiographic contrast containing Staphylococcus epidermidis showed that either adding the antibiotic to the intradiscal suspension or giving it intravenously 30 minutes before intradiscal inoculation of bacteria prevented any radiographic, macroscopic or histological signs of discitis; all the intervertebral disc cultures were negative. In a prospective clinical study of 127 consecutive patients having lumbar discography, the injected contrast contained cephazolin 1 mg per ml. None of the patients developed clinical or radiographic signs of discitis. We recommend the use of a suitable broad spectrum antibiotic in a single prophylactic dose whenever the intervertebral disc is entered.

Animals