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Biomedical subjects

S D Cook

Publications and source records attributed to S D Cook.

At least 55 records · Page 3Linked to original sources

Bone mineral density of the lumbar spine and proximal femur is decreased in children with sickle cell anemia.

Bone mineral density (BMD) was evaluated in the proximal femora (femoral neck, Ward's triangle, and greater trochanter) and lumbar spines of 25 black children and young adults with sickle cell anemia using dual-photon absorptiometry. Compared with normal subjects from the general population, the patients with sickle cell anemia exhibited lower bone mineral density values in all scan regions (approximately 6% to 21% lower than expected). These differences in the lumbar spine were significant for both girls and boys. When compared with normal black subjects from the general population, the girls with sickle cell anemia exhibited significantly lower lumbar spine bone mineral density, and the boys with sickle cell anemia exhibited significantly lower bone mineral density in the femoral neck and Ward's triangle. No consistent or significant correlations were found between the bone mineral density data and the patients' hematologic indices.

Absorptiometry, Photon↗

The effect of total lymphoid irradiation and low-dose steroids on T lymphocyte populations in multiple sclerosis: correlation with clinical and MRI status.

We have monitored the cell surface phenotypic changes occurring in T, B and NK cells of chronic progressive multiple sclerosis (MS) patients after total lymphoid irradiation (TLI) plus low-dose prednisone (TLI-LDP) therapy in comparison to sham TLI-LDP. TLI-LDP resulted in a marked reduction in the relative and absolute number of total CD3+ T cells, CD4+ helper T cells, CD4+ CD45RA+ naive T cells and CD19+ B cells for at least 1 year after treatment. No change occurred in the percent CD8+ T cells although the number of these cells declined after radiotherapy. The CD4/CD8 T cell ratio was also decreased. The relative percent of CD16+ NK cells increased steadily after TLI-LDP while the number of NK cells transiently declined but returned to baseline values 1 year later. An increase in the percent of CD2+ CD3- cells and a decrease in their number after therapy was also observed. In contrast, no significant changes in the number of T, B or NK cells were seen in the MS patients receiving sham TLI-LDP. These results provide further evidence that radiotherapy causes a reduction of immunocompetent T and B cells and that a population of possibly NK cells and/or immature T cells appears to be repopulating the circulation after TLI. In addition, a correlation was observed between alterations in lymphocyte populations and the presence or absence of contrast enhancing or new T2 lesions on brain magnetic resonance imaging (MRI) in the TLI-LDP treated MS patients. Patients devoid of contrast enhancing or new T2 lesions had a decreased percentage of CD3+ and CD4+ T cells prior to therapy and at six months following TLI-LDP compared to patients with such lesions. An association was also observed between stability in disease activity as determined on the Expanded Disability Status Scale and relative values of CD3 T cells.

Adult↗

Modified total lymphoid irradiation and low dose corticosteroids in progressive multiple sclerosis.

In a double-blind prospective randomized trial, we assessed the efficacy and safety of modified total lymphoid irradiation (TLI) plus low dose prednisone (TLI-LDP) as compared to sham TLI plus identical prednisone therapy (sham TLI-LDP) in 46 patients with progressive forms of multiple sclerosis (MS). No significant difference existed between groups at study entry in patient age, sex, duration of MS, or disability status. However, following treatment, significantly fewer TLI patients showed a sustained one point decline in the Expanded Disability Status Scale, the primary study endpoint, as compared to the sham TLI group using the Kaplan-Meier Product-limit survival analysis, (P<0.005). Risk for relapse requiring treatment with intravenous methylprednisolone was reduced by 54% in the TLI-treated group (P<0.05). Significantly fewer TLI-LDP patients had gadolinium enhancing plus new T2-weighted lesions (P=0.018) when compared to the sham group post-treatment. There was also a substantial and significant decrease in blood lymphocytes in the TLI-LDP group when compared to either pretreatment values or to sham TLI-LDP through at least 12 months post-therapy. Side effects secondary to TLI were generally mild and well-tolerated. These results further support the hypothesis that TLI and systemic immunosuppression have a beneficial effect in progressive forms of MS.

Adult↗

Acceleration of tibia and distal radius fracture healing in patients who smoke.

A low intensity ultrasound device was investigated as an accelerator of cortical and cancellous bone fracture healing in smokers and nonsmokers. Statistically significant reductions in healing time for smokers and nonsmokers were observed for tibial and distal radius fractures treated with an active ultrasound device compared with a placebo control device. The healing time for a tibial fracture was reduced 41% in smokers and 26% in nonsmokers with the active ultrasound device. Similarly, distal radius fracture healing time was reduced by 51% in smokers and 34% in nonsmokers with the active device. Treatment with the active ultrasound device also substantially reduced the incidence of tibial delayed unions in smokers and nonsmokers. The use of the active ultrasound device accelerates cortical and cancellous bone fracture healing, substantially mitigates the delayed healing effects of smoking, speeds the return to normal activity, and reduces the long-term complication of delayed union.

Adult↗

Multiple sclerosis in India: a case-control study of environmental exposures.

OBJECTIVES: To compare the rate of prior environmental exposures between Indian multiple sclerosis (MS) patients and controls in order to identify potential disease triggering factors. MATERIAL AND METHODS: A standard self-administered questionnaire regarding prior exposures was presented to 56 Indian MS patients and 147 other neural disease and healthy controls at two large medical centers in India. RESULTS: The rate of prior foreign travel, surgeries, blood transfusions, clinical chicken pox and mumps infections and exposure to cats and farm animals was not significantly different between MS patients and controls. However, clinical measles infection and dog exposure occurred significantly more often in the MS patients. CONCLUSION: These findings are consistent with but do not prove an association between prior measles infection, dog exposure and MS.

Adult↗

Serum sAPO-1/Fas levels in multiple sclerosis.

UNLABELLED: Soluble APO-1 (sAPO-1) may prevent apoptosis of lymphocytes induced by activation of the APO-1/Fas receptor. OBJECTIVES: To determine sAPO-1 levels in the serum of multiple sclerosis (MS) patients and controls in order to investigate if abnormal lymphocyte apoptosis occurs in this disease. METHODS: Serum samples from patients with MS, other neurological diseases, systemic lupus erythematosus and healthy controls were determined by enzyme-linked immunosorbent assay. RESULTS: We did not detect differences in mean serum sAPO-1 levels between patients with multiple sclerosis and controls. CONCLUSIONS: This preliminary study suggests that resistance of peripheral blood lymphocytes to apoptosis mediated by sAPO-1 is not likely to be a major factor in the development of autoreactive cells in MS.

Adult↗

Nerve growth factor antibody stimulates reactivation of ocular herpes simplex virus type 1 in latently infected rabbits.

Anti-nerve growth factor (anti-NGF) antibody has been shown to induce reactivation of latent herpes simplex virus type 1 (HSV-1) in vitro. We found that systemically administered anti-NGF induces ocular shedding of HSV-1 in vivo in rabbits harboring latent virus. Rabbits in which HSV-1 latency had been established were given intravenous injections of goat anti-NGF serum daily for 10 days beginning 42 days after primary viral infection. Tears were assayed for virus for 12 days beginning on the day of the first injection. All eight rabbits given high titer anti-NGF had infectious virus in their tears at least once during the 12-day period. Fifteen of 16 eyes were positive and the average duration of viral shedding for these eyes was 4.0 days. Latently infected rabbits receiving daily injections of nonimmune goat serum or saline for 10 consecutive days were controls. Only six of the 16 (38%) eyes from rabbits receiving nonimmune goat serum shed virus. Only one of 12 eyes from untreated rabbits shed virus. Sera from control rabbits had no detectable anti-NGF activity; titers in anti-NGF-treated rabbits ranged between 1:1000 and 1:10,000. NGF deprivation may act as a neuronal stressor and may share a common second messenger pathway with heat- or cold-stress induced reactivation of latent HSV-1.

Animals↗

Blood flow to the immature hip. Ultrasonic measurements in pigs.

We quantitatively analyzed blood flow through the major arteries supplying the pig's femoral head during various hip positions and following ligation of various vessels in order to identify the vascular abnormalities which may be responsible for the development of avascular necrosis during the treatment of developmental dysplasia of the hip. Our findings reveal that a decrease in total blood flow to the femoral head occurs when the hip is held in the frog leg position with ligation of the deep femoral artery and proximal ligation of the lateral femoral circumflex artery, and ligation of the deep femoral artery, together with the lateral femoral circumflex artery proximally. In contrast, neither distal ligation of the medial femoral circumflex artery nor lateral femoral circumflex artery alone nor holding the hip in the Lange position caused a statistically significant decrease in total flow. We also observed a unique steal effect on total proximal femoral blood flow, with the hip held in the frog leg position. In 4 of 7 pigs, we found a reversal of flow in the medial femoral circumflex artery.

Animals↗

A new in vivo method for the direct measurement of nutrient artery blood flow.

A new method of directly measuring nutrient artery blood flow using ultrasonic probes is described. These probes have provided reproducible results in our experiments. Advantages of ultrasonic probes include the direct measurement of blood flow through small arteries, ease of use, accuracy of measurement, applicability to a wide range of vessel diameters, the capability of chronically monitoring blood flow over time using permanently implanted probes, and the ability to use the method in conjunction with previous methods of bone blood flow measurement. The method is limited to the extent that only the contribution of the nutrient artery can be measured and total bone blood flow cannot be assessed. Tibial nutrient arterial flow and cardiac output were measured in adult mongrel dogs. Two experiments were performed: 1) bilateral baseline tibial nutrient artery blood flow measurements over time and 2) tibial nutrient blood flow comparing inhaled anesthesia (halothane/nitrous oxide/oxygen) and intravenous anesthesia (pentobarbital [Nembutal]). In 15 mongrel dogs, tibial nutrient artery blood flow averaged 1.46 +/- 0.72 mL/min (0.09 +/- 0.05 percent of cardiac output and 2.75 +/- 1.95 mL/min/100 g of bone). No significant difference in tibial nutrient artery blood flow was observed between animals given intravenous and inhaled anesthesia (P > .05). As a basic research tool, transit-time ultrasonic blood flow technology may be useful. The method is relatively easy to use and may be applied to experimental models designed to investigate various physiologic and pathologic states frequently encountered in orthopedics (eg, shock, sepsis, fractures).

Adjuvants, Anesthesia↗

Expiratory training in multiple sclerosis.

OBJECTIVE: To compare the effects of expiratory muscle training and sham training on respiratory muscle strength in patients with multiple sclerosis (MS). DESIGN: A randomized control trial; subjects were randomly assigned to either expiratory muscle training or sham training. SETTING: Training and measurement of respiratory muscle pressures were conducted in patients' homes. Weekly home visits were conducted to assure compliance with the training protocols and to obtain measurements. PATIENTS: Twenty subjects with clinically definite MS and decreased expiratory muscle strength entered the study; 10 subjects completed 3 months of expiratory training using a threshold training device and 5 subjects completed 3 months of sham training using the same device but without an expiratory training threshold load. MEASUREMENT: Respiratory muscle strength was assessed at baseline and after 1, 2, and 3 months of training; maximal inspiratory and expiratory pressures were used as measures of respiratory muscle strength. RESULTS: There was a significant increase in expiratory muscle strength after 3 months of training when the expiratory training group was compared to the sham group (p = .003); no significant change in inspiratory muscle strength was observed. CONCLUSIONS: The results of this pilot study suggest that the strength of the expiratory muscles of persons with MS can be increased through respiratory muscle training targeted to the expiratory muscles. Further research is indicated to determine if increasing the strength of the expiratory muscles in MS has an effect on clinical outcomes in this patient population.

Adolescent↗

Topographic analysis in pellucid marginal corneal degeneration and keratoglobus.

Pellucid marginal corneal degeneration (PMCD) is an uncommon cause of inferior peripheral corneal ectasia, affecting patients between the ages of 20 and 40 years. Although histopathologically it is considered a variant of keratoconus, it differs in that the marked corneal steepening occurs more inferiorly, above a narrow band of corneal stromal thinning concentric to the inferior limbus. Here we present two cases. The first case is a clinically typical bilateral PMCD with a characteristic pattern of irregular against-the-rule astigmatism on corneal topography. The second case had an uncommon presentation of hydrops in a clinically keratoglobic eye which showed a marked steepening of the inferior corneal periphery on corneal topography. The other eye showed both clinically and topographically the features of PMCD. Corneal topography suggested that in the second patient, PMCD may have preceded the development of keratoglobus. Keratoconus, PMCD and keratoglobus are considered to be associated as part of the spectrum of non-inflammatory corneal thinning disorders. However, although the finding of PMCD and keratoconus in fellow eyes has been reported, to the best of our knowledge progression from PMCD to keratoglobus has not previously been shown.

Corneal Diseases↗

Comparison between multiple sclerosis in India and the United States: a case-control study.

The prevalence of MS in India is low, and it is unclear whether the manifestations of the disease in India are similar to the United States. We carried out a case-control study to compare the disease in the two populations and used clinical, evoked potential, and MRI criteria to assess similarities and differences. Our results indicate that the rate of disease progression and frequency of involvement of the cerebral hemispheres, cerebellum, spinal cord, and brainstem were similar in the two populations. The visual system was more frequently involved in Indian patients. No Indian patient had a family history of MS; this suggests an environmental disease-triggering agent.

Adult↗

Osteogenic protein-1: biology and applications.

Osteogenic proteins, also referred to as BMPs, are a family of bone matrix polypeptides isolated from a variety of mammalian species. These proteins are members of the transforming growth factor-beta superfamily of molecules that contain a highly conserved 7 cysteine transforming growth factor-beta domain in their C-termini. Use of recombinantly produced human osteogenic protein-1, also referred to as BMP-7, implanted in conjunction with bovine bone derived Type 1 collagen or various non-proteinaceous biodegradable carriers into surgically created large diaphyseal segmental defects in animals leads to the regeneration of new bone that is fully functional biologically and biomechanically. Further study has shown that osteogenic protein-1 can be used as a bone graft substitute to promote spinal fusion and to aid in the incorporation of metal implants. Finally, osteogenic protein-1 shows promise as an agent for repair of osteochondral defects.

Amino Acid Sequence↗

Spinocerebellar degeneration and cerebral hypomyelination in a family.

The proband is a 24-year-old woman who developed symptoms of a spinocerebellar degeneration in early childhood. Neurological examination revealed normal cognitive function, optic atrophy, dysarthria, titubation, action tremors, increased deep tendon reflexes, Babinski's signs, and a spastic scissoring gait. The magnetic resonance imaging (MRI) showed an abnormal increased signal on long TR images involving white matter throughout the cerebral hemispheres, most striking in the subcortical white matter, and to a lesser degree in the brainstem, compatible with diffuse hypomyelinating or dysmyelinating diseases. Metabolic and chromosomal studies were normal. Her 49-year-old mother developed similar symptoms in her 20s and is now wheelchair-bound. Findings on neurological examination and MRI were similar to her daughter but more severe. The proband's maternal grandfather had a female cousin who had a neurological illness beginning in her 20s with similar symptoms and signs and died at the age of 44 years. Spinocerebellar degenerations are a group of syndromes with similar clinical manifestations but heterogeneous etiology. We report a family with spinocerebellar degeneration with distinct MRI findings compatible with hypomyelination or dysmyelination which has not heretofore been described. This family may represent a new spinocerebellar syndrome due to an abnormality of as yet an undetermined gene.

Adult↗

Simian immunodeficiency virus (human HIV-II) transmission in allograft bone procedures.

STUDY DESIGN: Infection of rhesus monkeys (Macaca mulatta) with simian immunodeficiency virus (SIV, HIV-II) was used to study disease transmission in allograft bone. Four allograft bone processing techniques--fresh, fresh frozen, double freeze-thaw, and double freeze-thaw with chemical decontamination--were evaluated. OBJECTIVES: To determine if SIV could be transmitted in allograft bone and if processing techniques could be used to eliminate the potential for disease transmission. SUMMARY OF BACKGROUND DATA: Although the risk of HIV transmission in bone allograft was reported to be low, HIV transmission had occurred. In all cases, frozen allograft was used. Donor screening and serologic testing significantly reduced the risk of transmission, although a window of time existed in which an individual was infected but had not seroconverted. Experimental infection of rhesus monkeys with SIV induced a disease syndrome similar to AIDS and provided an ideal model to study disease transmission. METHODS: Corticocancellous cylinders were obtained aseptically from SIV-infected rhesus monkeys. The grafts were randomly placed into one of four processing groups and implanted into noninfected animals. The presence of SIV antibody was monitored by serologic testing. After the monkeys were killed, the graft sites were studied by histology. RESULTS: All animals receiving fresh allograft or allograft bone that had been subjected to either single or double -70 C freeze-thaw cycles became infected with SIV. Animals receiving allograft that had been subjected to a double freeze-thaw cycle and chemical decontamination were disease-free after 26 weeks when the animals were killed. CONCLUSIONS: The results show that SIV (HIV-II) can be transmitted in bone allograft procedures. Although freeze-thaw cycles and lavaging to remove blood elements can reduce the infectivity of a graft, it appears chemical decontamination is necessary to provide a high level of confidence in its safety.

Animals↗

In vivo evaluation of demineralized bone matrix as a bone graft substitute for posterior spinal fusion.

STUDY DESIGN: Posterior lumbar spinal fusion segments were evaluated in 9 adult mongrel dogs 6, 12, and 26 weeks after implantation. Four sites on each animal received implants consisting of demineralized bone matrix alone, demineralized bone matrix with allograft bone, allograft bone alone, and autograft bone. Each unilateral fusion spanned one motion segment with one intervening vertebral level left undisturbed using T13-L7. The fusions were evaluated radiographically, mechanically, and histologically. OBJECTIVE: The purpose of this study was to determine the efficacy of demineralized bone matrix as a bone graft substitute for stable posterior spinal fusion. SUMMARY OF BACKGROUND DATA: Posterior spinal fusion is a procedure commonly performed for spinal stabilization. Increasing the incidence and speed of stable spinal fusion is a primary goal in spinal surgery. Concerns have developed regarding the graft material used to induce bone healing at the fusion site. The advent of osteoinductive materials, such as demineralized bone matrix, may eliminate the need to harvest autograft bone and may circumvent the immunologic response and lower osteogenic potential associated with allograft bone. METHODS: The quality of fusion and new bone formation was evaluated radiographically using plain films, computed tomography, and magnetic resonance imaging. After the dogs were killed, each fusion segment was evaluated mechanically in torsion to determine stiffness and histologically to determine qualitative parameters of new bone formation and remodeling. RESULTS: Radiographic studies showed that autograft bone sites achieved stable fusion by 26 weeks after surgery. Conversely, the demineralized bone matrix alone and with allograft bone demonstrated some new bone formation at 6 and 12 weeks, but did not achieve fusion by 26 weeks. The fusion sites of allograft bone alone showed minimal new bone formation at all time periods. Mechanically, the autograft fusion sites demonstrated torsional stability that was significantly greater than that of all other fusion sites at all time periods. The remaining fusion sites showed equivalent torsional stiffness at all time periods. Histologic analysis confirmed the radiographic and mechanical findings. CONCLUSIONS: The results indicate that demineralized bone matrix alone or with allograft bone is ineffective in achieving stable posterior spinal fusions.

Animals↗