Nutritional and hormonal control of skeletal-muscle cell growth and differentiation.
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Animal Nutritional Physiological Phenomena↗
Biomedical subjects
J M Dawson
Publications and source records attributed to J M Dawson.
A proton magnetic resonance spectroscopic study in ALS: correlation with clinical findings.
OBJECTIVE: To evaluate neuronal dysfunction in the motor region subcortical white matter in ALS using volumetric localized proton magnetic resonance spectroscopy (1H-MRS). METHODS: Sixteen patients with E1 Escorial definite, probable, or possible ALS and eight healthy age-matched control subjects were studied. The ALS patients were divided into those with limb onset (n = 8) and those with bulbar onset (n = 8). Measurements of the metabolic ratios N-acetylaspartate (NAA)/creatine and phosphocreatine (Cr+PCr), NAA/choline (Cho), and Cho/(Cr+PCr) were correlated with clinical assessments. RESULTS: We found no differences in the metabolic peak area ratios in the motor region when comparing the total ALS group and the control subjects. However, correlations were found between the NAA/(Cr+PCr) ratio and the E1 Escorial category (p = 0.03), the ALS severity scale (p = 0.01), and the Medical Research Council score (p = 0.06). No correlations were found between the NAA/(Cr+PCr) ratio and the Ashworth Spasticity Scale, reflex score, or disease duration (p > 0.16). Bulbar-onset patients had a lower NAA/(Cr+PCr) ratio in the motor region compared with limb-onset patients (p = 0.03). CONCLUSION: In vivo 1H-MRS of the subcortical white matter in the motor region is unlikely to be sensitive enough to detect early disease changes in ALS because there is considerable overlap between the metabolic peak area ratios from patients with ALS and normal control subjects. However, changes in the NAA/(Cr+PCr) metabolic peak area ratios correlate with clinical measures of disease severity, and this measure may be useful in monitoring disease progression.
Adult↗
Evaluation of bovine-derived bone protein with a natural coral carrier as a bone-graft substitute in a canine segmental defect model.
The efficacy of a bone-graft substitute (bovine-derived bone protein in a carrier of natural coral) in the healing of a segmental defect of a weight-bearing long bone was evaluated. Twenty dogs, divided into two groups, underwent bilateral radial osteotomies with creation of a 2.5 cm defect. On one side of each dog, the defect was filled with autogenous cancellous bone graft. Contralateral defects received, in a blinded randomized fashion, cylindrical implants consisting of natural coral (calcium carbonate) or calcium carbonate enhanced with a standard dose of bovine-derived bone protein (3.0 mg/implant; 0.68 mg bone protein/cm3). The limbs were stabilized with external fixators, and all animals underwent monthly radiographs. They were killed at 12 (group 1) or 24 (group 2) weeks, and regenerated bone was studied by biomechanical testing and histology. Radiographic union developed in all 20 radii with autogenous cancellous bone grafts and in all 10 of the radii with the composite implants. None of the radii with implants of calcium carbonate alone showed radiographic evidence of union. This represented a statistically significant difference between implant types. In addition, calcium carbonate implants both with and without bone protein demonstrated radiographic evidence of near total resorption of the radiodense carrier by 12 weeks. This resorption facilitated radiographic evaluation of healing. Mean values for biomechanical parameters of radii with the composite implants exceeded those for the contralateral controls at 12 and 24 weeks; the difference was statistically significant at 12 weeks. Histology revealed scant residual calcium carbonate carrier at either time in the defects with calcium carbonate implants; however, a moderate amount was present in defects with the composite implants. In these specimens, the residual carrier was completely surrounded by newly formed bone that may have insulated the calcium carbonate from further degradation. The present study used a carrier of granular calcium carbonate reconstituted with bovine type-I collagen to deliver an osteoinductive protein to the defect site. This carrier is of nonhuman origin (eliminating the risk of disease transmission or antigenicity) and resorbs rapidly. In this model, bovine-derived bone protein in a natural coral carrier performed consistently better than the gold standard autogenous cancellous bone graft in terms of the amount of bone formation and strength of the healed defect. This may have implications for removal of hardware or resumption of weight-bearing in certain clinical situations. These data also indicate that coralline calcium carbonate alone represents a poor option as a bone-graft substitute in this critical-sized segmental defect model.
Animals↗
Bovine-derived bone protein as a bone graft substitute in a canine segmental defect model.
OBJECTIVES: To evaluate the efficacy of a bone graft substitute in healing of a segmental defect of a weight-bearing long bone. DESIGN: An established canine model was used to perform a blinded, prospective, randomized study of the performance of bone graft substitute implants. This performance was compared with that of an accepted treatment modality (autograft) in a paired fashion. SETTING: An accredited animal research facility. SUBJECTS AND INTERVENTION: Twenty-eight dogs underwent bilateral radial osteotomies with creation of a 2.5-centimeter defect. On one side, the defect in every dog was filled with autogenous cancellous bone graft (ABG). Contralateral defects received, in a blinded, randomized fashion, cylindrical implants of demineralized bone matrix (DBM) allograft or DBM plus a constant dose (3.0 milligrams) of bovine-derived bone protein (DBM + BP). The defects were stabilized by external fixation. Subjects underwent monthly radiographs and were killed at six, twelve, or twenty-four weeks. Regenerate bone was studied by biomechanical testing and histology. Six animals were studied to determine the dose-response characteristics of the protein preparation. Three received implants containing 0.3 milligram of BP (group 1) and three received 1.0 milligram of BP (group 2). These animals were killed at twelve weeks of follow-up. RESULTS: All twenty-eight ABG radii (100 percent) progressed to radiographic union, as did thirteen of thirteen (100 percent) DBM + BP radii compared with only four of fifteen (27 percent) of DBM radii. The difference between union rates was statistically significant (p < 0.05). Mean values for most biomechanical parameters of DBM + BP radii exceeded those of their contralateral ABG controls at twelve and twenty-four weeks, whereas those for DBM implants did not. Histology revealed microscopic evidence of normal bone healing in all ABG and DBM + BP radii, whereas most DBM radii demonstrated nonunions. In the dose-response arm of the study, six of six ABG radii (100 percent) achieved union; zero of three (0 percent) of group 1 and two of three (67 percent) of group 2 radii achieved grossly stable unions. Biomechanical testing was consistent with radiographic results, indicating that the 3.0-milligram dose was the most effective of those studied. CONCLUSIONS: The DBM + BP composite implants were more effective at healing critical-sized segmental defects than DBM alone in this canine model when a 3.0-milligram per implant dose of BP was used. Biomechanical and histologic properties of the regenerated bone formed by DBM + BP implants was comparable to that of cancellous autograft.
Animals↗
An unusual consequence of stereotactic colloid cyst aspiration: case report.
The removal of a colloid cyst of the third ventricle by stereotactic cyst aspiration is frequently performed as an alternative to a transcortical-transventricular or transcallosal operative route. A consequence of a CT-guided stereotactic aspiration, where residual colloid cyst material has been dislodged into the lateral ventricle and likened to an intraventricular mouse, is described.
Brain Diseases↗
The spinal nail: a new implant for short-segment anterior instrumentation of the thoracolumbar spine.
The biomechanics of a new spinal implant were evaluated and its dependence on an anterior strut graft was determined. Six fresh-frozen adult porcine spines were used. An L3 corpectomy was created. The spinal nail was inserted intraosseously into the middle column of the L2-L4 vertebral bodies in a trough. Implant drill holes were made for proximal and distal locking bolts in L2 and L4. A locking plate bridged the L2 and L4 trough and anchored the exposed ends of the locking bolts. Testing was performed in axial compression, torsion, and flexion. The axial and torsional stability of the spine instrumented with the spinal nail are similar to results with other devices when used with anterior strut grafting. The axial and flexural stiffnesses of the instrumented spine are independent of strut grafting. This study suggests that this device may be useful for reconstruction of the anterior spine because of instability.
Animals↗
Chromosome preparations of both direct and long-term cultures from the same fragment of chorionic villi.
A simplified method is described for processing both direct preparations and long-term cultures from the same fragment of chorionic villi. Enzyme separation of the outer trophoblast layers (used for direct preparations) from the inner mesenchymal core (used to initiate long-term cultures) facilitates the utilization of the same fragments for the two procedures, without jeopardizing the success of either method. This has proved useful in cases where the sample was so small that only one method of chromosome preparation may have been possible using other techniques.
Cells, Cultured↗
Effect of long-term electrical stimulation on vascular supply and fatigue in chronically ischemic muscles.
Fast skeletal muscles of Sprague-Dawley rats [tibialis anterior (TA) and extensor digitorum longus (EDL)] were subjected to ischemia by unilateral ligation of the common iliac artery. In some animals, ischemia was combined with indirect electrical stimulation at 10 Hz either for 3 x 2 h (strenuous activity) or for 7 x 10-min bouts/day (mild activity). After 2 wk, muscle blood flow and fatigue were measured during 5-min isometric supramaximal twitch contractions at 4 Hz. Terminal arteriole diameters were assessed in TA by intravital microscopy at rest and during contractions. Vascular perfusion pressure in the muscles was estimated from measurements in the carotid and saphenous arteries below the site of ligation. Capillary supply was expressed in TA and EDL as capillary-to-fiber ratio on the basis of histochemical staining for capillaries. Strenuous stimulation of ischemic muscles increased their atrophy, failed to restore blood flow, and actually worsened fatigue. In contrast, mild stimulation improved perfusion pressure, increased capillary-to-fiber ratio in the glycolytic part of TA, restored dilatation of terminal arterioles during muscle contractions, and improved blood flow and muscle fatigue so that they were no longer significantly different from control muscles. Thus, an attenuated intermittent protocol may be indicated in the treatment of muscle ischemia.
Animals↗
Awareness of sexual partners' HIV status as an influence upon high-risk sexual behaviour among gay men.
OBJECTIVE: To evaluate the extent to which 'high-risk' sexual behaviour is influenced by awareness of partners' HIV status among gay men. DESIGN: Structured interviews and collection of saliva samples for anonymous linked testing for HIV-1 antibodies. SETTING: Genitourinary medicine clinics and the gay community. SUBJECTS: Men (n = 677) who reported sexual contact with another man in the last 5 years. RESULTS: The majority of respondents (63%) had had an HIV-antibody test. Analysis of data showed that in 15% of the respondents' 1380 partnerships, HIV status was known by both parties. However, the majority of partnerships involved only safe sex. Only 26% of the partnerships in which unprotected penetrative anal sex had occurred involved mutual knowledge of HIV status and was most likely to occur with regular rather than non-regular/causal partners. Logistic regression revealed that this latter association could not be explained in terms of mutual HIV status knowledge. CONCLUSIONS: Despite widespread HIV testing, the majority of gay men engaging in high-risk sex are unaware of their partner's HIV status.
Adolescent↗
Biomechanical analysis of three surgical approaches for lumbar burst fractures using short-segment instrumentation.
Burst fractures of the lumbar spine that are located below the thoracolumbar junction present a challenge when operative management is indicated. Short-segment instrumentation offers the advantage of incorporating fewer motion segments in the fusion, but may not provide adequate long-term stabilization. The goal of this study was to assess the axial stiffness and torsional rigidity of several short-segment instrumentation procedures. Compressive axial stiffness and torsional rigidity were measured in six intact porcine lumbar spines (L1-L5). A corpectomy was performed to simulate a burst fracture injury and decompression. Posterior instrumentation, posterior instrumentation with an anterior strut (a wood block), and anterior instrumentation with an anterior strut one level above and one level below the fracture site were applied as treatment strategies. VSP plates (Acromed, Cleveland, OH) for posterior instrumentation and the Kaneda system (Acromed, Cleveland, OH) for anterior instrumentation were used. Load-displacement and torque-angle plots were generated and used to calculate 144 estimates of axial stiffness and 144 estimates of torsional rigidity for these constructs. These analyses showed that, in comparison with the intact spine, posterior instrumentation alone was an average of 76% less stiff axially, posterior instrumentation with an anterior strut was 3% more stiff (not significantly different from intact), and anterior instrumentation with an anterior strut was 15% more stiff. Posterior instrumentation alone was an average of 30% less rigid in torsion, posterior instrumentation with an anterior strut was 26% less rigid, and anterior instrumentation with an anterior strut was 24% less rigid than the intact spine.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
Influence of diet and beta-agonist administration on plasma concentrations of growth hormone and insulin-like growth factor-1 in young steers.
The effect of feeding grass silage or a forage-concentrate (dried grass-barley) diet ad lib. to young cattle on growth rate, plasma growth hormone (GH) and insulin-like growth factor-1 (IGF-1) concentrations was examined. The effect of including the beta-adrenergic agonist cimaterol in the forage-concentrate diet was also investigated. Significantly higher growth rates were observed in animals fed on the forage-concentrate diet than in those fed on the silage diet (P < 0.001), and these were further enhanced by dietary inclusion of cimaterol (P < 0.05). Plasma GH levels were higher in the silage-fed animals (P < 0.001) but IGF-1 levels were significantly lower (P < 0.001) than in the forage-concentrate-fed animals. Cimaterol had no effect on mean plasma GH and IGF-1 concentrations. Nevertheless, plasma IGF-1 levels correlated positively with growth rate across all three treatments (r 0.84, P < 0.001, n 17). Spectral analysis of the GH data obtained for each animal was used to determine whether regular periodicities could be detected in the 24 h profile and whether they differed between the three treatment groups. Regular periodicities of four-five cycles/d were detected in the averaged GH profiles of the silage-fed and the control forage-concentrate-fed animals. In contrast, in animals given cimaterol regular GH cycles were not detectable at any of the frequencies tested. This suggests that cimaterol disrupts the rhythm of GH secretion without altering the overall mean concentrations. The data also suggest that due to an inadequate nutrient supply, the GH-IGF-1 regulatory mechanism was uncoupled in the cattle fed on silage, which may have contributed to the poor growth response of these animals.
Adrenergic beta-Agonists↗
Can changes in microcirculation explain capillary growth in skeletal muscle?
Capillary growth (increase in capillary/fibre (C/F) ratio by 20%) was elicited in skeletal muscles either by long-term increase in blood flow (5 weeks administration of prazosin in drinking water, 50 mg/l) or 7 days electrical stimulation (8 h/day at 10 Hz). Mechanisms that could explain it ((a) increased interaction of blood components with endothelial cells (due to increased haematocrit or decreased intermittency of flow); (b) increased velocity of flow and thus shear stress; (c) increased capillary diameters and thus wall tension) were studied in vivo. Red blood cell velocity (Vrbc), vessel diameters and intermittency of capillary flow were measured in superficially located capillaries in rat tibialis anterior muscles about 18 hours after the last treatment, in prazosin treated and chronically stimulated animals, and also in animals where red blood cell interaction with capillary endothelium was increased by elevating haematocrit from 43.2 +/- 1.7% to 60.9 +/- 0.72% by 11 weeks administration of CoCl2. Animals of comparable size and sex were used as controls. Capillaries in chronically stimulated muscles had increased Vrbc at rest (0.42 +/- 0.06 mm/s vs 0.27 +/- 0.04 in control muscles) and somewhat wider diameters, although the intermittency of flow was not different from control muscles. Capillaries in prazosin treated rats had a lower intermittency of flow, similar diameters and considerably higher Vrbc (0.53 +/- 0.06 mm/s) than control animals. CoCl2 treatment resulted in a similar intermittency of flow, did not alter capillary diameters or Vrbc and did not result in an increase in C/F ratio.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
Effect of beta-agonists on expression of calpain and calpastatin activity in skeletal muscle.
Administration of beta-adrenergic agonists to domestic species can lead to skeletal muscle hypertrophy, probably by reducing the rate of myofibrillar protein breakdown. Myofibrillar breakdown is associated with the calcium-dependent proteinase system (calpains I,II and calpastatin) whose activity also changes during beta-agonist treatment. A number of growth trials using the agonists cimaterol and clenbuterol with cattle, sheep, chicken and rat are reported which suggest a general mechanism whereby beta-agonists reduce calpain I activity, but increase calpain II and calpastatin activity in skeletal muscle. Parallel changes in specific mRNAs indicate that changes in gene expression or stabilisation of mRNA could in part explain the changes in activity.
Adrenergic beta-Agonists↗
The evaluation of patients with a suspected pituitary microadenoma: computer tomography compared to magnetic resonance imaging.
OBJECTIVES: To perform a prospective study to compare the ability of magnetic resonance imaging (MRI) and computer assisted tomography (CT) to predict the position of a tumour within the pituitary fossa and to assess the clarity of the image generated by the two modalities in patients with suspected pituitary microadenomas. DESIGN: Nineteen patients were investigated with CT and MRI scans and underwent trans-sphenoidal exploration of the pituitary fossa. Both scans were assessed blind and independently by three neuroradiologists, A, B, and C; A and B examined the CT scans and B and C the MRI scans. The predicted site was then compared to the size and position of the tumour at surgery. PATIENTS: Twenty-five patients were recruited and had both CT and MRI scans, 19 subsequently underwent trans-sphenoidal exploration of the pituitary fossa and formed the study population. RESULTS: The joint opinions of A and B of the CT scans were correct in 10/19, and those of B and C of the MRI scans were correct in 17/19 cases, P = 0.008. Observer agreement was used to assess the clarity of the image. A and B agreed about the site of the tumour on the CT scan in 14 of 19 cases (Kappa statistic 0.556); B and C agreed on the MRI scans in 19/19 cases (Kappa statistic 1), P = 0.025. After the exclusion of five cases found to be macroadenomas at surgery, the joint opinions of A and B of the CT scans were correct in 8/14, and those of B and C of the MRI scans were correct in 12/14 cases, P = 0.133. A and B agreed about the site of the tumour on the CT scan in 12/14 cases (Kappa statistic 0.653), B and C agreed on the MRI scans in 14/14 cases (Kappa statistic 1, no significant difference). CONCLUSIONS: In the assessment of suspected pituitary microadenomas MRI is the imaging technique of choice in view both of its greater diagnostic accuracy and the avoidance of radiation exposure.
Adenoma↗
Ovarian actinomycosis presenting as acute peritonitis.
A patient with acute peritonitis due to ovarian actinomycosis and the association of this disease with the intrauterine contraceptive device is discussed. Because adequate treatment requires prolonged antibiotics the diagnosis should be sure. Unfortunately if antibiotics are given pre-operatively culture is usually unsuccessful and thus careful examination of all removed material is essential. As many of these women are of child bearing age surgical intervention should aim to preserve fertility wherever possible.
Abscess↗
Consequences of an interference fit on the fixation of porous-coated tibial components in total knee replacement.
A linearly elastic, axisymmetrical finite-element model was developed in an attempt to explain observed long-term patterns of growth of bone into tibial components. This model, which represents a portion of the tibial tray, one peg, and the surrounding cancellous bone, was used to examine two conditions of fixation in the immediate postoperative period. The first was characterized by the use of an interference fit for initial fixation of the component and the second, by the use of an interference fit with the hole in the bone deeper than the length of the peg. Two conditions of long-term fixation were also examined. In one, the bone was assumed to have grown into all of the porous coating. In the other, the bone was assumed to have grown only into the peg, and a layer of fibrous tissue was assumed to have developed between the tray and the bone. An interference fit between the peg and the cancellous bone produced considerable residual radial stresses in the bone. These stresses provide conditions that are favorable for ingrowth of bone into the pegs because the bone at the interface is stressed, and these stresses inhibit relative motion at the bone-peg interface. However, the interference fit of the peg relieved the stresses in the cancellous bone under the tray of the implant. Lack of stress at this interface is consistent with relative motion and subsequent formation of a layer of fibrous tissue. Deepening of the hole for the peg in the cancellous bone did not diminish the effects of the interference fit. Stresses in the bone under the metal tray were relieved when a layer of fibrous tissue under the tibial tray was represented in the model.
Biomechanical Phenomena↗
Assessment of gall bladder dynamics, cholecystokinin release and the development of gallstones during octreotide therapy for acromegaly.
The development of gallstones is a well recognized complication of therapy with the long-acting somatostatin analogue, octreotide in patients with acromegaly. A group of nine acromegalic patients was treated with octreotide at doses of 300-600 micrograms daily for 8 months and the changes in fasting and post-prandial cholecystokinin release, and gall bladder motor function (determined by a radiosotopic technique) were assessed at regular intervals. In addition the development of any gallstones was determined by serial ultrasonography. Fasting cholecystokinin levels showed no significant change over 6 months, whereas the post-prandial levels demonstrated a significant decrease (p less than 0.01) during therapy, yet remained significantly higher than fasting levels. Twenty-four hours after commencing therapy gall bladder ejection fraction was decreased by 57 +/- 23 per cent and gall bladder ejection rate decreased by 63 +/- 19 per cent compared to the pretreatment values, whereas after 6 months' therapy a marked reduction in gall bladder ejection fraction (greater than 35 per cent) and gall bladder ejection rate (greater than 40 per cent) persisted in only four of nine patients. Three of these four patients with persistently impaired gall bladder motor function were subsequently shown to have developed either gallstones or biliary sludge during the course of therapy. We conclude that treatment with octreotide is associated with an impaired post-prandial release of cholecystokinin in all acromegalic patients, but gallstones only develop in those patients who, in addition, have evidence of a persistently impaired gall bladder motor response to cholecystokinin.
Acromegaly↗