Biomedical subjects
Publications and source records attributed to D P Moore.
The Ilizarov technique can allow new histiogenesis of soft tissue as well as bone. Three cases of wrist contracture successfully treated by this method are described. One patient had transient superficial pin site infections. There were no other complications. At 2 years follow-up there was no recurrence of contractures.
Glass-ionomer cements (GIC) offer several advantages over the conventional acrylic-based bone cements. The formation of an adhesive bond with bone and metals, a low setting exotherm and no systemic or local toxicity are some of the advantages cited. This study examines the in vivo biological and biomechanical behavior of two polyalkenoate cements (LG26 and LG30) implanted for 6 wk into the submetaphyseal spongiosa of the rabbit femur. Cements were implanted as both set cement rods and unset cement dough. Implantation of set rods resulted in the formation of variably mineralized osteoid/woven bone at the bone-cement interface. Mechanical (push-out) testing revealed the strength of this bone-cement interface was of similar magnitude to control (PMMA-rod implanted) animals. The bone of LG cement-dough implanted animals exhibited demineralization of pre-existing bone local to the site of implantation, accumulation of aluminum both locally and at a distance from the site of implantation, and defective mineralization of newly formed osteoid. The histological picture following LG implantation was strikingly similar to human renal osteodystrophy, in which skeletal accumulation of aluminum is a noted feature. The development of a GIC with low/no aluminum release from the unset cement dough is a priority in the further development of these cements for possible orthopaedic applications.
The Drosophila mei-S332 and ord gene products are essential for proper sister-chromatid cohesion during meiosis in both males and females. We have constructed flies that contain null mutations for both genes. Double-mutant flies are viable and fertile. Therefore, the lack of an essential role for either gene in mitotic cohesion cannot be explained by compensatory activity of the two proteins during mitotic divisions. Analysis of sex chromosome segregation in the double mutant indicates that ord is epistatic to mei-S332. We demonstrate that ord is not required for MEI-S332 protein to localize to meiotic centromeres. Although overexpression of either protein in a wild-type background does not interfere with normal meiotic chromosome segregation, extra ORD+ protein in mei-S332 mutant males enhances nondisjunction at meiosis II. Our results suggest that a balance between the activity of mei-S332 and ord is required for proper regulation of meiotic cohesion and demonstrate that additional proteins must be functioning to ensure mitotic sister-chromatid cohesion.
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Stress has, for many years, been linked to the onset of autoimmune disease and, in particular, autoimmune thyroid disease (AITD). Whilst the exact mechanism of this association is unknown, it is clear that episodes of stress can induce profound changes in the immune system. More specifically, recent studies from several laboratories have shown an association between the expression of stress proteins and, particularly, the Hsp70 family with AITD. Our own studies describe a thyroid-specific Hsp70 which shares antigenicity with the key thyroid autoantigen, thyroid peroxidase. Further studies on the molecular basis for this observation are, however, hampered by the lack of a suitably validated thyroid cell model. In this paper we compare the response of primary cultures of human thyrocytes to hyperthermia with the response seen in the immortalized human thyroid cell line HTori3. Both cell types responded in a broadly similar manner, synthesizing proteins from two of the major stress protein families, Hsp70 and Hsp90. In the primary human thyrocyte cultures the 70 kDa proteins showed a 7.5-fold increase and the 90 kDa proteins a 2.7-fold increase with hyperthermia whilst in the HTori3 cells the increases in response to hyperthermia were 10- and 6.5-fold, respectively. We also show a dose-dependent stress response in HTori3 cells cultured in the presence of arsenite ions. We conclude that the response of this highly differentiated and stable thyroid cell line to stress is similar to that seen in primary cultures of human thyroid cells and that these immortalized cells will afford a convenient and effective model for the further study of the role of stress in the pathology of AITD.
Familiarity with spasticity and its treatment options and a rational approach to care are necessary to achieve an optimal outcome in patients with this disorder. Not all spasticity needs to be treated. Functional problems experienced by the patient and feedback from caretakers should guide decisions of whether and how to treat. Primary care physicians may benefit from maintaining close working relationships with physical medicine and rehabilitation physicians (physiatrists), who are experienced in assessment of spasticity, especially in relation to function, and can help differentiate true spasticity from rigidity and contracture. After underlying exacerbating factors are ruled out, a treatment plan starting with conservative methods and advancing to more aggressive measures should be followed. Consultation with physiatrists may be useful in regard to antispasticity medications, nerve blocks, intrathecal pumps, and postrhizotomy care.
STUDY DESIGN: Statistical analysis of maturity and asymmetry criteria in adolescent idiopathic scoliosis. OBJECTIVES: To explore the hypothesis that scoliosis is a manifestation of developmental destabilization under physiologic stress. BACKGROUND: Advances in genetics and theoretical biology have broadened the understanding of morphogenesis and the controlling mechanisms for the development of the adult form. The morphologic genome can be viewed as a cybernetic control system, and the homeobox genes can be viewed as the master controls for the specific subroutines. Deformity will occur from a faulty "program" or a disturbance in the running of that program. An early and subtle indication of such an occurrence is failure of bilateral symmetry. METHODS: An analysis of variance in Cobb angle, age at diagnosis, and apical site in 327 girls with spinal curves 5 degrees or greater according to prospectively maintained scoliosis screening records was performed. Dermatoglyphics were compared in 114 female control individuals and 164 female patients with adolescent idiopathic scoliosis (minimum Cobb angle, 10 degrees), and then by subdivision into school screening (n = 86) and general clinic referrals (n = 78). RESULTS: Girls from the screening program (from the years 1979-1990) had statistically significant associations between age and apical vertebra, suggesting an age-deformity relationship independent of maturation and growth spurt. Girls with adolescent idiopathic scoliosis from a later cohort, both screened and unscreened, had increased directional asymmetry, as previously reported. There was a statistically significant increase in fluctuating asymmetry in general clinic referrals when compared with school screening referrals. CONCLUSIONS: Developmental instability can explain adolescent idiopathic scoliosis as part of wider developmental theory without the necessity of a disease process in the etiology. The differences between screening and general clinic referrals suggest the need for natural history studies, and treatment protocols also should consider the provenance of the individuals described.
STUDY DESIGN: Prints of palmar dermatoglyphics (epidermal ridges) of individuals with congenital vertebral anomaly were compared, using symmetry criteria, with those of healthy control individuals. Asymmetries have been reported in adolescent idiopathic scoliosis and, from other centers, in other congenital anomalies, such as cleft lip and palate. Application of these methods to congenital vertebral anomaly seemed promising. OBJECTIVES: To challenge the hypothesis that, in congenital vertebral anomaly, epigenesis was disrupted by nonspecific physiologic stress during the embryonic period, resulting in anatomic malformations. SUMMARY OF BACKGROUND DATA: Dermatoglyphics (palmar epidermal ridges) are formed at the end of the embryonic period under genetic control and do not change thereafter. They thus give an indication of the stability or otherwise of development at that early stage. This led to the hypothesis that congenital vertebral anomaly results from destabilization of genetic developmental control in the embryonic period. METHODS: The dermatoglyphics of 126 healthy control individuals and 99 people with congenital vertebral anomaly were compared quantitatively, using right-left differences of atd angles and ab, bc, and cd ridge counts. RESULTS: Fluctuating asymmetry (a significantly increased variance about the mean) was observed in individuals with congenital vertebral anomaly. This is a measure of instability of genetic development processes and the increased probability that these processes will be destabilized by environmental stress during ontogeny. They also showed an increased incidence of ridge dissociation, suggestive of a generalized insult during the embryonic period. CONCLUSIONS: These findings suggest that congenital vertebral anomalies arise from a nonspecific insult during the embryonic period that destabilizes the developmental control systems and may result in congenital malformations of any organ undergoing concurrent epigenesis.
Moyamoya is a disease characterized by occlusion of the internal carotid, anterior, and middle cerebral arteries with associated rich collateral flow that presents a cloudy appearance on angiogram resembling a puff of smoke. The disease is most often progressive with associated hemiparesis and cognitive impairment. The functional outcome of patients with moyamoya is not well described in the literature. We describe four women (ages 25-36) who were transferred to a rehabilitation service after an average 17 days (12-26 days) in an acute care setting. Initial functional impairment was estimated using the Functional Independence Measure (FIM) score after discharge from inpatient rehabilitation (23-53 days) and was compared to the Uniform Data System for Medical Rehabilitation (UDSMR) for "first stroke" patients. Average admission FIM scores were similar in the two groups. The patients with moyamoya had a higher discharge FIM, longer length of stay, and slower rate of progress. Data on long-term survival and functional level would be useful, but it appears patients with moyamoya disease may benefit from rehabilitation oriented toward neurological deficits.
We have developed a quick, non-invasive method for measuring the ability of an isolated preserved liver to regenerate high energy phosphate nucleotides without the need for biopsy. Using 31P MRS we have monitored the hepatic energetics of intact cold preserved pig liver using standard clinical harvesting and storage techniques. Following cold storage for 2 h the livers were hypothermically reperfused with oxygenated modified University of Wisconsin preservation fluid. Prior to reperfusion MRS detectable adenosine diphosphate plus adenosine triphosphate was negligible; however, the spectrum showed intense resonances from phosphomonoesters and inorganic phosphate, as a consequence of adenosine triphosphate hydrolysis during cold preservation. Following a 10-min period of hypothermic reperfusion, regeneration of adenosine triphosphate occurred with a concurrent decline in inorganic phosphate and phosphomonoester, both of which are associated with adenosine triphosphate synthesis. The capacity of the liver to regenerate adenosine triphosphate following a 24-h period of cold storage was reduced by approximately 40% (p < 0.01) of the total amount achieved following the shorter cold storage time. Adenosine triphosphate regeneration rates were biphasic and were decreased upon prolonged storage, with the initial rate being reduced from 40.6 x 10(-2).min-1 (standard deviation (sd) 2.70 x 10(-2).min-1) to 14.8 x 10(-2).min-1 (sd; 2.4 x 10(-2).min-1) and the secondary rate from 1.77 x 10(-2).min-1 (sd; 0.18 x 10(-2).min-1) to 0.84 x 10(-2).min-1 (sd; 0.45 x 10(-2).min-1). MR images of the liver during the period of hypothermic reperfusion were also performed providing an assessment for the degree of hepatic vascular perfusion. This non-invasive, 31P MRS assessment of hepatic energetics in a clinically relevant animal model has great potential for the understanding of graft preservation injury.
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The aim of this study was to assess the possibility of regenerating nucleotide triphosphates (NTP) in the pig liver following its harvest and subsequent storage on ice. This study has used a pig model that allowed human donor liver retrieval techniques and methods of storage to be utilized. In vitro phosphorus-31 nuclear magnetic resonance (31P-NMR) spectroscopy was used to evaluate the changes associated with phosphorus containing metabolites such as NTP, phosphomonoesters (PME), phosphodiesters (PDE), and inorganic phosphate (Po). During 4 hr storage NTP levels were reduced to undetectable levels but its regeneration was possible over a period of 2 hr of oxygenated hypothermic reperfusion. Resynthesized NTP reached values that were only 30% reduced from pre-harvest values. There was a corresponding reduction in Pi over the same period. Glycolytic intermediates, 3-phosphoglycerate and 2,3 diphosphoglycerate, both increased significantly during the period of storage and subsequently declined following hypothermic reperfusion. Cellular damage, indicated by the concentrations of glycerophosphorylcholine (GPC) and glycerophosphorylethanolamine (GPE) was minimal during cold storage. However upon hypothermic reperfusion, concentrations of GPC and GPE reduced, indicating a degree of cellular damage caused by reperfusion. This study has shown for the first time that is possible to regenerate high energy phosphate nucleotides following a period of hypothermic reperfusion in a large, clinically related animal model. This technique warrants investigation clinically to improve the outcome of orthotopic liver transplantation. It also provides a method to study the effects of different preservation fluids and methods of storage and organ reperfusion.
Attachment between the sister chromatids is required for proper chromosome segregation in meiosis and mitosis, but its molecular basis is not understood. Mutations in the Drosophila ord gene result in premature sister chromatid separation in meiosis, indicating that the product of this gene is necessary for sister chromatid cohesion. We isolated the ord gene and found that it encodes a novel 55 kDa protein. Some of the ord mutations exhibit unusual complementation properties, termed negative complementation, in which particular alleles poison the activity of another allele. Negative complementation predicts that protein-protein interactions are critical for ORD function. The position and nature of these unusual ord mutations demonstrate that the C-terminal half of ORD is essential for sister chromatid cohesion and suggest that it mediates protein binding.
There are no objective data available on the relative strengths of inguinal hernia repairs. The aim of this randomized controlled study was to measure th force required to disrupt laparoscopic and open mesh repairs in a porcine model. Eleven pigs had inguinal hernia repair following randomization to an open mesh group (n = 5) or a transabdominal preperitoneal laparoscopic group (n = 6). Four weeks after operation the pigs were killed and the pelvic girdles were mounted in a test jig on a mechanical testing machine. The applied disruption forces were measured and recorded. Mean(s.d.) force required to disrupt the normal inguinal canal (n = 11) was 68.6(30.1) N with no difference between groups. The open mesh repair required 110.3(41.4) N and the laparoscopic mesh 220.0(95.2) N. Both open and laparoscopic mesh repairs were stronger than the normal side (P < 0.03). The laparoscopic mesh repair was stronger than the open mesh repair (P = 0.04). This model provides a standardized method for mechanically testing inguinal hernia repairs in pigs. It confirms that both open and laparoscopic mesh hernia repairs are stronger than the non-herniated normal side at 4 weeks after operation. Laparoscopic mesh repair is stronger than open mesh repair. The weakest points of the repairs correlate well with those identified in clinical reports.
BACKGROUND: The recent demonstration of an etiologic role for Sydenham's chorea in obsessive-compulsive disorder has once again brought this disorder to psychiatric attention. Despite its traditional importance to psychiatry, there has not been a comprehensive review of Sydenham's chorea published for decades. METHOD: I utilized the Index Medicus and its predecessors, the Quarterly Cumulative Index Medicus and the Cumulative Index Medicus, to search for every English-language article on Sydenham's chorea written during the past 115 years and then read and compiled the articles and their pertinent references. RESULTS: Sydenham's chorea is a symptom of rheumatic fever and results from an autoimmune attack on the CNS. In addition to chorea, the acute attack is almost always characterized by psychiatric symptoms such as irritability, obsessions and compulsions, tics, and psychotic symptoms. Acutely, treatment involves valproic acid or haloperidol; steroids may also be appropriate. Chronic treatment with penicillin is required to prevent future attacks. In adult years, the neuropsychiatric sequelae of Sydenham's chorea include chorea gravidarum, some cases of obsessive-compulsive disorder, and possibly, certain cases of Tourette's syndrome and of schizophrenia. CONCLUSION: Sydenham's chorea is best considered a neuropsychiatric disorder, and most patients will benefit from psychiatric treatment. Certain cases of obsessive-compulsive disorder, and perhaps other adult psychiatric disorders as well, may benefit from approaches similar to those used for Sydenham's chorea.
Mutations in the Drosophila mei-S332 gene cause premature separation of the sister chromatids in late anaphase of meiosis I. Therefore, the mei-S332 protein was postulated to hold the centromere regions of sister chromatids together until anaphase II. The mei-S332 gene encodes a novel 44 kDa protein. Mutations in mei-S332 that differentially affect function in males or females map to distinct domains of the protein. A fusion of mei-S332 to the green fluorescent protein (GFP) is fully functional and localizes specifically to the centromere region of meiotic chromosomes. When sister chromatids separate at anaphase II, mei-S332-GFP disappears from the chromosomes, suggesting that the destruction or release of this protein is required for sister-chromatid separation.
STUDY DESIGN: This study analyzed the asymmetry of a nonspinal sensory system, comparing healthy children and those with adolescent idiopathic scoliosis. OBJECTIVES: To test the hypothesis that differences in neurologic functioning that have been observed in idiopathic scoliosis are confined to motor organization and that the etiology thus is a defect solely of the motor cortex. SUMMARY OF BACKGROUND DATA: Recent reports associating scoliosis convexity with equilibrium control, central processing, handedness, and motor lateralization have suggested that idiopathic scoliosis is connected causally with the motor cortex. METHODS: Dichotic listening tests were performed on 20 healthy children and 31 children with adolescent idiopathic scoliosis. This tests perceptual asymmetry, and thus the organization of cognitive processing in the brain, a higher function that is not associated with posture or motor function. RESULTS: Subjects with scoliosis were significantly more lateralized for linguistic processing than the control group, indicating they had a greater degree of left-right asymmetry throughout their cortical organization. CONCLUSION: In adolescent idiopathic scoliosis, the organization of the entire brain was more strongly lateralized than in subjects without scoliosis. It is unlikely that this caused or was caused by the spinal curvature. Subjects with adolescent idiopathic scoliosis showed generalized asymmetry of many functions and structures. An examination at the level of morphology and development is proposed.
STUDY DESIGN: Analysis of scoliosis screening in Dublin (1979-1990) of patients who passed significant levels (25 degrees and 40 degrees) and received orthotic treatment or surgery. OBJECTIVES: To reexamine the basis of school scoliosis screening. SUMMARY OF BACKGROUND DATA: The United States Preventive Services Task Force questioned the validity of school screening for adolescent idiopathic scoliosis because there is insufficient scientific evidence to justify it. METHODS: New entrants (1986-87) to the screening program were used to test the validity of the screening methods. The total screened population, proportions reaching significant Cobb angles or undergoing treatment, were compared across the time period. RESULTS: The sensitivity of the forward bend test in detecting or predicting 40 degrees scoliosis was 0.83, the specificity was 0.99, and the predictive value was 0.08. The proportion prescribed braces declined significantly (P < 0.01), but there was no significant change in those with scoliosis greater than 24 degrees (0.18%) or 39 degrees (.08%) nor was there a significant change in the numbers needing surgery (.045%). CONCLUSIONS: The incidence of significant scoliosis and of surgery is low and independent of changes in bracing policy. The validity of screening to cause significant change in prevalence must be challenged.