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Biomedical subjects

J L Marsh

Publications and source records attributed to J L Marsh.

At least 19 recordsLinked to original sources
PubMed2006

Reduction and pinning of pediatric supracondylar humerus fractures in the prone position.

Supracondylar humerus fractures are common pediatric injuries; the preferred treatment for displaced fractures is closed reduction and percutaneous pin fixation. We present a technique for closed reduction and pinning using prone-patient positioning. Prone positioning facilitates fracture reduction and safe pin placement while avoiding elbow hyperflexion. We prefer this technique to the commonly described method of fracture reduction and pinning with the patient supine.

Bone Nails↗
PubMed2006

Intra-articular calcaneal fractures treated nonoperatively and followed sequentially for 2 decades.

OBJECTIVE: To assess the sequential and long-term patient outcome after nonoperative treatment of a displaced intra-articular calcaneal fracture, and to determine if initial results remain stable or deteriorate in the second decade after the injury. DESIGN: Retrospective case series with sequential follow-up at 2 time points a decade apart. SETTING: University teaching hospital. MAIN OUTCOME MEASURES: At the first follow-up in 1990, hind feet were assessed with a computerized tomographic (CT) scan, radiographs, and with a 100 point score, the Iowa calcaneal score (ICS). At the second follow-up in 2000, the ICS was repeated and the patients completed the visual analog scale and the SF-36 questionnaire. RESULTS: In 1990, 15 of 24 hind feet had good or excellent results on the ICS. Sixteen of 19 patients returned to their preinjury level of employment. Subtalar arthrosis on the CT scan correlated with lower average scores [64 points vs. 82 points (P < 0.035)]. Ten years later in 2000, the average ICS had decreased from 74 points to 64 points (P < 0.03); however, in patients with no or minimal arthrosis detected on the 1990 CT scan, the scores remained stable with an average of 82 points, in 1990, and an average of 81 points in 2000 (P < 0.61). SUMMARY: These results suggest that after nonoperative treatment of closed displaced intra-articular calcaneus fractures, clinical results correlate with the presence of subtalar arthrosis on CT scans [except for those with grade V (spontaneous fusion)]. Patients with arthrosis grades III and IV have increased pain and deterioration in function in the second decade after injury compared with those with minimal arthrosis (grades I or II) or those who spontaneously fused their subtalar joint. Patients without arthrosis have good outcomes that remained stable over greater than 2 decades of follow-up.

Adult↗
PubMed2006

Tibial plafond fractures treated by articulated external fixation: a randomized trial of postoperative motion versus nonmotion.

OBJECTIVES: Assess whether postoperative ankle motion after fixation of a fracture of the tibial plafond, treated with articulated external fixation, leads to a better outcome when compared with similar treatment without postoperative ankle motion. DESIGN: Multicenter randomized trial. SETTING: Three Level I trauma centers. PATIENTS/PARTICIPANTS: Fifty-five patients were enrolled and entered into a Web-based database and randomized into 1 of 2 groups. Forty-one patients were evaluated at a 1-year follow-up visit, and 31 were seen at 2 years or longer after injury. INTERVENTION: Patients were treated with a hinged external fixator and limited internal fixation of the articular surface. They were divided postoperatively into two groups, 1 of which had a locked hinge and the other had a mobile hinge and a motion protocol. MAIN OUTCOME MEASUREMENTS: A general health status questionnaire, the SF-36 (short-form 36); a joint-specific ankle questionnaire, the Ankle Osteoarthritis Score (AOS); and range of motion (ROM) of the ankle joint. RESULTS: There were no significant differences between the two groups at either follow-up interval in the ankle ROM measurement, the AOS pain and disability scale, or the SF-36 physical component summary (PCS) and mental component summary (MCS) scales. CONCLUSIONS: These results indicate that treatment protocols that use long periods of cross-joint external fixation that immobilizes the ankle as definitive treatment result in similar patient outcomes compared to otherwise identical treatment protocols that incorporate and use an articulated hinge for ankle motion. However, the results should be interpreted with caution because the patient numbers were too small to detect potentially meaningful differences in outcomes and the follow-up was too short to assess for differences in the development of arthrosis.

Adult↗
PubMed2006

Lumbosacral nerve root avulsions: MR imaging demonstration of acute abnormalities.

Most of the previously reported lumbosacral nerve root avulsions presented with pseudomeningoceles at the time of delayed initial imaging. We report a case of traumatic lumbosacral nerve root injury associated with an isolated femur fracture and demonstrate the evolution of pseudomeningoceles following nerve root avulsions and edema in the perineural fat identified on the initial MR imaging.

Accidents, Traffic↗
PubMed2005

Clinical and cost effectiveness of mechanical support for severe ankle sprains: design of a randomised controlled trial in the emergency department [ISRCTN 37807450].

BACKGROUND: The optimal management for severe sprains (Grades II and III) of the lateral ligament complex of the ankle is unclear. The aims of this randomised controlled trial are to estimate (1) the clinical effectiveness of three methods of providing mechanical support to the ankle (below knee cast, Aircast brace and Bledsoe boot) in comparison to Tubigrip, and (2) to compare the cost of each strategy, including subsequent health care costs. METHODS/DESIGN: Six hundred and fifty people with a diagnosis of severe sprain are being identified through emergency departments. The study has been designed to complement routine practice in the emergency setting. Outcomes are recovery of mobility (primary outcome) and usual activity, residual symptoms and need for further medical, rehabilitation or surgical treatment. Parallel economic and qualitative studies are being conducted to aid interpretation of the results and to evaluate the cost-effectiveness of the interventions. DISCUSSION: This paper highlights the design, methods and operational aspects of a clinical trial of acute injury management in the emergency department.

Ankle Injuries↗
PubMed2005

Posterior fracture-dislocation of the proximal humerus: treatment by closed reduction and limited fixation: a report of four cases.

Four cases of posterior fracture dislocation of the proximal humerus were treated with closed reduction followed by immobilization and/or limited surgical fixation. All patients were adult males and sustained these isolated injuries in low-energy sporting trauma. Three patients followed for an average of 40 months postinjury had excellent results. These cases demonstrate the importance of adequate radiologic examination to avoid missed or delayed diagnosis and that closed reduction of these unusual injuries is frequently possible.

Adult↗
PubMed2005

Three-dimensional analysis of mandibular growth and tooth eruption.

Normal and abnormal jaw growth and tooth eruption are topics of great importance for several dental and medical disciplines. Thus far, clinical studies on these topics have used two-dimensional (2D) radiographic techniques. The purpose of the present study was to analyse normal mandibular growth and tooth eruption in three dimensions based on computer tomography (CT) scans, extending the principles of mandibular growth analysis proposed by Björk in 1969 from two to three dimensions. As longitudinal CT data from normal children are not available (for ethical reasons), CT data from children with Apert syndrome were employed, because it has been shown that the mandible in Apert syndrome is unaffected by the malformation, and these children often have several craniofacial CT scans performed during childhood for planning of cranial and midface surgery and for follow-up after surgery. A total of 49 datasets from ten children with Apert syndrome were available for study. The number of datasets from each individual ranged from three to seven. The first CT scan in each of the ten series was carried out before 1 year of age, and the ages for the 49 scans ranged from 1 week to 14.5 years. The mandible and the teeth were segmented and iso-surfaces generated. Landmarks were placed on the surface of the mandible, along the mandibular canals, the inner contour of the cortical plate at the lower border of the symphysis menti, and on the teeth. Superimposition of the mandibles in the longitudinal series was performed using the symphysis menti and the mandibular canals as suggested by Björk. The study supported the findings of stability of the symphysis menti and the mandibular canals as seen in profile view previously reported by Björk & Skieller in 1983. However, the mandibular canals were, actually, relocated laterally during growth. Furthermore, the position of tooth buds remained relatively stable inside the jaw until root formation started. Eruption paths of canines and premolars were vertical, whereas molars erupted in a lingual direction. The 3D method would seem to offer new insight into jaw growth and tooth eruption, but further studies are needed.

Acrocephalosyndactylia↗
PubMed2005

Expression of secreted Wnt antagonists in gastrointestinal tissues: potential role in stem cell homeostasis.

BACKGROUND: Wnt signalling dysregulation has been implicated in cancer, including colon and gastric cancer. Initiation of Wnt signalling is modulated by soluble Wnt antagonists (sWAs), including soluble frizzled related proteins, dickkopf (Dkk) proteins, and Wnt inhibitory factor-1 (Wif1). AIMS: To evaluate the role of sWAs in upper (gastric) and lower (colon) gastrointestinal tract tumorigenesis. METHODS: Dkk1-3, Wif1, and FrzB expression was evaluated by in situ RNA hybridisation on normal and malignant human gastric and colon tissues. Expression was graded semiquantitatively. RESULTS: Wif1, Dkk1, and Dkk2 were not expressed in normal gastric tissue. Dkk3 was expressed in some samples, with stronger expression in deep gastric glands. FrzB was expressed in several normal gastric samples, but not in matched tumour specimens. In contrast, Dkk1 and FrzB were not expressed in normal colon. Wif1 was expressed in most colon samples, with stronger expression at crypt bases. Dkk3 and Dkk2 expression was also concentrated at crypt bases. There were no differences between sWA expression in malignant colon and matched normal tissue. CONCLUSIONS: sWA expression differed between upper and lower gastrointestinal tract. The loss of FrzB in gastric cancer suggests that it acts as a tumour suppressor. The graded expression of Dkk3 in gastric tissue, and Dkk2, Dkk3, and Wif1 in colon tissue, with increased expression in the deep gastric glands/colonic crypt bases, where gastrointestinal stem cells reside, suggests that sWAs may be crucial Wnt signalling regulators in these tissues, and may contribute to stem cell pool maintenance. sWAs are important components of the gastrointestinal proliferative regulatory network.

Adaptor Proteins, Signal Transducing↗
PubMed2005

Ankle fractures in patients with diabetes mellitus.

Diabetes mellitus is considered an indicator of poor prognosis for acute ankle fractures, but this risk may be specific to an identifiable subpopulation. We retrospectively reviewed 42 patients with both diabetes mellitus and an acute, closed, rotational ankle fracture. Patients were individually matched to controls by age, gender, fracture type, and surgical vs non-surgical treatment. Outcomes were major complications during the first six months of treatment. We contrasted secondarily 21 diabetic patients with and 21 without diabetic comorbidities. Diabetic patients and controls did not differ significantly in total complication rates. More diabetic patients required long-term bracing. Diabetic patients without comorbidities had complication rates equal to their controls. Diabetic patients with comorbidities had complications at a higher rate (ten patients; 47%) than matched controls (three patients; 14%, p = 0.034). A history of Charcot neuroarthropathy led to the highest rates of complication. An increased risk of complications in diabetic patients with closed rotational fractures of the ankle are specific to a subpopulation with identifiable related comorbidities.

Adult↗
PubMed2004

Quantifying comminution as a measurement of severity of articular injury.

The severity of articular injury caused by a fracture of periarticular bone impacts patient prognosis. There currently are not good, objective methods for grading articular injury severity. Quantification of bone comminution from fracture image data, which has been possible in laboratory studies, may be a promising route. We show that tibial pilon fractures can be discriminated on the basis of de novo surface-apparent energy absorption.

Accidental Falls↗
PubMed2003

Methodologic issues in observational studies.

Assessment of orthopaedic treatments depends primarily on studies that analyze data abstracted from medical records or collected prospectively for research purposes. Because treatment in these studies is determined by the surgeon and the patient rather than controlled by the researcher, these studies are referred to as observational. Most orthopaedics research uses the observational study design because it is less expensive and more timely, includes more representative patients, and leaves medical decision-making under the control of the physician and the patient. Biases associated with observational studies are influenced greatly by study design, methods of data collection, and statistical analysis. All observational studies should report factors influencing relevance (characteristics of patients, treatments, and outcome measures), and factors that influence validity (methods to obtain information and patient risk factors that may differ between treatments). Improved standards for reporting observational studies will facilitate the interpretation of results and the comparison of studies with conflicting results.

Confounding Factors, Epidemiologic↗
PubMed2003

Altered protein acetylation in polyglutamine diseases.

Polyglutamine diseases are hereditary neurodegenerative disorders caused by the expansion of a CAG repeat in the disease gene. A dominant gain of function is associated with these expanded alleles. The resulting elongated polyglutamine repeats are thought to cause structural changes in the affected proteins, leading to aberrant interactions such as those that allow formation of extra- and intranuclear aggregates. However, self-association is not the only interaction the polyglutamine domain is capable of mediating. Many cellular proteins can be sequestered into inclusions or bound by more soluble forms of the mutant proteins. One group of proteins that binds to and whose activity may be altered by polyglutamines is Histone Acetyltransferases (HATs). HATs are responsible for the acetylation of histones and several other important proteins and this modification results in altered function of the target protein. HATs regulate cellular processes at levels as different as modifying transcriptional competence of chromosomes, temporal regulation of promoter activity and protein activation / inactivation. Recent studies show that the altered balance between protein acetylation and deacetylation may be a key process contributing to expanded polyglutamine-induced pathogenesis. The restoration of this balance is possible by the genetic or pharmacological reduction of the opposing enzyme group, i.e. the Histone Deacetylases (HDACs). Recent progress in HDAC research has made the development of inhibitors of specific HDAC family proteins possible and these compounds could be effective candidates for treatment of these devastating diseases.

Acetylation↗
PubMed2002

Expression of Wnt ligands and Frizzled receptors in colonic mucosa and in colon carcinoma.

AIMS: Signalling through the Wnt pathway is integrally associated with colon carcinogenesis. Although activating mutations in the genes for adenomatous polyposis coli (APC) and beta-catenin are clearly associated with colon cancer, less is understood about the role of the upstream secreted ligands (Wnts) and their receptors (frizzled, Fz) in this process. In other systems, increased Wnt signalling has been shown to alter the expression of components of this pathway. This study was designed to test the hypothesis that colon cancer is characterised by aberrant expression of specific Wnt genes and Fz receptors. METHODS: The expression of Wnt genes was assessed by in situ, antisense RNA hybridisation in paraffin wax embedded samples of normal and malignant human colon tissues with probes specific for the individual Wnt genes. The expression of Fz1 and Fz2 was determined by immunoperoxidase based antibody staining on human tissues. RESULTS: Changes in the expression of some ligands and receptors were seen in colon cancer. For example, Wnt2 mRNA was detected in colon cancer but was undetectable in normal colonic mucosa. Differential expression of Wnt5a in normal mucosa was also noted, with increased expression at the base of the crypts compared with the luminal villi and slightly increased expression in colon cancer. Wnt7a exhibited minimal expression in both normal and malignant colon tissues, whereas other Wnt ligands including Wnts 1, 4, 5b, 6, 7b, and 10b were expressed equally and strongly in both normal and malignant colon tissues. In defining cellular responses and phenotype, the type and distribution of Fz receptors may be as important as the pattern of Wnt ligand expression. No expression of Fz receptor 1 and 2 was seen in normal colonic mucosa and in well differentiated tumours. However, poorly differentiated tumours exhibited a high degree of Fz receptor expression, especially at the margin of cellular invasion. CONCLUSIONS: These data indicate that the expression of members of the Wnt signal transduction pathway, distinct from APC and beta-catenin, is integrally associated with the process of colon carcinogenesis. Wnt2, and possibly Wnt5a, may be involved in the progression from normal mucosa to cancer and the expression of Fz1/2 receptors may be involved in processes associated with tumour invasion. Altered expression of these Wnts and Fz receptors may prove useful as prognostic or diagnostic markers for patients with colon cancer.

Biomarkers, Tumor↗
PubMed2001

Histone deacetylase inhibitors arrest polyglutamine-dependent neurodegeneration in Drosophila.

Proteins with expanded polyglutamine repeats cause Huntington's disease and other neurodegenerative diseases. Transcriptional dysregulation and loss of function of transcriptional co-activator proteins have been implicated in the pathogenesis of these diseases. Huntington's disease is caused by expansion of a repeated sequence of the amino acid glutamine in the abnormal protein huntingtin (Htt). Here we show that the polyglutamine-containing domain of Htt, Htt exon 1 protein (Httex1p), directly binds the acetyltransferase domains of two distinct proteins: CREB-binding protein (CBP) and p300/CBP-associated factor (P/CAF). In cell-free assays, Httex1p also inhibits the acetyltransferase activity of at least three enzymes: p300, P/CAF and CBP. Expression of Httex1p in cultured cells reduces the level of the acetylated histones H3 and H4, and this reduction can be reversed by administering inhibitors of histone deacetylase (HDAC). In vivo, HDAC inhibitors arrest ongoing progressive neuronal degeneration induced by polyglutamine repeat expansion, and they reduce lethality in two Drosophila models of polyglutamine disease. These findings raise the possibility that therapy with HDAC inhibitors may slow or prevent the progressive neurodegeneration seen in Huntington's disease and other polyglutamine-repeat diseases, even after the onset of symptoms.

Acetylation↗
PubMed2001

Twisted gastrulation is a conserved extracellular BMP antagonist.

Bone morphogenetic protein (BMP) signalling regulates embryonic dorsal-ventral cell fate decisions in flies, frogs and fish. BMP activity is controlled by several secreted factors including the antagonists chordin and short gastrulation (SOG). Here we show that a second secreted protein, Twisted gastrulation (Tsg), enhances the antagonistic activity of Sog/chordin. In Drosophila, visualization of BMP signalling using anti-phospho-Smad staining shows that the tsg and sog loss-of-function phenotypes are very similar. In S2 cells and imaginal discs, TSG and SOG together make a more effective inhibitor of BMP signalling than either of them alone. Blocking Tsg function in zebrafish with morpholino oligonucleotides causes ventralization similar to that produced by chordin mutants. Co-injection of sub-inhibitory levels of morpholines directed against both Tsg and chordin synergistically enhances the penetrance of the ventralized phenotype. We show that Tsgs from different species are functionally equivalent, and conclude that Tsg is a conserved protein that functions with SOG/chordin to antagonize BMP signalling.

Animals↗
PubMed2001

Plasticity of the endocranial base in nonsyndromic craniosynostosis.

Limited in vivo data exist on the dysmorphology of the cranial base in nonsyndromic craniosynostosis. Few studies have documented the effect of calvarial surgery for synostosis on endocranial morphology. Previous work has suggested that the dysmorphology of the endocranial base is diagnostically specific for metopic, sagittal, and unicoronal sutures. The purpose of this study was to further evaluate the endocranial base in infants with nonsyndromic craniosynostosis by testing the hypothesis that the dysmorphology is, to some degree, a secondary deformation rather than a primary malformation. Three questions were addressed: (1) Can individuals reliably identify affected suture-specific endocranial-base morphology using standard templates? (2) Does calvarial surgery in infancy for craniosynostosis affect the perception of endocranial-base morphology? and (3) Does calvarial surgery in infancy for nonsyndromic craniosynostosis normalize the endocranial base?In this study, three-dimensional volumetric reconstructions from archived computed tomography digital data were processed using the ANALYZE imaging software. Dysmorphology was assessed by nine independent, blinded skilled observers who reviewed two separate sets of images of endocranial bases. Both sets contained images from the same patients: one set contained preoperative images, and the other contained images of the endocranial base 1 year after calvarial surgery. Observers were asked to sort each set into four suture-specific diagnostic groups: normal, unicoronal, metopic, and sagittal. Each set contained 10 patients with unicoronal synostosis, 10 with metopic synostosis, 10 with sagittal synostosis, and four normal patients. Seventy-eight percent of the total number of preoperative images were correctly sorted into the suture-specific diagnostic group, whereas only 55 percent of the total number of postoperative images were correctly matched. With regard to the individual sutures, the results were as follows (data are presented as preoperative accuracy versus postoperative accuracy): metopic, 76 percent versus 44 percent; sagittal, 58 percent versus 34 percent; unicoronal, 100 percent versus 79 percent; and normal, 83 percent versus 72 percent. Although 36 of 306 total images per group (12 percent) actually represented normal patients, the observers called 72 of 306 normal (24 percent) in the preoperative set versus 110 of 306 normal (36 percent) in the postoperative set. In conclusion, (1) the endocranial dysmorphology of nonsyndromic craniosynostosis is recognizably specific to the affected suture; (2) calvarial surgery for nonsyndromic craniosynostosis normalizes the endocranial base qualitatively with regard to the diminished ability of raters to identify the primary pathology; and (3) the documented postoperative changes in endocranial base morphology after calvarial surgery for nonsyndromic craniosynostosis in infancy indicates that a major component of that dysmorphology is a secondary deformity rather than a primary malformation.

Craniosynostoses↗