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Biomedical subjects

Jason Smith

Publications and source records attributed to Jason Smith.

At least 19 recordsLinked to original sources
PubMed2006

Percutaneous insertion of a proximal humeral locking plate: an anatomic study.

This cadaveric study sought to evaluate the feasibility of applying a locking proximal humerus plate with a novel minimally invasive technique. A unique pre-contoured locking plate was placed on cadaveric proximal humeri through a described minimally invasive approach. Proximity of the plate and screws to the axillary nerve and their respective surgical tracks were quantified. Safe screw hole placement with respect to the axillary nerve was determined. Risk of entrapment of the nerve beneath the plate was evaluated. Three of the holes near the middle of the locking plate consistently intersected the course of the axillary nerve and were unsafe for percutaneous placement of the screws. The axillary nerve could be palpated during the course of surgery and easily protected from injury. No entrapment of the axillary nerve occurred using this minimally invasive technique. The screw-in locking guide cannot be used with this technique as it caused tenting of the axillary nerve. Placement of a locking proximal humerus plate via a minimally invasive lateral trans-deltoid approach is safe if the locking screws are limited to superior and inferior holes. This can be done safely without entrapment of the axillary beneath the plate. Plate fixation of proximal humerus fractures may now be more desirable with the use of this approach.

Acromion↗
PubMed2006

Effect of culture conditions on the chemosensitivity of ovarian cancer cell lines.

The aim of this study was to define the chemosensitivity profile of a series of human ovarian cancer cell lines representing the human primary ovarian tumours under altered culture conditions and to compare the results with those from tumour-derived cells. In this study, we used a standardized ATP-based tumour chemosensitivity assay to measure the activity of cytotoxics in the seven ovarian carcinoma cell lines and ovarian tumour-derived cells. The use of adherence-free polypropylene plates and a serum-free medium slowed down cell proliferation in all cell lines tested, mimicking the slow growth rate of solid tumours in this type of plastic. The seeding density was optimized for each cell line and was in the range of 2000-4000 cells/well. Heterogenous sensitivity to different cytotoxics was observed in the seven ovarian cancer cell lines tested in the ATP-based tumour chemosensitivity assay. The human ovarian carcinoma cell line, OVCA433, was found to be the most resistant cell line and 75% of the drugs showed an Index(SUM) above 300. Our results suggest that the use of appropriate culture conditions i.e. a serum-free culture environment, adherence-free growth and optimum seeding density can induce cell lines to behave more like tumour-derived cells in response to cytotoxic agents. On the basis of the comparison of chemosensitivity profiles of tumour-derived cells and cell lines derived from the corresponding tumour, a panel of cell lines can be selected. Such a panel could be used to screen and develop anticancer drugs.

Adenosine Triphosphate↗
PubMed2005

Volume three-dimensional flow measurements using wavelength multiplexing.

Optically distinguishable seeding particles that emit light in a narrow bandwidth, and a combination of bandwidths, were prepared by encapsulating quantum dots. The three-dimensional components of the particles' displacement were measured within a volume of fluid with particle tracking velocimetry (PTV). Particles are multiplexed to different hue bands in the camera images, enabling an increased seeding density and (or) fewer cameras to be used, thereby increasing the measurement spatial resolution and (or) reducing optical access requirements. The technique is also applicable to two-phase flow measurements with PTV or particle image velocimetry, where each phase is uniquely seeded.

Algorithms↗
PubMed2005

Pregnancy-associated plasma protein-a is involved in matrix mineralization of human adult mesenchymal stem cells and angiogenesis in the chick chorioallontoic membrane.

Pregnancy-associated plasma protein A (PAPP-A) is an IGF binding protein 4 protease that can function to increase local IGF-I bioavailability. Aside from its assumed role during pregnancy, in vitro and in vivo studies have indicated roles for PAPP-A in IGF-I-mediated wound healing, vascular repair, and bone formation. Because bone morphogenetic protein 2 (BMP-2) is known to up-regulate Igf-I gene expression, we hypothesized that PAPP-A may be involved in BMP-2 mechanisms in bone formation. To test this hypothesis, we quantified gene expression of Papp-A in response to BMP-2 treatment and runt-related transcription factor 2, Osterix, and Igf-I in response to PAPP-A protein treatment in human adult mesenchymal stem cells. Our results demonstrate that BMP-2 directly up-regulated Papp-A gene and protein expression. Purified PAPP-A protein directly up-regulated runt-related transcription factor 2 and Igf-I gene expression but not Osterix. When added in combination with recombinant human BMP-2, PAPP-A increased matrix mineralization in the absence of dexamethasone. PAPP-A further demonstrated an angiogenic effect in the chick chorioallontoic membrane, which implicates a critical developmental role and possible therapeutic potential. Our findings suggest that PAPP-A functions in the formation of mineralized tissues through direct up-regulation of key genes. Furthermore, PAPP-A is involved in the formation of new blood vessels, which is essential for proper bone regeneration.

Adult↗
PubMed2005

Analysis of methoxypyrazines in wine using headspace solid phase microextraction with isotope dilution and comprehensive two-dimensional gas chromatography.

This study reports an optimized headspace-solid phase microextraction (HS-SPME) method for the determination of methoxypyrazines in wine. Analysis was performed by using comprehensive two-dimensional gas chromatography with novel detection capabilities, including nitrogen phosphorus detection (GC x GC-NPD) and time-of-flight mass spectrometry (GC x GC-TOFMS). In the latter, stable isotope dilution was performed for the quantitation of 2-methoxy-3-(2-methylpropyl) pyrazine (IBMP), using labelled 2-(2H3)methoxy-3-(2-methylpropyl)pyrazine (d3-IBMP) as the internal standard, and resolution of the two analogues was facilitated using the deconvolution capabilities of the TOFMS. This research represents the first report of HS-SPME with isotope dilution and GC x GC-TOFMS (GC x GC-IDTOFMS). Analysis by GC x GC-NPD enabled detection limits of 0.5 ng/L for the quantitation of IBMP, which was superior to that obtained using GC x GC-IDTOFMS (1.95 ng/L). Nevertheless, both methods were adequately sensitive for real wine analysis, yielding highly comparable IBMP concentrations of 26.1 and 27.8 ng/L, respectively, from a Sauvignon blanc wine. The complexity of the real wine headspace was simplified as a result of selective detection using GC x GC-NPD and, in the case of GC x GC-IDTOFMS, the use of extracted ion chromatograms (EICs).

Chromatography, Gas↗
PubMed2005

An evaluation of compliance with practice guidelines on interhospital trauma transfer.

STUDY OBJECTIVES: To prospectively evaluate compliance with current interhospital trauma transfer guidelines in South West Sydney, before and after an implementation programme was instituted. METHODS: A scoring system was developed to assess compliance with the 11 main components of the guideline. Baseline compliance was measured during an initial 3-month period (pre), followed by an implementation programme to alert staff at referring hospitals to the presence of the guidelines. Following this, compliance was again measured over 3 months (post). RESULTS: Twenty-two patients were transferred during the pre-implementation phase and 35 patients during the post-phase. Overall compliance with the guidelines increased from 62 to 67%. Mean pre-hospital compliance rose from 75 to 95%, and referring hospital compliance rose from 59 to 63%. While there was an improvement in compliance with the use of the dedicated trauma hotline (86-97%), the use of a transfer checklist (41-53%), and appropriateness of transfer (95-100%), none of these reached statistical significance. CONCLUSION: Practice guidelines have been developed to optimise the process of interhospital trauma transfers. An implementation programme met with limited success in improving compliance with the guidelines. Further work is needed to ensure awareness of these guidelines, with ongoing monitoring to ensure best practice and optimal patient outcome.

Adult↗
PubMed2005

Abdominal trauma: a disease in evolution.

BACKGROUND: The last decade has seen many changes in the way we investigate and manage abdominal injuries. This study assessed the pattern of abdominal injury and its investigation in patients admitted to a major trauma centre. METHODS: A retrospective registry review of all adult trauma patients admitted to Liverpool Hospital between January 1996 and December 2003 was undertaken. All adult trauma patients were included, identifying mechanism of injury, injury severity score, abbreviated injury score for the abdomen, investigations and intervention. The study period was divided (period 1 from 1996 to 1999, period 2 from 2000 to 2003) and the two periods compared to assess change. RESULTS: The study involved 1224 patients with abdominal injuries. Of these, 969 (79%) were a result of blunt trauma. The main causes were road accidents (61%), interpersonal violence (24%) and falls (7%). Penetrating injury increased from 16% to 25% between the two periods. There were 1274 intra-abdominal injuries, made up of 607 solid organ (liver (n = 220, 36%), spleen (n = 195, 32%), renal (n = 144, 24%) ), 291 hollow viscus (small bowel (n = 160, 55%), large bowel (n = 104, 36%) ) and 168 vascular. Four hundred and thirty-six (36%) patients underwent laparotomy, 65% for blunt trauma. Between the two periods there was a 46% decrease in the use of diagnostic peritoneal lavage, with a 40% increase in computed tomography and 325% increase in focused assessment with sonography for trauma. CONCLUSIONS: This study defined abdominal injury pattern and identified a significant shift in mechanism of injury and abdominal investigation at a major trauma centre during an 8-year study period. Abdominal trauma is indeed a disease in evolution.

Abdominal Injuries↗
PubMed2004

Internalized antigens must be removed to prepare hypoimmunogenic mesenchymal stem cells for cell and gene therapy.

Adult stem cells from human bone marrow stroma, referred to as mesenchymal stem cells or marrow stromal cells (hMSCs), are attractive candidates for clinical use. The optimal conditions for hMSC expansion require medium supplemented with fetal calf serum (FCS). Some forms of cell therapy will involve multiple doses, raising a concern over immunological reactions caused by medium-derived FCS proteins. By a sensitive fluorescence-based assay we determined that 7 to 30 mg of FCS proteins are associated with a standard preparation of 100 million hMSCs, a dosage that probably will be needed for clinical therapies. Here we present ex vivo growth conditions for hMSCs that reduce the FCS proteins to less than 100 ng per 100 million hMSCs, approximately a 100,000-fold reduction. The cells maintain their proliferative capacity and sustain their ability for multilineage differentiation. Experiments in rats demonstrate that rat MSCs grown in 20% FCS induce a substantial humoral response after repeated administrations, whereas cells grown under the conditions described in this study reduce the immunogenicity in terms of IgG response over 1000-fold to barely detectable levels. Our results have the potential to dramatically improve cellular and genetic therapies using hMSCs and perhaps other cells.

Adenosine Triphosphate↗
PubMed2003

Differentiation, cell fusion, and nuclear fusion during ex vivo repair of epithelium by human adult stem cells from bone marrow stroma.

To investigate stem cell differentiation in response to tissue injury, human mesenchymal stem cells (hMSCs) were cocultured with heat-shocked small airway epithelial cells. A subset of the hMSCs rapidly differentiated into epithelium-like cells, and they restored the epithelial monolayer. Immunocytochemistry and microarray analyses demonstrated that the cells expressed many genes characteristic of normal small airway epithelial cells. Some hMSCs differentiated directly after incorporation into the epithelial monolayer but other hMSCs fused with epithelial cells. Surprisingly, cell fusion was a frequent rather than rare event, in that up to 1% of the hMSCs added to the coculture system were recovered as binucleated cells expressing an epithelial surface epitope. Some of the fused cells also underwent nuclear fusion.

Animals↗
PubMed2003

Kyphoplasty--minimally invasive vertebral compression fracture repair.

OSTEOPOROSIS is a skeletal disorder that compromises bone strength, predisposing a person to an increased risk of fracture. An estimated 700,000 spinal fragility fractures, such as vertebral compression fractures, directly related to osteoporosis occur annually. KYPHOPLASTY, a minimally invasive fracture reduction procedure, has become a treatment option for osteoporotic fractures. A balloon is used in place of the conventional bone tamp to reduce the fracture and create a void in cancellous spinal bone. Polymethylmethacrylate, a cement-like material, is injected into the void to stabilize the fracture. EARLY DIAGNOSIS AND TREATMENT of vertebral compression fractures with kyphoplasty allows normal anatomy to be restored, ultimately decreasing the risk of patient morbidity.

Bone Cements↗
PubMed2003

Comparative genomics tools applied to bioterrorism defence.

Rapid advances in the genomic sequencing of bacteria and viruses over the past few years have made it possible to consider sequencing the genomes of all pathogens that affect humans and the crops and livestock upon which our lives depend. Recent events make it imperative that full genome sequencing be accomplished as soon as possible for pathogens that could be used as weapons of mass destruction or disruption. This sequence information must be exploited to provide rapid and accurate diagnostics to identify pathogens and distinguish them from harmless near-neighbours and hoaxes. The Chem-Bio Non-Proliferation (CBNP) programme of the US Department of Energy (DOE) began a large-scale effort of pathogen detection in early 2000 when it was announced that the DOE would be providing bio-security at the 2002 Winter Olympic Games in Salt Lake City, Utah. Our team at the Lawrence Livermore National Lab (LLNL) was given the task of developing reliable and validated assays for a number of the most likely bioterrorist agents. The short timeline led us to devise a novel system that utilised whole-genome comparison methods to rapidly focus on parts of the pathogen genomes that had a high probability of being unique. Assays developed with this approach have been validated by the Centers for Disease Control (CDC). They were used at the 2002 Winter Olympics, have entered the public health system, and have been in continual use for non-publicised aspects of homeland defence since autumn 2001. Assays have been developed for all major threat list agents for which adequate genomic sequence is available, as well as for other pathogens requested by various government agencies. Collaborations with comparative genomics algorithm developers have enabled our LLNL team to make major advances in pathogen detection, since many of the existing tools simply did not scale well enough to be of practical use for this application. It is hoped that a discussion of a real-life practical application of comparative genomics algorithms may help spur algorithm developers to tackle some of the many remaining problems that need to be addressed. Solutions to these problems will advance a wide range of biological disciplines, only one of which is pathogen detection. For example, exploration in evolution and phylogenetics, annotating gene coding regions, predicting and understanding gene function and regulation, and untangling gene networks all rely on tools for aligning multiple sequences, detecting gene rearrangements and duplications, and visualising genomic data. Two key problems currently needing improved solutions are: (1) aligning incomplete, fragmentary sequence (eg draft genome contigs or arbitrary genome regions) with both complete genomes and other fragmentary sequences; and (2) ordering, aligning and visualising non-colinear gene rearrangements and inversions in addition to the colinear alignments handled by current tools.

Amino Acid Sequence↗
PubMed2003

Displaced intra-articular calcaneal fractures: variables predicting late subtalar fusion.

OBJECTIVE: The goal of the current study was to analyze the prospective clinical outcome of patients who failed closed or open treatment of a displaced intra-articular calcaneal fracture. This cohort of patients required a secondary subtalar fusion by distraction bone-block arthrodesis. DESIGN: Review of prospective, randomized trial database. SETTING: Four level I trauma centers. PATIENTS: Between April 1, 1991 and December 31, 1997, 424 patients with 471 displaced intra-articular calcaneal fractures were involved in a large, multicenter, randomized trial. Forty-four patients who required subtalar fusion following initial treatment of a displaced intra-articular calcaneal fracture were compared to the population of patients who did not require subtalar fusion. The variables compared between the two groups included Böhler angles, two computed tomography classification systems, and clinical scores including SF-36, visual analogue score, and oral analogue score. INTERVENTION: Subtalar distraction bone-block arthrodesis with tricortical bone graft was used in all 45 feet. MAIN OUTCOME MEASUREMENTS: The following were examined: x-ray fracture classification, specifically Böhler angles and Essex-Lopresti classification; computed tomography classification, specifically Sanders and Crosby; clinical scores, specifically validated visual analogue score, general health survey scores, oral analogue score, and other factors (i.e., patient demographics including age, sex, profession, smoking history, and Worker's Compensation Board involvement. RESULTS: Initial treatment of the 44 patients in our study was nonoperative in 37 (84%) patients and operative (open reduction and internal fixation) in 7 (16%) (1 patient had bilateral heel fractures). Patients requiring fusion differed demographically from those patients not requiring fusion. Mean age was 39 years in both the fusion and nonfusion group. The fusion group had 97% males, whereas the nonfusion group had 89% males. Sixty-four percent of the fusion patients were Worker's Compensation Board claims, whereas 35% of the nonfusion group were Worker's Compensation Board claims. Of those that required fusion, 77% were heavy laborers. On average, the fusion group had a Böhler angle 15 degrees less than the nonfusion group. Forty-six percent of the fusion patients were Sanders-type IV initial fractures. Logistic regression analysis revealed that the primary predictors of requiring fusion were Worker's Compensation Board status (odds ratio = 3.03, 95% confidence interval = 1.41-6.57), Sanders-type IV (odds ratio = 5.48, 95% confidence interval = 1.57-19.18), Böhler angle <0 degrees (odds ratio = 10.64-95% confidence interval = 1.33-85.17), and nonoperative initial treatment (odds ratio = 5.86-95% confidence interval = 2.33-14.67). CONCLUSION: These data suggest that the amount of initial injury involved with the calcaneal fracture is the primary prognostic determinant of long-term patient outcome. Böhler angle on presentation of <0 degrees was 10 times more likely to require a secondary subtalar fusion than a Böhler angle on presentation of >15 degrees. Sanders-type IV calcaneal fractures were 5.5 times more likely to be fused than a simple Sanders type II fracture. Worker's Compensation Board patients were three times more likely to be fused than non-Worker's Compensation Board patients. Nonoperative care was six times more likely to lead to a late fusion as compared to open reduction and internal fixation treatment. Late fusion provided relief from pain and improved function as evidenced by an improvement in visual analogue score postsurgery. This study demonstrates that there is a distinct patient group with a displaced intra-articular calcaneal fracture who are at high risk of subtalar fusion. These include male Worker's Compensation Board patients who participate in heavy labor work with a fracture pattern with Böhler angle less than 0 degrees. If their initial treatment was nonoperative, the likelihood of requiring late subtalar fusion was significantly increased. Initial open reductional open reduction and internal fixation of patients with displaced intra-articular calcaneal fracture minimized the likelihood that subtalar fusion would be required.

Adolescent↗
PubMed2003

Lumbar end plate osteotomy in adult patients with scoliosis.

The maintenance of mobile segments in the lumbar spine may prevent complications associated with long fusions to the sacrum and permit improved postoperative patient function and mobility. The purpose of the current study was to describe the technique of end plate osteotomy for surgical treatment of fractional curves in the lumbosacral region. This technique serves to allow the end lumbar vertebra to become horizontal, to reduce lumbosacral fractional curves, and to create a stable end vertebra above the pelvis. A review of long-term clinical and radiographic outcomes in patients treated with the technique have been satisfactory. The authors show that the techniques of end plate osteotomy with concave osteophyte excision is a clinically valuable technique for the treatment of adults with fixed lumbosacral fractional curves.

Adult↗
PubMed2003

Sepsis in a renal transplant recipient due to Citrobacter braakii.

Cellulitis is usually caused by organisms such as beta-hemolytic streptococci and Staphylococcus aureus. Citrobacter are gram-negative bacilli that can cause opportunistic infections in immunocompromised hosts. They are rarely implicated in skin or soft tissue infections. The genus Citrobacter has been respeciated according to genetic relatedness. Citrobacter braakii refers to the genomospecies 6 of the Citrobacter freundii complex. There are no detailed studies of infections caused by the newly formed specific genetic species. We report a case of C. braakii infection in a renal transplant patient receiving immunosuppressive therapy. The patient's lower extremity cellulitis did not respond to conventional antibiotic therapy. Blood cultures grew C. braakii. Sensitivity studies and treatment with appropriate antibiotics resulted in prompt recovery. Immunosuppressive therapy in renal transplant recipients predisposes to infection by unusual pathogens, and this should be suspected when lack of a clinical response to conventional antibiotics is observed. We believe this is the first reported case of C. braakii cellulitis and bacteremia in a renal transplant recipient.

Anti-Bacterial Agents↗
PubMed2003

Crush injury and crush syndrome: a review.

Crush injuries and the subsequent systemic manifestations are well described, but there is limited evidence on which to base protocols for optimal management. Given that in most environments such in-juries are relatively rare, there is, however, an undoubted need for such guidelines. This article reviews the currently available evidence and summarizes the treatment options available.

Crush Syndrome↗
PubMed2003

Word reading and reading-related skills in adolescents with Williams syndrome.

BACKGROUND: Individuals with Williams syndrome have good spontaneous language despite low levels of intelligence. This study explores the relationship between intelligence, word decoding and reading-related skills in 20 individuals with Williams syndrome. METHODS: In addition to the KBIT, the participants were administered standardized measures of reading, vocabulary, rapid naming, phonological skills and an experimental measure of rhyme judgement. RESULTS: There was wide variability in the reading achievement among the individuals with WS. While some participants were unable to recognize letters of the alphabet, others scored within the normal range of tests of single word reading and decoding. Reading scores were correlated with intelligence as measured on KBIT matrices but not with the vocabulary measures. Reading also correlated with phonological awareness tasks yet, surprisingly, not with rapid naming. CONCLUSION: It is suggested that in individuals with retardation, intelligence rather than language and language-related skills predict achievements in word reading.

Adolescent↗