PubMed Health⌕ Search

Biomedical subjects

Jason A Smith

Publications and source records attributed to Jason A Smith.

18 recordsLinked to original sources
PubMed2006

The regioselective synthesis of aryl pyrroles.

Pyrrole is a unique aromatic molecule as it can readily undergo substitution at all five positions but obtaining the desired regioisomer can prove difficult to control. We now report our results on the regioselective arylation of pyrrole, utilizing selective halogenation and the Suzuki-Miyaura reaction to prepare C4-, C5- and C3-aryl derivatives. We have applied this methodology to the synthesis of lamellarin O dimethyl ether, an intermediate in the synthesis of lukinol A.

Benzene Derivatives↗
PubMed2006

Complications of chronic otitis media and cholesteatoma.

The incidence of complications of chronic otitis media and cholesteatoma has decreased since the proliferation of antibiotics early in the twentieth century. However, these complications continue to occur, and can be lethal if they are not identified and treated properly. Therapy for the complications associated with chronic otitis media, unlike that of acute otitis media, usually involves surgical intervention. As medical (antibiotic) therapy continues to improve, and new imaging techniques are introduced, less invasive treatment modalities may be shown to be as effective as the classic, time-tested, surgical options.

Anti-Bacterial Agents↗
PubMed2006

Proteomic comparison of needles from blister rust-resistant and susceptible Pinus strobus seedlings reveals upregulation of putative disease resistance proteins.

In order to characterize a hypersensitive-like reaction in selected Pinus strobus seedlings to Cronartium ribicola, a proteomic comparison of needles from resistant and susceptible seedlings was undertaken using two-dimensional gel electrophoresis (2-DE). The results revealed 19 polypeptides specific to resistant seedlings and seven of these specific to infected resistant seedlings. There were 13 polypeptides up-regulated (> or = 3-fold increase) in resistant family P327 in comparison to needle tissue from susceptible and mock-inoculated seedlings. Electrospray ionization liquid chromatography and tandem mass spectrometry was used to sequence 11 proteins from the 2-DE gels. Sequences obtained from electrospray ionization liquid chromatography and tandem mass spectrometry were used for MS-BLAST and Pro-ID database searches allowing identification with a 95 to 99% confidence level. Six proteins were determined to be homologs of proteins with known roles in disease resistance, five were determined to be homologs of members of the leucine-rich repeat (LRR) superfamily, and one was a homolog of heat shock protein 90, a protein that serves as a cofactor for certain LRR proteins. This is the first report of members of the LRR family with functional homologs in Pinus strobus and of a molecular basis for white pine blister rust resistance in Pinus strobus.

Amino Acid Sequence↗
PubMed2005

Towards high capacity latex-coated porous polymer monoliths as ion-exchange stationary phases.

The preparation of high capacity agglomerated monolithic ion-exchangers for capillary ion chromatography is described. Post-modification of reactive monoliths was investigated as an alternative to co-polymerisation of a suitable functional monomer with an overarching goal of increasing ion-exchange capacity. Direct sulfonation of poly styrene-co-divinyl benzene monoliths using concentrated sulfuric acid or chlorosulfonic acid was unsuccessful even for monoliths containing as low as 8% crosslinker. In contrast, chemical transformation of reactive monoliths containing glycidyl methacrylate was used to increase the ion-exchange capacity by up to more than thirty-fold with ion exchange capacities of 14-29 microequiv g(-1) achieved. Three different reactions were considered, including reaction with 4-hydroxybenenesulfonic acid under basic conditions; reaction with thiobenzoic acid followed by transformation to a reactive thiol and the subsequent oxidation to the sulfonic acid; and direct sulfonation with sodium sulfite. Of these, the reaction with sodium sulfite resulted in the most significant increase in the capacity and the best separation performance. In the isocratic mode separation efficiencies of over 13,500 plates m(-1) were observed (for iodate). The separation of seven inorganic anions was also demonstrated using a hydroxide gradient.

Chromatography, Ion Exchange↗
PubMed2005

A role for DNA mismatch repair protein Msh2 in error-prone double-strand-break repair in mammalian chromosomes.

We examined error-prone nonhomologous end joining (NHEJ) in Msh2-deficient and wild-type Chinese hamster ovary cell lines. A DNA substrate containing a thymidine kinase (tk) gene fused to a neomycin-resistance (neo) gene was stably integrated into cells. The fusion gene was rendered nonfunctional due to a 22-bp oligonucleotide insertion, which included the 18-bp I-SceI endonuclease recognition site, within the tk portion of the fusion gene. A double-strand break (DSB) was induced by transiently expressing the I-SceI endonuclease, and deletions or insertions that restored the tk-neo fusion gene's reading frame were recovered by selecting for G418-resistant colonies. Overall, neither the frequency of recovery of G418-resistant colonies nor the sizes of NHEJ-associated deletions were substantially different for the mutant vs. wild-type cell lines. However, we did observe greater usage of terminal microhomology among NHEJ events recovered from wild-type cells as compared to Msh2 mutants. Our results suggest that Msh2 influences error-prone NHEJ repair at the step of pairing of terminal DNA tails. We also report the recovery from both wild-type and Msh2-deficient cells of an unusual class of NHEJ events associated with multiple deletion intervals, and we discuss a possible mechanism for the generation of these "discontinuous deletions."

Animals↗
PubMed2004

Modeling branched polyethylene: copolymers possessing precisely placed ethyl branches.

A structural investigation of precise ethylene/1-butene (EB) copolymers has been completed using step polymerization chemistry. The synthetic methodology needed to generate four model copolymers is described; their primary and higher level structure is characterized. The copolymers possess an ethyl branch on every 9th, 15th, and 21st carbon along the backbone of linear polyethylene. Melting points and heats of fusion decrease with increased branch frequency. Differential scanning calorimetry and infrared spectroscopy show highly disordered crystal structures favoring ethyl branch inclusion. On the other hand, the EB copolymers contain high concentrations of kink and gauche defects independent of branch frequency. These model copolymers are compared with random copolymers produced using traditional chain chemistry and previously synthesized ADMET EP copolymers.

Journal Article↗
PubMed2004

Biomechanics of cervical laminoplasty: kinetic studies comparing different surgical techniques, temporal effects and the degree of level involvement.

Laminoplasty is a common surgical technique used to treat cervical myelopathy. Both voids and contradictory information exist in the literature with regard to the initial and long-term biomechanical consequences of cervical laminoplasty. In order to clarify the existing literature, as well as provide clinically useful information, we identified three specific aims: (1) to measure the long-term differences in kinetics between the open door laminoplasty (ODL) and French door laminoplasty (FDL) techniques; (2) to delineate differences in primary and long-term cervical motion after laminoplasty; and (3) to determine whether inclusion of additional levels in the laminoplasty procedure results in a change in immediate cervical biomechanics. The study design involved both an animal (caprine) model and in vitro surgical simulation. We kinematically evaluated the cervical spine specimens (C2-C7) by applying pure bending moment loads to the cephalad vertebra (C2), while constraining the caudal vertebra (C7). Resultant intervertebral rotations (C3-C6) were determined via stereophotogrammetry. Overall, the data indicate that both FDL and ODL significantly reduce range of motion 6 months postoperatively, compared with the un-operated spine. There were no significant differences between the two techniques after 6 months. We also showed that ODL produces a significant reduction in motion 6 months postoperatively compared with the immediate postoperative condition. Finally, the data indicated that extending the laminoplasty from two to four levels did not significantly change range of motion. The choice of technique should be based upon the surgeon's experience with these technically demanding procedures. In addition, initial stability considerations should not affect the decision to extend the laminoplasty to adjacent levels. Finally, the data also suggest that early changes in biomechanics should not be a major factor when considering whether immobilization of the cervical spine is necessary after laminoplasty. In fact, our temporal study, as well as previously reported clinical data, indicates that one should expect significantly decreased intervertebral motion 6 months after laminoplasty. Therefore, early physical therapy should be considered to preserve a more physiologic pattern of cervical range of motion.

Animals↗
PubMed2004

Legislative approaches to the obesity epidemic.

Legislative bodies in the United States have often passed laws to regulate food in its production, content, and sale. Additionally, legislatures have created economic policies that directly affect the food supply and determine both the type and quantity of food available. Legislatively-enacted federal programs, such as the National School Lunch Program, also provide opportunities to promote good nutrition. These traditional areas of legislation represent the most efficient means to affect the food environment legislatively. While exploring legislative solutions to obesity, it is also imperative to monitor attempts by the legislature to constrain other public health strategies by limiting private enforcement and limiting the regulatory freedom of traditional public health authorities.

Adult↗
PubMed2004

Determination of intrachromosomal recombination rates in cultured mammalian cells.

Recombination is involved in many important biological processes including DNA repair, gene expression, and generation of genetic diversity. Recombination must be carefully regulated so as to prevent the deleterious consequences that may result from rearrangements between dissimilar sequences in a genome. It is of considerable interest to study the mechanisms by which genetic rearrangements in mammalian chromosomes are regulated in order to understand better how genomic integrity is normally maintained and to gain insight into the types of genetic mutations that may destabilize the genome. To explore such issues in mammalian chromosomes, a suitable experimental system must be developed. In this chapter, we describe a model system for studying intrachromosomal recombination in cultured mammalian cells. We discuss two model recombination substrates, a method for stably introducing the substrates into cultured Chinese hamster ovary cells, and a method for determining rates of intrachromosomal recombination between sequences contained within the integrated substrates. The general approach described here should be applicable to the study of a variety of aspects of recombination in virtually any cultured mammalian cell line.

Animals↗
PubMed2003

Temperature and thermal dose distributions during intradiscal electrothermal therapy in the cadaveric lumbar spine.

STUDY DESIGN: Human cadaveric lumbar spines were used to assess the temperature and thermal dose distribution during intradiscal electrothermal therapy in vitro. OBJECTIVES: To determine whether intradiscal electrothermal therapy produces adequate tissue temperatures to denature annular collagen or ablate nerve cells. SUMMARY OF BACKGROUND DATA: Several hypothesized mechanisms for the effect of intradiscal electrothermal therapy have been suggested and include: 1) shrinkage of the nucleus and/or the annulus fibrosus by contraction of collagen fibers; and 2) thermal ablation of sensitive nerve fibers in the outer annulus. METHODS: Intradiscal electrothermal therapy was performed using the standard clinical protocol on 12 lumbar specimens in a 37.0 degrees C water bath using the SpineCath by Oratec. Temperatures were recorded simultaneously at 40 different locations in the disc. Thermal dose (Equivalent Minutes 43.0 degrees C) was calculated at each temperature point. RESULTS: The highest temperature measured (out of 520 points) was 64.0 degrees C and was within 1 mm of the heating coil. Temperatures in excess of 60 degrees C were all within 1 to 2 mm of the intradiscal electrothermal therapy catheter surface, the 50 to 60 degrees C range extended approximately 6 mm, above 48 degrees C extended approximately 7 mm, and above 45 degrees C extended to approximately 10 mm. Less than 2% of points achieved temperatures sufficient for collagen denaturation (>60 degrees C). On average, 42.5% of points accumulated >250 Equivalent Minutes 43.0 degrees C, a conservative common dose threshold for thermal necrosis of cells. The time history of thermal measurements demonstrated that the disc temperature had not reached steady state by the end of the heating protocol (16.5 minutes). CONCLUSIONS: Except for a very limited margin (1-2 mm) around the catheter, the temperature necessary to induce collagen shrinkage was not observed within the disc. Temperatures sufficient to ablate nerves were developed in some areas but were not reliably produced in clinically relevant regions, such as the posterior annulus. These results suggest that beneficial clinical outcomes may be critically dependent on probe placement or other factors unknown.

Cadaver↗
PubMed2003

Management of fixed sagittal plane deformity: outcome of combined anterior and posterior surgery.

STUDY DESIGN: Retrospective study of consecutive patient series. OBJECTIVES: To review the radiographic and clinical results of patients with preoperative fixed sagittal imbalance treated with combined anterior and posterior arthrodesis, and to determine factors that predict clinical outcome. SUMMARY OF BACKGROUND DATA: Combined anterior and posterior arthrodesis of the spine is useful in the management of fixed deformity involving the coronal and sagittal planes. The specific indications for combined surgery in the patient with regional and global imbalance have not been well defined. METHODS: Retrospective review of 25 consecutive patients treated with combined anterior and posterior spinal arthrodesis. Inclusion criteria included a preoperative global sagittal imbalance of at least 5 cm. Outcome variables included radiographic measures of preoperative, postoperative, and follow-up films, and a clinical assessment using the Modified SRS Outcomes Instrument and a review of postoperative complications. RESULTS: Twenty-five consecutive cases were reviewed. Mean age was 58 years (range 38-77), and mean follow-up was 55 months (range 24-81) for clinical and 44.5 (range 24-81) months for radiographic outcome variables. The mean preoperative sagittal imbalance was 10.5 cm (range 5.2-23.3), which improved to 2.9 cm (range 0-12.6) after surgery, and was maintained as 3.3 cm (range 0-13.5) at follow-up. Mean lumbar lordosis was -23 degrees (range +40 to -47) before surgery, and increased to -42 degrees at follow-up (range -20 degrees to -60 degrees ), an increase of 19 degrees. Patients with preoperative regional hypolordosis in the lumbar spine that was corrected surgically had the highest postoperative scores. The mean score for patient satisfaction with surgical management was 4.45 (range 2.5-5). Correlation analysis of clinical outcome domains demonstrated that patient satisfaction correlated poorly with domains of pain (r = 0.37, P = 0.1) and function (r = 0.4, P = 0.09). Within the domains, self-image showed highest correlation with patient satisfaction (r = 0.65, P = 0.006) and total score (r = 0.89, P = 0.0001). CONCLUSIONS: Patients with global sagittal imbalance of the spine were effectively treated with a combined anterior and posterior arthrodesis as measured by radiographic parameters. Patient satisfaction with surgery, and overall clinical outcomes were best in cases that resulted in an increase in lumbar lordosis. The subset of patients with preoperative regional hypolordosis of the lumbar spine has better outcomes than those with preoperative lumbar lordosis in the physiologic range.

Adult↗
PubMed2003

Modeling random methyl branching in ethylene/ propylene copolymers using metathesis chemistry: synthesis and thermal behavior.

The structure of random ethylene/propylene (EP) copolymers has been modeled using step polymerization chemistry. Six ethylene/propylene model copolymers have been prepared via acyclic diene metathesis (ADMET) polymerization and characterized for primary and higher level structure using in-depth NMR, IR, DSC, WAXD, and GPC analysis. These copolymers possess 1.5, 7.1, 13.6, 25.0, 43.3, and 55.6 methyl branches per 1000 carbons. Examination of these macromolecules by IR and WAXD analysis has demonstrated the first hexagonal phase in EP copolymers containing high ethylene content (90%) without the influence of sample manipulation (temperature, pressure, or radiation). Thermal behavior studies have shown that the melting point and heat of fusion decrease as the branch content increases. Further, comparisons have been made between these random ADMET EP copolymers, random EP copolymers made by typical chain addition techniques, and precisely branched ADMET EP copolymers.

Journal Article↗
PubMed2002

Predictors of flexibility and pain patterns in thoracolumbar and lumbar idiopathic scoliosis.

STUDY DESIGN: A retrospective evaluation of radiographs in patients with idiopathic scoliosis was undertaken to assess predictors of flexibility. OBJECTIVE: To evaluate potential predictors of flexibility in patients with thoracolumbar and lumbar scoliosis. SUMMARY OF BACKGROUND DATA: Curve flexibility is an important consideration in the operative management of idiopathic scoliosis. Flexibility of the major curve is a useful predictor of expected surgical correction, and flexibility of compensatory curves determines whether they are structural or nonstructural. An accurate assessment of curve flexibility has important implications on surgical approaches and planning for deformity correction. The role of age and curve magnitude in predicting curve flexibility has not been well defined. A quantitative assessment of changes in curve flexibility with age and progression of deformity may yield important insight into the change in surgical management options over time. METHODS: A retrospective review of 75 patients with idiopathic thoracolumbar and lumbar scoliosis (age range 13-78 years) was undertaken. Preoperative standing and side-bending radiographs of thoracolumbar and lumbar curves were evaluated. Cobb angles of structural and fractional curves, curve flexibility, presence of lateral listhesis, and axial and radicular pain were documented. Predictors of structural and fractional curve flexibility were evaluated with correlation and regression analysis. Correlation analysis was used to demonstrate an association between radiographic findings and the clinical presentation. RESULTS: Seventy-five patients had an average major curve magnitude of 56 degrees (range 34-82 degrees ) with flexibility averaging 55% (range 20-93%). Structural curve flexibility was highly inversely correlated with both curve magnitude (r = -0.7; P< 0.001) and with age (r = -0.6; P< 0.001). Lumbar fractional curve (L4-S1) flexibility showed a high inverse correlation with age (r = -0.65; P< 0.001) but did not show correlation with Cobb angle. Thoracic compensatory curves showed a moderate correlation with Cobb angle (r = 0.53). Structural and fractional curve flexibility showed high correlation with each other (r = 0.5-0.66). Regression analysis yielded a formula to predict the flexibility of the structural curve (FSC): FSC = 130 - (Cobb + Age/2). Axial pain was correlated with age (r = 0.63); however, it was not correlated with curve magnitude. CONCLUSION: We have shown that curve magnitude and patient age are the main predictors of structural flexibility. Every 10 degrees increase in curve magnitude over 40 degrees results in a 10% decrease in flexibility; every 10-year increase in age decreases flexibility of the structural curve by 5% and the lumbosacral fractional curve by 10%. Curve magnitude and age of the patients are significant predictors of curve flexibility. The demonstration of this association offers useful information in estimating how surgical options for deformity correction may change over time.

Adolescent↗
PubMed2002

Outcome and complications of long fusions to the sacrum in adult spine deformity: luque-galveston, combined iliac and sacral screws, and sacral fixation.

STUDY DESIGN: A retrospective study of adults with long fusion to the sacrum using three different fixations was performed. OBJECTIVE: To compare the long-term clinical results and complications associated with three methods of lumbosacral fixation for adult spine deformities: Luque-Galveston, combined iliac and sacral screws, and sacral screws. SUMMARY OF BACKGROUND DATA: The preferred technique for long fusion to the sacrum is controversial, and surgery for adult deformity is fraught with significant technical difficulties and high complication rates. No clinical study compares the long-term outcome of long fusion to the sacrum using these different methods of lumbosacral fixation. METHODS: This study included 54 consecutive patients who underwent elective combined anterior and posterior surgical reconstruction for adult spine deformity with a minimum follow-up period of 2 years. The patients were divided into three groups on the basis of the surgical method used for the posterior spine instrumentation. Group 1 consisted of 11 patients with smooth L-rod and segmental sublaminar wire instrumentation (Luque-Galveston technique). Group 2 consisted of 36 patients with posterior Isola segmental instrumentation and combined iliac and sacral screws. Group 3 consisted of 12 patients with Isola segmental instrumentation using bicortical sacral screws. Five patients were revised to another fixation group, giving a total of 59 cases. Radiographic, clinical results, and long-term outcome data were obtained using the modified Scoliosis Research Society (SRS) outcome instrument. RESULTS: There were 26 late complications. Pseudarthrosis developed in 10 patients, requiring revision surgery: 4 (36%) in the Group 1, 5 (14%) in Group 2, and 1 (8.5%) in Group 3. Comparison of the modified SRS outcomes showed no difference among the groups. The average SRS grand total score was 73.4% for Group 1, 70.9% for Group 2, and 62.6% for Group 3. Overall, 76% of the patients were satisfied with their outcome. The presence of perioperative complications or pseudarthrosis significantly correlated with a lower satisfaction score (P = 0.012 and P = 0.048, respectively). Sagittal plane decompensation significantly correlated with a higher pain score (P = 0.035). Patients with prior surgeries scored lower on the self-image questions than patients with no prior surgery (P = 0.007). CONCLUSIONS: Attention to sagittal balance is critical in these patients. Revision surgery is as safe and effective as primary surgery. According to the current findings, the Luque-Galveston fixation technique has an unacceptably high rate of pseudarthrosis, and this method is not recommended for adult deformities. Currently, the authors are using bicortical and triangulated sacral screws with an anterior interbody support in patients with good bone stock, but only when the spine balance is restored. Otherwise, they recommend using iliac fixation, although there is a higher rate of painful hardware, requiring removal.

Adult↗
PubMed2002

Does instrumented anterior scoliosis surgery lead to kyphosis, pseudarthrosis, or inadequate correction in adults?

STUDY DESIGN: Retrospective review of cases in which a single solid rod was used for the anterior correction of thoracolumbar and lumbar idiopathic scoliosis in adults. OBJECTIVES: To evaluate the efficacy and outcomes in these patients. SUMMARY OF BACKGROUND DATA: Anterior spinal fusion with instrumentation has been found to be kyphogenic in the treatment of scoliosis. Recent reports have shown an extremely high rate of pseudarthrosis and implant failure even in adolescents who have undergone anterior spinal fusion with a single flexible or rigid rod. METHODS: Fifteen consecutive adult patients with (average age, 37.5 years) had undergone anterior spinal fusion with a rigid rod were included in this study. One was lost to follow-up, leaving 14 patients with a complete radiographic follow-up of 44 months and clinical follow-up of 61 months. Patients were sent the Modified Scoliosis Research Society (SRS) Outcomes Instrument, charts were reviewed, and preoperative, postoperative, and final follow-up films of the entire spine were evaluated by independent reviewers uninvolved in the care of the patients. RESULTS: The average preoperative major curve was 50 degrees, which improved to 16 degrees at follow-up (a 66% correction). The average correction of the upper compensatory curve and lower fractional curve were 40% and 61%, respectively. The thoracolumbar sagittal plane alignment was maintained or improved in all patients (i.e., this surgery did not induce kyphosis in any patient). On average 0.9 levels were "saved" compared with levels chosen by the authors for posterior surgery. All patients achieved a solid fusion. Follow-up Modified SRS questionnaires revealed a satisfaction score 4.5 out of a possible score of 5, a pain score of 4.1 out of 5, a self-image score of 4.1 out of 5, a function score of 4.1 out of 5, and a mental health score of 4.0 out of 5, with an overall score of 82%. All patients but one were satisfied or extremely satisfied with the results of surgery. There was no incidence of implant breakage. CONCLUSIONS: The results of anterior spinal fusion using a single solid rod in adults with idiopathic scoliosis in this series are excellent, with 100% fusion rate, no development of kyphosis, and no incidence of hardware failure.

Adult↗