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Biomedical subjects

Jason Lee

Publications and source records attributed to Jason Lee.

At least 19 recordsLinked to original sources

Helical blade versus sliding hip screw for treatment of unstable intertrochanteric hip fractures: a biomechanical evaluation.

OBJECTIVE: To compare the fixation stability in the femoral head with sliding hip screw versus helical blade designs for unstable, intertrochanteric hip fractures. METHODS: A simulated, unstable intertrochanteric hip fracture was created in six pairs of cadaveric femurs. One of each pair was treated using an intramedullary nail with a sliding hip screw (ITST) for femoral head fixation and the other was treated with a nail with a helical blade (TFN). Each specimen was cyclically loaded with 750N vertical loads applied for 10, 100, 1000 and 10,000 cycles. Measurements for femoral head displacement, fracture fragment opening and sliding were made. Specimens were then loaded to failure. RESULTS: There was significantly more permanent inferior femoral head displacement in the ITST samples compared to the TFN samples after each cyclic loading (all p values<0.05). There was significantly more permanent fracture site opening and inferior displacement in the ITST group compared with the TFN group at 1000 and 10,000 cycles (p<0.05). Final loads to failure were not significantly different (p=0.51) between the two treatment groups. Nine specimens demonstrated fracture extension into the anteromedial cortex and subtrochanteric region and three specimens, which had an ITST implant, demonstrated a splitting fracture of the femoral head. CONCLUSION: This study demonstrated that fixation of the femoral head with a helical blade was biomechanically superior to fixation with a standard sliding hip screw in a cadaveric, unstable intertrochanteric hip fracture model.

Biomechanical Phenomena↗

Climacturia following radical prostatectomy: prevalence and risk factors.

PURPOSE: Following radical prostatectomy urine leakage during orgasm is a poorly defined entity. We defined the prevalence, quantity, bother and coping mechanisms associated with this complication, called climacturia. MATERIALS AND METHODS: A self-administered questionnaire was given to a cohort of sexually active men after radical prostatectomy. We inquired about the frequency, quantity, bother and coping mechanisms associated with climacturia. We also recorded uroflowmetry and an American Urological Association symptom score (International Prostate Symptom Score) in each patient. RESULTS: Of the 42 patients enrolled with a mean age of 58.9 years and average time since radical prostatectomy of 23.6 months climacturia was reported in 19 (45%). Of the men 68% reported that it happened rarely or only occasionally, while 21% reported that it occurred most of the time or always. In terms of urine quantity 58% of respondents reported only a few drops but 16% reported a loss of more than 1 ounce. Of the patients 52% percent reported no or minimal bother but 48% reported that climacturia caused significant bother. Only 21% of respondents thought that it was of significant bother to their partners. Of the respondents 84% emptied the bladder before intercourse and 11% used condoms. Age, Gleason score and time since surgery were not predictors of climacturia. No association between peak urine flow on uroflowmetry or International Prostate Symptom Score and climacturia was found. CONCLUSIONS: Climacturia is a common clinical entity, occurring in almost half of all patients after radical prostatectomy. It can be a significant problem with respect to urine volume loss, associated bother and condom use. Patients must be informed about this complication before undergoing radical prostatectomy.

Adaptation, Psychological↗

PIP2 activates TRPV5 and releases its inhibition by intracellular Mg2+.

The transient receptor potential type V5 channel (TRPV5) is a Ca2+-selective TRP channel important for epithelial Ca2+ transport. Intracellular Mg2+ causes a fast voltage-dependent block of the TRPV5 channel by binding to the selectivity filter. Here, we report that intracellular Mg2+ binding to the selectivity filter of TRPV5 also causes a slower reversible conformational change leading to channel closure. We further report that PIP2 activates TRPV5. Activation of TRPV5 by PIP2 is independent of Mg2+. Yet, PIP2 decreases sensitivity of the channel to the Mg2+-induced slow inhibition. Mutation of aspartate-542, a critical Mg2+-binding site in the selectivity filter, abolishes Mg2+-induced slow inhibition. PIP2 has no effects on Mg2+-induced voltage-dependent block. Thus, PIP2 prevents the Mg2+-induced conformational change without affecting Mg2+ binding to the selectivity filter. Hydrolysis of PIP2 via receptor activation of phospholipase C sensitizes TRPV5 to the Mg2+-induced slow inhibition. These results provide a novel mechanism for regulation of TRP channels by phospholipase C-activating hormones via alteration of the sensitivity to intracellular Mg2+.

Animals↗

Microarray-based detection of protein binding and functionality by gold nanoparticle probes.

We report a microarray format for the detection of proteins and protein functionality (kinase activity) based on marking either specific antibody-protein binding or peptide phosphorylation events by attachment of gold nanoparticles followed by silver deposition for signal enhancement. The attachment of the gold nanoparticles is achieved by standard avidin-biotin chemistry. The detection principle is resonance light scattering. Highly selective recognition of standard proteins (proteins A and G) down to 1 pg/mL for proteins in solution and 10 fg for proteins on the microarray spots is demonstrated. Enzyme activity of the kinase (PKA) is detected with high specificity down to a limit of 1 fg for an established peptide substrate (kemptide) on the microarray spots. Kinase inhibition by the inhibitor (H89) is shown, demonstrating the potential for high-throughput screening for inhibitors.

Gold↗

Best evidence topic report. Proteolytic enzymes for oesophageal meat impaction.

A short cut review was carried out to establish whether proteolytic enzymes are effective at resolving oesophageal meat impaction. Altogether 98 papers were found using the reported search, of which three presented the best evidence to answer the clinical question. The author, date and country of publication, patient group studied, study type, relevant outcomes, results and study weaknesses of these best papers are tabulated. A clinical bottom line is stated.

Ananas↗

Best evidence topic report. Effervescent agents for oesophageal food bolus impaction.

A short cut review was carried out to establish whether fizzy drinks alone are effective at resolving food bolus impaction. Altogether 46 papers were found using the reported search, of which six presented the best evidence to answer the clinical question. The author, date and country of publication, patient group studied, study type, relevant outcomes, results and study weaknesses of these best papers are tabulated. A clinical bottom line is stated.

Animals↗

A stochastic model for the detection of coherent motion.

A computational model is presented for the detection of coherent motion based on template matching and hidden Markov models. The premise of this approach is that the growth in detection sensitivity is greater for coherent motion of structured forms than for random coherent motion. In this preliminary study, a recent experiment was simulated with the model and the results are shown to be in agreement with the above premise. This model can be extended to be part of a more complex and elaborate computational visual system.

Algorithms↗

Complications of endovascular repair of high-risk and emergent descending thoracic aortic aneurysms and dissections.

PURPOSE: The advent of endovascular prostheses to treat descending thoracic aortic lesions offers an alternative approach in patients who are poor candidates for surgery. The development of this approach includes complications that are common to the endovascular treatment of abdominal aortic aneurysms and some that are unique to thoracic endografting. METHODS: We conducted a retrospective review of 60 emergent and high-risk patients with thoracic aortic aneurysms (TAAs) and dissections treated with endovascular prostheses over 4 years under existing investigational protocols or on an emergent compassionate use basis. RESULTS: Fifty-nine of the 60 patients received treatment, with one access failure. Thirty-five patients received treatment of TAAs. Four of these procedures were performed emergently because of active hemorrhage. Twenty-four patients with aortic dissections (16 acute, 8 chronic) also received treatment. Eight of the patients with acute dissection had active hemorrhage at the time of treatment. Three devices were used: AneuRx (Medtronic; n = 31), Talent (Medtronic; n = 27), and Excluder (Gore; n = 1). Nineteen secondary endovascular procedures were performed in 14 patients. Most were secondary to endoleak (14 of 19), most commonly caused by modular separation of overlapping devices (n = 8). Other endoleaks included 4 proximal or distal type I leaks and 2 undefined endoleaks. The remaining secondary procedures were performed to treat recurrent dissection (n = 1), pseudoaneurysm enlargement (n = 3), and endovascular abdominal aortic aneurysm repair (n = 1). One patient underwent surgical repair of a retrograde ascending aortic dissection after endograft placement. Procedure-related mortality was 17% in the TAA group and 13% in the dissection group, including 2 acute retrograde dissections that resulted in death from cardiac tamponade. Overall mortality was 28% at 2-year follow-up. CONCLUSION: Although significant morbidity and mortality remain, endovascular repair of descending TAAs and dissections in patients at high-risk patients can be accomplished with acceptable outcomes compared with traditional open repair. The major cause for repeat intervention in these patients was endoleak, most commonly caused by device separation. Improved understanding of these complications may result in a decrease in secondary procedures, morbidity, and mortality in these patients. The need for secondary interventions in a significant number of patients underscores the necessity for continued surveillance.

Adult↗

Noise exposure of music teachers.

A noise exposure survey was performed to assess the risk of hearing loss to school music teachers during the course of their activities. Noise exposure of 18 teachers from 15 schools was measured using noise dosimeters. The equivalent continuous noise level (L(eq)) of each teacher was recorded during single activities (classes) as well as for the entire day, and a normalized 8-hour exposure, termed the noise exposure level (L(ex)) was also computed. The measured L(eq) exceeded the 85-dBA limit for 78% of the teachers. L(ex) exceeded 85 dBA for 39% of the teachers. Limited recommendations on how to reduce the noise exposures are provided. The need for a hearing conservation program has also been emphasized.

Environmental Monitoring↗

Ectopic LT alpha beta directs lymphoid organ neogenesis with concomitant expression of peripheral node addressin and a HEV-restricted sulfotransferase.

Lymph node (LN) function depends on T and B cell compartmentalization, antigen presenting cells, and high endothelial venules (HEVs) expressing mucosal addressin cell adhesion molecule (MAdCAM-1) and peripheral node addressin (PNAd), ligands for naive cell entrance into LNs. Luminal PNAd expression requires a HEV-restricted sulfotransferase (HEC-6ST). To investigate LT alpha beta's activities in lymphoid organogenesis, mice simultaneously expressing LT alpha and LT beta under rat insulin promoter II (RIP) control were compared with RIPLT alpha mice in a model of lymphoid neogenesis and with LT beta-/- mice. RIPLT alpha beta pancreata exhibited massive intra-islet mononuclear infiltrates that differed from the more sparse peri-islet cell accumulations in RIPLT alpha pancreata: separation into T and B cell areas was more distinct with prominent FDC networks, expression of lymphoid chemokines (CCL21, CCL19, and CXCL13) was more intense, and L-selectin+ cells were more frequent. In contrast to the predominant abluminal PNAd pattern of HEV in LT beta-/- MLN and RIPLT alpha pancreatic infiltrates, PNAd was expressed at the luminal and abluminal aspects of HEV in wild-type LN and in RIPLT alpha beta pancreata, coincident with HEC-6ST. These data highlight distinct roles of LT alpha and LT alpha beta in lymphoid organogenesis supporting the notion that HEC-6ST-dependent luminal PNAd is under regulation by LT alpha beta.

Animals↗

Accuracy of three-dimensional simulation in the sizing of aortic endoluminal devices.

The purpose of this study is to examine the accuracy of a 3D simulation generated by inclusion of various intensity-selected portions of spiral CT data into a proprietary software program (Preview, Medical Media Systems, MMS) in preoperative and postoperative assessment of the anatomical features of abdominal aortic aneurysm (AAA). The accuracy of this software was measured against two other modalities-intravascular ultrasound (IVUS) and axial CT scan-using the IVUS as the reference. Eighty-five patients were included; 43 underwent AAA endovascular exclusion with Talent devices, and 42 with Aneurx devices. Measurement of proximal neck diameter was performed using IVUS, Preview software, and axial CT scan with manual calipers. Measurement of the AAA maximum diameter was performed using Preview software and axial CT scan; 253 measurements in the 85 patients were included. These measurements were compared by means of both linear regression and Bland-Altman agreement analysis. Our results showed that the 95% confidence interval between the Preview software and mean IVUS measurement of proximal AAA neck (3.1 and 2.5) is narrow enough for the software to be used in sizing AAA. This would be especially important for having the properly sized devices available preoperatively. The Preview software tended to be more accurate than CT scans although it was not statistically significant.

Aged↗

An alternative anesthetic technique for the morbidly obese patient undergoing endovascular repair of an abdominal aortic aneurysm.

UNLABELLED: Abdominal aortic aneurysms have been treated by open operative repair for many years. A frequent rate of morbidity is associated with the natural history of abdominal aortic aneurysms in combination with open surgical repair. Recently a new technique that is less surgically invasive has been developed as an alternative to open repair. The present case report outlines a less invasive anesthetic technique for the morbidly obese patient. IMPLICATIONS: This case report discusses a minimally invasive anesthetic approach towards the morbidly obese patient undergoing endovascular abdominal aortic aneurysm repair. It demonstrates a safe and cost-effective means of managing a patient with numerous comorbidities. We also discuss an anesthetic/surgical approach on how to provide maximum analgesia with minimal anesthesia.

Adult↗

Synthesis of [difluoro-(3-alkenylphenyl)-methyl]-phosphonic acids on non-crosslinked polystyrene and their evaluation as inhibitors of PTP1B.

A series of [difluoro-(3-alkenylphenyl)-methyl]-phosphonates were prepared on non-crosslinked polystyrene, a soluble polymer support. After cleavage from the support, the resulting phosphonic acids were examined for inhibition with protein tyrosine phosphatase 1B. Compound 20, bearing an alpha,beta-unsaturated allyl ester moiety, was the most potent of this series of compounds, being a reversible, competitive inhibitor with a K(i) of 8.0+/-1.4 microM.

Binding, Competitive↗

The difluoromethylenesulfonic acid group as a monoanionic phosphate surrogate for obtaining PTP1B inhibitors.

Three peptides, 7-9, bearing sulfono(difluoromethyl)phenylalanine (F(2)Smp, 2), a nonhydrolyzable, monoanionic phosphotyrosine mimetic, were prepared and evaluated as PTP1B inhibitors. The most effective inhibitor was the nonapeptide, ELEF(F(2)Smp)MDYE-NH(2), (9) which exhibited a K(i) of 360 nM. A comparison of F(2)Smp-bearing peptides 7 [DADE(F(2)Smp)LNH(2), K(i)=3.4 microM] and 8 [EEDE(F(2)Smp)LNH(2), K(i)=0.74 microM] with their phosphono(difluoromethyl)phenylalanine (F(2)Pmp)-bearing analogues indicated that F(2)Smp is not as effective a pTyr mimetic as F(2)Pmp by 100- to 130-fold. Although F(2)Smp is not as effective as F(2)Pmp, a comparison of peptide 7 with analagous peptides bearing other monoanionic pTyr mimetics recently reported in the literature indicates that F(2)Smp is about 65-fold more effective than any other non-hydrolyzable, monanionic pTyr mimetic reported to date. To further assess the difluoromethylenesulfonic acid (DFMS) group as a monoanionic phosphate mimetic, a series of 24 nonpeptidyl biaryl compounds bearing the DFMS group were prepared using polymer-supported methodologies and screened for PTP1B inhibition. Several of these compounds were selected for further study and their IC(50)'s compared to their difluoromethylenephosphonic (DFMP) analogues. The differences in IC(50)'s between the DFMS and DFMP non-peptidyl compounds was not as great as with the F(2)Smp- and F(2)Pmp-bearing peptides. Possible reasons for this and its implication to the design of small molecule PTP1B inhibitors is discussed.

Amino Acid Sequence↗

Stent-graft migration following endovascular repair of aneurysms with large proximal necks: anatomical risk factors and long-term sequelae.

PURPOSE: To evaluate the outcome of aortic endografts deployed in large infrarenal necks and to identify any association of preoperative aneurysm characteristics and postoperative morphological changes with the incidence of neck dilatation and device migration in this patient subset. METHODS: The records of 47 patients (41 men; mean age 74, range 55-84) with large aortic neck diameters treated with Talent stent-grafts from 1998 to 2001 were reviewed. Patients with anatomical criteria that precluded aneurysm exclusion with currently available devices were preferentially selected. Mean baseline aneurysm morphology included 27.6-mm (range 18-33.4) suprarenal and 28.1-mm (range 24-34) infrarenal neck diameters; the infrarenal neck length was 26 +/- 16 mm with angulation of 37 degrees +/- 18 degrees. Computed tomographic (CT) angiograms up to 3 years were analyzed using specialized interactive software; migration was defined as >1-cm change in the distance from the lower renal artery to the top of the device. Pre- and postoperative morphological characteristics of the aneurysm were compared between patients with and without migration. RESULTS: Of the 45 patients successfully treated, 40 had complete CT data for analysis. During a mean 17-month follow-up, 7 (17.5%) of the 40 devices exhibited distal migration. Six patients required secondary procedures; 5 were in the migration cohort. No preoperative anatomical characteristic or degree of neck dilatation over time was predictive of stent-graft migration. Aneurysm sac regression was significant at 1 (-0.09 +/- 4.90 mm) and 2 (-1.48 +/- 2.56 mm) years in endografts without migration (p<0.001). Distal endograft migration >1 cm predicted the need for secondary interventions (p<0.001), with 83% sensitivity and 94% specificity. CONCLUSIONS: Endovascular repair is successful in patients with large infrarenal necks and complex neck morphology. Changes in aneurysm remodeling over time were similar to reported observations in patients with more favorable neck criteria. Although no anatomical factor associated with migration could be identified from this analysis, distal displacement >1 cm correlated with the need for a secondary intervention.

Aged↗

Practice patterns of testing waived under the clinical laboratory improvement amendments.

OBJECTIVES: To determine operational practices in laboratories operating under a Certificate of Wavier (waived laboratories), or equivalent, under the Clinical Laboratory Improvements Amendments (CLIA) of 1988 when performing tests designated as having an insignificant risk of an erroneous result (ie, waived tests). METHODS: Waived laboratories that were part of the Centers for Disease Control and Prevention Laboratory Sentinel Monitoring Network project in the states of Arkansas, New York, and Washington were surveyed about their quality control (QC) and quality assurances (QA) practices when performing waived testing. Arkansas and Washington sent out similar questionnaires, whereas on-site surveys were conducted in New York. The survey in Arkansas and Washington also included nonwaived laboratories. The New York visits were designed to pilot test a regulatory inspection program for limited testing sites, which, in New York, are roughly equivalent to laboratories operating under a CLIA Certificate of Wavier and/or Provider-Performed Microscopy but are generally not located in physicians' offices. Laboratories visited in New York were selected from a list of limited testing sites and were representative of that population. RESULTS: Arkansas received responses from 211 facilities (37% response rate), of which 38% had Certificates of Waiver. Washington received responses from 190 waived laboratories (71% response rate) and from 116 nonwaived laboratories (32% response rate). In New York, 607 of the 2751 limited testing laboratories were visited. Reporting laboratories in all 3 states most frequently performed testing for glucose, urinalysis, urine human chorionic gonadotropin, occult blood, and group A Streptococcus antigen, although other waived tests were performed less frequently. Washington found that 57% of waived laboratories followed manufacturers' QC requirements. Arkansas found that 58% of laboratories doing waived tests that required liquid controls performed these controls, and 59% performing waived testing requiring electronic controls used these controls. In New York, 68% of the laboratories complied with the manufacturer's QC requirements for a variety of tests. Being accredited by an external organization or affiliated with a more complex laboratory improved compliance. Nonwaived laboratories in Washington and Arkansas complied with manufacturer's instructions at a higher rate than did waived laboratories. Similar deficiencies in following CLIA requirements were found in other areas of laboratory operation. CONCLUSIONS: Just more than half of waived laboratories in 3 diverse states follow manufacturer's instructions for recommended QC and QA. These instructions help ensure that the test will produce results that have an insignificant chance of an error. Although we did not study the impact of this and other findings on patient care, the results show that imposing good laboratory practices by regulation alone was insufficient to ensure quality laboratory results in any location evaluated. A system that can continually provide accessible education on laboratory practices, coupled with new thoughts on the regulatory environment, is in order.

Certification↗