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Biomedical subjects

S D Patterson

Publications and source records attributed to S D Patterson.

At least 19 recordsLinked to original sources

The detection of loose bodies in the elbow: the value of MRI and CT arthrography.

Our aim was to determine the clinical value of MRI and CT arthrography in predicting the presence of loose bodies in the elbow. A series of 26 patients with mechanical symptoms in the elbow had plain radiography, MRI and CT arthrography, followed by routine arthroscopy of the elbow. The location and number of loose bodies determined by MRI and CT arthrography were recorded. Pre-operative plain radiography, MRI and CT arthrography were compared with arthroscopy. Both MRI and CT arthrography had excellent sensitivity (92% to 100%) but low to moderate specificity (15% to 77%) in identifying posteriorly-based loose bodies. Neither MRI nor CT arthrography was consistently sensitive (46% to 91%) or specific (13% to 73%) in predicting the presence or absence of loose bodies anteriorly. The overall sensitivity for the detection of loose bodies in either compartment was 88% to 100% and the specificity 20% to 70%. Pre-operative radiography had a similar sensitivity and specificity of 84% and 71%, respectively. Our results suggest that neither CT arthrography nor MRI is reliable or accurate enough to be any more effective than plain radiography alone in patients presenting with mechanical symptoms in the elbow.

Adolescent↗

Osteoblastoma of the clavicle.

A 14-year-old female with a 1-year history of a painful clavicle mass underwent resection and reconstruction with an intercalated autograft and rigid plate fixation. The histopathology was diagnostic for osteoblastoma. Although a clavicle mass is a common entity following clavicle trauma, less common disorders such as bone tumors need to be considered in the differential diagnosis. Osteoblastoma is an uncommon, benign bone tumor representing 1% of all primary bone tumors. An extensive review of the literature reveals only one reported case of clavicular osteoblastoma.

Adolescent↗

Triple "E" syndrome: bilateral locked posterior fracture dislocation of the shoulders.

Bilateral locked posterior fracture dislocation of the shoulders is one of the least common injuries of the shoulder, and this injury has been suggested to be pathognomonic of seizures when diagnosed in the absence of trauma. The authors present a case of idiopathic bilateral locked posterior fracture dislocations of the shoulder, along with a review of the medical literature. The authors also present the "triple E syndrome," describing the possible etiologies of this injury: epilepsy (or any convulsive seizure), electrocution, or extreme trauma.

Adult↗

Automated LC-LC-MS-MS platform using binary ion-exchange and gradient reversed-phase chromatography for improved proteomic analyses.

A simple multidimensional liquid chromatography system utilizing an isocratic pump and a HPLC system is described for the comprehensive proteomic analysis of complex peptide digest mixtures by coupled LC-LC-MS-MS techniques. A binary ion-exchange separation was achieved through the use of a strong cation-exchange column followed by a reversed-phase column for data-dependent LC-MS-MS analysis of the unbound analytes, and following salt elution (and concomitant column reequilibration), the bound analytes. Off-line validation of the platform showed near quantitative recovery of fractionated peptides and essentially complete ion-exchange partitioning. In comparative analyses of a highly complex peptide digest mixture a >40% increase in the number of peptide and protein identifications was achieved using this multidimensional platform compared to an unfractionated control.

Amino Acid Sequence↗

Towards defining the urinary proteome using liquid chromatography-tandem mass spectrometry. II. Limitations of complex mixture analyses.

With an emphasis on obtaining a multitude of high quality tandem mass spectrometry spectra for protein identification, instrumental parameters are described for the liquid chromatography-tandem mass spectrometry analysis of trypsin digested unfractionated urine using a hybrid quadrupole-time-of-flight (Q-TOF) mass spectrometer. Precursor acquisition rates of up to 20 distinct precursors/minute in a single analysis were obtained through the use of parallel precursor selection (four precursors/survey period) and variable collision induced dissociation integration time (1 to 6 periods summed). Maximal exploitation of the gas phase fractionated ions was obtained through the use of narrow survey scans and iterative data-dependent analyses incorporating dynamic exclusion. The impact on data fidelity as a product of data-dependent selection of precursor ions from a dynamically excluded field is discussed with regards to sample complexity, precursor selection rates, survey scan range and facile chemical modifications. Operational and post-analysis strategies are presented to restore data confidence and reconcile the greatest number of matched spectra.

Amino Acid Sequence↗

Identification of incompletely processed potential carboxypeptidase E substrates from CpEfat/CpEfat mice.

In an attempt to identify peptides that may be involved in the obese phenotype observed in CpEfat/CpEfat mice (deficient in Carboxypeptidase E, CpE) samples from fourteen neuroendocrine tissues in wild-type and CpEfat/CpEfat mice were obtained. Peptides were purified from these tissues and potential CpE substrate peptides were enriched using an anhydrotrypsin column that captures peptides with basic C-termini. Bound peptides were subjected to tryptic digestion and followed by liquid chromatography-mass spectrometry analysis. The relative levels of CpEfat/CpEfat versus wild-type peptides were determined by comparison of the ion intensities. Peptide ions elevated in the CpEfat/CpEfat samples were identified by targeted liquid chromatography-tandem mass spectrometry. From those ions, 27 peptides derived from known neuropeptides (including CpE substrates) were identified, together with another 25 peptides from proteins not known to be components of the neuropeptide processing pathway. The known CpE substrates identified included the recently discovered proSAAS, granin-like neuroendocrine peptide precursor that inhibits prohormone processing. The approach demonstrated the feasibility of using an affinity-based method for identifying differences in specific classes of peptides between normal and mutant mice.

Amino Acid Sequence↗

Towards defining the urinary proteome using liquid chromatography-tandem mass spectrometry. I. Profiling an unfractionated tryptic digest.

The proteome of normal male urine from a commercial pooled source has been examined using direct liquid chromatography-tandem mass spectrometry (LC-MS/MS). The entire urinary protein mixture was denatured, reduced and enzymatically digested prior to LC-MS/MS analysis using a hybrid-quadrupole time-of-flight mass spectrometer (Q-TOF) to perform data-dependent ion selection and fragmentation. To fragment as many peptides as possible, the mixture was analyzed four separate times, with the mass spectrometer selecting ions for fragmentation from a subset of the entire mass range for each run. This approach requires only an autosampler on the HPLC for automation (i.e, unattended operation). Across these four analyses, 1.450 peptide MS/MS spectra were matched to 751 sequences to identify 124 gene products (proteins and translations of expressed sequence tags). Interestingly, the experimental time for these analyses was less than that required to run a single two-dimensional gel.

Amino Acid Sequence↗

Non-traditional study designs to demonstrate average bioequivalence for highly variable drug products.

OBJECTIVE: To demonstrate average bioequivalence, the ninety-percent confidence intervals (CI) on the ratio of geometric means for area under the concentration-time curve (AUC) and maximum observed plasma concentration (Cmax) must lie within 0.80-1.25. Demonstration of average bioequivalence (ABE) for highly variable drug products requires large numbers of subjects in a standard, adequately powered, two-period crossover. METHODS: Application of non-traditional study designs can help to meet this hurdle. Study design and analysis for replicate and group sequential-replicate study designs are presented and illustrated using examples. It is demonstrated how to use such approaches to meet the difficult regulatory hurdle of average bioequivalence for a highly variable drug product. RESULTS: To illustrate, data are provided from three separate ABE studies for a highly variable drug product at three dosage strengths. In all three studies, a replicate study design was used to compensate for high intrasubject variation. Additionally, for the last study, a group sequential study design was imposed to provide early evidence of conclusive results. CONCLUSION: Replicate designs and group-sequential designs in bioequivalence should be used to demonstrate average bioequivalence for highly variable drug products or when uncertain of true intrasubject variability in order to ensure conclusive study results.

Area Under Curve↗

Ilizarov hybrid external fixation for fractures of the distal radius: Part I. Feasibility of transfixion wire placement.

The advantages of Ilizarov external fixation, allowing early motion of adjacent joints during fixation of periarticular fractures, have not yet been applied to distal radius fractures. A magnetic resonance imaging study of 10 normal volunteers evaluated the safety of passing percutaneous transfixion pins across the distal radius in 3 forearm positions. Even in the optimal forearm position, the safe zones between the transfixion pin, vessel, nerve, or tendon was small, suggesting that open placement would be required. A cadaver study in 8 specimens demonstrated that the pins could be placed with an open technique using an aiming device and that the pins could be placed without limiting forearm rotation. The proximity of vital structures to transfixion pins dictates open placement to safely apply Ilizarov fixation to distal radius fractures.

Adult↗

Ilizarov hybrid external fixation for fractures of the distal radius: Part II. Internal fixation versus Ilizarov hybrid external fixation: Stability as assessed by cadaveric simulated motion testing.

The in vitro stability of an Ilizarov hybrid external fixator was compared with that of a dorsal 3.5-mm AO T-plate in 8 unpaired, fresh-frozen upper extremities. A specially designed testing device that used computer-controlled pneumatic actuators was used to simulate active finger, wrist, and forearm motions by applying loads to relevant tendons. A comminuted extra-articular distal radius fracture was modelled using a dorsally based wedge osteotomy. Fracture stability was assessed using an electromagnetic tracking device to measure motion across the fracture site after randomized application of the plate and the hybrid fixator. During simulated finger and wrist motions with the forearm pronated or supinated, motion of the distal fragment with the hybrid fixator applied was comparable to or statistically less than with the AO plate applied. During simulated forearm rotation, the stability provided by the 2 fixation types was similar, although the plate allowed statistically less radial-ulnar deviation of the fragment. In this model of a 2-part extra-articular distal radius fracture, the clinically meaningful stability of the Ilizarov hybrid external fixator was comparable to that of the dorsal AO plate.

Aged↗

An anthropometric study of the radial head: implications in the design of a prosthesis.

The dimensions of the native radial head were measured in 28 cadaveric upper extremities and radiographs of the contralateral elbows of 40 patients who had received a radial head replacement. The mean difference between the maximum and minimum radial head diameters was 1.7 +/- 0.7 mm (range, 0.12-3.27 mm). This variability suggests that although the native radial head is not circular, it does not have a consistently elliptic shape. The native radial head also is variably offset from the axis of the neck (4.2 +/- 2.5 mm), suggesting that a radial head hemiarthroplasty that precisely replicates normal anatomy would be difficult to achieve. There was a poor correlation between the radial head diameter and the medullary canal of the radial neck, suggesting that a modular implant system should be considered.

Aged↗

A biomechanical analysis of intrascaphoid compression using the 3.00 mm Synthes cannulated screw and threaded washer: an in vitro cadaveric study.

This study evaluated the compressive capabilities of the 3.0 mm Synthes cannulated screw and threaded washer. A transverse osteotomy was performed at the waist of eight cadaveric scaphoids and a custom-designed load cell was inserted before internal fixion with a 3.0 mm cannulated screw and threaded washer. The mean intrascaphoid compression achieved was 108 (SD, 60) N. This compressive force is comparable to that produced by standard cortical screws.

Aged↗

Muscle forces and pronation stabilize the lateral ligament deficient elbow.

The influence of muscle activity and forearm position on the stability of the lateral collateral ligament deficient elbow was investigated in vitro, using a custom testing apparatus to simulate active and passive elbow flexion. Rotation of the ulna relative to the humerus was measured before and after sectioning of the joint capsule, and the radial and lateral ulnar collateral ligaments from the lateral epicondyle. Gross instability was present after lateral collateral ligament transection during passive elbow flexion with the arm in the varus orientation. In the vertical orientation during passive elbow flexion, stability of the lateral collateral ligament deficient elbow was similar to the intact elbow with the forearm held in pronation, but not similar to the intact elbow when maintained in supination. This instability with the forearm supinated was reduced significantly when simulated active flexion was done. The stabilizing effect of muscle activity suggests physical therapy of the lateral collateral ligament deficient elbow should focus on active rather than passive mobilization, while avoiding shoulder abduction to minimize varus elbow stress. Passive mobilization should be done with the forearm maintained in pronation.

Collateral Ligaments↗

Outcome of plate fixation of olecranon fractures.

OBJECTIVES: To evaluate the functional outcome of plate fixation for displaced olecranon fractures, both simple and comminuted. DESIGN: Retrospective patient, chart, and radiographic review. SETTING: Academic teaching hospital. PATIENTS: Twenty-five patients who underwent plate fixation of displaced olecranon fractures by two surgeons were independently reviewed at an average follow-up of thirty-four months (range, 15-69 months). MAIN OUTCOME MEASUREMENTS: Physical capability was assessed by measuring range of motion and isometric elbow strength. Patient-rated outcomes were evaluated using the SF-36, DASH, Mayo Elbow Performance Index (MEPI), and visual analogue scales for patient satisfaction and pain. Radiographs were evaluated preoperatively, postoperatively, and at the time of final review. RESULTS: The average patient age was fifty-four years (range, 14-81 years). The Mayo classification of fractures was fourteen Type II and eleven Type III. An adequate reduction was maintained in all elbows until union. Physical capability measures indicated nonsignificant side-to-side differences in motion or strength, except for supination motion, which was reduced in the injured arm (p = 0.003). The MEPI-rated outcome was twenty-two excellent or good. Patient satisfaction was high (9.7/10), with a low pain rating (1/10). The mean DASH score was consistent with almost normal upper extremity function. The SF-36 showed no difference in physical health as compared with the average American population. Twenty percent of patients required plate removal because of prominence of the internal fixation. The outcome was not influenced by fracture pattern. CONCLUSION: Plate fixation is an effective treatment option for displaced olecranon fractures with a good functional outcome and a low incidence of complications.

Adolescent↗

Lack of effect of rosiglitazone on the pharmacokinetics of oral contraceptives in healthy female volunteers.

The effect of rosiglitazone (Avandia [BRL 49653C]) on the pharmacokinetics of ethinylestradiol and norethindrone was evaluated after repeat dosing of rosiglitazone with an oral contraceptive (OC; Ortho-Novum 1/35 containing norethindrone 1 mg and ethinylestradiol 0.035 mg) in a randomized, double-blind, placebo-controlled crossover study. Thirty-four healthy female volunteers received oral rosiglitazone (RSG) 8 mg + OC or matched placebo (P) + OC daily on days 1 to 14 of a 28-day OC dosing cycle; the alternate regimen was administered during a second cycle. Ethinylestradiol and norethindrone pharmacokinetics were determined from plasma concentrations on day 14. Lack of pharmacokinetic effect was prospectively defined as 90% CI for the point estimate (PE) of the ratio (RSG + OC):(P + OC) contained within a 20% equivalence range for both ethinylestradiol and norethindrone (analyzed by ANOVA). For RSG + OC and P + OC, respectively, mean ethinylestradiol AUC(0-24) was 1126 and 1208 pg.h/mL (PE: 0.92; 90% CI: 0.88-0.97), and mean norethindrone AUC(0-24) was 178 and 171 ng.h/mL (PE: 1.04; 90% CI: 1.00-1.07). Thus, rosiglitazone had no significant effects on the pharmacokinetics of ethinylestradiol or norethindrone. Coadministration of rosiglitazone with OCs does not induce metabolism of these synthetic sex steroids and is not expected to impair the efficacy of OCs or hormone replacement therapy.

Adult↗

Population and individual bioequivalence: lessons from real data and simulation studies.

The Food and Drug Administration (FDA) has proposed replacing the 1992 average bioequivalence (ABE) with population and individual bioequivalence (PBE & IBE), as outlined in the preliminary draft guidance of December 1997, which was subsequently replaced by the draft guidances of August 1999 and resolved in the final guidance of October 2000. This has led to considerable public debate among regulatory, academic, and industry experts at numerous conferences (e.g., FDA/AAPS March 1998, FDA/AAPS August-September 1999, FDA Pharmaceutical Sciences Advisory Committee September 1999) and in the literature. The final guidance calls for ABE to remain as the primary criterion by which new formulations may be judged ready for access to the marketplace. In addition, the FDA recommends the use of replicate study designs for the specific drug classes of controlled-release formulations and highly variable drugs. The final guidance also alludes to the possibility of a sponsor requesting alternative criteria such as PBE and IBE following consultation with the FDA. This procedure amounts to a data collection period during which data suitable to evaluate the operating characteristics of PBE and IBE would be generated, analyzed, and discussed among interested parties. A comprehensive review of currently available databases is useful in determining the ultimate value of this data collection period. This report provides an update to the previous publication by the authors. In all, 28 data sets from 20 replicate cross-over bioequivalence studies have been analyzed (n = 12-96) using the statistical methodology in the most recent FDA draft guidance. The results are presented below. ABE Pass: ABE Fail: Total: AUC/Cmax AUC/Cmax AUC/Cmax AUC/Cmax Pass PBE & IBE 20/14 1/3 21/17 Pass IBE only 1/0 0/0 1/0 Fail PBE and IBE 0/2 0/1 0/3 Fail IBE only 2/3 4/5 6/8 Total 23/19 5/9 28/28 Review of the database reveals many interesting features, most notably the lack of consistent results within a given data set across all three criteria. The sensitivity of subject-by-formulation interaction to sample size and inherent variability of the compounds is further explored through simulation studies. It is concluded that additional simulation assessments must be considered when evaluating the value of a data collection period for PBE and IBE assessment. It will be shown that definitive conclusions regarding some of the operating characteristics of PBE and IBE can be achieved through a combination of data-driven hypotheses followed by simulation studies to further evaluate the hypotheses. Some recommendations for further data collection will be made.

Data Collection↗

Arthroplasty with a metal radial head for unreconstructible fractures of the radial head.

BACKGROUND: Treatment of unreconstructible comminuted fractures of the radial head remains controversial. There is limited information on the outcome of management of these injuries with arthroplasty with a metal radial head implant. METHODS: The functional outcomes of arthroplasties with a metal radial head implant for the treatment of twenty-five displaced, unreconstructible fractures of the radial head in twenty-four consecutive patients (mean age, fifty-four years) were evaluated at a mean of thirty-nine months (minimum, two years). There were ten Mason type-III and fifteen Mason-Johnston type-IV injuries. Two of these injuries were isolated, and twenty-three were associated with other elbow fractures and/or ligamentous injuries. RESULTS: At the time of follow-up, Short Form-36 (SF-36) summary scores suggested that overall health-related quality of life was within the normal range (physical component = 47 +/- 10, and mental component = 49 +/- 13). Other outcome scales indicated mild disability of the upper extremity (Disabilities of the Arm, Shoulder and Hand score = 17 +/- 19), wrist (Patient-Rated Wrist Evaluation score = 17 +/- 21 and Wrist Outcome Score = 60 +/- 10), and elbow (Mayo Elbow Performance Index = 80 +/- 16). According to the Mayo Elbow Performance Index, three results were graded as poor; five, as fair; and seventeen, as good or excellent. The poor and fair outcomes were associated with concomitant injury in two patients, a history of a psychiatric disorder in three, comorbidity in two, a Workers' Compensation claim in two, and litigation in one. Subjective patient satisfaction averaged 9.2 on a scale of 1 to 10. Elbow flexion of the injured extremity averaged 140 degrees +/- 9 degrees; extension, -8 degrees +/- 7 degrees; pronation, 78 degrees +/- 9 degrees; and supination, 68 degrees +/- 10 degrees. A significant loss of elbow flexion and extension and of forearm supination occurred in the affected extremity, which also had significantly less strength of isometric forearm pronation (17%) and supination (18%) as well as significantly less grip strength (p < 0.05). Asymptomatic bone lucencies surrounded the stem of the implant in seventeen of the twenty-five elbows. Valgus stability was restored, and proximal radial migration did not occur. Complications, all of which resolved, included one complex regional pain syndrome, one ulnar neuropathy, one posterior interosseous nerve palsy, one episode of elbow stiffness, and one wound infection. CONCLUSIONS: Patients treated with a metal radial head implant for a severely comminuted radial head fracture will have mild-to-moderate impairment of the physical capability of the elbow and wrist. At the time of short-term follow-up, arthroplasty with a metal radial head implant was found to have been a safe and effective treatment option for patients with an unreconstructible radial head fracture; however, long-term follow-up is still needed.

Adolescent↗