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Biomedical subjects

J P Foley

Publications and source records attributed to J P Foley.

34 records · Page 2Linked to original sources

Enantiomeric separations of basic pharmaceutical drugs by micellar electrokinetic chromatography using a chiral surfactant, N-dodecoxycarbonylvaline.

A novel surfactant with a chiral head group, (R)- or (S)-N-dodecoxycarbonylvaline (DDCV), was used to achieve enantiomeric separations of twenty basic pharmaceutical compounds by micellar electrokinetic chromatography (MEKC). Most of these compounds were beta-agonists (anti-asthmatic, bronchodilators) or beta-antagonists (anti-hypertension, anti-angina). DDCV can separate polar as well as more hydrophobic chiral analytes in the same buffer system. The selectivities for these enantiomeric pairs range from 1.03 to 1.23 with good efficiencies. Separations utilizing DDCV are easy to optimize and allow for exact enantiomeric migration order reversal by switching the enantiomeric form of the surfactant. Buffer systems were assessed to minimize Joule heating and to optimize the repeatability of parameters such as migration time, relative migration time, selectivity, peak areas and area ratios. An electrolyte system consisting of 25 mM DDCV, 100 mM zwitterionic CHES (2-[N-cyclohexylamino]ethanesulfonic acid) and 10 mM triethylamine (TEA) was most effective for these runs. The precision for migration times, relative migration times and selectivities was better than 1%, 0.1% and 1% R.S.D., respectively, while the precision for the area ratios ranged from 1% to 4%. The possible effect of analyte structure on selectivity, efficiency and precision of peak area was studied.

Chromatography, Liquid↗

Anionic-zwitterionic mixed micelles in micellar electrokinetic chromatography: sodium dodecyl sulfate-N-dodecyl-N,N-dimethylammonium-3-propane-1-sulfonic acid.

A zwitterionic surfactant, N-dodecyl-N,N-dimethylammonium-3-propane-1- sulfonic acid (SB-12), was used in combination with an anionic surfactant, sodium dodecyl sulfate (SDS), to form a novel pseudostationary phase for use in micellar electrokinetic chromatography. This mixed micellar system was characterized in terms of analyte retention, selectivity, efficiency, elution range, and resolution; and compared to results obtained using only SDS. A typically used SDS concentration, 20 mM, was chosen as a reference to which comparisons could be drawn. With 20 mM SDS, the optimum concentration range of 10-20 mM SB-12 provided efficiencies that were 2-4 times greater than with SDS alone, with minimal (< 15%) changes in the elution range and electroosmotic flow. The addition of 40 and 60 mM SB-12 also resulted in efficiencies on average of 600,000-800,000 theoretical plates/m, but at a significant reduction in the elution range and peak capacity. Retention factors (k') for the various neutral analytes increased by 20% with addition of 10 mM SB-12 and by approximately 60% with addition of 40 and 60 mM SB-12, while operating currents remained constant as SB-12 was added. Geometrical isomers p-nitrotoluene and m-nitrotoluene, that co-eluted with 20 mM SDS, were baseline resolved with the addition of 10 mM SB-12; in addition, methylene selectivity was greatest at this composition. No capillary wall interactions or coating effects were observed with the SDS-SB-12 mixed micellar system, in contrast to previously studied anionic-non-ionic mixed micellar system, SDS-Brij 35. Consequently, migration times were very repeatable (< or = 1.2% R.S.D.).

Anions↗

Retroperitoneal imaging with third and fourth generation computed axial tomography in clinical stage I nonseminomatous germ cell tumors.

OBJECTIVES: To examine the accuracy rate of abdominal staging using third and fourth generation computed tomography (CT) scanning in clinical Stage I testicular nonseminoma patients. METHODS: Between January 1985 and August 1993, 57 patients presented to our center with clinical Stage I testicular nonseminoma. Retroperitoneal computed tomographic staging studies were interpreted to be normal preoperatively in the entire group. In addition, tumor marker values were normal or returned to normal postorchiectomy within the appropriate half-life intervals. All patients were subjected to radical or modified retroperitoneal lymph node dissection (19% and 72%, respectively). Original abdominal CT scans (preretroperitoneal lymph node dissection) were available for blinded retrospective re-review in 16 cases (7 pathologic Stage II, 9 pathologic Stage I). RESULTS: Nineteen of 57 (33%) patients were upstaged at surgery including 6 patients (11%) who demonstrated II B volume disease. Third and fourth generation CT scanning of the retroperitoneum yielded a 66% accuracy rate in this population. Six out of 7 pathologic Stage II pre-lymph node dissection abdominal CT scans that were available for blinded re-review revealed nonpathologic nodes by size criteria in the primary landing zone for the corresponding original tumor. CONCLUSIONS: Our data suggests that for clinical Stage I nonseminoma in the 1985 to 1993 era, undue reliance was placed on a less than ideal staging test. The 33% false-negative rate reported showed no improvement over earlier reports and reaffirms concern for relying solely on third or fourth generation CT imaging of the retroperitoneum in the staging of clinical Stage I nonseminomatous germ cell tumor (NSGCT) patients. The presence of any number of lymph nodes in the expected primary landing zone, regardless of size, should raise serious suspicion for occult nodal disease.

False Negative Reactions↗

A retention index for micellar electrokinetic chromatography.

A retention index system has been developed for micellar electrokinetic chromatography (MEKC). Three homologous series: alkyl aryl ketones (phenones), 1-nitroalkanes, and alkylbenzenes were studied for use as retention index standards. Micellar systems consisting of sodium dodecyl sulfate (SDS), SDS/Brij 35 (polyoxyethylene lauryl ether), and SDS/SB-12 (N-dodecyl-N, N-dimethylammonium-3-propane-1-sulfonic acid) were used as pseudostationary phases. In addition, three organic modifiers: acetonitrile, methanol, and 1-propanol were used with SDS to evaluate their effect on the retention indices calculated for a set of neutral compounds. Retention indices for the neutral compounds did not vary significantly over the range of surfactant concentrations employed for each of the micellar systems (RSD < 2.0% for non-extrapolated retention indices). However, in the systems where an organic modifier was employed, the calculated retention indices showed some variation (RSD < 3.0%) at different SDS concentrations. The 1-nitroalkanes were found to be the most suitable for use as retention index standards. Alkyl aryl ketones were found to be effective retention index standards for more hydrophobic solutes, but they were not effective for very hydrophilic solutes even with a large amount of organic modifier added to the operating buffer. The alkylbenzenes were too hydrophobic (highly retained) than the alkyl aryl ketones and, therefore, cannot be recommended for use as retention index standards in MEKC.

Chromatography↗

Flow cytometric and quantitative histological parameters to predict occult disease in clinical stage I nonseminomatous testicular germ cell tumors.

The goal of this study was to determine if deoxyribonucleic acid (DNA) flow cytometric and quantitative histological parameters could predict occult metastases in clinical stage I nonseminomatous testicular cancer. Archival paraffin primary tumor tissue was available from 36 clinical stage I nonseminomatous germ cell testicular cancer patients who all had retroperitoneal lymphadenectomy and followup defining 2 groups: pathological stage I (23) and occult pathological stage II (13). Archival blocks were microdissected and individual histological components were subjected to flow cytometry. In addition, the primary histology was reevaluated for vascular invasion and per cent composition of histological components of embryonal carcinoma and other histologies. For flow cytometry parameters, no tumor was uniformly diploid, and the DNA index and per cent S phase cells were not useful in differentiating stages. Although mean per cent S phase for the aneuploid cell population and proliferative index were significantly greater for stage II cases by univariate logistic regression analysis, they are approximately 70% accurate in predicting occult disease as single tests and were not significant by multivariate analysis. The calculation of per cent embryonal carcinoma was also significantly greater in stage II cancer by univariate logistic regression testing and remained significant by multivariate analysis. Vascular invasion was marginally predictive of occult disease but was also not significant by multivariate analysis. Calculating the percentage of embryonal carcinoma of a primary testicular tumor may be a useful method to assess clinical stage I cancer patients for risk of occult disease. A larger study is needed to confirm the importance of per cent embryonal carcinoma and to clarify further if flow cytometry in combination is useful.

DNA, Neoplasm↗

Endoscopically controlled placement of urethrovesical anastomotic sutures after radical retropubic prostatectomy.

Radical retropubic prostatectomy is a challenging surgical procedure. One of the technically demanding aspects of this surgery is the urethrovesical anastomosis. We have used a 21F cystoscope in selected patients to enhance the quality of our urethrally placed anastomotic sutures. This technique may be a beneficial adjunct in those cases in which delineation of the transected urethral margin is difficult to identify secondary to urethral retraction and should be considered an addition to the presently available armamentarium of maneuvers used to make the urethrovesical anastomosis technically easier and more precise.

Anastomosis, Surgical↗

Celiac axis and superior mesenteric artery injury associated with left radical nephrectomy for locally advanced renal cell carcinoma.

The superior mesenteric artery and celiac axis were inadvertently ligated during left radical nephrectomy for a large upper pole renal carcinoma with massive perihilar and periaortic adenopathy. Computer-generated 3-dimensional illustrations created from the computerized tomography scan demonstrated the close proximity between these visceral branches and the adenopathy mass complex, and showed how this bulky disease may interfere with surgical anatomy. When left radical nephrectomy is performed for locally advanced and/or bulky node-positive renal neoplasms, surgeons must be cognizant of the location of the major visceral arterial branches and possible anatomical distortions.

Carcinoma, Renal Cell↗

Anthropometric comparison of cyclists from different events.

An anthropometric analysis was conducted upon 36 competitive male cyclists (mean age 23.4 years) who had been competing on average for 8.2 years. Cyclists were allocated to one of four groups; sprint, pursuit, road and time trial according to their competitive strengths. The sample included cyclists who were classified as category 1, 2, 3 or professional (British Cycling Federation and Professional Cycling Association). The sprint cyclists were significantly shorter and more mesomorphic than the other three groups (p less than 0.05). The time trialists were the tallest, most ectomorphic group, having the longest legs (p less than 0.01), the highest leg length/height ratio (p less than 0.05) and the greatest bitrochanteric width (p less than 0.05). The pursuit and road cyclists were found to have similar physiques, which were located between those of the sprinters and time trialists. The biomechanical implications of these differences in physique may be related to the high rate of pedal revolutions required by sprinters and the higher gear ratios used by time trialists.

Adult↗

Penalizing recidivist drunk drivers in Indiana: impediments to implementation.

In 1983, Indiana enacted a law mandating that anyone convicted a second or subsequent time of Operating While Intoxicated (OWI) receive a minimum of 48 consecutive hours in jail or 10 days of community service. A representative random sample of Indiana counties was used to determine the extent of implementation of this law by the courts in 1984 and 1985. Analysis of the 1984 data concluded that nearly 70% of the cases did comply with the law in its first year of implementation. However, 13.8% of the recidivists received neither jail nor community service. Another 17.6% served some jail time and/or community service, but not of a sufficient length to comply with the law. Overall compliance increased to 75% in 1985, while the proportion who received neither jail nor community service increased to 17%. Several specific causes for noncompliance are identified and recommendations for their correction are offered. It is felt that the Indiana experience described in this paper will prove instructive to other states with newly-strengthened OWI laws.

Alcoholic Intoxication↗

Treatment of coccidioidomycosis osteomyelitis with itraconazole in a horse. A brief report.

Itraconazole, a tricyclic azole effective against a number of deep mycotic diseases, was used to treat a Quarter Horse filly with coccidioidomycosis. The horse was almost normal after 90 days of treatment. Five months after discontinuing itraconazole treatment, the filly had severe neck pain and neurologic signs from recurrence of coccidioidomycosis and was treated with itraconazole for an additional 6 months. Her clinical condition improved to almost normal and the filly has remained normal for 2 years. There was no evidence of drug toxicity.

Animals↗

Determination of avoparcin in animal formulations by capillary electrophoresis.

The separation of two closely related glycopeptides, alpha- and beta-avoparcin, which differ by the presence or absence of a Cl atom, is achieved by capillary zone electrophoresis (CZE) using 20 mM borate (pH 9.2) in bare, fused-silica capillaries. The pKa values of these two glycopeptides are determined from spectrophotometric titrations of the mixture. Absorption spectra recorded between pH 3 and 12 produced a maximum pH transition at 258 nm. Titration data fitted to two sigmoidal functions reveal pKas of 7.99 for beta-avoparcin and 10.3 for alpha-avoparcin. The differing pH dependence of the effective electrophoretic mobilities of alpha- and beta-avoparcin resulted in an optimum pH of 9.2 (roughly the average of the pKa values) for their separation. Borate is shown to be necessary for the optimal CZE separation. A linear dynamic range of 0.5-50 ppm is achieved with regression coefficients of 0.9999. The limit of detection ranges from 0.2 to 0.5 ppm using a pressure injection of 15 sec in a 50-cm (effective length) fused-silica capillary with UV detection. Finally, the effects of sodium dodecyl sulfate (SDS) concentration in the migration buffer on apparent mobility, efficiency, migration times, and resolution are discussed. The addition of 75 mM SDS to the running buffer allows baseline resolution of alpha- and beta-avoparcin, including its minor components. Both the CZE and micellar electrokinetic chromatography (MEKC) separations of alpha- and beta-avoparcin are highly reproducible and can readily be applied to the analysis of avoparcin bulk drug and formulated products.

Animals↗