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Biomedical subjects

Larry Miller

Publications and source records attributed to Larry Miller.

13 recordsLinked to original sources
PubMed2006

Use of endoluminal ultrasound to evaluate gastrointestinal motility.

The use of high-frequency ultrasound transducers in the gastrointestinal tract (GI) has already yielded remarkable findings concerning the anatomy, physiology and pathophysiology of the GI tract and of various motility disorders. These transducers have made completely invisible portions of the GI tract (the longitudinal smooth muscle, muscles of the upper esophageal sphincter, components of the gastroesophageal junction high-pressure zone, and the muscle of the anal sphincter complex) accessible to investigation. Use of simultaneous ultrasound and manometry has allowed the exploration of the normal physiology of peristaltic contraction. The components of the high-pressure zone of the distal and proximal esophagus have been isolated and the movement of these components has been studied individually and as a group. Various esophageal motility disorders have been investigated including achalasia, scleroderma, Barrett's esophagus and diffuse esophageal spasm. The possible etiology of the symptoms of esophageal chest pain and heartburn (sustained esophageal contractions of the longitudinal smooth muscle), have been studied. The possible underlying pathophysiology of GERD (the missing gastric clasp and sling fiber pressure profile) has been explored. Three-dimensional high-frequency ultrasound imaging has allowed the peristaltic contraction sequence to be viewed in a completely new and unique manner. The biomechanics of both esophageal contraction and the gastroesophageal junction high-pressure zone have been investigated and the mechanical advantage of esophageal shorting has been studied. The mechanism of action of standard surgical and newer endoscopic therapies for GERD has been defined. Future applications of this technology are limited only by our imagination.

Endosonography↗
PubMed2005

Stability problems of polyether ether ketone and ethylene-tetrafluoroethylene copolymer tubing in simulated moving bed operation.

Polymeric capillaries made from polyether ether ketone (PEEK) or ethylene-tetrafluoroethylene copolymer (Tefzel) are considered as highly inert and chemically resistant materials used as standard equipment in HPLC and simulated moving bed (SMB) applications. During several racemate separations using a SMB unit equipped with these tubes a formation of micro-holes was observed. All separations had in common that a high content of an alkane was used in the mobile phase. The patterns of damage and possible reasons causing the leakages of the capillaries are discussed. Polymeric tubing had to be replaced by stainless steel capillaries for the enantiomer separations in order to ensure safety of workers, GMP status of products and control leakages.

Chromatography, High Pressure Liquid↗
PubMed2005

A retrospective review of enteroclysis in patients with obscure gastrointestinal bleeding and chronic abdominal pain of undetermined etiology.

Our purpose was to determine the diagnostic utility of enteroclysis in the evaluation of obscure gastrointestinal bleeding and abdominal pain of unknown etiology. This is a retrospective review of 97 consecutive patients (mean age, 54.1+/-17.5 [SD] years; 49 male and 48 female) who underwent enteroclysis at Temple University Hospital from January 1994 to October 2001 for the evaluation of obscure GI bleeding or chronic abdominal pain of undetermined etiology. Prior to enteroclysis all patients had an EGD and colonoscopy, which were nondiagnostic for their symptoms. Sixty-three patients (64.9%) had enteroscopy performed prior to enteroclysis that was also negative. Enteroclysis results were defined as positive based on anatomical or functional abnormalities. Analysis of the data included the percentage yield of positive exams, the percentage of positive results per symptom category, and the percentage of patients with a change in clinical management based on positive enteroclysis results. Ninety-seven patients underwent enteroclysis. The indications for enteroclysis were obscure GI bleeding in 67 patients (69.1%) and chronic abdominal pain in 30 patients (30.9%). The number of positive exams was 19 (19.6%). Fourteen of the 67 patients with the indication of GI bleeding had a positive exam (21%), while 5 of the 30 patients with chronic abdominal pain had a positive result (16.7%). There was a change in clinical management due to the enteroclysis results in 10 patients: 7 patients with GI bleeding (10%) and 3 patients with chronic abdominal pain (10%). Positive enteroclysis findings included adhesions (7), filling defects and masses (5), strictures (2), small bowel diverticulosis (1), mucosal abnormalities (3), and a motility disorder (1). The overall positive yield for enteroclysis was 19.6%, with a yield of 16.7% for chronic abdominal pain and 21% for gastrointestinal bleeding. Enteroclysis results changed the clinical management in approximately 10% of the patients.

Abdominal Pain↗
PubMed2005

Simplified method of hepatic fibrosis quantification: design of a new morphometric analysis application.

INTRODUCTION: Semiquantitative evaluation of liver specimens is considered the standard method for measuring fibrosis; however, these systems lack the precision of a quantitative technique. METHODS: We developed an image analysis application (FibroXact) that automates and simplifies color segmentation. Trichrome slides were scanned and the program was used to evaluate each pixel based upon hue, lightness, and saturation values. Percent fibrosis was automatically calculated after thresholding. RESULTS: Linear regression demonstrated a strong relationship between the FibroXact result and the semiquantitative result (P<0.001). CONCLUSION: We have developed an image analysis application to quantify liver fibrosis. Correlation between our results and a standard semiquantitative system was demonstrated.

Azo Compounds↗
PubMed2004

Resolution of a racemic pharmaceutical intermediate. A comparison of preparative HPLC, steady state recycling, and simulated moving bed.

Preparative HPLC and simulated moving bed (SMB) chromatography were used to resolve significant quantities of a racemic pharmaceutical intermediate. In addition, smaller scale studies using closed-loop recycling and steady state recycling (SSR) were performed so that a meaningful comparison of all these techniques could be made using the same real world separation. A highly optimized, six-column SMB process was clearly the superior technique and was used for the process-scale (247 kg of racemate) resolution. At the more moderate lab-scale (33 kg of racemate and 19 kg of racemate), a frequently used but less optimized eight-column SMB process was used. It was found that SSR was comparable to the lab-scale SMB process in productivity and solvent consumption. Thus, it appears that SSR can be a useful choice at such moderate scales. Finally, at moderate scales when neither SSR nor SMB is available, it was found that acceptable results were obtained with both closed-loop recycling and with a two-step preparative process.

Chromatography, High Pressure Liquid↗
PubMed2003

Batch and simulated moving bed chromatographic resolution of a pharmaceutical racemate.

The preparative chromatographic resolution of racemates has become over the past few years a standard approach for the generation of enantiomers in pharmaceutical research and development. This paper will discuss the chromatographic resolution of a racemic pharmaceutical intermediate. Initial analytical method development to determine the best preparative conditions will be presented. Batch resolution of kg quantities of racemate followed by the simulated moving bed resolution of tens and hundreds of kg of racemate will also be discussed. Finally the different approaches used for the separation will be compared.

Chromatography, Liquid↗
PubMed2003

The role of endoscopy in the treatment of esophageal varices, 2002-2003.

Great strides have been made in the endoscopic and radiologic therapy of esophageal varices in the past few years. With the advent of variceal band ligation and transjugular intrahepatic portosystemic shunt, almost every acute variceal bleed can be controlled. In addition, over the past decade great strides have been made in the noninvasive imaging and pressure measurement of esophageal varices. Yet, the mortality rate from variceal bleeding has not changed significantly and the pharmacologic therapy of esophageal varices and the prophylaxis of the initial variceal bleed has lagged behind these other interventional advances. These authors believe that progress in these areas has been slow because the pathophysiology and hemodynamics of esophageal varices are not well understood. It is through progress in the areas of endoluminal ultrasound imaging of esophageal varices and noninvasive pressure measurement that progress has finally been made in the area of the pathophysiology of variceal bleeding. In this update, two novel ideas regarding the pathophysiology of variceal bleeding are described. The first regards increased variceal pressure during peristaltic contraction. The second describes increased variceal pressure with increasing intraabdominal pressure. These new observations suggest a new pathophysiology in the cause of variceal bleeding and imply new methods to prevent and treat variceal bleeding. This update and review of esophageal varices is given in five sections: new developments in the pathophysiology of esophageal variceal bleeding, screening for esophageal varices, prediction of variceal bleeding, treatment of esophageal varices and new modalities to evaluate esophageal varices.

Journal Article↗
PubMed2003

Risk of esophageal variceal bleeding based on endoscopic ultrasound evaluation of the sum of esophageal variceal cross-sectional surface area.

OBJECTIVE: The aim of this study was to evaluate the risk of future variceal bleeding, based on the endoscopic ultrasound measurement of the sum of the cross-sectional surface area (CSA) of all of the esophageal varices in the distal esophagus. METHODS: Twenty-eight patients with portal hypertension and esophageal varices, but no prior history of variceal bleeding, were evaluated using endoscopic ultrasound (20-MHz ultrasound probe, Microvasive, Boston, MA; Olympus, Tokyo, Japan). The entire esophagus was imaged, and an image was selected at a point where the varices appeared the largest. This image was digitized, and the sum of the CSA of all of the varices was measured (Image Pro Plus, Silver Springs, MD) by an investigator blinded to the patients' clinical status. The follow-up time for each patient was calculated (time to first bleed, time to liver transplantation, time to death, or time to the end of study). The Cox Proportional Hazards Model was used to determine if there was a significant difference between the sums of the CSA in the patients who bled compared with those who did not bleed. An OR was calculated to determine the risk of future variceal bleeding based on the sum of the CSA as measured in cm(2)/month. Positive and negative predictive values were calculated for future variceal bleeding. RESULTS: Six of 28 patients (21%) experienced esophageal variceal bleeding on follow-up. The mean CSA +/- SEM of the sum of the esophageal varices in these patients was 0.77 cm(2) +/- 0.31 cm(2) (range 0.07-2.09 cm(2)). The mean time to bleeding was 15.5 months +/- 4.95 months (range 1-29 months). Twenty-two of 28 patients (79%) did not experience variceal bleeding. The mean CSA +/- SEM of the sum of the varices in these patients was 0.36 cm(2) +/- 0.08 cm(2) (range 0.02-1.19 cm(2)). The mean time to follow-up was 35.7 months +/- 6.69 months (range 1.2-103.2 months). The sum of the CSA between the patients who bleed and those who did not bleed was significantly different at the p < 0.018 level. The OR for the risk of variceal bleeding for each one cm(2) difference in the sum of the CSA per month was 6.34. Using a cutoff of 0.45 cm(2), the sensitivity and specificity for future variceal bleeding was 83% and 75%, respectively. CONCLUSIONS: There is a significant difference (p < 0.018) in the sum of the esophageal variceal CSA between those patients who will experience future variceal bleeding and those who will not. There is a 76-fold increase per year in the risk of future variceal bleeding for each one cm(2) increase in variceal CSA. Using a cutoff value for the CSA of 0.45 cm(2), the sensitivity and specificity for future variceal bleeding above and below this point is 83% and 75%, respectively.

Adult↗
PubMed2002

A new device for measuring esophageal variceal pressure.

BACKGROUND: Esophageal varices are a frequent source of bleeding in patients with cirrhosis. Elevated intravariceal pressure is associated with variceal bleeding. There is no simple, easy-to-use device for noninvasive measurement of intravariceal pressure. The purposes of this study were to develop a noninvasive method for measuring intravariceal pressure, and to develop a model of esophageal varices that can be used to test this pressure measurement device. METHODS: A variceal pressure measurement device was constructed by placing a 20 MHz US transducer in a latex balloon catheter sheath and attaching the catheter to a pressure transducer. The pressure measurement device was passed though the accessory channel of a large-channel endoscope and tested in blinded fashion by using tip deflection to compress each of 4 variceal models with the device. The pressure within each model was measured 10 times by 2 separate investigators blinded to the actual pressures. The mean (SD) pressure was calculated for each model. The variceal models were made of nitrocellulose dialysis tubing filled with water. Each "varix" had the same diameter but a different intraluminal pressure (5.5, 10, 15, 21.5 mm Hg). OBSERVATIONS: The correlation coefficient between the actual and measured "varix" pressures for the first investigator (L.S.M.) was r = 0.96: 99% CI [0.93, 0.98]. For the varix models with pressures of 21.5, 15, 10, and 5.5 the percent errors were, respectively, 9.5, 3.9, 5.1, and 0.7. The correlation coefficient between the actual and measured varix pressures for the second investigator (Q.D.) was r = 0.97: 99% CI [0.94, 0.98]. For the varix models with pressures of 21.5, 15, 10, and 5.5 the percent errors were, respectively, 10.3, 3.4, 9.8, and 1.1. The correlation coefficient between the 2 investigators (L.S.M., Q.D.) for the varix model pressures was r = 0.97: 99% CI [0.95, 0.99]. CONCLUSION: The variceal pressure measuring device developed for this study measured intravariceal pressure in a model varix with a low percent error and high correlation to the actual pressures. Intraobserver and interobserver variability was low.

Catheterization↗
PubMed2002

An analysis of the binding of cocaine analogues to the monoamine transporters using tensor decomposition 3-d QSAR.

The conformation and alignment of cocaine analogues bound to the monoamine transporter proteins were explored using the tensor decomposition 3-D QSAR method. It is proposed from these calculations that the bound conformation of these ligands to the three transporter proteins has the 3beta-aryl substituent in a conformation in which the aryl group is orthogonal or approximately orthogonal to the tropane ring. Based on these results, rigid and semi-rigid tropane analogues were designed, synthesized and their affinities for the monoamine transporters were determined.

Biogenic Monoamines↗