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Biomedical subjects

B R Lee

Publications and source records attributed to B R Lee.

At least 55 records · Page 3Linked to original sources

The EndoHand: comparison with standard laparoscopic instrumentation.

Laparoscopic instrumentation is constantly being refined in an attempt to achieve the proficiency, flexibility, and tactile feedback that would be available if the human hand were small enough to be used in laparoscopic surgery. The EndoHand (DAUM GmbH, Schwerin, Germany) is a novel laparoscopic three-fingered hand developed as an advancement over standard laparoscopic tools. Grasping and manipulation ability, dexterity, and tactile feedback were compared with those of current laparoscopic instrumentation. Experiments included measurement of achievable angles of approach to a fixed point behind a 2-cm-tall obstruction, completion time and error rates during a pelvic trainer dexterity task, and tactile feedback using a device invented to simulate tissue resistance. Subjectively, the EndoHand was able to pick up a range of objects similar to those graspable by a Babcock clamp. More complex types of manipulation were possible with the EndoHand because of its wrist joint. The range of approach angles to the fixed point was 35 degrees to 90 degrees with the EndoHand and 70 degrees to 90 degrees with the straight instruments. The dexterity of the EndoHand was significantly less than that of the other two instruments, as measured by time (P = 0.0002) and errors (P = 0.02). Standard instruments were also more accurate in the tactile feedback trials (P = 0.02). The EndoHand is a prototype of a unique new generation of laparoscopic instruments. Although it falls short in both dexterity and tactile feedback, significant promise is shown in its ability to perform sophisticated manipulation of objects and its flexibility to work at a larger range of angles to the target tissue. The EndoHand may be most useful on the nondominant hand of the surgeon to assist with positioning and holding tissue in a specific orientation. Clinical trials will determine its eventual role in laparoscopic surgery.

Confidence Intervals↗

Clinical study of combined penetrating keratoplasty, pars plana vitrectomy with temporary keratoprosthesis, and pars plana seton implant.

PURPOSE: To assess the effectiveness of a combined procedure (pars plana vitrectomy with temporary keratoprosthesis, penetrating keratoplasty, and pars plana seton implant) in preserving vision and controlling intraocular pressure (IOP). METHODS: We reviewed the course of visual acuity, IOP, graft clarity, retinal status, and complications in 18 patients who underwent the above procedure during one operating sitting. RESULTS: Preoperative diagnoses were varied. The majority of patients had pseudophakic bullous keratopathy and failed corneal transplants with glaucoma. Preoperative mean visual acuity was hand motions. Preoperative mean IOP was 27+/-13 mm Hg. Initially, all patients had attached retina. With a mean follow-up of 17+/-9 months, six patients had improved vision greater than 2 lines and 10 had unchanged vision. Only two patients lost vision greater than 2 lines. The final average IOP was 16+/-6 mm Hg and only one eye had a pressure above 22 mm Hg. Three eyes were classified as complete failures; two of the three became phthisical. Two patients developed rhegmatogenous detachments requiring further surgery. CONCLUSION: The combined procedure offers reasonable improvement in vision, good pressure control, and a tolerable number of complications. It is a useful procedure in eyes that probably would not have been treatable otherwise.

Adolescent↗

Nuclear morphometry and prognosis in favorable histology Wilms' tumor: A prospective reevaluation.

PURPOSE: This study was designed to evaluate the ability of a previously published nuclear morphometry discriminant function to predict disease-free survival in patients with Wilms' tumor. PATIENTS AND METHODS: We identified 218 patients with stage I-IV Wilms' tumor of favorable histology who were entered onto the National Wilms' Tumor Study (NWTS) between January 1, 1990 and April 15, 1994. The nuclear morphometry score was calculated for each patient as follows: MV(f) = (0.02 x AGE) + (1.17 x SNRF) + (90.6 x LEFD) - 94, with AGE denoting age at diagnosis in months, SNRF the skewness of the nuclear roundness factor, and LEFD the lowest value of nuclear ellipticity as measured by the feret diameter method. Relative risks of relapse were estimated for the total score and for each of its components. Sensitivity and specificity were determined for the criterion of "MV(f) is greater than -0.35" as a predictor of relapse. RESULTS: By contrast with previously published results, neither the SNRF nor the LEFD made any contribution to the prediction of disease-free survival. Sensitivity and specificity of the criterion of "MV(f) is greater than -0.35" were 71% and 56%, respectively. CONCLUSION: Re-evaluation of a published nuclear morphometry score showed that it did not predict disease-free survival in patients with Wilms' tumor. The earlier study very likely overestimated the predictive power of nuclear morphometry by using the same data set both to develop the score and to evaluate its properties. Because of the huge number of combinations of nuclear morphometry measurements that may enter into the multivariate discriminant function, use of appropriate statistical methods is essential to estimate accurately the sensitivity and specificity.

Child↗

Clinical decision making using teleradiology in urology.

OBJECTIVE: Using a personal computer-based teleradiology system, we compared accuracy, confidence, and diagnostic ability in the interpretation of digitized radiographs to determine if teleradiology-imported studies convey sufficient information to make relevant clinical decisions involving urology. Variables of diagnostic accuracy, confidence, image quality, interpretation, and the impact of clinical decisions made after viewing digitized radiographs were compared with those of original radiographs. MATERIALS AND METHODS: We evaluated 956 radiographs that included 94 IV pyelograms, four voiding cystourethrograms, and two nephrostograms. The radiographs were digitized and transferred over an Ethernet network to a remote personal computer-based viewing station. The digitized images were viewed by urologists and graded according to confidence in making a diagnosis, image quality, diagnostic difficulty, clinical management based on the image itself, and brief patient history. The hard-copy radiographs were then interpreted immediately afterward, and diagnostic decisions were reassessed. All analog radiographs were reviewed by an attending radiologist. RESULTS: Ninety-seven percent of the decisions made from the digitized radiographs did not change after reviewing conventional radiographs of the same case. When comparing the variables of clinical confidence, quality of the film on the teleradiology system versus analog films, and diagnostic difficulty, we found no statistical difference (p > .05) between the two techniques. Overall accuracy in interpreting the digitized images on the teleradiology system was 88% by urologists compared with that of the attending radiologist's interpretation of the analog radiographs. However, urologists detected findings on five (5%) analog radiographs that had been previously unreported by the radiologist. CONCLUSION: Viewing radiographs transmitted to a personal computer-based viewing station is an appropriate means of reviewing films with sufficient quality on which to base clinical decisions. Our focus was whether decisions made after viewing the transmitted radiographs would change after viewing the hard-copy images of the same case. In 97% of the cases, the decision did not change. In those cases in which management was altered, recommendation of further imaging studies was the most common factor.

Decision Making↗

Telemedicine and surgical robotics: urologic applications.

Medical treatment can be improved through integration and application of advances in technology, computers, and engineering. Accuracy and reliability are essential characteristics of any mechanical system, and with the evolution of machines capable of precise movements, the integration of medicine and machine is achievable. Early mechanical devices were effective in performing simple, repetitive tasks but were not sophisticated enough for independent function. In the automobile industry, robots could work on the assembly line executing these cyclic tasks. These machines could execute simple, reiterative movements without integrating new information from the environment. In this day and age, robots have evolved into sophisticated mechanical devices that can "react" to data detected in the environment to determine the next course of events. They have evolved from the assembly line to the operating room, assisting surgeons during surgery to participating in remote telesurgical procedures.

Journal Article↗

A novel method of surgical instruction: international telementoring.

Telemedicine is the use of communication technologies to deliver health care. Telesurgical telementoring represents an advanced form of telemedicine, whereby an experienced surgeon can guide and teach practicing surgeons new operative techniques utilizing current video technology, medical robots, and high-band-width telecommunications. This technology can potentially enhance surgeons' education, increase patients' access to experienced surgeons, and decrease the likelihood of complications due to inexperience with new techniques. A personal computer-based system was developed to immerse a surgical specialist into a distant operating room utilizing public telephone lines. Telesurgical laparoscopic telementoring has successfully been implemented in 27 prior operations between the Johns Hopkins Bayview Medical Center and the Johns Hopkins Hospital, whereby the two institutions were separated by 3.5 miles. We report our experience in performing three successful international surgical telementoring operations, one in Innsbruck, Austria, and two in Bangkok, Thailand.

Adrenalectomy↗

Laparoscopic visual field. Voice vs foot pedal interfaces for control of the AESOP robot.

BACKGROUND: In order for robotic devices to be introduced successfully into surgical practice, the development of transparent surgeon/machine interfaces is critical. METHODS: This study evaluated the standard foot pedal for the AESOP robot compared to a voice control interface. Speed, accuracy, learning curves, durability of learning at 2 weeks, and operator-interface failures were analyzed in an ex vivo model. RESULTS: Foot control was faster and had less operator-interface failures. Voice control was more accurate as measured by "pass points." The foot control learning curve reached a plateau at the third trial, while the voice control did not fully plateau. Durability of learning favored the foot control but was not significantly different. CONCLUSIONS: Currently, the voice control is more accurate and has the advantage of not requiring the surgeon to look away from the operative field. However, it is slower and may require more attention as an interface. As voice recognition software continues to advance, speed and transparency are anticipated to improve.

Equipment Design↗

A quantitative histologic analysis of collagen subtypes: the primary obstructed and refluxing megaureter of childhood.

OBJECTIVES: To analyze and identify collagen subtypes in the primary obstructed and refluxing megaureter of childhood. METHODS: Anticollagen monoclonal antibodies to collagen types I, III, and IV were used in control ureters (n = 4), obstructed (n = 7), and refluxing (n = 13) megaureters. Additionally, all were stained with Masson's trichrome to further define the extracellular matrix. After staining and serial sectioning, representative ureteral sections, focusing on the muscularis and lamina propria regions, were digitized and analyzed with a color image analysis system. RESULTS: Immunohistochemical studies demonstrated increases in collagen types I and III for both obstructed and refluxing megaureters compared with controls (P <0.05). Collagen type IV was not detected in statistically significant amounts in any ureter. In control ureters most was type I (83% +/- 9%) collagen. Obstructed megaureters produced similar results with virtually all collagen being type I (84% +/- 26%) with very little type III collagen present, 5.3% +/- 3%. Refluxing megaureters contained only 55% +/- 15% type I collagen. However, there was an increase in type III collagen (16% +/- 4%) versus (4.5% +/- 2%) in controls (P <0.05). CONCLUSIONS: These data suggest that the greater contribution of type III collagen may play a role in the pathophysiology of refluxing megaureters. Because type III collagen is a less distensible fiber, it may cause an intrinsically stiffer ureter and play a role in the lower surgical success in the reimplantation of refluxing megaureters.

Antibodies, Monoclonal↗

Utility of the harmonic scalpel for laparoscopic partial nephrectomy.

Laparoscopic partial nephrectomy (LPN) remains a technically challenging procedure largely because of the lack of methods for obtaining consistent parenchymal hemostasis. The objective of this study was to determine if the extent of resection influences the ability of the harmonic scalpel to achieve hemostasis and to define the cases in which the harmonic scalpel is appropriate for LPN. Thirty LPNs were performed in a 25-kg domestic pig model. The blunt blade of the laparoscopic harmonic scalpel (LaparoSonic Coagulating Shears; Ethicon Endo-Surgery, Cincinnati, OH) at power level 5 was used to divide the parenchyma. Control of the renal hilar vessels was not obtained. Three standardized types of resections were performed: I = peripheral wedge biopsy; II = upper- or lower-pole nephrectomy; and III = heminephrectomy. Bleeding was graded on a scale from 0 to 4: 0 = no hemostasis; 1 = steady bleeding; 2 = moderate bleeding; 3 = parenchymal oozing; and 4 = dry. Hemostasis grades of 2 or less were clinically significant bleeding necessitating supplemental coagulation. The mean hemostasis scores showed a significant (P < 0.02) trend toward inadequate hemostasis with increasing extent of resection: 3.3 for Type I, 3.0 for Type II, and 2.4 for Type III. The percent of kidneys with grade 2 bleeding or worse was 9% for Type I surgery, 25% for Type II, and 57% for Type III. Successful hemostasis with the harmonic scalpel correlates with the extent of parenchymal resection in the porcine model. Most wedge excisions can be done with the harmonic scalpel alone, whereas larger resections necessitate supplemental coagulation. On the basis of this study, heminephrectomies with the harmonic scalpel are not recommended because of the high incidence of significant hemorrhage.

Animals↗

International surgical telementoring: our initial experience.

INTRODUCTION: Telesurgical laparoscopic telementoring has successfully been implemented between the Johns Hopkins Bayview Medical Center and the Johns Hopkins Hospital in 27 prior operations. In this previously reported series, telerobotic mentoring was achieved between two institutions 3.5 miles away. We report our experience in performing two international surgical telementoring operations. PURPOSE: To determine the clinical utility of international surgical telementoring during laparoscopic surgical procedures. METHOD: A laparoscopic adrenalectomy was telementored between Innsbruck, Austria (5,083 miles) and Baltimore, MD. As well, a laparoscopic varicocelectomy was telementored between Bangkok, Thailand and Baltimore, MD (10,880 miles) both over three ISDN lines (384 kbps) with an approximate 1 sec delay. RESULTS: Both procedures were successfully accomplished with an uneventful postoperative course. CONCLUSION: International telementoring is a viable method of instructing less experienced laparoscopic surgeons through potentially complex laparoscopic procedures, as well as potentially improving patient access to specialty care.

Adrenalectomy↗

Role of macrophages and macrophage-derived cytokines in the pathogenesis of Kilham rat virus-induced autoimmune diabetes in diabetes-resistant BioBreeding rats.

The diabetes-resistant BioBreeding (DR-BB) rat, derived from diabetes-prone forebears, does not normally develop spontaneous insulitis or diabetes, but when infected with Kilham rat virus (KRV) this animal develops autoimmune diabetes similar to the diabetes-prone BioBreeding (DP-BB) rat. In this study, we attempted to determine whether macrophages and macrophage-derived cytokines play a role in the development of KRV-induced diabetes in DR-BB rats. Seventy-eight percent of DR-BB rats treated with KRV and poly(I:C) develop diabetes, whereas depletion of macrophages with liposome-encapsulated dichloromethylene diphosphonate (lip-Cl2MDP) in KRV and poly(I:C)-treated DR-BB rats results in the near-complete prevention of insulitis and diabetes. Measurement of the macrophage-derived cytokines IL-12, TNF-alpha, and IL-1beta revealed a selective increase of their expression, after KRV infection, in the splenic lymphocytes and the pancreatic islets. Measurement of CD4+ T cell-derived cytokines revealed that IL-2 and IFN-gamma cytokine gene expression closely correlates with an elevation of IL-12, but IL-4 and IL-10 do not change. Depletion of macrophages before the isolation of splenic lymphocytes from DR-BB rats treated with KRV and poly(I:C) resulted in the loss of ability to transfer diabetes to young DP-BB rats. On the basis of these observations, we conclude that macrophages and macrophage-derived cytokines play a critical role in the cascade of events leading to the destruction of pancreatic beta cells, culminating in the development of insulin-dependent diabetes mellitus.

Animals↗

Chinaberry poisoning in two dogs.

Two young dogs became acutely ill following ingestion of fallen fruit from a chinaberry tree (Melia azedarach). Clinical signs of poisoning developed within hours and were characteristic of gastrointestinal and CNS disturbances. Despite prompt and aggressive emergency treatment, neither dog survived longer than 36 hours after the onset of clinical signs of poisoning. Necropsy of 1 dog revealed severe renal congestion, moderate hepatic congestion, and a moderate amount of serosanguineous fluid in the abdominal cavity. To the best of our knowledge, previous reports of chinaberry poisoning of dogs are lacking. However, chinaberry poisoning is well documented in human beings and other animals. Therefore, we strongly recommend that dogs, in addition to other animals, have restricted access to chinaberry trees and their fruit to prevent potential poisoning.

Animals↗

The first step in sugar transport: crystal structure of the amino terminal domain of enzyme I of the E. coli PEP: sugar phosphotransferase system and a model of the phosphotransfer complex with HPr.

BACKGROUND: The bacterial phosphoenolpyruvate (PEP): sugar phosphotransferase system (PTS) transports exogenous hexose sugars through the membrane and tightly couples transport with phosphoryl transfer from PEP to the sugar via several phosphoprotein intermediates. The phosphate group is first transferred to enzyme I, second to the histidine-containing phosphocarrier protein HPr, and then to one of a number of sugar-specific enzymes II. The structures of several HPrs and enzymes IIA are known. Here we report the structure of the N-terminal half of enzyme I from Escherichia coli (EIN). RESULTS: The crystal structure of EIN (MW approximately 30 kDa) has been determined and refined at 2.5 A resolution. It has two distinct structural subdomains; one contains four alpha helices arranged as two hairpins in a claw-like conformation. The other consists of a beta sandwich containing a three-stranded antiparallel beta sheet and a four-stranded parallel beta sheet, together with three short alpha helices. Plausible models of complexes between EIN and HPr can be made without assuming major structural changes in either protein. CONCLUSIONS: The alpha/beta subdomain of EIN is topologically similar to the phosphohistidine domain of the enzyme pyruvate phosphate dikinase, which is phosphorylated by PEP on a histidyl residue but does not interact with HPr. It is therefore likely that features of this subdomain are important in the autophosphorylation of enzyme I. The helical subdomain of EIN is not found in pyruvate phosphate dikinase; this subdomain is therefore more likely to be involved in phosphoryl transfer to HPr.

Amino Acid Sequence↗

Importance of the region around glycine-338 for the activity of enzyme I of the Escherichia coli phosphoenolpyruvate:sugar phosphotransferase system.

The gene encoding enzyme I of the phosphoenolpyruvate:sugar phosphotransferase system from an Escherichia coli enzyme I mutant was cloned and sequenced. The mutation was shown to be a guanine to adenine transition resulting in an altered protein in which glycine-338 was replaced by aspartic acid. The enzyme I structural gene was mutated to change glycine-338 to a variety of other amino acid residues. Fermentation tests indicated that glycine-338 could be mutated to alanine with no gross loss in phosphotransferase activity, while mutation to valine, glutamic acid, aspartic acid, arginine, histidine, or asparagine led to significant loss of activity. An expression vector for enzyme I was mutated to change glycine-338 to a variety of other amino acid residues and highly purified mutant proteins were prepared. Analysis of phosphorylation of the proteins by PEP indicated that mutation of glycine-338 to alanine had little effect on phosphorylation, mutation to valine substantially decreased phosphorylation, change to histidine or arginine drastically diminished phosphorylation, and mutation to aspartic or glutamic acids abolished phosphorylation activity. Mutation at glycine-338 influences the autophosphorylation rather than the phosphoryl transfer activity of enzyme I.

Amino Acid Sequence↗

Importance of the carboxyl-terminal domain of enzyme I of the Escherichia coli phosphoenolpyruvate: sugar phosphotransferase system for phosphoryl donor specificity.

The first protein component of the Escherichia coli phosphoenolpyruvate: sugar phosphotransferase system (PTS) is the 64-kDa protein enzyme I (EI), which can be phosphorylated by phosphoenolpyruvate (PEP) and carry out phosphotransfer to the acceptor heat-stable protein (HPr). The isolated amino-terminal domain (EIN) of E. coli EI is no longer phosphorylated by PEP but retains the ability to participate in reversible phosphotransfer to HPr. An expression vector was constructed for the production of large amounts of EIN, and conditions were developed for maximal expression of the protein. A three-column procedure is described for purification to homogeneity of EIN; a 500-ml culture yields approximately 80 mg of pure protein in about a 75% yield. Intact E. coli EI is effective in phosphotransfer from PEP to HPr from E. coli but not to the HPrs from Bacillus subtilis or Mycoplasma capricolum. Phosphotransfer from EI to enzyme IIAglc (EIIAglc) from E. coli or M. capricolum requires the intermediacy of HPr. The phosphorylated form of EIN is capable of more general phosphotransfer; it will effect phosphotransfer to HPrs from E. coli, B. subtilis, and M. capricolum as well as to EIAglc from E. coli. These studies demonstrate that the carboxyl-terminal domain of EI confers on the protein the capability to accept a phosphoryl group from PEP as well as a discriminator function that allows the intact protein to promote effective phosphoryl transfer only to E. coli HPr.

Amino Acid Sequence↗

Increase in activity for the C-terminal Pro-X bond by site-directed mutagenesis of Gly137 to Ala in carboxypeptidase Z.

A mutant carboxypeptidase Z from Absidia zychae in which Gly137 was replaced by Ala by site-directed mutagenesis was constructed and expressed in Saccharomyces cerevisiae YPH250. The mutant enzyme hydrolyzed C-terminal Pro-X bonds (X = amino acid) more efficiently than the wild-type enzyme and sequentially released amino acids from the C-termini of oligopeptides.

Alanine↗

Evaluation of smooth muscle and collagen subtypes in normal newborns and those with bladder exstrophy.

PURPOSE: Many patients who undergo bladder exstrophy closure as newborns, subsequent epispadias repair and later bladder neck reconstruction become completely continent yet complications can occur. After successful initial exstrophy closure and later epispadias repair some patients may fail to gain sufficient capacity for bladder neck reconstruction or satisfactory capacity and continence after bladder neck reconstruction. In an attempt to understand the pathogenesis of these failures we compared bladder biopsies from normal neonates and those with exstrophy. MATERIALS AND METHODS: Bladder biopsies obtained from the midline of the bladder wall just above the base of the trigone from 12 newborns with exstrophy were compared to bladder sections from 9 neonatal cadavers. All bladder specimens were stained with monoclonal antibodies against type I, III or IV collagen and a subset was further stained with Masson's trichrome to define the extracellular matrix. All specimens were then analyzed using a color digital image analysis system. RESULTS: At initial examination of the extracellular matrix there was an increase in the collagen-to-smooth muscle ratio from 0.38 in controls to 1.2 in newborns with exstrophy, comprising an increase in collagen and decrease in smooth muscle. The collagen component of the extracellular matrix was then further defined to quantitate the amount of each collagen type (I, III and IV) deposited. We then evaluated the ratio of collagen type-to-total collagen sampled. Compared to control bladders there was no statistical difference in the amount of type I or IV in the bladders of newborns with exstrophy at initial closure. However, there was a 3-fold increase in type III collagen (0.14 +/- 0.05 to 0.46 +/- 0.2%, p < 0.001) in the bladders of neonatal controls versus newborns with exstrophy. CONCLUSIONS: This alteration in collagen makeup may represent an earlier developmental stage of the exstrophy bladder at birth, which then remodels and changes after successful initial closure. Further studies are underway to examine the collagen composition of bladders at bladder neck reconstruction, failed closures and augmentation.

Biopsy↗