Biomedical subjects

J Tsao

Publications and source records attributed to J Tsao.

At least 19 recordsLinked to original sources

PubMed2006

Spatiotemporal patterns of host-seeking Ixodes scapularis nymphs (Acari: Ixodidae) in the United States.

The risk of Lyme disease for humans in the eastern United States is dependent on the density of host-seeking Ixodes scapularis Say nymphal stage ticks infected with Borrelia burgdorferi. Although many local and regional studies have estimated Lyme disease risk using these parameters, this is the first large-scale study using a standardized methodology. Density of host-seeking I. scapularis nymphs was measured by drag sampling of closed canopy deciduous forest habitats in 95 locations spaced among 2 degrees quadrants covering the entire United States east of the 100th meridian. Sampling was done in five standardized transects at each site and repeated three to six times during the summer of 2004. The total number of adults and nymphs of the seven tick species collected was 17,972, with 1,405 nymphal I. scapularis collected in 31 of the 95 sites. Peak global spatial autocorrelation values were found at the smallest lag distance (300 km) and decreased significantly after 1,000 km. Local auto-correlation statistics identified two significant high-density clusters around endemic areas in the northeast and upper Midwest and a low-density cluster in sites south of the 39th parallel, where only 21 nymphs were collected. Peak nymphal host-seeking density occurred earlier in the southern than in the most northern sites. Spatiotemporal density patterns will be combined with Borrelia prevalence data as part of a 4-yr survey to generate a nationwide spatial risk model for I. scapularis-borne Borrelia, which will improve targeting of disease prevention efforts.

Animals↗

PubMed2001

Unifying linear prior-information-driven methods for accelerated image acquisition.

In the ongoing quest for faster imaging and higher spatial resolution, several methods have been developed to speed up data acquisition by incorporating prior information about the object being imaged. This study shows that many of these methods can be integrated into a single common equation. The unified framework provides a conceptual link that facilitates comparison among these methods to reveal their strengths and weaknesses. By considering the limitations of existing methods, a new member in this class of methods was developed. The broad-use linear acquisition speed-up technique (BLAST) uses the estimated amount of change within the FOV as prior information. BLAST has the flexibility of incorporating a variable amount of prior information to avoid the misleading appearance of "phantom features," which arise from overconstraining the reconstruction. Examples from dynamic imaging and MR thermometry are shown.

Body Temperature↗

PubMed2001

OspA immunization decreases transmission of Borrelia burgdorferi spirochetes from infected Peromyscus leucopus mice to larval Ixodes scapularis ticks.

Recombinant outer surface protein A (OspA) vaccination of wild animal reservoirs has potential application for reducing Borrelia burgdorferi transmission in nature and subsequent risk of human infection. As a major reservoir host, the white-footed mouse (Peromyscus leucopus) is a candidate for a vaccination program designed to reduce infection prevalence in vector ticks. In this study we characterized the effect of various levels of immunization with recombinant OspA-glutathione transferase fusion protein on transmission dynamics from infected P. leucopus to larval ticks. Control mice were vaccinated with glutathione transferase alone. All mice were experimentally infected with B. burgdorferi before vaccination. The immune responses of the immunized mice were assessed by enzyme-linked immunosorbent assay for antibodies to OspA. Transmission of B. burgdorferi from infected mice was determined by xenodiagnosis with uninfected larval ticks. Spirochetes in ticks were counted by direct immunofluorescence assay. The concentration of antibody to OspA increased with each OspA vaccination but most markedly after the first and second vaccinations. In comparison with control mice, there was reduced transmission by OspA-vaccinated mice to uninfected ticks. One, two, or three doses of OspA reduced infection prevalence in xenodiagnostic ticks by 48%, 92%, or 99% and the numbers of spirochetes per tick by 84%, 98%, or 99%, respectively. This study suggests that vaccination of P. leucopus with OspA could reduce transmission to the tick vector in nature despite prior infection of the reservoir host.

Animals↗

PubMed2001

Extension of finite-support extrapolation using the generalized series model for MR spectroscopic imaging.

In magnetic resonance (MR) imaging, limited data sampling in k-space leads to the well-known Fourier truncation artifact, which includes ringing and blurring. This problem is particularly severe for MR spectroscopic imaging, where only 16-24 points are typically acquired along each spatial dimension. Several methods have been proposed to overcome this problem by incorporating prior information in the image reconstruction. These include the generalized series (GS) model and the finite-support extrapolation method. This paper shows the connection between finite-support extrapolation and the GS model. In particular, finite-support extrapolation is a limiting case of the GS model, when the only available prior information is the support region. The support region refers to those image portions with nonzero intensities, and it can be estimated in practice as the nonbackground region of an image. By itself, the support region constitutes a rather weak constraint that may not lead to considerable resolution gain. This situation can be improved by using additional prior information, which can be incorporated systematically with the GS model. Examples of such additional prior information include intensity estimates of anatomical structures inside the support region.

Artifacts↗

PubMed2000

Sialylation of the host receptor may modulate entry of demyelinating persistent Theiler's virus.

Theiler's murine encephalomyelitis virus (TMEV) is a picornavirus of the Cardiovirus genus. Certain strains of TMEV may cause a chronic demyelinating disease, which is very similar to multiple sclerosis in humans, associated with a persistent viral infection in the mouse central nervous system (CNS). Other strains of TMEV only cause an acute infection without persistence in the CNS. It has been shown that sialic acid is a receptor moiety only for the persistent TMEV strains and not for the nonpersistent strains. We report the effect of sialylation on cell surface on entry and the complex structure of DA virus, a persistent TMEV, and the receptor moiety mimic, sialyllactose, refined to a resolution of 3.0 A. The ligand binds to a pocket on the viral surface, composed mainly of the amino acid residues from capsid protein VP2 puff B, in the vicinity of the VP1 loop and VP3 C terminus. The interaction of the receptor moiety with the persistent DA strain provides new understanding for the demyelinating persistent infection in the mouse CNS by TMEV.

Animals↗

PubMed2000

Impaired steroidogenic factor 1 (NR5A1) activity in mutant Y1 mouse adrenocortical tumor cells.

Mutants isolated from the Y1 mouse adrenocortical tumor cell line (clones 10r-9 and 10r-6) are resistant to ACTH because they fail to express the melanocortin-2 receptor (MC2R). In this study, we show that a luciferase reporter plasmid driven by 1,800 bp of the proximal promoter region of the MC2R was expressed poorly in the mutant cells compared with parent Y1 cells. The differential expression of the MC2R in parent and mutant cells resulted from impaired activity of the orphan nuclear receptor NR5A1 (SF1) on the promoter as determined by 5'-deletion analysis. Furthermore, the activity of an SF1 expression plasmid on an SF1-dependent reporter plasmid was compromised in mutant clones. The site-specific DNA binding properties of SF1 from parent and mutant cells did not differ as determined in electrophoretic mobility shift assays, and the addition of the activation domain of VP16 to the amino terminus of SF1 restored the transcriptional activity of the protein. In addition, the levels of SF1 and other cofactors including WT1, CBP/p300, and steroid receptor coactivator 1 did not differ appreciably between parent and mutant cells. Taken together, these results suggest that ACTH resistance in the mutant clones resulted from a defect that affected the activation properties of SF1 rather than its DNA binding activity. Consistent with the observed impairment in SF1 function, other SF1-dependent genes, including Cyp11b1 and steroidogenic acute regulatory protein (StAR), were poorly expressed and global steroidogenesis, as evidenced by the metabolism of 22(R)-hydroxycholesterol to steroid products, was impaired. Interestingly, MC2R, Cyp11a, Cyp11b1, and StAR transcripts were not affected to the same degree, suggesting that each of these genes may have a different absolute requirement for SF1. These mutants thus provide an experimental paradigm to identify factors that influence SF1 function and to evaluate the relative importance of SF1 in the expression of genes essential for adrenal steroidogenesis.

Adrenal Cortex Hormones↗

PubMed1999

The preterm prediction study: failure of midtrimester cervical sialidase level elevation to predict subsequent spontaneous preterm birth.

OBJECTIVE: Our objective was to determine any associations among midtrimester cervical fluid sialidase activity, bacterial vaginosis, and subsequent spontaneous preterm birth. STUDY DESIGN: In this nested case-control study all patients (n = 126) with spontaneous preterm birth at <35 weeks' gestation and selected control subjects delivered at >/=37 weeks' gestation (n = 126, matched for race, parity, and center) were derived from women enrolled in the multicenter National Institute of Child Health and Human Development Preterm Prediction Study. Sialidase activity and presence of bacterial vaginosis according to Gram stain were determined in cervical swabs and vaginal smears, respectively, obtained at 22 weeks' to 24 weeks 6 days' gestation. RESULTS: The mean +/- SD sialidase activities were similar in case patients and control subjects (0.64 +/- 1.60 vs 0.41 +/- 0.94 nmol. mL-1. min-1, P =.21). Neither sialidase activity above the 90th percentile (10.3% vs 9.5%, P =.8) nor sialidase activity above the 95th percentile (7.9% vs 4. 8%, P =.3) of control specimens (>1.43 and >2.23 nmol. mL-1. min-1, respectively) was associated with spontaneous preterm birth. The frequency of combinations of bacterial vaginosis and elevated sialidase activity was similar (P >/=.63 with either cutoff) in case patients and control subjects. Sialidase activity was significantly higher among women with bacterial vaginosis than among those without bacterial vaginosis (1.35 +/- 1.87 vs 0.03 +/- 0.14 nmol. mL-1. min-1, P <.0001). CONCLUSIONS: Elevated cervical fluid sialidase activity at 22 to 24 weeks' gestation did not distinguish women at increased risk for spontaneous preterm birth, nor did it discriminate a subgroup of patients who had bacterial vaginosis associated with spontaneous preterm birth.

Case-Control Studies↗

PubMed1998

Fully automated establishment of stereotaxic image orientation in six degrees of freedom for technetium-99m-ECD brain SPECT.

UNLABELLED: Anatomical localization requires establishing an anatomical space within the image matrix. We developed a fast, fully automated method to establish the image orientation for 99mTc-ethylcysteinate dimer (ECD) brain SPECT images. METHODS: The image orientation of ECD brain SPECT images was established in four stages. First, the brain surface was edge-detected as an isosurface at an adaptive threshold. Second, a "convex hull" was determined for the isosurface to minimize regional variability in brain shape. A principal axis transformation and a symmetry vector analysis were applied to the convex hull to resolve the craniocaudal direction and to estimate the midsagittal plane. Third, the brain orientation was refined from this estimate by location of the interhemispheric fissure, the tentorial groove and the frontotemporal groove on the isosurface. Last, the intercommissural (anterior commissure-posterior commissure, or AC-PC) line was detected on the midsagittal slice, and the Talairach grid was scaled to fit the maximal brain dimensions from the AC-PC line. RESULTS: The average absolute errors were 2.3 degrees +/- 1.5 degrees and 1.08 mm +/- 1.11 mm for the midsagittal plane (n = 24) and 2.04 degrees +/- 0.80 degrees, 2.0% +/- 1.8% of the brain length and 2.3% +/- 2.2% of the brain height for the AC-PC line (n = 8). In addition, this program successfully established the image orientation in 94 of 100 clinical ECD brain SPECT studies. Processing time was <40 sec for 128 x 128 x 50 matrices on a DEC Alpha workstation. CONCLUSION: We have developed a fast, robust and fully automated method that determines the orientation of ECD brain SPECT images. This objective method of standardizing the image orientation should be useful for anatomical localization and clinical interpretation of these images.

Adult↗

PubMed1997

Consequences of lost gallstone.

Laparoscopic cholecystectomy has become the treatment of choice in the management of calculus gallbladder disease. Intraperitoneal gallstone loss is not uncommon; it occurs in up to 40% of cases. Often, the stones are left unretrieved and are thought to be inconsequential. We present a series of patients who have had serious sequela from gallstones in the peritoneal cavity. We performed a retrospective study of the management of six patients with complications from intraperitoneal gallstones. The patients presented with a variety of complaints, from fevers to pneumonia to a colo-cutaneous fistula. Presentation ranged from immediately postoperatively to 18 months after surgery. Diagnosis included perihepatic abscesses and colo-biliary fistula. General anesthesia was usually necessary for removal of the stones. All patients have resolved following the removal of the gallstones. Our recommendation is to attempt to avoid spillage through careful dissection and retrieve any lost stones. The defect in the gallbladder can be closed with a clip. Whether the procedure should be converted to an open one to retrieve all the stones remains open to debate. The surgeon should be aware of the possible consequences of the lost gallstone.

Biliary Fistula↗

PubMed1997

Minimally invasive management of low-grade and benign gastric tumors.

BACKGROUND: Benign gastric tumors and tumors of low-grade malignancy can be safely removed laparoscopically. METHODS: Seven patients were considered candidates for laparoscopic resection of gastric tumors. Inclusion criteria included small tumor size (less than 6 cm), exophytic or endophytic tumor morphology, and benign characteristics. Indications for surgical intervention included bleeding, weight loss, and need for tissue diagnosis. Patients ranged in age from 38 to 70. There were five female and two male patients. All patients underwent preoperative upper GI endoscopy. The procedures were performed using a four- or five-port technique. An Endo-GIA (US Surgical Company, Norwalk, Connecticut) was used to amputate those tumors located on the serosal surface of the stomach. Tumors on the mucosal surface were exposed via a gastrotomy, then likewise amputated using an Endo-GIA. The gastrotomy closure was then either hand sewn or stapled. Operating time ranged from 95 to 225 min. RESULTS: Final pathologic diagnoses included lipoma, lymphoma, leiomyoma, and leiomyosarcoma. There was a 28% conversion rate. There were no complications. Length of postoperative stay ranged from 4 to 7 days. There have been no tumor recurrences in 6-38-month follow-up. CONCLUSIONS: Minimally invasive management of benign and low-grade gastric tumors can be performed safely with excellent short- and long-term results.

Adult↗

PubMed1996

Amplification of the transketolase gene in desensitization-resistant mutant Y1 mouse adrenocortical tumor cells.

As shown previously, mutants of the Y1 mouse adrenocortical tumor cell line that resist agonist-induced desensitization of adenylyl cyclase have elevated levels of a 68-kDa protein (designated p68), suggesting a possible relationship between p68 and the regulation of adenylyl cyclase activity. In the present study, cDNA cloning and sequencing were used to identify p68 as mouse transketolase. Cells overexpressing p68 exhibited a 17.4-fold increase in transketolase enzymatic activity relative to parental Y1 cells and a 28-fold amplification of the transketolase gene as determined by Southern blot hybridization analysis. Using fluorescent in situ hybridization analysis, the transketolase gene was mapped to mouse chromosome 16B1 and to human chromosome 3p21.2. Transketolase gene amplification was associated with telomeric fusion of the chromosome 16 pair together with the appearance of multiple copies of the transketolase gene throughout a different chromosome. The relationship between overexpression of transketolase and desensitization resistance was evaluated in somatic cell hybrids formed between a desensitization-resistant adrenal cell line and a desensitization-sensitive rat glial cell line. In these hybrids, transketolase overexpression behaved dominantly, whereas desensitization resistance behaved recessively. These results dissociate the desensitization resistance phenotype from overexpression of transketolase and suggest that desensitization resistance may have resulted from disruption of an essential regulatory gene in conjunction with the amplification event.

Adenylyl Cyclases↗

PubMed1996

Mutations to forskolin resistance result in loss of adrenocorticotropin receptors and consequent reductions in levels of G protein alpha-subunits.

A family of mutants isolated from the Y1 mouse adrenal cell line on the basis of their resistance to the growth inhibitory effects of forskolin have an underlying mutation that affects the activity of adenylyl cyclase. As part of the mutant phenotype, adenylyl cyclase is partially resistant to activation by forskolin, completely insensitive to ACTH, and fully responsive to NaF; the levels of Gs alpha and G1 alpha in plasma membrane fractions are decreased; and the activity of G beta/gamma is impaired. In the present study, we examine the basis for the complex phenotype associated with forskolin resistance to better understand the factors that contribute to the regulation of adenylyl cyclase activity. We demonstrate that the resistance of these mutants to ACTH results from the failure to express ACTH receptor transcripts. Transfection of these mutants with a gene encoding the mouse beta 2-adrenergic receptor led to the recovery of transformants with normal receptor-G protein coupling and with increased levels of Gs alpha and G1 alpha that approached those in parental Y1 cells. These beta 2-adrenergic receptor transformants, nonetheless, remained resistant to forskolin and ACTH. Two spontaneous Y1 mutants, Y6 and OS3, previously characterized as ACTH-resistant clones that failed to accumulate ACTH receptor transcripts, were shown to be forskolin resistant and to contain less Gs alpha in membrane fractions, indicating that forskolin resistance, failure to express the ACTH receptor, and the consequent reduction in Gs alpha are closely linked. Expression of the human ACTH receptor in Y6 and OS3 cells restored ACTH-responsive adenylyl cyclase activity and increased the level of Gs alpha, but did not otherwise reverse the forskolin-resistant phenotype. Together, these results demonstrate that mutations to forskolin resistance have downstream consequences that result in the loss of ACTH receptor expression and the consequent reduction in levels of membrane-associated G alpha subunits. The results further suggest that G protein-coupled receptors may have a stabilizing influence on G alpha subunits associated with the cell membrane. According to current models, forskolin activates adenylyl cyclase by forming a ternary complex with adenylyl cyclase and Gs alpha. Our results suggest that this model may be incomplete and that an additional component, acting directly or indirectly, is required for optimal activation of adenylyl cyclase by forskolin.

Adenylyl Cyclases↗

PubMed1995

Adrenocorticotropin-resistant mutants of the Y1 adrenal cell line fail to express the adrenocorticotropin receptor.

This report examines the basis for adrenocorticotropin (ACTH) resistance in two mutant clones (Y6 and OS3) derived from the ACTH-responsive Y1 mouse adrenocortical tumor cell line. These two mutants were originally characterized by their failure to respond to ACTH with increased adenylyl cyclase activity and as a consequence were resistant to the steroidogenic effects of the hormone. We now demonstrate that ACTH resistance in the Y6 and OS3 mutants results from the failure to express the gene encoding the ACTH receptor. Whereas parental Y1 cells express ACTH receptor transcripts at low levels and are stimulated by ACTH or 8-bromo-cAMP to increase the accumulation of ACTH receptor transcripts approximately twofold, the Y6 and OS3 mutants do not express receptor transcripts either in the presence or absence of 8-bromo-cAMP. The gene encoding the ACTH receptor appears to be present in the Y6 and OS3 mutants, as determined by Southern blot hybridization analysis. Moreover, in the Y6 mutant the ACTH receptor gene appears to be silenced by a modification that is reversed following the growth of the cells as tumors in mice. Clonal isolates of Y6 cells grown as tumors recover the ability to express ACTH receptor transcripts at low but detectable levels and acquire the ability to respond to ACTH with increased adenylyl cyclase activity. Finally, Y6 and OS3 cells transformed with a gene encoding the mouse beta 2-adrenergic receptor respond to the beta-adrenergic agonist, isoproterenol, in a manner that is indistinguishable from the similarly transformed parent Y1 cell line. These latter results demonstrate the functional integrity of the adenylyl cyclase system in the ACTH-resistant mutants and indicate that the failure to express ACTH receptor transcripts limits the responsiveness of these clones.

Adenylyl Cyclases↗

PubMed1995

Biliary tract complications of laparoscopic cholecystectomy are detected more frequently with routine intraoperative cholangiography.

Controversy over whether intraoperative cholangiography (IOC) should be done routinely has intensified since the advent of laparoscopic cholecystectomy (LC). As yet, no study has demonstrated a clear benefit to its use, although their have been suggestions in the literature that routine use may confer an advantage to detection of injuries. One-hundred seventy-seven biliary tract complications occurring secondary to LC were identified from the combined data of seven institutions. The goal of this retrospective study was to examine the impact of IOC on the occurrence, recognition, and correction of such complications. The complications identified include 39 cystic duct leaks, 69 major ductal leaks or strictures, and 69 major ductal transection or excision injuries. Whether IOC was performed was known in 157 (88%) patients with 53 patients definitely having and 104 not having an IOC. Data concerning IOC were unavailable in 20 cases. More injuries were detected intraoperatively in the group having IOC (P < 0.001). Conversion of the LC to a laparotomy, often for repair of the injury, occurred more commonly in the group having a correctly interpreted IOC (P < 0.001). Conversion resulted in detection of injuries sooner, resulting in fewer operative procedures to correct the injury (P < 0.001). A transecting injury was prevented in at least seven patients when no visualization of the proximal biliary tree was documented by IOC. These partial ductal incisions were treated by t-tube placement. Incorrect interpretation of the IOC occurred in at least eight patients, with no identification of the proximal biliary tree in six.(ABSTRACT TRUNCATED AT 250 WORDS)

Bile Ducts↗

PubMed1994

In vitro proteolytic activity and active-site identification of the human cytomegalovirus protease.

Human cytomegalovirus (HCMV) encodes a protease that cleaves itself and the HCMV assembly protein. Two proteolytic processing sites within the protease were identified at Ala 256-Ser 257 (release site) and Ala 643-Ser 644 (maturation site). Identification of rP5-P4' and mP4-P6' as the minimal peptide substrates spanning the release and maturation cleavage sites, respectively, demonstrated a requirement for residues flanking the conserved core in substrate recognition and hydrolysis, which are unique to HCMV. Kinetic parameters determined for release-site-derived and maturation-site-derived peptides revealed a 10-fold increase in kcat/Km for a maturational peptide (mP4-P8') over release-site peptide (rP5-P5'). Experimental results with a panel of class-specific protease inhibitors were consistent with the protease being a member of the serine or cysteine family of proteases. Further investigation revealed that the HCMV protease activity decreased with incorporation of [14C]iodoacetic acid, but when approximately 4.5 mol 14C were incorporated/mol enzyme, the enzyme retained approximately 20% of its original activity, indicating that hydrolysis does not require a cysteine nucleophile. Analysis of diisopropyl-fluorophosphate-inactivated protease by mass spectrometry indicated a stoichiometry of 1 diisopropyl phosphate/protease molecule, suggesting that hydrolysis requires a single serine nucleophile. The residue modified by diisopropyl fluorophosphate was identified as Ser132 by modification with 3H-labeled diisopropyl fluorophosphate, peptide mapping and Edman degradation. This residue and the region in which it is found is highly conserved among the herpes virus proteases. These data demonstrates that HCMV protease is a serine protease and that Ser132 is the active-site nucleophile.

Amino Acid Sequence↗

PubMed1994

Orientation of peptide fragments from Sos proteins bound to the N-terminal SH3 domain of Grb2 determined by NMR spectroscopy.

NMR spectroscopy has been used to characterize the protein-protein interactions between the mouse Grb2 (mGrb2) N-terminal SH3 domain complexed with a 15-residue peptide (SPLLPKLPP-KTYKRE) corresponding to residues 1264-1278 of the mouse Sos-2 (mSos-2) protein. Intermolecular interactions between the peptide and 13C-15N-labeled SH3 domain were identified in half-reverse-filtered 2D and 3D NOESY experiments. Assignments for the protons involved in interactions between the peptide and the SH3 domain were confirmed in a series of NOESY experiments using a set of peptides in which different leucine positions were fully deuterated. The peptide ligand-binding site of the mGrb2 N-terminal SH3 domain is defined by the side chains of specific aromatic residues (Tyr7, Phe9, Trp36, Tyr52) that form two hydrophobic subsites contacting the side chains of the peptide Leu4 and Leu7 residues. An adjacent negatively charged subsite on the SH3 surface is likely to interact with the side chain of a basic residue at peptide position 10 that we show to be involved in binding. The peptide-binding site of the SH3 is characterized by large perturbations of amide chemical shifts when the peptide is added to the SH3 domain. The mGrb2 N-terminal SH3 domain structure in the complex is well-defined (backbone RMSD of 0.56 +/- 0.21 calculated over the backbone N, C alpha, and C atoms of residues 1-54). The structure of the peptide in the complex is less well-defined but displays a distinct orientation.(ABSTRACT TRUNCATED AT 250 WORDS)

Adaptor Proteins, Signal Transducing↗

PubMed1994

Characteristics of biliary tract complications during laparoscopic cholecystectomy: a multi-institutional study.

We collected the records of 81 patients with biliary tract injuries occurring during laparoscopic cholecystectomy (LC) who were referred to 3 referral centers during a 33-month (May 1990 to March 1993) period. All records were reviewed to provide data concerning the anatomy of the lesion induced, method of injury, timing of injury detection, role of intraoperative cholangiography (IOC), methods of treatment, and outcome of these injuries. Injuries were classified by our own method as follows: (1) cystic duct leaks (n = 15), (2) bile leaks and/or ductal strictures (n = 27), and (3) ductal transections or excisions (n = 39). Peak occurrence by quarter of the year was 4th quarter, 1990 (Lahey), and 3rd quarter, 1991 (Mason), and 1st quarter, 1992 (Mayo). The majority (62%) of the injuries were recognized after LC. At the time of LC, 31 of 81 (38%) injuries were recognized and converted to open procedures. Data regarding IOC were available in 63 of 81 (78%) cases. In patients in whom IOC was not performed, 14 of 38 (37%) operations were converted; if an IOC was obtained and interpreted correctly, 13 of 21 (62%) operations were converted. Primary repair was attempted in 11 leaks and/or strictures, but 36% required additional treatment. Primary repair was used in six transections or excisions, and 17% have required further intervention. In patients who had biliary-enteric bypass (BEB) performed outside (17) versus at the referral institution (29), 94% (16 patients) versus 0%, respectively, required additional operative (e.g., revision of a hepaticojejunostomy) or nonoperative (e.g., radiologic or endoscopic stenting or balloon dilation) procedures. When used as initial therapy or after a primary ductal repair, stents (with or without balloon dilation) resolved 100% of simple cystic duct leaks and 91% of leaks and/or strictures. In conclusion, the peak incidence of LC-related biliary injuries appears to have passed. A completed and correctly interpreted IOC increases the chance of detection of biliary injuries intraoperatively and should assist surgeons who use routine IOC. Nonsurgical techniques allow treatment of most simple cystic duct leaks, major ductal leaks and/or strictures, and postoperative BEB strictures, although follow-up is limited. The poor results of pre-referral BEB is not surprising since all of these patients were selected for referral because their treatments had not been successful.

Bile Ducts↗

PubMed1994

Further evidence that one of the earliest alterations in colorectal carcinogenesis involves APC.

Colorectal cancer is hypothesized to arise after the accumulation of multiple mutations in critical oncogenes or tumor suppressor genes. The relative timing of each mutation is unknown because the exact number and types of mutations differ between tumors. However, for every mutation except the first, tumor heterogeneity must exist until clonal dominance is reestablished. This principle was applied to mutant APC genes in eight colorectal adenomas. The APC mutations were homogeneously present throughout the adenomas, including those less than 1 cm in size, but absent from the normal polyp stalks. In one adenoma with APC and c-K-ras mutations, both mutations were simultaneously present in only a small discrete portion, suggesting that the c-K-ras mutation was acquired after the APC mutation. These findings suggest that when mutations in APC occur, they are usually one of the first events in colorectal carcinogenesis or provide such a strong selective advantage that intratumor heterogeneity is seldom observed.

Adenoma↗