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Biomedical subjects

S Chou

Publications and source records attributed to S Chou.

At least 19 recordsLinked to original sources

Heterogenous and homogenous catalytic oxidation by supported gamma-FeOOH in a fluidized-bed reactor: kinetic approach.

Oxidation of benzoic acid (BA) by H2O2 was performed with a novel supported gamma-FeOOH catalyst in a circulating fluidized-bed reactor (CFBR). This study focused mainly on determining the proportions of homogeneous catalysis and heterogeneous catalysis in this CFBR. Also studied herein was how pH, H2O2 concentration, and BA concentration affect the oxidation of BA. Experimental results indicate that the decomposition rate of H2O2 was proportional to its concentration and that the oxidation rate of BA depended on both H2O2 and BA concentrations. The change in the rate constant of heterogeneous catalysis by pH was described in terms of ionization fractions of surface hydroxyl group. From the mathematical deduction, we can infer thatthe reaction rate associated with ...Fe(III)OH2+ is markedly higher than that with ...Fe(III)OH. Conclusively, although heterogeneous catalysis contributes primarily to the oxidation of BA at pH 4.4-7.0, the homogeneous catalysis is of increasing importance below pH 4.4 because of the reductive dissolution of gamma-FeOOH.

Benzoic Acid↗

Testing of alkaline and enzymatic hydrolysis pretreatments for fat particles in slaughterhouse wastewater.

Four pretreatments to hydrolyse and/or reduce the size of fat particles in slaughterhouse wastewater (SHW) were tested: sodium hydroxide and three lipases of plant, bacterial and animal (pancreatic) origin. Hydrolysing agents and SHW containing between 2.5 and 3 g/l of fat particles were mixed at room temperature for 4 h. Additions of 5-400 meq NaOH/l did not increase soluble COD (SCOD) in SHW, but the average particle size was reduced to 73% +/- 7% of the initial average particle size (D(in)) at NaOH concentrations ranging from 150 to 300 meq/l. Pretreatment with pancreatic lipase PL-250 reduced the average particle size to a maximum of 60% +/- 3% of D(in). As D(in) was decreased from 359 to 68 microns, the enzyme concentration required to obtain the maximum particle size reduction increased from 200 to 1000 mg/l. A 4-h pretreatment with PL-250 also increased the free long-chain fatty acid (LCFA) concentration to a maximum of 15.5 mg/l, indicating some solubilization of the pork fat particles in SHW. SCOD was not significantly increased by the pretreatment, but SCOD was not found to be a good indicator of enzymatic lipolysis because of enzyme adsorption on the fat particle surface. Pancreatic lipase appeared more efficient with beef fat than pork fat, possibly because beef fat contains less polyunsaturated fatty acids than pork fat. The bacterial lipase LG-1000 was also efficient in reducing average fat particle size, but high doses (> 1000 mg/l) were required to obtain a significant reduction after 4 h of pretreatment. SCOD was not increased by pretreatment with LG-1000. No particle size reduction or changes in SCOD were noted after 4 h of pretreatment with the plant lipase EcoSystem Plus. It was concluded that PL-250 was the best pretreatment to hydrolyse fat particles in SHW. However, its impact on the efficiency of a downstream anaerobic digestion process remains to be tested.

Abattoirs↗

Mining time dependency patterns in clinical pathways.

Clinical pathways are widely adopted by many large hospitals around the world in order to provide high-quality patient treatment and reduce the length of hospital stay of each patient. The development of clinical pathways is a lengthy process, and may require the collaboration among physicians, nurses, and staffs in a hospital. However, the individual differences cause great variances in the execution of clinical pathways. It calls for a more dynamic and adaptive process to improve the performance of clinical pathways. This paper reports a data mining technique we have developed to discover the time dependency pattern of clinical pathways for managing brain stroke. The mining of time dependency pattern is to discover patterns of process execution sequences and to identify the dependent relation between activities in a majority of cases. By obtaining the time dependency patterns, we can predict the paths for new patients when he/she is admitted into a hospital; in turn, the health care procedure will be more effective and efficient.

Algorithms↗

Treatment of progressive hepatitis C recurrence after liver transplantation with combination interferon plus ribavirin.

Hepatitis C virus (HCV) recurrence after orthotopic liver transplantation (OLT) is common, although the majority of cases are mild. A subset of transplant recipients develops progressive allograft injury, including cirrhosis and allograft failure. Minimal data are available on the safety and efficacy of antiviral treatment in this group of patients. The aim of this study is to review our experience in the treatment of moderate to severe HCV recurrence with combination interferon-alpha2b and ribavirin (IFN/RIB). Between October 1993 and October 1999, a total of 197 patients underwent OLT for HCV-related liver failure. This study describes 12 transplant recipients with moderate to severe recurrence treated with IFN/RIB. All patients met at least 1 of the following inclusion criteria: (1) moderate to severe inflammation (grade III to IV) on allograft biopsy, (2) bridging fibrosis on allograft biopsy, or (3) severe cholestasis attributable solely to HCV recurrence. Two patients had undergone re-OLT for allograft cirrhosis secondary to HCV recurrence and now had evidence of progressive HCV in their second allografts. Appropriate dose reductions of both IFN and RIB, as well as initiation of granulocyte colony-stimulating factor (G-CSF), for marked leukopenia were recorded. IFN/RIB therapy was started 60 to 647 days post-OLT, and duration of therapy ranged from 39 to 515 days. Seven patients were administered G-CSF to successfully treat leukopenia. Six of the 12 patients (50%) became HCV RNA negative by polymerase chain reaction. One of these 6 patients (no. 1) was HCV RNA negative at 6 months but chose to discontinue therapy because of intolerable side effects, experienced a relapse, and was HCV RNA positive at 12 months. Two of the remaining 5 patients were HCV RNA negative at 2 and 9 months off therapy. For the entire group, there was a statistically significant decrease in serum biochemical indices assessed at initiation of therapy and 1, 3, and 6 months into therapy. Most patients required dose reductions of both IFN and RIB. Five patients died; 3 patients died of liver-related complications that included severe intrahepatic biliary cholestasis, severe HCV recurrence, and chronic rejection with profound cholestasis. In the subset of HCV-positive liver transplant recipients with moderate to severe recurrence, combination IFN/RIB therapy resulted in complete virological response (serum RNA negative) in 6 of 12 patients ( approximately 50%). However, only 1 of 12 patients (8.3%) had sustained virological clearance after cessation of IFN/RIB therapy. Dose reductions of both IFN and RIB were required in most patients. The use of G-CSF (sometimes preemptively) allowed correction of leukopenia and full-dose antiviral therapy. Multicenter trials using combination therapy to identify factors predictive of response are needed in the subset of patients with progressive allograft injury.

Adult↗

Sequencing of cytomegalovirus UL97 gene for genotypic antiviral resistance testing.

The widespread use of ganciclovir (GCV) to treat cytomegalovirus (CMV) infections in immunosuppressed patients has led to the development of drug resistance. Phenotypic assays for CMV drug resistance are presently too time-consuming to be therapeutically useful. To support the development of genotypic assays for GCV resistance, the complete sequences of the UL97 phosphotransferase genes in 28 phenotypically GCV-sensitive CMV clinical isolates were determined. The gene was found to be highly conserved, with nucleotide sequence identity among strains ranging from 98.6 to 100% and amino acid sequence identity of >99%. Primers for a genotypic assay were designed to amplify codons 400 to 707, because all known UL97 mutations conferring drug resistance occur at three sites within this region. This part of the UL97 gene was amplified from over 50 clinical isolates, and two sequencing reactions for the coding strand were successfully used to identify GCV resistance mutations. This genotypic assay can be performed in 48 h using genomic DNA extracted from cell monolayers at very low levels of virus infectivity, thus rapidly providing therapeutically useful results.

Amino Acid Sequence↗

A deletion mutation in region V of the cytomegalovirus DNA polymerase sequence confers multidrug resistance.

A patient with AIDS and cytomegalovirus (CMV) retinitis received ganciclovir and foscarnet for 20 and 5 months, respectively, with evidence of periodic disease progression. After this therapy, a CMV isolate from the patient was resistant to ganciclovir, foscarnet, and cidofovir. Sequence analysis showed a known ganciclovir resistance mutation in the viral UL97 phosphotransferase (L595F) and a new mutation in conserved region V of the DNA polymerase gene (pol) sequence (codons 981-982 deleted). The pol mutation was transferred to a laboratory CMV strain (Towne) by homologous recombination and selection with either ganciclovir or foscarnet. Recombinant viruses containing this deletion showed a 6-8-fold increased ganciclovir resistance and a 3-5-fold increased resistance to both foscarnet and cidofovir, compared with the wild-type CMV. A single mutation in region V of CMV pol can, therefore, confer multiple drug resistance in a clinical isolate.

Acquired Immunodeficiency Syndrome↗

Pitfalls in the interpretation of MIBG scans in cervical neuroblastoma.

Cervical neuroblastoma (CNB) is relatively rare, accounting for less than 5% of these tumors. Because it arises from the cervical sympathetic chain, complete resection will leave the child with Horner's syndrome in a high proportion of cases. Advances in technology have allowed for the development of diagnostic and imaging modalities more specific to the disease. One of these has been the advent of radiolabeled meta-iodobenzylguanidine (MIBG) to assess the primary tumor and focal metastatic involvement. This nuclide is also taken up by normal salivary-gland tissue; this may be altered, however, in the presence of sympathetic denervation. We present a case of a primary CNB associated with Horner's syndrome, which led to confusion in interpretation of the subsequent MIBG scan. We alert the reader to potential pitfalls in the use of this examination in this disease entity.

3-Iodobenzylguanidine↗

Detection of unsuspected colonic abnormalities using the pneumocolon technique during small bowel meal examination.

AIMS: The pneumocolon technique in small bowel meal examination is used to obtain double-contrast views of the distal ileum. The purpose of this study was to determine the proportion of cases in which an overhead pneumocolon radiograph demonstrated clinically relevant findings in the colon. METHODS: The overhead pneumocolon radiographs in 151 patients who underwent small bowel meals were evaluated retrospectively. A chart review was performed on those patients with positive colonic findings to determine if the suspected abnormalities affected patient management. RESULTS: Colonic abnormalities were identified in 34 of the 151 patients. One patient had a previously undiagnosed ascending colonic cancer; 17 had evidence of acute or chronic colitis; 13 had diverticulosis; one had a caecal polyp; one had an ileosigmoid fistula; one had a filling defect in the ascending colon. In 25 cases the colonic abnormality was visible only on the pneumocolon radiograph and not on the preceding single-contrast images. Management was altered by the colonic findings in seven cases. False-positive findings occurred in two cases. CONCLUSIONS: A routine overhead radiograph following use of the pneumocolon technique is a useful adjunct to small bowel meal examination as it can yield unsuspected and clinically significant colonic findings.Chou, S. (2000). Clinical Radiology55, 459-464.

Adolescent↗

A nine-codon deletion mutation in the cytomegalovirus UL97 phosphotransferase gene confers resistance to ganciclovir.

A deletion mutation (codons 595 to 603) in the cytomegalovirus (CMV) UL97 gene was recently reported after sequence analysis of leukocyte DNA from a patient receiving ganciclovir. The corresponding viral phenotype was examined by transfer of this mutation to a laboratory CMV strain (strain Towne). The recombinant virus was resistant to ganciclovir (8.4-fold increase in the 50% inhibitory concentration), was sensitive to foscarnet, and replicated normally in cell culture.

Antiviral Agents↗

A standardized plaque reduction assay for determination of drug susceptibilities of cytomegalovirus clinical isolates.

Twelve laboratories collaborated in formulating and testing a standardized plaque reduction assay for cytomegalovirus (CMV) cell-associated clinical isolates. Four characterized and plaque-purified CMV strains, as well as six coded clinical isolates obtained after antiviral therapy, were distributed and tested. Good agreement was obtained for four of the clinical isolates, but a broad distribution of results was obtained for two isolates. Analysis of these results indicates the problems associated with clinical isolates, including the large genetic variability and the highly cell-associated phenotype. This collaborative effort, by addressing these problems, represents a significant step toward the development of a standardized assay.

Antiviral Agents↗

Preferential accessibility of the yeast his3 promoter is determined by a general property of the DNA sequence, not by specific elements.

Yeast promoter regions are often more accessible to nuclear proteins than are nonpromoter regions. As assayed by HinfI endonuclease cleavage in living yeast cells, HinfI sites located in the promoters of all seven genes tested were 5- to 20-fold more accessible than sites in adjacent nonpromoter regions. HinfI hypersensitivity within the his3 promoter region is locally determined, since it was observed when this region was translocated to the middle of the ade2 structural gene. Detailed analysis of the his3 promoter indicated that preferential accessibility is not determined by specific elements such as the Gcn4 binding site, poly(dA-dT) sequences, TATA elements, or initiator elements or by transcriptional activity. However, progressive deletion of the promoter region in either direction resulted in a progressive loss of HinfI accessibility. Preferential accessibility is independent of the Swi-Snf chromatin remodeling complex, Gcn5 histone acetylase complexes Ada and SAGA, and Rad6, which ubiquitinates histone H2B. These results suggest that preferential accessibility of the his3 (and presumably other) promoter regions is determined by a general property of the DNA sequence (e.g., base composition or a related feature) rather than by defined sequence elements. The organization of the compact yeast genome into inherently distinct promoter and nonpromoter regions may ensure that transcription factors bind preferentially to appropriate sites in promoters rather than to the excess of irrelevant but equally high-affinity sites in nonpromoter regions.

Adaptor Proteins, Signal Transducing↗

Efficacy and safety of patient-controlled analgesia for morbidly obese patients following gastric bypass surgery.

BACKGROUND: Adequate postoperative pain control is important to reduce potential cardiopulmonary complications. It is often difficult to determine dosages of narcotics for morbidly obese patients following Roux-en-Y gastric bypass (RYGBP) due to respiratory depression. Individualization of analgesic therapy, patient-controlled analgesia (PCA), can provide optimal dosage for pain control and minimize the side-effects. METHOD: 25 morbidly obese patients who received PCA with morphine sulfate following RYGBP. PCA settings we re as follows: morphine, 20 microg/kg of ideal body weight, 10-minute lock out interval and 80 % of a calculated amount for a 4-hour limit. W e measured arterial blood gas, heart rate, mean arterial pressure, arterial oxygen saturation, respiratory rate, opioid amount, patient satisfaction, visual analog pain scale (VAS), and the incidence of nausea, vomiting, pruritus and sedation. RESULTS: Average morphine usage was 44.2+/-28.7 mg during the day of surgery (DOS); 49.1+/-27.4 mg during POD (postoperative day) #1; and 36.6+/-22.8 mg during POD#2 (p < 0.01). 24 patients were satisfied with their pain control on POD#1. VAS was 5.4+/-2.1 on the day of surgery, but remained below 4 thereafter. Arterial oxygen saturation and vital signs were maintained without significant changes. 5 patients experienced mild sedation on the day of surgery and 3 patients experienced mild sedation on POD#1. 1 patient experienced nausea and vomiting and 4 patients had pruritus; however, none required treatment. CONCLUSION: PCA is safe and effective for morbidly obese patients following RYGBP.

Adult↗

Donor polymorphism of tumor necrosis factor gene: relationship with variable severity of hepatitis C recurrence after liver transplantation.

BACKGROUND: Hepatitis C-related liver failure is the leading indication for liver transplantation worldwide. Although histologic recurrence is identified in the majority of patients, the spectrum of allograft injury is wide. To date, most studies have focused on the contribution of immunosuppression and viral factors. We hypothesized that the allograft plays a significant role in determining timing and severity of hepatitis C virus (HCV) recurrence. The purpose of this analysis was to determine if genetic polymorphisms of the tumor necrosis factor (TNF) locus were associated with the highly variable severity of HCV recurrence. METHODS: Thirty-one HCV-seropositive liver transplant recipients with long-term follow-up were studied. Genomic DNA was extracted from archived donor spleens which corresponded to each patient. We performed polymerase chain reaction amplification, followed by sequencing for two promoter TNF-alpha variants (at positions -238 and -308), and restriction fragment length analysis for four polymorphic loci within the TNF-beta gene (NcoI, TNFc, aa13, and aa26). RESULTS: The relative prevalence of polymorphisms corresponded to distributions previously reported in normal control populations. Twenty-two of 31 (71%) patients received a donor liver homozygous for the wild type allele (TNF1) at the -308 TNF-alpha promoter region. The interval to histologic recurrence was significantly shorter and severity of HCV allograft hepatitis was significantly greater in patients with one or two TNF308.2 alleles. At last follow-up biopsy, 5 of 9 (56%) patients with a TNF308.2 donor liver had evidence of severe histological activity index as compared to 2 of 22 (9%) of patients receiving a donor liver homozygous for the TNF1 allele (P = 0.01). There was no correlation between rejection rates and the presence of any TNF-alpha or TNF-beta alleles. TNF-beta polymorphisms within the donor liver did not correlate with severity of HCV recurrence. CONCLUSIONS: The donor TNF-alpha promoter genotype may influence the inflammatory response to HCV reinfection of the graft and contribute to accelerated graft injury. If the association between this genetic marker (TNF308.2) and disease progression is confirmed, it could improve our understanding of HCV pathogenesis and influence donor selection and patient management.

Alleles↗

Seat belt fracture with late development of an enterocolic fistula in a child. A case report.

STUDY DESIGN: A case report of a 9-year-old boy treated at a pediatric trauma center for a flexion-extension spiral fracture with late development of an enterocolic fistula subsequent to a high-velocity motor vehicle accident. OBJECTIVES: To increase the awareness of possible delayed bowel complications associated with flexion-distraction injuries of the spine in children. SUMMARY OF BACKGROUND DATA: Flexion-distraction fractures of the spine in children wearing lap seat belts, so-called "Chance" fractures, are an increasingly common result of high-velocity collisions. This type of fracture, referred to as a seat-belt fracture, is often associated with duodenal or jejunal tears. Although such intra-abdominal injuries are common in such fractures secondary to this type of trauma, the occurrence of an enterocolic fistula has never been reported. METHODS: A review of all pediatric Chance fractures managed at the Children's Hospital of Eastern Ontario, as well as a literature review of all reported series of flexion-distraction injuries to the spine in children, were performed. RESULTS: The subtle and prolonged symptomatology of this lesion and its similarity to a cast syndrome is emphasized. CONCLUSION: Because the orthopedic surgeon is usually the primary care-giver for children with this type of seat-belt trauma, an appreciation of the possibility of a delayed onset enterocolic fistula with its symptomatology is essential to avoid prolonged morbidity.

Accidents, Traffic↗

Novel mutation in the CMV UL97 gene associated with resistance to ganciclovir therapy.

Cytomegalovirus (CMV) strains resistant to ganciclovir have been associated with specific mutations in the UL97 and UL54 genes. The UL97 gene of a CMV strain isolated from a renal transplant recipient before and after 438 days of ganciclovir treatment was amplified by polymerase chain reaction and sequenced. A novel mutation resulting in deletion of codons 595 to 603 was identified in the viral DNA from specimens obtained after, but not before, prolonged ganciclovir therapy. Clinical and virological resolution of CMV disease occurred after switching to foscarnet therapy. Although many ganciclovir resistance mutations have been mapped to the UL97 codon range 591-607, this one is unusual in that it involves deletion of half these codons. Because UL97 seems to be necessary for effective CMV replication, this deletion suggests that much of codons 591-607 can be removed without destroying the biological function of UL97, and that this codon range can be altered in various ways to affect ganciclovir susceptibility. Rapid, flexible genotypic assays directed at this part of UL97 may facilitate the early recognition of ganciclovir resistance.

Adult↗

Association of multispecific CD4(+) response to hepatitis C and severity of recurrence after liver transplantation.

BACKGROUND & AIMS: After liver transplantation for hepatitis C virus (HCV), reinfection of the allograft invariably occurs. Indirect evidence suggests that the cellular immune response may play a central role. The purpose of this analysis was to determine the correlation between HCV-specific peripheral CD4(+) T-cell responses and the severity of recurrence after liver transplantation. METHODS: Fifty-eight HCV-seropositive patients, including 43 liver transplant recipients with at least 1 year of histological follow-up, were studied. Peripheral blood mononuclear cells (PBMCs) were isolated from fresh heparinized blood and stimulated with either recombinant HCV antigens (core, E2, NS3, NS4, and NS5) or control antigens. RESULTS: Fourteen (40%) of 35 patients with mild or no evidence of histological recurrence within their allografts responded to at least 1 of the HCV antigens. Eleven responded to NS3, 5 to all the nonstructural antigens, and 3 to the HCV core polypeptide alone. In contrast, in the 8 patients with severe HCV recurrence, no proliferation in response to any of the HCV antigens was seen (P = 0. 03) despite responses to the control antigens. CONCLUSIONS: Despite immunosuppression, HCV-specific, major histocompatibility complex class II- restricted CD4(+) T-cell responses are detectable in patients with minimal histological recurrence after liver transplantation. In contrast, PBMCs from patients with severe HCV recurrence, despite being able to proliferate in response to non-HCV antigens, fail to respond to the HCV antigens. These findings suggest that the inability to generate virus-specific T-cell responses plays a contributory role in the pathogenesis of HCV-related graft injury after liver transplantation. It is hoped that further characterization of the immunoregulatory mechanisms related to recurrent HCV will provide the rationale for novel therapeutic strategies and diminish the incidence of inevitable graft loss.

CD4-Positive T-Lymphocytes↗

Antiviral drug resistance in human cytomegalovirus.

Drug-resistant cytomegalovirus (CMV) should be considered when viral shedding persists after several weeks of therapy. The problem is most likely to arise in the setting of a severely immunosuppressed host with continuing or relapsing disease. Not all treatment failure can be attributed to drug resistance. The testing of CMV isolates for drug resistance in cell culture is time-consuming and labor-intensive, but recent advances in understanding of the genetics of resistance have resulted in rapid genotypic assays for specific mutations in the viral UL97 phosphotransferase or UL54 DNA polymerase genes that can predict resistance and cross-resistance to specific drugs. This information may help in the selection of alternative therapy.

Antiviral Agents↗

Transcriptional activation in yeast cells lacking transcription factor IIA.

The general transcription factor IIA (TFIIA) forms a complex with TFIID at the TATA promoter element, and it inhibits the function of several negative regulators of the TATA-binding protein (TBP) subunit of TFIID. Biochemical experiments suggest that TFIIA is important in the response to transcriptional activators because activation domains can interact with TFIIA, increase recruitment of TFIID and TFIIA to the promoter, and promote isomerization of the TFIID-TFIIA-TATA complex. Here, we describe a double-shut-off approach to deplete yeast cells of Toa1, the large subunit of TFIIA, to <1% of the wild-type level. Interestingly, such TFIIA-depleted cells are essentially unaffected for activation by heat shock factor, Ace1, and Gal4-VP16. However, depletion of TFIIA causes a general two- to threefold decrease of transcription from most yeast promoters and a specific cell-cycle arrest at the G2-M boundary. These results indicate that transcriptional activation in vivo can occur in the absence of TFIIA.

Cell Cycle↗