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Biomedical subjects

C Lim

Publications and source records attributed to C Lim.

At least 19 recordsLinked to original sources

Randomised controlled trials of homeopathy in hyperactive children: treatment procedure leads to an unconventional study design. Experience with open-label homeopathic treatment preceding the Swiss ADHD placebo controlled, randomised, double-blind, cross-over trial.

BACKGROUND: Treatment of patients with attention deficit hyperactivity disorder (ADHD) with homeopathy is difficult. The Swiss randomised, placebo controlled, cross-over trial in ADHD patients (Swiss ADHD trial) was designed with an open-label screening phase prior to the randomised controlled phase. During the screening phase, the response of each child to successive homeopathic medications was observed until the optimal medication was identified. Only children who reached a predefined level of improvement participated in the randomised, cross-over phase. Although the randomised phase revealed a significant beneficial effect of homeopathy, the cross-over caused a strong carryover effect diminishing the apparent difference between placebo and verum treatment. METHODS: This retrospective analysis explores the screening phase data with respect to the risk of failure to demonstrate a specific effect of a randomised controlled trial (RCT) with randomisation at the start of the treatment. RESULTS: During the screening phase, 84% (70/83) of the children responded to treatment and reached eligibility for the randomised trial after a median time of 5 months (range 1-18), with a median of 3 different medications (range 1-9). Thirteen children (16%) did not reach eligibility. Five months after treatment start, the difference in Conners Global Index (CGI) rating between responders and non-responders became highly significant (p = 0.0006). Improvement in CGI was much greater following the identification of the optimal medication than in the preceding suboptimal treatment period (p < 0.0001). CONCLUSIONS: Because of the necessity of identifying an optimal medication before response to treatment can be expected, randomisation at the start of treatment in an RCT of homeopathy in ADHD children has a high risk of failure to demonstrate a specific treatment effect, if the observation time is shorter than 12 months.

Adolescent↗

Array-based comparative genomic hybridization facilitates identification of breakpoints of a novel der(1)t(1;18)(p36.3;q23)dn in a child presenting with mental retardation.

Monosomy of distal 1p36 represents the most common terminal deletion in humans and results in one of the most frequently diagnosed mental retardation syndromes. This deletion is considered a contiguous gene deletion syndrome, and has been shown to vary in deletion sizes that contribute to the spectrum of phenotypic anomalies seen in patients with monosomy 1p36. We report on an 8-year-old female with characteristics of the monosomy 1p36 syndrome who demonstrated a novel der(1)t(1;18)(p36.3;q23). Initial G-banded karyotype analysis revealed a deleted chromosome 1, with a breakpoint within 1p36.3. Subsequent FISH and array-based comparative genomic hybridization not only confirmed and partially characterized the deletion of chromosome 1p36.3, but also uncovered distal trisomy for 18q23. In this patient, the duplicated 18q23 is translocated onto the deleted 1p36.3 region, suggesting telomere capture. Molecular characterization of this novel der(1)t(1;18)(p36.3;q23), guided by our clinical array-comparative genomic hybridization, demonstrated a 3.2 Mb terminal deletion of chromosome 1p36.3 and a 200 kb duplication of 18q23 onto the deleted 1p36.3, presumably stabilizing the deleted chromosome 1. DNA sequence analysis around the breakpoints demonstrated no homology, and therefore this telomere capture of distal 18q is apparently the result of a non-homologous recombination. Partial trisomy for 18q23 has not been previously reported. The importance of mapping the breakpoints of all balanced and unbalanced translocations found in the clinical laboratory, when phenotypic abnormalities are found, is discussed.

Child↗

Renal disease burden following liver transplantation.

UNLABELLED: Significant chronic kidney disease (CKD) occurs following orthotopic liver transplant (OLT). Since CKD is associated with increased cardiovascular events, mortality, and hepatic allograft dysfunction, early recognition of CKD and implementation of changes may improve the long-term outcome. The purpose of this study was to determine the burden of renal disease following OLT. PATIENTS AND METHODS: We retrospectively reviewed our OLT recipients from 1997 until 2004. We calculated glomerular filtration rates (GFR) using the Modification of Diet in Renal Disease study (MDRD) method. The GFRs were further subdivided into pre-MELD and post-MELD eras. RESULTS: During the study period, we performed 407 OLTs. We censored data from living donor liver transplants (n = 14), combined liver-kidney transplants (n = 12), and from patients whom we did not have complete data for 6 months after transplant (n = 40). Mean MELD score at the time of transplant was 18 +/- 7 (mean +/- standard deviation). The mean GFR at 6 months following OLT was 63.7 +/- 30.2 mL/min per 1.73 m(2). Only 14% (n = 47) of our patients had normal renal function at 6 months, while 78% (n = 266) of our patients had mild to moderate risk for renal failure. Eight percent (n = 28) had stage 4 or 5 CKD. There were no differences between the pre-MELD and post-MELD GFRs. CONCLUSIONS: The burden of renal disease is significant in our patient population at 6 months posttransplantation. It may be important to introduce CKD management as early as 6 months after transplant to impact the outcomes of OLT recipients.

Adult↗

Outcome after one-stage repair of tetralogy of Fallot.

AIM: The purpose of this study was to evaluate the outcome after one-stage repair of tetralogy of Fallot (TOF). METHODS: Between May 1997 and December 2002, 240 patients with a median age of 9 months (1 month-48 years) underwent one-stage repair of TOF. Closure of ventricular septal defect (VSD) was accomplished through the right atrium in 171 (71.3%) patients and through the right ventricle in 69 (28.7%) patients. For the reconstruction of the right ventricular outflow tract (RVOT), transannular repair was performed in 151 (62.9%) patients, and non-transannular repair was performed in 89 (37.1%) patients. Follow-up was complete, averaging 40+/-17.6 months (3 months-5.8 years). RESULTS: There were 2 (0.8%) operative deaths. Between early repair group (age under 6 months) and late repair group (age above 6 months), there were no differences in the method of RVOT reconstruction (transannular vs non-transannular) and the need for branch pulmonary artery angioplasty. Early repair group had more transventricular VSD closure than late repair group (46% vs 22%, P < 0.05). Duration of inotropic support and intensive care unit (ICU) stay were longer in the early repair group (P < 0.05). Five patients required reoperations due to RVOT obstruction (n = 3), and residual VSD (n = 2). Kaplan-Meier freedom from reoperation at 5 years was 98.3+/-1%. Nine patients underwent catheter intervention for branch pulmonary artery stenosis. Freedom from reintervention at 5 years was 95.4+/-1.5%. All survivors are currently asymptomatic. CONCLUSIONS: One-stage repair of TOF could be performed with low mortality and morbidity. Especially, early one-stage repair in symptomatic infant could be performed with low risk, eliminating the need for palliative procedures.

Abnormalities, Multiple↗

The neurological and cognitive sequelae of cardiac arrest.

BACKGROUND: Although cardiac arrest (CA) is commonly cited as a cause of amnesia, patients referred to the authors' center with a diagnosis of "amnesia" after CA rarely have isolated memory deficits. OBJECTIVE: To determine whether CA is a cause of pure amnesia and to assess patterns of cognitive deficits after CA. METHODS: The authors used cognitive assessment of 11 consecutive patients referred for memory deficits after CA, targeted at deficit domains identified in the literature reviews, and analysis of specific case reports and prospective studies of cognition after CA. RESULTS: The most common pattern of impairment in their patients was a combination of memory and motor deficits with variable executive impairment. No patient had isolated memory impairment. The case reports do not support the claim that isolated amnesia is a residual of CA; most cases of isolated amnesia are caused by subacute episodes of anoxia or excitotoxic injury. The prospective reports identify highly variable patterns of impairment, but isolated amnesia remains rare. CONCLUSIONS: Diffuse, sudden ischemic-hypoxic injury caused by cardiac arrest (CA) does not preferentially damage memory systems. Subacute or stepwise hypoxic or excitotoxic injury may cause isolated hippocampal injury and amnesia. The common pattern of impairment in the postacute phase after CA is a combination of memory, subtle motor, and variable executive deficits.

Adolescent↗

In vitro inhibitory effect of gossypol from gossypol-acetic acid, and (+)- and (-)-isomers of gossypol on the growth of Edwardsiella ictaluri.

AIM: This study was conducted to evaluate the toxic effect of gossypol from gossypol-acetic acid, and (+)- and (-)-isomers of gossypol on the growth of Edwardsiella ictaluri. METHODS AND RESULTS: Inhibitory effect of various concentrations of gossypol on the growth of E. ictaluri was determined. Bacterial recovery was performed by preincubation of bacteria in medium containing various concentrations of gossypol and subsequent activation of bacteria by inoculating on gossypol-free plates. Concentrations of racemic gossypol, (+)-gossypol and (-)-gossypol of 1.5 microg ml(-1) or higher significantly reduced the number of bacterial colonies compared with that of the control. The growth of E. ictaluri was completely inhibited on agar plates supplemented with 3 microg ml(-1), regardless of the forms of gossypol. The inhibitory effect of (+)-gossypol was higher than that of (-)-gossypol or gossypol-acetic acid. Recovery of E. ictaluri was <50% for all three forms of gossypol at concentrations of 5 microg ml(-1). Bacterial recovery remained relatively constant (6.5%) at gossypol concentrations from 10 to 100 microg ml(-1). Complete killing of E. ictaluri was not reached at gossypol levels up to 100 microg ml(-1). CONCLUSION: Gossypol-acetic acid, and (+)- and (-)-optical isomers have anti-bacterial effect against E. ictaluri. The results suggest the action is bacteriostatic rather than bactericidal. SIGNIFICANCE AND IMPACT OF THE STUDY: The therapeutic effect of gossypol against E. ictaluri may be useful in controlling enteric septicaemia of catfish.

Anti-Bacterial Agents↗

SAG1 is a host-targeted antigen for protection against toxoplasma gondii infection.

We previously reported that SAG1 transgenic (tg) mice have an elevated susceptibility resulting from their inability to elicit strong Th1-based protection against Toxoplasma gondii infection. Here, we demonstrate that SAG1 tg mice were protected against T. gondii infection, characterized by a decline in IFN-gamma levels, following administration of a lethal dose of T. gondii. Moreover, immunization with T. gondii homogenate conferred protection and induced production of IgG, with IgG1 and IgG2a subclasses driven by Th2 and Th1 responses, respectively, in both SAG1 tg and wild-type (wt) mice. IgG titers were significantly higher from day 10 after immunization in wt mice compared to those in SAG1 tg mice. There were no significant differences observed in levels of IgG1 in both groups. However, significantly lower IgG2a titers were measured in the sera from SAG1 tg mice on days 10, 15 and 20. IFN-gamma levels in sera were significantly lower in SAG1 tg mice compared to those in wt mice on day 20 after immunization. When challenged with a lethal dose of the Beverley strain of T. gondii, 80 and 100% survival rates were observed in SAG1 tg and wt mice, respectively, indicating that SAG1 tg mice were protected to a lesser extent from challenge due to the decrease in protective immunity. These results suggest that SAG1 plays a critical role in eliciting protection, hence a target antigen for the development of protective Th1-based responses against T. gondii infection in mice.

Animals↗

Feed deprivation of channel catfish, Ictalurus punctatus (Rafinesque), influences organosomatic indices, chemical composition and susceptibility to Flavobacterium columnare.

Withholding feed has been suggested as a strategy to manage infectious disease of channel catfish, Ictalurus punctatus (Rafinesque). In a previous study, we demonstrated that deprivation of feed for as little as 7 days reduced innate resistance of catfish to Flavobacterium columnare. This study was conducted to evaluate the effect of feeding regimens [no feeding (NF), fed once every other day to satiation (FEOD) and fed once daily to satiation (FD)] on organosomatic indices, physiological changes and susceptibility of channel catfish to F. columnare. Fish that were not fed for 2 and 4 weeks had a significant increase (P < 0.05) in gutted weight:-wet weight ratio and decrease in other organosomatic indices [gut index (GI), mesenteric fat index (MFI) and hepatosomatic index (HSI)]. Haematology was not effected by feeding regimen except at week 4, when a significantly higher haemoglobin level was observed in the NF fish. Serum protein did not differ at week 2, but the level at week 4 of the NF fish (35.91 mg mL(-1)) was significantly lower than that of the FD fish (41.77 mg mL(-1)). Significantly lower (P < 0.05) blood glucose (39.5 and 40.3 mg dL(-1)) and liver glycogen (1.7 and 1.8 mg g(-1)) were seen in the NF fish at weeks 2 and 4, respectively, as compared with blood glucose and liver glycogen levels of FD fish (67.5 and 92.8 mg dL(-1) and 46.5 and 52.6 mg g(-1) at weeks 2 and 4, respectively) and FEOD (82.8 and 85.5 mg dL(-1) and 45.1 and 51.4 mg g(-1) at weeks 2 and 4, respectively). Mortality in the NF fish caused by F. columnare (78%) was significantly higher (P < 0.05) than mortality in the FD and FEOD treatments (0.0 and 1.7%, respectively). Blood glucose and liver glycogen showed the same trend of low values for NF fish following challenge (week 6). Blood glucose, liver glycogen, GI and HSI are sensitive indicators for channel catfish deprived of feed (NF) for 4 weeks. Blood glucose and liver glycogen levels around 40 mg dL(-1) and 2 mg g(-1), respectively, are indicative of starvation in juvenile channel catfish. Moreover, NF fish were susceptible to F. columnare infection. Thus, it is suggested that in the absence of natural food, juvenile channel catfish should be fed at least once every other day to apparent satiation to maintain normal physiological function and improve resistance to F. columnare.

Animals↗

Preparing a human membrane and secreted protein-enriched cDNA library using PCR primers derived from a genomic database.

We describe here a strategy for preparing a human membrane and secreted protein (MSP)-enriched cDNA library based on human MSP- and non-MSP-encoding cDNA sequences in the databases. The signal peptide parts of the MSP-encoding cDNA sequences, which currently comprise about half of the estimated total number in humans, were analyzed for common patterns. These patterns form a 'minimal' set of polymerase chain reaction primer candidates of length varying from 9 to 21 nt. The products stemming from each primer candidate were determined and the results allowed us to obtain an 'optimal' mixed-length primer set. Ninety-six percent of the primers in this set were predicted to yield </=10% undesired products, and the desired MSP-cDNA products could be easily separated by gel electrophoresis. The present analysis establishes a methodology for preparing a cDNA library that enables the analysis of individual MSPs. This methodology may also help identify new MSPs. As many cell regulatory processes are mediated by secreted proteins and their membrane-bound receptors, the preparation of a MSP-enriched cDNA library should benefit research on MSPs.

Amino Acid Sequence↗

The transcriptional activity of cAMP response element-binding protein-binding protein is modulated by the latency associated nuclear antigen of Kaposi's sarcoma-associated herpesvirus.

A multifunctional transcription co-activator, cAMP response element-binding protein-binding protein (CBP)interacts with a number of cellular factors and participates in cell growth, transformation, and development. It is also targeted by many viral proteins for their transcriptional activity or for the regulation of cellular processes. Here, we report that the C/H3 region of CBP is targeted by the latency associated nuclear antigen (LANA) of Kaposi's sarcoma-associated herpesvirus (KSHV). LANA interferes with the interaction between CBP and c-Fos, a representative C/H3 region binding, cellular transcription factor, in vivo and in vitro. In addition, we found that LANA inhibits the transcriptional activity and the in vitro histone acetyltransferase activity of CBP, suggesting that LANA modulates the global transcriptional activities of infected cells through the interaction with CBP. These results indicate that KSHV follows one of the conserved strategies, which other viruses utilize for influencing the cellular processes.

Acetyltransferases↗

Characterization and regulation of Schizosaccharomyces pombe gene encoding thioredoxin.

A cDNA coding thioredoxin (TRX) was isolated from a cDNA library of Schizosaccharomyces pombe by colony hybridization. The 438 bp EcoRI fragment, which was detected by Southern hybridization, reveals an open reading frame which encodes a protein of 103 amino acids. The genomic DNA encoding TRX was also isolated from S. pombe chromosomal DNA using PCR. The cloned sequence contains 1795 bp and encodes a protein of 103 amino acids. However, the C-terminal region obtained from the cDNA clone is -Val-Arg-Leu-Asn-Arg-Ser-Leu, whereas the C-terminal region deduced from the genomic DNA appears to contain -Ala-Ser-Ile-Lys-Ala-Asn-Leu. This indicates that S. pombe cells contain two kinds of TRX genes which have dissimilar amino acid sequences only at the C-terminal regions. The heterologous TRX 1C produced from the cDNA clone could be used as a subunit of T7 DNA polymerase, while the TRX 1G from the genomic DNA could not. The upstream sequence and the region encoding the N-terminal 18 amino acids of the genomic DNA were fused into the promoterless beta-galactosidase gene of the shuttle vector YEp357 to generate the fusion plasmid pYKT24. Synthesis of beta-galactosidase from the fusion plasmid was found to be enhanced by hydrogen peroxide, menadione and aluminum chloride. It indicates that the expression of the cloned TRX gene is induced by oxidative stress.

Aluminum Chloride↗

Intraaortic balloon pump therapy facilitates posterior vessel off-pump coronary artery bypass grafting in high-risk patients.

BACKGROUND: Displacement of the heart to expose posterior vessels during coronary artery bypass grafting (CABG) without cardiopulmonary bypass (off-pump CABG, or OPCAB) may impair cardiac function. We used the intraaortic balloon pump (IABP) preoperatively to reduce operative risk and to facilitate posterior vessel OPCAB in high-risk patients with left main coronary artery disease (> 75% stenosis), intractable resting angina, postinfarction angina, left ventricular dysfunction (ejection fraction < 35%), or unstable angina. METHODS: One hundred and forty-two consecutive patients who underwent multivessel OPCAB including posterior vessel revascularization were studied prospectively. The patients were divided into group I (n = 57), which received preoperative or intraoperative IABP, and group II (n = 85), which did not receive IABP. In group I, there were 34 patients with left main coronary artery disease, 24 patients with intractable resting angina, 8 patients with left ventricular dysfunction, 5 patients with postinfarction angina, and 40 patients with unstable angina. Seven patients received intraoperative IABP support owing to hemodynamic instability during OPCAB. RESULTS: There was no operative mortality in group I and 1 death in group II. The average number of distal anastomoses was not different between group I and group II (3.4 +/- 0.9 versus 3.5 +/- 0.9, p = not significant). There were no significant differences in the number of posterior vessel anastomoses per patient. There were no differences in ventilator support time, length of stay in the intensive care unit, hospital stay, and morbidity between the two groups. There was one IABP-related complication in group I. CONCLUSIONS: IABP therapy facilitates posterior vessel OPCAB in high-risk patients, and surgical results are comparable with those in lower-risk patients.

Aged↗

Off-pump coronary artery bypass may decrease the patency of saphenous vein grafts.

BACKGROUND: There is concern that a hypercoagulable status is caused after coronary artery bypass grafting without cardiopulmonary bypass (off-pump coronary artery bypass grafting, or OPCAB) and may potentially endanger the patency of the anastomosis. The aims of this study were: (1) to compare 1-year graft patency after OPCAB with that of conventional coronary artery bypass grafting (CABG) and that of on-pump beating CABG; and (2) to demonstrate any differences in patency of various conduits among the three groups. METHODS: We analyzed the results of 122 consecutive OPCAB cases (group 1) compared with those of 65 consecutive conventional CABG cases (group II) and those of 19 consecutive on-pump beating CABG cases (group III). In group I, coronary angiography (CAG) was performed immediately postoperatively and 1 year after surgery. In groups II and III, CAG was performed 1 year after surgery. Graft patency was graded as grade A (excellent), grade B (fair), or grade O (occluded). RESULTS: The average number of distal anastomoses in groups I, II, and III were 3.1 +/- 1.1, 3.7 +/- 0.9, and 3.6 +/- 0.9, respectively. In group I, postoperative CAG was performed in 92% of patients (112/122) before discharge. The patency rate (grade A + B) was 96.4% (162/168) for arterial grafts, and 85.6% (160/187) for saphenous vein grafts (SVG). One-year follow-up CAG was performed in 74% of patients (90/122). The patency rate was 97.8% (132/135) for arterial grafts and 67.9% (106/156) for SVG. In group II, 1-year follow-up CAG was performed in 65% of patients (42/65). The patency rate (grade A + B) was 93.5% (43/46) for arterial grafts and 88.3% (98/111) for SVG. In group III, 1-year follow-up CAG was performed in 89% of patients (17/19). The patency rate (grade A + B) was 100% (19/19) for arterial grafts and 86.8% (33/38) for SVG. CONCLUSIONS: Our results demonstrate that the patency rate ot SVG after OPCAB was significantly lower than that of arterial grafts in the early postoperative CAG (p < 0.001), and was also significantly lower than those of SVG of group II (p < 0.001) and group III (p < 0.01) in the postoperative 1-year CAG, although there was no significant difference in 1-year patency of arterial grafts among the three groups. Our data suggest that a specific perioperative anticoagulant therapy may be advisable in patients undergoing OPCAB with SVG.

Anastomosis, Surgical↗

Free energy decomposition of protein-protein interactions.

A free energy decomposition scheme has been developed and tested on antibody-antigen and protease-inhibitor binding for which accurate experimental structures were available for both free and bound proteins. Using the x-ray coordinates of the free and bound proteins, the absolute binding free energy was computed assuming additivity of three well-defined, physical processes: desolvation of the x-ray structures, isomerization of the x-ray conformation to a nearby local minimum in the gas-phase, and subsequent noncovalent complex formation in the gas phase. This free energy scheme, together with the Generalized Born model for computing the electrostatic solvation free energy, yielded binding free energies in remarkable agreement with experimental data. Two assumptions commonly used in theoretical treatments; viz., the rigid-binding approximation (which assumes no conformational change upon complexation) and the neglect of vdW interactions, were found to yield large errors in the binding free energy. Protein-protein vdW and electrostatic interactions between complementary surfaces over a relatively large area (1400--1700 A(2)) were found to drive antibody-antigen and protease-inhibitor binding.

Animals↗