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Biomedical subjects

C H Lim

Publications and source records attributed to C H Lim.

At least 19 recordsLinked to original sources

The outcome of suspected upper gastrointestinal bleeding with 24-hour access to upper gastrointestinal endoscopy: a prospective cohort study.

BACKGROUND AND STUDY AIM: The aim was to evaluate the 30-day mortality after endoscopy for suspected upper gastrointestinal bleed, following the implementation of national audit guidelines at our hospital. PATIENTS AND METHODS: All patients with suspected upper gastrointestinal bleeding, referred for endoscopy to our teaching hospital between October 2001 and December 2003, were included in a prospective cohort study. RESULTS: A total of 716 patients with suspected upper gastrointestinal tract haemorrhage were referred for urgent endoscopy. The median age was 69 years (interquartile range 51 - 80 years). Bleeding from peptic ulcer remained the single most common endoscopic diagnosis (40 %). The overall re-bleeding rate for all patients with a gastrointestinal haemorrhage was 10 %. The overall 30-day mortality rate was 14.6 %. This was not significantly different from the mortality rate in 1995 of 10.5 % ( P = 0.11). Patients who died were significantly older (78 vs. 67 years, 95 %CI of the difference 5 to 12, P < 0.001). However, in only 29 % (30/105) was gastrointestinal haemorrhage stated in the death certificate as a factor which contributed to their death. CONCLUSIONS: Our results show that implementing the good practice guideline has a limited impact on overall mortality because of contributing factors that are beyond the control of clinicians.

Aged↗

Evaluation of subchronic inhalation toxicity of dimethyl disulfide in rats.

This study was carried out to investigate the potential subchronic inhalation toxicity of dimethyl disulfide (DMDS) via whole-body exposure in F344 rats. Groups of 10 rats of each sex were exposed to DMDS vapor by whole-body exposure at concentrations of 0, 5, 25, or 125 ppm for 6 h/day, 5 days/wk for 13 wk. All the rats were sacrificed at the end of treatment period. During the test period, clinical signs, mortality, body weights, food consumption, ophthalmoscopy, urinalysis, hematology, serum biochemistry, gross findings, organ weights, and histopathology were examined. At 25 ppm, a decrease in the body weight gain, food intake, aspartate aminotransferase (AST), alanine aminotransferase (ALT), and blood urea nitrogen (BUN) was observed in the males, but not in the females. However, at 125 ppm, a decrease in the body weight gain, food intake, and thymus weight and an increase in the weights of adrenal glands were observed in both genders. Serum biochemical investigations revealed a decrease in the AST, ALT, BUN, creatine phosphokinase (CPK), and triglyceride levels and an increase in the glucose level. In contrast, no treatment-related effects were observed in the 5 ppm group. The toxic potency of DMDS was slightly higher in males than that in females. In these experimental conditions, the target organ was not determined in rats. The no-observed-adverse-effect concentration (NOAEC) was found to be 5 ppm, 6 h/day for male rats and 25 ppm, 6 h/day for female rats.

Alanine Transaminase↗

Retinocollicular synaptogenesis and synaptic transmission during formation of the visual map in the superior colliculus of the wallaby (Macropus eugenii).

Spontaneous retinal activity has been implicated in the development of the topographic map in the superior colliculus (SC) but a direct demonstration that it reaches the colliculus is lacking. Here we investigate when the retinocollicular projection is capable of transmitting information from the retina in a marsupial mammal, the wallaby (Macropus eugenii). The projection develops postnatally, allowing in vivo analysis throughout development. Quantification of retinocollicular synaptogenesis has been combined with electrophysiology of the development and characteristics of retinocollicular transmission, including in vivo and in vitro recording in the same animals. Prior to postnatal day (P) 12-14 in vitro recording detected only presynaptic activity in retinal axons in the colliculus, in response to stimulation of the optic nerve. Postsynaptic responses, comprising both N-methyl-d-aspartate (NMDA) and non-NMDA responses, were first detected in vitro at P12-14 and retinal synapses were identified. In contrast, postsynaptic responses to optic nerve stimulation could not be detected in vivo until P39, around the time that retinal axons begin arborizing. Around this age density and numbers of total synapses began increasing in the retinorecipient layers of the colliculus. By P55-64, the numbers of retinal synapses had increased significantly and density and numbers of retinal and total synapses continued to increase up to P94-99. During this time the map is undergoing refinement and degenerating axons and synapses were present. The discrepancy between in vitro and in vivo onset of functional connections raises the question of when retinal activity reaches collicular cells in the intact, unanaesthetized animal and this will require investigation.

2-Amino-5-phosphonovalerate↗

Necrotizing fasciitis of the lower limb: an outcome study of surgical treatment.

Necrotizing fasciitis is a limb- and life-threatening rapidly spreading infection affecting the deep fascia with secondary necrosis of the subcutaneous tissue. It requires immediate medical attention and emergency surgery to prevent morbidity and death. This study was undertaken to determine its co-morbidity and risk factors affecting the outcome of its surgical treatment. This is a retrospective review of 36 cases of necrotizing fasciitis of the lower limb treated in our center between 1998 and 2002. Only 19% of the cases were correctly diagnosed upon admission and 48.6% were initially diagnosed as 'cellulitis'. Diabetes mellitus was the most common co-morbid. Pseudomonas, Staphylococcus, Streptococcus and Enterobactericae were the common pathogens isolated. Ten patients (27.8%) had major amputation as part of radical debridement. The overall mortality rate was 36% with laboratory parameters: high serum urea and creatinine, and low haemoglobin levels were predictors for higher mortality. Poor white cell response which is common in diabetic patients and a delay in surgical debridement were. notable attributes to a higher mortality. Necrotizing fasciitis is a serious infection associated with significant morbidity and mortality. A poor white blood cell response, high serum urea and creatinine, and low haemoglobin level were the predictors for mortality. Early diagnosis and prompt treatment are of paramount importance in the treatment of this infection.

Adult↗

Prospective study of acute gastrointestinal bleeding attributable to anti-inflammatory drug ingestion in the Yorkshire region of the United Kingdom.

OBJECTIVE: To assess the general use of all non-steroidal anti-inflammatory drugs (NSAID) and their relation to upper gastrointestinal bleeding in view of National Institute for Clinical Excellence guidelines published in July 2001 in the UK. METHODS: Cross sectional study on all patients who were referred for endoscopy for suspected upper gastrointestinal bleeding in six hospitals in Yorkshire region of the UK. RESULTS: One hundred and sixty three patients presented for endoscopy for suspected upper gastrointestinal bleeding, 43 patients were taking at least one ulcerogenic drug, and 120 were not. The mean age difference between these two groups was eight years (p<0.01). The absolute difference between the proportion of patients with peptic ulcer disease/erosion (PUD) in NSAID with/without aspirin group and no ulcerogenic drug group was 31% (p = 0.02). The difference between the proportion of PUD in cyclo-oxygenase 2 with/without aspirin group and no ulcerogenic drug group was 30% (p = 0.1). The overall 30 days mortality rate was 14.1%. CONCLUSIONS: Elderly patients are being inappropriately prescribed conventional NSAIDs. NSAIDs with or without aspirin use are still associated with a significant risk of upper gastrointestinal bleeding in the era of cyclo-oxygenase 2 selective agents. Substitution with cyclo-oxygenase 2 selective NSAIDs is not without risk of upper gastrointestinal bleeding.

Anti-Inflammatory Agents, Non-Steroidal↗

Oesophageal haematoma and associated Mallory-Weiss tear.

Intramural oesophageal haematoma is a rare condition that may present as vomiting or haematemesis. Mallory-Weiss tear has been proposed as a possible aetiology but the evidence to support this is circumstantial. A case of oesophageal haematoma associated with evidence of Mallory-Weiss tear on endoscopy that helps to support this hypothesis is presented.

Aged↗

Bioequivalence of pravastatin tablet formulations assessed in Korean males.

AIM: Determination of the bioequivalence of 2 pravastatin tablet formulations manufactured in Korea. PATIENTS AND METHODS: Twenty-three healthy male Korean volunteers received each of the 2 pravastatin formulations at a dose of 20 mg in a 2 x 2 crossover study. There was a 1-week washout period between doses. Plasma concentrations of pravastatin were monitored using high-performance liquid chromatography over a period of 8 hours after administration. AUC(0-8h) (the area under the plasma concentration-time curve from time zero to the last measured time in plasma, 8 h) was calculated using the linear-log trapezoidal method. Cmax (maximum plasma drug concentration) and tmax (time to reach Cmax) were compiled from the plasma concentration-time data. Analysis of variance was carried out using logarithmically transformed AUC(0-8h) and Cmax and untransformed tmax. RESULTS: The point estimates and 90% confidence intervals for AUC(0-8h) (parametric) and Cmax (parametric) were 1.067 (0.968 to approximately 1.176) and 1.074 (0.999 to approximately 1.155), respectively, satisfying the bioequivalence criteria of the European Committee for Proprietary Medicinal Products and the US Food and Drug Administration guidelines. The corresponding value of tmax was 0.000 (-0.250 to approximately 0.250). CONCLUSION: These results indicate that the 2 medications of pravastatin are bioequivalent and, thus, may be prescribed interchangeably.

Adult↗

Ten year follow up of ulcerative colitis patients with and without low grade dysplasia.

BACKGROUND AND AIMS: Low grade dysplasia (LGD) is believed to predispose to colorectal cancer (CRC), and proctocolectomy has been advocated when this is identified. Between 1978 and 1990, 160 patients with longstanding extensive ulcerative colitis (UC) were recruited for annual colonoscopic surveillance and 40 developed LGD at some stage. We report the outcome of this cohort 10 years after the original study ended. METHODS: Retrospective cohort study and histopathological review of the original diagnoses of LGD. The outcome of 158/160 (98.8%) patients was established in 2000. RESULTS: Of the 128 patients still alive and with an intact colon at the end of 1990, two were not traceable, 29 had LGD, and 97 had no dysplasia (controls). After 10 years, high grade dysplasia (HGD) or CRC developed in 3/29 LGD (10%) and in 4/97 controls (4.0%). Kaplan-Meier analysis from 1991 to death or colectomy did not show a statistically significant difference between the two groups (log rank test p=0.63). Histopathological review demonstrated the unreliability of LGD diagnosis. Agreement between pathologists was uniformly poor: kappa <0.4 for all comparisons. CONCLUSION: LGD diagnosis is not sufficiently reliable to justify prophylactic colectomy. Conservative management of established LGD cases should not be ruled out.

Adult↗

Synthesis and binding affinities of 2 beta-(3-iodoallyloxycarbonyl)-3 beta-(4-substituted-aryl)tropane analogues as ligands for the dopamine transporter studies.

Tropane analogues from cocaine, which is known to be one of the most reinforcing and addictive compounds, were designed, synthesized, and characterized for inhibition of presynaptic uptake of dopamine (DA) in brain. Eight new derivatives of 3 beta-aryl-2 beta-(3-iodoallyloxycarbonyl)tropanes were synthesized and tested for their potential abilities to displace [(3)H]2 beta-carbomethoxy-3 beta-(4-fluorophenyl)tropane (WIN 35,428) binding to the rat striatal membranes.

Animals↗

Xenobiotic response in humanized double transgenic mice expressing tetracycline-controlled transactivator and human CYP1B1.

The cytochrome P450 enzymes (P450s or CYPs) are a superfamily of hemeproteins that catalyze the monooxygenation of a wide range of endobiotic and xenobiotic substrates. A typical strategy in toxicological research and testing involves applying a toxicant at high doses for a short period to homogeneous animals under controlled conditions. However, the conditions of this approach have very little in common with actual human exposure. Transgenic (Tg) mice carrying human genes encoding a drug-metabolizing enzyme (CYP) offer a solution to many of the difficulties in the evaluation of chemical toxicity. It has been demonstrated that the expression of human CYP transgenes under the control of mammalian-inducible promoters exhibits relatively poor fold increases after induction. In this study, we used the tetracycline-regulated (tet) promoter system to increase the expression of the human CYP1B1 (hCYP1B1) gene in the tissues of transgenic mice. By mating two lineages of transgenic mice, double transgenic (dTg) mice expressing both tTA and hCYP1B1 genes under the control of the tet promoter were successfully produced, into which the two transgenes were introduced in an embryo. The expression pattern of tTA-driven hCYP1B1 transgene featured a fold induction of more than 3 to 12 in the brain, heart, and lung and 2- to 4-fold induction in the liver, kidney, and intestine upon doxycycline removal. Immunohistochemical staining with hCYP1B1 antibody was also increased by the removal of doxycycline. In addition, the activities of CYP liver microsomes in the dTg mice without doxycycline showed an increase compared to that in the dTg mice treated with doxycycline. The level of activities correspond to the levels of human CYP1B1 protein expression in the Tg mice (-dox) that was increased by 2-fold induction as compared to that of the dTg mice with doxycycline. Thus, overproduction in Tg can be purified and the activity of purified human CYP1B1 can be characterized by alterations to the coding sequence in order to solve the physiological function of this enzyme in a humanized in vivo system. It is also possible to examine the activity of purified human CYP1B1 using several environmental toxicants such as procarcinogens.

Animals↗

Occlusive myocardial infarction: investigation of bis-gadolinium mesoporphyrins-enhanced T1-weighted MR imaging in a cat model.

PURPOSE: To test whether bis-gadolinium mesoporphyrins-enhanced magnetic resonance (MR) imaging can accurately depict irreversibly damaged myocardium in occlusive myocardial infarction. MATERIALS AND METHODS: Ten cats were subjected to 90 minutes of occlusion of the left anterior descending coronary artery. Bis-gadolinium mesoporphyrins-enhanced T1-weighted MR imaging was performed in the cats for 6 hours. Histopathologic examinations with 2'3'5-triphenyl tetrazolium chloride (TTC) staining and electron microscopy were performed on the resected specimens. The time course and pattern of signal intensity enhancement were evaluated. The size of the infarcted myocardium was estimated on the MR images by measuring the size of the signal intensity-enhanced area. RESULTS: In eight of 10 cats, it was impossible to distinguish infarcted myocardium from normal myocardium at visual inspection of T1-weighted MR images. The contrast ratio between infarcted and normal myocardium did not increase significantly over time. In one of the two remaining cats, a doughnut pattern of signal intensity enhancement was noted. The other cat showed intensely homogeneous enhancement of infarcted myocardium at MR imaging. The size of the area of signal intensity enhancement at MR imaging in these two cats was accurately mapped to that of the infarction on the TTC-stained specimens. CONCLUSION: Occlusive myocardial infarction cannot be accurately detected at bis-gadolinium mesoporphyrins-enhanced MR imaging.

Animals↗

Application of breath-hold T2-weighted, first-pass perfusion and gadolinium-enhanced T1-weighted MR imaging for assessment of myocardial viability in a pig model.

The purpose of this study was to correlate the abnormal signal area on various magnetic resonance (MR) images to the infarct area on pathologic examination and to assess the myocardial viability on the basis of MR images. T2-weighted, first-pass perfusion, and delayed gadolinium-enhanced T1-weighted images were used as "one-stop examinations" in a pig model of reperfused myocardial infarction. The results of each MR image were compared with those of 2,3, 5-triphenyltetrazolium chloride (TTC) staining. The abnormal signal areas on T2-weighted and Gd-enhanced T1-weighted images were larger than the infarct areas on TTC staining (34.7% and 32.3% vs. 28.3%; P< 0.05), whereas the nonperfused areas on perfusion images were correlated (25.6% vs, 28.3%; P = 0.139). Electron microscopic examination showed severely distorted ultrastructures in the infarct areas and mildly damaged ultrastructures in the peri-infarct areas. Perfusion images probably reflected the infarct areas, whereas T2-weighted and Gd-enhanced T1-weighted images seemed to include peri-infarct as well as infarct areas.

Animals↗

Irreversibly damaged myocardium at MR imaging with a necrotic tissue-specific contrast agent in a cat model.

PURPOSE: To investigate the capability of a necrosis-avid magnetic resonance (MR) contrast agent, bis-gadolinium mesoporphyrins, for assessment of irreversibly damaged myocardium and to evaluate the time course of signal enhancement in the reperfused myocardium. MATERIALS AND METHODS: Nine cats were subjected to 90 minutes of occlusion of the left anterior descending coronary artery followed by 90 minutes of reperfusion. Contrast material-enhanced T1-weighted spin-echo images were obtained for 12 hours in five cats and 6 hours in four cats. Pathologic examinations of the resected specimens were performed with 2'3'5-triphenyl tetrazolium chloride (TTC) histochemical staining and electron microscopy. The size of enhanced area on MR images was compared with that of irreversibly damaged myocardium with TTC staining. The time course of signal enhancement was evaluated. RESULTS: The size of enhanced area on MR images was well correlated with that of irreversibly damaged myocardium with TTC staining. Maximum enhancement occurred 1-3 hours after administration of the contrast material, with mean enhancement of 171% that of normal myocardium. Electron microscopic examinations showed severe myocardial damage in the irreversibly damaged myocardium but only mild edematous changes in the reversibly damaged myocardium. CONCLUSION: MR images enhanced with bis-gadolinium mesoporphyrins provide accurate sizing of irreversibly damaged myocardium with a strong and persistent signal enhancement in the reperfused myocardium.

Animals↗

Medical radiologic technologist review: effects on a population-based breast cancer screening program.

PURPOSE: To evaluate the effects of medical radiologic technologist review of mammograms in a population-based breast cancer screening program. MATERIALS AND METHODS: A technologist review pilot project was incorporated into the Regina, Saskatchewan, Canada, reading center. Technologists received special training in mammographic interpretation. They reviewed all 27,863 mammograms obtained at the center from July 1995 to September 1996 that were reviewed by a radiologist and selected cases for second blind reading by another radiologist. When the two radiologists' readings were in agreement, the report was sent. When the readings differed, a third opinion was obtained from the program's consulting radiologist. Changes in the number of mammograms interpreted as abnormal and the number of cancers detected were assessed. RESULTS: The technologist review was responsible for the detection of nine cancers missed at the first radiologist's interpretation. Technologists were very discriminating; only 391 cases (1.4%) were sent for double reading. The positive predictive value of screening did not change significantly (7.5% without review, 8.1% with review; P > .20). CONCLUSION: A substantial number of cancers were found with the technologist review. The number of mammograms interpreted as abnormal was reduced slightly. The technologist review proved to be a cost-effective alternative to double reading by two radiologists.

Breast Neoplasms↗

GABAergic modulation of axonal conduction in the developing rat retinotectal pathway.

The effect of gamma-aminobutyric acid (GABA) on nerve conduction was investigated in the developing rat optic nerves in vitro. Antidromic compound action potentials (CAP) were suppressed by GABA, with increasing attenuation in older preparations. Enhancement of CAP amplitude using bicuculline was observed in postnatal days 4-5 suggesting the presence of endogenous GABA activity. Our findings suggest that the role of electrical activity in the refinement of the retinotectal projection could be limited by the GABAergic action on axonal conduction.

Animals↗

Onset of optic nerve conduction and synaptic potentials in superior colliculus of fetal rats studied in vitro.

This article describes the onset of electrical excitability and synaptic transmission in the retinocollicular pathway of the fetal and early postnatal rat, utilizing a novel in vitro preparation. Although the optic nerve is visible in embryonic day (E) 14 brain, its stimulation produced no response in the superior colliculus (SC) until E16 when a low voltage simple negative wave was evoked. At E17 these potentials were blocked rapidly, completely, and reversibly when choline was substituted for sodium or with the addition of cobalt ions. In the course of establishing the block with either of the above agents the latency of response increased, indicating an action on axonal transmission. By E20 the collicular evoked potential showed a short followed by a longer latency wave. The latter was blocked by the glutamate antagonist kynurenic acid, with latency unaffected. Further examination of potentials with the addition of glutamatergic receptor subtype blockers aminophosphonopentanoic acid (APV) and 6-cyano-7-nitroquinoxaline-2,3-dione/6,7-dinitroquinoxaline- 2,3-dione (CNQX/DNQX) showed a clear abolition of the elicited potentials by E20 and older. Thus, fetal rat optic nerve fibers are capable of conduction in response to electrical stimulation as soon as they reach the SC at E16. Both sodium and calcium are involved. GABA-mediated modulation of axonal conduction is evident by E18. Glutaminergic synaptic transmission is established by E20. The timetable of fetal onset of capability to conduct and support synaptic transmission in the retinocollicular pathway is earlier than had previously been reported in vivo in the rat in which the superior colliculus neurones are said not to be driven by the optic nerve until 6 days post natal. This has relevance to the possible role of impulse activity in development of the pathway.

Animals↗