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Biomedical subjects

T H Ng

Publications and source records attributed to T H Ng.

At least 19 recordsLinked to original sources

Influence of respiration and portal pressure on transabdominal duplex Doppler ultrasound measurement of portal blood flow: a porcine model for experimental studies.

Transabdominal duplex Doppler ultrasonography (TDDU) is commonly used for measuring hepatic blood flow (HBF) in clinical practice. Flow velocity and the cross-sectional area (CSA) of vessels are obtained separately and used to compute blood flow. Respiration and changes in portal pressure are known to cause variations in the CSA of the portal vein, but the impact of these parameters on TDDU measurement of portal blood flow is unclear. Eight Yorkshire pigs (20.7-25.1 kg) were used for the study. TDDU determination of portal blood flow was carried out using CSA of the portal vein obtained at inspiration (maximal) and at expiration (minimal) for computation, and the differences obtained were compared. Determination of HBF was carried out simultaneously on the same animals using diisopropyliminodiacetic acid (DISIDA) clearance. A physiological increase in portal pressure was then created by 50% hepatectomy and TDDU measurement similarly carried out on the second postoperative day. Computing portal blood flow in the intact liver using maximal and minimal CSA gave rise to a mean difference of 7.0 ml kg(-1) min(-1) (P < 0.001). A significant correlation was obtained between HBF and portal flow computed from maximal CSA (Pearson's correlation = 0.85, P < 0.033). The respiratory index of the portal vein (maximal CSA/minimal CSA) decreased from 1.5 to 1.2 after hepatectomy, which also caused a 90% increase in portal pressure. Respiration and portal pressure thus significantly impact on TDDU determination of HBF, and in this porcine model, computation using maximal CS more accurately reflects HBF.

Animals↗

Implantation of a nerve ending into a vein.

Neuromas can be painful and physically and psychologically disabling. Among the many methods of treatment available, translocation away from noxious stimuli, such as implantation in muscle or bone, has been used. Veins are easily available and accessible to nerves. The outcome of a nerve ending implanted into a vein and the effects of the implanted nerve on the vein have not been studied. This study evaluated neuroma prevention with a new technique that involves implanting a nerve ending into a vein. The medial branches of the right femoral nerve of 20 rats were transected at midthigh level. The distal segments were excised. The proximal segments were implanted into the femoral vein. The epineurium was sutured to the tunica adventitia using interrupted 10-0 Ethilon sutures. The left side served as controls where the proximal nerve stumps were left lying in their beds. The animals were sacrificed 12 weeks after the operation. Histologic analysis of 12 controls showed neuromas. Twelve implanted nerves showed neuromas that were smaller than those of the controls. The difference was statistically significant. The regenerated nerve fibers were found within the adventitia and muscular wall of the vein. There was no extension of nerve tissue into the vessel lumen and no thrombosis of the vein. Electron microscopic study on the other eight rats showed abnormal large myelinated fibers in the controls and in the implanted nerves. The fibers in the implanted group were degenerated.

Animals↗

A non-invasive isotope dilution technique for quantifying hepatic blood flow using radiolabelled red blood cells.

Clinically significant changes in hepatic haemodynamics accompany the development of portal hypertension, hepatocellular carcinoma, liver metastases and liver cirrhoses, and after major liver resection. Hepatic blood flow parameters, such as hepatic arterial flow (HAF), hepatic portal flow (HPF), total hepatic blood flow (THBF) and hepatic perfusion index (HPI), are useful adjuncts to the diagnosis of liver pathology, the evaluation of disease progress and prognostication. Here, we describe a non-invasive method that combines the measurement of these parameters in a single study in real time. Red blood cells from eight pigs were labelled with 99Tc(m) using an in-vitro method and re-injected into the pigs. Data acquisition over the heart, lungs, liver and kidneys was started immediately and a blood sample was obtained 15 min post-injection. Hepatic arterial flow was determined from the ratio of the maximum gradients between the integrated time-activity curve of the left ventricle and the first-pass time-activity curve of the liver before the peak of the kidneys time-activity curve. The hepatic perfusion index was determined by comparing the slope of the liver time-activity curve before and after the kidney peak. Hepatic portal flow was determined from the hepatic arterial flow and the hepatic perfusion index, and total hepatic blood flow was determined as the sum of arterial and portal flow. The results were compared against those obtained from a clearance method using 99Tc(m)-DISIDA. The average hepatic perfusion index was 0.38, and the average hepatic arterial flow and hepatic portal flow were 168.3 +/- 52.9 and 274.6 +/- 60.1 ml x min(-1) respectively. The average total hepatic blood flow was 442.8 +/- 53.5 ml x min(-1), while the total hepatic flow determined by 99Tc(m)-DISIDA clearance was 419.7 +/- 62.6 ml x min(-1). No significant difference in total hepatic blood flow was found between the two methods. The results of this study show that it is possible to obtain all hepatic haemodynamics data in a single study using a non-invasive method.

Animals↗

Pigmented central neurocytoma: case report and literature review.

A case of pigmented central neurocytoma is reported. The tumor showed histologic, immunophenotypic, and ultrastructural features of central neurocytoma. The pigment consisted of an intimate association of lipofuscin and neuromelanin. Pigmented neuroepithelial tumors are rare, and the pigments may be neuromelanin or melanin. Pigmented central neurocytoma has not been described to date. The low proliferation rate of the tumor suggests a delayed turnover of tumor cells as a possible cause of lipofuscin accumulation. Autocatalytic peroxidation of lipofuscin is a possible mechanism of neuromelanin formation.

Adult↗

End-to-side anastomosis of transected nerves to prevent neuroma formation.

Neuroma can be painful and physically and psychologically disabling. Among the many methods of treatment available, one of the more successful is centrocentral nerve union with an autologous graft. However, it cannot be used in small nerves that lack two fascicles. This study evaluated neuroma prevention in an end-to-side anastomosis, a new technique applicable to all nerves. The lateral branch of the right sciatic nerve in 20 rats was transected at the midthigh level. The proximal segment was looped back to the main nerve and an end-to-side epineural anastomosis was performed. The lateral branch of the left sciatic nerve was transected to serve as a control, and the proximal nerve stump was closed by interrupted epineural sutures. The animals were sacrificed 12 weeks after the operation. Histologic analysis of specimens from the 12 controls showed neuroma formation. Specimens from 12 side-to-end anastomoses contained regenerated nerve tissues and formed smaller masses compared with that of the controls. The regenerated tissues at the anastomoses were orientated more orderly than were tissues from the controls in 75% of cases. The differences were statistically significant. Electron microscopic study on specimens from the remaining eight controls showed the presence of abundant large abnormal myelinated fibers (10-15 microns) with thick irregular myelin sheaths scattered among smaller myelinated fibers (2-10 microns) that had thin myelin sheaths. In the remaining eight end-to-side anastomoses, large abnormal myelinated fibers were absent. The myelinated fibers were 2 to 10 microns in diameters and had a normal appearance with thin myelin sheaths. End-to-side anastomosis formed a smaller mass of regenerated nerve tissues. Ultrastructurally they were formed better and orientated more orderly resembling normal nerve.

Anastomosis, Surgical↗

A simple method of blood pressure measurement in the pig using a neonatal cuff.

The pig is a commonly used large animal model in experimental studies. Few non-invasive techniques exist however for the measurement of blood pressure in the porcine model. This study evaluates the novel use of the easily available neonatal blood pressure cuff for measuring blood pressure in the pig. Six Yorkshire pigs were used for the study. Blood pressure measurements obtained by the application of neonatal blood pressure cuff (Hewlett Packard) around the base of the tail were compared with results obtained from intra-arterial measurements in the normotensive range as well as in experimentally created hypertensive (intravenous dopamine) and hypotensive (hypovolaemic shock) ranges. Results of the two techniques are closely correlated (Pearson's coefficient = 0.95, 0.97, 0.90). Systematic bias was however detected at the extremes of hypertensive and hypotensive blood pressure. Analysis of the limits of agreement (method of Bland and Altman) showed that neonatal blood pressure cuff measurements fall within--2 to 2.5 mmHg of the readings obtained from the invasive technique (95% confidence interval). The neonatal blood pressure cuff technique is a good substitute for the standard invasive intra-arterial measurement of blood pressure in the pig model.

Animals↗

A practical technique of colour image analysis: applications in experimental research.

Commercially available colour image analysers are relatively expensive. We describe a cheaper alternative developed by the Department of Experimental Surgery, Singapore General Hospital using an assembly of optical and computer equipment commonly available in the research laboratory. This manual colour imaging system is comparable to the commercial model in terms of functional capabilities and accuracy, except that it takes a longer time to process and analyse images and is unable to measure colour density. However, it is capable of not only analysing microscopic images of stained histological tissue sections but also X-ray images and images of large pathological specimens. In the case of commercial models, different systems have to be used to analyse images from different types of specimens. This system was developed in 1987 and has since been used successfully in a number of experimental studies. It has been applied to the measurement of parameters defining eye anatomical configuration, delineating the extent of tissue necrosis and fibrosis after therapeutic treatment and surgery, the development of new bone formation in fracture healing and to quantitative studies in liver regeneration. Due to its accuracy, low cost and versatility, this system should be within the means of even the most modest research laboratory.

Humans↗

Optimal flexible designs in phase II clinical trials.

In the conduct of a phase II cancer clinical trial, patients usually enter in two stages. If the response rate from the first stage is low, then the study terminates. Within various two-stage designs, Simon proposed the optimal and minimax criteria. In the co-operative group setting, practical considerations make it difficult to arrive at the planned sample size exactly. Green and Dahlberg proposed and compared several flexible designs. In this paper, we explicitly define a flexible design as a collection of two-stage designs where the first stage size is in a set of consecutive values (n1, ..., nk) and the second stage size is also in another set of consecutive values (N1, ..., Nk), and each of k2 possible designs has the same probability of occurrence. We apply Simon's optimal and minimax criteria to flexible designs for phase II trials in order to minimize the number of patients tested on an ineffective drug.

Clinical Trials, Phase II as Topic↗

Evaluation of recommendations for replication-competent retrovirus testing associated with use of retroviral vectors.

With input from the gene therapy community, CBER is actively examining the recommendations for RCR testing during retroviral vector production, production of ex vivo-transduced cells, and in patients who receive such material. Our initial recommendations were made at a time when our experience with RCR detection assays and clinical use of retroviral vectors was limited. As the gene therapy field has matured, there is an increasing amount of data available on RCR detection assays and from monitoring of patients in clinical trials. The cumulative data give assurance that RCR detection assays in use are of sufficient sensitivity to provide a margin of safety to patients: no patients to date have evidence of RCR infection. However, CBER encourages members of the gene therapy community to continue to submit data to the FDA or to publish data that will enhance the cumulative data base on RCR testing assays, experience with different VPC, and patient monitoring. Based on the analysis of data accumulated to data, and ongoing discussions with members of the gene therapy community, CBER is proposing to discuss changes to the current RCR testing recommendations, as summarized below. RCR testing during production of retroviral vector and ex vivo-transduced cells. Development of characterized standards for RCR testing of supernatant and cells should allow comparison of assay sensitivity. One proposal under consideration is to apply statistical methods to determine how much material needs to be tested independent of the size of the production lot. Data and discussion are still needed to define a limit concentration and a value for probability of detection for RCR testing, while maintaining an appropriate margin of safety. These modifications of RCR testing strategies could lead to improvements in assay sensitivity. Additional discussion and data are also needed to evaluate the current recommendations of the testing for ex vivo-transduced cells: should both cells and supernatant be tested in all cases? RCR testing during patient follow-up. The time points required for RCR testing during patient follow-up need examination. One proposal under consideration is to sample and assay at three time points during the first year of treatment (e.g., 4-6 weeks, 3 months, and 1 year post-treatment). Further discussion is needed to define appropriate additional follow-up. Choice of assays to detect surrogate markers for RCR infection (i.e., serologic or PCR-based assays) should consider mode of vector administration and the patient population. Positive results with such assays should be pursued by direct culture assay to obtain and characterize the infectious viral isolate. These proposals will be the focal point for the discussion at the Retroviral Vector Breakout Session at the 1997 FDA/NIH Gene Therapy Conference. After the 1997 FDA/NIH Gene Therapy Conference, CBR plans to propose revised recommendations for RCR testing for public comment.

Cell Transformation, Viral↗

Short segment Barrett's oesophagus: prevalence, diagnosis and associations.

BACKGROUND: Prevalence of short segment Barrett's (SSB) oesophagus, defined as the absence of macroscopic Barrett's but histologically identifiable intestinal metaplasia, has been reported to be 18% based on haematoxylin and eosin (H&E) staining. AIMS: To define the prevalence of SSB oesophagus using H&E and alcian blue staining and to determine whether SSB oesophagus is associated with inflammation at the gastro-oesophageal junction (GOJ). SUBJECTS: Consecutive patients (n = 158) presenting for endoscopy completed a structured interview. METHODS: Two biopsy specimens taken from the GOJ were stained with H&E, alcian blue and Giemsa. A third specimen was obtained from the distal oesophagus. Intestinal metaplasia was diagnosed if goblet cells were definitely identified by two independent observers. RESULTS: SSB oesophagus was present in 46 (prevalence 36%, 95% confidence interval (CI) 28.5-43.5) using alcian blue staining. If H&E had been the sole staining method used, 50% cases of intestinal metaplasia would have been overlooked. There were no cases of intestinal metaplasia identified by H&E but missed by alcian blue staining. Logistic regression analysis identified age (odds ratio (OR) per decade 1.03, 95% CI 1.01-1.06), histological oesophagitis (OR 3.2, 95% CI 1.4-7.2) and inflammation at the gastrooesophageal junction (OR 5.9, 95% CI 2.2-15.6) as independent risk factors for SSB oesophagus. CONCLUSION: Unrecognised SSB oesophagus is highly prevalent in patients presenting for diagnostic upper endoscopy if alcian blue staining is applied.

Adult↗

Increased drug reactions in HIV-1-positive patients: a possible explanation based on patterns of immune dysregulation seen in HIV-1 disease. The Military Medical Consortium for the Advancement of Retroviral Research (MMCARR).

Drug reactions are common in HIV-1 disease, with the incidence having been reported to increase with increasing stage and with CD4+ T-cell counts below 200/microliters. However, there have been numerous reports of patients in which rechallenge, dosing changes or continued therapy have resulted in no recurrence or else clearing of the eruption. We followed 974 HIV-1-positive patients for 46 months as a part of a military study of HIV-1 disease. Within this group there were a total of 283 drug eruptions, with cutaneous manifestations in 201 patients in which clinical characteristics were noted and 86 patients in which cutaneous biopsies were performed. Serological evidence of reactivation or acute Epstein-Barr virus (EBV) or cytomegalovirus (CMV) infections were also noted, as well as peripheral eosinophilia. The incidence of drug eruptions significantly increased with increasing Walter Reed stage and decreasing CD4 counts and CD4/CD8 ratio, as well as with increasing age and in patients with increased numbers of other dermatological diagnoses. In addition, white patients had significantly more drug eruptions than did black. Serological or culture evidence of acute or reactivated EBV or CMV was significantly increased in patients with drug eruptions. The majority of the eruptions were maculopapular or morbilliform with a predominantly perivascular mononuclear cell infiltrate. HIV-1 positive patients have an increased incidence of drug reactions, the incidence having been reported to increase in patients with less than 200 CD4+ T cells/microliter. However, at very low T4 counts, especially those less than 25/microliter, and at a CD4/CD8 ratio of less than 0.10, the probability of reactions to trimethoprim-sulphamethoxazole (TMP-SMZ) is decreased in late-stage HIV-1 patients. Maculopapular or morbilliform eruptions are the most common clinical presentations, often accompanied by one or more of the following: fever, arthralgias, eosinophilia, and serum transaminase elevation. Histologically the majority of these eruptions show a perivascular mononuclear cell infiltrate, sometimes with focal interface changes and apoptotic, necrotic cells within the epidermis. Acute hypersensitivity reactions and toxic epidermal necrolysis (TEN) or Stevens-Johnson's syndrome (SJS) with diffuse epidermal apoptosis and necrosis have also been less commonly described. In a study of cutaneous manifestations in an HIV-1 positive military population, drug reactions were evaluated in terms of clinical features, histopathology, demographic features and laboratory findings.

Adolescent↗

Huntington's disease in Hong Kong Chinese: epidemiology and clinical picture.

In a territory-wide survey of Huntington's disease (HD) in the Chinese population of Hong Kong, 20 patients from 11 families were identified from 1984 to 1991, giving a low period prevalence of 3.7 per 10(6) population. Six patients had died by 1991, hence the point prevalence was even lower, being 2.5 per 10(6) population. The male to female ratio was 3:1. No paternal transmission effect on the age of onset was observed. Apart from these differences, the clinical and pathological features were similar to those seen in the West.

Adult↗

Anaesthesia for animals in experimental research.

Animal anaesthesia is a wide and varied subject considering the great number of available animal models, each having its characteristic tolerance and reaction to anaesthesia and its behavioural peculiarity. It is more often than not that experimental researchers tend to give scant attention to animal anaesthesia in the preparation of a research protocol as a result of which their research findings can become difficult or impossible to interpret. This article outlines the fundamental anaesthetic requirements and techniques in various animals and the practices adopted by the Department of Experimental Surgery, Singapore General Hospital. Consideration in the choice of anaesthetic drugs in various animal models and experimental situations, and problems of animal handling before and after anaesthesia are highlighted.

Acid-Base Equilibrium↗

Pattern of cerebral atherosclerosis in Hong Kong Chinese. Severity in intracranial and extracranial vessels.

BACKGROUND AND PURPOSE: The clinical pattern of stroke and the angiographic distribution of cerebral atherosclerosis in Chinese are different from those in Caucasians. Pathological data from autopsy studies are lacking. METHODS: The intracranial and extracranial arteries supplying the brains of 114 consecutive Chinese patients undergoing autopsy in a regional general hospital were examined by computer-assisted morphometric analysis under a microscope as well as by macroscopic grading for atherosclerotic narrowing. The severity was correlated with various atherosclerosis-related factors. RESULTS: Atherosclerosis of the intracranial cerebral vessels was more severe than that of the extracranial vessels. The distal branches of the intracranial vessels were also commonly involved. Hypertension and diabetes mellitus were identified as factors associated only with intracranial atherosclerosis (p < 0.001), whereas ischemic heart disease was associated with atherosclerosis in both the intracranial (p < 0.001) and extracranial (p = 0.012) vessels. Smoking was associated with narrowing of the extracranial vessels only (p = 0.0054). CONCLUSIONS: Compared with figures from Caucasian and Japanese populations, the extent of intracranial atherosclerosis is much more severe in Hong Kong Chinese, whereas atherosclerotic narrowing of the extracranial carotid artery is less severe in Hong Kong Chinese than in Caucasians.

Adolescent↗

Central neurocytoma: its differentiation from intraventricular oligodendroglioma.

Two patients with intraventricular tumours are presented. Both had similar features on light microscopic examination. On the basis of the specific immunohistochemical staining patterns and the ultrastructural findings, one was diagnosed as a central neurocytoma while the other was diagnosed as an intraventricular oligodendroglioma. The possibility of central neurocytoma should be considered in all young patients including children presenting with an intraventricular lesion. Definitive diagnosis requires electron microscopic and immunohistochemical studies.

Adult↗

Delayed myelopathy after a stab wound with a retained intraspinal foreign body: case report.

A case of delayed myelopathy appearing 15 years after a stab wound to the thoracic spine with a retained foreign body in the spinal canal is reported. Severe inflammatory reaction to iron corrosion was found, with granuloma and sterile pus formation. Removal of the foreign body and partial excision of the granuloma resulted in clinical improvement. Reaction to foreign body corrosion is believed to be the major cause of delayed neurologic deficit and is an important guideline for removal of asymptomatic intraspinal foreign bodies.

Foreign Bodies↗

Unusual gastrointestinal complications in neurosurgery.

Nine neurosurgical patients with unusual gastrointestinal complications are presented. Their diagnostic clinical features, as well as pitfalls in their diagnosis are highlighted. A high index of clinical suspicion of these unusual complications is important as patients' decreased level of consciousness and concomitant steroid therapy often complicates the clinical presentation. Progressive abdominal distension and absent or sluggish bowel sounds were the most consistent clinical features in comatose patients with peritonitis, whereas, high fever and markedly elevated white cell counts were often absent.

Adult↗