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Biomedical subjects

C C Tan

Publications and source records attributed to C C Tan.

At least 37 records · Page 2Linked to original sources

Leukemia-associated retinoic acid receptor alpha fusion partners, PML and PLZF, heterodimerize and colocalize to nuclear bodies.

In acute promyelocytic leukemia (APL), the typical t(15;17) and the rare t(11;17) translocations express, respectively, the PML/RARalpha and PLZF/RARalpha fusion proteins (where RARalpha is retinoic acid receptor alpha). Herein, we demonstrate that the PLZF and PML proteins interact with each other and colocalize onto nuclear bodies (NBs). Furthermore, induction of PML expression by interferons leads to a recruitment of PLZF onto NBs without increase in the levels of the PLZF protein. PML/RARalpha and PLZF/RARalpha localize to the same microspeckled nuclear domains that appear to be common targets for the two fusion proteins in APL. Although PLZF/RARalpha does not affect the localization of PML, PML/RARalpha delocalizes the endogenous PLZF protein in t(15;17)-positive NB4 cells, pointing to a hierarchy in the nuclear targeting of these proteins. Thus, our results unify the molecular pathogenesis of APL with at least two different RARalpha gene translocations and stress the importance of alterations of PLZF and RARalpha nuclear localizations in this disease.

Animals↗

Effect of cisapride on functional dyspepsia in patients with and without histological gastritis: a double-blind placebo-controlled trial.

In the present double-blind placebo-controlled study the effect of cisapride on functional dyspepsia was evaluated in patients with and without histological gastritis. Patients with functional dyspepsia and whose symptoms persisted after a 2 week run-in period with antacid treatment were randomized to receive cisapride (10 mg) or matching placebo three times daily for 4 weeks. Symptoms of epigastric pain, bloating, nausea, belching, early satiety and heartburn were graded on a four-point scale based on patients' feedback and diary card recording. A global response was also formulated by the investigators. One hundred and four patients entered the study and 76 completed the trial, comprising 36 patients with histological gastritis and 40 patients without gastritis. Symptom scores in both gastritis and non-gastritis groups were significantly improved by both cisapride and placebo; however, the improvement was not statistically different between the two treatment groups. Cisapride produced a good or better global response in 58% of subjects with histological gastritis and in 53% of subjects without gastritis compared with 47% and 52%, respectively, of patients on placebo; this difference was not statistically significant. Gastric histology did not influence the effect of cisapride on the symptoms of functional dyspepsia.

Adult↗

Magnetically levitated motor for rotary blood pumps.

The noncontact rotary pumps under development for use as artificial heart pumps are highly efficient and can prevent thrombus formation. In these pumps magnetic bearings have been widely used to support the rotors to avoid any physical contact. The use of magnetic bearings, however, has led to requirements for the control of a large degree of freedom and for a separate driving motor. This paper introduces 2 types of levitated motors, each of which uses a combination of a rotary motor and a magnetic bearing. These motors are suitable for use in artificial blood pumps because they are small in size and can replace contact components. The radial type levitated motor has the merit of being small in size and capable of controlling the 2 degrees of freedom in the x and y directions. The axial type motor controls only one degree of freedom in the z direction. This paper also introduces the theoretical background of the functions of the motor and magnetic bearing. Experimental results of tests of the proposed motor show a great potential for its application in rotary blood pumps.

Algorithms↗

Erythropoietin production in rats with post-ischemic acute renal failure.

To study the role of erythropoietin (Epo) in the pathogenesis of anemia in acute renal failure (ARF), organ Epo mRNA was measured by RNase protection assay in rats with ARF induced by a one hour-occlusion of the left renal artery. Hematocrit was significantly decreased two hours, 24 hours and one week after renal artery occlusion. A significant reduction in serum haptoglobin at two hours and an increase in serum LDH at 24 hours indicated that hemolysis was the likely cause of the initial fall in hematocrit. However, despite the reduced hematocrit, serum Epo concentrations were not significantly different from controls, suggesting that the anemia is maintained because of lack of an appropriate Epo response. Right renal Epo mRNA levels were not significantly different in all groups, but Epo mRNA levels in post-ischemic kidneys were 50 to 67% lower than in contralateral kidneys. However, Epo mRNA in the post-ischemic kidney was increased sixfold by acute hemorrhage, a rise comparable to the ninefold increase observed in contralateral kidneys. In ARF rats exposed to 7.5% O2 for four hours, right kidney Epo mRNA increased 200-fold over normoxic levels, to a value similar to sham-operated hypoxic controls. Epo mRNA in the post-ischemic kidney also increased 200-fold, to 50% of the level in the contralateral kidney. Hepatic Epo mRNA levels were elevated to comparable levels in both groups. In this ARF model, mild anemia is associated with relative Epo deficiency. In the post-ischemic kidney, a substantial capacity for Epo production is retained but the sensitivity of the Epo response to blood oxygen availability is significantly reduced.

Acute Kidney Injury↗

Throat spray for upper gastrointestinal endoscopy is quite acceptable to patients.

BACKGROUND AND STUDY AIMS: The use of sedation in upper gastrointestinal endoscopy is widespread, mainly because of the belief that patients are likely to tolerate the procedure better. The aim of the present study was to assess patients' response to the policy of actively persuading them to accept a throat spray for upper gastrointestinal endoscopy. PATIENTS AND METHODS: Three hundred patients who had recently undergone endoscopy were sent a questionnaire; 244 of them responded (81%). Data on age, sex, procedure tolerance, anxiety levels, and future choice of sedation or throat spray for repeat procedures were sought. The results were analysed using the chi-squared test. RESULTS: One hundred and ninety-two (79%) chose, or were persuaded to have, throat spray, and only nine (5%) had to be transferred to sedation. Thirty-two percent of patients who had throat spray tolerated endoscopy well, compared to 70% of those who chose sedation. One hundred and nineteen throat spray patients (62%) showed a low level of reluctance to undergo repeat endoscopy, compared to 37 (71%) sedated patients (not significant). One hundred and forty-four throat spray patients (76%) expressed satisfaction with the throat spray, but if given a choice, only 124 (66%) would choose throat spray again. Male patients, those with lower anxiety levels, and those over 50 years old, tolerated endoscopy with throat spray better, showed less reluctance to undergo repeat endoscopy, and were more likely to choose throat spray again. Those who had any previous experience of endoscopy under sedation were less likely to choose throat spray again. CONCLUSION: The present study shows that the use of throat spray for diagnostic endoscopy is quite acceptable to patients. For safety reasons, we should be encouraging greater use of throat spray in routine diagnostic upper gastrointestinal endoscopy.

Adolescent↗

Ranitidine reduces phosphate binding in dialysis patients receiving calcium carbonate.

BACKGROUND: In a previous controlled study we showed that ranitidine significantly reduced the phosphate binding of aluminium hydroxide in patients with renal failure, probably increasing intragastric pH. METHODS: In this study we have investigated the effect of ranitidine on the phosphate binding of calcium carbonate in fifteen dialysis patients. Ranitidine 300 mg or a placebo tablet was taken before breakfast for two 4-week periods in a double-blind crossover trial with no washout period. The mean daily dose of calcium carbonate was 2 g and neither the dose nor the patient's diet was changed during the study period. Blood was taken at 2-weekly intervals for serum phosphate, calcium, albumin, and alkaline phosphatase measurements, and at the end of each treatment period for parathyroid hormone (PTH) level. RESULTS: Serum phosphate concentrations were significantly higher during the ranitidine than the placebo phase, 1. 78 (+/-0.43 SD) versus 1.59 (+/-0.49 SD) mmol/l (P<0.001). Serum calcium, albumin, PTH, and alkaline phosphatase concentrations did not differ between the two treatment periods. CONCLUSION: This study shows that ranitidine has a significant adverse effect on the phosphate binding of calcium carbonate in patients with renal failure.

Adult↗

Paracetamol and its metabolites in saliva and plasma in chronic dialysis patients.

1. Many pharmacokinetic studies on paracetamol are based on saliva paracetamol concentrations. The utility of saliva in patients with chronic renal failure is unclear. In this study, concentrations of saliva and plasma paracetamol and its major metabolites, sulphate and glucuronide conjugates were determined at 0.5, 1, 2 and 3 h after the ingestion of 1 g paracetamol in 20 patients with endstage renal failure. Ten haemodialysis patients were studied on a non-haemodialysis day and during a haemodialysis session. The other 10 patients were on chronic ambulatory peritoneal dialysis. 2. The plasma paracetamol concentrations attained in all groups were not different from those reported previously in healthy subjects. Mean +/- s.d. plasma paracetamol concentrations at 0.5 h in haemodialysis patients on a non-haemodialysis day, during haemodialysis and in those on chronic ambulatory peritoneal dialysis were 15.3 +/- 8.2, 21.5 +/- 10.9 and 18.2 +/- 12.3 micrograms ml-1 respectively. 3. The saliva paracetamol concentrations were highly variable and unpredictable. Saliva paracetamol concentrations at 1, 2 and 3 h after ingestion in the haemodialysis group during haemodialysis were 31.5 +/- 20.1, 14.1 +/- 10.4 and 7.3 +/- 3.8 micrograms ml-1 respectively, significantly (P < 0.05; paired t-test) higher than the corresponding plasma paracetamol concentrations which were 11.0 +/- 2.8, 6.5 +/- 2.8 and 3.2 +/- 0.9 micrograms ml-1 respectively. 4. Correlation coefficients between saliva and plasma paracetamol concentrations in haemodialysis patients on a non-haemodialysis day and during haemodialysis and in chronic ambulatory peritoneal dialysis patients were poor; r = 0.58 (P < 0.0002); r = 0.40 (P < 0.02); and r = 0.13 (P = 0.49) respectively. 5. Three hours after paracetamol ingestion, plasma paracetamol, sulphate and glucuronide concentrations were significantly (P < 0.05) reduced in haemodialysis patients during haemodialysis when compared with the same patients on a non-haemodialysis day (paired t-test) and to the chronic ambulatory peritoneal dialysis group (Kruskal-Wallis ANOVA) except for plasma glucuronide. This indicates the effective removal of paracetamol and metabolites by haemodialysis. In contrast, chronic ambulatory peritoneal dialysis seemed to remove glucuronide only. 6. In the light of the poor correlation between saliva and plasma paracetamol in dialysis patients in this study, we would like to caution against using saliva paracetamol concentrations for pharmacokinetic studies in this group of patients.

Acetaminophen↗

A rare case of dermatitis herpetiformis requiring parenteral heparin for long-term control.

We report a patient with controlled coeliac disease but severe dermatitis herpetiformis who was intolerant of dapsone and sulphapyridine. She ultimately had to be treated with parenteral heparin which brought about involution of the skin lesions with symptomatic relief within 1 week. The mechanism of action of heparin is uncertain but may be related to the inhibition of the formation of proteases generated from polymorphs by the clotting process. The treatment is associated with great difficulties in administration over the long term and associated with the risk of haemorrhage. This case illustrates these problems.

Celiac Disease↗

Plasma activity of contact coagulation factors in patients with IgA nephritis.

Intraglomerular coagulation, initiated by the local activation of contact coagulation factors, has been suggested as one possible factor causing glomerular injury in IgA nephritis. The plasma activity of factor XII, prekallikrein and high molecular weight (HMW) kininogen were measured in 24 patients with biopsy-proven IgA nephritis and in 123 normal controls, using an activated partial thromboplastin time assay with the appropriate factor-deficient plasma as substrate. IgA patients had significantly lower plasma activity of factor XII (45.5% +/- 28.3% against 80.7% +/- 31.8%; mean +/- standard deviation, P < 0.001), prekallikrein (37.7% +/- 24.5% against 119.8% +/- 37.7%; P < 0.001) and HMW kininogen (72.8% +/- 37.8% against 119.1% +/- 42.8%; P < 0.001) when compared with controls. In the IgA patients, there was no significant correlation between factor XII, prekallikrein and HMW kininogen activity and 24-hour total urinary protein excretion, suggesting that the reduced plasma activity was not due to increased urinary loss of the coagulation factors. One possible explanation for these results is that the intrinsic coagulation pathway is activated in patients with IgA nephritis.

Adult↗

Chili protects against aspirin-induced gastroduodenal mucosal injury in humans.

Capsaicin, the pungent ingredient of chili, has a gastroprotective effect against experimental gastric mucosal injury in animals. Such an effect has not, however, been documented in humans to date. Eighteen healthy volunteers with normal index endoscopies underwent two studies four weeks apart. Each subject took 20 g chili orally with 200 ml water in one study and 200 ml water in another study. In each case this was followed half an hour later by 600 mg aspirin BP with 200 ml water. Endoscopy was repeated 6 hr later. Gastroduodenal mucosal damage was assessed by a previously validated scoring system. The median gastric injury score after chili was 1.5 compared to 4 in the control group (P < 0.05), demonstrating a gastroprotective effect of chili in human subjects.

Adult↗

Acute cyclosporine A nephrotoxicity in a renal allograft recipient with hypothyroidism.

Cyclosporine A (CsA) is an important immunosuppressant in kidney transplantation. Acute CsA nephrotoxicity secondary to high drug levels is a well-recognized complication in the immediate posttransplant period. Cyclosporine A is metabolized in the body by the hepatic cytochrome P-450 enzyme system. We present a case of a hypothyroid patient who developed toxic blood CsA levels and acute nephrotoxicity with standard doses of CsA. A reduction of CsA levels led to an improvement of allograft function. Correction of the hypothyroid state resulted in the normalization of CsA requirements, but overcorrection led to an increased requirement of CsA. Thyroid dysfunction should be considered as an interacting factor in the metabolism of CsA.

Cyclosporine↗

Local effects of colorectal cancer are well palliated by endoscopic laser therapy.

We review the results of treating the local effects of 26 cases of inoperable colorectal cancer with Nd:YAG laser. There were 16 men and 10 women of mean age 75, with 17 (65%) rectal, eight (31%) sigmoid and one (4%) ascending colon cancer. They presented with symptoms primarily of obstruction in 12 patients (46%), bleeding in 10 (39%) and diarrhoea in four (15%). Initial therapy to relieve symptoms required a mean of 1.5 (1-3) laser treatments over a mean of 1.5 (1-2) weeks. Twelve patients (46%) had total relief and 12 (46%) had partial relief. Sixteen patients received follow-up maintenance therapy, with laser treatments performed over a mean interval of 7.3 (1-20) weeks. One died at first follow-up treatment; all but two of the others were well maintained by laser treatment alone. Three patients (12%) suffered complications, with two deaths (8%), one due to cardiac failure and the other due to stercoral perforation of the colon. Four patients remained alive after a mean follow-up period of 51 (9-84) months. The mean survival of the others was 5 (0-23) months. Laser palliation for colorectal cancer is efficacious and relatively safe, allows improved quality of survival in 92% of patients after initial treatment, and, alone, can satisfactorily keep patients relatively free of local symptoms in 88% of patients surviving into the follow-up period.

Aged↗

Using regions and indices in EPG data reduction.

This note describes how dynamic electropalatography (EPG) can be used for the acquisition and analysis of articulatory data. Various data reduction procedures developed to analyze the electropalatographic data are reported. Specifically, these procedures concern two interesting areas in EPG data analysis--first, the novel use of speaker-specific articulatory regions and second, the development of arithmetic indices to quantify time-varying articulatory behavior and reflect reduction and coarticulation.

Electric Stimulation↗

Treatment of hepatitis B surface antigen carriers in the early stage of the infection using recombinant alpha-interferon with steroid priming.

BACKGROUND: Alpha-interferon has been found to inhibit hepatitis B virus (HBV) replication in Chinese patients with chronic HBV infection although a sustained effect was rarely achieved in those with normal pretreatment serum alanine amino transferase (ALT) levels. Prednisolone priming has been found to be beneficial over treatment with interferon alone in these subjects. We studied the effect of steroid pre-treatment followed by recombinant interferon alpha-2a in the treatment of asymptomatic HBV carriers with positive hepatitis Be antigen (HBeAg), hepatitis B viral DNA (HBV-DNA) and minimal changes in liver histology. METHODS: The treatment regimen included a 6-week prednisolone priming, a 2 week rest followed by 14 weeks of three times weekly 9 mega units of interferon alpha-2a injection and 52 weeks of follow-up. There were seven patients in the treatment group and seven controls. RESULTS: The mean age, pre-treatment ALT (normal in all except for one in each of the treatment and control groups), HBV-DNA levels and histological scores were similar in the two groups. Serum HBV-DNA levels fell in six patients during treatment and became undetectable in two of them by the end. During follow-up, serum HBV-DNA returned to pre-treatment levels in all patients. None of the treated patients had HBeAg sero-conversion and none of the controls had spontaneous clearance of HBV-DNA or sero-conversion of HBeAg. No improvement of liver histology was observed in any of the treated patients. There were only mild flu-like side-effects noted and interferon alpha-2a was well tolerated at the doses given among treated patients. CONCLUSION: Prednisolone priming followed by interferon alpha-2a treatment has no beneficial effect on HBV carriers in the early stages of chronic hepatitis B infection.

Adult↗