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Biomedical subjects

M Tan

Publications and source records attributed to M Tan.

At least 19 recordsLinked to original sources
PubMed2006

Death on the kidney waiting list--good candidates or not?

The waiting list for a kidney or simultaneous pancreas-kidney transplant is growing, and waiting times are getting longer. As a consequence, transplant candidates are dying while waiting for a transplant. In a retrospective analysis, we studied whether patients on our list who died while waiting were good candidates. From January 1, 2002, through September 30, 2004, 85 candidates on our list died. Of these, 71% were waiting for a first transplant; 62% had a current panel-reactive antibody (PRA) level of 0%. Of the 85 candidates who died, the mean (+/-SD) age was 53 +/- 11 years; mean waiting time from listing to death, 979 +/- 749 days. The most common cause of death was cardiovascular disease. Many of those candidates who died while waiting were young, first-transplant candidates with a low PRA level. But only limited information was available; prospective studies are necessary to determine whether or not they were, in fact, good candidates.

Adult↗
PubMed2006

Upregulation and activation of PKC alpha by ErbB2 through Src promotes breast cancer cell invasion that can be blocked by combined treatment with PKC alpha and Src inhibitors.

Although ErbB2 is known to enhance breast cancer metastasis, the signaling events responsible for this remain elusive. Alpha-isozyme of protein kinase C (PKCalpha), which is involved in cancer development and progression, has been suggested to be activated by ErbB2 without direct evidence. In addition, the roles of PKCalpha in ErbB2-mediated cancer cell malignancy have not been clearly identified. In this study, we investigated whether ErbB2 can activate PKCalpha and determined what role PKCalpha plays in ErbB2-mediated breast cancer cell invasion. We expressed wild-type and mutant ErbB2 with altered signaling capacities in MDA-MB-435 breast cancer cells and revealed that overexpression or activation of ErbB2 in MDA-MB-435 cells upregulated and activated PKCalpha and that downregulation of ErbB2 by small-interfering RNA decreased the expression and activity of PKCalpha in BT474 breast cancer cells. These in vitro results were supported by data from breast cancer patient samples. In 150 breast cancer tumor samples, ErbB2-overexpressing tumors showed significantly higher positive rates of PKCalpha membrane immunohistochemistry staining than that of ErbB2-low-expressing tumors. Mechanistically, we found that PKCalpha is co-immunoprecipitated with Src and PKCalpha expression and activity can be decreased by Src inhibitor PP2 and by the expression of a dominant-negative mutant of Src. Moreover, ErbB2-mediated upregulation of urokinase-type plasminogen activator receptor (uPAR) is reduced by either the PKCalpha inhibitor Go6976 or the Src inhibitor PP2, and the combination of Go6976 with PP2 is superior to either agent alone in suppressing uPAR expression and cell invasion. These results demonstrate that PKCalpha is critical for ErbB2-mediated cancer cell invasion and provide valuable insights for current and future PKCalpha and Src inhibitor clinical trials.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2006

Autologous stem cell transplantation followed by consolidation chemotherapy for patients with multiple myeloma.

Although high-dose therapy and autologous stem cell transplant (ASCT) is superior to conventional chemotherapy for treatment of myeloma, most patients relapse and the time to relapse depends upon the initial prognostic factors. The administration of non-cross-resistant chemotherapies during the post-transplant period may delay or prevent relapse. We prospectively studied the role of consolidation chemotherapy (CC) after single autologous peripheral blood stem cell transplant (auto-PBSCT) in 103 mostly newly diagnosed myeloma patients (67 patients were < or =6 months from the initial treatment). Patients received conditioning with BCNU, melphalan+/-gemcitabine and auto-PBSCT followed by two cycles of the DCEP+/-G regimen (dexamethasone, cyclophosphamide, etoposide, cisplatin+/-gemcitabine) at 3 and 9 months post-transplant and alternating with two cycles of DPP regimen (dexamethasone, cisplatin, paclitaxel) at 6 and 12 months post-transplant. With a median follow-up of 61.2 months, the median event-free survival (EFS) and overall survival (OS) are 26 and 54.1 months, respectively. The 5-year EFS and OS are 23.1 and 42.5%, respectively. Overall, 51 (49.5%) patients finished all CC, suggesting that a major limitation of this approach is an inability to deliver all planned treatments. In order to improve results following autotransplantation, novel agents or immunologic approaches should be studied in the post-transplant setting.

Adult↗
PubMed2005

Pioglitazone elicits long-term improvements in insulin sensitivity in patients with type 2 diabetes: comparisons with gliclazide-based regimens.

AIMS/HYPOTHESIS: Recent studies have demonstrated that pioglitazone (PIO) has beneficial effects on insulin sensitivity compared with placebo in patients with type 2 diabetes. The effects of PIO and gliclazide (GLIC)-based therapy on insulin sensitivity have not previously been directly compared. This analysis aimed to compare the effects of 52 weeks of treatment with PIO (30-45 mg/day) and GLIC (80-320 mg/day), both titrated to maximum tolerable doses, as monotherapy or in combination with metformin (MET), on insulin sensitivity and lipid parameters known to be related to insulin sensitivity in patients with type 2 diabetes. METHODS: We performed an analysis of 1,880 patients with inadequately controlled type 2 diabetes (HbA1c 7.5-11.0%) who were participants in two parallel-group, double-blind, double-dummy, randomised, multicentre, clinical trials. Measures of insulin sensitivity and lipids were assessed. RESULTS: The PIO- and GLIC-based regimens produced similar levels of glycaemic control (HbA1c). In both trials, insulin sensitivity as assessed using the homeostasis model assessment was improved in patients receiving PIO, but decreased in those receiving GLIC (mean change, baseline to endpoint: PIO 15.5, GLIC -15.6; p<0.001 and PIO+MET 18.9, GLIC+MET -5.3; p<0.001). Improvements in the atherogenic index of plasma (mean change: PIO -0.17, GLIC -0.08; p<0.001 and PIO+MET -0.17, GLIC+MET -0.02; p<0.001), triglycerides (mean change, mmol/l: PIO+MET -0.62, GLIC+MET -0.22; p<0.001) and NEFA (mean change, mmol/l: PIO+MET -0.12, GLIC+MET-0.05; p<0.001) were greater in PIO-treated patients than in patients receiving GLIC. CONCLUSIONS/INTERPRETATION: The PIO-based regimens resulted in improved insulin sensitivity and more favourable insulin sensitivity-related lipid profiles compared with the GLIC-based regimens. These benefits may be important in the management of cardiovascular risk in patients with type 2 diabetes.

Adult↗
PubMed2005

Congenital anomaly rate in offspring of mothers with diabetes treated with insulin lispro during pregnancy.

AIM: To determine the rate of major congenital anomalies in offspring of a large group of women with diabetes mellitus treated with insulin lispro (Humalog). METHODS: This multinational, multicentre, retrospective study included mothers with diabetes mellitus (diagnosed prior to conception) who were treated with insulin lispro for at least 1 month before conception and during at least the first trimester of pregnancy. Anomalies were assessed by two independent dysmorphologists not affiliated with the sponsor. RESULTS: The charts of 496 women were reviewed for 533 pregnancies resulting in 542 offspring (500 live births, 31 spontaneous and seven elective abortions, and four stillbirths). Mothers' characteristics: mean (+/- SD) age was 29.9 (+/- 5.2) years, 85.6% were Caucasian and 97.2% had Type 1 diabetes mellitus. Insulin lispro continued to be the main mealtime insulin for more than 96% of the women during the second and third trimester. The dysmorphologists determined that 27 (5.4%) offspring had major congenital anomalies and 2 (0.4%) offspring had minor congenital anomalies. CONCLUSIONS: The rate of major congenital anomalies was 5.4% [95% CI (3.45%, 7.44%)] for offspring of mothers with diabetes mellitus treated with insulin lispro before and during pregnancy. The current published rates of major anomalies in infants born to mothers with diabetes treated with insulin are between 2.1 and 10.9%. This suggests that the anomaly rate with insulin lispro treatment does not differ from the published major congenital anomaly rates for other insulin treatments.

Abnormalities, Drug-Induced↗
PubMed2005

Attention deficit and hyperactivity disorder, methylphenidate, and epilepsy.

Attention deficit hyperactivity disorder (ADHD) is characterised by inattention, impulsivity, and hyperactivity. The DSM-IV diagnosis of ADHD requires the presence of six of nine items or features that must have been present for at least six months, to have had an onset before 7 years of age, and to have resulted in significant distress or impairment.1 In the general population, the prevalence of ADHD is approximately 5%.2 There is a high co-morbidity of epilepsy and attentional and behavioural problems,3,4 including ADHD, and it has been estimated that at least 20% of patients with epilepsy may present with features of ADHD.5.

Attention Deficit Disorder with Hyperactivity↗
PubMed2005

Mucormycosis presenting with painful ophthalmoplegia.

Mucormycosis is a rare fungal infection that can involve the sino-orbito-cerebral region. Sino-orbito-cerebral mucormycosis is most common in patients who are immunocompromised or have diabetes mellitus, severe malnutrition or burns. This condition can be fatal if it is not diagnosed early and treated aggressively. This article presents 4 cases of mucormycosis, including 2 with orbital apex syndrome, 1 with cavernous sinus syndrome, and 1 with multiple cranial nerve involvement. All of the patients were presented with painful ophthalmoplegia. The predisposing factors for mucormycosis included diabetes mellitus (three patients) and chronic leukemia (one patient). In all cases, mucormycosis was diagnosed by examining endoscopic sinus drainage material and was treated with surgical debridement and amphotericin B. Two patients with central nervous system involvement died. The others have survived, but still exhibiting various neurologic abnormalities after aggressive treatment. Patients with mucormycosis rarely present with orbital apex syndrome. The possibility of mucormycosis should be investigated in any patient with painful ophthalmoplegia, and prompt otorhinolaryngologic examination is recommended to ensure rapid diagnosis and treatment.

Aged↗
PubMed2004

Activation of a rice endogenous retrotransposon Tos17 in tissue culture is accompanied by cytosine demethylation and causes heritable alteration in methylation pattern of flanking genomic regions.

Tos17 is a copia-like, cryptic retrotransposon of rice, but can be activated by tissue culture. To study possible epigenetic mechanism controlling activity of Tos17, we subjected three rice lines (the parental line cv. Matsumae and two introgression lines, RZ2 and RZ35) that harbor different copies of the element to tissue culture. For each line, we investigated transcription and transposition of Tos17 in seed plants, calli and regenerated plants, cytosine-methylation status at CG and CNG positions within Tos17, effect of 5-azacytidine on methylation status and activity of Tos17, and cytosine-methylation states in genomic regions flanking original and some newly transposed copies of Tos17 in calli and regenerated plants. We found that only in introgression line RZ35 was Tos17 transcriptionally activated and temporarily mobilized by tissue culture, which was followed by repression before or upon plant regeneration. The activity and inactivity of Tos17 in calli and regenerated plants of RZ35 are accompanied by hypo- and hyper-CG methylation and hemi- and full CNG methylation, respectively, within the element, whereas immobilization of the element in the other two lines is concomitant with near-constant, full hypermethylation. Treatment with 5-azacytidine induced both CG and CNG partial hypomethylation of Tos17 in two lines (Matsumae and RZ35), which, however, was not accompanied by activation of Tos17 in any line. Heritable alteration in cytosine-methylation patterns occurred in three of seven genomic regions flanking Tos17 in calli and regenerated plants of RZ35, but in none of the five regions flanking dormant Tos17 in the other two lines.

Azacitidine↗
PubMed2004

Role of zinc in the pathogenesis and treatment of prostate cancer: critical issues to resolve.

The most consistent and persistent biochemical characteristic of prostate cancer (PCa) is the marked decrease in zinc and citrate levels in the malignant cells. This relationship provides compelling evidence that the lost ability of the malignant cells to accumulate zinc is an important factor in the development and progression of prostate malignancy. In addition, this relationship provides a rational basis for the concept that restoration of high zinc levels in malignant cells could be efficacious in the treatment and prevention of PCa. Epidemiological studies regarding dietary zinc effects on PCa have been conflicting and confusing. The purpose of this presentation is to present a current state of information regarding zinc relationships in the pathogenesis and treatment of PCa. We also hope to bring more attention to the medical and research community of the critical need for concerted clinical and basic research regarding zinc and PCa.

Apoptosis↗
PubMed2004

The value of Bilicheck as a screening tool for neonatal jaundice in term and near-term babies.

AIMS: To determine the accuracy of Bilicheck in assessing serum bilirubin. To evaluate the effectiveness of Bilicheck as a screening device in a population of jaundiced term and near-term babies. METHODS: Prospective evaluation of paired Bilicheck measurements and serum bilirubin in 300 babies. RESULTS: There was a strong correlation between Bilicheck and serum bilirubin. The mean difference between Bilicheck and serum bilirubin was -10.7 micromol/l, but the 95% limits of agreement were wide at -80 micromol/l to +60 micromol/l. Bilicheck identified significant jaundice (serum bilirubin above 250 micromol/l) with a sensitivity (95% confidence interval) of 91% (88% to 94%) and specificity of 66% (60% to 71%). The area under the receiver operator characteristic curve was 0.85. There were five false negatives, all of whom had a serum bilirubin below 300 micromol/l. If Bilicheck had been used as a screening device, there would have been a 55% decrease in blood samples taken in these babies. CONCLUSION: Bilicheck cannot be used to measure serum bilirubin in term and near-term babies with jaundice, but is an effective screening method, which can be used to safely reduce the number of blood tests in these babies.

Bilirubin↗
PubMed2004

Mobilized retrotransposon Tos17 of rice by alien DNA introgression transposes into genes and causes structural and methylation alterations of a flanking genomic region.

Tos17 is a copia-like endogenous retrotransposon of rice, which can be activated by various stresses such as tissue culture and alien DNA introgression. To confirm element mobilization by introgression and to study possible structural and epigenetic effects of Tos17 insertion on its target sequences, we isolated all flanking regions of Tos17 in an introgressed rice line (Tong35) that contains minute amount of genomic DNA from wild rice (Zizania latifolia). It was found that there has been apparent but limited mobilization of Tos17 in this introgression line, as being reflected by increased but stable copy number of the element in progeny of the line. Three of the five activated copies of the element have transposed into genes. Based on sequence analysis and Southern blot hybridization with several double-enzyme digests, no structural change in Tos17 could be inferred in the introgression line. Cytosine methylation status at all seven CCGG sites within Tos17 was also identical between the introgression line and its rice parent (Matsumae)-all sites being heavily methylated. In contrast, changes in structure and cytosine methylation patterns were detected in one of the three low-copy genomic regions that flank newly transposed Tos17, and all changes are stably inherited through selfed generations.

3' Flanking Region↗
PubMed2004

Breath carbon monoxide as an indication of smoking habit in the military setting.

INTRODUCTION: The breath carbon monoxide (CO) monitor has been shown to be an effective tool in predicting smoking habits. This study aims to assess whether the breath CO level can be employed to determine a person's smoking habit in the military setting and to analyse various factors that can influence the breath CO levels. METHODS: 155 navy personnel were questioned on their smoking habits in phase one of the study. The subjects were explained the objective of the study and instructed to provide two breaths into the CO monitor (EC-50 Smokerlyser, Bedford Instruments, Kent, UK). In a subsequent single blind study, 40 trainees were not told of the purpose of the study and were assessed via a questionnaire and smokerlyser estimation. Descriptive statistics were used to examine the data and assess distribution. Depending on the distribution, a two-sample t test or Mann-Whitney U test were used to test for a significant difference between CO levels among smokers and non-smokers. RESULTS: In phase one, the mean breath CO levels were 11.6 (plus or minus 6.2) ppm for smokers and (1.9 plus or minus 0.9) ppm for non-smokers (p-value less than 0.0001). A cut-off level of 5 ppm gave a sensitivity of 96 percent and a specificity of 98 percent. The high CO levels were clustered within five hours of the last cigarette smoked. Therefore, this value may not reliably predict smoking habits if an individual smoked more than five hours before the test. Of the 40 subjects in phase two, five smokers who stated that their last cigarette smoked was 48 hours before the breath test had a mean CO level greater than 5 ppm. (range of 5.5 to 18.0 ppm). On further questioning, all admitted to having smoked on the day of the test. CONCLUSION: The breath CO monitor has good potential for use as an adjunct in future smoking control assessments and a reading greater than 5 ppm strongly suggests that the military outpatient is a smoker.

Adult↗
PubMed2003

Nonablative dermal remodeling with a 585-nm, 350-microsec, flashlamp pulsed dye laser: clinical and ultrastructural analysis.

BACKGROUND: A nonablative 350-microsec, 585-nm, flashlamp pulsed dye laser is currently being used for the treatment of rhytides. OBJECTIVE: To analyze both clinical rhytid improvement and electron microscopic evidence of ultrastructural changes after treatment with a nonablative 350-microsec, 585-nm, flashlamp pulsed dye laser. RESULTS: At 6 months after two treatments, 40% of the treated subjects noted mild improvement in rhytid appearance. Nontreating physician evaluation revealed some degree of improvement in 50% of the treated subjects. Mild improvement in quality and texture of the skin was also reported by 50% of the subjects. Electron microscopic evaluation showed ultrastructural changes that are consistent with new collagen formation. CONCLUSION: Treatment with a nonablative 350-microsec, 585-nm, flashlamp pulsed dye laser can lead to both clinical and electron microscopic evidence of improvement in photo-damaged skin.

Humans↗
PubMed2002

The effect of octreotide on kainate-induced wet dog shakes and seizure activity in male and female rats.

Systemic kainic acid (KA) administration to rats triggers wet dog shakes (WDS) followed by epileptic seizures. Although WDS are often associated with the occurrence of seizures, we have recently shown that following nitric oxide (NO) synthesis inhibition, the number of WDS decreased; subsequently the onset of seizure activity was shortened, and the number of convulsions was increased. Somatostatin (SS), whose release appears to be controlled by NO, inhibits seizure activity. There are sex differences in seizure susceptibility as well as in SS and NO activities in brain. The present study was undertaken to assess the effect of octreotide (OC), a stable SS analogue, on KA-induced WDS and seizures in rats, with emphasis on possible sex differences. WDS and seizures were induced by KA in male and female (proestrus) Sprague Dawley rats; OC or saline was injected 30 min before KA and the behavior was monitored for 120 min after KA. Octreotide increased the number of WDS and decreased the number of convulsions; this effect was more pronounced in males. Onset of KA-induced seizure activity was earlier in females than males; however, there was no effect of OC on seizure latency. Seizure activity started after the termination of WDS. These results show OC has opposite effects on WDS and convulsions, in that it stimulates the former and inhibits the latter. These results support our previous findings that WDS and seizure activity involve separate mechanisms and suggest that WDS may have an inhibitory effect on limbic seizures.

Analysis of Variance↗
PubMed2001

Persistent expression of cyclin D1 disrupts normal photoreceptor differentiation and retina development.

The differentiation of neuronal cells in the developing mammalian retina is closely coupled to cell cycle arrest and proceeds in a highly organized manner. Cyclin D1, which regulates cell proliferation in many cells, also drives the proliferation of photoreceptor progenitors. In the mouse retina, cyclin D1 protein normally decreases as photoreceptors mature. To study the importance of the down-regulation of cyclin D1 during photoreceptor development, we generated a transgenic mouse in which cyclin D1 was persistently expressed in developing photoreceptor cells. We observed numerous abnormalities in both photoreceptors and other nonphotoreceptor cells in the retina of these transgenic mice. In particular, we observed delayed opsin expression in developing photoreceptors and alterations in their number and morphology in the mature retina. These alterations were accompanied by disorganization of the inner nuclear and plexiform layers. The expression of cyclin D1 caused excess photoreceptor cell proliferation and apoptosis. Loss of the p53 tumor suppressor gene decreased cyclin D1-induced apoptosis and led to microscopic hyperplasia in the retina. These findings are distinct from other mouse models in which the retinoblastoma gene pathway is disrupted and suggest that the IRBP-cyclin D1 mouse model may recapitulate an early step in the development of retinoblastoma.

Animals↗
PubMed2001

Pseudoaneurysm of the superior mesenteric artery after pancreas transplantation treated by endovascular stenting.

Pseudoaneurysm after pancreas transplantation can have serious consequences, including rupture, hemorrhage, and graft loss. We describe a 38-year-old patient who presented with a pseudoaneurysm of the donor superior mesenteric artery 1 month after pancreas transplantation. Selective arteriography was performed and the lesion was repaired with endovascular placement of a 28-mm covered stent. Laparotomy was avoided. The pancreatic graft was continuing to function well 9 months later. As far as we know, this minimally invasive approach was not previously reported. According to published series, pseudoaneurysms often occur secondary to infection and require operative intervention necessitating graft pancreatectomy. Patients can present with serious symptoms including hypotension and shock. Therefore, it is important to detect pseudoaneurysm in a timely manner. Computed tomography and Doppler ultrasound are important diagnostic tools in this regard. We demonstrated the utility of endovascular stenting in the treatment of pseudoaneurysm after pancreas transplantation. When used in a timely manner in well selected patients, endovascular stenting can abrogate the need for operative intervention and its attendant morbidity.

Adult↗