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Biomedical subjects

E Yap

Publications and source records attributed to E Yap.

12 recordsLinked to original sources

Academic achievement, close up work parameters, and myopia in Singapore military conscripts.

AIM: To determine the relation of refractive error to environmental factors, including close up work, in Singapore military conscripts. METHODS: A cross sectional study was conducted on 429 Singapore military conscripts. Non-cycloplegic refraction and A-scan biometry were performed in both eyes. A detailed questionnaire was administered by in-person interview to obtain information about current and past near work activity, extra tuition lessons, educational experiences, and family demographics. RESULTS: Myopia associated with the conscript having been educated in the (gifted, special, or express) educational streams (adjusted odds ratio (OR) = 3.8, 95% confidence interval CI 2.0-7.3), and having completed pre-university education (OR=4.1, 95% CI 1.9-8.8). The reported close up work activity at age 7 years did correlate with age of onset of myopia (p<0.001). In parallel, supplemental tuition lessons in primary school has (OR=2.6, 95% CI 1.4-4.9) associated with conscript myopia. Parental myopia was positively associated with myopia (p<0.001), but this relation disappeared when adjusted for environmental factors. Current (p=0.83) and past close up work activity at age 7 years (p=0.13) did not correlate with myopia. CONCLUSION: Educational level and educational stream positively related to myopia. A relation was observed with reported close up work activity in early childhood and with tuition classes during elementary school, but not with current close up work activity. These results underscore the strong influence of environment in myopia pathogenesis but a role for close up work activity remains indeterminate.

Adult↗

Myopia: gene-environment interaction.

INTRODUCTION: Myopia has reached epidemic proportions in Japan, Hong Kong, Taiwan and Singapore. This review summarises the evidence for environmental and genetic factors as well as gene-environment interaction for myopia for both epidemiologic studies as well as animal models. METHODS: A literature review was conducted after a Medline search on articles on the genetic or environmental aetiology of myopia in animal or epidemiologic studies. Articles on the methodology of gene-environment studies were also reviewed. All articles reviewed were articles published in peer-reviewed journals. RESULTS: Cross-sectional studies have found a positive association between myopia and near work activity such as reading and writing. Likewise, laboratory research has shown that environmental factors such as visual deprivation may lead to the development of myopia in animals. While linkage studies in humans are currently being conducted to identify possible markers for myopia in the human genome, several neurotransmitters, modulators and growth factors that influence refractive development have already been identified in animal models that may help identify candidate genes. Epidemiologic studies have also evaluated the combined effects of hereditary factors, environmental factors and gene-environment interaction on myopia development. CONCLUSIONS: Both genes and environmental factors may be related to myopia. There are no conclusive studies at present, however, that identify the nature and extent of possible gene-environment interaction. Further linkage analysis, affected sib-pair studies, and family-based association studies may better identify the nature of gene-environment interaction.

Animals↗

Cauda equina syndrome after spinal anaesthesia in a patient with severe vascular disease.

PURPOSE: Spinal anaesthesia is selected for many lower extremity surgical procedures each year in the United States with a high degree of safety and efficacy. Even when adverse neurological outcomes have occurred, anatomical abnormality or coagulopathy have been implicated in the majority of cases. Epinephrine is used in high concentrations in many of these anaesthetics to increase the duration and intensity of the block. Although epinephrine is known to decrease spinal cord blood flow, its use in normal patients has not caused complications. We report a case where spinal anaesthesia with bupivacaine and epinephrine resulted in anterior spinal artery compromise and the development of a cauda equina syndrome postoperatively. CLINICAL FEATURES: A 57-yr-old man with severe coronary artery and peripheral vascular disease was scheduled for incision and drain of an abscess of the left thigh. He received an atraumatic dural puncture and injection of 12.5 mg bupivacaine with 0.2 ml 1:1000 epinephrine. During onset, he experienced a severe, painful sensation of the thighs which resolved with development of the block. Postoperatively, he was noted to have exacerbation of proximal muscle weakness and decreased perineal sensation and rectal tone. Subsequent EMG studies demonstrated proximal neuron loss consistent with cauda equina syndrome, presumed to be related to insufficiency of the anterior spinal artery. CONCLUSION: Routine use of epinephrine in spinal anaesthesia for patients with multi-organ vascular disease should be considered carefully because of the possibility of vascular insufficiency of the spinal cord which would be exaggerated by the vasoconstrictive effect of epinephrine.

Anesthesia, Spinal↗

Molecular genetic analysis of TGF-beta1 in ovarian neoplasia.

Malignant ovarian tumours have been associated with a loss of autocrine growth inhibition by transforming growth factor-beta. This study aimed to detect abnormalities in the gene structure, expression and localization of TGF-beta1, in paraffin-embedded samples from 31 ovarian neoplasias (21 malignant, 5 borderline and 5 benign). Gene mutations in the region coding for the active protein were detected by PCR-SSCP analysis of exons 5, 6 and 7. mRNA expression and localization was studied by nonisotopic in situ hybridization (NISH) using cDNA probes generated by the reverse transcriptase polymerase chain reaction (RT-PCR), and immunohistochemistry, using antibodies against both intracellular and extracellular (matrix-associated) forms of TGF-beta1. Four mutations were found: one in exon 6 (serous adenocarcinoma), one in exon 7 (Mullerian tumor), and two in exons 5 and 6 from a serous cystoadenoma. TGF-beta1 mRNA was expressed in 87% and proteins in 90% of ovarian tumours. Most tumours expressing large amounts of TGF-beta1 mRNA, also contained a large number of protein binding sites. In malignant tumors, TGF beta1 was more strongly expressed in high-grade ovarian carcinomas with a cystic-papillary pattern than in tumours with a solid growth pattern. Normal ovarian tissue (follicles, granulosa cells) adjacent to tumor showed weak epithelial labeling and staining. Gene mutation did not correlate with histological type of tumor, mRNA or protein expression. TGF-beta1 mutation and abnormalities in its expression seem to occur in benign and malignant ovarian tumors, and could be involved in their pathogenesis. TGF beta1 gene mutations may act in multistage ovarian neoplasia, by reducing epithelial cell responsiveness to TGF-beta1 negative growth control.

Adenocarcinoma↗

Molecular genetic analysis of TGF beta1 in breast cancer.

Conflicting data suggest that TGF-beta1 can either inhibit or promote the progression of breast cancer. To determine the biological role of TGF beta1 in mammary carcinoma, in this study we examined the gene structure, expression and localization of TGF-beta1 using paraffin-embedded samples from 32 (27 IDC, 1 ILC, 1 DCIS, 1 ADH) breast lesions. Gene mutations in the region coding for the active protein were investigated by PCR-SSCP of exons 5, 6, and 7. mRNA -TGF-beta1 expression and distribution was examined by NISH using cDNA probes generated by RT-PCR and immunohistochemistry. We detected two mutations in exon 6 TGF-beta1 from IDC; and TGF beta1 mRNA and proteins in 28 (87%) of the tumors. Invasive breast carcinomas had more intense TGF-beta1 activity than CIS and than normal tissue adjacent to tumor. TGF beta1 mRNA and proteins were higher at the edge of the tumor than in the center and were also higher in less differentiated breast neoplasms. TGF-beta1 mRNA transcription and protein levels did not correlate either with TGF-beta1 exon 6 mutation or type and grade of differentiation of breast tumors. These observations suggest that TGF beta1 mutations in breast neoplasms might cause loss or inactivation of the growth inhibitory effects of TGF-beta1. They also support the proposed role of TGF-beta1 in the pathogenesis of breast cancer.

Breast Neoplasms↗

TGF-beta1 in colonic neoplasia: a genetic molecular and immunohistochemical study.

Transforming growth factor-beta proteins are key regulators of cellular growth and differentiation. To understand the role of TGF-beta in colonic tumour progression, 47 paraffin embedded samples from colonic tumours (13 adenomas, and 34 adenocarcinomas) were studied. Gene mutations in the region coding for the active protein were studied by PCR SSCP analysis of exons 5, 6, and 7. TGF-beta1 mRNA expression and localization were studied by NISH using cDNA probes generated by RT-PCR. Protein distribution was investigated by immunohistochemistry using antibodies against both intracellular and extracellular forms. Three mutations were found: one in exon 5 (Dukes C) and two in exon 7 (Dukes C and A). TGF-beta1 mRNA was observed in 9 (69%) of 13 adenomas and in 30 (88%) of 34 adenocarcinomas. Levels of TGF-beta1 mRNA and proteins were higher in colorectal carcinomas than in colorectal adenomas. Tubular adenomas associated with dysplasia showed greater expression of TGF-beta1 than adenomas without dysplasia and than non-neoplastic colonic mucosa. In dysplasia and cancer, epithelial neoplastic cells and stromal cells were positive for TGF-beta1. In normal tissue endothelial cells and granulocytes sporadically showed immunoreactivity for TGF-beta1, whereas epithelial cells were all negative. The three mutations in TGF-beta1 exons 5, 6 and 7 found in colorectal adenocarcinomas suggest that TGF-beta1 mutation may play a role in colorectal carcinogenesis and that the presence of the mutant form contributes to the transformed state. Our two other findings, the loss of staining gradient in normal colonic mucosa and the higher levels of TGF-beta1 mRNA and proteins in colorectal carcinomas than in colorectal adenomas, indicate that the de-regulation of TGF-beta1 expression may occur as an early event in colorectal carcinogenesis. Although TGF-beta1 expression is generally a reflection of cellular differentiation, tumour grade is not associated with TGF-beta1 mRNA expression. Beside being present in the epithelial cells of the colonic tumours, TGF-beta1 mRNA also occurred in the stroma: its localization in the macrophages adjacent to tumour strongly suggests that TGF-beta1 could be secreted by macrophages. This hypothesis should lead to new therapeutic strategies for colorectal carcinoma.

Adenocarcinoma↗

Increased expression of the cyclin D1 gene in Barrett's esophagus.

Previous studies have found a 3-10-fold amplification and overexpression of the cyclin D1 gene in about 32% of human esophageal squamous cell carcinoma. The purpose of this study was to evaluate the prevalence of increased expression of the cyclin D1 protein in Barrett's esophagus. Using 69 formalin-fixed and paraffin-embedded human esophageal specimens, which had been removed endoscopically or obtained at surgery during 1993 and 1994, all immunohistochemical analyses were performed using an avidin-biotin complex immunoperoxidase technique. Increased nuclear expression of the cyclin D1 protein was noted in 32 of 69 samples (46%; 44% of the samples from males and 50% of the samples from females). Positive nuclear staining for the cyclin D1 protein in Barrett's disease with intestinal metaplasia was found in 38% of the male cases and 25% of the female cases, whereas in gastric metaplasia it was positive in 33% of men and 48% of women. Nuclear accumulation of the cyclin D1 protein was also found in both dysplastic and nondysplastic lesions, and it was not associated with sex, age, or cigarette or alcohol consumption. Samples from patients taking proton pump inhibitors tended to be less frequently positive (32%) for cyclin D1 nuclear staining when compared to patients taking H2 antagonists (45%) or antacids (55%). These studies suggest that increased expression of cyclin D1 is an early event in the tumorigenic process of esophageal adenocarcinomas and that the increased expression of this gene might predispose the epithelium to malignant transformation.

Adenocarcinoma↗

Simultaneous double-isotope autoradiographic measurement of local cerebral glucose metabolic rate and acid-base status in rat brain.

We developed a double-isotope autoradiographic method for the simultaneous measurement of the local cerebral metabolic rate for glucose (1CMRG) and index of regional acid-base status (rABI) in single brain slices using [2-14C]deoxy-D-glucose (DG) and 5,5-dimethyl-[2-14C]oxazolidine-2,4,dione (DMO). After iv isotope administration, paper chromatography separates plasma DMO from DG activity using a methanol-methylene chloride solvent system. Initial tissue autoradiograms depict regional DMO plus DG and DG metabolite distribution. After 14 days in a well-ventilated hood, 97.5 +/- 0.5% of all DMO is lost from tissue sections by sublimation, and a second autoradiogram depicts DG plus DG metabolite distribution. Retention of brain lipids does not alter beta-particle self-absorption, avoiding problems associated with isotope extraction with solvents. Autoradiograms are digitized and converted to isotope-content images. The second autoradiogram is used for 1CMRG computation. After subtracting the second regional isotope-content value from the first, the DMO content is obtained and used to compute rABI. Application of this method to normal animals yields expected values for 1CMRG and rABI. This method is amenable to whole-slice digitization and creation of functional images of 1CMRG and ABI followed by pixel-by-pixel correlations of the two variables, making this a potentially valuable tool for the investigation of the relationships between glucose metabolism and brain acid-base balance.

Acid-Base Equilibrium↗

An unusual cause of acute chest pain during epidural anesthesia.

BACKGROUND AND OBJECTIVES: Selective sympathetic denervation during epidural anesthesia results in a small, active gut. These changes can also result in selective activity in one segment of the gut that is absent in other segments. CASE REPORT: A 61-year-old male was scheduled for bilateral total knee replacement during epidural anesthesia. Following onset of the epidural block, he experienced severe left-sided chest pain. Surgery was canceled. A portable chest radiograph revealed a widened mediastinum, and he underwent angiography to rule out a dissecting thoracic aortic aneurysm. The left subclavian artery could not be visualized, and an MRI was obtained, which was normal. After his return to the intensive care unit, he had a large bowel movement and his chest pain resolved. CONCLUSION: Selective activity of the gastrointestinal tract during the onset of epidural anesthesia created a visceral pain, which effectively simulated pain with a cardiovascular origin.

Anesthesia, Epidural↗