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Biomedical subjects

T L Yang

Publications and source records attributed to T L Yang.

At least 19 recordsLinked to original sources

Metastatic angiosarcoma to the thyroid.

BACKGROUND: Angiosarcoma (AS) in non-alpine areas is exceptionally rare, and so is metastatic AS to the thyroid. The difficulties and controversies associated with its diagnosis and management are highlighted in this case report. METHOD: Case report. RESULTS: A Chinese gentleman with AS metastatic to the thyroid presented a year after radiotherapy to his scalp AS. There was rapid expansion of the metastasis over 2 weeks and invasion of the pyriform fossa caused dysphagia and haemoptysis. The diagnosis was established by paraffin histology of the tumour post-hemithyroidectomy, after repeated fine-needle aspiration cytology was not diagnostic. Patient opted for external beam radiotherapy to the pyriform fossa instead of pharyngolaryngectomy. Residual pyriform tumour was treated with brachytherapy delivered via nasogastric tube. Unfortunately, the patient died 4 months later due to cardiac failure which was unrelated to his oncologic condition. CONCLUSION: AS metastatic to the thyroid is possible. The unexpectedly acute presentation and difficulties associated with diagnosis and management are highlighted. A useful method of delivering brachytherapy to the pyriform fossa is described.

Aged↗

Abnormality of the DNA double-strand-break checkpoint/repair genes, ATM, BRCA1 and TP53, in breast cancer is related to tumour grade.

The role of the DNA double-strand-break (DSB) checkpoint/repair genes, ATM, BRCA1 and TP53, in sporadic breast cancer requires clarification, since ATM and BRCA1 mutations are rare in sporadic tumours. In an attempt to explain this phenomenon, we postulated that (i) in addition to genetic deletion, abnormal expression of DSB checkpoint/repair proteins might abolish the function of these genes and (ii) there might be a combined effect of individual defective genes during breast cancer pathogenesis. Using a largely homogenous group of 74 specimens of early-onset (< or =35 years of age) infiltrating ductal carcinomas, we examined associations between pathological grade and genetic deletion and/or abnormal protein expression of ATM, BRCA1 and TP53. The results showed that high-grade tumours displayed a high frequency of loss of heterozygosity (LOH) at, and/or abnormal expression of, ATM, BRCA1 and TP53. Multigenetic analysis showed abnormalities in BRCA1 to be independently associated with high-grade tumours. ATM and TP53 appeared to play an assistant role, abnormalities in these genes significantly increasing the possibility of poor differentiation in tumours with abnormalities in BRCA1. Furthermore, a higher number of abnormalities (LOH or abnormal expression) in these three genes correlated with poor tumour differentiation. Thus, this study suggests that combined changes in several DSB checkpoint/repair genes belonging to a common functional pathway are associated with breast cancer pathogenesis.

Adult↗

Intracranial germ cell tumour: experience of a Singaporean institution over 11-year period.

BACKGROUND: Intracranial germ cell tumours (IGCT) are rare. We present our experience in Therapeutic Radiology Department, National Cancer Centre, Singapore. METHODS: A retrospective study was conducted through case notes review on 25 patients with IGCT referred between January 1988 and January 1999. RESULTS: The median age at diagnosis was 13 years (range 6-22). The tumours were mainly pineal germinoma (72%). Median follow-up for living patients was 2.57 years (range 0.12-10.8). Median radiotherapy (RT) dose to whole brain, primary site and spine was 35.3,54 and 30 Gys respectively. Four to six cycles of BEP or JEB chemotherapy (CM) were given in 10 patients. As for the whole study group, the seven-year overall survival (OS) and recurrence-free survival (RFS) were 86% (95% CI 72-100) and 78% (95% CI 60-100) respectively. The 10-year OS and RFS were 65% (95% CI 36-100) and 78% (95% CI 60-100) respectively. The germinoma group had 75% 10-year OS and 86% 10-year RFS. Mixed germinoma and non-germinoma germ cell tumours (NGGCT) group had 50% one-year RFS and 44% two-year OS. Acute side-effects of RT and CM were minimal. There was no statistically significant difference in side-effects when treatment modalities were compared. CONCLUSION: In the treatment of intracranial germinoma, we recommend biopsy and CSRT. Primary chemotherapy (+/- low-dose cranial RT) should be used in the protocol or clinical trial settings. Chemo-radiotherapy is recommended for mixed germinoma and NGGCT. A multicentre trial is needed to address various controversial issues.

Adolescent↗

Recurrent nasopharyngeal carcinoma presenting as diffuse dermal lymphatic infiltration in the neck: three case reports.

BACKGROUND: Any malignancy has the propensity to metastasize to skin. The frequency of skin metastases vary in different tumors and occur in about 0.7% to 10% of all patients diagnosed with cancer. It is rare in nasopharyngeal carcinoma. METHOD: Three cases of relapsed nasopharyngeal carcinoma with diffuse dermal involvement were described. Their clinical presentation, results of investigations, and response to treatment were reviewed. Literature review of similar forms of presentation was done by means of a MEDLINE search. RESULTS: At the time of dermal relapse, all three patients had a uniform clinical picture of facial, periorbital, and lip swelling associated with stridor and dysphagia. Histologic findings showed dermal infiltrates of malignant cells, and CT scan showed diffuse infiltration of the subcutaneous tissue. Despite chemotherapy, the clinical course was relentless. CONCLUSION: This report describes a presentation of disease that is underdiagnosed and heightens awareness of oncologists to this form of recurrence in nasopharyngeal carcinoma.

Adult↗

Use of pulsed-field gel electrophoresis to investigate an outbreak of Serratia marcescens infection in a neonatal intensive care unit.

Serratia marcescens is a well-recognized hospital-acquired pathogen, which has been associated with a number of specific outbreaks, particularly in critically ill neonates. We used pulsed-field gel electrophoresis (PEGE) typing to analyse an outbreak in a neonatal intensive care unit (NICU). We included samples from nine patients, three handwashes and ten environmental isolates from an outbreak (February to August 1999) in addition to four patient isolates from different wards of our hospital during the same time period. The clinical presentations of the outbreak included bacteraemia (four cases), pneumonia (three cases), umbilical wound infection (one case) and conjunctivitis (one case). Nine outbreak isolates exhibited an identical PFGE fingerprint, while the epidemiologically unrelated strains demonstrated distinct patterns. Epidemiological investigation failed to reveal a common source of the outbreak, although the epidemic S. marcescens strain was isolated from hand-washes and doors of incubators. We concluded that cross-transmission via transient contamination of hands was the major route for this outbreak. Strict handwashing practices, the cohorting and isolation of colonized and infected patients, and the regular dis-infection of incubators are crucial steps for preventing the transmission of S. marcescens in an NICU. This PFGE method is highly discriminatory for the thorough epidemiological investigation of an outbreak of S. marcescens.

Cross Infection↗

Nasal schwannoma: a case report and clinicopathologic analysis.

According to the literature, half of the schwannoma cases occur in the head and neck areas and only less than 4% occur in the sinonasal tract. In this case, a 39-year-old male patient, with a-year-long progressive left side nasal obstruction and purulent rhinorrhea, is presented. The CT reveals a mass filling the left nasal cavity and nasopharyngeal space, with bony erosion of the inferior turbinate and medial maxillary bone. During surgical intervention, the mass is found to originate from the medial side of the left middle turbinate with maxillary sinusitis and inferior turbinate atrophy. The pathological examination reveals a noncapsulated tumor with palisading cellular arrangement and high cellular density. The pathological findings and nervous origin of the tumor are discussed after an extensive review of the literature.

Humans↗

Spontaneous thrombosis in mice carrying the factor V Leiden mutation.

A polymorphism in coagulation factor V, factor V Leiden (FVL), is the major known genetic risk factor for thrombosis in humans. Approximately 10% of mutation carriers experience clinically significant thrombosis in their lifetime. In a small subset of patients, thrombosis is associated with coinheritance of other prothrombotic gene mutations. However, the potential contribution of additional genetic risk factors in the majority of patients remains unknown. To gain insight into the molecular basis for the variable expressivity of FVL, mice were generated carrying the homologous mutation (R504Q [single-letter amino acid codes]) inserted into the endogenous murine Fv gene. Adult heterozygous (FvQ/+) and homozygous (FvQ/Q) mice are viable and fertile and exhibit normal survival. Compared with wild-type mice, adult FvQ/Q mice demonstrate a marked increase in spontaneous tissue fibrin deposition. No differences in fetal development or survival are observed among FvQ/Q, FvQ/+ or control littermates on the C57BL/6J genetic background. In contrast, on a mixed 129Sv-C57BL/6J genetic background, FvQ/Q mice develop disseminated intravascular thrombosis in the perinatal period, resulting in significant mortality shortly after birth. These results may explain the high degree of conservation of the R504/R506 activated protein C cleavage site within FV among mammalian species and suggest an important contribution of other genetic factors to the thrombosis associated with FVL in humans. (Blood. 2000;96:4222-4226)

Activated Protein C Resistance↗

Rescue of fatal neonatal hemorrhage in factor V deficient mice by low level transgene expression.

Factor V (FV) is a critical component of the coagulation cascade. FV-deficient patients suffer moderate to severe bleeding, though residual FV activity is detectable in nearly all cases. In contrast, FV-deficient mice die either during mid-embryogenesis, or of massive perinatal hemorrhage. In order to examine the requirements for FV in murine embryogenesis and hemostasis, we generated transgenic mouse lines expressing a Fv minigene under control of either the tissue-specific albumin (Malb) or rat platelet factor 4 (Rpf4) promoter. A total of 12 Malb and 3 Rpf4 lines were analyzed. Though expression in the target tissue was detectable in most lines by RT-PCR, only low levels of transgene expression were achieved (<3% of endogenous Fv in all lines). Despite a low level of Fv transgene expression, rescue of the lethal Fv-/- phenotype was observed with one of the Malb transgenic (Tg+) lines. However, rescue appeared to be incomplete with continued loss of >1/2 of expected Tg+,Fv-/- mice in early embryogenesis. Rescued Tg+,Fv-/- mice have undetectable FV (<0.1%) in both plasma and platelet compartments, but survive the perinatal period and mature to adulthood without spontaneous hemorrhage. We conclude that FV present at <0.1% is sufficient to support postnatal survival. Failure of the Malb transgene to rescue the midembryonic block suggests that FV expression is required during mammalian development at higher levels or with a different tissue-specific or temporal pattern. Taken together, these data may explain the observation of residual FV activity in most human FV-deficient patients due to early embryonic lethality in those absolutely deficient, and suggest that minimal levels of FV expression, below the level of detection, also may be sufficient to support survival in humans.

Acute Disease↗

Prognostic factors in 677 patients in Singapore with nondisseminated nasopharyngeal carcinoma.

BACKGROUND: The objective of the current study was to describe the survival of nasopharyngeal carcinoma (NPC) patients in Singapore, verify the prognostic value of the revised 1997 TNM staging system, and develop a multivariate prognostic model for NPC. In addition, the authors also examined the prognostic value of characteristics of lymph node spread and parapharyngeal involvement. METHODS: A prospectively maintained database containing clinical and computed tomography scan data was used to reclassify 677 NPC patients treated between 1992 and 1994 according to the new staging system. Records were linked with the death registry to ascertain the patient's vital status and date of death. Overall and stage specific survival were analyzed using the Kaplan-Meier method and the log rank test. Univariate and multivariate Cox proportional hazards regression analysis were used to obtain prognostic models. RESULTS: Two hundred seventy-four deaths (40.5%) occurred. The 5-year survival rate was 56.6% (95% confidence interval [95% CI], 52.3%, 60.7%). The stage specific 5-year survival rates were: Stage I, 88%; Stage IIA, 75%; Stage IIB, 74%; Stage III, 60%; Stage IVA, 35%; and Stage IVB, 28%. TNM stage was found to be a statistically significant prognostic factor (P < 0.0001). Cranial nerve (hazard ratio [HR]: 2.77), orbit (HR: 5.71), and intracranial involvement (HR: 2.46) conferred a particularly bad prognosis in univariate analysis. Independently significant prognostic factors were age; lymph node status; and paraoropharyngeal, cranial nerve, orbit, and nasal involvement. Among lymph node positive patients, independently significant prognostic lymph node characteristics were Ho level and laterality. Although parapharyngeal involvement appeared to be prognostically unimportant, paraoropharyngeal involvement distinguished a subgroup with a poorer prognosis (HR: 1.84; 95% CI, 1.45, 2.34; P < 0.0001). Lateral spread to the medial infratemporal fossa and beyond also was found to confer a poorer prognosis. CONCLUSIONS: The results of the current study show that the revised 1997 TNM staging system is prognostically useful. Subdivision into paraoropharyngeal involvement and using the medial infratemporal fossa to delineate prognostically significant lateral spread should be considered in future revisions.

Adolescent↗

Transient apoptosis elicited by insulin in serum-starved glioma cells involves Fas/Fas-L and Bcl-2.

The expression of fas gene in glioma cells varies with growth stage. When insulin-elicited transient apoptosis of glioma cells was in progress, the expression of fas gene increased at both transcriptional and translational levels. In contrast, the expression of fas-L gene in glioma cells remained constant. Apoptosis occurred in the cells having high level of surface Fas protein. When the expression of Fas-L in U-373MG cells was suppressed by ribozyme, the insulin-elicited transient apoptosis vanished. Overexpression of Bcl-2 in U-373MG cells did not alter significantly the cell cycle progression and the expression of fas gene. However, these cells were resistant to insulin-trigged death. Therefore, insulin-elicited apoptosis involved Fas-related death signal, and which could be prevented by the protective effect of Bcl-2.

Antigens, Surface↗

Phase II trial of a paclitaxel and carboplatin combination in Asian patients with metastatic nasopharyngeal carcinoma.

PURPOSE: An earlier phase II trial of paclitaxel in patients with metastatic nasopharyngeal carcinoma (NPC) demonstrated a response rate of 22%. Hence we proceeded to study the combination of paclitaxel and carboplatin in these patients. PATIENTS AND METHODS: The 21-day regimen was as follows: i.v. paclitaxel 175 mg/m2 over three hours preceded by standard premedications, followed by i.v. carboplatin dosed at AUC of six infused over one hour. Only chemotherapy-naive patients with histological diagnoses of undifferentiated carcinoma of the nasopharynx, systemic metastases and radiologically measurable lesions were eligible. RESULTS: Thirty-two patients were accrued to this study. Twenty patients (62%) had at least two sites of metastasis. The main grade 3-4 toxicity was neutropenia (31%). Nine patients (28%) developed neutropenic sepsis, which caused the demise of one of them. Twenty-four patients (75%) responded to treatment, with one (3%) attaining a complete response. The median time to progression of disease was seven months and the median survival was 12 months. At one year, 52% of the patients were alive. CONCLUSIONS: The combination of paclitaxel and carboplatin is an active regimen in NPC. Its convenience of administration and good tolerability make it an attractive alternative regimen to consider for patients with metastatic disease.

Adult↗

The removal of beta-2-microglobulin by an immunoadsorption wall.

The accumulation of beta-2-microglobulin (beta2M) in collagen-rich tissues has been proven to be the main cause of dialysis related amyloidosis. However, it remains uncertain which technique for the removal of beta2M can be used without compromising the advantages of other dialysis strategies. A new concept, an immunoadsorption wall, which combines the principles of immunoisolation and immunoadsorption is proposed to remove beta2M. The present investigations suggested that the application of the concept to clinical use is feasible and worthwhile. The concept, if validated, will help shape a novel multitask type of artificial kidney based on the combination of different separation technologies.

Antibodies↗

Seeing big things: overestimation of heights is greater for real objects than for objects in pictures.

In six experiments we demonstrate that the vertical-horizontal illusion that is evoked when viewing photographs and line drawings is relatively small, whereas the magnitude of this illusion when large objects are viewed is at least twice as great. Furthermore, we show that the illusion is due more to vertical overestimation than horizontal underestimation. The lack of a difference in vertical overestimation between pictures and line drawings suggests that vertical overestimation in pictures depends solely on the perceived physical size of the projection on the picture surface, rather than on what is apparent about an object's represented size. The vertical-horizontal illusion is influenced by perceived physical size. It is greater when viewing large objects than small pictures of these same objects, even when visual angles are equated.

Humans↗

Small functional adrenal cortical adenoma: treatment with CT-guided percutaneous acetic acid injection--report of three cases.

Two patients with Conn syndrome and one patient with Cushing syndrome underwent computed tomography (CT)-guided tumor ablation with a total of 5-11 mL of 50% acetic acid injected into their adrenal nodule (1.3-3.3 cm in diameter). No major complications were encountered during or after the procedure. All patients were symptom free with normal laboratory test results for at least 1-year follow-up. CT images showed complete cystic change with tumor size regression. Our preliminary results suggest that percutaneous acetic acid injection is a safe and effective alternative for treatment of small functional adrenal cortical adenoma.

Acetic Acid↗

Primary carcinoma of the gallbladder: results of surgery--a retrospective study.

BACKGROUND: The development of hepatobiliary imaging modalities has resulted in earlier detection of gallbladder cancer. This is a retrospective evaluation of surgical resection of gallbladder cancer. METHODS: Records of 58 patients with gallbladder carcinoma who underwent surgical resection in the past 14 years were examined. Patients were staged according to the Nevin system: six had Nevin stage I disease; 10, stage II; 9, stage III; four, stage IV; and 24 had stage V cancer. Forty-three patients were thought to have resectable lesions. Of these, 14 had extended cholecystectomy, 21 simple cholecystectomy, seven simple cholecystectomy with biliary drainage and one patient had radical cholecystectomy with pancreaticoduodenectomy. Prognoses were analyzed in relation to pathologic staging and surgical procedures. RESULTS: The overall one-year and five-year survival rates were 50% and 19.2%, respectively. The five-year survival rate for Nevin stage I was 100%; for stage II, 60%; stage III, 33%; stage IV, 25% and for stage V, 0%. Radical surgery led to a better cumulative survival rate for Nevin stages III and IV (p < 0.01) than did simple cholecystectomy. Five Stage II cases were treated with simple cholecystectomy but two patients had early metastasis. Four stage III patients underwent simple cholecystectomy and three had metastasis within one year. CONCLUSIONS: Based on these results, stage III and IV tumors require extended procedures for better survival. A high index of suspicion for the disease, careful intraoperative examination of the gallbladder specimen and earlier, more aggressive treatment may improve patient survival.

Adult↗

Nosocomial gram-negative bacteremia in critically ill patients: epidemiologic characteristics and prognostic factors in 147 episodes.

Although gram-positive organisms are the most common causes of nosocomial bloodstream infections, gram-negative bacteremia carries higher risks of severe sepsis, septic shock, and death among critically ill patients in intensive care units (ICUs). We performed a prospective epidemiologic analysis of nosocomial gram-negative bacteremia episodes among ICU patients and sought to identify risk factors for mortality among these patients. All episodes of nosocomial gram-negative bacteremia documented in five ICU wards of our hospital during a 2-year period were included. There were 147 episodes (124 patients) of gram-negative bacteremia documented during the study period. The overall mortality rate was 36.1%, and 77.4% of all deaths were directly related to the bloodstream infection. Gram-negative bacteremia was associated with prolonged ICU stay (45.7 d vs 6.1 d for all ICU patients). The most common isolate was Acinetobacter baumannii, followed by Burkholderia cepacia and Enterobacter cloacae. The most frequent source of infection was the lower respiratory tract (32.0%). Of the agents tested, ciprofloxacin, imipenem, and ceftazidime were the most active against the clinical isolates. Multivariate logistic regression analysis identified the presence of septic shock (odds ratio, OR = 17.66, p < 0.001) and rapidly fatal and ultimately fatal underlying conditions (OR = 3.47, p = 0.032) as being independent risk factors for mortality. Early appropriate antibiotic treatment did not result in significant improvement in survival. These findings suggest that prevention of lower respiratory tract colonization and nosocomial pneumonia are crucial for reducing the incidence of nosocomial gram-negative bacteremia in the ICU. Serious underlying illnesses and septic shock were the most important risk factors for death in these patients.

Adult↗

Imaging diagnosis of insufficiency fracture of the sacrum.

BACKGROUND: Insufficiency fracture of the sacrum has been recognized as a major cause of lower back pain, especially in elderly osteoporotic patients with or without underlying malignancy and/or prior pelvic radiotherapy. Its diagnosis cannot be readily made from its nonspecific clinical features. Consequently some cases may be mistaken for bone metastases, causing patients to receive inappropriate diagnostic measures and management. Recognition of the spectrum of imaging features is the basis of correct diagnosis and treatment. METHODS: The imaging studies of 14 cases (12 women and 2 men; age range, 60-84 years; mean age, 70 years) of sacral insufficiency fracture were reviewed retrospectively. These included 14 radiographs, six bone scintigraphs, eight computerized tomography (CT) scans and 12 magnetic resonance (MR) imaging studies. Six patients had a history of malignancy. Diagnosis was made by characteristic imaging findings, and clinical and radiographic follow-up for one to 3.5 years. RESULTS: Five cases of sacral insufficiency fracture were suspected based on radiographic findings of fracture lines (2 cases) and focal sclerosis (3 cases). Seven cases were diagnosed by CT findings of linear fractures (7 cases) and focal sclerosis (2 cases). Nine MR examinations demonstrated characteristic vertical bands of marrow edema. A hypointense fracture line was identified in eight cases. The remaining two MR imaging studies disclosed nonspecific focal marrow edema. An early case, which appeared normal on CT scan, showed marrow edema on MR imaging. The positive and diagnostic rates were both 36% for plain radiographs, 88% for CT scans, and 100% and 83%, respectively, for MR images. CONCLUSIONS: Plain radiographs are often unrewarding. Although MR imaging is the most sensitive tool, fracture lines are best demonstrated and diagnosed using CT. Due to the better diagnostic rate, popularity and cost effectiveness, CT is recommended as the definitive modality for confirming diagnosis of insufficiency fracture of the sacrum.

Aged↗