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Biomedical subjects

S Y Chan

Publications and source records attributed to S Y Chan.

At least 19 recordsLinked to original sources

Assessing optimal fermentation type for bio-hydrogen production in continuous-flow acidogenic reactors.

In this study, the optimal fermentation type and the operating conditions of anaerobic process in continuous-flow acidogenic reactors was investigated for the maximization of bio-hydrogen production using mixed cultures. Butyric acid type fermentation occurred at pH>6, propionic acid type fermentation occurred at pH about 5.5 with E(h) (redox potential) >-278mV, and ethanol-type fermentation occurred at pH<4.5. The representative strains of these fermentations were Clostridium sp., Propionibacterium sp. and Bacteriodes sp., respectively. Ethanol fermentation was optimal type by comparing the operating stabilities and hydrogen production capacities between the fermentation types, which remained stable when the organic loading rate (OLR) reached the highest OLR at 86.1kgCOD/m(3)d. The maximum hydrogen production reached up to 14.99L/d.

Bacteria, Anaerobic↗

Synthesis of PHAs from waster under various C:N ratios.

Polyhydroxyalkanoates (PHAs) production was carried out under various C:N ratios. A ratio of 100 resulted best polymer yield. C-source was an important factor in synthesis. For example, as the ratio of valeric acid (C5) to butyric acid (C4) in N-free medium was increased, the mole fraction of HV in the copolymer increased. When soy waste was used as a C-source a copolymer, a high HV mole fraction (HB:HV, 75:25) was produced while when malt waste was used, a much lower HV mole fraction (HB:HV, 90:10) was generated. It was concluded that activated sludge bacteria could be induced to produce PHAs using food wastes as C-sources and this could be the basis for production of biodegradable plastics.

Alcaligenes↗

Multifocal venous malformations: two interesting case presentations.

INTRODUCTION: Multiple venous abnormalities involving the orbit, head and neck regions have been previously described. We present two similar cases of low-flow orbital venous vascular malformations (VVMs) in association with multiple low-flow VVMs in the head and neck as well as in the peripheral limb. Literature search revealed that this association has not been previously reported. METHODS: Retrospective review of two patients with multifocal VVMs was performed. RESULTS: Case 1: A 46 year-old Chinese female had a history of multiple vascular lesions involving the right orbit, the tongue, right neck region, right arm and one finger. Valsalva manoeuvre resulted in distension of these lesions. CT scan of the orbits demonstrated bilateral low-flow VVMs. CT angiogram also revealed multiple developmental venous anomalies in the brain. Case 2: A 16 year-old Chinese female had a history of multiple venous malformations involving the neck, left forearm and oral region. Dynamic manoeuvres demonstrated the distensible nature of these lesions. MRI scans of the orbits showed bilateral extraconal low-flow VVMs. Similar mass lesions were seen on MRI scans of the neck. CONCLUSIONS: Multiple cervicofacial venous malformations with developmental abnormalities of the intracranial venous system have been described previously. However, their associations with similar VVMs in the peripheral limb regions have not been reported. Our cases illustrate this rare association. VVMs appear to be benign in nature with symptoms mainly due to mass effect. Management can be conservative in the absence of any sight threatening complication.

Adolescent↗

Laser ablation of foetal microcystic lung lesion: successful outcome and rationale for its use.

OBJECTIVE: A foetus with an echodense, microcystic lung lesion complicated by non-immune hydrops has a high mortality rate. Because of the limited treatment options available, laser ablation was offered in an attempt to reduce the size of the lesion and reduce hydrops fetalis. METHODS AND RESULTS: A 25-year-old nulliparous woman presented at 21 weeks gestation. Ultrasound revealed a male foetus with a large microcystic right sided lung lesion that completely occupied the right hemithorax causing marked mediastinal deviation. The foetus was hydropic with polyhydramnios. Percutaneous laser ablation of the large microcystic lung lesion was performed under direct ultrasound control. At a power setting of 45 W, and using a 400 microm Nd:YAG laser fibre, the core of the lesion was photocoagulated in pulses lasting 5 s at 5 s intervals. The total target dose was 1683 J. This led to a marked but temporary reduction in amniotic fluid volume. The patient was commenced on sulindac and amniodrainage was performed at 27 weeks as reaccumulation of the polyhydramnios occurred. Pre-eclampsia complicated the pregnancy at 38 weeks gestation and an emergency caesarean section was performed. The baby underwent a thoracotomy and lobectomy at 48 h of age, made a good recovery, and is currently well 8 weeks post-delivery. CONCLUSIONS: In cases of cystic lung lesion complicated by hydrops, laser ablation should be considered as a treatment option.

Adenoma↗

SMGA gels for the skin permeation of haloperidol.

Small molecule gelling agent (SMGA) gels were developed using the gelator GP-1 in the solvents, namely, isostearyl alcohol (ISA) and propylene glycol (PG), to deliver haloperidol through the skin. The concentrations of the drug, haloperidol, the enhancer, farnesol and the gelator, GP-1 are 3 mg/ml, 5% (w/v) and 5% (w/v), respectively. The study employed a three-factor full factorial statistical design to investigate the influence of factor level changes on the permeability coefficient and permeation lag-time of haloperidol. Gels were prepared by raising temperature to 120 degrees C, followed by natural cooling under room temperature of 22+/-1 degrees C. The rheological properties of the gels were examined with a strain-controlled dynamic mechanical method. The in vitro permeation study was conducted with automated flow-through type cells. The gels successfully incorporated the drug and enhancer without losing their aesthetic properties. The in vitro human skin permeation study showed the permeation of the drug in ISA-based gels reached the pseudo steady state faster than PG-based gels and were less affected by gelator. PG-based gels delivered the drug at a faster rate with the incorporation of the enhancer. GP-1 did not influence the drug permeation rate but it increased permeation lag-time. The co-existence of gelator or enhancer increased the lag-time to a larger extent than when used separately. The novel SMGA gels are suitable for topical or transdermal delivery.

Administration, Cutaneous↗

Conditioned medium from keloid keratinocyte/keloid fibroblast coculture induces contraction of fibroblast-populated collagen lattices.

BACKGROUND: Keloid scars represent a pathological response to cutaneous injury. Overproliferation of fibroblasts and overproduction of collagen characterize these abnormal scars. The pathology of these scars remains poorly understood. The role of epithelial-mesenchymal interactions in keloid pathogenesis and scar contracture has recently been explored. OBJECTIVES: To test our hypothesis that epithelial-mesenchymal interactions play a major role in modulating keloid scar contracture. METHODS: A coculture model was employed wherein keloid and normal keratinocytes were cocultured with keloid or normal fibroblasts, and the conditioned media from day 5 cocultures were collected to study the effect of the paracrine secretions on contraction of an in vitro fibroblast-populated collagen lattice (FPCL) model. RESULTS: Keloid keratinocyte/keloid fibroblast coculture conditioned media brought about increased contraction of the collagen lattice compared with non-cocultured conditioned media. When keloid fibroblasts populated the collagen lattice, significantly increased lattice contraction was induced compared with lattices populated by normal fibroblasts. The addition of antitransforming growth factor (TGF)-beta neutralizing antibody to the conditioned media produced an attenuation of the contraction of the FPCLs. When keloid and normal fibroblasts were cultured on chamber slides and treated with conditioned media from coculture and non-coculture series, immunohistochemical analysis demonstrated an increased expression of alpha-smooth muscle actin (a marker for fibroblast differentiation into myofibroblasts) in fibroblasts exposed to conditioned media from coculture. CONCLUSIONS: These data indicate that epithelial-mesenchymal interactions are likely to play a major role in scar contracture and scar pathogenesis, and underscore the role of TGF-beta1 as a key player in keloid pathogenesis.

Actins↗

Huge renal angiomyolipomas in tuberous sclerosis complex.

Tuberous sclerosis complex (TSC) is an autosomal dominance disorder with variable penetrance. Renal angiomyolipoma (AML) is one of the commonest urological manifestations. These lesions may cause significant morbidity and mortality. We report two patients with multiple and huge renal angiomyolipomas presenting with gross haematuria. They subsequently underwent unilateral nephrectomy. The difficulty in diagnosis and controversies in management will be briefly discussed.

Adolescent↗

The role of PTEN and its signalling pathways, including AKT, in breast cancer; an assessment of relationships with other prognostic factors and with outcome.

PTEN is a novel tumour suppressor gene located on chromosome 10. PTEN mutations are believed to exert their effects through the putative PI3K-AKT-mTOR signalling pathway. Specifically, loss of PTEN leads to activation of AKT, which in turn promotes anti-apoptotic and pro-cell cycle entry pathways believed to be essential in tumourigenesis. Whilst PTEN mutations are frequent in a variety of sporadic cancers and inherited cancer syndromes, it is not clear how frequently PTEN mutations and immunohistochemical loss of PTEN expression occur in sporadic breast cancer. This study used tissue microarrays (TMAs) to assess wild-type PTEN and pAKT immunohistochemical staining in 670 and 691 cases, respectively, of primary operable breast cancer. Scores of 0, 1, and 2 were given for negative, weakly positive, and strongly positive degrees of immunoreactivity, respectively. In addition, immunohistochemical assessment of epidermal growth factor receptor (EGFR), Her2, and proliferation by MIB1 expression was performed on the same TMAs and the scores were compared with those of PTEN and pAKT. Eight per cent of cases did not express wild-type PTEN. No correlation was observed between patient, tumour and outcome variables and PTEN. pAKT expression correlated inversely with adverse tumour variables such as tumour grade (p< 0.001) and correlated positively with ER status (p< 0.001). No correlation was seen between either PTEN or AKT and EGFR, Her2 or MIB1. No association of PTEN or pAKT was seen in Kaplan-Meier or multivariate analysis for overall survival. The results indicate that loss of PTEN expression is infrequent in breast cancer. PTEN and AKT do not appear to be prognostic markers. The study argues against the current model of a simple linear tumourigenic PTEN-PI3K-AKT-mTOR pathway in breast cancer. It also suggests that, in this group of breast cancers, the most common upstream regulator of AKT may be ER rather than PTEN, EGFR or Her2.

Adult↗

Metastatic carcinoma of the breast with tubular features: differences compared with metastatic ductal carcinoma of no specific type.

AIMS: To compare the metastatic pattern at presentation and the prognosis with metastases of 48 patients with carcinomas with tubular features (45 tubular mixed and three pure tubular) and 302 patients with tumours of ductal of no special type (DNST). MATERIALS AND METHODS: We carried out a retrospective study from a prospectively maintained database of all patients who developed metastatic disease from carcinoma of the breast in Nottingham, U.K., since 1997. We recorded site of first presentation with metastatic disease, radiological features, histological features and characteristics of the primary tumour. RESULTS: The group of patients with tubular features were older at metastatic presentation (63.9 years vs 59.6 years; P=0.012), had a longer disease-free interval (87 months vs 34 months: P<0.001) and a longer survival with metastases (P<0.002). This group were less likely to have liver metastases (23% vs 41%; P=0.028), in particular multiple liver metastases (50% vs 71%; P=0.015) than the patients with DNST. Other factors known to be associated with prolonged survival, such as low histological grade of the primary invasive tumour and positive oestrogen receptor (ER) status, were more common in the group of patients with tumours with tubular features (Grade 1: 33% vs 3%; Grade 2: 42% vs 25%; Grade 3: 25% vs 72%; P<0.001), (ER positivity 76% vs 52%; P=0.009). When patients with grade 2 tumours were compared, the age at metastatic presentation, disease-free interval and the presence of multiple liver metastases were still significantly different between the two groups. CONCLUSION: Patients with metastatic breast carcinoma with tubular features have a longer survival with metastases than patients with metastatic DNST carcinoma. This improved survival can be explained by better well-recognised prognostic features, such as metastatic site pattern, histological grade, ER status and disease-free interval.

Adenocarcinoma↗

Brain metastases from breast cancer: identification of a high-risk group.

AIMS: Brain metastases from breast cancer are an uncommon initial presentation of metastatic breast cancer, but brain metastases commonly occur later in women's metastatic illness. The aims of this study were to document the type, frequency, and temporal occurrence of brain metastases from breast cancer as well as the survival of women with such metastases, and to attempt to identify a subgroup of women at high risk of brain metastases who may benefit from pre-emptive medical intervention. MATERIALS AND METHODS: The radiological reports of all women presenting with metastases aged under 70 years who had subsequently died were examined. The type, frequency, temporal occurrence and survival with brain metastases were documented. Correlations were sought between the frequency of brain metastases and age at metastatic presentation, tumour grade, histological type and oestrogen receptor (ER) status. RESULTS: Of 219 patients who had died with metastatic disease and who were under 70 years of age at metastatic presentation, 49 (22%) developed brain metastases. The development of brain metastases was related to young age (P = 0.0002), with 43% of women under 40 years developing brain metastases. Brain metastases were more common in women whose tumours were ER negative (38%) compared with women with ER-positive disease (14%) (P = 0.0003). By combining age and ER status, it is possible to identify a group of women (age under 50 years and ER negative) with a 53% risk of developing brain metastases. This group included many women who had chemotherapy for visceral metastases, and 68% had either stable disease or disease response at other sites at the time of brain metastases presentation. CONCLUSION: It is possible to identify a subgroup of women with metastatic breast cancer at high risk of brain metastases who may benefit from pre-emptive medical intervention, such as screening or prophylactic treatment.

Adult↗

The use of topotecan for relapsed ovarian cancer in accordance with the National Institute for Clinical Excellence Guidance 2001: the Nottingham experience.

AIMS: The topoisomerase-1 inhibitor, topotecan, is an established chemotherapy agent for the treatment of relapsed ovarian cancer after the failure of platinum-based chemotherapy, and is an established treatment choice at first relapse. In line with National Institute for Clinical Excellence (NICE) guidance, topotecan has been used at Nottingham City Hospital for the last 2 years. MATERIALS AND METHODS: A retrospective audit, over the period September 2001 to September 2002, was carried out to assess response rates and side-effects for patients with relapsed ovarian cancer who were treated with topotecan. Twenty-five patients received topotecan as a 30-min intravenous infusion for 5 consecutive days, every 21 days. The starting dose was either 1.5 mg/m2/day (n = 22) or 1.25 mg/m2/day (n = 3). Patient response was monitored by physical examination and serological CA125 tumour marker level. Radiological assessment was by computed tomography. RESULTS: Eighteen (72%) patients had their previous platinum-based treatment less than 6 months before topotecan therapy. Thirteen patients received topotecan therapy as second-line, seven as third-line and five as > or = fourth-line treatment. Twenty-two (88%) patients who received more than one cycle of chemotherapy were evaluable for response. A clinical benefit was observed in 11 (44%) patients (two [8%] partial response and nine [36%] stable disease). Seven patients achieving clinical benefit received topotecan as second-line treatment. Dose was reduced from 1.5 to 1.25 mg/m2/day in six patients after the first cycle of topotecan. Twelve (48%) patients had dose delay of at least 1 week. Grade 3/4 neutropenia, observed in nine (36%) patients, was the main dose-limiting toxicity. One patient died as a result of treatment. CONCLUSION: The Nottingham experience with topotecan in platinum-resistant ovarian cancer has been encouraging, even in such a heavily pre-treated patient population. There is a better chance of response if the patients receive topotecan at first relapse. The haematological toxicity is significant but manageable with dose reduction and dose delay.

Adult↗

Patterns of metastatic breast carcinoma: influence of tumour histological grade.

AIM: To assess if the pattern of metastatic spread of carcinoma of the breast varies according to tumour histological grade. MATERIALS AND METHODS: The clinical details, histological features of the primary tumour, and imaging findings at presentation of patients with metastatic breast cancer have been recorded prospectively since 1997. The pattern of metastatic spread, age at metastasis, metastasis-free interval (MFI), and length of survival with metastases were analysed by tumour grade. RESULTS: There was a significant association between histological high-grade tumours and high frequency of intra-pulmonary metastases (p=0.013); liver metastases (p=0.039); para-aortic lymphadenopathy (p=0.022) and metastatic presentation under 50 years of age (p=0.003). A significant correlation was also demonstrated between histological low-grade tumours and increased frequency of pleural disease (p=0.020); increased frequency of bone metastases (p=0.004); prolonged MFI (MFI>5 years; p<0.0001); and increased length of survival (p<0.0001). CONCLUSION: There is a correlation between patterns of metastatic spread and tumour histological grade. This partly explains the negative prognostic value of high tumour grade, as metastases from grade 3 tumours more commonly occur at sites associated with a worse prognosis. This finding may also prove useful in interpreting imaging in patients who have a history of breast cancer and undergo subsequent imaging because of new symptoms.

Age Factors↗

Low dose BCG as adjuvant therapy for superficial bladder cancer and literature review.

BACKGROUND: Bacillus Calmette-Guerin (BCG) at low doses has long been employed as prophylactic and therapeutic treatment for superficial cancer of the urinary bladder, aiming at reducing toxicity while maintaining efficacy. A retrospective review was reported, together with a review of the literature with respect to a low dose BCG regimen. METHODS: Forty-five consecutive patients with superficial bladder cancer (Ta or T1) with one or more of the appropriate criteria (grade above 1, stage above a, size >1 cm, multiple or recurrent), after complete transurethral resection, received 27 mg Connaught strain BCG weekly for 6 weeks. There was no maintenance therapy. Patients were evaluated with urine cytology and cystoscopy. Recurrence, progression and death were analysed. RESULTS: With a median follow up of 14 (range 3-61) months, 24 (53%) of the 45 patients responded to one course of 6 weekly BCG without recurrence. A further group of 13 (29%) patients responded to a second course of BCG on recurrence. Disease progressed in one (2.2%) patient. Two (4.4%) patients died of an unrelated condition. There was no disease specific mortality. Side-effects were common but well tolerated, with only two (4.4%) cases of treatment interruption. CONCLUSIONS: Low dose BCG could be an alternative option of adjuvant therapy for superficial bladder cancer with acceptable toxicity and good compliance.

Adjuvants, Immunologic↗

What are the needs of students? An experience from a district based health promoting schools project in Hong Kong.

A district based needs assessment as conducted over the past year to uderstand the health problems and the health education needs of the students in Tai Po district, Hong ong. 6879 primary one to primary six students from eighteen rimary schools, participating in a district based Health Promoting Schools Project in Hong Kong, were invited to complete a self-administrated questionnaire which was partly adapted from the Centre for Diseases and Control (CDC)'s Youth Risk Behaviour Surveillance Survey. The results presented a holistic picture of the health and needs of primary students with respect to their general health status, mental health, body weight and dietary behaviour, exercise, preventive health care, tobacco use, alcohol and other drug use, school environment and school health education. It provides baseline information for the project to prioritize the problems and strategically plan health promotion 'programmes with reference to the concept of Health Promoting Schools by the World Health Organization.

Adolescent↗

Prognostic factors for patients with hepatic metastases from breast cancer.

Median survival from liver metastases secondary to breast cancer is only a few months, with very rare 5-year survival. This study reviewed 145 patients with liver metastases from breast cancer to determine factors that may influence survival. Data were analysed using Kaplan-Meier survival curves, univariate and multivariate analysis. Median survival was 4.23 months (range 0.16-51), with a 27.6% 1-year survival. Factors that significantly predicted a poor prognosis on univariate analysis included symptomatic liver disease, deranged liver function tests, the presence of ascites, histological grade 3 disease at primary presentation, advanced age, oestrogen receptor (ER) negative tumours, carcinoembryonic antigen of over 1000 ng ml(-1) and multiple vs single liver metastases. Response to treatment was also a significant predictor of survival with patients responding to chemo- or endocrine therapy surviving for a median of 13 and 13.9 months, respectively. Multivariate analysis of pretreatment variables identified a low albumin, advanced age and ER negativity as independent predictors of poor survival. The time interval between primary and metastatic disease, metastases at extrahepatic sites, histological subtype and nodal stage at primary presentation did not predict prognosis. Awareness of the prognostic implications of the above factors may assist in selecting the most appropriate treatment for these patients.British Journal of Cancer (2003) 89, 284-290. doi:10.1038/sj.bjc.6601038 www.bjcancer.com

Adult↗