Treatment of basal cell carcinoma with topical methylaminolaevulinate photodynamic therapy in an organ-transplant recipient.
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Biomedical subjects
Publications and source records attributed to S K Tan.
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The surgeon of the new millennium has come a long way from his humble beginnings in the Middle Ages as the lowly barber-surgeon. The skills and techniques developed by outstanding surgeons like Astley Cooper of the 19th century have withstood the test of time and have been refined by subsequent generations of surgical masters. The scientific basis of modern surgery was put on a firm footing in the early 19th century through the discovery of anaesthesia and microorganisms as a cause of many diseases and surgical complications. The 20th century brought about rapid progress in medicine, information technology (IT) and the life sciences, and closed with a big bang with the completion of the sequencing of the human genome. For the surgeon of the 21st century to remain relevant, he must embrace the concept of the Total Surgeon. Not doing so will render him irrelevant in the course of time, for having good surgical technique alone is insufficient. He must also lead in scientific endeavours to push the frontiers of the life sciences in attempts to solve the insoluble, and be scholarly in thought, attitude and behaviour. In other words, he must be a Surgeon-Scientist-Scholar.
Since the beginning of time, our ancestors have been plagued by illnesses and injuries that are not too different from today's diseases. Evidence from prehistoric times and ancient civilisations have shown man's attempts at trying to understand the nature and treatment of these conditions. It was not till the early 19th century that the scientific basis of modern medicine was firmly established when microorganisms were discovered and found to be the cause of many of these illnesses. The 20th century saw quantum leaps made in the understanding of the function of the human body and the therapeutic measures aimed at restoration of any such malfunction. The end of the last millennium was marked by historic achievements made in the Life Sciences, in particular the completion of the sequencing of the Human Genome--the code of life. The beginning of the 21st century has already seen many breakthroughs in medical sciences, especially in the fields of stem cell technology and gene therapy. The number of known illnesses directly related to genetic defects or abnormalities have increased exponentially. Many of today's scourges can be prevented or more effectively treated. Our ability to utilise this new knowledge to combat the ravages of the ageing process and its associated illnesses--degenerative diseases and cancers offer much hope for the future.
With patellar thickness averaging 24.0 mm and 21.9 mm in Singapore men and women undergoing total knee arthroplasty, achievement of precut thickness is difficult if the recommended residual bony thickness of 15 mm is maintained. We retrospectively compared the clinical outcome of 56 patellae resurfaced 12 mm (mean residual thickness, 13.7 mm). Both groups were comparable in terms of demographic characteristics, presentation, precut patellar thickness, and operative details (P> .05). Knee scores (P= .627), extensor mechanism function (P= .625), and postoperative range of motion (P= .344) were comparable. Differences in the overall (P= .167) and patellar (P= .061) complication rates as determined by chi-square test on the SPSS 10.0 program were not significant, although there were 4 patella-related complications in group 2. Increased patella-related complications may be associated with an excessive patellar composite of the patellofemoral articulation. A residual patellar thickness of <12 mm did not appear to affect the clinical outcome in this series.
Thirty-seven patients were studied for an average of 32.1 months after canal-expansive laminoplasty for the treatment of multiple-level cervical stenosis caused by spondylosis, ossification of posterior longitudinal ligament, prolapsed intervertebral disc, and other conditions. Short-term and medium-term results were recorded clinically, using the scoring system proposed by the Japanese Orthopedic Association. The canal expansion was also recorded with radiological studies. The improvement rate was good to excellent in 58.3% of the patients. Postoperative neurological deterioration occurred in only four patients. Poorer results were observed in female patients and in those in whom surgery was delayed. Surgery within 12 months of onset of symptoms gave good results. Serious complications occurred in only two patients. There were 12 patients who were treated with the single trap-door (unilateral) laminoplasty and 25 patients treated with the double trap-door (sagittal splitting of the spinous processes) laminoplasty; their results were compared. There was no significant difference in neurological outcome between the two methods.
This essay is designed as a brief historical examination of the Cantonese female cross-dressing star Yam Kim-Fei, whose hundreds of films and opera performances in the '50s and '60s have made her one of the century's most celebrated transvestite artists. While her craft has often been relegated to studies of gender alone, I assert that the traditions of Chinese operatic transvestism she employs are not merely a relativist historical-artistic mode without political relevance but can be justifiably reclaimed for the purposes of queer interpretation and spectatorship-for indeed their original intent coincides very well with what we call "queer" today.
BACKGROUND/AIM OF STUDY: The results of primary total knee arthroplasties have improved over the years but some still fail, requiring revision. Revision total knee arthroplasty is technically more difficult and has not enjoyed the same success rates as the index operation. The aim of this retrospective study was to review the results of revision total knee arthroplasties carried out at our centre. This is the first study in Singapore on revision total knee arthroplasty. METHODS: A retrospective study where 17 patients (18 knees) had been followed up since their revision operations were clinically assessed. Based on the Knee Society Clinical Scoring System, they were assigned separate knee and function scores (each having a maximum possible 100). RESULTS: The mean knee score was 76 (range 35-93), which rates as good. Of the 18 knees, 67% had excellent or good knee scores. By comparison, the mean function score was 56 (range 0-90) which rates as poor and 33% had excellent or good function scores. CONCLUSION: Revision total knee arthroplasty achieves good and excellent results in spite of technical difficulties often associated with the revision operation. The difference in mean knee and function scores emphasises that many other factors such as physical strength and stamina affect function. Nevertheless, 15 patients were able to walk out of their house and around their neighbourhood for varying distances. This satisfied their expectations and the poor mean function score may reflect different expectations of patients overseas from whence this scoring system originated.
INTRODUCTION: The prevalence of deep vein thrombosis after total knee replacement has been quoted to be between 46% and 84% in the Western literature. The aims of this study were to determine its prevalence in the Singapore population and to assess the need for prophylaxis against deep vein thrombosis. MATERIALS AND METHODS: We examined data on 100 consecutive patients undergoing total knee replacement at the Adult Reconstructive Service, Department of Orthopaedic Surgery, Singapore General Hospital and assessed the possible risk factors: age, sex, weight, previous surgery, unilateral or bilateral surgery, postoperative rehabilitation, tourniquet and operating time. Functional and knee scores based on the Knee Society Clinical Rating System were also assessed. No prophylaxis was given to these patients. These patients underwent a duplex scan of both lower limbs on the seventh postoperative day. Treatment was instituted only if proximal deep vein thrombosis was detected. RESULTS: The overall incidence of deep vein thrombosis was 14% with 64.3% of it occurring distally. Deep vein thrombosis was more common in bilateral total knee replacement (22.2%) compared to unilateral total knee replacement (13.2%). Partial thrombosis was present in 71.4% and occurred predominantly in the ipsilateral leg. There was no evidence of propagation. Only 1 patient developed pulmonary embolism and was treated successfully but there was no evidence of deep vein thrombosis on duplex scan in this patient. CONCLUSION: There was no significant difference in the risk factors between patients who did and those who did not develop deep vein thrombosis.
Acetylcholine (ACh), synthesized in the pituitary, can act locally to modulate pituitary function. We used rat primary anterior pituitary (AP) cells to investigate how ACh affects pituitary prolactin (PRL) secretion in the presence or absence of known PRL regulators: thyrotropin-releasing hormone (TRH), 17beta-estradiol (E(2)) and triiodothyronine (T(3)). Cultured AP cells were prepared from ovariectomized rats and pretreated with diluent, 0.6 nM E(2), 10 nM T(3), or E(2) plus T(3) for 5 days, then challenged with various doses of ACh or muscarinic receptor agonists (oxotremorine or carbachol) and TRH (100 nM) for 20 min. Significant ACh (10(-5) M) suppression of both basal and TRH-induced PRL secretion was not evident in diluent-, E(2)- or T(3)-pretreated cells, but observed only in cells pretreated with both E(2) and T(3). Moreover, in E(2) plus T(3)-pretreated cells, oxotremorine and carbachol, like ACh (10(-7)-10(-5) M), suppressed both responses in a dose- related manner. Pertussis toxin (PTX; 100 ng/ml) as well as atropine (a muscarinic receptor antagonist; 1 mM) blocked these effects of cholinomimetics. ACh also inhibited both PRL responses elicited by drugs elevating intracellular cAMP (10 microM forskolin) or Ca(2+) (1 microM Bay K-8644) in a PTX-sensitive manner. ACh inhibition of basal PRL secretion was unaltered by intracellular Ca(2+) mobilization blockers, TMB-8 (100 microM) and thapsigargin (1 microM), but abrogated by the nitric oxide synthase inhibitor (300 microM L-NAME). ACh inhibition of TRH-induced PRL secretion was accentuated by TMB-8 and alleviated by thapsigargin or L-NAME. In summary, muscarinic inhibition of either basal or TRH-induced PRL secretion was augmented by E(2) and T(3), and involved the PTX-sensitive cAMP/Ca(2+) pathways. Furthermore, nitric oxide mediated the basal rather than TRH-induced PRL response to ACh, whereas the intracellular Ca(2+) mobilization concerned the TRH-induced rather than the basal PRL response to ACh. Thus, ACh synthesized in the AP appears to inhibit basal vs. TRH-induced PRL secretion via different mechanisms.
Resection of a vertebral body for spine tumour or fracture results in a vertebral gap which has to be bridged by autogenous graft, allograft, bone cement or metal spacer. Recently, there have been several metal spacers in the market. We have designed a titanium vertebral spacer which is extensible by way of a threaded mechanism. Coating with hydroxyapatite enables bone ingrowth onto the surface of the titanium spacer. Biomechanical analysis, using the Instron biaxial electro-servohydraulic testing machine, showed that the segment bridging the spacer was rigid and stiffer than the adjacent vertebral body motion segment. Histological study showed that there was bone growth across the vertebral gap indicating fusion had taken place.
BACKGROUND: The pathogenesis of glomerular damage in glomerulonephritis (GN) is not fully understood. Several studies have suggested that reactive oxygen molecules play a role in renal disease. It is known that, during GN, mesangial cells are activated. In a previous study, we demonstrated that in vitro interleukin (IL)-1 plus IL-6 stimulated cultured human mesangial cell (HMC) activation to release free oxygen radicals. METHODS: In this study, we measured hydrogen peroxide (H2O2) and superoxide anion (O2-) levels after stimulation by IL-1 plus IL-6 in cultured HMCs. We then infused H2O2 directly into the left renal arteries of Sprague-Dawley rats. We also infused the culture supernatants of HMCs after stimulation by IL-1 plus IL-6 into the left renal arteries of rats. Two hours after stopping the infusion, the kidneys were removed and fixed using Carson's modified Millonig's buffer for electron microscopy. RESULTS: Both 100 microM H2O2 and supernatants of HMCs stimulated by IL-1 10 U/ml plus IL-6 1,000 U/ml caused similar glomerular damage, including blebbing and sloughing of endothelial cells, and denuded basement membrane in glomeruli. When 100 microM H2O2 or supernatants of cytokine-activated HMCs were infused into renal arteries, they caused hematuria and proteinuria. CONCLUSIONS: These results suggest that activated HMCs may secrete free radicals and cause glomerular damage.
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This study examined phosphatidylinositol 4-phosphate (PtdIns4P) synthesis in caveolae that have been suggested to be discrete signaling microdomains of the plasma membrane and are enriched in the marker protein caveolin. Caveolin-rich light membranes (CLMs) were isolated from A431 cells by detergent-free, discontinuous density-gradient centrifugation method. The CLM fraction was separated from the bulk of the cellular protein and was greatly enriched in PtdIns, PtdIns4P, and phosphatidylinositol 4, 5-bisphosphate (PtdIns(4,5)P2) and an adenosine-sensitive type II PtdIns 4-kinase activity. Preparation of CLMs by an OptiPrep-based cell fractionation procedure confirmed the co-localization of PtdIns 4-kinase and caveolin. Electron microscopy confirmed that an anti-caveolin antiserum immunopurified vesicles from CLMs that were within the size range described for caveolae in other systems. Co-immunoprecipitated PtdIns 4-kinase activity could utilize endogenous PtdIns, present within the caveolae-like vesicles, to produce PtdIns4P. The addition of recombinant phosphatidylinositol transfer protein increased PtdIns 4-kinase activity both in immunoisolated caveolae and CLMs. However, less than 1% of the total cellular PtdIns and PtdIns 4-kinase activity was present in caveolae-like vesicles, indicating that non-caveolar light membrane rafts are the main site for cellular PtdIns4P production.
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We investigated the mechanisms by which transforming growth factor (TGF)-beta2 inhibited prolactin mRNA expression in GH3 rat pituitary tumor cells. Maximal inhibition was observed with cells exposed to 5 ng/ml TGF-beta2 for 24 hr. Continuous presence of the hormone during the entire period was not necessary because exposure of cells to TGF-beta2 for 20 min was sufficient to trigger the same extent of prolactin mRNA inhibition at 24 hr as with its persistent presence. The action of TGF-beta2 could be abolished by cycloheximide or EGTA, suggesting the requirement of a newly synthesized protein and extracellular Ca2+. The response of prolactin mRNA to TGF-beta2 was inhibited by preincubation of cells with phorbol-12-myristate-13-acetate, which down-regulated protein kinase C (PKC). The activities of both the cytosolic and membrane PKC were significantly reduced at 20 min after TGF-beta2 addition, and inhibition continued to 24 hr, the last time point analyzed. However, the ratio of cytosolic to membrane PKC was not altered by TGF-beta2. Inhibition of PKC did not require the sustained presence of TGF-beta2. In vitro kinase assays of the immunoprecipitated PKC demonstrated that the activities of alpha, epsilon, mu, and zeta isozymes were significantly decreased in the TGF-beta2-treated cells, whereas that of PKClambda was not affected. Western blotting did not reveal any change in PKCepsilon steady state protein levels, suggesting TGF-beta2 inhibits PKC activity through a post-translational mechanism. Our results support that inhibition of PKC activity is an early event mediating TGF-beta2-inhibited prolactin mRNA expression in GH3 cells.
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BACKGROUND: Twenty-two consecutive revisions for failed metal-backed patellar components following total knee arthroplasty in 17 patients were retrospectively reviewed. All had similar total condylar knee prosthesis inserted with retention of the posterior cruciate ligament and resurfacing of the patella with a metal-backed component. There were 3 male and 14 female patients. RESULTS: The mean time to failure of the patellar component was 60 months (range 26 to 93 months). The majority of patients presented with metallic crepitus (86.4%) and knee pain (72.7%). At surgery, full thickness polyethylene wear exposing the metal-backing was present in 81.8% with surface damage of the femoral components present in 40.9%. All 22 cases underwent successful isolated patellar component revision with all polyethylene patellar components. CONCLUSION: Resurfacing of the patella in total knee arthroplasty with metal-backed patellar components carries a significant risk of early failure and the use of these components is no longer practised at our institution.
Transforming growth factor-beta 1 (TGF-beta 1) synthesized in the pituitary may act as an autocrine/paracrine regulator of lactotrope function. We examined the effects of TGF-beta 1 on PRL messenger RNA (mRNA), PRL synthesis, and PRL secretion in cultured anterior pituitary (AP) cells from rats at different ages. APs excised from ovariectomized female Sprague-Dawley rats, either young(2-3 months old; average serum PRL: 9 ng/ml), middle-aged (11-12 months old; average serum PRL: 133 ng/ml), or old (24 months old; average serum PRL: 159 ng/ml), were dispersed and cultured for 5 days. Then, cells were washed and challenged with increasing doses of TGF-beta 1 (0-100 ng/ml) for 1-48 h in serum-free medium. Northern blot analysis showed an increase in basal PRL mRNA levels, and a decrease in responsiveness to TGF-beta 1 with age. TGF-beta 1 suppressed PRL mRNA in a dose- and time-dependent manner in cells from young rats. Maximum inhibition was observed at 0.5-1 ng/ml of TGF-beta 1. At 0.5 ng/ml TGF-beta 1, significant reduction in PRL mRNA was detected at 6 h, and maximum inhibition was observed at 12-48 h post TGF-beta 1 incubation. Cells from middle-aged rats were less responsive to TGF-beta 1, whereas cells from old rats did not seem to respond under our experimental conditions. In addition to its effect on PRL mRNA in young AP cells, TGF-beta 1 dose dependently inhibited the rate of PRL synthesis, as indicated by reduced [35S]methionine incorporation into immunoprecipitated PRL. Responsiveness of PRL synthesis to TGF-beta 1 inhibition also decreased with age; however, significant inhibition by TGF-beta 1 on PRL synthesis could still be observed in old AP cells. Analysis by RIA demonstrated that young AP cells produced lower levels (15 micrograms/10(6) cells.24 h) of PRL in culture medium than old AP cells (32 micrograms/10(6) cells.24 h). TGF-beta 1 decreased medium PRL levels in old AP cells as efficaciously as in young AP cells. Significant reduction in medium PRL secreted by young AP cells was observed at 3 h when changes in both PRL mRNA and PRL synthesis were not evident. Taken together, our data suggest that TGF-beta 1 affects PRL production at multiple levels. Moreover, its inhibition on PRL synthesis and mRNA expression, but not on PRL secretion, is age-related. Thus, TGF-beta 1 may play an important role in regulating lactotrope function during aging.