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Adiponectin may have an antiatherogenic effect by reducing endothelial activation. We hypothesized that plasma adiponectin levels were correlated with endothelial function. Plasma adiponectin level was determined by an in-house RIA assay using a rabbit polyclonal antibody in 73 type 2 diabetic patients and 73 controls. Endothelium-dependent and independent vasodilation of the brachial artery was measured by high-resolution vascular ultrasound. Plasma adiponectin level was lower in diabetic patients than in controls (4.73 +/- 1.96 vs. 7.69 +/- 2.80 microg/ml, respectively; P < 0.001), and they also had impaired endothelium-dependent (5.6 +/- 3.6 vs. 8.6 +/- 4.5%, respectively; P < 0.001) and -independent vasodilation (13.3 +/- 4.9 vs. 16.5 +/- 5.6%, respectively; P < 0.001). Plasma adiponectin correlated with endothelium-dependent vasodilation in controls (P = 0.02) and diabetic patients (P = 0.04). On general linear-model univariate analysis, brachial artery diameter, the presence of diabetes, plasma adiponectin, and high-density lipoprotein were significant independent determinants of endothelium-dependent vasodilation. In vitro experiments showed that endothelial cells expressed adiponectin receptors, and adiponectin increased nitric oxide production in human aortic endothelial cells. In conclusion, low plasma adiponectin level is associated with impaired endothelium-dependent vasodilation, and the association is independent of diabetes mellitus. Adiponectin may act as a link between adipose tissue and the vasculature.

This paper discusses the object-oriented software design for an automatic blending system. By combining the advantages of a programmable logic controller (PLC) and an industrial control PC (ICPC), an automatic blending control system is developed for a chemical plant. The system structure and multithread-based communication approach are first presented in this paper. The overall software design issues, such as system requirements and functionalities, are then discussed in detail. Furthermore, by replacing the conventional dynamic link library (DLL) with virtual X device drivers (VxD's), a practical and cost-effective solution is provided to improve the robustness of the Windows platform-based automatic blending system in small- and medium-sized plants.

Invasive aspergillosis is a highly lethal disease in immunocompromised hosts especially with central nervous system involvement. In a review of 2380 liver transplants performed over 14 years, 13 out of 15 fungal brain abscesses were due to Aspergillus species and only one patient survived [Arch Surg, 132 (1997) 304]. Dematiaceous fungi while less readily recognised, often have a more favorable outcome [Transplantation, 63 (1997) 160]. We report a Xylophypha bantiana cerebral abscess in a liver transplant recipient initially identified as a branching mould on histology that had a successful outcome due to aggressive appropriate treatment.

Objective: Acromegalic patients have been shown to have an increase in the concentrations of small dense low-density lipoprotein (LDL) and remnant-like lipoprotein particles (RLP). These lipoproteins are atherogenic and may contribute to the cardiovascular risk of these patients. The aim of this study was to determine whether treatment of acromegaly using Sandostatin LAR could lower these atherogenic lipoproteins., Methods: Fourteen patients with active acromegaly were recruited and Sandostatin LAR, a long-acting somatostatin analogue, was given every 4 weeks by intramuscular injection for 6 months. Fasting lipids, lipoproteins, lipolytic enzymes were determined at baseline, 12 and 24 weeks after treatment. Small dense LDL was measured using density gradient ultracentrifugation and RLP-cholesterol (RLP-C) by an immunoseparation assay., Results: There was already a marked reduction in GH and IGF-1 by week 8 and, in all subjects, IGF-1 levels within their respective age-specific normal range were achieved. At week 12, plasma triglyceride significantly decreased (P < 0.01) and both HDL2 (P < 0.01) and HDL3 (P < 0.01) subfractions increased. A reduction was seen in small dense LDL concentration (P < 0.05) and RLP-C (P < 0.05). Lipoprotein lipase (LPL) activity increased (P < 0.01) and the magnitude of the increase in LPL activity correlated with the increase in HDL at 3 months (r = 0.55, P < 0.05) but not with the changes in plasma triglyceride, small dense LDL or RLP-C. The improvement in plasma lipids and lipoproteins persisted until the end of the study., Conclusion: Sandostatin LAR is effective in the treatment of acromegaly and is associated with favourable changes in plasma lipids and a reduction in small dense LDL and RLP-C.

Background: Phospholipid transfer protein (PLTP) and cholesteryl ester transfer protein (CETP) remodel circulating lipoproteins and play a role in the antiatherogenic reverse cholesterol transport pathway. The present study determined whether abnormalities in the LDL subfraction pattern in type 2 diabetic patients were related to changes in lipid transfer proteins., Methods: Low-density lipoprotein (LDL) subfractions were measured by density gradient ultracentrifugation and plasma PLTP and CETP activities by radiometric assays in 240 diabetic patients and 136 controls., Results: The diabetic patients had lower LDL-I (P < 0.001) and higher LDL-III concentrations than the controls (P < 0.001). Plasma PLTP activity was increased (P < 0.001) whereas no significant differences were seen in CETP activity. In the diabetic patients, small, dense LDL-III correlated with plasma triglyceride (r = 0.18, P < 0.01), HDL (r = -0.14, P < 0.05), PLTP (r = 0.29, P < 0.001) and CETP activity (r = 0.15, P < 0.05). Linear regression analysis showed that plasma PLTP activity, triglyceride and age were the major determinants of LDL-III concentration (r2 = 28%, P < 0.001). The univariate relationship between CETP and LDL-III was no longer significant after adjusting for PLTP activity., Conclusions: The increase in plasma PLTP activity was independently associated with small, dense LDL concentrations in type 2 diabetes. Hence, elevated PLTP activity might have both antiatherogenic and pro-atherogenic potential in these patients.

One of the major challenges in medical domain is the extraction of comprehensible knowledge from medical diagnosis data. In this paper, a two-phase hybrid evolutionary classification technique is proposed to extract classification rules that can be used in clinical practice for better understanding and prevention of unwanted medical events. In the first phase, a hybrid evolutionary algorithm (EA) is utilized to confine the search space by evolving a pool of good candidate rules, e.g. genetic programming (GP) is applied to evolve nominal attributes for free structured rules and genetic algorithm (GA) is used to optimize the numeric attributes for concise classification rules without the need of discretization. These candidate rules are then used in the second phase to optimize the order and number of rules in the evolution for forming accurate and comprehensible rule sets. The proposed evolutionary classifier (EvoC) is validated upon hepatitis and breast cancer datasets obtained from the UCI machine-learning repository. Simulation results show that the evolutionary classifier produces comprehensible rules and good classification accuracy for the medical datasets. Results obtained from t-tests further justify its robustness and invariance to random partition of datasets.

Today there is an array of therapeutic modalities available for the patients with hepatocellular carcinoma (HCC). However, surgery, be it resection or transplantation, offers the only hope of long-term disease-free survival. Unfortunately, because the majority of HCC in Asia is associated with cirrhosis, surgical resection is restricted to only a small proportion of these patients. However, in selected candidates resection may offer a 5-year survival of up to 70%. With the clinical application of adult-to-adult living donor liver transplantation, an increasing number of patients with small HCC and decompensating cirrhosis are undergoing transplantation., (Copyright 2002 Blackwell Publishing Asia Pty Ltd)

This study provides estimates for the cost of smoking in Singapore in 1997.A first attempt for Singapore, the paper reports on two different methods used, namely, the human capital approach and the demographic approach. These two measures are similar in that they compare the economic cost of smoking in the actual situation with the hypothetical alternative where there had been no smoking. The direct cost of smoking includes the amount spent on hospital care for five main diseases related to smoking whilst the indirect cost includes the value of lost income. The mortality cost of smoking is derived from the aetiological fractions of these diseases. The results from the human capital approach show that the social cost of smoking in 1997 ranged from S$673 million to S$839 million. Assuming there has been no smoking since 1990, calculations from the demographic approach indicate that national output would have increased by S$614 million in 1998. Nonetheless, the results from both approaches show that most of the cost of smoking is incurred by males.

This paper presents the optimal control of drug scheduling in cancer chemotherapy using a distributed evolutionary computing software. Unlike conventional methods that often require gradient information or hybridization of different approaches in drug scheduling, the proposed evolutionary optimization methodology is simple and capable of automatically finding the near-optimal solutions for complex cancer chemotherapy problems. It is shown that different number of variable pairs in evolutionary representation for drug scheduling can be easily implemented via the software, since the computational workload is shared and distributed among multiple computers over the Internet. Simulation results show that the proposed evolutionary approach produces excellent control of drug scheduling in cancer chemotherapy, which are competitive or equivalent to the best solutions published in literature.

Methods: Twenty orbital defects (2 x 2 cm) were created in ten adult Yorkshire pigs. Two software products (Velocity and Mimix) were evaluated with regard to image processing, three-dimensional reconstruction, and fabrication of individually shaped polycaprolactone (PCL) scaffolds to reconstruct these defects. Four different techniques were tested for the reconstruction: group 1 = no reconstruction, group 2 = polylactide sheet, group 3 = PCL scaffold, group 4 = bone marrow-coated PCL scaffold. The pigs were sacrificed at 3 months., Results: In group 1 soft tissue scar formation could be found, but without any new bone. Group 2 showed a thick fibrous capsule around the PLLA sheet, whereas at the border zone of the defect signs of new bone formation could be detected. In group 3 the PCL scaffolds were filled with fibrous tissue and some areas that showed new bone formation (6.4% of the area of the defect). In group 4 the new bone formation (17.8% of the area of the defect) was significantly higher in quantity than in group 3., Conclusion: The PCL scaffold coated with bone marrow seems to be a material that effectively provides osteoinduction with formation of new bone. Long-term results at 12 months are still pending.

Endothelial dysfunction is frequently found in diabetic subjects. This study was performed to investigate whether atorvastatin therapy was able to reverse endothelial dysfunction in type 2 diabetes and, if so, whether the effect was due to its antiinflammatory action. Eighty patients (baseline low density lipoprotein, 4.37 +/- 0.71 mmol/liter) were randomized to atorvastatin (10 mg daily for 3 months, followed by 20 mg daily for 3 months) or placebo in a double blind study. Endothelial function was assessed by high resolution vascular ultrasound, and high sensitivity C-reactive protein (CRP) was assessed by immunoturbidimetric assay. Diabetic patients had higher CRP (P < 0.01) than matched nondiabetic controls, and both endothelium-dependent and independent vasodilation were impaired (P < 0.01). Atorvastatin (10 and 20 mg) lowered plasma cholesterol by 32.9% and 38.0%, triglyceride by 15.4% and 23.1%, and low density lipoprotein by 43.4% and 50.1%, respectively. At 6 months, plasma CRP decreased in the atorvastatin group compared with baseline (P < 0.05). Endothelium-dependent vasodilation improved in the atorvastatin group compared with the placebo group (P < 0.05). The percent change in endothelium-dependent vasodilation at 6 months correlated with the percent change in CRP (r = -0.44; P < 0.05), but not with changes in plasma lipids. In conclusion, treatment with atorvastatin in type 2 diabetes led to a significant improvement in endothelium-dependent vasodilation, which might be partly related to its anti-inflammatory effect.

Primary osteosarcoma of the sphenoid bone is an extremely rare condition. This paper presents a case of a lady with recurrent oesteosarcoma of the sphenoid bone who had resection of the tumour via a combined neurosurgical and craniofacial procedure and reconstruction with a free flap and bone graft. It details the diagnosis, treatment and follow-up of this unusual condition.

Objectives: Sleep apnoea has been reported to occur in subjects with acromegaly. This study evaluates the relationship among biochemical activity, sleep apnoeic activity and upper airway anatomic profile in acromegaly, and the effect of Sandostatin LAR, a long-acting somatostatin analogue, on these parameters., Patients: Fourteen subjects with acromegaly were recruited., Measurements: Subjects were assessed at baseline and those with apnoea-hypopnoea index (AHI) > or = 5 were reassessed after 6 months of treatment with Sandostatin LAR 20-30 mg IMI 4-weekly. Biochemical activity was assessed with levels of GH and IGF-1. Sleep disordered breathing was assessed with overnight polysomnography. Upper airway anatomic profile was defined with computerized tomographic cephalometry., Results: Of 14 subjects (age 42.0 +/- 8.1 years, mean +/- SD; 11 men) at baseline, there was a positive correlation between GH and tongue length (VT; P = 0.004), and between AHI and cephalometric indices: length of soft palate (PMU; P = 0.002); mandibular plane-hyoid bone distance (MPH; P = 0.017), maximum thickness of soft palate (Max-SP; P = 0.018) and VT (P = 0.027). Eight patients had sleep disordered breathing (AHI > or = 5) which was predominantly obstructive in nature (AHI = 29.4 +/- 22.6). After treatment, there were significant improvements in hormonal profile: GH, mU/l (before, 51.5 +/- 27.8; after, 8.0 +/- 7.4; P = 0.017) and IGF-1, nmol/l (before, 95.5 +/- 23.4; after, 35.0 +/- 12.4; P = 0.012); sleep-disordered breathing: AHI (before, 29.4 +/- 22.6; after, 13.4 +/- 11.12; P = 0.025), snoring episodes (before, 486 +/- 240; after, 165 +/- 170; P = 0.05); cephalometric indices, mm: MPH (before, 18.8 +/- 12.1; after, 14.8 +/- 8.4; P = 0.018), VT (before, 72.3 +/- 4.4; after, 69.7 +/- 4.3; P = 0.05). There was a positive correlation between the reduction in GH and AHI (r = 0.738, P = 0.037)., Conclusions: The findings demonstrated that there was correlation between sleep apnoea severity and soft tissue overgrowth at the upper airway region in acromegaly. They also suggest that Sandostatin LAR improved obstructive sleep apnoea in acromegaly, and the effect might be partly mediated via a reduction in upper airway soft tissue, in particular that of the tongue, concomitant with a reduction in GH levels.

Palmoplantar pustulosis (PPP) is a chronic, relapsing, pustular eruption affecting the palms and soles for which treatment is often difficult and frustrating. Short-term colchicine has been used to treat PPP with variable response. We report on the successful treatment of 3 patients with severe, therapy-resistant, chronic PPP. We observed significant reduction in the frequency of pustular eruptions and the number of pustules with maximum tolerable doses of colchicine treatment for up to 12 months.

Genetic variation in the hepatic lipase (HL) gene (LIPC) promoter is an important determinant of HL activity in Caucasians. As HL activity is increased in patients with type 2 diabetes mellitus, we have investigated whether the -514 C-to-T polymorphism acted independently of type 2 diabetes to regulate HL activity. The frequency of this polymorphism and its effect on plasma HL activity and lipids were examined in 203 Chinese patients with type 2 diabetes and 205 controls. The frequency of the T allele was 0.343 and 0.376 in male and female diabetic patients, respectively, compared with 0.371 and 0.372 in male and female controls. The effect of LIPC genotype on HL activity was similar between men and women, and between diabetic patients and non-diabetic controls, with the lowest HL activity being found in those subjects with the TT genotype. On multivariate analysis, gender, LIPC genotype, the presence of type 2 diabetes and body mass index were independent predictors of HL activity, accounting for 22, 9, 5 and 3%, respectively, of the variance in HL activity (whole model adjusted R(2)=0.39, P<0.0001). The T allele was associated with higher high-density lipoprotein in the controls but not in the diabetic patients, and no associations were found between LIPC genotype and low-density lipoprotein subfractions in either groups. In conclusion, despite the higher frequency of the T allele in Chinese than in Caucasians, gender was the best predictor for HL activity, with LIPC gene polymorphism and type 2 diabetes making relatively smaller contributions to the variation in HL activity.

A number of different processing techniques have been developed to design and fabricate three-dimensional (3D) scaffolds for tissue-engineering applications. The imperfection of the current techniques has encouraged the use of a rapid prototyping technology known as fused deposition modeling (FDM). Our results show that FDM allows the design and fabrication of highly reproducible bioresorbable 3D scaffolds with a fully interconnected pore network. The mechanical properties and in vitro biocompatibility of polycaprolactone scaffolds with a porosity of 61 +/- 1% and two matrix architectures were studied. The honeycomb-like pores had a size falling within the range of 360 x 430 x 620 microm. The scaffolds with a 0/60/120 degrees lay-down pattern had a compressive stiffness and a 1% offset yield strength in air of 41.9 +/- 3.5 and 3.1 +/- 0.1 MPa, respectively, and a compressive stiffness and a 1% offset yield strength in simulated physiological conditions (a saline solution at 37 degrees C) of 29.4 +/- 4.0 and 2.3 +/- 0.2 MPa, respectively. In comparison, the scaffolds with a 0/72/144/36/108 degrees lay-down pattern had a compressive stiffness and a 1% offset yield strength in air of 20.2 +/- 1.7 and 2.4 +/- 0.1 MPa, respectively, and a compressive stiffness and a 1% offset yield strength in simulated physiological conditions (a saline solution at 37 degrees C) of 21.5 +/- 2.9 and 2.0 +/- 0.2 MPa, respectively. Statistical analysis confirmed that the five-angle scaffolds had significantly lower stiffness and 1% offset yield strengths under compression loading than those with a three-angle pattern under both testing conditions (p < or = 0.05). The obtained stress-strain curves for both scaffold architectures demonstrate the typical behavior of a honeycomb structure undergoing deformation. In vitro studies were conducted with primary human fibroblasts and periosteal cells. Light, environmental scanning electron, and confocal laser microscopy as well as immunohistochemistry showed cell proliferation and extracellular matrix production on the polycaprolactone surface in the 1st culturing week. Over a period of 3-4 weeks in a culture, the fully interconnected scaffold architecture was completely 3D-filled by cellular tissue. Our cell culture study shows that fibroblasts and osteoblast-like cells can proliferate, differentiate, and produce a cellular tissue in an entirely interconnected 3D polycaprolactone matrix., (Copyright 2001 John Wiley & Sons, Inc.)

Standard microvascular anastomosis using only sutures is a well-established and successful technique; however, it is time-consuming and may cause vessel narrowing, needle trauma, and tissue reaction. The authors' hypothesis was that 2-octylcyanoacrylate could simplify microvascular anastomosis and reduce wall trauma and reaction. End-to-end anastomoses of the femoral arteries were performed in 20 adult rats. Each animal served as its own control. The time taken for each anastomosis (from first stitch to release of clamps) was noted, and the patency assessed. At day 7, the anastomoses were reassessed for patency, and the vessels evaluated histologically. 2-octylcyanoacrylate reduced the need to insert more sutures. Anastomotic time in the study group was statistically significantly shorter (p < 0.001), and the patency rate was 90 percent, compared to 85 percent with the standard suture technique. There was also less intense inflammatory reaction, with fewer foreign-body granulomata. This is the first report on the use of 2-octylcyanocrylate, currently approved for cutaneous use, for vessel anastomosis. Further work on the biomechanics and long-term histologic effects will be carried out. 2-octylcyanoacrylate has the potential for simplifying and improving the patency rates of arterial microanastomosis.

Serum leptin levels are decreased in patients with acromegaly and rise after GH is normalized by surgical treatment. We have evaluated the effect of Sandostatin LAR on leptin levels in acromegalic patients since there are recent data to suggest that somatostatin, in addition to its GH lowering effect, also reduces serum leptin levels in humans. Nineteen patients with active acromegaly were studied. Eleven patients received monthly injection of Sandostatin LAR and eight patients underwent transsphenoidal surgery. Serum concentrations of leptin, GH, IGF-1 and insulin were measured before and after treatment. Serum leptin concentrations were lower in patients with active acromegaly than controls matched for age, sex and body mass index (BMI) [2.79 microg/l (2.60) vs. 4.41 microg/l (5.07); median (inter-quartile range); P < 0.01]. A positive correlation between serum leptin concentrations and BMI was observed in the controls (r = 0.46, P < 0.05) but not in the acromegalic patients before treatment (r = 0.32, ns). In the group of patients treated with Sandostatin LAR, a marked reduction in GH and IGF-1 was achieved by week 8 and GH and IGF-1 remained suppressed throughout the 6 months of treatment. There was no change in BMI. A significant increase in leptin levels only became evident after 6 months of treatment [2.99 microg/l (2.60) vs. 4.21 microg/l (3.84), P < 0.05]. Leptin levels also significantly increased after transsphenoidal surgery [3.05 microg/l (5.73) vs. 5.19 microg/l (4.93), P < 0.05]. The positive correlation between serum leptin concentrations and BMI was restored in acromegalic patients both after treatment with Sandostatin LAR (r = 0.62, P < 0.05) and after surgery (r = 0.81, P < 0.05). Leptin concentrations were decreased in patients with active acromegaly and lowering GH by either Sandostatin LAR or transsphenoidal surgery led to an increase in leptin concentrations.

Introduction: Liver transplantation is a curative treatment modality in children with end stage liver disease in Alagille syndrome., Clinical Picture: We report a 3-year-old child with this condition who had severe hypercholesterolaemia, pruritus and extensive xanthomatosis., Treatment: Liver transplantation was performed in this patient., Outcome: He recovered well with normalisation of his lipid profile. This procedure also resulted in resolution of the disfiguring xanthomatosis.

Human cadaveric allograft is the most commonly used alternative wound closure material for excised burn wounds when limited donor sites or the overall patient condition does not permit immediate grafting with autologous skin.The Skin Bank in Singapore has supplied a total of 33,000 cm(2) of cryopreserved cadaveric allograft to the Burns Centre in Singapore for the early post-burn treatment of 17 severely burned patients with body surface area (BSA) burn wounds averaging 58% (range 33-90). An average of 13% (range 3-30%) cadaveric allograft was transplanted on 17 patients. Seven patients had recovered from their burn injuries and ten patients died of multiple complications related to their burn injuries. Our clinical observation has shown good adherence of cadaveric allograft when applied on clean and debrided wound bed after 4-7 days of post-operation.The availability of cadaveric allograft permits early excision and wound coverage before the patients' condition is further compromised. Our clinical experience using cryopreserved cadaveric allograft is proving to be indispensable in the management of patients with severe burns.

This paper presents an interactive graphical user interface (GUI) based multiobjective evolutionary algorithm (MOEA) toolbox for effective computer-aided multiobjective (MO) optimization. Without the need of aggregating multiple criteria into a compromise function, it incorporates the concept of Pareto's optimality to evolve a family of nondominated solutions distributing along the tradeoffs uniformly. The toolbox is also designed with many useful features such as the goal and priority settings to provide better support for decision-making in MO optimization, dynamic population size that is computed adaptively according to the online discovered Pareto-front, soft/hard goal settings for constraint handlings, multiple goals specification for logical "AND"/"OR" operation, adaptive niching scheme for uniform population distribution, and a useful convergence representation for MO optimization. The MOEA toolbox is freely available for download at http://vlab.ee.nus.edu.sg/-kctan/moea.htm which is ready for immediate use with minimal knowledge needed in evolutionary computing. To use the toolbox, the user merely needs to provide a simple "model" file that specifies the objective function corresponding to his/her particular optimization problem. Other aspects like decision variable settings, optimization process monitoring and graphical results analysis can be performed easily through the embedded GUIs in the toolbox. The effectiveness and applications of the toolbox are illustrated via the design optimization problem of a practical ill-conditioned distillation system. Performance of the algorithm in MOEA toolbox is also compared with other well-known evolutionary MO optimization methods upon a benchmark problem.

The lower trapezius island myocutaneous flap is a useful flap in head and neck reconstruction. It is thin and pliable and can reach defects in most areas of the head and neck. Its usefulness in head and neck reconstruction has often been limited or discouraged by reports of significant failure rates. In this study, the vascular anatomy and clinical use of the extended lower trapezius myocutaneous flap based solely on the dorsal scapular artery system are elucidated, and experience gained performing 20 flaps over the past 5 years by using the extended lower trapezius myocutaneous flap is reported. The vascular anatomy of the dorsal scapular artery system is reviewed in 13 fresh cadaveric dissections by using methylene blue, latex injection studies, and radiologic examination.

This paper develops a novel genetic algorithm (GA) based methodology for optimal tuning of a reported fuzzy dispatching system for a fleet of automated guided vehicles in a flexible manufacturing environment. The reported dispatching rules are transformed into a continuously adaptive procedure to capitalize the on-line information available from a shop floor at all times. Simulation results obtained show that the GA is very powerful and effective to achieve optimal fuzzy dispatching rules for higher shop floor productivity and operational efficiency.

We report a successful living related liver transplantation from a donor with von Willebrand's disease. With proper preparation, a substantial liver resection can be performed safely in such patients, and the transplanted liver will function normally.

The synthetic steroid 7alpha-methyl-19-nortestosterone (MENT) is a potent androgen that is resistant to 5alpha-reductase. It thus has decreased activity at the prostate and may have advantages over testosterone-based regimens in long term treatment or as part of a male contraceptive. Administration to eugonadal men results in suppression of gonadotropins, but its ability to support androgen-dependent behavior has not been investigated. For sustained release administration, MENT acetate was used, because its diffusion characteristics were more suitable for use in implants. However, upon release the acetate is rapidly hydrolyzed, and MENT is the biologically active moiety in circulation. We studied the effects of MENT on sexual interest and activity, spontaneous erection, and mood states in comparison with testosterone enanthate (TE) in 20 Caucasian and Chinese hypogonadal men recruited in Edinburgh and Hong Kong (n = 10 in each center). Outcomes were measured using a combination of daily diaries, semistructured interviews, and questionnaires. Nocturnal penile tumescence (NPT) was also recorded in the Edinburgh group. After withdrawal of androgen replacement treatment (wash-out phase) for a minimum of 6 weeks, subjects were randomized to two groups in a cross-over design. Drug treatment regimens were of 6-week duration and consisted of two implants, each containing 115 mg MENT acetate, inserted s.c. into the upper arm and removed after 6 weeks and two injections of TE (200 mg, i.m.) 3 weeks apart. MENT treatment resulted in stable plasma MENT concentrations of 1.4 +/- 0.1 nmol/L after 3 weeks and 1.3 +/- 0.1 nmol/L after 6 weeks (mean +/- SEM; all men). Nadir testosterone concentrations were 3.6 +/- 0.6 nmol/L at the end of the wash-out phase and 9.4 +/- 0.6 nmol/L 3 weeks after each injection. There were no differences in hormone concentrations between centers. There were no adverse toxicological effects. There were only minor differences between the two treatments. Both MENT and TE treatment resulted in significant increases in sexual interest and activity, spontaneous erection (both by self-report and NPT measurement), and increases in positive moods, with decreases in negative moods in the Edinburgh group. In the Hong Kong group, both treatments increased waking erection, with a trend toward increased sexual interest and activity. Mood states appeared to be less affected during the wash-out phase than in Edinburgh men and showed no significant response to either treatment. These results demonstrate that MENT has similar effects on sexual activity and mood states as testosterone in hypogonadal men. As NPT is a physiological androgen-dependant outcome, these data provide further evidence for the androgenicity of MENT. The lack of detected effect of either androgen in Hong Kong men other than on waking erection illustrates the importance of the cultural context of symptomatology and its measurement. The appropriate dose of MENT remains to be determined, but these results support its development as a potential androgen replacement therapy.

We report a case of locally advanced carcinoma of the rectum invading the bladder and prostate in a young man treated initially with neoadjuvant chemoradiotherapy. This was followed by an en bloc resection of the tumour, partial cystectomy and prostatectomy and an abdominal perineal resection. The urinary bladder was reconstructed and a new bladder neck reimplanted into the proximal urethra where the sphincter had been preserved. There was extensive radiation changes to the perineal skin where a wide excision had been performed. The pelvic defect was reconstructed with a pedicled transpelvic rectus abdominis myocutaneous flap. The patient recovered uneventfully and remains well with no clinical evidence of recurrence 18 months post-operatively. In very selected cases there is a definite role for neoadjuvant therapy and enbloc resection of the tumour followed by reconstruction of the perineum.

Recent studies have suggested that hypercholesterolemia is associated with endothelial dysfunction. In patients with type 2 diabetes mellitus, dyslipidemia is mainly characterized by hypertriglyceridemia, low high density lipoprotein, and a preponderance of small dense low density lipoprotein (LDL) particles. We have examined the relationships among LDL subfractions, the susceptibility of LDL to oxidation in vitro, and endothelial function in type 2 diabetes mellitus. LDL subfractions were measured by density gradient ultracentrifugation. The susceptibility of LDL to oxidation was determined by measuring the kinetics of conjugated dienes formation during copper-mediated oxidation of LDL. Endothelium-dependent and independent vasodilation of the brachial artery were assessed by high resolution vascular ultrasound. Diabetic patients had a higher concentration of small dense LDL-III than matched controls (P < 0.01). The lag phase of conjugated dienes formation was shorter in the diabetic patients (P < 0.05), and the rate of LDL oxidation was faster (P < 0.05). Both endothelium-dependent (P < 0.01) and independent dilation of the brachial artery (P < 0.01) were impaired in the diabetic patients. On multivariate analysis, the rate of oxidation and LDL-III concentration accounted for 12% and 6%, respectively, of the variation in endothelium-dependent vasodilation (adjusted r2 = 0.18; P < 0.05), whereas LDL-III concentration and the maximum amount of conjugated dienes formed accounted for 27% and 5%, respectively, of the variation in endothelium-independent vasodilation (adjusted r2 = 0.32; P < 0.01) in the diabetic patients. In conclusion, endothelial and smooth muscle cell dysfunction in type 2 diabetes were related to abnormalities in LDL subfractions and in LDL oxidation.

Patients with non-insulin-dependent diabetes mellitus (NIDDM) are known to have abnormalities in their low density lipoprotein (LDL) subclass pattern with a preponderance of small dense LDL. The present study was performed to define the roles of lipolytic enzymes (hepatic and lipoprotein lipase) and cholesteryl ester transfer protein (CETP) in determining the distribution of LDL subfractions in these patients. LDL subfractions were measured by density gradient ultracentrifugation in 137 patients with NIDDM (75 male, 62 female) and 140 matched controls (80 male, 60 female). The male diabetic patients had a lower concentration of LDL-I (P < 0.01) and a higher concentration of LDL-III than the controls (P < 0.01). In the female diabetic patients, both LDL-I (P < 0.001) and LDL-II concentrations (P < 0.05) were significantly lower than the controls whereas LDL-III was increased (P < 0.001). Hepatic lipase (HL) was significantly increased in both the male and female diabetic patients (P < 0.01, P < 0.05, respectively) compared to their controls. No significant changes were seen in plasma lipoprotein lipase (LPL) and CETP activity. On multivariate analysis, plasma triglyceride (TG), CETP and HL accounted for 10, 5 and 3% of the variability in LDL-III, respectively, in the diabetic patients (adjusted R2 = 0.18, P = 0.0003). Our findings would support the hypothesis that plasma triglyceride influences LDL particles through a cycle of lipid exchange via the action of CETP. LDL become enriched in triglyceride and are then acted on by HL to produce a population of small dense lipid-poor LDL.

This was an association study of genetic polymorphisms to compare the distribution of the genotypes and alleles of the HpaII polymorphism of the atrial natriuretic peptide (ANP) gene in hypertensive patients and normotensive controls. The setting was an outpatient clinic run by a University Department handling referrals from primary care. The patient cohort was composed of 217 subjects, consisting of 109 healthy controls and 108 patients with newly diagnosed or documented hypertension. The genomic DNA was extracted from peripheral blood leukocytes, amplified by polymerase chain reaction, and digested with the restriction enzyme HpaII. H1 and H2 alleles were identified after electrophoresis. The main outcome measures were to identify the frequencies of ANP genotypes and alleles in hypertensive patients and normotensive controls. The H1H1, H1H2, and H2H2 genotypes occurred in 1%, 19%, and 80% of controls and 3%, 18%, and 80% of hypertensive patients, respectively. The frequencies of the H1 and H2 alleles were 0.11 and 0.89 in controls and 0.12 and 0.88 in hypertensive patients. The frequencies of the ANP genotypes and alleles did not differ significantly between controls and hypertensive patients. Our findings differed from previous reports and suggested that this polymorphism is not associated with hypertension in this population.

Background: The objective of this study was to explore the role of the polymerase chain reaction (PCR) fo the detection of Mycobacterium tuberculosis DNA as a diagnostic aid in cutaneous tuberculosis using routinely processed skin biopsy specimens., Methods and Results: A wide range of clinical specimens representing different forms of cutaneous tuberculosis and so-called tuberculids were studied. A sensitive and specific PCR assay targeting the sequence IS6110 of Mycobacterium tuberculosis complex was used. The specimens were categorized as follows. 1 Acid-fast bacilli (AFB) positive on biopsy (nine specimens from seven patients who were immunocompromised). PCR was positive in five specimens. Of these, one specimen was culture positive and three specimens were culture negative. 2 AFB negative on biopsy: (a) tuberculosis verrucosa cutis (23 specimens); (b) lupus vulgaris (three specimens); (c) cutaneous tuberculosis clinically suspected (six specimens). PCR was negative in all specimens. 3 Tuberculids.' (a) erythema induratum/nodular vasculitis (20 specimens); (b) papulonecrotic tuberculid (two specimens); (c) erythema nodosum (20 specimens). PCR was negative in all specimens., Conclusions: The role of PCR in clinical dermatologic practice, at this stage, may be in differentiating between cutaneous tuberculosis and atypical mycobacterial infections in the context of an immunocompromised patient where AFB can be demonstrated on biopsy and cultures may be negative. In this clinical situation, PCR allows the prompt diagnosis and early institution of appropriate therapy. We have not found PCR to be a useful complement to the clinical and histologic diagnosis of "paucibacillary" forms of cutaneous tuberculosis.

1. Angiotensin-converting enzyme (ACE) genotypes in hypertensive patients were studied in order to delineate their cardiovascular risk due to the ACE gene. We hypothesized that the distribution of ACE genotypes may change with age because of the risk of myocardial infarction associated with the homozygous deletional (DD) genotype. 2. A total of 223 subjects were recruited from the Hypertension Outpatient Clinic of the Sai Ying Pun Hospital with consent. They consisted of 75 patients with newly diagnosed or documented hypertension, 46 patients with ischaemic heart disease and 102 normal controls. Genomic DNA was extracted from peripheral leucocytes and amplified by polymerase chain reaction. Insertion (I) or deletion (D) alleles were identified after electrophoresis. The frequencies of ACE genotypes and alleles were measured in three age groups: < 50 years, 50-59 years and > or = 60 years. 3. A significant correlation between ACE genotype and age was found (P = 0.03). The relative frequency of the D allele in those under 50 years of age was similar in controls and hypertensive patients (0.40 vs 0.41; P = 0.94), but was significantly lower in patients > or = 50 years compared with those patients < 50 years of age (0.22 vs 0.41; P = 0.01). 4. The observed decrease in frequency of the DD genotype in older hypertensive patients is consistent with the increase in cardiovascular risk associated with the D allele and raises the possibility that the DD genotype may increase the risk of premature death, at least in the population studied.

To investigate the effect of thyroid dysfunction on high-density lipoprotein (HDL) metabolism, we measured HDL subfractions, apolipoprotein A-I containing particles (LpA-I and LpA-I:A-II), and the activities of enzymes involved in the remodeling and metabolism of HDL [namely hepatic lipase (HL), lipoprotein lipase, and cholesteryl ester transfer protein (CETP)] in 18 hyperthyroid and 17 hypothyroid patients before and after treatment. HDL was subfractionated by density gradient ultracentrifugation, and LpA-I was analyzed by electroimmunodiffusion. The major changes were found in the HDL2 subfraction and in LpA-I particles. HDL2-C and LpA-I were reduced in hyperthyroidism (P < 0.01, P < 0.05, respectively) and increased in hypothyroidism (both P < 0.05) compared with their respective euthyroid matched controls. Changes in HDL2-cholesterol were reversed after treatment in both hyper- and hypothyroid patients, and LpA-I also decreased in the hypothyroid patients after treatment. HL (P < 0.05) and CETP activities (P < 0.05) were elevated in hyperthyroidism and reduced in hypothyroidism (P < 0.05, P < 0.01 respectively) and both were related to free T4 levels. The changes in HDL2-C and LpA-I correlated significantly with changes in HL after treatment but not with CETP or lipoprotein lipase. In summary, HDL metabolism was altered in thyroid dysfunction, and the effect of thyroid hormone on HDL was mediated mainly via its effect on HL activity.

This is a retrospective review of the use of microvascular flaps in the salvage of severely injured lower limb. From January 1992 to December 1994, we treated 10 patients using 10 microvascular flaps; 8 patients with Type III compound tibial fractures and 2 patients with infected implants following internal fixation of comminuted tibial fractures. The size of soft tissue defect ranged from 6 x 3 cm to 20 x 10 cm. One patient had a 6 cm bony defect. Soft tissue cover was achieved in 9 patients using microvascular muscle flaps with meshed split skin grafts and 1 patient using a scapula osteocutaneous flap. They were performed within 5 to 27 days following injury or removal of implants (mean 18 days). All the microvascular flaps were successful (100%). One re-exploration was performed. The mean period of hospitalization following microsurgical flap cover was 16.8 days. Eight out of 10 patients were followed up for a mean period of 48 months. All the 8 lower limbs were successfully salvaged. Three out of 8 patients (37.5%) had chronic osteomyelitis which required sequestrectomy and bone grafting. No amputation was necessary. Two patients required adjunctive cancellous bone grafting to accelerate bony union. Six out of 8 patients (75%) achieved bony union and full weight bearing capacity. The use of microvascular flap in achieving soft tissue cover plays an important role in the salvage of severely traumatized lower limb. Microvascular muscle flap is preferred when only soft tissue defect is present. Successful soft tissue cover facilitates secondary bone grafting procedures. Although the timing of surgery per se does not adversely affect the success rate of microvascular flaps, delayed soft tissue cover is associated with a high chronic infection rate (37.5%). An adequate surgical debridement is crucial in reducing the complication of deep infection.

Objectives: Gonadal steroids are important regulators of lipoprotein metabolism. The aims of this study were to determine the effects of a minimum effective dose of testosterone replacement on high density lipoprotein (HDL) subfractions and apolipoprotein (apo) A-I containing particles (lipoprotein (Lp)A-I) and LpA-I:A-II) in hypogonadal men with primary testicular failure and to investigate the underlying mechanisms of these changes., Measurements: Eleven Chinese hypogonadal men were started on testosterone enanthate 250 mg intramuscularly at 4-weekly intervals. HDL was subfractionated by density gradient ultracentrifugation and LpA-I was analysed by electro-immunodiffusion after 3, 6 and 12 weeks of treatment. Plasma cholesteryl ester transfer protein (CETP) activity and lipolytic enzymes activities in post-heparin plasma were measured to determine the mechanisms underlying testosterone-induced changes in HDL., Results: The dosage of testosterone enanthate used in the present study resulted in suboptimal trough testosterone levels. No changes were seen in plasma total cholesterol, triglyceride, low density lipoprotein cholesterol (LDL-C,) apo B and apo(a) after 12 weeks. There was a drop in HDL3-C compared to baseline (0.82 +/- 0.17 mmol/l vs. 0.93 +/- 0.13, P < 0.01) whereas a small but significant increase was seen in HDL2-C (0.21 +/- 0.13 mmol/l vs. 0.11 +/- 0.09, P < 0.05). Plasma apo A-I decreased after treatment (1.34 +/- 0.25 g/l vs. 1.50 +/- 0.29, P < 0.01), due to a reduction in LpA-I:A-II particles (0.86 +/- 0.18 g/l vs. 0.99 +/- 0.24, P < 0.01). No changes were observed in the levels of LpA-I particles. No significant changes were seen in plasma CETP and lipoprotein lipase activities after testosterone replacement but there was a transient increase in hepatic lipase (HL) activity at weeks 3 and 6. The decrease in HDL correlated with the increase in HL activity (r = 0.62, P < 0.05)., Conclusions: Testosterone replacement in the form of parenteral testosterone ester given 4-weekly, although unphysiological, was not associated with unfavourable changes in lipid profiles. The reduction in HDL was mainly in HDL3-C and in LpA-I:A-II particles and not in the more anti-atherogenic HDL2 and LpA-I particles. The changes in HDL subclasses were mainly mediated through the effect of testosterone on hepatic lipase activity.

Background/aim of Study: Liver transplantation was first performed in 1967, and has become an accepted form of treatment worldwide for chronic liver diseases, acute liver failure and certain metabolic diseases. We document our experience in Singapore over the last 7 years since the first transplant was performed in 1990., Method: Retrospective study at National University Hospital, Singapore., Results: Twenty-two operations (10 paediatric and 12 adults) have been performed with the last 17 having been performed in the last 17 months. Currently, there are 15 survivors (68%) since 1990, and percentage survival is even better if one considers the cases from the last 17 months when the majority of cases (17 transplants-77%) were performed (77% survival). The most common indication for transplant was biliary atresia for the paediatric group, while the adults were transplanted for hepatitis B and C cirrhosis, primary biliary cirrhosis, and fulminant liver failure. Tacrolimus is the main immunosuppression (10 patients), with the remaining 5 patients on cyclosporine. Various surgical techniques (living donor, graft reduction) have been employed successfully to provide a complete transplant service. Hospital and ICU stays are within normal limits and the hospital charges range from a low of S$30,000 to S$141,000., Conclusion: Liver transplantation has become a reality in Singapore with outcomes comparable to other transplant centres. The shortage of donors remains the greatest stumbling block for further expansion.

Background: Cutaneous complications arising from exposure to Chinese proprietary medicines known to contain inorganic arsenic have been rarely reported., Objective: Our purpose was to study the nature, incidence, and sequelae of patients with chronic arsenicism and to review the literature on arsenic-induced skin diseases., Methods: Case records of patients with cutaneous lesions related to chronic arsenicism seen from January 1990 to December 1996 were reviewed. Patients were interviewed and a complete skin and systemic examination was performed. Data on demography, history of arsenic ingestion, and type and distribution of skin lesions and visceral malignancy were collated., Results: Seventeen Chinese patients (11 men, six women) were identified; their mean age was 64.5 years. Fourteen patients (82%) had exposure to Chinese proprietary medicines known to contain inorganic arsenic, and three had environmental arsenic exposure from well water. The mean age of these 14 patients was 17.6 years; mean duration of arsenic intake was 6.4 years. Seventeen patients had Bowen's disease; of these, 70% had 2 to 10 lesions. Of the 17 patients with arsenical keratoses on the palms, 76% had 2 to 10 lesions. Of the 14 patients (82%) with plantar arsenical keratoses, 64% had 11 to more than 50 lesions. Eleven patients (65%) had macular hypopigmentation. Seven patients (41%) had 11 squamous cell carcinomas (SCCs); three of the seven had more than one lesion. Fifty-five percent of SCCs arose from preexisting keratotic lesions (n = 4) or Bowen's disease (n = 2), and 45% arose de novo. One patient each (6%) had multiple basal cell carcinomas, laryngeal carcinoma, and metastatic SCC. The latency periods for the development of arsenical keratoses, Bowen's disease, and SCC were 28, 39, and 41 years, respectively. Patients with SCC were significantly older at the start of arsenic exposure and had significantly more palmar arsenical keratoses than those without SCC., Conclusion: Exposure to Chinese proprietary medicines containing inorganic arsenic poses a risk for the development of cutaneous and systemic malignancies. Long-term follow-up is necessary for tumor detection because of long latency periods. Surveillance programs are important to restrict the sale of Chinese proprietary medicines that may contain inorganic arsenic.

Thyroid dysfunction is associated with multiple changes in lipoprotein metabolism, and we have determined the effects of thyroid dysfunction on plasma cholesteryl ester transfer protein (CETP) activity. CETP is a plasma protein that mediates the exchange of cholesteryl ester and triglyceride between plasma lipoproteins and plays an important role in high-density lipoprotein metabolism and in the reverse cholesterol transport pathway. Plasma CETP activity was assayed in 18 hyperthyroid and in 17 hypothyroid patients, before and after treatment, by measuring the transfer of cholesteryl esters from exogenous radiolabeled high-density lipoprotein to apolipoprotein B-containing lipoproteins. Plasma CETP activity was increased in hyperthyroid patients, compared with their matched controls (22.11 +/- 8.92% transferred/5 microL.4 h vs. 16.75 +/- 6.48, P < 0.05), whereas in hypothyroid patients, plasma CETP activity was decreased (11.14 +/- 4.84% transferred/5 microL.4 h vs. 17.26 +/- 7.13, P < 0.01). Plasma CETP activity decreased after treatment of thyrotoxicosis, although a significant change was observed, mainly in the severely thyrotoxic patients with free T4 > 100 pmol/L (n = 11, 25.61 +/- 8.12% transferred/5 microL.4 h vs. 21.71 +/- 7.84, P < 0.05). In the hypothyroid patients, there was a significant increase in plasma CETP activity after thyroxine replacement (11.14 +/- 4.84% transferred/5 microL.4 h vs. 15.46 +/- 6.71, P < 0.01). There was a strong positive correlation between log(free T4) and plasma CETP activity (r = 0.51, P < 0.001). In summary, both hyper- and hypothyroidism are associated with significant changes in plasma CETP activity, and these changes are corrected when the patients have been rendered euthyroid.