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Biomedical subjects

K S Lam

Publications and source records attributed to K S Lam.

At least 19 recordsLinked to original sources
PubMed2003

Wrist function after excision of the pisiform.

The pisiform bone may provide mechanical stability to the ulnar column of the wrist by preventing triquetral subluxation. Thus, surgical excision of the pisiform might cause loss of function to the wrist. We performed a functional evaluation of 20 hands in 20 patients who had undergone pisiformectomy for pisotriquetral joint dysfunction. At a mean follow-up of 65 months, 15 patients had complete relief of symptoms and five continued with mild discomfort. Compared with the unaffected wrist, there were no significant differences in grip strength and wrist movement, static strength and dynamic power. We conclude that pisiformectomy for pisotriquetral joint dysfunction can be safely recommended because restoration of function with a painless wrist is the normal outcome.

Adolescent↗
PubMed2003

The first patient with locally acquired dengue fever in Hong Kong.

This report is of the first locally acquired case of dengue fever. The diagnosis was made even in the absence of a history of travel outside Hong Kong. The patient was a 21-year-old man, who presented with high fever, leukopenia, thrombocytopenia, and elevated liver enzymes. His haematocrit revealed mild haemoconcentration but the albumin was normal throughout the course of the illness. His blood pressure remained low with no tachycardia or overt shock syndrome. The pyrexia subsided 4 days after admission to hospital and all haematological and biochemical abnormalities eventually normalised. The pathogenesis, diagnostic criteria of dengue haemorrhagic fever and dengue shock syndrome, and control of dengue infection are discussed.

Adult↗
PubMed2002

The importance of early diagnosis in the management of proximal tibiofibular dislocation: a 9- and 5-year follow-up of a bilateral case.

Unilateral fibula head dislocation is an uncommon injury. Ogden in 1974 reviewed the literature and detected 108 cases [J. Bone Joint Surg. 56(A) (1974) 145-154]. There since have been few reported cases. Bilateral fibula head dislocation only has been reported once [Rheumatol. Int. 5(1) (1984) 45-47]. We report a patient who had developed bilateral fibula head dislocations, each side independently over a 5-year period. We emphasise the rarity of the injury, the necessity of prompt recognition and reduction, and the uncertainty for best management of this injury.

Adult↗
PubMed2002

The effect of space flight on the production of actinomycin D by Streptomyces plicatus.

The effect of space flight on production of the antibiotic actinomycin D by Streptomyces plicatus WC56452 was examined onboard the US Space Shuttle mission STS-80. Paired space flight and ground control samples were similarly prepared using identical hardware, media, and inoculum. The cultures were grown in defined and complex media under dark, anaerobic, thermally controlled (20 degrees C) conditions with samples fixed after 7 and 12 days in orbit, and viable residuals maintained through landing at 17 days, 15 h. Postflight analyses indicated that space flight had reduced the colony-forming unit (CFU) per milliliter count of S. plicatus and increased the specific productivity (pg CFU(-1)) of actinomycin D. The antibiotic compound itself was not affected, but its production time course was altered in space. Viable flight samples also maintained their sporulation ability when plated on agar medium postflight, while the residual ground controls did not sporulate.

Dactinomycin↗
PubMed2002

To establish the normal bone mineral density reference database for the Singapore male.

INTRODUCTION: The objective of this study was to establish the normal bone mineral density (BMD) reference curve for the Asian Singapore male. MATERIALS AND METHODS: Three hundred and eighty-three male subjects were enrolled; comprising of 309 Chinese, 44 Malays and 30 Indians resident in Singapore. Bone mineral density was measured at the lumbar spine and left hip using a Hologic QDR 4500 Elite dual-energy X-ray absorptiometry (DXA) scanner. RESULTS: The mean peak BMD for the average lumbar spine and the neck of femur was 1.006 g/cm2 and 0.97 g/cm2, respectively. The mean peak BMD was taken at the 20 to 24 years age group at both the hip and spine based on data distribution for the various age groups. The BMD corresponding to -2.5 standard deviations from the peak adult value was 0.719 g/cm2 for the average lumbar spine and 0.655 g/cm2 for the neck of femur. CONCLUSION: This Asian male BMD reference database, which is 10% and 5% lower than corresponding values from the Caucasian reference database, allows for more accurate diagnosis of osteoporosis in Asian males.

Absorptiometry, Photon↗
PubMed2001

Immunoreactivity of organic mimeotopes of the E2 component of pyruvate dehydrogenase: connecting xenobiotics with primary biliary cirrhosis.

In primary biliary cirrhosis (PBC), the major autoepitope recognized by both T and B cells is the inner lipoyl domain of the E2 component of pyruvate dehydrogenase. To address the hypothesis that PBC is induced by xenobiotic exposure, we took advantage of ab initio quantum chemistry and synthesized the inner lipoyl domain of E2 component of pyruvate dehydrogenase, replacing the lipoic acid moiety with synthetic structures designed to mimic a xenobiotically modified lipoyl hapten, and we quantitated the reactivity of these structures with sera from PBC patients. Interestingly, antimitochondrial Abs from all seropositive patients with PBC, but no controls, reacted against 3 of the 18 organic modified autoepitopes significantly better than to the native domain. By structural analysis, the features that correlated with autoantibody binding included synthetic domain peptides with a halide or methyl halide in the meta or para position containing no strong hydrogen bond accepting groups on the phenyl ring of the lysine substituents, and synthetic domain peptides with a relatively low rotation barrier about the linkage bond. Many chemicals including pharmaceuticals and household detergents have the potential to form such halogenated derivatives as metabolites. These data reflect the first time that an organic compound has been shown to serve as a mimeotope for an autoantigen and further provide evidence for a potential mechanism by which environmental organic compounds may cause PBC.

Amino Acid Sequence↗
PubMed2001

Automatic Edman microsequencing of peptides containing multiple unnatural amino acids.

It is now routine using automatic Edman microsequencing to determine the primary structure of peptides or proteins containing natural amino acids; however, a deficiency in the ability to readily sequence peptides containing unnatural amino acids remains. With the advent of synthetic peptide chemistry, combinatorial chemistry, and the large number of commercially available unnatural amino acids, there is a need for efficient and accurate structure determination of short peptides containing many unnatural amino acids. In this study, 35 commercially available alpha-unnatural amino acids were selected to determine their elution profile on an ABI protein sequencer. Using a slightly modified gradient program, 19 of these 35 PTH amino acids can be readily resolved and distinguished from common PTH amino acids at low picomole levels. These unnatural amino acids in conjunction with the 20 natural amino acids can be used as building blocks to construct peptide libraries, and peptide beads isolated from these libraries can be readily microsequenced. To demonstrate this, we synthesized a simple tripeptide "one-bead one-compound" combinatorial library containing 14 unnatural and 19 natural amino acids and screened this library for streptavidin-binding ligands. Microsequencing of the isolated peptide-beads revealed the novel motif Bpa-Phe(4-X)-Aib, wherein X = H, OH, and CH3.

Amino Acids↗
PubMed2001

Synthetic peptides inhibit adhesion of human tumor cells to extracellular matrix proteins.

Human tumor cell progression and metastasis are partially dependent on the ability of a tumor cell to adhere to the proteins of the extracellular matrix (ECM) and survive at the distant location. Six novel D-amino acid-containing peptides were analyzed for their ability to adhere to human prostate tumor cells, support tumor cell adhesion, and inhibit tumor cell adhesion to ECM proteins or human dermal fibroblasts. Of these, two peptides called RZ-3 (kmviywkag) and HYD-1 (kikmviswkg) bound to tumor cell surfaces and compared favorably with the previously reported AG-73 (RKRLQVQLSIRT) L-amino acid peptide, as determined by fluorescence-activated cell sorting analysis. A scrambled peptide derivative of HYD-1, called HYDS-1 (wiksmkivkg), was not active. The RZ-3, HYD-1, and AG-73 peptides supported maximal cancer cell adhesion at 5 microg, 10 microg, and 50 microg/well, respectively. The ECM proteins fibronectin, laminin 1, and collagen IV supported maximal cell adhesion at 1 microg, >10 microg, and 50 microg/well, respectively. Prostate tumor cell adhesion to immobilized RZ-3 and HYD-1 peptides was inhibited by alpha2-6- and beta1-integrin-blocking antibodies. Conversely, tumor cell adhesion to a beta1-integrin-specific antibody was blocked by both RZ-3 and HYD-1. Epithelial cell adhesion to dermal fibroblasts was inhibited by HYD-1 and unaffected by the scrambled peptide, HYDS-1. Cell adhesion to immobilized peptides was unaffected by EDTA. The soluble RZ-3 and HYD-1 peptides inhibited tumor cell adhesion to each of the immobilized four ECM proteins (1.0 microg/well) in a time- and concentration-dependent manner. The IC(50) of the RZ-3 peptide for blocking adhesion to fibronectin, laminin 1, laminin 5, and collagen IV was 2.4 microg, 1.8 microg, 4.6 microg, and 2.8 microg/well, respectively. The IC(50) of the HYD-1 peptide for blocking adhesion to fibronectin, laminin 1, laminin 5, and collagen IV was 6.9 microg, 5.7 microg, >10 microg, and 6.2 microg/well, respectively. Taken together, these results indicate that RZ-3 and HYD-1 are biologically active D-amino acid-containing peptides that can themselves support tumor cell adhesion and can inhibit tumor cell adhesion to immobilized ECM proteins or dermal fibroblasts.

Carcinoma, Squamous Cell↗
PubMed2001

Attomole level protein sequencing by Edman degradation coupled with accelerator mass spectrometry.

Edman degradation remains the primary method for determining the sequence of proteins. In this study, accelerator mass spectrometry was used to determine the N-terminal sequence of glutathione S-transferase at the attomole level with zeptomole precision using a tracer of (14)C. The transgenic transferase was labeled by growing transformed Escherichia coli on [(14)C]glucose and purified by microaffinity chromatography. An internal standard of peptides on a solid phase synthesized to release approximately equal amounts of all known amino acids with each cycle were found to increase yield of gas phase sequencing reactions and subsequent semimicrobore HPLC as did a lactoglobulin carrier. This method is applicable to the sequencing of proteins from cell culture and illustrates a path to more general methods for determining N-terminal sequences with high sensitivity.

Carbon Radioisotopes↗
PubMed2001

Prospective evaluation of cancer clinical trial accrual patterns: identifying potential barriers to enrollment.

PURPOSE: Well-conducted cancer clinical trials are essential for improving patient outcomes. Unfortunately, only 3% of new cancer patients participate in clinical trials. Barriers to patient accrual in cancer clinical trials must be identified and overcome to increase patient participation. MATERIALS AND METHODS: We prospectively tracked factors that potentially affected patient accrual into cancer clinical trials at the University of California Davis Cancer Center. Oncologists seeing new outpatients were asked to complete questionnaires regarding patient characteristics and the physician's decision-making on patient eligibility, protocol availability, and patient opinions on participation. Statistical analysis was performed to correlate these parameters with subsequent protocol accrual. RESULTS: There were 276 assessable patients. At the initial visits, physicians did not consider clinical trials in 38% (105/276) of patients principally because of a perception of protocol unavailability and poor performance status. Physicians considered 62% (171/276) of patients for participation in clinical trials. Of these, only 53% (91/171) had an appropriate protocol available for site and stage of disease. Seventy-six of 90 patients (84%) with available protocols met eligibility criteria for a particular study. Only 39 of 76 patients (51%) agreed to participate in cancer clinical trials, for an overall accrual rate of 14% (39/276). The remainder (37/76, 49%) declined trial participation despite meeting eligibility criteria. The most common reasons were a desire for other treatment (34%), distance from the cancer center (13%), patient refusal to disclose reason (11%), and insurance denial (8%). Patients with private insurance were less likely to enroll in clinical trials compared to those with government-funded insurance (OR, 0.34; P =.03; 95% CI, 0.13 to 0.9). CONCLUSION: Barriers to cancer clinical trial accrual can be prospectively identified and addressed in the development and conduct of future studies, which may potentially lead to more robust clinical trials enrollment. Investigation of patient perceptions regarding the clinical trials process and the role of third party-payers is warranted.

Adolescent↗
PubMed2001

Central obesity predicts the worsening of glycemia in southern Chinese.

AIMS: The association between obesity and type 2 diabetes has been found to be consistent across different ethnic populations. Our aim was to study the contribution of obesity to the development of type 2 diabetes in a non-obese Chinese population with a high prevalence of diabetes (9.8% in 1995-1996). METHODS: Six-hundred and forty-four non-diabetic subjects were recruited from the Hong Kong Cardiovascular Risk Factor Prevalence Study (1995-1996). This was a community-based population study which involved the use of a 75 g oral glucose tolerance test and 1985 World Health Organization diagnostic criteria. Their glycemic status was reassessed at 2 y. RESULTS: In subjects with impaired glucose tolerance (n=322), the annual progression rate to diabetes (4.8%; 95% CI 2.5-7.1%), was 8-fold that in control subjects (0.6%; 95% CI 0.0-1.4%; P<0.001). Baseline waist-hip ratio (WHR; OR per unit increase=1.05; 95% CI 1.02-1.07, P=0.0003) and post-load 2 h plasma glucose (OR per unit increase=2.02; 95% CI 1.76-2.34, P<0.0001) were significantly associated with glycemic status at 2 y in stepwise polytomous logistic regression analysis. Subjects with high baseline waist circumference or WHR (> or =median) were more likely to have worsening of glucose tolerance at 2 y than those with low waist circumference (<median; conversion to diabetes, OR 3.8, P=0.001) or WHR (<median; conversion to diabetes, OR 2.8, P=0.019). CONCLUSION: Abdominal obesity, readily assessed by the measurement of WHR or waist circumference, was for the first time shown prospectively to be independently associated with the deterioration of glucose tolerance in a Chinese population.

Abdomen↗
PubMed2001

Effect of Sandostatin LAR on serum leptin levels in patients with acromegaly.

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.

Acromegaly↗
PubMed2001

Effect of Sandostatin LAR on sleep apnoea in acromegaly: correlation with computerized tomographic cephalometry and hormonal activity.

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.

Acromegaly↗
PubMed2001

Heterogeneous response of antimitochondrial autoantibodies and bile duct apical staining monoclonal antibodies to pyruvate dehydrogenase complex E2: the molecule versus the mimic.

The 2-oxo-acid dehydrogenase complexes and, in particular, the E2 component of the pyruvate dehydrogenase complex (PDC) are the target of antimitochondrial antibodies (AMA). More than 95% of primary biliary cirrhosis (PBC) patients have detectable levels of autoantibodies to PDC-E2 and in general these react with a region of the molecule that contains the prosthetic group lipoic acid (LA). LA is vital to the function of the enzyme, although there is conflicting evidence as to whether its presence is required for PDC-E2 recognition by AMA. Some, but not all, monoclonal antibodies (mAbs) to PDC-E2 produce an intense staining pattern at the apical surface of bile duct epithelial cells (BEC) in patients with PBC, and it has been argued that the molecule at the apical surface of PBC bile duct cells is a modified form of PDC-E2 or a cross-reactive molecule, acting as a molecular mimic. Herein, we characterize the epitopes recognized by 4 anti-PDC-E2 mAbs that give apical staining patterns (3 mouse and 1 human). In particular, by using a combination of recombinant antigens, competitive inhibition assays, and a unique peptide-on-bead assay, we determined that these apically staining mAbs recognize 3 or 4 distinct epitopes on PDC-E2. More importantly, this suggests that a portion spanning the entire inner lipoyl domain of PDC-E2 can be found at the BEC apical surface. In addition, competition assays with patient sera and a PDC-E2-specific mAb showed significant epitope overlap with only 1 of the 3 mouse mAbs and showed a differential response to the peptide bound to beads. These findings further highlight the heterogeneous response of patient autoantibodies to the inner lipoyl domain of PDC-E2.

Amino Acid Sequence↗
PubMed2001

The clinicopathological features and importance of p53, Rb, and mdm2 expression in phaeochromocytomas and paragangliomas.

AIMS: Phaeochromocytomas and paragangliomas are uncommon. The aims of this study were to analyse the characteristics and the possible roles of p53, Rb, and mdm2 alterations in these tumours. METHODS: The clinicopathological features of 65 patients (31 men, 34 women) with phaeochromocytomas or paragangliomas were analysed. The tumours were studied for the expression of p53, Rb, and mdm2 by immunohistochemical methods. RESULTS: Thirty nine of the patients had phaeochromocytomas and 26 had paragangliomas. Bilateral tumours were noted in eight of the patients and malignant tumours were seen in 13. Paragangliomas were often small, non-functional, and presented incidentally, whereas phaeochromocytomas were usually large, functional, and symptomatic. p53 overexpression, loss of Rb expression, and mdm2 overexpression were seen in four, 43, and 37 of the patients, respectively. Three of the four patients with p53 overexpression had bilateral tumours. Loss of Rb expression was often found in phaeochromocytomas, whereas mdm2 overexpression was more frequently seen in paragangliomas. The 10 year survival rate of patients with malignant tumours was 45%. Two patients died of tumour metastases more than 10 years after resection of the primary tumours. CONCLUSIONS: Phaeochromocytomas and paragangliomas had distinctive clinical features and genetic alterations. The prognosis of patients with these tumours was related to the malignant potential. p53 overexpression, more common in bilateral phaeochromocytomas and paragangliomas, could be a marker for this tumour subgroup.

Adolescent↗
PubMed2001

A randomized controlled trial of low-dose recombinant human growth hormone in the treatment of malnourished elderly medical patients.

High-dose recombinant human GH (rhGH) has been shown to improve the nutritional status of malnourished older adults. It is uncertain whether low-dose rhGH is effective and whether its effect on nutritional status will lead to any improvement in physical function. There is also no data on the outcome after a short course of rhGH treatment. The objectives of this study were to determine the efficacy of low-dose rhGH treatment for 4 weeks in malnourished elderly patients, its effect on physical functions, and the intermediate term outcome after a 4-week rhGH treatment. The study design was a randomized, placebo-controlled, double-blind trial conducted in a university teaching hospital. The patients were 19 medically stable malnourished elderly subjects. Intervention in the rhGH group was as follows: rhGH (Saizen, Serono, Switzerland) 0.09 IU/kg body weight (BW) 3 times weekly were given together with appropriate dietary intervention as prescribed by the dietitian. In the placebo group, equal volumes of normal saline per kilogram BW were given 3 times weekly together with the dietary intervention. The baseline demographic, anthropometric, nutritional, and hematological variables, measures of physical function, and insulin-like growth factor I levels in both groups were comparable. Compared with the placebo group, the GH-treated group showed a more rapid gain in BW (after 3 weeks, +1.27 +/- 0.36 vs. -0.28 +/- 0.37 kg; P = 0.008), total lean body mass (change after 3 weeks by bio-impedance analysis, +1.45 +/- 0.36 vs. -0.37 +/- 0.48 kg; P = 0.009) and a faster improvement in 5-m walking time (decrease after 4 weeks, 23.79 +/- 9.41 vs. 0.45 +/- 4.62 sec; P = 0.047). The hemoglobin level rose more in the rhGH than the placebo groups (change at 8 weeks, +0.84 +/- 0.34 vs. -0.42 +/- 0.29 g/dL; P = 0.012). Serum albumin level also showed a greater delayed increase in the rhGH group than in the placebo group (change at 8 weeks, +5.1 +/- 0.8 vs. 1.6 +/- 1.2 g/dL; P = 0.023). There was no statistically significant difference for other nutritional variables. There was a greater rise in the mean serum insulin-like growth factor I level at 4 weeks in the GH than in the placebo groups (197 +/- 58 vs. 54 +/- 26 U/L; P = 0.034). The improvement in the rhGH group gradually diminished on follow-up and became statistically insignificant 8 weeks after stopping rhGH treatment. There were no GH-related adverse effects. Low-dose rhGH was an effective and safe adjuvant to dietary augmentation for stable malnourished elderly subjects. It led to a faster gain in total lean body mass, which was associated with greater improvement in walking speed when compared with dietary intervention alone. There were no apparent side effects.

Aged↗