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Biomedical subjects

C W Lam

Publications and source records attributed to C W Lam.

At least 55 records · Page 3Linked to original sources
PubMed2001

Whole blood mercury concentrations in sub-fertile men in Hong Kong.

We aimed to investigate the association between whole blood mercury concentrations and semen quality in sub-fertile men. Fifty-nine male partners of infertile couples attending the Assisted Reproduction Unit of the Chinese University of Hong Kong between 1997 and 1998 were recruited into our study. Blood was taken from each subject for whole blood mercury concentration and hormone profile. Semen samples were obtained for computer assisted semen analysis using the Hobson sperm tracker. The semen parameters and hormone profile were compared between subjects with normal and those with elevated mercury concentrations. Twenty-one subjects (35.6%) had a whole blood mercury concentration higher than the normal range (0-50 nmol/l). All parameters of the semen analysis including the concentration of sperm, percentage of morphologically normal sperm, percentage of motile sperm, curvilinear velocity, straight-line velocity, average path velocity, and amplitude of lateral head displacement, were reduced in those with elevated blood mercury concentrations, although the difference was not statistically significant. We failed to demonstrate a statistically significant effect on the measurement of semen quality, but other adverse effects cannot be excluded. From a public heath perspective, these findings confirm that mercury toxicity is a potentially serious problem affecting the local community.

Adult↗
PubMed2001

Hepatic iron storage in very low birthweight infants after multiple blood transfusions.

OBJECTIVE: To investigate the effect of multiple blood transfusions on hepatic iron storage in preterm, very low birthweight (VLBW) infants. METHODS: Seventeen VLBW infants who died within the first six months of life and underwent postmortem examination were studied. Serum ferritin, iron, and total iron binding capacity were measured within the week before the infants' death. Liver iron concentration was quantitatively determined by atomic absorption spectrophotometry and semiquantitatively assessed by histochemical liver iron grading. The clinical characteristics and the iron results were compared between infants receiving < 100 ml of blood (group A) and those receiving >/= 100 ml (group B). Spearman's correlation coefficient was used to evaluate the relation between the volume of blood transfused and serum/liver iron concentrations. Statistically significant variables associated with liver iron concentration were further subjected to multivariate stepwise regression analysis. RESULTS: Infants in group B had significantly higher serum iron (p < 0.01), serum ferritin (p < 0.01), and liver iron concentration (p < 0.01) than those in group A. The total and net volume of blood transfused were significantly associated with liver iron concentration (p < 0.001, r = 0.86; p < 0.001, r = 0.71 respectively), semiquantitative histochemical liver iron grading (p < 0.001, r = 0.80; p < 0.005, r = 0.71 respectively), and serum ferritin (p < 0.001, r = 0.84; p < 0.01, r = 0.69 respectively). In addition, both liver iron concentration and liver iron grading were found to be significantly associated with serum ferritin (p < 0.001, r = 0.76; p < 0.005, r = 0.68 respectively). Multivariate stepwise regression analysis indicated that the (log) liver iron concentration was significantly associated with the (log) volume of blood transfusion (p < 0.001; regression coefficient 0.39, SE 0.09), after adjustment for gestational age (R(2) = 0.84). CONCLUSIONS: This study showed a significant positive relation between the volume of blood transfused and the liver iron concentration in preterm VLBW infants. Although the transfusional blood volume correlated closely with the amount of iron deposited in hepatic tissues, clinical manifestations of iron overload were not observed. Carers should be aware of this potential harmful effect before prescribing blood or routine iron supplement to vulnerable preterm infants.

Blood Transfusion↗
PubMed2001

Refractory hypotension in preterm infants with adrenocortical insufficiency.

Five preterm, very low birthweight infants with severe hypotension and adrenocortical insufficiency are described. The profound hypotension was resistant to volume expansion and inotrope treatment, but responded promptly to corticosteroid treatment. A human corticotrophin releasing hormone (hCRH) test performed before corticosteroid treatment showed adequate pituitary response, and the endocrine dysfunction was identified at the adrenal level. Corticosteroid treatment should be considered and could be life saving in severely hypotensive preterm infants who do not respond to conventional treatment with volume expanders and inotropes.

Adrenal Insufficiency↗
PubMed2001

Simvastatin increases serum osteocalcin concentration in patients treated for hypercholesterolaemia.

Animal studies, experimental models on cell lines, and epidemiological case-control studies have all suggested the possibility that 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors have a beneficial effect on bone metabolism. However, all epidemiological studies are not prospective in nature and based on either measurement of bone mineral density or fracture risk. They also differ in recruitment criteria, definition of statin exposure, and outcome assessment. We performed a first prospective study using specific biochemical bone markers on 17 hypercholesterolaemic non-osteoporotic subjects treated with a therapeutic dose of simvastatin 20 mg daily for 4 weeks. Our results show that serum osteocalcin concentration increased significantly (p-value < 0.05) 4 weeks after therapy, whereas other bone markers including serum bone-specific alkaline phosphatase activity, urine deoxypyridinoline, and urine cross-linked N-telopeptides of type I collagen did not show any significant changes. Our data support that simvastatin causes a beneficial effect on bone metabolism as reflected by an increase in serum osteocalcin concentration. This added beneficial effect of statins on bone metabolism could potentially allow statins to become the first effective anabolic agent for the treatment of osteoporosis. We urge that priority should be given to a randomised controlled study to re-evaluate this group of drugs.

Adult↗
PubMed2001

Effect of low molecular weight heparin on bone metabolism and hyperlipidemia in patients on maintenance hemodialysis.

The effect of low molecular weight heparin (LMWH) on serum lipid profile in hemodialysis remains controversial and its effect on bone metabolism has not been studied. A crossover study was conducted in 40 patients on stable hemodialysis using unfractionated heparin (UFH) for more than 24 months. These patients were then treated with a LMWH (nadroparin-Ca) for 8 months during hemodialysis and subsequently switched back to UFH for 12 months. Serum lipid profile, biochemical markers for bone metabolism, and bone densitometry (BMD) were monitored at four-month intervals while all medications remained unchanged. Cholesterol (TC), triglyceride (TG), low-density lipoprotein-cholesterol (LDL-C), lipoprotein(a) (Lp(a)), apolipoprotein B (Apo B) were raised in 35%, 29%, 12%, 24% and 24% of patients respectively. High-density lipoprotein-cholesterol (HDL-C) and apolipoprotein A1 (Apo A-1) were reduced in 47% and 9% of patients. Bone-specific alkaline phosphatase (BALP) and intact osteocalcin (OSC), both reflecting osteoblastic activity, were raised in 65% and 94% of patients. Tartrate-resistant acid phosphatase (TRACP) reflecting osteoclastic activity and parathyroid hormone (PTH) were elevated in 35% and 88% of patients. Following LMWH treatment, TC, Tg, Lp(a) and Apo B were reduced by 7%, 30%, 21% and 10% respectively (p<0.05 or <0.01) while Apo A-1 were raised by 7% (p<0.01). Simultaneously, TRACP was reduced by 13% (p<0.05). These biochemical changes were detected soon after 4 months of LMWH administration. Although BMD values in our patients were lower than those of age-matched normal subjects, significant changes were not observed with LMWH treatment. After switching back to UFH for hemodialysis, these biochemical indices reverted to previous values during UFH treatment with a significant higher level in TC and Apo B while serum Apo A-1 remained elevated. Our study suggests LMWH may partially alleviate hyperlipidemia and, perhaps, osteoporosis associated with UFH administration in patients on maintenance hemodialysis.

Adult↗
PubMed2000

Molecular prognostication of nasopharyngeal carcinoma by quantitative analysis of circulating Epstein-Barr virus DNA.

We investigated the prognostic implication of pretreatment plasma/serum EBV DNA concentration, as measured by real-time quantitative PCR, in nasopharyngeal carcinoma (NPC). In 91 prospectively recruited NPC patients, those with recurrence or metastasis within the first year after treatment had a higher median plasma EBV DNA concentration than those without events (41,756 copies/ml versus 5,807 copies/ml; P < 0.001, Mann-Whitney rank-sum test). In multivariate logistic regression analysis, plasma EBV DNA was an independent prognostic indicator for early clinical events [relative risk = 3.8 (95% confidence interval, 1.6-9.2 for each 10-fold increase in plasma EBV DNA concentration; P = 0.003)]. In a second cohort of 139 NPC patients followed-up for a median period of 2,027 days (interquartile range, 597-2,335 days), serum EBV DNA was found to be a significant variable associated with NPC-related death in multivariate Cox's regression analysis [relative risk = 1.6 (95% confidence interval, 1.1-2.1 for each 10-fold increase in serum EBV DNA concentration; P = 0.007)]. The quantitation of circulating EBV DNA may thus allow improved prognostication of NPC.

Adult↗
PubMed2000

Prenatal diagnosis of glycogen storage disease type 1b using denaturing high performance liquid chromatography.

Glycogen storage disease type 1b (GSD1b) is an autosomal recessive inborn error of metabolism caused by deficiency of glucose-6-phosphate translocase (G6PT1). Current laboratory diagnosis for GSD1b is established by a functional enzyme assay of glucose-6-phosphatase in both fresh and detergent-treated liver homogenates. This procedure requires liver biopsy and is impractical for routine prenatal diagnosis owing to the high morbidity of fetal liver biopsy. Recently, the gene for GSD1b has been cloned and the prevalent mutations in different ethnic groups have been determined. In this study, prenatal molecular diagnosis was performed for a Chinese family in which a previous child was born homozygous for the G149E mutation. We detected genomic sequence variants by heteroduplex formation, followed by denaturing high performance liquid chromatography (DHPLC). With this method, post-PCR analysis was shortened to 7 min. In the case we analysed, PCR products amplified from the fetal DNA yielded a single peak in the chromatogram, indicating a homozygous state in the fetus. When wild-type PCR products were mixed with fetal PCR products, two peaks were observed, indicating that the fetus was homozygous for the parental (G149E) mutation. Sequencing results confirmed this diagnosis. As a result, the pregnancy was terminated and the diagnosis was confirmed on DNA analysis of the aborted fetus. We show here that DNA mutation analysis can be used in the prenatal diagnosis of GSD1b and that DHPLC promises to be a robust technique for this and other prenatal molecular diagnoses.

Abortion, Eugenic↗
PubMed2000

A crossover study of triptorelin and leuprorelin acetate.

OBJECTIVE: To compare the potency, side effects, and duration of action of triptorelin and leuprorelin acetate after i.m. injections. DESIGN: Prospective, double-blind crossover clinical study. SETTING: A teaching hospital. PATIENT(S): Fifty-four patients with pelvic endometriosis. INTERVENTION(S): Twenty-seven patients had three doses of i.m. triptorelin (3.75 mg) followed by three doses of i.m. leuprorelin acetate at 4-week intervals. Twenty-one patients had three doses of i.m. leuprorelin acetate (3.75 mg) followed by three doses of i.m. triptorelin, also at 4-week intervals. MAIN OUTCOME MEASURE(S): Menopausal symptoms, time taken for menstruation to return, serum E(2), FSH, LH levels, lipid profiles, and liver function tests. RESULT(S): The potencies of triptorelin and leuprorelin acetate in lowering the serum E(2), FSH, and LH levels were comparable. The severity of menopausal symptoms, changes in the lipid profile and liver function parameters were similar after triptorelin and leuprorelin acetate. The resurgence of ovarian activities and the spontaneous return of menstruation occurred significantly earlier after leuprorelin acetate than triptorelin. CONCLUSION(S): Both drugs are equally potent in down-regulating the pituitary-ovarian function, and their side effects are similar. Triptorelin has a longer duration of drug action and can be administered over a longer interval period.

Adult↗
PubMed2000

Changes of cytokine profiles during peritonitis in patients on continuous ambulatory peritoneal dialysis.

Continuous ambulatory peritoneal dialysis (CAPD) has emerged as an important dialysis treatment modality worldwide. One of the major complications is bacterial peritonitis, which may result in subsequent technique failure because of loss of peritoneal clearance or peritoneal fibrosis. Bacterial peritonitis leads to the release of proinflammatory cytokines from resident and infiltrating cells in the peritoneal cavity. We studied 35 patients undergoing CAPD with acute bacterial peritonitis. All patients treated with antibiotics for 2 weeks after the clinical diagnosis of peritonitis had a good recovery. Peritoneal dialysate effluent (PDE) was collected on days 1, 3, 5, 10, 21, and 42 after the start of treatment. Cell populations were monitored by flow cytometry. PDE levels of interleukin-1beta (IL-1), IL-6, transforming growth factor-beta (TGF-beta), and basic fibroblast growth factor (FGF) were measured by enzyme-linked immunosorbent assay. Gene transcription of TGF-beta in macrophages from PDE was measured by quantitative polymerase chain reaction. Bacterial peritonitis was associated with a sharp increase in total cell and neutrophil counts (400-fold) in PDE up to 3 weeks after peritonitis despite clinical remission (P < 0.0001). There was an increased absolute number of macrophages during the first 3 weeks despite the reduced percentage of macrophages among total cells in PDE compared with noninfective PDE. There was a progressive increase in the percentage of mesothelial cells or dead cells in the total cell population in PDE over the entire 6-week period. PDE levels of IL-1, IL-6, TGF-beta, and FGF increased markedly on day 1 before their levels decreased gradually. PDE levels of these cytokines or growth factors were significantly greater than those in noninfective PDE (n = 76) throughout the study period (P < 0.01). Similarly, TGF-beta complementary DNA (cDNA) molecules per macrophage were significantly greater than those of macrophages in noninfective PDE throughout this period (P < 0.01). There was no significant correlation between PDE levels of TGF-beta and TGF-beta cDNA molecules per macrophage, suggesting that peritoneal macrophages are not the only source of TGF-beta in PDE. We conclude there is an active release of proinflammatory cytokines and sclerogenic growth factors through at least 6 weeks despite apparent clinical remission of peritonitis. The peritoneal cytokine networks after peritonitis may potentially affect the physiological properties of the peritoneal membrane.

Bacterial Infections↗
PubMed2000

Umbilical cord blood transplantation for Maroteaux-Lamy syndrome (mucopolysaccharidosis type VI).

Severe Maroteaux-Lamy syndrome (mucopolysaccharidosis type VI) is usually fatal by early adulthood. Bone marrow transplantation is the only form of definitive enzyme replacement therapy available. A 5-year-old boy with Maroteaux-Lamy syndrome has successful recovery of bone marrow and enzymatic functions after umbilical cord blood transplant from his unaffected HLA-identical brother. Busulphan (16 mg/kg) and cyclophosphamide (200 mg/kg) were used as preparative chemotherapy with short methotrexate and long cyclosporin as prophylaxis against graft-versus-host disease (GVHD). A total of 6.08 x 10(7)/kg nucleated cells and 2.92 x 10(5)/kg CD34+ cells were transplanted with neutrophil engraftment achieved on day 26. There was no evidence of acute and chronic GVHD. Fifteen months after transplant, a normal level of N-acetylgalactosamine-4-sulphatase activity was achieved despite mixed chimerism. There was clinical improvement of hepatosplenomegaly, facial and skin features, joint mobility and resolution of suppurative middle ear effusion. He returned to school and continued to perform well in academic studies. We report here the first successful umbilical cord blood transplant as treatment of Maroteaux-Lamy syndrome.

Adult↗
PubMed2000

Role of caspases in dexamethasone-induced apoptosis and activation of c-Jun NH2-terminal kinase and p38 mitogen-activated protein kinase in human eosinophils.

Eosinophils are the principal effector cells for the pathogenesis of allergic inflammation. Glucocorticoids such as dexamethasone have long been used therapeutically for eosinophilia in allergic inflammation by inducing eosinophil apoptosis, but little is known about the intracellular mechanisms mediating dexamethasone-induced apoptosis. In the present study, we investigated the effect of dexamethasone on three mitogen-activated protein kinases (MAPK) involved in the intracellular signalling pathway: c-Jun NH2-terminal kinase (JNK), p38 MAPK and extracellular signal-regulated kinase (ERK). We found that dexamethasone could activate JNK and p38 MAPK in a time-dependent manner but not ERK. Further, SB 203580, a specific p38 MAPK inhibitor, was additive with dexamethasone in inducing eosinophil apoptosis, while JNK1/2 antisense phosphorothioate oligodeoxynucleotides did not show any significant effect. These suggest that dexamethasone-induced JNK1/2 and p38 MAPK activation are not crucial to the induction of apoptosis. Pretreatment of eosinophils with benzyloxycarbonyl-Val-Ala-Asp-fluoromethylketone (Z-VAD.FMK), a broad-spectrum caspase inhibitor, could inhibit dexamethasone-induced apoptosis in eosinophils dose-dependently. Moreover, Z-VAD.FMK partially inhibited dexamethasone-activated JNK and p38 MAPK activities. However, dexamethasone treatment did not activate specific caspase-3, -8 activity in eosinophils compared with spontaneous apoptosis. We therefore conclude that dexamethasone-induced apoptosis and activation of JNK and p38 MAPK activity in eosinophils are regulated by caspases but not through the common apoptosis-related caspase-3, -8 as in other cell types. Elucidation of the important role of caspases in eosinophil apoptosis may facilitate the development of more specific and effective treatment for allergic inflammation.

Amino Acid Chloromethyl Ketones↗