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Biomedical subjects

C Lam

Publications and source records attributed to C Lam.

At least 55 records · Page 3Linked to original sources
PubMed1995

A comparison of colour Doppler sonography and the pelvic arteriogram in assessment of patients with gestational trophoblastic disease.

OBJECTIVE: To assess whether colour Doppler sonography can replace pelvic arteriography in the assessment of patients with gestational trophoblastic disease. DESIGN: An observational study in which patients with gestational trophoblastic disease were assessed with both pelvic arteriography and colour Doppler sonography. SETTING: The oncology unit of the Department of Obstetrics and Gynaecology, University of Hong Kong. The unit is the main tertiary referral centre for treatment of trophoblastic diseases in Hong Kong. SUBJECTS: Thirty-two consecutive women referred over an 18 month period. MAIN OUTCOME MEASURES: The site of localisation of the tumour and the size of the tumour as assessed by both methods. RESULTS: Eleven patients had a spontaneous fall of beta-hCG titres and did not have pelvic arteriograms performed. The remaining 21 patients had both investigations performed. Four patients had no evidence of abnormal pelvic vessels either on colour Doppler sonography or on pelvic arteriography. Their raised beta hCG titres were due to metastatic disease elsewhere. In the remaining patients the location of the tumour vessels was found to be concordant between the two methods of imaging. Measurements of the mean diameter of tumour bulk by the two methods also agreed well (r = 0.93, P < 0.0001). Pelvic arteriogram over-estimated the size of the tumour in two patients by 2 and 3 cm, respectively, but this did not alter the risk categories of the patients. CONCLUSION: Colour Doppler sonography is a noninvasive technique that can replace pelvic arteriography in the assessment of patients with trophoblastic diseases.

Angiography↗
PubMed1994

Purification, crystallization and preliminary X-ray diffraction analysis of recombinant human neutrophil-activating peptide 2 (rhNAP-2).

The potent activator and chemoattractant for human neutrophils, neutrophil-activating peptide 2 (NAP-2), has been cloned and expressed in Escherichia coli. The protein has been purified to homogeneity (> 98%) by a series of chromatographic techniques, including reversed phase HPLC. The biological activity of recombinant human NAP-2 (rhNAP-2), characterized by the induction of elastase release from human neutrophils, was found to be comparable to natural NAP-2. rhNAP-2 has been crystallized by the hanging drop vapor diffusion method. The crystals belong to space group P222 with unit cell dimensions of a = 30.8 A, b = 39.5 A and c = 95.3 A. A packing density of 3.8 A3/Da with a solvent content of approximately 68% is obtained when one molecule per asymmetric unit is assumed. The crystals were shown to diffract to beyond 2.0 A on a conventional X-ray source. They are stable to X-rays for several days and are thus suitable for high resolution structure determination.

Amino Acid Sequence↗
PubMed1994

The relationship between the thrombotic and infectious complications of central venous catheters.

OBJECTIVES: To assess the frequency of thrombotic and infectious complications of long-term use of vascular catheters in cancer patients and to determine whether the two types of complication are related. DESIGN: Case series. SETTING: A 500-bed tertiary cancer center. PATIENTS: Seventy-two cancer patients. INTERVENTIONS: During a 16-month period, postmortem examinations of catheterized veins and contralateral uncatheterized veins were done on all patients with indwelling central venous catheters who met study criteria. MAIN OUTCOME MEASURES: Catheter-related septicemia determined by clinical and microbiological data as well as postmortem pathology; venous pathological changes such as mural hemorrhage, thrombosis, calcification, ulceration, and inflammation. RESULTS: Premortem clinical and microbiological data were obtained retrospectively on all patients. Pathological changes were noted in 35 catheterized veins (49%) compared with five contralateral control veins (9.2%) (P < .001). Mural thrombi were noted in 27 catheterized veins (38%) compared with only one contralateral control vein (1.4%) (P < .001). Other pathological changes consisted of four central venous catheter-related mural thrombi (5.6%) in the right atrium and four instances (5.6%) of nonbacterial thrombotic endocarditis, three involving the tricuspid and one the mitral valves. Seven patients had catheter-related septicemia. Of the 31 patients with mural thrombosis of the catheterized vein or right atrium, seven developed catheter-related septicemia, whereas none of the 41 patients with normal catheterized veins and atria developed catheter-related septicemia (P < .01). CONCLUSIONS: Thrombotic complications are common in catheterized veins and are often associated with catheter sepsis.

Adolescent↗
PubMed1994

Umbilical artery Doppler velocimetry compared with fetal heart rate monitoring as a labor admission test.

A total of 155 patients admitted in early labor to the delivery unit of the University of Hong Kong were recruited into a study comparing the value of umbilical artery Doppler velocimetry and fetal heart rate (FHR) monitoring in early labor as an admission test. FHR monitoring for 30 min was recorded on admission, and umbilical A/B ratio was simultaneously performed. The FHR tracing was scored according to the Lyons score by a third independent observer after delivery. Outcome variables studied included small for gestational age (SGA), intrapartum FHR abnormalities, operative deliveries for fetal distress, umbilical cord pH, Apgar scores, admission into the special care baby unit, and a combination of the variables. It was found that at cut-off values of Lyons score < 7 and umbilical A/B ratio > 2.6 at term, about 19% of cases were abnormal for either tests, with only a few cases of overlap. Umbilical A/B ratio was found to be significantly correlated with SGA. The sensitivity and positive predictive values were, however, low. Both tests were relatively poor predictors for most of the outcome variables studied. Interestingly, FHR monitoring did not seem to have any advantage over Doppler velocimetry as a labor admission test. Further larger scale studies to evaluate their usefulness in medium and low risk populations are indicated.

Apgar Score↗
PubMed1994

Prediction of the role of granulocyte-macrophage colony-stimulating factor in animals and man from in vitro results.

The possibility of predicting the clinical effects of cytokines from in vitro data is discussed, using GM-CSF as an example. GM-CSF incubated with bone marrow cells has been shown to induce proliferation and colony formation, predominantly of the colony-forming unit granulocyte and granulocyte-macrophage types. Daily treatment of normal monkeys with GM-CSF resulted in transient neutropenia followed by neutrophilia. After withdrawal of GM-CSF the neutrophil levels returned to baseline. Predictably, GM-CSF administration results in accelerated neutrophil recovery in patients with chemotherapy-induced neutropenia. GM-CSF has also been shown to induce microbial killing by neutrophils and monocytes in vitro. This activity translated into a dose-related protection of GM-CSF-pretreated mice infected with lethal doses of micro-organisms. Interleukin-3 (IL-3) increases the cellularity of the bone marrow and GM-CSF can induce mobilization of bone marrow cells into the peripheral blood. Therefore, it was predicted and subsequently proved that a combination of these cytokines is synergistic, increasing the yields of peripheral blood progenitor cells which could be collected and then retransplanted into patients undergoing myeloablative chemotherapy. Monkeys injected with recombinant human IL-3 and GM-CSF had increased antibody titres to human IL-3 compared with monkeys given IL-3 alone, suggesting a potential use of GM-CSF which was not predicted from its in vitro results, that of vaccine adjuvancy.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Hematocrit modifies the circulatory control of systemic and myocardial oxygen utilization in septic sheep.

OBJECTIVE: To describe the relationship between hematocrit and oxygen utilization before and after the onset of a hyperdynamic septic state. DESIGN: Prospective, observational study. SETTING: Laboratory of a large university-affiliated medical school. SUBJECTS: Thirty mature sheep, each weighing 30 to 40 kg (0.9 to 1.1 m2 body surface area). INTERVENTIONS: After baseline measurements, cecal ligation and perforation were used to establish an intra-abdominal source of infection. The abdominal wound was closed and animals were studied on the second postoperative day. An increase in cardiac output of > or = 30% was used to arbitrarily define the onset of sepsis. Repeat measurements were performed and the animal was killed. RESULTS: The circulatory response to this septic insult included an increase in both cardiac index (change, baseline to sepsis, delta +2.24 +/- 0.75 L/min/m2; p < .01) and myocardial blood flows (delta +76.4 +/- 56 mL/100 g/min; p < .01). We found a negative correlation between the hematocrit and cardiac index (r2 = .21; p < .01) during the septic study, and noted that the amount (p < .01) of this correlation was significantly greater in the septic than the nonseptic study. Concurrently, the negative correlation observed between hematocrit and whole-body oxygen extraction (r2 = .21; p < .01) was significantly lower (p < .01) across the range of hematocrit values examined during the septic study vs. the similar relationship in the nonseptic study (r2 = .27; p < .01). The increase in myocardial oxygen consumption paralleled the relationship between cardiac work and hematocrit in the septic study, and was accompanied by increases in both myocardial blood flows (r2 = .25; p < .01) and myocardial oxygen extraction (r2 = .35; p < .01). CONCLUSIONS: The normal circulatory compensation to anemia in hyperdynamic sepsis includes increases in cardiac index and whole-body oxygen extraction, although greater reliance is likely placed on the use of systemic flow reserve to maintain tissue oxygen uptake in septic vs. healthy study conditions. Furthermore, increased reliance on myocardial oxygen extraction in sepsis suggests that the normal flow-reserve supporting myocardial oxygen availability may be limited in this syndrome.

Animals↗
PubMed1994

Microvascular perfusion is impaired in a rat model of normotensive sepsis.

We hypothesized that normotensive sepsis affects the ability of the microcirculation to appropriately regulate microregional red blood cell (RBC) flux. An extensor digitorum longus muscle preparation for intravital study was used to compare the distribution of RBC flux and the functional hyperemic response in SHAM rats and rats made septic by cecal ligation and perforation (CLP). Using intravital microscopy, we found that sepsis was associated with a 36% reduction in perfused capillary density (from 35.3 +/- 1.5 to 22.5 +/- 1.0 capillaries/mm of test line) and a 265% increase in stopped-flow capillaries (from 0.9 +/- 0.2 to 3.3 +/- 0.4 capillaries/mm); the spatial distribution of perfused capillaries was also 72% more heterogeneous. Mean intercapillary distance (ICD) increased 30% (from 25.7 +/- 0.8 to 33.5 +/- 1.6 microns), and the proportion of capillary pairs with intercapillary distances > 33.8 microns (the 75th percentile of ICDSHAM) was greater with sepsis. Mean capillary RBC velocity increased 17% in CLP rats (391 vs 333 microns/s). Laser Doppler flowmetry was used to assess the functional hyperemic response of the extensor digitorum longus muscle before and after a period of maximal twitch contraction designed to increase oxygen demand. RBC flux was 36% lower in the CLP rats at rest. After contraction, RBC flux increased in both SHAM and CLP rats; however, the relative increase was less in the CLP group. We concluded that sepsis affects the ability of the skeletal muscle microcirculation to appropriately distribute RBC flux and to respond to increases in oxygen need.

Animals↗
PubMed1994

Limitations of transvaginal sonography and color Doppler imaging in the differentiation of endometrial carcinoma from benign lesions.

We conducted this study to test the hypothesis that transvaginal ultrasonography and color Doppler imaging of the uterine arteries are complementary methods in the assessment of patients with postmenopausal bleeding. Sixty-seven patients were studied. Seventeen suffered from endometrial carcinoma, 12 from benign endometrial lesions (six polyp, six hyperplasia) and 38 had no organic pathology. Transvaginal ultrasonography was found to be superior to CDI in the detection of pathologic conditions of the endometrium, but neither method can distinguish benign lesions from their malignant counterparts. CDI does not give additional information over that obtained by transvaginal ultrasonography in the assessment of patients with postmenopausal bleeding, and the limitations of both methods in the differentiation of endometrial carcinoma from benign lesions need to be recognized.

Arteries↗
PubMed1994

Protection of mice from mortality caused by living and heat-killed bacteria by SDZ MRL 953.

Protective effects of SDZ MRL 953, a monosaccharidic lipid A analog with a reduced toxicity, were investigated in models of experimental septic shock caused by injections of LPS, and inoculations of heat-killed or live bacteria. Female B6D2F1 mice were challenged with a combination of galactosamine (800 mg/kg) plus various doses of heat-killed isolates of Escherichia coli, Pseudomonas aeruginosa, Salmonella typhimurium, and Staphylococcus aureus or LPS from Salmonella abortus equi. In some experiments, isolates of living bacteria at sublethal inocula were also combined with galactosamine. More than 90% of the animals died within 24 hr when the challenge was performed either simultaneously with or up to 4 hr after an intraperitoneal administration of galactosamine. No death was observed when galactosamine was omitted or administered after the microbial or LPS challenge. Pretreatment of the animals with SDZ MRL 953 (1-10 mg/kg) rendered the animals resistant to the lethal effects of both bacterial and LPS challenge in a time- and dose-dependent manner. The levels of TNF-alpha in control mice rose to greater than 600 pg/ml 2 hr postbacterial or LPS challenge, but were below detection in animals pretreated with SDZ MRL 953. Protection against both the infection and the toxicity of heat-killed bacteria or LPS was also achieved when murine anti-TNF-alpha monoclonal antibody was administered prophylactically. Together, these data suggest that SDZ MRL 953 enhances the resistance of mice against the toxicity of heat-killed gram-negative bacteria and S. aureus, and attenuates host responses to living bacteria which may lead to irreversible shock and death.

Animals↗
PubMed1993

Type-I interferons are potent inhibitors of interleukin-8 production in hematopoietic and bone marrow stromal cells.

Interleukin-8 (IL-8) is produced by many cell types upon stimulation with bacterial products or inflammation-associated cytokines such as tumor necrosis factor-alpha and IL-1. Interferons (IFNs) represent another group of cytokines that are induced by similar stimuli in inflammatory reactions. We show now that type-I IFNs are potent inhibitors of IL-8 expression in vitro and in vivo. A significant reduction of both secretion of IL-8 protein and accumulation of IL-8 mRNA in vitro was observed in several cell types comprising peripheral blood mononuclear cells (PBMNC) from healthy donors and from patients with chronic myelogenous leukemia (CML), the myelomonocytic cell line THP-1, and bone marrow (BM) stromal cells as a representative model for BM microenvironment. By contrast, in lipopolysaccharide-stimulated polymorphonuclear phagocytes IFN failed to suppress IL-8 expression. In untreated patients with CML, a constitutive expression of IL-8 mRNA was detected in freshly isolated PBMNC that was markedly reduced 5 hours after therapeutic application of IFN-alpha. The mechanism of IL-8 downregulation was studied more in detail in the THP-1 cell line. The experiments showed that de novo protein synthesis was not required for the inhibitory effect. RNA decay analysis and nuclear run-on assays suggest that in THP-1 cell line the inhibition of IL-8 expression is predominantly regulated at the posttranscriptional level.

Bone Marrow↗
PubMed1993

An international perspective on the cholesterol debate.

For the past 5 years there has been an intensive debate and a number of conflicting guidelines suggesting what general practitioners (GPs) should do to screen and manage hyperlipidaemia. At a WONCA seminar in Vancouver in 1992, policies and guidelines from Canada, the UK, The Netherlands, New Zealand, Hong Kong and the USA were reviewed. It was concluded that cholesterol policy and guidelines tend to be influenced more by political and economic factors than by evidence of health benefit. International guidelines for cholesterol screening and management would be of minimal value, as GPs would have to interpret the epidemiological evidence of benefit from lipid screening and lipid lowering strategy in the context of each patient to arrive at optimum management.

Adult↗
PubMed1993

Recombinant human interleukin-8 restores function in neutrophils from patients with myelodysplastic syndromes without stimulating myeloid progenitor cells.

Prognosis in myelodysplastic syndrome (MDS) is not only correlated closely with blast cell count in bone marrow and chromosomal abnormalities but also correlated with decreased leucocyte count and function leading to acquisition of lethal infections. Recently, clinical trials in MDS have focused on the application of haemopoietic growth factors such as G-CSF or GM-CSF, which have proven to increase neutrophil count and function. However, these cytokines carry the risk of stimulating the malignant clone, particularly in patients with increased blast cell count. Therefore, investigation of cytokines which are able to stimulate neutrophil function without the potential risk of stimulating haemopoietic progenitor cells may be relevant for MDS. As the stimulatory effect of interleukin-8 on neutrophil function is well known, we investigated whether recombinant human IL-8 is also able to improve the function of neutrophils gained from patients with MDS. Using three different techniques--the E. coli killing assay (8 patients), the production of reactive oxygen as determined by cytochrome c reduction (7 patients) and chemiluminescence (8 patients)--a significant stimulation of neutrophil function at a concentration of 10 nm IL-8 was found in all test systems. No correlation with FAB classification was evident. On the other hand, IL-8 only mildly stimulated growth of myeloid progenitor cells in bone marrow culture of healthy individuals and MDS patients. This minimal stimulation was blocked by a neutralizing antibody directed against GM-CSF, suggesting an indirect effect of IL-8 via secondary GM-CSF release. Thus, IL-8 is able in vitro to repair the functional abnormalities of neutrophils from patients with MDS but has only a marginal influence on myeloid progenitor cells.

Blood Bactericidal Activity↗
PubMed1992

Recombinant human granulocyte-macrophage colony-stimulating factor stimulates superoxide anion and hydrogen peroxide production in human neutrophils.

The effect of purified recombinant human granulocyte-macrophage colony-stimulating factor (GM-CSF) on the oxidative metabolism of human peripheral blood granulocytes was investigated. The respiratory burst of granulocytes was assessed in individual cells by flow cytometry utilizing the oxidation of the nonfluorescent 2',7'-dichlorofluorescein (DCFH) to the highly fluorescent DCF by hydrogen peroxide (H2O2). Treatment with GM-CSF caused granulocytes to produce H2O2 without addition of a second stimulus. The amount of H2O2 produced correlated with the concentration of GM-CSF administered. Also, GM-CSF did not prime the granulocytes for enhanced H2O2 production in response to N-formylmethionyl-leucyl-phenylalanine (f-MLP). Consecutive stimulation of granulocytes with GM-CSF and f-MLP resulted in additive production of H2O2. GM-CSF also induced granulocytes to release superoxide anion (O2-) in a dose-dependent manner, when the respiratory burst was assessed by a conventional cytochrome c reduction assay. In contrast to hydrogen superoxide production, GM-CSF significantly (p < 0.001) enhanced f-MLP-stimulated release of superoxide anion over that expected from the additive effects of the two agonists.

Amino Acid Sequence↗
PubMed1992

Interleukin-8 stimulates calcium transients and promotes epidermal cell proliferation.

The presence of large amounts of biologically active interleukin-8 (IL-8) in psoriatic involved skin suggests that it may contribute, in part, to the changes observed in psoriasis, including hyperproliferation of keratinocytes. To examine the effect of IL-8 on epidermal growth, we monitored cytosolic free Ca++ transients in human keratinocytes adult skin epidermis calcium reduced level, temperature elevated (HaCat) cells and normal keratinocytes loaded with the cell permeable, acetoxymethyl derivative, indo-1AM. Addition of IL-8 (0.06-47 nM) to the HaCat cells induced rapid rises in cytosolic free Ca++ from resting levels of 145 +/- 38 to peak levels of 889 +/- 10 nM. The induced rises in Ca++ were transient and concentration dependent. Half maximal effect was observed at 1.2 nM. Normal keratinocytes also responded to IL-8 (6 nM) by rises in cytosolic free Ca++ from a pre-stimulated level of 269 nM to transient peak value of 393 nM. In addition, IL-8 promoted epidermal cell proliferation. Polyclonal anti-IL-8 antibody blocked IL-8-induced calcium changes and proliferation. Under similar conditions, human neutrophils also responded to IL-8 in a similar dose range by a rapid and transient mobilization of Ca++. The findings indicate that IL-8 has a wider range of responsive target cells than hitherto thought and acts as an autocrine growth factor.

Calcium↗
PubMed1992

Effects of flurbiprofen and suprofen on the miotic activity of 1% acetylcholine and 0.01% carbachol.

The nonsteroidal antiinflammatory agents (NSAIAs) flurbiprofen and suprofen applied topically to reduce miosis may counteract the desired effects of miotics used during ocular surgery. In a pigmented rabbit model, 1% acetylcholine was shown to cause a greater, significant initial (for the first 30 minutes) constriction (P less than .05) than 0.01% carbachol in eyes pretreated with flurbiprofen and suprofen. From 2 to 8 hours, NSAIA pretreatment had a greater miotic effect with carbachol than with acetylcholine. There were no significant differences between flurbiprofen and suprofen on the miotic effect of carbachol or acetylcholine.

Acetylcholine↗
PubMed1991

High prevalence of undiagnosed diabetes among Chinese patients with ischaemic stroke.

We reviewed the prevalence of diabetes mellitus, hypertension and cigarette smoking in 176 Chinese patients with acute stroke, classified, on computed tomographic findings, as intracerebral haemorrhage or cerebral infarction. In all patients with no known history of diabetes, a 75 g OGTT was done 3-6 months after ictus and interpreted using WHO criteria. The overall prevalence of diabetes and impaired glucose tolerance (IGT) was 33.5% and 21.0%, respectively, with a higher prevalence being found in patients with cerebral infarction (P less than 0.05). Forty percent of those with diabetes were previously undiagnosed - all but 2 had ischaemic stroke. Compared to reported findings in the general population, an increased prevalence of hypertension, and possibly also cigarette smoking was found in patients with both stroke categories. On the other hand, significant hypercholesterolaemia was not found in patients of either category. In view of the high prevalence of undiagnosed diabetes among these stroke patients and the increased morbidity and mortality associated with diabetes mellitus, screening for diabetes is recommended especially in those with ischaemic stroke. If a fasting plasma glucose of greater than or equal to 6 mmol/l was used for the initial screening of undiagnosed diabetes in this group of patients, the sensitivity and specificity values would have been 78% and 94%, respectively. Whether this cut-off value can be cost-effectively employed for mass screening remains to be confirmed by studies involving larger numbers of stroke patients.

Blood Glucose↗
PubMed1991

Recombinant murine granulocyte-macrophage colony-stimulating factor augments neutrophil recovery and enhances resistance to infections in myelosuppressed mice.

The ability of recombinant murine granulocyte-macrophage colony-stimulating factor (rmGM-CSF) to protect myelosuppressed mice against lethal infections was evaluated. In mice myelosuppressed by cyclophosphamide, subcutaneously administered rmGM-CSF was a potent stimulus of granulopoiesis by increasing the number of GM-CSF-responsive precursor cells in bone marrow followed by a profound neutrophilia. Neutrophil recovery was augmented by rmGM-CSF in a dose-dependent manner at daily doses of 0.6-5.0 micrograms/mouse. In addition, rmGM-CSF increased the functional activity of circulating neutrophils at similar doses. When rmGM-CSF was administered to neutropenic mice before experimentally induced Pseudomonas aeruginosa, Staphylococcus aureus, or Candida albicans infections, it protected against these lethal infections, resulting in increased numbers of survivors. These data suggest that rmGM-CSF protects neutropenic mice from lethal infections, probably by augmenting neutrophil recovery after myelosuppression and activation of mature cells.

Animals↗