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Biomedical subjects

W Lam

Publications and source records attributed to W Lam.

At least 37 records · Page 2Linked to original sources
PubMed1998

Rhodococcus equi lung abscess complicating Evan's syndrome treated with corticosteroid.

We report a case of Rhodococcus equi, an unusual pathogen, causing a right upper lobe lung abscess in a patient with Evan's syndrome (auto-immune haemolytic anaemia and thrombocytopenia) who was treated with high-dose corticosteroid therapy. The patient was treated successfully with clarithromycin, vancomycin, ciprofloxacin and imipenen which appear to be effective in combination for this unusual condition in which the treatment regimen has been controversial.

Actinomycetales Infections↗
PubMed1997

Cuneiform nucleus stimulation-induced sympathoexcitation: role of adrenoceptors, excitatory amino acid and serotonin receptors in rat spinal cord.

Stimulation of the midbrain cuneiform nucleus has previously been shown to produce increases in arterial blood pressure and lumbar sympathetic nerve activity. While this sympathoexcitatory effect is, in part, due to excitation of premotor sympathoexcitatory neurons in the rostral ventrolateral medulla, the specific spinal neurotransmitter systems recruited by cuneiform nucleus stimulation remains to be elucidated. In this study, mean arterial pressure, resting and cuneiform nucleus stimulation-evoked lumbar sympathetic nerve activity were analysed following intrathecal injections of an excitatory amino acid antagonist (kynurenic acid), alpha1-adrenoceptor antagonist (prazosin) and a serotonin receptor antagonist (methiothepin) in anesthetized, paralysed male Sprague-Dawley rats. Mean arterial pressure and resting sympathetic nerve discharge were decreased by all treatments (n = 6/group) compared to the vehicle control group. Intermittent electrical stimulation of the cuneiform nucleus produced a bimodal sympathoexcitatory response, of which the short latency peak was significantly attenuated (43% reduction) by intrathecal kynurenate whereas the long latency peak was reduced by intrathecal prazosin (decrease of 21%) and methiothepin (38% attenuation). These results are consistent with the significant roles of excitatory amino acid, alpha1-adrenergic and serotonin receptors in modulating the activity of sympathetic vasomotor preganglionic neurons supplying the lumbar sympathetic nerve trunk, and suggest the existence of at least three neuronal groups and/or pathways associated with the sympathoexcitatory response to cuneiform nucleus stimulation.

Animals↗
PubMed1997

Bidirectional pigment granule migration in isolated retinal pigment epithelial cells requires actin but not microtubules.

In the teleost retinal pigment epithelium (RPE), melanin pigment granules disperse into long apical projections in the light and reaggregate into the cell body in the dark. To investigate the cytoskeletal mechanisms responsible for these movements, we have examined the effects of cytoskeletal inhibitors on pigment granule transport in cultured, dissociated RPE cells using time-lapse video microscopy. The kinetics of pigment granule transport during normal aggregation and dispersion are quite distinct: during aggregation, all pigment granules undergo simultaneous, nonsaltatory centripetal movement (mean velocity 3.6 microm/min); during dispersion, individual granules undergo independent, bidirectional saltatations (mean velocities 3.7 microm/min centrifugal; 1.1 microm/min centripetal). Nocodazole disruption of microtubules within the RPE apical projections had little effect on the kinetics of pigment granule movement, and essentially no effect on extent of pigment granule aggregation or dispersion, or on maintenance of the fully aggregated or fully dispersed states. In contrast, cytochalasin D (CD) treatment blocked net aggregation and dispersion of pigment granules, and compromised maintenance of the fully aggregated and dispersed states. These observations suggest that the actin cytoskeleton plays an important role in both centripetal and centrifugal transport of pigment granules in teleost RPE cells.

Actins↗
PubMed1997

Early and late results of excision of choledochal cysts.

BACKGROUND/PURPOSE: Reports on the late results of choledochal cyst excision with hepaticojejunostomy in children are relatively few. METHODS: Of the 84 patients who had choledochal cyst who came under our care, 79 have had definitive surgery, three are awaiting surgery, one is being observed with Caroli's disease, and the parents of one child have refused surgery. Thirty-eight patients treated decades ago had internal drainage procedures. Since 1972, 41 patients have had cyst excision with hepaticojejunostomy using a 40-cm Roux loop without an antireflux procedure. Early complications in those who underwent cyst excision with hepaticojejunostomy included anastomotic leak in three patients who required reoperation, cholangitis in two, and fluid collection in the gall-bladder bed that required no intervention in one. RESULTS: During a follow-up period ranging from 4 months to 17 years (mean, 8.5 years), anastomotic stricture, cholangitis, and intrahepatic stone formation developed in two children after being well for 8 years and over 11 years. These children required additional surgical procedures to overcome their problems. Asymptomatic intrahepatic stones 2 years after cyst excision with hepaticojejunostomy developed in a third child. There was no mortality in the entire group that underwent cyst excision and they are all enjoying a good quality of life. CONCLUSIONS: Careful, long-term follow-up is important in children who have choledochal cyst excision with hepaticojejunostomy.

Adolescent↗
PubMed1997

Neuronal activation in the forebrain following electrical stimulation of the cuneiform nucleus in the rat: hypothalamic expression of c-fos and NGFI-A messenger RNA.

Forebrain neuronal connections associated with the cardiovascular response to unilateral, low-intensity, electrical stimulation of the mesencephalic cuneiform nucleus were examined in the halothane-anesthetized and paralysed rat by in situ hybridization histochemistry using specific 35S-labelled oligonucleotides for detection of c-fos and nerve growth factor inducible-A gene (NGFI-A) messenger RNAs. Stimulation of the cuneiform nucleus led to increases in mean arterial pressure and heart rate, whereas no cardiovascular response was observed in animals stimulated in the inferior colliculus or in sham-operated animals [see concurrent mid- and hindbrain study [Lam W. et al. (1996) Neuroscience 71, 193-211]. Cuneiform nucleus stimulation was associated with increased c-fos and NGFI-A messenger RNA levels bilaterally in the ventromedial, dorsomedial and lateroanterior hypothalamic nuclei, lateral and anterior hypothalamic areas, and ipsilaterally in the medial amygdaloid nucleus, at levels significantly greater than those in inferior colliculus-stimulated, sham-operated and naive, unoperated animals. C-fos, but not NGFI-A, messenger RNA expression was increased bilaterally in the piriform cortex and subparafascicular thalamic nucleus. These results are consistent with the existence of direct and indirect projections between the cuneiform nucleus and the aforementioned activated areas, the functions of which may include the control of reproduction and metabolism, as well as cardiovascular regulation. The ipsilateral nature of responses in certain brain areas may be explained by the absence of decussating pathways and/or the presence of multisynaptic connections which attenuate bilateral signal transmission. The existence of structures that are known to receive afferent projections from the cuneiform nucleus, but that were not activated, may be explained by synaptic depolarization not reaching the threshold for immediate early gene expression or by a net inhibitory effect on innervated neurons. Characterization of these activated forebrain regions using other compatible labelling techniques should further elucidate the mechanisms by which these central nervous system structures are integrated in the response to stimulation of the cuneiform nucleus.

Animals↗
PubMed1997

3-hydroxy-3-methylglutaryl coenzyme A reductase of Sulfolobus solfataricus: DNA sequence, phylogeny, expression in Escherichia coli of the hmgA gene, and purification and kinetic characterization of the gene product.

The gene (hmgA) for 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase (EC 1.1.1.34) from the thermophilic archaeon Sulfolobus solfataricus P2 was cloned and sequenced. S. solfataricus HMG-CoA reductase exhibited a high degree of sequence identity (47%) to the HMG-CoA reductase of the halophilic archaeon Haloferax volcanii. Phylogenetic analyses of HMG-CoA reductase protein sequences suggested that the two archaeal genes are distant homologs of eukaryotic genes. The only known bacterial HMG-CoA reductase, a strictly biodegradative enzyme from Pseudomonas mevalonii, is highly diverged from archaeal and eukaryotic HMG-CoA reductases. The S. solfataricus hmgA gene encodes a true biosynthetic HMG-CoA reductase. Expression of hmgA in Escherichia coli generated a protein that both converted HMG-CoA to mevalonate and cross-reacted with antibodies raised against rat liver HMG-CoA reductase. S. solfataricus HMG-CoA reductase was purified in 40% yield to a specific activity of 17.5 microU per mg at 50 degrees C by a sequence of steps that included heat treatment, ion-exchange chromatography, hydrophobic interaction chromatography, and affinity chromatography. The final product was homogeneous, as judged by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The substrate was (S)- not (R)-HMG-CoA; the reductant was NADPH not NADH. The Km values for HMG-CoA (17 microM) and NADPH (23 microM) were similar in magnitude to those of other biosynthetic HMG-CoA reductases. Unlike other HMG-CoA reductases, the enzyme was stable at 90 degrees C and was optimally active at pH 5.5 and 85 degrees C.

Acyl Coenzyme A↗
PubMed1997

Effects of dietary lipid modification on adrenoceptor-mediated cardiovascular responsiveness and baroreflex sensitivity in normotensive subjects.

To examine the effects of short-term dietary lipid modification on alpha- and beta-adrenoceptor-mediated cardiovascular responsiveness, 19 normal volunteers consumed either a high-fat or a low-fat diet for 2 weeks in an open, randomized, crossover study of 6 weeks' duration. Diets were balanced for sodium and potassium content. Adrenoceptor-mediated cardiovascular responsiveness was assessed by measuring blood pressure and heart rate responses to incremental infusions of phenylephrine and isoprenaline. Baroreflexes were studied by examining heart rate responses to phenylephrine and to the Valsalva manoeuvre. Total plasma cholesterol and low-density lipoprotein cholesterol levels both fell significantly (by 22% and 26%, respectively), on the low-fat compared with the high-fat diet, as did resting supine blood pressures and heart rate (by 6 mmHg systolic and 3 mmHg diastolic, and 5 beats/min). These changes were accompanied by a significant reduction in the systolic blood pressure response to isoprenaline. Blood pressure responses to phenylephrine and baroreflex sensitivity did not change. These results suggest that dietary fat intake alters cardiac beta-adrenergic reactivity without significant effects on vascular alpha-adrenoceptor mediated responses or baroreflexes.

Adult↗
PubMed1997

Comparison of whole body MRI and radioisotope bone scintigram for skeletal metastases detection.

OBJECTIVE: To compare whole body magnetic resonance imaging (MRI) using fast sequences with radioisotope bone scintigraphy (BS) for the detection of metastases in the entire skeleton. METHODS AND RESULTS: In forty-four patients suffering from carcinoma of lung, breast and prostate whole body MRI could generally be accomplished in about 39 minutes and it was shown to have a higher skeletal metastases detection compared with BS in the spine, pelvis, limb bones, sternum, scapula, and clavicle, but lower in the ribs and skull. CONCLUSIONS: We think for addressing the status of skeletal metastases only, bone scintigram is still preferred over whole body MRI. When bone scintigram is unavailable, whole body MRI is a practical and acceptable alternative especially when extra-osseous metastases are also of concern.

Adult↗
PubMed1996

Increased nerve growth factor inducible-A gene and c-fos messenger RNA levels in the rat midbrain and hindbrain associated with the cardiovascular response to electrical stimulation of the mesencephalic cuneiform nucleus.

Functional neuronal connections associated with the cardiovascular response to unilateral low-intensity electrical stimulation of the mesencephalic cuneiform nucleus were examined in the halothane-anaesthetized and paralysed rat by in situ hybridization histochemistry using specific 35S-labelled oligonucleotides for detection of nerve growth factor inducible-A gene (NGFI-A) and c-fos messenger RNAs. Stimulation of the cuneiform nucleus increased mean arterial pressure and heart rate by 20 +/- 0.5 mmHg and 35 +/- 3 b.p.m., respectively, while no significant cardiovascular response was observed in animals stimulated in the inferior colliculus or in sham-operated animals. Cuneiform nucleus stimulation produced increased NGFI-A and c-fos messenger RNA levels in the Kölliker-Fuse and parabrachial nuclei ipsilaterally, and the cuneiform nucleus, dorsal periaqueductal gray and caudal ventrolateral medulla bilaterally at levels significantly greater than those in inferior colliculus-stimulated, sham-operated and naive, unoperated animals. NGFI-A, but not c-fos, messenger RNA expression was increased bilaterally in the caudal portion of the nucleus of the solitary tract and inferior olive. These results are consistent with previous neuroanatomical tract-tracing studies of afferent and efferent pathways from the cuneiform nucleus and indicate that these midbrain and hindbrain structures may be involved in the pressor and tachycardic responses associated with stimulation of the cuneiform nucleus. The ipsilateral nature of responses in certain brain areas may be explained by the absence of decussating pathways and/or the presence of multisynaptic connections which attenuate bilateral signal transmission. Characterization of these activated neuronal structures using other compatible labelling techniques should further elucidate the mechanisms by which these central nervous system structures are integrated in the cardiovascular responses to stimulation of the cuneiform nucleus.

Animals↗
PubMed1995

Effect of dorsal periaqueductal grey lesion on baroreflex and cardiovascular response to air-jet stress.

Certain areas within the periaqueductal grey (PAG) have been implicated in cardiovascular regulation. The influence of excitotoxic lesions of the caudal dorsal periaqueductal grey on the baroreceptor-heart rate reflex and the cardiovascular response to air-jet stress was examined in awake Wistar-Kyoto rats. Pressor (11 +/- 2 mmHg) and tachycardic (25 +/- 4 beats/min) responses to air-jet were not influenced by the lesion. Similarly, the resting MAP and HR were unchanged. However, the gain of the baroreflex was reduced from -3.9 +/- 0.1 to -2.8 +/- 0.3 beats/min per mmHg and the upper threshold was increased from 120 +/- 5 to 135 +/- 7 mmHg in the lesioned group. These observations suggest that although the caudal dorsal PAG does not appear to exert a tonic influence on vasomotor tone or mediate the air-jet response, it may provide a facilitatory input to the baroreceptor-heart rate reflex.

Animals↗
PubMed1995

Effects of pravastatin on cardiovascular reactivity to norepinephrine and angiotensin II in patients with hypercholesterolemia and systemic hypertension.

This study was conducted to examine the effects of short-term cholesterol reduction on cardiovascular reactivity in mildly hypertensive patients. Seven male and 7 female patients, aged 34 to 68 years, received pravastatin (40 mg/day) or matched placebo for 3 weeks in a randomized, double-blind, crossover study. Cardiovascular reactivity was assessed by measurement of blood pressure (BP) responses to incremental infusions of angiotensin II and norepinephrine, by cold pressor testing and isometric exercise. Compared with placebo, pravastatin caused significant reductions in plasma total and low-density lipoprotein cholesterol levels, which averaged 20% and 31%, respectively (both p < 0.0001), and in diastolic BP responses (expressed as the infusion rate required to raise BP by 20 mm Hg) to both angiotensin II (7.3 +/- 3.0 vs 9.7 +/- 4.7 ng/kg/min, p = 0.05) and norepinephrine (0.15 +/- 0.13 vs 0.38 +/- 0.33 micrograms/kg/min, p = 0.03). Systolic BP responses were similar with both treatments. Body weight, resting BP, and maximal BP responses to physical stressors were similar with each treatment.

Adult↗
PubMed1995

Efficacy of pravastatin in combination with captopril in hypertensive patients.

OBJECTIVE: To determine the efficacy of pravastatin in the treatment of primary hypercholesterolaemia in patients being treated with captopril for hypertension. DESIGN: A double-blind parallel group study comparing 12 weeks of pravastatin therapy (20-40 mg/day) with placebo. PARTICIPANTS: 25 patients (age, 37-73 years) with mild-to-moderate hypertension and hypercholesterolaemia (total cholesterol level, 5.5-8.8 mmol/L). RESULTS: Pravastatin reduced total cholesterol levels by 22% (from 7.1 +/- 0.29 [SEM] to 5.5 +/- 0.25 mmol/L; P < 0.001) and low-density-lipoprotein cholesterol levels by 32% (from 5.0 +/- 0.32 to 3.4 +/- 0.28 mmol/L; P < 0.001) in four weeks and these levels were maintained for the 12 weeks of therapy. Pre-pravastatin values returned three weeks after stopping therapy. Levels of total cholesterol, cholesterol fractions and triglycerides remained constant or deteriorated in the placebo group. Pravastatin therapy was well tolerated. An integrated coronary risk score showed a 40% reduction in risk. CONCLUSION: This study indicates that pravastatin (combined with captopril) is an effective cholesterol-lowering drug, but that treatment needs to be maintained.

Adult↗
PubMed1995

Environments of the four tryptophans in the extracellular domain of human tissue factor: comparison of results from absorption and fluorescence difference spectra of tryptophan replacement mutants with the crystal structure of the wild-type protein.

The local environments of the four tryptophan residues of the extracellular domain of human tissue factor (sTF) were assessed from difference absorption and fluorescence spectra. The difference spectra were derived by subtracting spectra from single Trp-to-Phe or Trp-to-Tyr replacement mutants from the corresponding spectrum of the wild-type protein. Each of the mutants was capable of enhancing the proteolytic activity of factor VIIa showing that the mutations did not introduce major structural changes, although the mutants were more susceptible to denaturation by guanidinium chloride. The difference spectra indicate that the Trp residues are buried to different extents within the protein matrix. This evaluation was compared with the x-ray crystal structure of sTF. There is excellent agreement between predictions from the difference spectra and the environments of the Trp residues observed in the x-ray crystal structure, demonstrating that difference absorption and particularly fluorescence spectra derived from functional single-Trp replacement mutants can be used to obtain information about the local environments of individual Trp residues in multi-tryptophan proteins.

Base Sequence↗
PubMed1994

Short term effects of pravastatin on blood pressure in hypercholesterolaemic hypertensive patients.

In this study, which was primarily designed to determine the lipid-lowering efficacy of pravastatin in the setting of background antihypertensive therapy with ACE inhibitors and calcium antagonists, we took the opportunity to examine whether pravastatin interacts with antihypertensive therapy to produce additional falls in blood pressure. This may help clarify the mechanism of action of pravastatin's rapid beneficial effects on cardiovascular morbidity. We treated 25 hypertensive hypercholesterolaemic patients with 12 weeks of either pravastatin or placebo in this double blind, placebo controlled parallel group study. Placebo treatment did not alter plasma lipids, whereas 12 weeks' treatment with pravastatin reduced total cholesterol by 27% (from 7.1 +/- 0.27 to 5.2 +/- 0.18, p < 0.001 compared with placebo) and low density lipoprotein cholesterol by 35% (from 4.9 +/- 0.36 to 3.2 +/- 0.17, p < 0.001). There were no changes in systolic or diastolic blood pressure either following 12 weeks' treatment or 3 weeks' withdrawal of pravastatin. Thus, pravastatin remains efficacious as a lipid lowering agent in the presence of antihypertensive therapy but does not enhance the blood pressure lowering action of these drugs. Therefore it is unlikely that blood pressure reduction is the mechanism by which pravastatin mediates its reported short term effects on cardiovascular morbidity.

Blood Pressure↗
PubMed1992

Comparison of the pharmacokinetics and pharmacodynamics of perindopril, cilazapril and enalapril.

1. The pharmacokinetic and pharmacodynamic responses to enalapril, perindopril and cilazapril have been studied in essential hypertensives (2, 4 and 8 mg perindopril and 2.5 mg cilazapril, single dose and steady state) and normotensive volunteers (10 mg enalapril, single dose). 2. Plasma levels of the active diacid compounds reached similar peaks after single dose administration of the drugs. However, perindoprilat levels persisted for 5 days whereas cilazaprilat levels were not detectable beyond 12 h. 3. The higher levels of perindoprilat were associated with a greater inhibition of plasma angiotensin-converting enzyme (ACE) activity in both acute and steady state studies. 4. The potency of the active diacids in inhibiting plasma ACE activity was perindoprilat greater than cilazaprilat greater than enalaprilat. 5. There was a close relationship between plasma concentration, ACE inhibition and blood pressure decrease. Although both cilazapril and perindopril administration reduced blood pressure in hypertensive subjects, only perindopril exerted 24 h blood pressure control at the doses used.

Adult↗
PubMed1990

Cimetidine-associated adverse reaction.

Cimetidine, a histamine2-receptor antagonist, is used in the treatment and prophylaxis of peptic ulcer disease. Its use is relatively free of serious adverse reactions and only a few accounts of hypersensitivity exist. We report a case of intravenous cimetidine-associated adverse reaction characterized by junctional rhythm, bradycardia, and hypotension apparently not secondary to rapid intravenous cimetidine infusion. The adverse reaction was reproduced upon rechallenge. No previous accounts of this reaction appear clearly defined in the literature nor have such reactions been confirmed by rechallenge.

Aged↗