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Biomedical subjects

A Lee

Publications and source records attributed to A Lee.

At least 217 records · Page 12Linked to original sources
PubMed2000

Homozygous 2bp deletion in the human factor VII gene: a non-lethal mutation that is associated with a complete absence of circulating factor VII.

We report the case of a 5-year-old boy with severe factor VII deficiency. The affected child presented at the age of 8 months and again at 18 months with bleeding from the gastrointestinal tract but the diagnosis of factor VII deficiency was not made until the age of 3 years. He was treated with fresh frozen plasma and subsequently factor VII concentrates and to date remains well. To identify the causative mutation, the factor VII gene was screened by SSCP and direct sequence analysis. A single homozygous 2 bp deletion (-CT) mutation was identified in exon 1a removing nucleotides 27/28 (codons 52/53). Both parents, who were first cousins, were heterozygous for the mutation. The mutation located in the prepropeptide of factor VII, results in a complete absence of factor VII in plasma. This case indicates that a complete absence of plasma factor VII is not necessarily a lethal condition.

Child, Preschool↗
PubMed2000

A comparison of the safety and efficacy of oral anticoagulation for the treatment of venous thromboembolic disease in patients with or without malignancy.

The optimal long-term treatment of acute venous thromboembolism (VTE) in patients with malignancy remains undefined. In particular, based on current evidence, it is uncertain whether secondary prophylaxis using standard intensity oral anticoagulant therapy is associated with higher risks of bleeding and recurrent thrombosis in patients with cancer than in those without cancer. This study compared the outcome of anticoagulation courses in 95 patients with malignancy with those of 733 patients without malignancy. All patients were participants in a large, nation-wide population study and were prospectively followed from the initiation of their oral anticoagulant therapy. Based on 744 patient-years of treatment and follow-up, the rates of major (5.4% vs 0.9%), minor (16.2% vs 3.6%) and total (21.6% vs 4.5%) bleeding were statistically significantly higher in cancer patients compared with patients without cancer. Bleeding was also a more frequent cause of early anticoagulation withdrawal in patients with malignancy (4.2% vs. 0.7%; p <0.01; RR 6.2 (95% CI 1.95-19.4). There was a trend towards a higher rate of thrombotic complications in cancer patients (6.8% vs. 2.5%; p = 0.058; RR 2.5 [CI 0.96-6.5]) but this did not achieve statistical significance. In the group of patients with cancer, the bleeding rate was high across the different INR categories and was independent of the temporally associated International Normalized Ratio (INR). In contrast, the bleeding rate was increased only with INR values greater than 4.5 in the group of patients without cancer. The rate of thrombotic events was significantly higher in both cohorts when the INR was less than 2.0. In conclusion, patients with malignancy treated with oral anticoagulants have a higher rate of bleeding and possibly an increased risk of recurrent thrombosis compared with patients without malignancy. Safer and more effective anticoagulant therapy is needed for this challenging group of patients.

Administration, Oral↗
PubMed2000

Treating depression in general practice: factors affecting patients' treatment preferences.

We performed a cross-sectional survey of general practice attenders to determine their preferences regarding treatment for depression and characteristics associated with such preferences. Counselling was more popular than drug therapy (antidepressants), particularly among women, those who believed antidepressants are addictive, and those who had received such treatment in the past.

Adult↗
PubMed2000

Bedside assessment of swallowing: a useful screening tool for dysphagia in an acute geriatric ward.

AIM: Dysphagia is common in the elderly and is associated with increased morbidity and mortality. We undertook a prospective study to determine the usefulness of a simple bedside swallowing test in terms of (1) detecting previously undiagnosed dysphagia, (2) agreement of the doctor's assessment with that of the speech therapist, (3) impact on subsequent feeding modality, (4) predicting risk of subsequent pneumonia. METHOD: Patients in an acute geriatric ward who had no contra-indications to oral feeding were subjected to a bedside swallowing assessment by a geriatrician within 24 hours of admission. All patients found to be dysphagic were subsequently re-assessed by a speech therapist within 48 hours. In addition, every fifth patient deemed to have normal swallowing by the doctor was assessed by the speech therapist. RESULTS: Sixty-five patients were studied. The doctor's assessment was in very good agreement with the assessment of the speech therapist (kappa = 0.87). Patients found to have dysphagia using the doctor's assessment protocol had an increased risk of developing pneumonia during their hospitalization (relative risk R.R.: 9.9 confidence interval C.I.: 1.2-81.2). Cough on swallowing and delayed swallowing were both found to be associated with an increased risk of developing pneumonia during the period of hospitalization (R.R.: 4.2, C.I.: 1.2-14.4; R.R.: 5.3, C.I.: 1.1-26.3 respectively). CONCLUSION: A simple bedside swallowing test can be used as an effective screening tool in detecting hitherto undiagnosed dysphagia. The validity of this tool in the diagnosis of aspiration requires further investigation.

Acute Disease↗
PubMed2000

Youth health promotion and health promoting schools: what should be the aims?

The school plays a very important role in health education and promotion at the crucial stage of childhood and adolescence. It develops personal character, skills, attitude and physique, in addition to imparting knowledge. To sustain the concerted effort to address inter-wined social, educational, psychological and health needs of children, training and ongoing reinforcement must be given to teachers. A task force made up of parents, teachers, administrators, students and health professionals must be formed to develop core values, visions, goals and activities; and to provide new direction for health education and promotion. The 'Health Promoting Schools' Programme of the CUHK was launched in 1999 with the aim to promote physical, emotional and intellectual development of students through healthy and hygienic practices. The programme has also conducted researches on health of students, prioritise and evaluate relevant programmes. Recent research studies revealed that students in higher grades had more physical and psychological health problems, probably due to heavy workload and less emphasis on health education in their formal curriculum. Another research study has shown the lack of concrete school policies in health education. It is therefore important to develop policies, practices and structures, as well as regular curricular reviews to promote health of the school children. The "Health Promoting Schools' Programme has already initiated several district based health promotion programmes to pave the way for the formation of local task force on youth health promotion.

Adolescent↗
PubMed1999

Should adolescents be vaccinated against hepatitis A: the Hong Kong experience.

Hong Kong is a well developed city in the center of an endemic region for hepatitis A. The age at which hepatitis A occurs has shifted from childhood and adolescence to adults like many western countries. There is a high chance of outbreaks with the introduction of infection from neighbouring countries. Reducing the susceptibility of a population by vaccination can eliminate the diseases but updated sero-epidemiological data is needed to analyse the level of natural immunity, and identify those susceptible to infection for preventive measures. This study conducted amongst secondary school children seeks to identify those who are at risk and to obtain data on the present sero-prevalence of anti-HAV. Overall prevalence of anti-HAV in this age group was 7% increasing with age. Analysed by multiple regression model, those students living in mainland China over 3 years had odds ratio of 31.6 (95% c. i. 17.4-57.3) compared with those born in Hong Kong. Students with a father in a skilled occupation and an education level of secondary school or above, and both parents with secondary education or above, had an odds ratio of 0.22 (95% c.i. 0.07-0.7) and 0.35 (95% c.i. 0. 17-0.72) associated with presence of anti-HAV, respectively. Improved socio-economic state exposes higher proportion of the population at risk. Immunisation is worthwhile to be considered for the adolescents in Hong Kong. Prevaccination screening is cost effective only for those adolescents who are most likely to have natural immunity.

Adolescent↗
PubMed1999

Moderate hypothermia for uncontrolled intracranial hypertension in acute liver failure.

BACKGROUND: Increased intracranial pressure as a complication of acute liver failure has a mortality of about 90% in patients who do not respond to treatment with mannitol and ultrafiltration. We investigated the safety and efficacy of moderate hypothermia for uncontrolled increase in intracranial pressure in patients with acute liver failure. METHODS: We studied seven consecutive patients aged 16-46 years (five women, four candidates for orthotopic liver transplantation [OLT]) with acute liver failure who fulfilled criteria for poor-prognosis liver failure and had increased intracranial pressure that was unresponsive to two treatments with mannitol and ultrafiltration. We used cooling blankets to lower the patients' core temperature to 32-33 degrees C. Patients who were not suitable candidates for OLT (patients 1-3) were cooled for 8 h and then gradually rewarmed over 1 h to a baseline temperature of 37 degrees C. Patients who were suitable candidates for OLT (patients 4-7) were cooled before and during the OLT procedure. We measured cerebral blood flow and metabolic indices before and after cooling. FINDINGS: The four patients who were candidates for OLT were successfully maintained until transplantation with 13 (range 10-14) h of hypothermia. The three patients who were unsuitable candidates for OLT died after rewarming. Intracranial pressure before cooling was 45 (25-49) mm Hg and was reduced in all patients to 16 (13-17) mm Hg (p<0.05). Cerebral blood flow decreased from 103 (25-134) mL 100 g(-1) min(-1) before cooling to 44 (24-75) mL 100 g(-1) min(-1) after cooling (p<0.05). The corresponding changes for cerebral perfusion pressure was an increase from 45 (37-56) mm Hg to 70 (60-78) mm Hg (p<0.05) and for cardiac index a decrease from 9.8 (7-13) to 5.1 (4.3-6.1) L per min per m2 of body surface area. During hypothermia there was no significant relapse of increased intracranial pressure. Arterial ammonia and cerebral uptake of ammonia were significantly reduced with cooling. No adverse effects of hypothermia were observed. INTERPRETATION: Moderate hypothermia is useful in the treatment of uncontrolled increase in intracranial pressure in patients with acute liver failure and may serve as a bridge to OLT.

Acute Disease↗
PubMed1999

Identification of a novel tropomodulin isoform, skeletal tropomodulin, that caps actin filament pointed ends in fast skeletal muscle.

Tropomodulin (E-Tmod) is an actin filament pointed end capping protein that maintains the length of the sarcomeric actin filaments in striated muscle. Here, we describe the identification and characterization of a novel tropomodulin isoform, skeletal tropomodulin (Sk-Tmod) from chickens. Sk-Tmod is 62% identical in amino acid sequence to the previously described chicken E-Tmod and is the product of a different gene. Sk-Tmod isoform sequences are highly conserved across vertebrates and constitute an independent group in the tropomodulin family. In vitro, chicken Sk-Tmod caps actin and tropomyosin-actin filament pointed ends to the same extent as does chicken E-Tmod. However, E- and Sk-Tmods differ in their tissue distribution; Sk-Tmod predominates in fast skeletal muscle fibers, lens, and erythrocytes, while E-Tmod is found in heart and slow skeletal muscle fibers. Additionally, their expression is developmentally regulated during chicken breast muscle differentiation with Sk-Tmod replacing E-Tmod after hatching. Finally, in skeletal muscle fibers that coexpress both Sk- and E-Tmod, they are recruited to different actin filament-containing cytoskeletal structures within the cell: myofibrils and costameres, respectively. All together, these observations support the hypothesis that vertebrates have acquired different tropomodulin isoforms that play distinct roles in vivo.

Actins↗
PubMed1999

Identification of a mammalian brain sulfate transporter.

Sulfate is an essential anion involved in many biosynthetic and pharmacological reactions. Sulfate is an important constituent of myelin membranes in the brain; however, very little is known as to how sulfate enters brain cells. In this study, our aim was to determine whether the mammalian brain possesses a sulfate transporter. Injection of rat brain poly A(+) RNA into Xenopus oocytes led to an induction of Na(+)-independent sulfate transport, which was inhibited by oxalate, probenecid, phenol red, thiosulfate and DIDS. Hybrid depletion using sat-1 antisense oligodeoxyribonucleotides led to a complete inhibition of brain mRNA-induced sulfate transport in Xenopus oocytes, suggesting the presence of a functional sat-1 transcript in the brain. By RT-PCR, sat-1 mRNA was detected throughout the rat brain and in situ hybridisation showed highest sat-1 expression in the hippocampus and cerebellum. This is the first study to identify and characterise a functional mammalian brain sulfate transporter.

Animals↗
PubMed1999

Ca2+/calmodulin binds to and modulates P/Q-type calcium channels.

Neurotransmitter release at many central synapses is initiated by an influx of calcium ions through P/Q-type calcium channels, which are densely localized in nerve terminals. Because neurotransmitter release is proportional to the fourth power of calcium concentration, regulation of its entry can profoundly influence neurotransmission. N- and P/Q-type calcium channels are inhibited by G proteins, and recent evidence indicates feedback regulation of P/Q-type channels by calcium. Although calcium-dependent inactivation of L-type channels is well documented, little is known about how calcium modulates P/Q-type channels. Here we report a calcium-dependent interaction between calmodulin and a novel site in the carboxy-terminal domain of the alpha1A subunit of P/Q-type channels. In the presence of low concentrations of intracellular calcium chelators, calcium influx through P/Q-type channels enhances channel inactivation, increases recovery from inactivation and produces a long-lasting facilitation of the calcium current. These effects are prevented by overexpression of a calmodulin-binding inhibitor peptide and by deletion of the calmodulin-binding domain. Our results reveal an unexpected association of Ca2+/calmodulin with P/Q-type calcium channels that may contribute to calcium-dependent synaptic plasticity.

Amino Acid Sequence↗
PubMed1999

Dominant-negative inhibition of receptor-mediated endocytosis by a dynamin-1 mutant with a defective pleckstrin homology domain.

The dynamins are 100 kDa GTPases involved in the scission of endocytic vesicles from the plasma membrane [1]. Dynamin-1 is present in solution as a tetramer [2], and undergoes further self-assembly following its recruitment to coated pits to form higher-order oligomers that resemble 'collars' around the necks of nascent coated buds [1] [3]. GTP hydrolysis by dynamin in these collars is thought to accompany the 'pinching off' of endocytic vesicles [1] [4]. Dynamin contains a pleckstrin homology (PH) domain that binds phosphoinositides [5] [6], which in turn enhance both the GTPase activity [5] [7] [8] and self-assembly [9] [10] of dynamin. We recently showed that the dynamin PH domain binds phosphoinositides only when it is oligomeric [6]. Here, we demonstrate that interactions between the dynamin PH domain and phosphoinositides are important for dynamin function in vivo. Full-length dynamin-1 containing mutations that abolish phosphoinositide binding by its PH domain was a dominant-negative inhibitor of receptor-mediated endocytosis. Mutated dynamin-1 with both a defective PH domain and impaired GTP binding and hydrolysis also inhibited receptor-mediated endocytosis. These findings suggest that the role of the PH domain in dynamin function differs from that seen for other PH domains. We propose that high-avidity binding to phosphoinositide-rich regions of the membrane by the multiple PH domains in a dynamin oligomer is critical for dynamin's ability to complete vesicle budding.

Binding Sites↗
PubMed1999

Alpha2A-adrenergic receptors are primarily presynaptic heteroreceptors in the C1 area of the rat rostral ventrolateral medulla.

The 2A subtype of the alpha-adrenergic receptor (alpha2A-AR) is necessary for the hypotensive effects of clonidine and other sympathoinhibitory adrenergic agonists. This hypotensive response appears to be due to the inhibition of sympathoexcitatory reticulospinal neurons found in the rostral ventrolateral medulla (RVL), including neurons of the C1 adrenergic cell group. The cellular mechanisms underlying this inhibition have not been established. Thus, this study examined the ultrastructural relationships between profiles containing alpha2AAR-immunoreactivity (alpha2AAR-I) and those containing the catecholamine synthesizing enzyme tyrosine hydroxylase (TH) to determine potential cellular substrates for alpha2A-AR inhibition of C1 neuron activity. Consistent with previous light microscopic studies, alpha2AAR-I was found in perikarya and large dendrites and the majority of these profiles also contained TH-labeling (approximately 70% of 140). However, alpha2AAR-I in these cells was primarily found within endosomes and Golgi complexes and in clusters associated with the endoplasmic reticula, probable sites for synthesis and/or trafficking of receptors. In contrast, most of the alpha2AAR-I profiles (n=646) in the RVL were axons and axon terminals (approximately 68%) which lacked TH immunoreactivity. alpha2AAR-labeled axons were small and unmyelinated and labeled terminals usually formed symmetric synapses on the shafts of catecholaminergic or unlabeled dendrites. Most of these alpha2AAR-labeled axons were found in close proximity to TH-labeled profiles and approximately one-fifth (17% of 408) of the alpha2AAR-labeled axons and axon terminals directly contacted TH-labeled profiles, mostly dendrites. These studies suggest that alpha2AARs in the C1 area of the RVL function primarily as heteroreceptors on presynaptic axons and terminals of non-catecholaminergic cells, some of which provide inhibitory synaptic input to C1 neurons. These receptors may be activated by catecholamines released either from the dendrites of C1 neurons or from the terminals of other catecholaminergic neurons via volume transmission.

Animals↗
PubMed1999

What are the symptoms of varicose veins? Edinburgh vein study cross sectional population survey.

OBJECTIVE: To define the relations between age, sex, lower limb symptoms, and the presence of trunk varicose veins on clinical examination. DESIGN: Cross sectional population study. SETTING: 12 general practices with catchment areas geographically and socioeconomically distributed throughout Edinburgh. PARTICIPANTS: An age stratified random sample of 1566 people (699 men and 867 women) aged 18-64 selected from the computerised age-sex registers of participating practices. MAIN OUTCOME MEASURES: Self administered questionnaire on the presence of lower limb symptoms and physical examination to determine the presence and severity of varicose veins. RESULTS: Women were significantly more likely than men to report lower limb symptoms such as heaviness or tension, swelling, aching, restless legs, cramps, and itching. The prevalence of symptoms tended to increase with age in both sexes. In men, only itching was significantly related to the presence and severity of trunk varices (linear test for trend, P=0.011). In women there was a significant relation between trunk varices and the symptoms of heaviness or tension (P</=0.001), aching (P</=0.001), and itching (P</=0.005). However, the level of agreement between the presence of symptoms and trunk varices was too low to be of clinical value, especially in men. CONCLUSIONS: Even in the presence of trunk varices, most lower limb symptoms probably have a non-venous cause. Surgical extirpation of trunk varices is unlikely to ameliorate such symptoms in most patients.

Adolescent↗
PubMed1999

Mitochondrial DNA deletions in human cardiac tissue show a gross mosaic distribution.

The variability of mitochondrial DNA (mtDNA) deletional patterns has been investigated in adjacent slices of human heart atrium. Using quantitative PCR we found differential abundances of one particular mtDNA deletion, that of 4977 bp (mtDNA4977), among sets of adjacent slices of right atrial trabeculae pectinatae from 10 subjects. Some subjects had relatively constant abundance of mtDNA4977 among the tissue slices, while others covered a wide range. A qualitative PCR procedure was used to visualize the patterns of multiple deletions within an 8.64-kb segment of the mtDNA genome, in the same set of atrial trabeculae samples. Some subjects showed completely different multiple deletional patterns in each of the trabeculae slices analyzed. There was no correlation between the variation of the abundance of mtDNA4977 and that of the multiple deletions. The results are consistent with the notion that the occurrence of mtDNA deletions during aging is a random process, involving their production throughout the lifetime of an individual. In this view, the patterns of new deletions are superimposed on those already accumulated by propagation and segregation of mutations formed earlier in life.

Adult↗
PubMed1999

Millipore filter cell block preparation: an alternative to cell block in nongynecologic specimens of limited cellularity.

The use of membrane filters to concentrate cytology specimens was first described by Seal (Cancer 1956; 9:866-868). We report on a technique in which a portion of Papanicolaou-stained Millipore filter (Millipore Corp, Bedford, MA) preparation can be converted into a paraffin block for hematoxylin-eosin (H&E) preparations and immunocytochemical analysis (ICC). Seven cases with moderate cellularity and no cell block preparation were retrieved from our cytopathology files. The specimens included: 4 pleural effusions with metastatic adenocarcinoma, and 3 FNA specimens (1 metastatic melanoma, 1 metastatic adenocarcinoma, and 1 thyroid/papillary carcinoma). The filter was removed from the slide, cut in half, and subjected to paraffin embedding in the usual fashion (postfixed in 10% neutral-buffered formalin). Four-micron-thick sections were cut onto Probe-On (Fisher Scientific, Pittsburgh, Pa) slides. ICC was performed using the avidin-biotin-peroxidase complex technique and capillary gap technology. Antibodies included CAM5.2, AE1/AE3, CEA, CD15, LCA, PanCK, S100, HMB45, and thyroglobulin. All cases showed excellent preservation of cellular morphology on H&E. ICC performed on Millipore filter cell block preparations showed specific antibody staining patterns with preservation of cellular details. All antibodies showed their specific staining patterns with clean background and lack of nonspecific staining. This technique has the following advantages: 1) offers an alternative to cell blocks in moderately cellular specimens; 2) clean background; 3) preservation of cytology specimens for future studies.

Adenocarcinoma↗